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Rationale: In the phase III, 52-week ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial in chronic obstructive pulmonary disease (COPD) (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) significantly reduced all-cause mortality compared with glycopyrrolate/formoterol fumarate (GFF).,However, 384 of 8,509 patients were missing vital status at Week 52 in the original analyses.,Objectives: To assess the robustness of the ETHOS mortality findings after additional data retrieval for patients missing Week 52 vital status in the original analyses.,Methods: Patients with moderate to very severe COPD and prior history of exacerbation received twice-daily dosing with 320/18/9.6 μg of BGF (BGF 320), 160/18/9.6 μg of BGF (BGF 160), 18/9.6 μg of GFF, or 320/9.6 μg of budesonide/formoterol fumarate (BFF) (all delivered via a single metered-dose Aerosphere inhaler).,Time to death (all-cause) was a prespecified secondary endpoint.,Measurements and Main Results: In the final retrieved dataset, which included Week 52 vital status for 99.6% of the intent-to-treat population, risk of death with BGF 320 was significantly lower than GFF (hazard ratio, 0.51; 95% confidence interval, 0.33-0.80; unadjusted P = 0.0035).,There were no significant differences in mortality when comparing BGF 320 with BFF (hazard ratio, 0.72; 95% confidence interval, 0.44-1.16; P = 0.1721), nor were significant differences observed when comparing BGF 160 against either dual comparator.,Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis.,Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320, BGF 160, GFF, and BFF groups, respectively.,Conclusions: Using final retrieved vital status data, triple therapy with BGF 320 reduced the risk of death compared with GFF, but was not shown to significantly reduce the risk of death compared with BFF, in patients with COPD.,Triple therapy containing a lower dose of inhaled corticosteroid (BGF 160) was not shown to significantly reduce the risk of death compared with the dual therapy comparators.

This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks.,The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over weeks 12-24.,Secondary endpoints included symptoms, health-related quality of life, and safety.,Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint.,In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference − 4 mL; P = 0.8316).,BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints.,BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI.,All treatments were well tolerated.,Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β2-agonist), as well as symptoms and exacerbations relative to dual therapies.,Findings support BGF MDI use in Chinese patients with moderate to very severe COPD.,ClinicalTrials.gov NCT02497001.,The online version of this article (10.1007/s12325-020-01266-5) contains supplementary material, which is available to authorized users.

The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation.,The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD.,Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited.,Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses.,A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected.,The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%).,A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients.,Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population.,In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population.,The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.

Rhinovirus (RV) is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations, and primarily infects bronchial epithelial cells.,Immune responses from BECs to RV infection are critical in limiting viral replication, and remain unclear in COPD.,The objective of this study is to investigate innate immune responses to RV infection in COPD primary BECs (pBECs) in comparison to healthy controls.,Primary bronchial epithelial cells (pBECs) from subjects with COPD and healthy controls were infected with RV-1B.,Cells and cell supernatant were collected and analysed using gene expression microarray, qPCR, ELISA, flow cytometry and titration assay for viral replication.,COPD pBECs responded to RV-1B infection with an increased expression of antiviral and pro-inflammatory genes compared to healthy pBECs, including cytokines, chemokines, RNA helicases, and interferons (IFNs).,Similar levels of viral replication were observed in both disease groups; however COPD pBECs were highly susceptible to apoptosis.,COPD pBECs differed at baseline in the expression of 9 genes, including calgranulins S100A8/A9, and 22 genes after RV-1B infection including the signalling proteins pellino-1 and interleukin-1 receptor associated kinase 2.,In COPD, IFN-β/λ1 pre-treatment did not change MDA-5/RIG-I and IFN-β expression, but resulted in higher levels IFN-λ1, CXCL-10 and CCL-5.,This led to reduced viral replication, but did not increase pro-inflammatory cytokines.,COPD pBECs elicit an exaggerated pro-inflammatory and antiviral response to RV-1B infection, without changing viral replication.,IFN pre-treatment reduced viral replication.,This study identified novel genes and pathways involved in potentiating the inflammatory response to RV in COPD.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the history of this debilitating lung condition.,Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support.,The last 2 decades have seen a substantial increase in our understanding of the best way to manage the respiratory failure suffered by many patients during this high-risk period.,This review article examines the evidence underlying supplemental oxygen therapy during exacerbations of COPD.,We first discuss the epidemiology and pathophysiology of respiratory failure in COPD during exacerbations.,The rationale and evidence underlying oxygen therapy, including the risks when administered inappropriately, are then discussed, along with further strategies for ventilatory support.,We also review current recommendations for best practice, including methods for improving oxygen provision in the future.

Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services.

Many patients with chronic obstructive pulmonary disease (COPD) receive inhaled corticosteroids (ICSs) without a clear indication, and thus, the impact of ICS withdrawal on disease control is of great interest.,DACCORD is a prospective, noninterventional 2-year study in the primary and secondary care throughout Germany.,A subgroup of patients were taking ICS prior to entry - 1,022 patients continued to receive ICS for 2 years; physicians withdrew ICS on entry in 236 patients.,Data from these two subgroups were analyzed to evaluate the impact of ICS withdrawal.,Patients aged ≥40 years with COPD, initiating or changing COPD maintenance medication were recruited, excluding patients with asthma.,Demographic and disease characteristics, prescribed COPD medication, COPD Assessment Test, exacerbations, and lung function were recorded.,There were few differences in baseline characteristics; ICS withdrawn patients had shorter disease duration and better lung function, with 74.2% of ICS withdrawn patients not exacerbating, compared with 70.7% ICS-continued patients.,During Year 1, exacerbation rates were 0.414 in the withdrawn group and 0.433 in the continued group.,COPD Assessment Test total score improved from baseline in both groups.,These data suggest that ICS withdrawal is possible with no increased risk of exacerbations in patients with COPD managed in the primary and secondary care.

The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004.

Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes.,However, very little attention has been paid to the timing of the failure.,This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor.,The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony.,The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation.,The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure.,However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate.,Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance.,Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV.,Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation.

Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence.

COPD is a leading cause of morbidity and mortality worldwide.,Patients suffer from refractory breathlessness, unrecognized anxiety and depression, and decreased quality of life.,Palliative care improves symptom management, patient reported health-related quality of life, cost savings, and mortality though the majority of patients with COPD die without access to palliative care.,There are many barriers to providing palliative care to patients with COPD including the difficulty in prognosticating a patient’s course causing referrals to occur late in a patient’s disease.,Additionally, physicians avoid conversations about advance care planning due to unique communication barriers present with patients with COPD.,Lastly, many health systems are not set up to provide trained palliative care physicians to patients with chronic disease including COPD.,This review analyzes the above challenges, the available data regarding palliative care applied to the COPD population, and proposes an alternative approach to address the unmet needs of patients with COPD with proactive primary palliative care.

FEV1 is universally used as a measure of severity in COPD.,Current thresholds are based on expert opinion and not on evidence.,We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients.,We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS).,Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival.,A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%).,Overall 975 (28.1%) patients died at 5 years.,The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56-69%, severe 36-55%, and very severe ≤35%.,Survival at 5 years was 0.89 for patients with FEV1≥70 vs.,0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69-7.74).,The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001).,Prognostic reliability is maintained at 1, 3, 5, and 10 years.,In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear.,The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56-69%, 36-55%, and ≤35%.,These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs.

Epigenetics changes have been shown to be affected by cigarette smoking.,Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD).,We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers.,We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina’s Infinium HumanMethylation450 BeadChip.,Our data revealed that the differentially methylated genes were related to top canonical pathways (e.g., G beta gamma signaling, mechanisms of cancer, and nNOS signaling in neurons), disease and disorders (organismal injury and abnormalities, cancer, and respiratory disease), and molecular and cellular functions (cell death and survival, cellular assembly and organization, cellular function and maintenance) in patients with COPD.,The genome-wide DNA methylation analysis identified suggestive genes, such as NOS1AP, TNFAIP2, BID, GABRB1, ATXN7, and THOC7 with DNA methylation changes in COPD lung tissues that were further validated by pyrosequencing.,Pyrosequencing validation confirmed hyper-methylation in smokers and patients with COPD as compared to non-smokers.,However, we did not detect significant differences in DNA methylation for TNFAIP2, ATXN7, and THOC7 genes in smokers and COPD groups despite the changes observed in the genome-wide analysis.,Our study suggests that DNA methylation in suggestive genes, such as NOS1AP, BID, and GABRB1 may be used as epigenetic signatures in smokers and patients with COPD if the same is validated in a larger cohort.,Future studies are required to correlate DNA methylation status with transcriptomics of selective genes identified in this study and elucidate their role and involvement in the progression of COPD and its exacerbations.,The online version of this article (doi:10.1186/s13148-017-0335-5) contains supplementary material, which is available to authorized users.

On-going airway inflammation is characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD).,However, the key factors determining the decrease in lung function, an important clinical parameter of COPD, are not clear.,Genome-wide linkage analyses provide evidence for significant linkage to airway obstruction susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster.,Moreover, a genetic variation in the defensin beta 1 (DEFB1) gene was found to be associated with COPD.,Therefore, we hypothesized that DEFB1 is differently regulated and expressed in human lungs during COPD progression.,Gene expression of DEFB1 was assessed in bronchial epithelium and BAL fluid cells of healthy controls and patients with COPD and using bisulfite sequencing and ChIP analysis, the epigenetic control of DEFB1 mRNA expression was investigated.,We can demonstrate that DEFB1 mRNA expression was significantly increased in bronchopulmonary specimen of patients with COPD (n = 34) vs. healthy controls (n = 10) (p<0.0001).,Furthermore, a significant correlation could be detected between DEFB1 and functional parameters such as FEV1 (p = 0.0024) and the FEV1/VC ratio (p = 0.0005).,Upregulation of DEFB1 mRNA was paralleled by changes in HDAC1-3, HDAC5 and HDAC8 mRNA expression.,Whereas bisulfite sequencing revealed no differences in the methylation state of DEFB1 promoter between patients with COPD and controls, ChIP analysis showed that enhanced DEFB1 mRNA expression was associated with the establishment of an active histone code.,Thus, expression of human DEFB1 is upregulated and related to the decrease in pulmonary function in patients with COPD.

The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 μg) versus tiotropium monotherapy (TIO 5 μg) for reducing moderate-to-severe exacerbations of COPD.,This is a prespecified analysis of the DYNAGITO data in Japanese patients.,Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe exacerbation in the previous 12 months.,Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 μg: n=226, TIO 5 μg: n=235) were Japanese.,The primary endpoint was the annualized rate of moderate-to-severe COPD exacerbations.,The key secondary endpoint was the time to first moderate-to-severe COPD exacerbation, and other secondary endpoints included the annualized rate of exacerbations leading to hospitalization, time to first COPD exacerbation leading to hospitalization, and all-cause mortality.,Safety data were analyzed descriptively.,Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434).,The risk of a first moderate-to-severe COPD exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant.,The annualized rate of COPD exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654).,The adverse event incidence was balanced between treatment arms.,In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations.,Both treatments were well tolerated.

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY

The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment.

The purpose of this study was to quantify the walking time and frequency of postural changes in daily life in patients with chronic obstructive pulmonary disease (COPD) using a new triaxial accelerometer system.,Twenty-six elderly patients with stable COPD (age 76.8 ± 6.2 years; percent forced expiratory volume in one second [%FEV1] 52.9% ± 26.3%) and 20 age-matched elderly subjects (age 73.0 ± 4.2 years; %FEV1 124.0% ± 22.3%) participated in the study.,The subjects’ time spent walking (slow, fast), standing, sitting, and lying down and the frequency of their postural changes (getting up, standing up) were assessed for 7 consecutive days using an Activity Monitoring And Evaluation System (A-MES™).,We analyzed the relationships among walking times, frequency of postural changes, and physiologic factors in both COPD patients and controls.,The COPD patients’ total walking time, including slow (<2 km/hour) and fast (≥2 km/hour) walking, and their frequency of standing up were significantly lower than those of the age-matched controls (P < 0.01).,The fast walking time in daily life was significantly correlated with the 6-minute walking distance, quadriceps femoris muscle force, and dyspnea (P < 0.01).,These results suggest that both slow (<2 km/hour) and fast (≥2 km/hour) walking time and frequency of postural changes is significantly decreased in COPD patients compared with healthy elderly subjects.,The data also suggest that the COPD patients’ different walking times in daily life are significantly correlated with exercise capacity and dyspnea.,The 6-minute walking distance had the strongest correlation with fast walking time.

Factors associated with reduced daily physical activity (DPA) in patients with COPD are still controversial.,Physical inactivity in COPD increases risk of cardiovascular disease, frequent exacerbations, reduced health status, and increased symptoms.,We hypothesised that reduced DPA in patients with COPD is independent of traditional risk factors including age and spirometry.,In this cross-sectional study, DPA (over 7 days) was assessed on 88 community stable patients with COPD and 40 controls free from cardiorespiratory disease.,Spirometry, body composition, number of exacerbations, handgrip strength (HGS), modified Medical Research Council (mMRC), arterial stiffness, 6-min walking distance (6MWD) and BODE index were also determined.,Frequent exacerbation was defined as ≥2 and non-frequent exacerbation < 2.,Patients with COPD had reduced DPA and exercise capacity compared with controls similar in age, BMI and gender, p < 0.001.,Frequent exacerbators had less DPA than infrequent exacerbators and both less than controls, p < 0.001.,Patients with higher BODE index were less active than those with lower index.,Time spent on moderate activity was related to cardiovascular risk factors including arterial stiffness.,The DPA in patients was independent of age, gender, spirometry, body composition and HGS, p > 0.05.,The level of breathlessness was superior to lung function in predicting the level of DPA.,The level of DPA in COPD was independent of traditional risk factors.,Breathlessness score is a better predictor of the DPA than lung function and handgrip strength.

Although β-blockers are an established therapy in heart failure (HF) guidelines, including for patients with chronic obstructive pulmonary disease (COPD), there remain concerns regarding bronchoconstriction even with cardioselective β-blockers.,We wished to assess the real-life use of β-blockers for patients with HF and comorbid COPD.,We evaluated data from the Optimum Patient Care Research Database over a period of 1 year for co-prescribing of β-blockers with either an ACE inhibitor (ACEI) or angiotensin-2 receptor blocker (ARB) in patients with HF alone versus HF+COPD.,Association with inhaler therapy was also evaluated.,We identified 89 861 patients with COPD, 24 237 with HF and 10 853 with both conditions.,In patients with HF+COPD, the mean age was 79 years; 60% were male, and 27% had prior myocardial infarction.,Of patients with HF+COPD, 22% were taking a β-blocker in conjunction with either ACEI/ARB (n=2416) compared with 41% of patients with HF only (n=10 002) (adjusted OR 0.54, 95% CI 0.51 to 0.58, p<0.001).,Among HF+COPD patients taking inhaled corticosteroid (ICS) with long-acting β-agonist (LABA) and long-acting muscarinic antagonist, 27% of patients were taking an ACEI/ARB with β-blockers (n=778) versus 46% taking an ACEI/ARB without β-blockers (n=1316).,Corresponding figures for those patients taking ICS/LABA were 20% (n=583) versus 48% (n=1367), respectively.,These data indicate a substantial unmet need for patients with COPD who should be prescribed β-blockers more often for concomitant HF.

Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide.,Identifying COPD-associated DNA methylation marks in African-Americans may contribute to our understanding of racial disparities in COPD susceptibility.,We determined differentially methylated genes and co-methylation network modules associated with COPD in African-Americans recruited during exacerbations of COPD and smoking controls from the Pennsylvania Study of Chronic Obstructive Pulmonary Exacerbations (PA-SCOPE) cohort.,We assessed DNA methylation from whole blood samples in 362 African-American smokers in the PA-SCOPE cohort using the Illumina Infinium HumanMethylation27 BeadChip Array.,Final analysis included 19302 CpG probes annotated to the nearest gene transcript after quality control.,We tested methylation associations with COPD case-control status using mixed linear models.,Weighted gene comethylation networks were constructed using weighted gene coexpression network analysis (WGCNA) and network modules were analyzed for association with COPD.,There were five differentially methylated CpG probes significantly associated with COPD among African-Americans at an FDR less than 5 %, and seven additional probes that approached significance at an FDR less than 10 %.,The top ranked gene association was MAML1, which has been shown to affect NOTCH-dependent angiogenesis in murine lung.,Network modeling yielded the “yellow” and “blue” comethylation modules which were significantly associated with COPD (p-value 4 × 10-10 and 4 × 10-9, respectively).,The yellow module was enriched for gene sets related to inflammatory pathways known to be relevant to COPD.,The blue module contained the top ranked genes in the concurrent differential methylation analysis (FXYD1/LGI4, gene significance p-value 1.2 × 10-26; MAML1, p-value 2.0 × 10-26; CD72, p-value 2.1 × 10-25; and LPO, p-value 7.2 × 10-25), and was significantly associated with lung development processes in Gene Ontology gene-set enrichment analysis.,We identified 12 differentially methylated CpG sites associated with COPD that mapped to biologically plausible genes.,Network module comethylation patterns have identified candidate genes that may be contributing to racial differences in COPD susceptibility and severity.,COPD-associated comethylation modules contained genes previously associated with lung disease and inflammation and recapitulated known COPD-associated genes.,The genes implicated by differential methylation and WGCNA analysis may provide mechanistic targets contributing to COPD susceptibility, exacerbations, and outcomes among African-Americans.,Trial Registration: NCT00774176, Registry: ClinicalTrials.gov, URL: www.clinicaltrials.gov, Date of Enrollment of First Participant: June 2004, Date Registered: 04 January 2008 (retrospectively registered).,The online version of this article (doi:10.1186/s12931-016-0459-8) contains supplementary material, which is available to authorized users.

Blood eosinophil counts have been documented as a good biomarker for patients with chronic obstructive pulmonary disease (COPD) using inhaled corticosteroid (ICS) therapy.,However, the effectiveness and safety of prescribing high or medium dose of ICS for patients with different eosinophil counts are unknown.,A post hoc analysis of a previous prospective randomized study was performed for COPD patients using higher dose (HD: Fluticasone 1,000 μg/day) or medium dose (MD: Fluticasone 500 μg/day) of ICS combined with Salmeterol (100 μg/day).,Patients were classified into two groups: those with high eosinophil counts (HE ≥3%) and those with low eosinophil counts (LE <3%).,Lung function was evaluated with forced expiratory volume in 1 second, forced vital capacity, and COPD assessment test.,Frequencies of acute exacerbation and pneumonia were also measured.,Two hundred and forty-eight patients were studied and classified into higher eosinophil (HE) (n=85, 34.3%) and lower eosinophil (LE) groups (n=163, 65.7%).,The levels of forced expiratory volume in 1 second were significantly increased in patients of HE group treated with HD therapy, compared with the other groups (HE/HD: 125.9±27.2 mL vs HE/MD: 94.3±23.7 mL, vs LE/HD: 70.4±20.5 mL, vs LE/MD: 49.8±16.7 mL; P<0.05) at the end of the study.,Quality of life (COPD assessment test) markedly improved in HE/HD group than in MD/LE group (HE/HD: 9±5 vs LE/MD: 16±7, P=0.02).,The frequency of acute exacerbation was more decreased in HE/HD group patients, compared with that in LE/MD group (HE/HD: 13.5% vs LE/MD: 28.7%, P<0.01).,Pneumonia incidence was similar in the treatment groups (HE/HD: 3.2%, HE/MD: 2.6%, LE/HD: 3.5%, LE/MD 2.8%; P=0.38).,The study results support using blood eosinophil counts as a biomarker of ICS response and show the benefits of greater improvement of lung function, quality of life, and decreased exacerbation frequency in COPD patients with blood eosinophil counts higher than 3%, especially treated with higher dose of ICS.

The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease.,High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region.,A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD.,The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design.,This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A-D for simplicity and clarity.,At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed.,Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues.,Bronchodilators should not be discontinued except in the case of significant side effects.,At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation.,Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation.

Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.

Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide.,We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients.,This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia.,The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life.,Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea.,These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons).,Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV1], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George’s Respiratory Questionnaire [SGRQ] total score, P = 0.001).,Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV1, P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006).,In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life.

COPD is prevalent in Western society and its incidence is rising in the developing world.,Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden.,Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease.,COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality.,Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use.,Erythromycin has been shown to decrease the rate of COPD exacerbations.,Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life.,Noninvasive ventilation is associated with improved quality of life.,Long-term oxygen therapy improves mortality but only in hypoxic COPD patients.,The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of.,Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates.,Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles.

Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms.

Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.

It is widely recognized that health-related quality of life (HRQL) is impaired in patients with Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of research on longitudinal associations of COPD and HRQL.,This study examined the effects of COPD in early stages of disease on HRQL over ten years in a working-age general population setting in Southern Germany while considering the influence of common comorbidities.,In the population-based KORA F4 study (2006-08) 1,321 participants aged 41-61 years performed spirometry and reported information on HRQL (measured by the generic SF-12) and comorbidities.,For the same participants, HRQL information was available seven years before and three years after the lung function test from the previous S4 (1999-2001) and the F4L follow-up study (2010).,Using linear mixed models, the physical and mental component summary scores (PCS-12 / MCS-12) of the SF-12 were compared over time between COPD groups.,7.8% of participants were classified as having COPD (according to the LLN definition and the Global Lungs Initiative), 59.4% of them in grade 1.,Regression models showed a negative cross-sectional association of COPD grade 2+ with PCS-12 which persisted when comorbidities were considered.,Adjusted mean PCS-12 scores for the COPD grade 2+ group were reduced (−3.5 (p = 0.008) in F4, −3.3 (p = 0.014) in S4 and −4.7 (p = 0.003) in F4L) compared to the group without airflow limitation.,The size of the COPD effect in grade 2+ was similar to the effect of myocardial infarction and cancer.,Over ten years, a small decline in PCS-12 was observed in all groups.,This decline was larger in participants with COPD grade 2+, but insignificant.,Regarding MCS-12, no significant cross-sectional or longitudinal associations with COPD were found.,Despite small HRQL differences between COPD patients in early disease stages and controls and small changes over ten years, our results indicate that it is important to prevent subjects with airflow limitation from progression to higher grades.,Awareness of HRQL impairments in early stages is important for offering early interventions in order to maintain high HRQL in COPD patients.

Chronic obstructive pulmonary disease (COPD) progresses very slowly and the majority of patients are therefore elderly.,COPD is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli and there are increasing evidences for a close relationship between premature aging and chronic inflammatory diseases.,Thus, COPD is considered to be a disease of an accelerating aging.,In this review, we collected the evidence for roles of aging on pathogenesis of COPD and considered future therapeutic strategy for COPD based on this senescence hypothesis.,Since calorie restriction has been proved to extend lifespan, many efforts were made to clarify the molecular mechanism of aging.,Aging is defined as the progressive decline of homeostasis that occurs after the reproductive phase of life is complete, leading to an increasing risk of disease or death due to impaired DNA repair after damage by oxidative stress or telomere shortening as a result of repeated cell division.,During aging, pulmonary function progressively deteriorates; innate immunity is impaired and pulmonary inflammation increases, accompanied by structural changes, such as an enlargement of airspaces.,Noxious environmental gases, such as cigarette smoke, may worsen these aging-related events in the lung or accelerate aging of the lung due to reduction in anti-aging molecules and/or stimulation of aging molecules.,Aging signaling are complex but conserved in divert species, such as worm, fruit fry, rodent and humans.,Especially the insulin like growth factor (IGF-1) signaling was well documented.,Geroprotectors are therapeutics that affect the root cause of aging and age-related diseases, and thus prolong the life-span of animals.,Most of geroprotectors such as melatonin, metformin, rapamycin and resveratrol are anti-oxidant or anti-aging molecule regulators.,Therefore, geroprotection for the lung might be an attractive approach for the treatment of COPD by preventing premature aging of lung.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.

Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models.,The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously.,In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs.,Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs).,Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs.,Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection.,The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14.,A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs.,Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection.,These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke.,These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.

We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route.,Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month.,After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT.,After 1 week, mice were euthanized.,Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue.,In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC).,Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor.,Only BM-MSCs (IV > IT) increased the number of M2 macrophages.,In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2.

COPD exacerbations accelerate disease progression.,To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation (AECOPD) frequency and duration.,403 COPD patients, GOLD stage II-IV, aged 44-76 years were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years.,Examined baseline predictors were sex, age, body composition, smoking, AECOPD the last year, GOLD stage, Charlson comorbidity score (CCS), hypoxemia (PaO2<8 kPa), cough, use of inhaled steroids, and the inflammatory markers leucocytes, C-reactive protein (CRP), neutrophil gelatinase associated lipocalin (NGAL), soluble tumor necrosis factor receptor 1 (sTNF-R1), and osteoprotegrin (OPG).,Negative binomial models with random effects were fitted to estimate the annual incidence rate ratios (IRR).,For analysis of AECOPD duration, a generalized estimation equation logistic regression model was fitted, also adjusting for season, time since inclusion and AECOPD severity.,After multivariate adjustment, significant predictors of AECOPD were: female sex [IRR 1.45 (1.14-1.84)], age per 10 year increase [1.23 (1.03-1.47)], >1 AECOPD last year before baseline [1.65 (1.24-2.21)], GOLD III [1.36 (1.07-1.74)], GOLD IV [2.90 (1.98-4.25)], chronic cough [1.64 (1.30-2.06)] and use of inhaled steroids [1.57 (1.21-2.05)].,For AECOPD duration more than three weeks, significant predictors after adjustment were: hypoxemia [0.60 (0.39-0.92)], years since inclusion [1.19 (1.03-1.37)], AECOPD severity; moderate [OR 1.58 (1.14-2.18)] and severe [2.34 (1.58-3.49)], season; winter [1.51 (1.08-2.12)], spring [1.45 (1.02-2.05)] and sTNF-R1 per SD increase [1.16 (1.00-1.35)].,Several COPD characteristics were independent predictors of both AECOPD frequency and duration.

We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination.

Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies.,The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses.,FULFIL co-primary endpoint data have been previously reported.,FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β2-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations.,A subset participated for 52 weeks.,Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD™ (E-RS: COPD), St George’s Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.,FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period.,FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR.,At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).,These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR.,The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.,ClinicalTrials.gov number: NCT02345161.,GSK.,The online version of this article (10.1007/s12325-017-0650-4) contains supplementary material, which is available to authorized users.

Symptomatic relief is an important treatment goal for patients with COPD.,To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines.,The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need.,The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation.,The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.,This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international).,Subjects completed the E-RS as part of a daily eDiary.,Tests of reliability, validity, and responsiveness were conducted in each dataset.,In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74).,RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV1% predicted (−0.19, −0.14, −0.15); St.,George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests.,Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity.,RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001).,RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001).,Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.,Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.,MPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516,The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users.

Little is known of how to organize non-malign palliative care, and existing knowledge show that patients with COPD live with unmet palliative needs and low quality of life.,With the intent to improve palliative care for patients with COPD, we changed the structure of our outpatient clinic from routine visits by a pulmonary specialist to a structure where each patient was assigned a nurse, offered annual advance care planning dialogues, and ad hoc pulmonary specialist visits.,The aim of this study was to explore COPD patients’ experiences with a new and altered palliative organization.,The design was interpretive description as described by Thorne.,We conducted ten semi-structured interviews with patients with severe COPD from January 2017 to December 2017.,Patients described how the professional relationship and the availability of their nurse was considered as the most important and positive change.,It made the patients feel safe, in control, and subsequently influenced their ability to self-manage their life and prevent being hospitalized.,The patients did not emphasize the advanced care planning dialogues as something special or troublesome.,We showed that it is relevant and meaningful to establish a structure that supports professional relationships between patient, nurse and physician based on patients needs.,The new way of structuring the outpatient care was highly appreciated by COPD patients and made them feel safe which brought confidence in self-management abilities.,The online version of this article (10.1186/s12904-019-0410-0) contains supplementary material, which is available to authorized users.

Chronic obstructive pulmonary disease and lung cancer are leading causes of death with comparable symptoms at the end of life.,Cross-national comparisons of place of death, as an important outcome of terminal care, between people dying from chronic obstructive pulmonary disease and lung cancer have not been studied before.,We collected population death certificate data from 14 countries (year: 2008), covering place of death, underlying cause of death, and demographic information.,We included patients dying from lung cancer or chronic obstructive pulmonary disease and used descriptive statistics and multivariable logistic regressions to describe patterns in place of death.,Of 5,568,827 deaths, 5.8% were from lung cancer and 4.4% from chronic obstructive pulmonary disease.,Among lung cancer decedents, home deaths ranged from 12.5% in South Korea to 57.1% in Mexico, while hospital deaths ranged from 27.5% in New Zealand to 77.4% in France.,In chronic obstructive pulmonary disease patients, the proportion dying at home ranged from 10.4% in Canada to 55.4% in Mexico, while hospital deaths ranged from 41.8% in Mexico to 78.9% in South Korea.,Controlling for age, sex, and marital status, patients with chronic obstructive pulmonary disease were significantly less likely die at home rather than in hospital in nine countries.,Our study found in almost all countries that those dying from chronic obstructive pulmonary disease as compared with those from lung cancer are less likely to die at home and at a palliative care institution and more likely to die in a hospital or a nursing home.,This might be due to less predictable disease trajectories and prognosis of death in chronic obstructive pulmonary disease.,Structured palliative care similar to that offered to cancer sufferers should be in place for patients with chronic lung disease.,Joachim Cohen at Vrije University in Brussels and co-workers examined international death certificate data collected from 14 countries to determine place of death for patients with lung cancer and chronic obstructive pulmonary disease (COPD).,While patients with COPD suffer similar symptoms to lung cancer in their final days, few COPD patients receive palliative care or achieve the common wish of dying at home.,This may be partly due to the inherent unpredictability of final-stage COPD compared with lung cancer.,Cohen’s team found that, with the exception of Italy, Spain, and Mexico, patients with COPD were significantly more likely to die in hospital than at home.,They highlight the need for improved COPD palliative care provision.

This study aimed to measure the true burden of COPD by calculating incremental direct and indirect costs.,Direct medical resource use, productivity metrics, and COPD-specific resource use and costs were also evaluated.,This was a retrospective, observational, matched cohort study using administrative claims data from the Truven Health MarketScan® Commercial Claims and Encounters and the Health and Productivity Management databases (2007-2010).,Working-age (18-65 years) patients with COPD were identified as having at least one hospitalization or one emergency department visit or two outpatient visits.,Patients in the non-COPD cohort did not have a diagnosis of COPD during the study period.,Outcomes were evaluated in the first full calendar year after the year of identification (index).,Of the 5,701 patients with COPD identified, 3.6% patients were frequent exacerbators (≥2), 10.4% patients were infrequent exacerbators (1), and 86% patients were non-exacerbators (0).,When compared with the 17,103 patients without COPD, the incremental direct cost of COPD was estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623; P<0.001).,Loss in productivity was significantly greater in patients with COPD, with an average of 5 more days/year of absence from work and incremental indirect costs from short-term disability of $641 (P<0.001).,Direct costs for frequent exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were significantly higher than those for non-exacerbators ($11,395, P<0.001).,Working-age patients with COPD incur statistically significantly higher direct and indirect costs and use more resources compared with those who do not have COPD.

Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services.

Background and objective: Viruses are important aetiological agents of acute exacerbation of COPD (AECOPD).,Their reported prevalence varies from region to region.,This systematic review calculated the prevalence of respiratory viral infections in AECOPD.,Methods: A systematic search was performed using Medline, and references of relevant articles and conference proceedings were hand searched.,Articles for review were selected based on the following criteria: (i) prospective or cross‐sectional study, (ii) original research, (iii) viral detection used the highly sensitive techniques of PCR and/or Reverse Transcriptase PCR (RT‐PCR), (iv) viral prevalence in AECOPD defined, and (v) full paper available in English.,We assessed the study quality and extracted data independently and in duplicate using a pre‐defined data extraction form.,Weighted mean prevalence (WMP) was calculated and a forest plot was constructed to show the dispersion.,Results: Eight studies met the inclusion criteria.,The WMP of respiratory viral infection in AECOPD was 34.1% (95% CI: 23.9-44.4). picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2-27.3), followed by influenza; 7.4% (95% CI: 2.9-12.0), respiratory syncytial virus; 5.3% (95% CI: 1.6-9.0), corona viruses; 3.1% (95% CI: 0.4-5.8), parainfluenza; 2.6% (95% CI: 0.4-4.8), adenovirus; 1.1% (95% CI: −1.1 to 3.3), and human metapneumovirus; 0.7% (95% CI: −0.3 to 1.8).,Maximum WMP was observed in studies from Europe followed by the USA, Australia and Asia.,Picorna was the most common virus detected in Western countries whereas influenza was most common in Asia.,Conclusions: This systematic review demonstrated that viruses are strongly associated with AECOPD, with the highest detection rates of viruses being in Europe.,The geographical epidemiology of viruses may have important therapeutic implications for management of AECOPD.,Viruses are an important cause of acute exacerbation of COPD (AECOPD).,This systematic review calculated the weighted mean prevalence (WMP) of respiratory viruses detected in patients with AECOPD.,The overall WMP was 34.1% (95% CI: 23.9‐44.4), and picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2‐27.3).

Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD).,Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors.,In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner.,Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation.,Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations.,In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation.

Protein tyrosine phosphatase 1B (PTP1B) has anti-inflammatory potential but PTP1B responses are desensitized in the lung by prolonged cigarette smoke exposure.,Here we investigate whether PTP1B expression impacts lung disease severity during respiratory syncytial viral (RSV) exacerbations of chronic obstructive pulmonary disease (COPD).,Ptp1b-/- mice infected with RSV exhibit exaggerated immune cell infiltration, damaged epithelial cell barriers, cytokine production and increased apoptosis.,Elevated expression of S100A9, a damage-associated molecular pattern molecule, was observed in the lungs of Ptp1b-/- mice during RSV infection.,Utilizing a neutralizing anti-S100A9 IgG antibody, it was determined that extracellular S100A9 signaling significantly impacts lung damage during RSV infection.,Pre-exposure to cigarette smoke desensitized PTP1B activity, which coincided with enhanced S100A9 secretion and inflammation in wild type animals during RSV infection.,S100A9 levels in human bronchoalveolar lavage fluid had an inverse relationship with lung function in healthy subjects, smokers and COPD subjects.,Fully differentiated human bronchial epithelial cells isolated from COPD donors cultured at the air liquid interface secreted more S100A9 than cells from healthy donors or smokers following RSV infection.,Together, these findings show that reduced PTP1B responses contribute to disease symptoms in part by enhancing S100A9 expression during viral-associated COPD exacerbations.

Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality.,RSV is able to evade antiviral defenses to persist in the lungs of COPD patients.,Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established.,Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice.,RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice.,This infiltration of cells was most pronounced around the vasculature and bronchial airways.,By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure.,Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression.,In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure.,RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity.,This is significant as these phosphatases counter smoke-induced inflammation and protease expression.,Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice.,Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression.

Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations.,Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.,Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.,Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg following a run-in on their COPD therapies.,Time to ACM was prespecified.,Additional vital status data collection and subsequent analyses were performed post hoc.,Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI.,For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI.,Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient’s COPD.,Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations.

We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination.

The role of the epithelial-mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke.,Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT.,CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers.,Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-β1.,CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM.,ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-β1 treatment.,CSE or TGF-β1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent.,Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.

Epithelial-mesenchymal transition (EMT) plays a crucial role in small airway fibrosis of patients with chronic obstructive pulmonary disease (COPD).,Increasing evidence suggests that the urokinase plasminogen activator receptor (uPAR) is involved in the pathogenesis of COPD.,Increased uPAR expression has been implicated in the promotion of EMT in numerous cancers; however the role of uPAR in EMT in small airway epithelial cells of patients with COPD remains unclear.,In this study, we investigated the degree of EMT and uPAR expression in lung epithelium of COPD patients, and verified the effect of uPAR on cigarette smoke extract (CSE)-induced EMT in vitro.,The expression of EMT biomarkers and uPAR was assessed in lung epithelium specimens from non-smokers (n = 25), smokers (n = 25) and non-smokers with COPD (n = 10) and smokers with COPD (n = 18).,The role of uPAR on CSE-induced EMT in human small airway epithelial cells (HSAEpiCs) was assessed by silencing uPAR expression in vitro.,Markers of active EMT and uPAR expression were significantly increased in the small airway epithelium of patients with COPD compared with controls.,We also observed a significant correlation between uPAR and vimentin expression in the small airway epithelium.,In vitro, CSE-induced EMT in HSAEpiCs was associated with high expression of uPAR, and targeted silencing of uPAR using shRNA inhibited CSE-induced EMT.,Finally, we demonstrate that the PI3K/Akt signaling pathway is required for uPAR-mediated EMT in HSAEpiCs.,A uPAR-dependent signaling pathway is required for CSE-induced EMT, which contributes to small airway fibrosis in COPD.,We propose that increased uPAR expression in the small airway epithelium of patients with COPD participates in an active EMT process.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world.,It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD.,The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected.,The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors.,In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity.,In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke.,We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress.

The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally.

Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD.,This was a multicenter, double-blind, randomized, placebo-controlled study.,Patients (aged ≥ 40 years with baseline FEV1 ≤ 65% predicted, FEV1 > 0.50 L, FEV1/FVC ≤ 70%, and ≥ 15 pack-year smoking history) received arformoterol (n = 420) or placebo (n = 421) for 1 year.,The primary assessment was time from randomization to respiratory death or first COPD exacerbation-related hospitalization.,Among 841 patients randomized, 103 had ≥ 1 primary event (9.5% vs 15.0%, for arformoterol vs placebo, respectively).,Patients who discontinued treatment for any reason (39.3% vs 49.9%, for arformoterol vs placebo, respectively) were followed for up to 1 year postrandomization to assess for primary events.,Fewer patients receiving arformoterol than placebo experienced COPD exacerbation-related hospitalizations (9.0% vs 14.3%, respectively).,Twelve patients (2.9%) receiving arformoterol and 10 patients (2.4%) receiving placebo died during the study.,Risk for first respiratory serious adverse event was 50% lower with arformoterol than placebo (P = .003).,Numerically more patients on arformoterol (13; 3.1%) than placebo (10; 2.4%) experienced cardiac serious adverse events; however, time-to-first cardiac serious adverse event was not significantly different.,Improvements in trough FEV1 and FVC were greater with arformoterol (least-squares mean change from baseline vs placebo: 0.051 L, P = .030 and 0.075 L, P = .018, respectively).,Significant improvements in quality of life (overall St.,George’s Hospital Respiratory Questionnaire and Clinical COPD Questionnaire) were observed with arformoterol vs placebo (P < .05).,Arformoterol demonstrated an approximately 40% lower risk of respiratory death or COPD exacerbation-related hospitalization over 1 year vs placebo.,Arformoterol was well-tolerated and improved lung function vs placebo.,ClinicalTrials.gov; No.: NCT00909779; URL: www.clinicaltrials.gov

Formoterol is a beta2-agonist that has both short and long acting bronchodilator effects.,Beta2-agonists used as bronchodilators have been synthesized as racemates that comprise (R,R) and (S,S)-enantiomers.,Compounds that are beta2-selective derive their bronchodilator effect from an interaction between the (R,R)-enantiomer and the beta2-adrenoceptor.,Arformoterol is the (R,R)-enantiomer and is distinguished from the more commonly used racemic (RR/S,S)-diasteriomer of formoterol.,Overall literature on the use of arformoterol in COPD is very preliminary.,There is some in vitro data that demonstrate significant bronchodilation and inhibition of inflammation with arformoterol, and these effects may be more pronounced than those caused by racemic formoterol.,There are limited clinical trial data that demonstrate that arformoterol produces significant improvement in lung function in COPD; however, many of the subjects involved had marked baseline airway reversibility.,Arformoterol has been very well tolerated in clinical trials and could potentially be used only once every 24 hours (due to its prolonged effect).,It can only be given in nebulized form.,Arformoterol can potentially be given with other inhaled medications.

Chronic Obstructive Pulmonary Disease (COPD) is currently the fifth leading cause of death in Australia, and there are marked differences in mortality trends between men and women.,In this study, we have sought to model and forecast age related changes in COPD mortality over time for men and women separately over the period 2006-2025.,Annual COPD death rates in Australia from 1922 to 2005 for age groups (50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80-84, 85+) were used.,Functional time series models of age-specific COPD mortality rates for men and women were used, and forecasts of mortality rates were modelled separately for men and women.,Functional time series models with four basis functions were fitted to each population separately.,Twenty-year forecasts were computed, and indicated an overall decline.,This decline may be slower for women than for men.,By age, we expect similar rates of decline in men over time.,In contrast, for women, forecasts for the age group 75-79 years suggest less of a decline over time compared to younger age groups.,By using a new method to predict age-specific trends in COPD mortality over time, this study provides important insights into at-risk age groups for men and women separately, which has implications for policy and program development.

Chronic obstructive pulmonary disease (COPD) remains a major public health problem that affects the quality of life of patients, however smoking cessation may emeliorate the functional effects of COPD and alter patient quality of life.,The aim of this study was to validate the Clinical COPD Questionnaire (CCQ) into Greek and with such to evaluate the quality of life in patients with different stages of COPD, as also assess their quality of life before and after smoking cessation.,The internal validity of questionnaire was high (Cronbach's a = 0.92).,The reliability of equivalent types in 16 stabilized patients also was high (ICC = 0.99).,In general the domains within the CCQ were strongly correlated with each other, while each domain in separate was strongly correlated with the overall CCQ score (r2 = 0.953, r2 = 0.915 and r2 = 0.842 in regards to the functional, symptomatic and mental domain, respectively).,The CCQ scores were also correlated with FEV1, (r2 = -0.252, p < 0.001), FEV1/FVC, (r2 = -0.135, p < 0.001) as also with the quality of life questionnaire SF-12 (r2 = -0.384, p < 0.001).,Smoking cessation also lead to a significant reduction in CCQ score and increase in the SF-12 score.,The self administered CCQ indicates satisfactory validity, reliability and responsiveness and may be used in clinical practice to assess patient quality of life.,Moreover the CCQ indicated the health related quality of life gains attributable to smoking cessation among COPD patients, projecting smoking cessation as a key target in COPD patient management.

There are few publications on quality measurement of COPD health state according to the severity level using EQ-5D in Korea.,The present study aimed to evaluate the health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD) in terms of disease severity in Korea.,Totally two hundred patients with COPD were consecutively recruited in one tertiary hospital of Korea.,Each respondent was asked to fill out the questionnaire through a face-to-face interview after providing informed consent.,The questionnaire included general and clinical characteristics as well as the EQ-5D and Clinical COPD Questionnaire (CCQ).,HRQoL was evaluated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and severity of breathlessness.,The adjusted mean EQ-5D index scores were 0.83, 0.88, 0.81 and 0.60 in stage I, II, III and IV, respectively.,The EQ-5D index tended to decrease with GOLD criteria.,The adjusted mean EQ-Visual Analog Scale (VAS) scores ranged from 65.1 in stage IV to 73.9 in stage I.,The CCQ total scores deteriorated with an increasing GOLD stage and severity of breathlessness (all P < 0.001).,The correlation between CCQ total score and EQ-5D index was −0.69.,Our study shows that HRQoL in COPD measured by EQ-5D and CCQ worsens with the GOLD stage and severity of breathlessness.,EQ-5D and CCQ could be useful instruments for an evaluation of HRQoL in COPD patients in Korea.

Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations.,However, it is unclear if forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differ in predictive value.,Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed.,Patients were grouped into quintiles for each lung function parameter (FEV1 %predicted, FVC %predicted, FEV1/FVC).,The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations.,Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.,Compared to Q1 (<53.5% FEV1 predicted), increasing FEV1 quintiles (Q2 53.5-457.5% predicted, Q3 57.5-461.6% predicted, Q4 61.6-465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-40%), 23% (7-36%), and 30% (15-42%) risk reduction, respectively).,In contrast, a significant risk reduction (21% (4-35%)) was seen only between Q1 and Q5 quintiles of FVC.,Neither FEV1 nor FVC was associated with cardiovascular risk.,Increased FEV1 and FEV1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase).,Our results suggest that FEV1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization and is associated with considerable mortality, for which clinicians are seeking useful and easily obtained biomarkers for prognostic evaluation.,This study aimed to determine the potential role of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as prognostic makers for hospital mortality in patients with AECOPD.,We included 303 patients with AECOPD in this retrospective study.,Clinical characteristics, NLR, PLR, and serum levels of C-reactive protein (CRP) and other data were collected.,Relationships between NLR/PLR and CRP were evaluated by Pearson’s correlation test.,Receiver operating characteristics curve and the area under the curve (AUC) were used to assess the ability of NLR and PLR to predict hospital mortality in patients with AECOPD.,Mean levels of NLR and PLR of all patients with AECOPD were 7.92±8.79 and 207.21±148.47, respectively.,NLR levels correlated with serum CRP levels (r=0.281, P<0.05).,The overall hospital mortality rate was 12.21% (37/303).,Levels of NLR and PLR were signifi-cantly higher among non-survivors compared to survivors of AECOPD (both P<0.05).,At a cut-off value of 6.24, the sensitivity and specificity of the NLR in predicting hospital mortality were 81.08% and 69.17%, respectively, with an AUC of 0.803.,At a cut-off of 182.68, the corresponding sensitivity, specificity and AUC of PLR were 64.86%, 58.27%, and 0.639.,The combination of NLR, PLR, and CRP increased the prognostic sensitivity.,NLR and PLR levels were increased in non-survivor patients with AECOPD, and the NLR may be simple and useful prognostic marker for hospital mortality in patients with AECOPD.,More studies should be carried out to confirm our findings.

Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD.,Traditional CV risk scores have been tested in different populations but not uniquely in COPD.,The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown.,We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.,Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used.,Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.,Five UK centres interested in COPD.,Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.,Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.,New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.,Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD.,The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction.,CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all).,However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).,Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.,ID 11101.

Studies have suggested that chronic obstructive pulmonary disease (COPD) is commonly misdiagnosed and misclassified in primary care, but less is known about the quality of diagnosis in specialist respiratory care.,To measure the accuracy of COPD diagnosis and classification of airway obstruction in primary care and at a specialist respiratory centre, and to explore associations between misdiagnosis and misclassification and a range of explanatory factors.,Data were obtained for 1,205 referrals to a specialist respiratory centre between 2007 and 2010.,Standard analysis methods were used.,The majority of patients were referred for pulmonary rehabilitation (676/1,205, 56%).,Of 1,044 patients with a primary care diagnosis of COPD, 211 (20%) had spirometry inconsistent with COPD.,In comparison, of 993 specialist centre diagnoses, 65 (6.5%) had inconsistent spirometry.,There was poor agreement between the airflow obstruction grade recorded on the referral and that based on spirometry (kappa=0.26, n=448), whereas agreement between the respiratory centre assessment of airflow obstruction and spirometry was good (kappa=0.88, n=1,016).,Referral by practice nurse was associated with accuracy of airflow obstruction classification in primary care (OR 1.85, 95% CI 1.33 to 2.57).,Males were more likely than females to have an accurate specialist care classification of airway obstruction (OR 1.40, 95% CI 1.01 to 1.93).,Grade of airway obstruction changed between referral and assessment in 56% of cases.,In primary care, a proportion of patients diagnosed with COPD do not have COPD, and misclassification of grade of airflow obstruction is common.,Misdiagnosis and misclassification is less common in the specialist care setting of BreathingSpace.

Short-term exposure to major air pollutants (O3, CO, NO2, SO2, PM10, and PM2.5) has been associated with respiratory risk.,However, evidence on the risk of chronic obstructive pulmonary disease (COPD) exacerbations is still limited.,The present study aimed at evaluating the associations between short-term exposure to major air pollutants and the risk of COPD exacerbations.,After a systematic search up until March 30, 2016, in both English and Chinese electronic databases such as PubMed, EMBASE, and CNKI, the pooled relative risks and 95% confidence intervals were estimated by using the random-effects model.,In addition, the population-attributable fractions (PAFs) were also calculated, and a subgroup analysis was conducted.,Heterogeneity was assessed by I2.,In total, 59 studies were included.,In the single-pollutant model, the risks of COPD were calculated by each 10 μg/m3 increase in pollutant concentrations, with the exception of CO (100 μg/m3).,There was a significant association between short-term exposure and COPD exacerbation risk for all the gaseous and particulate pollutants.,The associations were strongest at lag0 and lag3 for gaseous and particulate air pollutants, respectively.,The subgroup analysis not only further confirmed the overall adverse effects but also reduced the heterogeneities obviously.,When 100% exposure was assumed, PAFs ranged from 0.60% to 4.31%, depending on the pollutants.,The adverse health effects of SO2 and NO2 exposure were more significant in low-/middle-income countries than in high-income countries: SO2, relative risk: 1.012 (95% confidence interval: 1.001, 1.023); and NO2, relative risk: 1.019 (95% confidence interval: 1.014, 1.024).,Short-term exposure to air pollutants increases the burden of risk of COPD acute exacerbations significantly.,Controlling ambient air pollution would provide benefits to COPD patients.

Rhinovirus (RV) is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations, and primarily infects bronchial epithelial cells.,Immune responses from BECs to RV infection are critical in limiting viral replication, and remain unclear in COPD.,The objective of this study is to investigate innate immune responses to RV infection in COPD primary BECs (pBECs) in comparison to healthy controls.,Primary bronchial epithelial cells (pBECs) from subjects with COPD and healthy controls were infected with RV-1B.,Cells and cell supernatant were collected and analysed using gene expression microarray, qPCR, ELISA, flow cytometry and titration assay for viral replication.,COPD pBECs responded to RV-1B infection with an increased expression of antiviral and pro-inflammatory genes compared to healthy pBECs, including cytokines, chemokines, RNA helicases, and interferons (IFNs).,Similar levels of viral replication were observed in both disease groups; however COPD pBECs were highly susceptible to apoptosis.,COPD pBECs differed at baseline in the expression of 9 genes, including calgranulins S100A8/A9, and 22 genes after RV-1B infection including the signalling proteins pellino-1 and interleukin-1 receptor associated kinase 2.,In COPD, IFN-β/λ1 pre-treatment did not change MDA-5/RIG-I and IFN-β expression, but resulted in higher levels IFN-λ1, CXCL-10 and CCL-5.,This led to reduced viral replication, but did not increase pro-inflammatory cytokines.,COPD pBECs elicit an exaggerated pro-inflammatory and antiviral response to RV-1B infection, without changing viral replication.,IFN pre-treatment reduced viral replication.,This study identified novel genes and pathways involved in potentiating the inflammatory response to RV in COPD.

Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users.

A combination of inhaled corticosteroid and long-acting beta2 agonist (ICS/LABA) is used frequently to treat chronic obstructive pulmonary disease (COPD) patients.,The aim of the study was to determine whether prescribing ICS/LABA to COPD patients in primary care in 2009/10 was within the GOLD guidelines and whether and to what degree patient characteristics were associated with prescription of these drugs by GPs.,This was a cross-sectional study in seven Norwegian GP practices.,Patients registered with a diagnosis of asthma or COPD in the previous five years were included.,Among the 376 patients included in the analysis, 149 patients had COPD, defined as a post-bronchodilator FEV1/FVC <0.7 and 55.6% of these patients were treated with ICS/LABA.,The rate of prescribing was significantly higher in the COPD patients also diagnosed with asthma than in those with COPD as the only diagnosis, 66.7%, and 39.0%, respectively (P = 0.001).,The prescribing rate in the latter subgroup would have been 18.6% if the 2007 GOLD guidelines had been followed.,One or more exacerbations in the previous year was the strongest predictor of ICS/LABA prescribing in the COPD patients who were not registered with a concomitant diagnosis of asthma (OR 3.2, 95% CI 1.0-10.0) but this association was limited to the patients with severe disease (FEV1% predicted <50) (OR 13.5, 95% CI 1.8-101.1).,Cardiovascular disease was associated with decreased ICS/LABA prescribing (OR 0.4, 95% CI 0.2-0.8) in the COPD group.,A Kappa coefficient of 0.32 was found between the actual prescribing rate and that recommended in the 2007 GOLD guidelines.,Overprescribing of ICS/LABA for the COPD patients was shown.,Previous exacerbation was a strong predictor of ICS/LABA prescribing only in patients with severe COPD.,Because of the low emphasis on previous exacerbation when prescribing for COPD patients with mild to moderate disease, the actual prescribing rate agreed more closely with the GOLD guidelines from 2007 than with those published in 2011.,Cardiovascular disease was associated with decreased prescribing, indicating that GPs adjust the treatment in cases with multimorbidity.

Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.

Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.

Lung cancer has been the most common death causing cancer in the world for several decades.,This study is focused on the metabolite profiling of plasma from lung cancer (LC) patients with three control groups including healthy non-smoker (NS), smokers (S) and chronic obstructive pulmonary disease patients (COPD) samples using gas chromatography-mass spectrometry (GC-MS) in order to identify the comparative and distinguishing metabolite pattern for lung cancer.,Metabolites obtained were identified through National Institute of Standards and Technology (NIST) mass spectral (Wiley registry) and Fiehn Retention Time Lock (RTL) libraries.,Mass Profiler Professional (MPP) Software was used for the alignment and for all the statistical analysis. 32 out of 1,877 aligned metabolites were significantly distinguished among three controls and lung cancer using p-value ≤ 0.001.,Partial Least Square Discriminant Analysis (PLSDA) model was generated using statistically significant metabolites which on external validation provide high sensitivity (100%) and specificity (78.6%).,Elevated level of fatty acids, glucose and acids were observed in lung cancer in comparison with control groups apparently due to enhanced glycolysis, gluconeogenesis, lipogenesis and acidosis, indicating the metabolic signature for lung cancer.

Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required.

Patients with COPD experience exacerbations that may require hospitalization.,Patients do not always feel supported upon discharge and frequently get readmitted.,A Self-management Program of Activity, Coping, and Education for COPD (SPACE for COPD), a brief self-management program, may help address this issue.,To investigate if SPACE for COPD employed upon hospital discharge would reduce readmission rates at 3 months, compared with usual care.,This is a prospective, single-blinded, two-center trial (ISRCTN84599369) with participants admitted for an exacerbation, randomized to usual care or SPACE for COPD.,Measures, including health-related quality of life and exercise capacity, were taken at baseline (hospital discharge) and at 3 months.,The primary outcome measure was respiratory readmission at 3 months.,Seventy-eight patients were recruited (n=39 to both groups).,No differences were found in readmission rates or mortality at 3 months between the groups.,Ten control patients were readmitted within 30 days compared to five patients in the intervention group (P>0.05).,Both groups significantly improved their exercise tolerance and Chronic Respiratory Questionnaire (CRQ-SR) results, with between-group differences approaching statistical significance for CRQ-dyspnea and CRQ-emotion, in favor of the intervention.,The “Ready for Home” survey revealed that patients receiving the intervention reported feeling better able to arrange their life to cope with COPD, knew when to seek help about feeling unwell, and more often took their medications as prescribed, compared to usual care (P<0.05).,SPACE for COPD did not reduce readmission rates at 3 months above that of usual care.,However, encouraging results were seen in secondary outcomes for those receiving the intervention.,Importantly, SPACE for COPD appears to be safe and may help prevent readmission with 30 days.

Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs.,No systematic review has examined the effectiveness of interventions designed to improve medication adherence.,Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords.,Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English.,Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria.,Of the 1,186 papers identified, seven studies met inclusion criteria.,Methodological quality of the studies was variable.,Five studies identified effective interventions.,Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams.,Further research is needed to establish the most effective and cost effective interventions.,Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations.,Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored.

Chronic obstructive pulmonary disease (COPD) patients present a high prevalence of cardiovascular disease.,This excess of comorbidity could be related to a common pathogenic mechanism, but it could also be explained by the existence of common risk factors.,The objective of this study was to determine whether COPD patients present greater cardiovascular comorbidity than control subjects and whether COPD can be considered a risk factor per se.,1200 COPD patients and 300 control subjects were recruited for this multicenter, cross-sectional, case-control study.,Compared with the control group, the COPD group showed a significantly higher prevalence of ischemic heart disease (12.5% versus 4.7%; P < 0.0001), cerebrovascular disease (10% versus 2%; P < 0.0001), and peripheral vascular disease (16.4% versus 4.1%; P < 0.001).,In the univariate risk analysis, COPD, hypertension, diabetes, obesity, and dyslipidemia were risk factors for ischemic heart disease.,In the multivariate analysis adjusted for the remaining factors, COPD was still an independent risk factor (odds ratio: 2.23; 95% confidence interval: 1.18-4.24; P = 0.014).,COPD patients show a high prevalence of cardiovascular disease, higher than expected given their age and the coexistence of classic cardiovascular risk factors.

Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy.

The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation.,The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD.,Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited.,Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses.,A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected.,The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%).,A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients.,Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population.,In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population.,The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.

The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.

It is extremely important to objectively take a view of population health to provide useful information to decision makers, health-sector leaders, researchers, and informed citizens.,This study aims to examine the burden of disease in Korea as of 2015, and to study how the burden of disease changes with the passage of time.,We used results from the Korean National Burden of Disease and Injuries Study 2015 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive disability-adjusted life years (DALYs) by gender and age groups from 2007 to 2015.,DALYs were calculated as the sum of the years of life lost (YLLs) and the years lived with disability (YLDs).,In 2015, the burden of disease for Korean people was calculated at 29,476 DALYs per 100,000 population.,DALYs caused by low back pain were the highest, followed by diabetes mellitus and chronic obstructive pulmonary disease.,The burden of disease showed a consistently increasing trend from 2007 to 2015.,Although YLLs have been on the decrease since 2011, the increase in YLDs has contributed to the overall rise in DALYs.,The DALYs per 100,000 population in 2015 increased by 28.1% compared to 2007.,As for the diseases for which the burden of disease is substantially increasing, it is needed to establish appropriate policies in a timely manner.,The results of this study are expected to be the basis for prioritizing public health and health care policies in Korea.

Early diagnosis of chronic obstructive pulmonary disease (COPD) in primary care settings is difficult to achieve chiefly due to lack of availability of spirometry.,This study estimated the prevalence of airflow limitation among chronic smokers using a handheld spirometer in this setting.,This is a cross-sectional study performed on consecutive patients who were ≥40 years old with ≥10 pack-years smoking history.,Face-to-face interviews were carried out to obtain demographic data and relevant information.,Handheld spirometry was performed according to a standard protocol using the COPd-6 device (Model 4000, Vitalograph, Ennis, Ireland) in addition to standard spirometry.,Airflow limitation was defined as ratio of forced expiratory volume in 1 s (FEV1)/forced expiratory volume in 6 s <0.75 (COPd-6) or FEV1/forced vital capacity <0.7.,Multiple logistic regression analyses were used to determine predictors of airflow limitation.,A total of 416 patients were recruited with mean age of 53 years old.,The prevalence of airflow limitation was 10.6% (n = 44) with COPd-6 versus 6% as gauged using standard spirometry.,Risk factors for airflow limitation were age >65 years (odds ratio (OR) 3.732 95% confidence interval (CI): 1.100-1.280), a history of ‘bad health’ (OR 2.524, 95% CI: 1.037-6.142) and low to normal body mass index (OR 2.914, 95% CI: 1.191-7.190).,In a primary care setting, handheld spirometry (COPd-6) found a prevalence of airflow limitation of ∼10% in smokers.,Patients were older, not overweight and had an ill-defined history of health problems.,Prevalence of COPD is unknown in Malaysia.,The prevalence of COPD using a handheld spirometer (COPd-6TM) was 10.6% versus 6% as gauged using standard spirometry.,Predictors of COPD were older age, lower BMI and a history of ‘bad health’.,Case-finding for COPD should be targeted in this special population.

Is the neutrophil to lymphocyte ratio (NLR) associated with lung function decline and chronic obstructive pulmonary disease risk at the population level?,This cohort study of 1549 US veterans with more than 30 years of follow-up found that higher NLR was associated with lower lung function and higher chronic obstructive pulmonary disease risk.,Additionally, NLR was associated with AHRR hypomethylation, the top DNA methylation signature of lung function changes, which may mediate the adverse association of NLR-related inflammation with lung function.,These findings suggest that NLR may be a useful, readily obtainable, and inexpensive tool to identify people with high risks of lung function impairment and chronic obstructive pulmonary disease.,This cohort study examines the associations of neutrophil to lymphocyte ratio with lung function and risk of chronic obstructive pulmonary disease among US veterans with up to 30 years of follow-up.,Chronic obstructive pulmonary disease (COPD) is a critical public health burden.,The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood.,To explore the associations of NLR with lung function decline and COPD risks.,This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking.,This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018.,A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD.,Data were analyzed from September 2019 to January 2020.,The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit.,The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits.,The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria.,Both outcomes were measured as each visit.,Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF.,Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function.,Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline.,Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function.,These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization and is associated with considerable mortality, for which clinicians are seeking useful and easily obtained biomarkers for prognostic evaluation.,This study aimed to determine the potential role of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as prognostic makers for hospital mortality in patients with AECOPD.,We included 303 patients with AECOPD in this retrospective study.,Clinical characteristics, NLR, PLR, and serum levels of C-reactive protein (CRP) and other data were collected.,Relationships between NLR/PLR and CRP were evaluated by Pearson’s correlation test.,Receiver operating characteristics curve and the area under the curve (AUC) were used to assess the ability of NLR and PLR to predict hospital mortality in patients with AECOPD.,Mean levels of NLR and PLR of all patients with AECOPD were 7.92±8.79 and 207.21±148.47, respectively.,NLR levels correlated with serum CRP levels (r=0.281, P<0.05).,The overall hospital mortality rate was 12.21% (37/303).,Levels of NLR and PLR were signifi-cantly higher among non-survivors compared to survivors of AECOPD (both P<0.05).,At a cut-off value of 6.24, the sensitivity and specificity of the NLR in predicting hospital mortality were 81.08% and 69.17%, respectively, with an AUC of 0.803.,At a cut-off of 182.68, the corresponding sensitivity, specificity and AUC of PLR were 64.86%, 58.27%, and 0.639.,The combination of NLR, PLR, and CRP increased the prognostic sensitivity.,NLR and PLR levels were increased in non-survivor patients with AECOPD, and the NLR may be simple and useful prognostic marker for hospital mortality in patients with AECOPD.,More studies should be carried out to confirm our findings.

The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes.,FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations.,In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50 μg once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use.,This post-hoc analysis included 2557 men and 805 women.,Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ≥2 exacerbations in the previous year.,Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73-0.91], 0.89 [0.74-1.07] in men and women, respectively).,Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70-0.89] and 0.76 [0.63-0.91] in men and women, respectively).,Results were similar for all (mild/moderate/severe) exacerbations.,Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women.,The smaller sample size for women may account for some observed discrepancies in treatment responses.,Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC.,Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis.,Post hoc analysis of the FLAME study.,ClinicalTrials.gov number: NCT01782326.,Registered 1 February 2013.

Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men.,Whether female adult smokers are biologically more susceptible to COPD is unknown.,This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.,A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.,Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants).,There was heterogeneity in gender-related results across the studies.,However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers.,Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008).,Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).,As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers.,Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings.

Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.,Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.,Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.,Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.,Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.,Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each.,In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up.,Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively.,The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6).,The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003).,All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).,Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.,Trial registration Clinical Trials.gov NCT01146392.

Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes.,Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes.,To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations.,In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV1 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation.,Sputum total cell counts (9.0 versus 7.9 × 106/mL), eosinophils (0.3 versus 0.2 × 106/mL), neutrophils (6.1 versus 5.8 × 106/mL), and lymphocytes (0.07 versus 0.02 × 106/mL) increased significantly during an exacerbation compared to stable disease.,A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation.,These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-α (TNF-α) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection.,Sputum TNF-α level during an exacerbation had the best test characteristics to predict a bacterial infection.,Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations.,The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways.,Sputum TNF-α is a candidate marker for predicting airway bacterial infection.

Exercise intolerance is a major issue affecting many people with COPD.,Six-minute walking distance (6MWD) is a widely used indicator of exercise capacity in patients with COPD.,The process is strenuous and time-consuming, especially for patients who have muscle wasting.,Anthropometric indicators that reflect body lean mass, such as body mass index (BMI), mid-arm circumference (MAC), and calf circumference (CC), may have value in predicting exercise intolerance.,This study attempted to determine the abilities of simple anthropometric indicators including BMI, MAC, and CC in reflecting the exercise intolerance of COPD patients.,We recruited 136 nonhospitalized ambulatory COPD patients without acute conditions from a general hospital in Taiwan.,Each subject’s BMI, MAC, and CC were measured, and they were examined with pulmonary function tests and a 6-minute walk test.,Among the three anthropometric indicators examined, CC showed the strongest correlation with the 6MWD, followed by MAC and BMI.,CC was also strongly associated with functional capacity, followed by MAC, according to the receiver operating characteristic curves.,CC and MAC, but not BMI, were significantly associated with exercise intolerance according to logistic regression models that controlled for potential confounders.,Among the three variables examined, CC and walking distance may have the strongest association in COPD patients.,CC may have value in serving as an adjunct to 6MWD in evaluating exercise intolerance of patients with COPD.

Chronic obstructive pulmonary disease (COPD) is a disease associated with dyspnea, fatigue, and exercise intolerance.,The degree of functional debility and level of exercise capacity greatly influences quality of life and mortality in patients with COPD, and the measures of exercise capacity are to be an integral part of patient assessment but often not feasible in routine daily practice, resulting in likely suboptimal care.,There is a need for simple ways to identify functional decline in the clinical setting in order to guide resources to preventive interventions or proper care, including palliative care.,Gait speed, or measuring how long it takes for a patient to walk a short distance, takes very little time and space, and can serve as a candidate measure of physical function in COPD.,Gait speed has been shown to be an indicator of disability, health care utilization, and survival in older adults.,It is a simple, reliable, and feasible measure to perform in the clinic and has been promoted as the next vital sign, providing insight into patients’ functional capacity.,Gait speed is mainly determined by exercise capacity but reflects global well-being as it captures many of the multisystemic effects of disease severity in COPD rather than pulmonary impairment alone.,It is an excellent screening measure for exercise capacity and frailty; in COPD, the usual gait speed (4-m course with rolling start) has been very accurate in identifying clinically relevant benchmarks of the 6-minute walk test, poor (<350 m) and very poor (<200 m) 6-minute walk test distances.,A specific cut-off point of 0.8 m · s−1 had a positive predictive value of 69% and negative predictive value of 98% in predicting very poor exercise capacity.,The increasing evidence on gait speed is promising as a simple test that can inform the clinician about many important functional aspects of the COPD patient.,Further work will likely show the strength of gait speed as a predictive marker of hospitalizations, re-admissions, and mortality.,Instead of relying on the “eyeball test” regarding the patient’s frailty or exercise capacity, a gait speed in its simplicity represents a much more solid assessment.,Furthermore, repeat measures over serial clinic visits may show a pattern and further guide a change in therapy, whether it be medications, rehabilitation, or even initiation of palliative care discussions.

COPD is a common disease of the respiratory system.,Inflammation, cellular senescence and necroptosis are all pathological alterations of this disease, which may lead to emphysema and infection that aggravate disease progression.,Mitochondria acting as respiration-related organelles is usually observed with abnormal changes in morphology and function in CS-stimulated models and COPD patients.,Damaged mitochondria can activate mitophagy, a vital mechanism for mitochondrial quality control, whereas under the persistent stimulus of CS or other forms of oxidative stress, mitophagy is impaired, resulting in insufficient clearance of damaged mitochondria.,However, the excessive activation of mitophagy also seems to disturb the pathology of COPD.,In this review, we demonstrate the variations in mitochondria and mitophagy in CS-induced models and COPD patients and discuss the underlying regulatory mechanism of mitophagy and COPD, including the roles of inflammation, senescence, emphysema and infection.

Chronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality.,Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD.,The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival.,This was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE.,Plasma cfDNA levels of COPDE patients were compared to those of matched stable COPD patients and healthy controls.,Multivariable and Cox regression analyses were used to assess the association of cfDNA levels with blood gas parameters and long-term survival.,A total of 62 patients (46 males, forced expiratory volume in 1 second [FEV1] 38%±13%) were included.,The median cfDNA levels on admission for COPDE patients was 1,634 ng/mL (interquartile range [IQR] 1,016-2,319) compared to 781 ng/mL (IQR 523-855) for stable COPD patients, matched for age and disease severity, and 352 ng/mL (IQR 209-636) for healthy controls (P<0.0001, for both comparisons). cfDNA was correlated with partial arterial pressure of carbon dioxide (PaCO2, r=0.35) and pH (r=−0.35), P=0.01 for both comparisons.,In a multivariable analysis, PaCO2 was the only independent predictor of cfDNA.,Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO2), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV1% (hazard ratio 1.92, 95% confidence interval 0.93-3.95, P=0.08).,Plasma cfDNA might offer a novel technique to identify COPD patients at increased risk of poor outcomes, but the prognostic utility of this measurement requires further study.

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder partially resistant to glucocorticoids.,A reduced histone deacetylase (HDAC) activity has been proposed to explain this resistance.,Haemophilus influenzae frequently colonizes the airways of COPD patients, where it enhances inflammation.,The effects of Haemophilus influenzae on HDAC activity have not been investigated before.,The effects of the presence or absence of Haemophilus influenzae ex-vivo and in vitro were studied.,To this end, we determined: (1) cytokine release in alveolar macrophages (AM) from 7 patients with COPD, 5 healthy smokers, 6 healthy non-smokers and (2) HDAC activity, nuclear factor kappa B (NF-κB) activation in a macrophage-like cell line (PMA-transformed U937 cells) co-cultured with epithelial cells.,Experiments were repeated with dexamethasone (1 μM) and/or the HDAC enhancer theophylline (10 μM).,Haemophilus influenzae induced a steroid-resistant inflammatory response in AM from COPD and controls and decreased HDAC activity, activated NF-κB and induced the secretion of several cytokines (IL-6, IL-8, IL-1β, IL-10 and TNF-α) (p < 0.001 for all comparisons) in the macrophage-like cell line.,Dexamethasone reduced NF-κB activation but it did not modify HDAC activity.,The addition of theophylline to dexamethasone increased HDAC activity and suppressed cytokine release completely, without modifying NF-κB activation.,These results indicate that Haemophilus influenzae reduces HDAC activity and induces a NF-κB mediated inflammatory response that is only partially suppressed by glucocorticoids irrespective of having COPD.,Yet, the latter can be fully restored by targeting HDAC activity.,The online version of this article (doi:10.1186/s12890-015-0155-3) contains supplementary material, which is available to authorized users.

There is large variation in the therapeutic response to inhaled corticosteroids (ICS) in COPD patients.,We present a pooled analysis of our previous studies investigating the effects of corticosteroids on lung macrophages, in order to robustly determine whether corticosteroid sensitivity in COPD cells is reduced compared to controls, and also to evaluate the degree of between individual variation in drug response.,Data from 20 never smokers (NS), 27 smokers (S) and 45 COPD patients was used.,Lung macropahges had been stimulated with lipopolysaccharide (LPS), with or without the corticosteroid dexamethasone, and tumour necrosis factor (TNF)-α, interleukin (IL)-6 and chemokine C-X-C motif ligand (CXCL) 8 production was measured.,There was no difference in the anti-inflammatory effects of corticosteroids when comparing group mean data of COPD patients versus controls.,The inhibition of TNF-α and IL-6 was greater than CXCL8.,The effects of corticosteroids varied considerably between subjects, particularly at lower corticosteroid concentrations.,We confirm that overall corticosteroid sensitivity in COPD lung macrophages is not reduced compared to controls.,The varied effect of corticosteroids between subjects suggests that some individuals have an inherently poor corticosteroid response.,The limited suppression of lung macrophage derived CXCL8 may promote neutrophilic inflammation in COPD.,The online version of this article (doi:10.1186/s12931-015-0260-0) contains supplementary material, which is available to authorized users.

Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases.,Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids.,Biologicals targeting the Th2-eosinophil nexus such as anti-interleukin (IL)-4, anti-IL-5, and anti-IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers.,This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies.,In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients.,Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists.,Currently, several other novel mediator-targeted drugs are undergoing clinical trials.,As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes.,The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients.

There are limited data on the risk of pulmonary disease in patients with diabetes.,The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes.,We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California.,Age and sex data were available for all cohort members (n = 1,811,228).,Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit.,Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort.,No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes.,These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio [HR] 1.08 [95% CI 1.03-1.12], COPD HR 1.22 [1.15-1.28], pulmonary fibrosis HR 1.54 [1.31-1.81], and pneumonia HR 1.92 [1.84-1.99]).,The risk of pneumonia and COPD increased significantly with increasing A1C.,Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer.,This increased risk may be a consequence of declining lung function in patients with diabetes.

This report updates surveillance results for COPD in the United States.,For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed.,In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD.,From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019).,In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD.,From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001).,In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD.,Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033).,There were 133,575 deaths (63.1 per 100,000) from COPD in 2010.,The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163).,Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001).,Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed.,Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States.

The American Lung Association of Minnesota (ALAMN) was granted access to a 2004 administrative claims data from an upper mid-Western, independent practice association model health plan.,Claims information, including demographics, prevalence, medication and oxygen therapy, and health care utilization, was extracted for 7,782 patients with COPD who were 40 years of age and older.,In addition, ALAMN conducted a survey of 1,911 patients from Minnesota diagnosed with COPD.,The survey queried the patients about demographics, treatment, medications, limitations, wants, and needs.,This article compares and contrasts the information gained through the health plan administrative claims database with the findings from the COPD patient survey in areas of age, gender, types of provider primarily responsible for COPD care, spirometry use, medication therapy, pulmonary rehabilitation, oxygen therapy, and health care utilization.,Primary care practitioners provided a majority of the COPD-related care.,The claims evidence of spirometry use was 16%-62% of COPD patients had claims evidence of COPD-related medications. 25% of patients reported, and 23% of patients had claims evidence of, a hospitalization during the observation year. 16% of patients reported using pulmonary rehabilitation programs.,The results indicate there is an opportunity to improve COPD diagnosis and management.

Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow obstruction and accelerated decline of forced expired volume in 1 second (FEV1).,Alpha-1-antitrypsin deficiency is a genetic cause of COPD and associated with more rapid decline in lung function, even in some never smokers (NS) but the potential for individualized assessment to reveal differences when compared to group analyses has rarely been considered.,We analyzed decline in post-bronchodilator FEV1 and gas transfer (% predicted) over at least 3 years (mean= 6.11, 95% CI 5.80-6.41) in our unique data set of 482 patients with alpha-1-antitrypsin deficiency (PiZ) to determine individual rates of decline, implications for prognosis, and potential clinical management.,There was a marked variation in individual rates of FEV1 decline from levels consistent with normal aging (observed in 23.5% of patients with established COPD, 57.5% of those without) to those of rapidly declining COPD.,Gas transfer did not decline in 12.8% of NS and 20.7% of ex-smokers with established COPD (33.3% and 25.0%, respectively, for those without COPD).,There was no correlation between decline in gas transfer and FEV1 for those with COPD, although a weak relationship existed for those without (r=0.218; P<0.025).,These data confirm differing individual rates of lung function decline in alpha-1-antitrypsin deficiency, indicating the importance of comprehensive physiological assessment and a personalized approach to patient management.

Exercise tolerance is an important parameter in patients with COPD and a primary goal of treatment is to reduce dyspnea to facilitate physical activities and improve health-related quality of life.,This review examines the link between expiratory flow limitation and dyspnea to explain the rationale for the use of bronchodilators and review the characteristics of different types of exercise tests, with specific focus on which tests are likely to show a response to bronchodilators.,An earlier literature search of studies published up to 1999 assessed the effects of bronchodilatort therapy on dypsnea and exercise tolerance among patients with COPD.,This current review examines the clinical evidence published since 1999.,Thirty-one randomized studies of exercise tolerance associated with short- and long-acting β2-agonists and anticholinergics were identified.,Evidence for the efficacy of bronchodilators in enhancing exercise capacity is often contradictory and possibly depends on the exercise test and study methodology.,However, further studies should confirm the benefit of long-acting bronchodilators in improving spontaneous everyday physical activities.

In addition to clinical comorbidities, psychological and neuropsychological problems are frequent in COPD and may affect pulmonary rehabilitation delivery and outcome.,The aims of the study were to describe a COPD population in a rehabilitative setting as regards the patients depressive symptoms, anxiety, mild cognitive impairment (MCI) and self-reported adherence and to analyze their relationships; to compare the COPD sample MCI scores with normative data; and to investigate which factors might predict adherence to prescribed physical exercise.,This was a multicenter observational cross-sectional study.,Of the 117 eligible stable COPD inpatients, 84 were enrolled according to Global initiative for chronic Obstructive Lung Disease (GOLD) criteria (mainly in Stage III-IV).,The assessment included Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), anxiety, depression and self-reported pharmacological and nonpharmacological adherence.,From the MMSE, 3.6% of patients were found to be impaired, whereas from the MoCA 9.5% had a likely MCI.,Patients referred had mild-severe depression (46.7%), anxiety (40.5%), good pharmacological adherence (80.3%) and difficulties in following prescribed diet (24.1%) and exercise (51.8%); they struggled with disease acceptance (30.9%) and disease limitations acceptance (28.6%).,Most of them received good family (89%) or social (53%) support.,Nonpharmacological adherence, depression, anxiety and MCI showed significant relations with 6-minute walking test, body mass index (BMI) and GOLD.,Depression was related to autonomous long-term oxygen therapy modifications, disease perception, family support and MCI.,In the multivariate logistic regression analysis, higher BMI, higher depression and lower anxiety predicted lower adherence to exercise prescriptions (P=0.0004, odds ratio =0.796, 95% CI =0.701, 0.903; P=0.009, odds ratio =0.356, 95% CI =0.165, 0.770; and P=0.05, odds ratio =2.361, 95% CI =0.995, 5.627 respectively).,In COPD patients, focusing on pharmacological and nonpharmacological adherence enhance the possibility of tailored pulmonary rehabilitation programs.

The role of anxiety and depression in the physical activity (PA) of patients with COPD is controversial.,We prospectively assessed the effect of symptoms of anxiety and depression on PA in COPD patients.,We evaluated anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), PA (Dynaport® accelerometer), and other relevant characteristics in 220 COPD patients from five European countries at baseline and at 6 and 12 months of follow-up.,HADS score was categorized as: no symptoms (score 0-7), suggested (8-10), and probable (>11) anxiety or depression.,We estimated the association between anxiety and depression at t (baseline and 6 months) and PA at t+1 (6 and 12 months) using regression models with a repeated measures approach.,Patients had a mean (standard deviation) age of 67 (8) years, forced expiratory volume in 1 second 57 (20)% predicted.,At baseline, the prevalence of probable anxiety and depression was 10% and 5%, respectively.,In multivariable models adjusted by confounders and previous PA, patients performed 81 fewer steps/day (95% confidence interval, −149 to −12, P=0.02) per extra point in HADS-depression score.,HADS-anxiety symptoms were not associated with PA.,In COPD patients, symptoms of depression are prospectively associated with a measurable reduction in PA 6 months later.

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es

The effects of anti-inflammatory drugs in COPD patients may vary between different cell types.,The aim of the current study was to assess the anti-inflammatory effects of the corticosteroid budesonide and a p38 MAPK inhibitor (AZD7624) on different cell types obtained from COPD patients and healthy controls.,Eight healthy smokers, 16 COPD infrequent exacerbators, and 16 frequent COPD exacerbators (≥2 exacerbations in the last year) were recruited for bronchoscopy and blood sampling.,The anti-inflammatory effects of budesonide and AZD7624 were assessed on cytokine release from lipopolysaccharide-stimulated alveolar macrophages and peripheral blood mononuclear cells and polyinosinic:polycytidylic acid-stimulated bronchial epithelial cells.,The anti-inflammatory effects of budesonide varied greatly within a patient according to the cell type studied.,Bronchial epithelial cells showed the lowest sensitivity to budesonide, while peripheral blood mononuclear cells showed the greatest sensitivity.,AZD7624 had a greater effect than budesonide on cytokine production from bronchial epithelial cells.,Exacerbation frequency did not influence corticosteroid sensitivity.,We observed variable corticosteroid and p38 MAPK inhibitor anti-inflammatory responses within the same individual depending on the cell type studied.,These findings support the use of multiple anti-inflammatory strategies in COPD patients due to differences between cell types.

The study aims at investigating the influence of several factors on the probability of receiving one of the two tiotropium formulations (Respimat or Handihaler).,Drug utilisation study.,All residents in the Region Umbria, Italy, aged ≥45 years, who received prescriptions of tiotropium during 2011-2012.,Two groups of patients were studied: (1) incident users of the two tiotropium formulations (ie, without tiotropium prescriptions in the previous 6 months); (2) switchers from Handihaler to Respimat.,Users of the two formulations were compared with regard to baseline characteristics and medical history.,The adjusted OR of receiving Respimat was estimated for several factors.,Incident users of the two formulations (4390 participants) had similar characteristics.,They were older and with more comorbidities than patients included in randomised control trials (RCTs).,Among prevalent users of Handihaler, the probability of switching to Respimat was greater in patients with severe respiratory disease (users of ≥4 respiratory drugs: adjusted OR=4.62; 95% CI 2.46 to 8.69) and among β-blocker users (adjusted OR=1.76; 95% CI 1.13 to 2.75).,Age above 75 years and lipid-lowering drug use reduced the probability of switching.,A positive association was also found between neurological conditions and the use of Respimat.,When starting tiotropium treatment, the choice between the two formulations is weakly affected by comorbidities and chronic obstructive pulmonary disease severity.,Instead, these characteristics influence the likelihood of switching from Handihaler to Respimat.,Since tiotropium users in clinical practice are more severe than those included in RCTs, further aetiological studies are needed to compare the safety profile of the two formulations in routine care.

Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven.

Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation.

This report updates surveillance results for COPD in the United States.,For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed.,In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD.,From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019).,In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD.,From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001).,In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD.,Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033).,There were 133,575 deaths (63.1 per 100,000) from COPD in 2010.,The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163).,Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001).,Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed.,Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States.

The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.,Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD.,Physician-diagnosed GERD was ascertained by questionnaire.,Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD.,We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models.,Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs).,To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.,GERD was reported by 29% of subjects with female predominance.,Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs.,13.4.0%, p < 0.0001).,Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs.,1.8, p < 0.0001), and poorer quality of life (QOL) scores (St.,George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs.,34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs.,41.4, p < 0.0001).,In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006).,During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included.,PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.,In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up.,These associations are maintained after controlling for PPI use.,The PPI-exacerbations association could result from confounding-by-indication.

► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

Conventional measures to evaluate COPD may fail to capture systemic problems, particularly musculoskeletal weakness and cardiovascular disease.,Identifying these manifestations and assessing their association with clinical outcomes (ie, mortality, exacerbation and COPD hospital admission) is of increasing clinical importance.,To assess associations between 6 min walk distance (6MWD), heart rate, fibrinogen, C reactive protein (CRP), white cell count (WCC), interleukins 6 and 8 (IL-6 and IL-8), tumour necrosis factor-alpha, quadriceps maximum voluntary contraction, sniff nasal inspiratory pressure, short physical performance battery, pulse wave velocity, carotid intima-media thickness and augmentation index and clinical outcomes in patients with stable COPD.,We systematically searched electronic databases (August 2018) and identified 61 studies, which were synthesised, including meta-analyses to estimate pooled HRs, following Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Shorter 6MWD and elevated heart rate, fibrinogen, CRP and WCC were associated with higher risk of mortality.,Pooled HRs were 0.80 (95% CI 0.73 to 0.89) per 50 m longer 6MWD, 1.10 (95% CI 1.02 to 1.18) per 10 bpm higher heart rate, 3.13 (95% CI 2.14 to 4.57) per twofold increase in fibrinogen, 1.17 (95% CI 1.06 to 1.28) per twofold increase in CRP and 2.07 (95% CI 1.29 to 3.31) per twofold increase in WCC.,Shorter 6MWD and elevated fibrinogen and CRP were associated with exacerbation, and shorter 6MWD, higher heart rate, CRP and IL-6 were associated with hospitalisation.,Few studies examined associations with musculoskeletal measures.,Findings suggest 6MWD, heart rate, CRP, fibrinogen and WCC are associated with clinical outcomes in patients with stable COPD.,Use of musculoskeletal measures to assess outcomes in patients with COPD requires further investigation.,CRD42016052075.

Low concentrations of hemoglobin have previously been demonstrated in many patients with COPD.,There is evidence of anemia as a prognostic factor in acute exacerbations, but the detailed relationship between concentrations of hemoglobin and mortality is not known.,A register-based cohort of patients admitted for the first time to Danish hospitals for acute exacerbations of COPD from 2007 through 2012 was established.,Age, sex, comorbidities, medication, renal function, and concentrations of hemoglobin were retrieved.,Sex-specific survival analyses were fitted for different rounded concentrations of hemoglobin.,The cohort encompassed 6,969 patients.,Hemoglobin below 130 g/L was present in 39% of males and below 120 g/L in 24% of females.,The in-hospital mortality rates for patients with hemoglobin below or above these limits were 11.6% and 5.4%, respectively.,After discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22-1.73), adjusted HR 1.37 (95% CI 1.15-1.64).,Compared to hemoglobin 120 g/L, the HR for females with hemoglobin 110 g/L was 1.4 (95% CI 1.17-1.68), adjusted HR 1.28 (95% CI 1.06-1.53).,In conclusion, low concentrations of hemoglobin are frequent in COPD patients with acute exacerbations, and predict long-term mortality.

Goblet cell hyperplasia is a classic but variable pathologic finding in COPD.,Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described.,We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.,We recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers.,Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue.,Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane.,Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.,Healthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects.,COPD subjects had a greater GCD than nonsmokers.,When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD.,When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD.,This finding was also seen in those with CB in the COPD group alone.,In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates.,All other covariates were not significant predictors of GCD or MVD.,Current smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction.,This provides clinical and pathologic correlation for smokers with and without COPD.

The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD) patients has been well documented, but less is known about the role played by the large airways.,Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients.,The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM) area and the extracellular matrix (ECM) protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes.,Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin.,ECM protein deposition was measured at both subepithelial, and ASM layers.,The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects.,An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity.,A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls.,These findings indicate that airway remodeling also affects the large airways in COPD patients who have greater deposition of ECM proteins in the subepithelial layer and a larger smooth muscle area than control smoker subjects.,These changes may contribute to chronic airflow obstruction in COPD patients.

The Spanish COPD guideline (GesEPOC) classifies COPD into four clinical phenotypes based on the exacerbation frequency and dominant clinical manifestations.,In this study, we compared the disease-specific health-related quality of life (HRQoL) of patients with different clinical phenotypes.,This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018.,Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George’s Respiratory Questionnaire for COPD (SGRQ-c).,Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS).,The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes (P<0.001).,Patients who were AE CB had significantly higher total CAT score than those with ACOS (P=0.033), AE NON-CB (P=0.001), and NON-AE (P<0.001).,Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB (P=0.001) and NON-AE (P<0.001).,However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS (P=0.187).,There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them.,Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components.,Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components.

COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features.,In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry.,The severity of the airflow limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management.,However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1.,At present, there is a lack of reliable and simple blood biomarkers to confirm and further assess the diagnosis of COPD.,However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes.,Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and “frequent exacerbators”.,Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as “asthma COPD overlap syndrome”.,Several other phenotypes have been proposed, but require validation against clinical outcomes.,Defining phenotypes requires the assessment of multiple factors indicating disease severity, its impact, and its activity.,Recognition and validation of COPD phenotypes has an important role to play in the selection of evidence-based targeted therapy in the future management of COPD, but regardless of the diagnostic terms, patients with COPD should be assessed and treated according to their individual treatable characteristics.

The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance.,The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments.,There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations.,A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff)/formoterol fumarate (6 µg/puff)/glycopyrronium bromide (12.5 µg/puff) has been developed as a hydrofluoroalkane pressurized metered dose inhaler.,Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation.,This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients.

Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD).,The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD.,This study was performed as a systematic literature review.,Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action.,In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status.,Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance.,Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet.,Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD.

To describe the characteristics and prognosis of patients with COPD admitted to the hospital due to SARS-CoV-2 infection.,The SEMI-COVID registry is an ongoing retrospective cohort comprising consecutive COVID-19 patients hospitalized in Spain since the beginning of the pandemic in March 2020.,Data on demographics, clinical characteristics, comorbidities, laboratory tests, radiology, treatment, and progress are collected.,Patients with COPD were selected and compared to patients without COPD.,Factors associated with a poor prognosis were analyzed.,Of the 10,420 patients included in the SEMI-COVID registry as of May 21, 2020, 746 (7.16%) had a diagnosis of COPD.,Patients with COPD are older than those without COPD (77 years vs 68 years) and more frequently male.,They have more comorbidities (hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, kidney failure) and a higher Charlson Comorbidity Index (2 vs 1, p<0.001).,The mortality rate in COPD patients was 38.3% compared to 19.2% in patients without COPD (p<0.001).,Male sex, a history of hypertension, heart failure, moderate-severe chronic kidney disease, presence of cerebrovascular disease with sequelae, degenerative neurological disease, dementia, functional dependence, and a higher Charlson Comorbidity Index have been associated with increased mortality due to COVID-19 in COPD patients.,Survival was higher among patients with COPD who were treated with hydroxychloroquine (87.1% vs 74.9%, p<0.001) and with macrolides (57.9% vs 50%, p<0.037).,Neither prone positioning nor non-invasive mechanical ventilation, high-flow nasal cannula, or invasive mechanical ventilation were associated with a better prognosis.,COPD patients admitted to the hospital with SARS-CoV-2 infection have more severe disease and a worse prognosis than non-COPD patients.

Chronic obstructive pulmonary disease (COPD) has become a major cause of morbidity and mortality worldwide.,Increasing evidence indicates that aberrantly expressed microRNAs (miRNAs) are involved in the pathogenesis of COPD.,However, an integrative exploration of miRNA-mRNA regulatory network in COPD plasma remains lacking.,The microarray datasets GSE24709, GSE61741, and GSE31568 were downloaded from the GEO database and analyzed using GEO2R tool to identify differentially expressed miRNAs (DEMs) between COPD and normal plasma.,The consistently changing miRNAs in the three datasets were screened out as candidate DEMs.,Potential upstream transcription factors and downstream target genes of candidate DEMs were predicted by FunRich and miRNet, respectively.,Next, GO annotation and KEGG pathway enrichment analysis for target genes were performed using DAVID.,Then, PPI and DEM-hub gene network were constructed using the STRING database and Cytoscape software.,Finally, GSE56768 was used to evaluate the hub gene expressions.,A total of nine (six upregulated and three downregulated) DEMs were screened out in the above three datasets.,SP1 was predicted to potentially regulate most of the downregulated DEMs, while YY1 and E2F1 could regulate both upregulated and downregulated DEMs. 1139 target genes were then predicted, including 596 upregulated DEM target genes and 543 downregulated DEM target genes.,Target genes of DEMs were mainly enriched in PI3K/Akt signaling pathway, mTOR signaling pathway, and autophagy.,Through the DEM-hub gene network construction, most of the hub genes were found to be potentially modulated by miR-497-5p, miR-130b-5p, and miR-126-5p.,Among the top 12 hub genes, MYC and FOXO1 expressions were consistent with that in the GSE56768 dataset.,In the study, potential miRNA-mRNA regulatory network was firstly constructed in COPD plasma, which may provide a new insight into the pathogenesis and treatment of COPD.

Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients.,Here, we determined whether there is any significant sex-related differences in FEV1 responses to ipratropium bromide.,Data from the Lung Health Study (n = 5887; 37% females) were used to determine changes in FEV1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5 years.,Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients.,After 4 months, ipratropium therapy increased FEV1 by 6.0% in female and 2.9% in male subjects from baseline values (p = 2.42 × 10− 16).,This effect was modified by body mass index (BMI) such that the biggest improvements in FEV1 with ipratropium were observed in thin female subjects (p for BMI ∗ sex interaction = 0.044).,The sex-related changes in FEV1 related to ipratropium persisted for 2 years (p = 0.0134).,Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p = 6.86 × 10− 8).,Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females.,Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs.,Female patients are thus more likely to benefit from ipratropium than male COPD patients.,•Ipratropium; a muscarinic antagonist bronchodilator is more effective in female COPD patients compared to males.,•The effect was modified by body mass index (BMI) such that thin female subjects respond better.,•Female compared with male lungs had greater gene expression for the M3/M2 ratio of muscarinic receptors.,Ipratropium; a muscarinic antagonist bronchodilator is more effective in female COPD patients compared to males.,The effect was modified by body mass index (BMI) such that thin female subjects respond better.,Female compared with male lungs had greater gene expression for the M3/M2 ratio of muscarinic receptors.,Most evidence used to support bronchodilator therapy in COPD has been generated in therapeutic trials with predominately male patients.,Here, we determined whether there are any significant sex-related differences in lung function responses to the bronchodilator ipratropium bromide.,After 4 months, ipratropium therapy increased lung function in females twice as much as males.,This effect was modified by body mass index (BMI) such that the biggest improvements in lung function with ipratropium were observed in thin female subjects.,Female compared with male lungs had greater gene expression for ipratropium receptors.,Female patients are likely to benefit more from ipratropium than male COPD patients.

The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms.,The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.,In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.,The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.,Overall, 676 patients completed the study.,The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met.,QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001).,QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001).,QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use.,However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC.,Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%).,The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).,These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.

Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD.,Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD.,Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”.,These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation.,In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells.,Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs).,Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD.,This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide.,Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease.,We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors.,Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103).,We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions.,We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice.,HRVs are isolated from nasal and lung fluid from subjects with AE-COPD.,Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection.,HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells.,Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells.,Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD.,HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD.,Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD.

COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal.,Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD.,Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases.,Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice.,Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study.,Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study) or in week 14, 16, 18 and 20 (chronic study).,Inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lung tissue.,Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.,In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment.,Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers.,In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis.,Emphysema and atherosclerosis development were unaffected after MSC treatment.,These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

Stem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration.,However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury.,In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche.,We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats.,The MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson’s trichrome staining, immunohistochemistry, and real-time PCR.,The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay.,rAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats.,HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection.,Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions.,Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats.,MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling.

The forced mid-expiratory flow (FEF25-75%) value is a potentially sensitive marker of obstructive peripheral airflow.,We aimed to assess whether FEF25-75% can be an early predictor of chronic obstructive pulmonary disease (COPD).,Between July 1, 2007 and June 31, 2009, we identified 3624 patients who underwent a pulmonary function test (PFT) in Gangnam Severance Hospital.,We selected 307 patients aged over 40 years without COPD who had normal PFT results at baseline and who had follow-up PFT records more than 1 year later.,A FEF25-75% z-score less than −0.8435 was considered low.,We defined COPD as a forced expiratory volume in one second/forced vital capacity value of less than 0.7 before July 31, 2019.,Among 307 patients, 91 (29.6%) had low FEF25-75% at baseline.,After 10 years, the incidence rate of COPD in the low FEF25-75% group was significantly higher than that in the normal FEF25-75% group (41.8% vs 7.4%; P-value<0.001).,The Cox proportional hazard model showed that age (hazard ratio [HR] 1.09; P-value<0.001), smoking status (occasional smoker HR, 4.59; P-value<0.001 and long-term smoker HR, 2.18; P-value=0.023), and low FEF25-75% (HR, 3.31; P-value<0.001) were predictive factors for the development of COPD.,The FEF25-75% value in patients with normal lung function is a useful predictor for the development of COPD.,We should carefully monitor patients who present with low FEF25-75% values, even if they have normal lung function.

There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters.,We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation.,Asthmatic patients (n = 171), patients with COPD (n = 81), and healthy subjects (n = 49) recruited from a single center underwent QCT and clinical characterization.,Proximal airway percentage wall area (%WA) was significantly increased in asthmatic patients (62.5% [SD, 2.2]) and patients with COPD (62.7% [SD, 2.3]) compared with that in healthy control subjects (60.3% [SD, 2.2], P < .001).,Air trapping measured based on mean lung density expiratory/inspiratory ratio was significantly increased in patients with COPD (mean, 0.922 [SD, 0.037]) and asthmatic patients (mean, 0.852 [SD, 0.061]) compared with that in healthy subjects (mean, 0.816 [SD, 0.066], P < .001).,Emphysema assessed based on lung density measured by using Hounsfield units below which 15% of the voxels lie (Perc15) was a feature of COPD only (patients with COPD: mean, −964 [SD, 19.62] vs asthmatic patients: mean, −937 [SD, 22.7] and healthy subjects: mean, −937 [SD, 17.1], P < .001).,Multiple regression analyses showed that the strongest predictor of lung function impairment in asthmatic patients was %WA, whereas in the COPD and asthma subgrouped with postbronchodilator FEV1 percent predicted value of less than 80%, it was air trapping.,Factor analysis of QCT parameters in asthmatic patients and patients with COPD combined determined 3 components, with %WA, air trapping, and Perc15 values being the highest loading factors.,Cluster analysis identified 3 clusters with mild, moderate, or severe lung function impairment with corresponding decreased lung density (Perc15 values) and increased air trapping.,In asthmatic patients and patients with COPD, lung function impairment is strongly associated with air trapping, with a contribution from proximal airway narrowing in asthmatic patients.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic airway inflammation and emphysema, and is caused by exposure to noxious particles or gases, e.g. cigarette smoke.,Smoking and oxidative stress lead to accelerated formation and accumulation of advanced glycation end products (AGEs), causing local tissue damage either directly or by binding the receptor for AGEs (RAGE).,This study assessed the association of AGEs or RAGE in plasma, sputum, bronchial biopsies and skin with COPD and lung function, and their variance between these body compartments.,Healthy smoking and never-smoking controls (n = 191) and COPD patients (n = 97, GOLD stage I-IV) were included.,Autofluorescence (SAF) was measured in the skin, AGEs (pentosidine, CML and CEL) and sRAGE in blood and sputum by ELISA, and in bronchial biopsies by immunohistochemistry. eQTL analysis was performed in bronchial biopsies.,COPD patients showed higher SAF values and lower plasma sRAGE levels compared to controls and these values associated with decreased lung function (p <0.001; adjusting for relevant covariates).,Lower plasma sRAGE levels significantly and independently predicted higher SAF values (p < 0.001).,One SNP (rs2071278) was identified within a region of 50 kB flanking the AGER gene, which was associated with the gene and protein expression levels of AGER and another SNP (rs2071278) which was associated with the accumulation of AGEs in the skin.,In COPD, AGEs accumulate differentially in body compartments, i.e. they accumulate in the skin, but not in plasma, sputum and bronchial biopsies.,The association between lower sRAGE and higher SAF levels supports the hypothesis that the protective mechanism of sRAGE as a decoy-receptor is impaired in COPD.,The online version of this article (doi:10.1186/s12931-016-0363-2) contains supplementary material, which is available to authorized users.

Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required.

This paper proposes a mathematical framework for understanding how the structural changes in the COPD lung reflect in model parameters.,The core of the analysis is a correlation between the heterogeneity in the lung as COPD degree changes (GOLD II, III and IV) and the nonlinearity index evaluated using the forced oscillation technique.,A low frequency evaluation of respiratory impedance models and nonlinearity degree is performed since changes in tissue mechanics are related to viscoelastic properties.,Simulation analysis of our model indicates a good correlation to expected changes in heterogeneity and nonlinear effects.,A total of 43 COPD diagnosed patients are evaluated, distributed as GOLD II (18), GOLD III (15) and GOLD IV (10).,Experimental data supports the claims and indicate that the proposed model and index for nonlinearity is well-suited to capture COPD structural changes.

: To verify the accordance of functional and morphometric parameters during the development of emphysema.,: BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days.,Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed.,To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma.,: We only observed decreases in tissue elastance and tissue damping on the 28th day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema.,However, only the mean linear intercept values remained increased until the 40th day.,The volume proportion of collagen fibers was increased from the 15th day to the 40th day, whereas the volume proportion of elastic fibers was only increased on the 40th day.,The number of macrophages increased beginning on the 1st day.,The expression of metalloproteinase 12 was increased from the 3rd day until the 40th day.,However, 8-isoprostane expression was only increased on the 1st and 3rd days.,: In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics.,Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process.

Tiotropium is a long-acting inhaled anticholinergic developed for the treatment of chronic obstructive pulmonary disease (COPD) and has been available since 2002.,We sought to update an evaluation of the safety of tiotropium in the HandiHaler® formulation as significant clinical trial data have become available over time.,Pooled analysis of adverse event reporting from phase III and IV tiotropium HandiHaler® clinical trials with the following characteristics was performed: randomized, double-blind, parallel group, placebo-controlled design, tiotropium 18 μg once-daily dosing, COPD indication, duration of at least four weeks.,Incidence rates by treatment group, rate differences (tiotropium-placebo), and 95% confidence intervals were determined.,Twenty-six trials were identified involving 17,014 patients.,Mean age was 65 years, mean forced expiratory volume in one second was 1.16 L (41% predicted), 76% men.,Total exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient-years (placebo).,Tiotropium was associated with a reduced risk (expressed as rate difference [95% confidence interval] per 100 patients-years at risk) for an adverse event (−17.5 [−22.9, −12.2]), serious adverse event (−1.41 [−2.81, −0.00]) and a fatal event (−0.63 [−1.14, −0.12]).,A reduced risk was present for adverse events that were cardiac (−0.79 [−1.48, −0.09]), lower respiratory (−14.2 [−17.0, −11.5]) and for a composite endpoint of major adverse cardiovascular events (−0.45 [−0.85, −0.05]).,Typical expected inhaled anticholinergic effects such as dry mouth, constipation, and urinary difficulties were observed in the safety database.,The safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD.

The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003

Acute myocardial infarction is a major cause of hospitalization and death in patients with chronic obstructive pulmonary disease (COPD); however, temporal trends in the management and clinical outcomes of these patients remain unclear.,We conducted an observational study by using a representative sample of 1 million beneficiaries from the Taiwan National Health Insurance Research Database.,Comorbidities, in‐hospital treatment, and outcomes were compared for patients with acute myocardial infarction with and without COPD between 2004 and 2013.,Temporal trends in treatment and outcomes were analyzed.,We included 6770 patients admitted to hospitals with acute myocardial infarction diagnoses, of whom 1921 (28.3%) had COPD.,Fewer patients with COPD received β‐blockers (adjusted odds ratio 0.66, 95% CI 0.59-0.74), angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (adjusted odds ratio 0.83, 95% CI 0.73-0.93), statins, anticoagulants, dual antiplatelets, and coronary interventions.,These patients had higher mortality (in hospital: adjusted hazard ratio 1.25 [95% CI 1.11-1.41]; 1 year: adjusted hazard ratio 1.20 [95% CI 1.09-1.32]) and respiratory failure risk during admission.,Temporal trends showed little improvement in mortality in patients with COPD over 10 years.,Multivariable logistic regression indicated that dual antiplatelets, β‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers, statins, coronary angiography, and coronary artery bypass grafting surgery were significantly correlated with improved mortality in patients with COPD.,In Taiwan, a lower proportion of patients with COPD received evidence‐based therapies for acute myocardial infarction than did patients without COPD, and their clinical outcomes were inferior.,Limited improvement in mortality was observed over the preceding 10 years and is attributable to the underuse of evidence‐based treatments.

Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD).,Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases.,But the effects of beta-blockers on outcomes in patients with COPD remain controversial.,The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD.,An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD.,The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD.,Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included.,The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD.,The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71).,In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.,The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD.,Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients.

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD).,Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.,Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors.,Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.,236 COPD patients from five European centres were included.,Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”.,After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14.,Both demonstrated good model fit (person separation index >0.7).,Confirmatory factor analysis supported the bidimensional structure.,Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.,Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.,Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patientshttp://ow.ly/LJqP8

Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what “physical activity” means to COPD patients and how their perspective is best measured is poorly understood.,We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments).,116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III-IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised.,Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity.,The themes were similar irrespective of country, demographic or disease characteristics.,Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period.,For the first time, our approach provides comprehensive insight on physical activity from the COPD patients’ perspective.,The PROactive PRO instruments’ content validity represents the pivotal basis for empirically based item reduction and validation.,Conceptual framework as basis of PROactive PRO instruments to assess physical activity from COPD patient perspectivehttp://ow.ly/ytJoS

Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.

The influence of gender on the expression of COPD has received limited attention.,Quality of Life (QoL) has become an important outcome in COPD patients.,The aim of our study was to explore factors contributing to gender differences in Quality of Life of COPD patients.,In 146 men and women with COPD from a pulmonary clinic we measured: Saint George's Respiratory Questionnaire (SGRQ), age, smoking history, PaO2, PaCO2, FEV1, FVC, IC/TLC, FRC, body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC), degree of comorbidity (Charlson index) and exacerbations in the previous year.,We explored differences between genders using Mann-Whitney U-rank test.,To investigate the main determinants of QoL, a multiple lineal regression analysis was performed using backward Wald's criteria, with those variables that significantly correlated with SGRQ total scores.,Compared with men, women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01, symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p = 0.01).,SGRQ total scores correlated in men with: FEV1% (-0.378, p < 0.001), IC/TLC (-0.368, p = 0.002), PaO2 (-0.379, p = 0.001), PaCO2 (0.256, p = 0.05), 6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index (0.380, p = 0.001) and MMRC (0.654, p < 0.001).,In women, the scores correlated only with FEV1% (-0.293, p = 0.013) PaO2 (-0.315, p = 0.007), exacerbations (0.290, p = 0.013) and MMRC (0.628, p < 0.001).,Regression analysis (B, 95% CI) showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8), IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women manifested the highest independent associations with SGRQ scores.,In moderate to severe COPD patients attending a pulmonary clinic, there are gender differences in health status scores.,In turn, the clinical and physiological variables independently associated with those scores differed in men and women.,Attention should be paid to the determinants of QoL scores in women with COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide.,Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations.,Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation.,Long-acting β2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD.,The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects.,Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe.,Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA.,Several other agents are in the late stages of development, most of which offer once-daily dosing.,The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations.,These evolving treatments will provide new opportunities and challenges in the management of COPD.

The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.,From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort).,Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables.,Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort).,The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.,A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively.,In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02-1.11] for per 80 mg of budesonide).,Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline.,In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).,This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE.,ICS should be judiciously used in indicated COPD patients.

COPD is a common chronic disease with genetic predisposition.,TRPV1 is mainly expressed in peripheral neuron which widely exists in entire respiratory tract.,In present study, we aimed to study the relationship between single nucleotide polymorphisms (SNPs) of transient receptor potential vanilloid-1 (TRPV1) and the risk of chronic obstructive pulmonary disease (COPD) or COPD combined with pulmonary hypertension (PH) in Chinese Han population.,A total of 1019 individuals, including 506 healthy volunteers and 513 COPD patients (150 patients combined with PH among them) were recruited in this study.,Genomic DNA were extracted and sequenced.,Genotype and allele frequencies of the TRPV1 SNPs among COPD, COPD combined with PH and control groups were compared.,Then, the association of TRPV1 SNPs and smoking status were analyzed.,Genotype frequencies of SNP rs3744683 had a significant difference in COPD patients with PH patients compared with control (p = 0.006) or COPD patients without PH patients (p = 0.016).,Likewise, SNP rs3744683 was remarkedly associated with the risk of COPD (p = 0.004) in current-smoker groups which phenomenon was not observed in nonsmoker or former-smoker groups.,Compared with the control group, there was a significant difference for the distribution of SNP rs4790521 alleles in the COPD group (p = 0.041).,For further, logical regression analysis showed that SNP rs3744683 genotype of “TC” was a protective factor for PH in COPD patients compared with the genotype of “TT” (OR = 0.364, 95%CI = 0.159-0.829, p = 0.016).,Our findings firstly revealed the relevance between TRPV1 SNPs and the risk for COPD/COPD combined with PH.

Pulmonary hypertension (PH) is a common complication of chronic respiratory disease.,Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae.,However, the association between DM and PH in chronic respiratory disease remains unclear.,In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease.,We prospectively analyzed 386 patients in our hospital with chronic respiratory disease.,An echocardiographic pressure gradient between the right atrium and the right ventricle of ≥ 40 mmHg was defined as PH.,We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH.,Of the 386 patients, 42 (10.9%) were diagnosed as having PH.,The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group.,Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients.,DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease.

It remains unclear whether eosinophilia is useful for in guiding inhaled corticosteroid (ICS) therapy in chronic obstructive pulmonary disease (COPD) patients.,The goal of this study is to evaluate the risk of acute exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality with various levels of eosinophil counts among COPD patients using ICS.,A cohort study was conducted using the UK Clinical Practice Research Datalink.,Patients were aged 40+ and had COPD (n = 32 693).,Current users of ICS were stratified by relative and absolute eosinophil counts to determine the risk of outcomes with blood eosiniphilia using Cox regression analysis.,Among COPD patients, current use of ICS was not associated with a reduced risk of acute COPD exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality.,Stratification of ICS use by absolute or relative eosinophil counts did not result in significant differences in risk of COPD exacerbations or hospitalisations/accident and emergency visits.,However, all‐cause mortality was reduced by 12% to 24% among patients with eosinophilia.,COPD‐related acute exacerbations or hospitalisations/accident and emergency visits were not reduced with eosinophilia among users of ICS with COPD.,However, all‐cause mortality was reduced by 12% to 24%.,These findings are potentially important and require further evaluation in prospective studies.

In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations.,To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels.,The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications.,Three-year survival between groups was compared using Kaplan-Meier analysis.,Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos.,Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%).,For all cutoffs, there was no difference between Eos+ and Eos− groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories).,In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival.,In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis.,These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping.

The prevalence of chronic obstructive pulmonary disease (COPD), a common and preventable chronic disease, is on the increase, and so are the financial and social burdens associated with it.,The management of COPD is particularly challenging, as patients have complex health and social needs requiring life-long monitoring and treatment.,In order to address these issues and reduce the burden imposed by COPD, the development of innovative disease management models is vital.,Nurses are in a key position to assume a leading role in the management of COPD since they frequently represent the first point of contact for patients and are involved in all stages of care.,Although evidence is still limited, an increasing number of studies have suggested that nurse-led consultations and interventions for the management of COPD have the potential to impact positively on the health and quality of life of patients.,The role of nurses in the management of COPD around the world could be significantly expanded and strengthened.,Providing adequate educational opportunities and support to nurses, as well as addressing funding issues and system barriers and recognising the importance of the expanding roles of nurses, is vital to the well-being of patients with long-term medical conditions such as COPD and to society as a whole, in order to reduce the burden of this disease.

The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry.,Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis.,We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted.,Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD).,We then used logistic regression to investigate predictors of correct interpretation.,Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care.,Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality.,Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction.,Historical records for asthma diagnosis significantly decreased odds of correct interpretation.,The quality of the spirometry procedure undertaken in primary care is high.,However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care.,The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes.

Breathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (“over-perception”).,Pulmonary rehabilitation profoundly affects breathlessness, without influencing lung function.,Learned associations influence brain mechanisms of sensory perception.,We hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations.,In 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during a breathlessness-related word-cue task (using functional magnetic resonance imaging), and clinical and psychological measures of breathlessness.,Changes in ratings of breathlessness word cues positively correlated with changes in activity in the insula and anterior cingulate cortex.,Changes in ratings of breathlessness-anxiety negatively correlated with activations in attention regulation and motor networks.,Baseline activity in the insula, anterior cingulate cortex and prefrontal cortex correlated with improvements in breathlessness and breathlessness-anxiety.,Pulmonary rehabilitation is associated with altered neural responses related to learned breathlessness associations, which can ultimately influence breathlessness perception.,These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.,Pulmonary rehabilitation improves breathlessness by recalibrating the brain's sensory perception networkshttp://ow.ly/crhy30cQerx

Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD).,However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression.,Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance.,As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry.,Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status.,Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill) using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation.,In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea.,This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance.,Also discussed are the benefits of pulmonary rehabilitation and the potential role of pharmacologic treatment in symptomatic patients with mild COPD.

Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters.

Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation.,Why some patients are susceptible to colonisation is not understood.,We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity.,The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD.,Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls.,BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls.,NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation.,When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM.,We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway.,Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients.,This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.

COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue.

Socioeconomic status (SES) is a strong social determinant of health.,There remains a limited understanding of the association between SES and COPD prevalence among low- and middle-income countries where the majority of COPD-related morbidity and mortality occurs.,We examined the association between SES and COPD prevalence using data collected in Argentina, Bangladesh, Chile, Peru, and Uruguay.,We compiled lung function, demographic, and SES data from three population-based studies for 11,042 participants aged 35-95 years.,We used multivariable alternating logistic regressions to study the association between COPD prevalence and SES indicators adjusted for age, sex, self-reported daily smoking, and biomass fuel smoke exposure.,Principal component analysis was performed on monthly household income, household size, and education to create a composite SES index.,Overall COPD prevalence was 9.2%, ranging from 1.7% to 15.4% across sites.,The adjusted odds ratio of having COPD was lower for people who completed secondary school (odds ratio [OR] =0.73, 95% CI 0.55-0.98) and lower with higher monthly household income (OR =0.96 per category, 95% CI 0.93-0.99).,When combining SES factors into a composite index, we found that the odds of having COPD was greater with lower SES (interquartile OR =1.23, 95% CI 1.05-1.43) even after controlling for subject-specific factors and environmental exposures.,In this analysis of multiple population-based studies, lower education, lower household income, and lower composite SES index were associated with COPD.,Since household income may be underestimated in population studies, adding household size and education into a composite index may provide a better surrogate for SES.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and the traditional variables extracted from computed tomography (CT) images may not be sufficient to describe all the topological features of lung tissues in COPD patients.,We employed an unsupervised three-dimensional (3D) convolutional autoencoder (CAE)-feature constructor (FC) deep learning network to learn from CT data and derive tissue pattern-clusters jointly.,We then applied exploratory factor analysis (EFA) to discover the unobserved latent traits (factors) among pattern-clusters.,CT images at total lung capacity (TLC) and residual volume (RV) of 541 former smokers and 59 healthy non-smokers from the cohort of the SubPopulations and Intermediate Outcome Measures in the COPD Study (SPIROMICS) were analyzed.,TLC and RV images were registered to calculate the Jacobian (determinant) values for all the voxels in TLC images.,3D Regions of interest (ROIs) with two data channels of CT intensity and Jacobian value were randomly extracted from training images and were fed to the 3D CAE-FC model. 80 pattern-clusters and 7 factors were identified.,Factor scores computed for individual subjects were able to predict spirometry-measured pulmonary functions.,Two factors which correlated with various emphysema subtypes, parametric response mapping (PRM) metrics, airway variants, and airway tree to lung volume ratio were discriminants of patients across all severity stages.,Our findings suggest the potential of developing factor-based surrogate markers for new COPD phenotypes.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation.,Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment.,Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process.,Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions.,This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with lung function decline, lower quality of life, and increased mortality, and can be prevented by pharmacological treatment and rehabilitation.,To examine management including examination, treatment, and planned follow-up of COPD exacerbation visits in primary care patients and to explore how measures and management at exacerbation visits are related to subsequent exacerbation risk.,A clinical population of 775 COPD patients was randomly selected from 56 Swedish primary healthcare centres.,Data on patient characteristics and management of COPD exacerbations were obtained from medical record review and a patient questionnaire.,In the study population of 458 patients with at least one exacerbation, Cox regression analyses estimated the risk of a subsequent exacerbation with adjustment for age and sex.,During a follow-up period of 22 months, 238 patients (52%) had a second exacerbation.,A considerable proportion of the patients were not examined and treated as recommended by guidelines.,Patients with a scheduled extra visit to an asthma/COPD nurse following an exacerbation had a decreased risk of further exacerbations compared with patients with no extra follow-up other than regularly scheduled visits (adjusted hazard ratio 0.60 (95% confidence interval 0.37 to 0.99), p=0.045).,Guidelines for examination and emergency treatment at COPD exacerbation visits are not well implemented.,Scheduling an extra visit to an asthma/COPD nurse following a COPD exacerbation may be associated with a decreased risk of further exacerbations in primary care patients.

Clinical guidelines for management of patients with chronic obstructive pulmonary disease (COPD) include recommendations based on high levels of evidence, but gaps exist in their implementation.,The aim of this study was to examine the perspectives of medical practitioners regarding implementation of six high-evidence recommendations for the management of people with COPD.,Semi-structured interviews were conducted with medical practitioners involved with care of COPD patients in hospital and general practice.,Interviews sought medical practitioners’ experience regarding implementation of smoking cessation, influenza vaccination, pulmonary rehabilitation, guideline-based medications, long-term oxygen therapy for hypoxemia and plan and advice for future exacerbations.,Interviews were audiotaped, transcribed verbatim and analyzed using content analysis.,Nine hospital-based medical practitioners and seven general practitioners participated.,Four major categories were identified which impacted on implementation of the target recommendations in the care of patients with COPD: (1) role clarity of the medical practitioner; (2) persuasive communication with the patient; (3) complexity of behavioral change required; (4) awareness and support available at multiple levels.,For some recommendations, strength in all four categories provided significant enablers supporting implementation.,However, with regard to pulmonary rehabilitation and plans and advice for future exacerbations, all identified categories that presented barriers to implementation.,This study of medical practitioner perspectives has indicated areas where significant barriers to the implementation of key evidence-based recommendations in COPD management persist.,Developing strategies to target the identified categories provides an opportunity to achieve greater implementation of those high-evidence recommendations in the care of people with COPD.

Patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular events.,This study evaluated the association between high-sensitivity cardiac troponin I concentration and cardiovascular events in patients with COPD and heightened cardiovascular risk.,In a double-blind randomized controlled trial, 16,485 patients with COPD and cardiovascular disease or risk factors were randomized to once daily inhaled placebo, fluticasone furoate (100 μg), vilanterol (25 μg), or their combination.,Plasma high-sensitivity cardiac troponin I concentrations were measured in a subgroup of 1,599 patients.,Outcomes were on-treatment cardiovascular events and COPD exacerbations over a median of 18 months, and cardiovascular death over a median of 27 months.,Baseline plasma cardiac troponin I concentrations were above the limit of detection (1.2 ng/l) in 1,542 (96%) patients.,Concentrations were unaffected by inhaled therapies at 3 months (p > 0.05).,Compared with the lowest quintile (cardiac troponin <2.3 ng/l), patients in the highest quintile (≥7.7 ng/l) were at greater risk of cardiovascular events (hazard ratio [HR] 3.7; 95% confidence interval [CI]: 1.3 to 10.1; p = 0.012) and cardiovascular death (HR: 20.1; 95% CI: 2.4 to 165.2; p = 0.005) after adjustment for risk factors.,By contrast, there were no differences in exacerbations between quintiles (HR: 1.1; 95% CI: 0.8 to 1.5; p = 0.548).,In patients with COPD and heightened cardiovascular risk, plasma cardiac troponin I concentrations are a specific and major indicator of future cardiovascular events and cardiovascular death.,Inhaled therapies did not affect cardiac troponin I concentrations consistent with their neutral effect on mortality and cardiovascular outcomes.,(Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease [SUMMIT]; NCT01313676)

Influenza is a frequent cause of exacerbations of chronic obstructive pulmonary disease (COPD).,Exacerbations are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression, death, and ultimately, substantial healthcare-related costs.,Despite longstanding recommendations to vaccinate vulnerable high-risk groups against seasonal influenza, including patients with COPD, vaccination rates remain sub-optimal in this population.,We conducted a systematic review to summarise current evidence from randomised controlled trials (RCTs) and observational studies on the immunogenicity, safety, efficacy, and effectiveness of seasonal influenza vaccination in patients with COPD.,The selection of relevant articles was based on a three-step selection procedure according to predefined inclusion and exclusion criteria.,The search yielded 650 unique hits of which 48 eligible articles were screened in full-text.,Seventeen articles describing 13 different studies were found to be pertinent to this review.,Results of four RCTs and one observational study demonstrate that seasonal influenza vaccination is immunogenic in patients with COPD.,Two studies assessed the occurrence of COPD exacerbations 14 days after influenza vaccination and found no evidence of an increased risk of exacerbation.,Three RCTs showed no significant difference in the occurrence of systemic effects between groups receiving influenza vaccine or placebo.,Six out of seven studies on vaccine efficacy or effectiveness indicated long-term benefits of seasonal influenza vaccination, such as reduced number of exacerbations, reduced hospitalisations and outpatient visits, and decreased all-cause and respiratory mortality.,Additional large and well-designed observational studies would contribute to understanding the impact of disease severity and patient characteristics on the response to influenza vaccination.,Overall, the evidence supports a positive benefit-risk ratio for seasonal influenza vaccination in patients with COPD, and supports current vaccination recommendations in this population.,The online version of this article (doi:10.1186/s12890-017-0420-8) contains supplementary material, which is available to authorized users.

The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient.,Older patients are at risk for COPD and its components-emphysema, CB, and bronchiectasis.,Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD.,Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB.,Organisms include the more‐common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.,Less‐common nonenteric, gram‐negative organisms including Pseudomonas aeruginosa, gram‐positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis.,Risk‐stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB.,These guidelines have not been prospectively validated for the general population and especially not for the elderly population.,Using a risk‐stratification approach for elderly patients, first‐line antibiotics (e.g., amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more‐limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB.,Second‐line antibiotics (e.g., amoxicillin/clavulanic acid, second‐ or third‐generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.

Chronic obstructive pulmonary disease (COPD) remains a major health problem, strongly related to smoking.,Despite the publication of practice guidelines on prevention and treatment, not all patients with the disease receive the recommended healthcare, particularly with regard to smoking cessation advice where applicable.,We have developed a tailored implementation strategy for enhancing general practitioners’ adherence to the disease management guidelines.,The primary aim of the study is to evaluate the effects of this tailored implementation intervention on general practitioners’ adherence to guidelines.,A pragmatic two-arm cluster randomized trial has been planned to compare care following the implementation of tailored interventions of four recommendations in COPD patients against usual care.,The study will involve 18 general practices (9 in the intervention group and 9 in the control group) in Poland, each with at least 80 identified (at the baseline) patients with diagnosed COPD.,The nine control practices will provide usual care without any interventions.,Tailored interventions to implement four recommendations will be delivered in the remaining nine practices.,At follow-up after nine months, data will be collected for all 18 general practices.,The primary outcome measure is physicians’ adherence to all four recommendations: brief anti-smoking advice, dyspnea assessment, care checklist utilization and demonstration to patients of correct inhaler use.,This measurement will be based on data extracted from identified patients’ records.,Additionally, we will survey and interview patients with chronic obstructive pulmonary disease about the process of care.,The results of this trial will be directly applicable to primary care in Poland and add to the growing body of evidence on interventions to improve chronic illness care.,This trial has been registered with Clinical Trials Protocol Registration System.,Trial number: NCT01893476.

COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features.,In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry.,The severity of the airflow limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management.,However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1.,At present, there is a lack of reliable and simple blood biomarkers to confirm and further assess the diagnosis of COPD.,However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes.,Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and “frequent exacerbators”.,Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as “asthma COPD overlap syndrome”.,Several other phenotypes have been proposed, but require validation against clinical outcomes.,Defining phenotypes requires the assessment of multiple factors indicating disease severity, its impact, and its activity.,Recognition and validation of COPD phenotypes has an important role to play in the selection of evidence-based targeted therapy in the future management of COPD, but regardless of the diagnostic terms, patients with COPD should be assessed and treated according to their individual treatable characteristics.

The six-second spirometry has been proposed as an alternative to diagnose airflow limitation, although its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unknown.,The purpose of this study was to determine the prognostic value of the postbronchodilator forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio and FEV6 in COPD patients.,The study population consisted of 2,614 consecutive stable patients with COPD.,The patients were monitored for an average period of 4.3 years regarding mortality, hospitalizations by COPD exacerbations, diagnosis of lung cancer, and annual lung function decline.,The overall rate of death was 10.7 (95%CI: 8.7-12.7) per 1000 person-years.,In addition to male gender, age and comorbidity, FEV6 (hazard ratio [HR]: 0.981, 95%CI: 0.968-0.003) and FEV1/FEV6 quartiles (lowest quartile (<74% pred.): HR 3.558, 95%CI: 1.752-7.224; and second quartile (74-84% pred.): HR 2.599, 95%CI: 1.215-5.561; versus best quartile (>0.89% pred.)) were independently associated with mortality, whereas FEV1 was not retained in the model. 809 patients (30.9%) had at least one hospital admission due to COPD exacerbation.,In addition to sex, age, smoking and comorbidity, FEV1 and FEV1/FEV6 quartiles were independent risk factors of hospitalization.,FEV6 was the only spirometric parameter independently related with lung function annual decline, while the FEV6 and FEV1/FEV6 quartiles were independent risk factors for lung cancer.,In a general COPD outpatient population, airflow obstruction assessed by the FEV1/FEV6 is an independent risk factor for both death and hospitalization.

Oxidative stress (OS) plays a key role in the muscle impairment and exercise capacity of COPD patients.,However, the literature reveals that systemic OS markers show great heterogeneity, which may hinder the prescription of effective antioxidant supplementation.,This study therefore aimed to identify OS markers imbalance of COPD patients, relative to validated normal reference values, and to investigate the possibility of systemic OS profiles.,We measured systemic enzymatic/nonenzymatic antioxidant and lipid peroxidation (LP) levels in 54 stable COPD patients referred for a rehabilitation program.,The main systemic antioxidant deficits in these patients concerned vitamins and trace elements.,Fully 89% of the COPD patients showed a systemic antioxidant imbalance which may have caused the elevated systemic LP levels in 69% of them.,Interestingly, two patient profiles (clusters 3 and 4) had a more elevated increase in LP combined with increased copper and/or decreased vitamin C, GSH, and GPx.,Further analysis revealed that the systemic LP level was higher in COPD women and associated with exercise capacity.,Our present data therefore support future supplementations with antioxidant vitamins and trace elements to improve exercise capacity, but COPD patients will probably show different positive responses.

The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed.,We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II).,Blood was taken once in Control I and 4 times (every month) in Control II.,In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively.,Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I.,In Control II, the similar differences as compared to Control I were observed throughout the study.,Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E.,COPD is accompanied by oxidative stress.,A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters.

Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations.

The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.

Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition, and progresses with acute exacerbations.,(AE).,During AE, levels of acute phase reactants such as C-reactive protein (CRP) and inflammatory cells in the circulation increase.,Soluble urokinase-type plasminogen activator receptor (suPAR) levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation.,The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD) and response to treatment.,The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment.,We found that fibrinogen (P<0.001), CRP (P<0.001), and suPAR (P<0.001) were significantly higher in patients with AE-COPD than in healthy controls.,Fibrinogen (P<0.001), CRP (P=0.001), and suPAR (P<0.001) were significantly decreased by the seventh day of treatment.,However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD.,There was a correlation between fibrinogen, CRP, and suPAR.,However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression.,In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively).,Serum suPAR was negatively correlated with forced expiratory volume in 1 second (r=−478, P=0.001).,suPAR is a marker of acute inflammation.,It is well correlated with such inflammation markers as CRP and fibrinogen. suPAR can be used as a predictor of AE-COPD and in monitoring response to treatment.

The diagnosis of COPD is not always consistent with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy in daily clinical practice, especially in primary care.,This study aimed to estimate the overall COPD prevalence and severity, to identify differences between newly and previously diagnosed patients, and to evaluate the potential COPD overtreatment in a smoking population attending a primary care spirometry surveillance program.,A study was conducted in 10 primary health care centers of Central Greece during a 7-month period.,Eligible participants were aged ≥40 years and were either current smokers or exsmokers.,A total of 186 subjects were included (68% males, mean age 62.3±12.6 years, mean life-time tobacco exposure 50 pack-years).,COPD prevalence was 17.8%, identified to be higher in elderly males.,Forty-two percent of the COPD group were newly diagnosed patients, who were of younger age, current smokers, presented with less dyspnea and better health status, and mainly appeared with mild-to-moderate disease.,Interestingly, 61.4% of non-COPD and 85.7% of newly diagnosed COPD individuals had been using inhaled medication under primary care provider’s prescription without ever undergoing spirometry or further evaluation by a pulmonologist; thus, the phenomena of COPD overdiagnosis and missed diagnosis came into the spotlight.,Moreover, only 26.3% of known COPD patients were properly medicated according to GOLD guidelines, while half of them were inappropriately treated with triple inhaled therapy.,We reported a significant prevalence of COPD in smoking population attending this spirometry program.,A remarkable proportion of COPD patients were undiagnosed and made case finding worthwhile.,Underutilization of spirometry in the diagnosis and management of COPD as well as general practitioners’ nonadherence to the GOLD treatment guidelines was confirmed by our data.,These findings highlight the need for a major overhaul and culture change in primary care settings of Central Greece.

Low adherence to Global initiative for chronic Obstructive Lung Disease (GOLD) guideline recommendations has been reported worldwide.,There has been no study on the adherence to GOLD guidelines for COPD treatment in Turkey.,To investigate the rates of adherence to GOLD 2010 guidelines for COPD treatment among pulmonologists.,A multi-center, cross-sectional, observational study was carried out in eleven pulmonary outpatient clinics across Turkey.,Adherence to GOLD was evaluated through hospital records.,Demographic and clinical data were recorded.,Study included 719 patients (mean age: 62.9±9.7 years; males 85.4%) of whom 16 was classified as GOLD Stage I, 238 as II, 346 as III, and 119 as IV, and only 59.5% received appropriate treatment.,Rates of guideline adherence varied across GOLD stages (I, 6.3%; II, 14.7%; III, 84.4%; and IV, 84%).,Causes of inappropriate therapies were overtreatment (Stage I, 100% and Stage II, 91.1%), undertreatment (Stage III, 3.3% and Stage IV, 10.9%) and lack of treatment (Stage II, 3.8%; Stage III, 2.3%; and Stage IV, 5.9%).,The most preferred regimen (43.4%) was long-acting β2-agonist-inhaled corticosteroid-long-acting muscarinic antagonist.,Overall, 614 patients (89%) received treatment containing inhaled corticosteroid.,Pulmonologists in Turkey have low rates of adherence to GOLD guidelines in COPD treatment.,Inappropriateness of therapies was due to overtreatment in early stages and excessive use of inhaled corticosteroid (ICS) in all disease stages.

Although, to our knowledge, there has been no exhaustive or credible review of the evidence of the disease burden of COPD in China, COPD has become an increasing public health concern to the Chinese medical community.,The purpose of this article is to review the evidence and evaluate and clarify the disease burden of COPD in China with the aim of improving effective management.,We reviewed previous studies of COPD in China, which included data on prevalence, mortality, disease burden, risk factors, diagnosis, and management by searching related Web sites, including PubMed, ProQuest, and Thomson Reuters' Web of Knowledge, as well as major Chinese databases and government Web sites.,Reported COPD prevalence varied between 5% and 13% in different provinces/cities across China.,In 2008, COPD ranked fourth as a leading cause of death in urban areas and third in rural areas.,In addition, COPD accounted for 1.6% of all hospital admissions in China in that year.,The high prevalence of smoking and biomass fuel use acted as major contributors to the high occurrence of COPD in China.,Management of COPD in China should focus on adjusting the distribution of medical resources and on addressing public health policies to facilitate earlier diagnosis in rural areas, aim to reduce smoking prevalence, improve patients' self-management, and keep physicians' knowledge up to date and consistent with current guidelines.,COPD is one of the most challenging medical issues facing China because of its influence on both personal and public health and its impact on the economy.,Optimal management strategies should be adopted and strengthened immediately.

COPD is a global health concern, and is a major cause of chronic morbidity and mortality worldwide.,According to the World Health Organization, it is currently the sixth leading cause of death in the world, and further increases in the prevalence and mortality of the disease is predicted for the coming decades.,These increases are mainly linked to the epidemic of tobacco exposure and indoor and outdoor air pollution in Asian countries.,The burden of COPD in Asia is currently greater than that in developed Western countries, both in terms of the total number of deaths and the burden of disease, as measured in years of life lost and years spent living with disability.,The types of health-care policies and the practice of medicine vary considerably among the regions of Asia and have an impact on the burden of disease.,Treatment aims in Asian countries are based on evidence-based management guidelines.,Barriers to the implementation of disease management guidelines are related to issues of resource conflict and lack of organizational support rather than cultural differences in medical practice.,To reduce this burden of COPD in Asian countries, there is a need for a multifaceted approach in improving awareness of prevalence and disease burden, in facilitating accurate diagnosis of COPD among chronic respiratory diseases, in championing health policies that reduce the burden of the main risk factors for COPD and in the wider use of evidence-based management for COPD.

The global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and it has become a major public health burden worldwide, including in Vietnam.,A large body of preclinical and clinical studies supports the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of lung injury, including COPD.,The aim of this trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary intervention in combination with standard COPD medication treatments in patients with moderate-to-severe COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 and Vietnam Ministry of Health’s guidelines.,This matched case-control phase I/II trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between June 2020 and December 2021.,In this study, 40 patients will be enrolled and assigned into two age-matched, gender-matched and COPD condition-matched groups, including a UC-MSC group and a control group.,Both groups will receive standard COPD medication treatment based on the GOLD 2019 guidelines and the Vietnam Ministry of Health protocol.,The UC-MSC group will receive two doses of thawed UC-MSC product with an intervention interval of 3 months.,The primary outcome measures will include the incidence of prespecified administration-associated adverse events and serious adverse events.,The efficacy will be evaluated based on the absolute changes in the number of admissions, arterial blood gas analysis, lung function and lung fibrosis via CT scan and chest X-ray.,The clinical evaluation will be conducted at baseline and 3, 6 and 12 months postintervention.,Ethical approval was secured from the Ethical Committee of Vinmec International Hospital (number:166/2019/QĐ-VMEC) and Vietnam Ministry of Health (number:2002/QĐ-BYT).,The results will be reported to trial collaborators, publication in peer-reviewed academic journals.,NCT04433104.

Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole.,Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished.,In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential.,The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea).,After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest.,The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein.,The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease.,Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects.,Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease.,This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no.,14764, CONEP report 233/2009).

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.

Hospital treatment of chronic obstructive pulmonary disease (COPD) frequently does not follow published evidences.,This lack of adherence can contribute to the high morbidity, mortality and readmissions rates.,The European Quality of Care Pathway (EQCP) study on acute exacerbations of COPD (NTC00962468) is undertaken to determine how care pathways (CP) as complex intervention for hospital treatment of COPD affects care variability, adherence to evidence based key interventions and clinical outcomes.,An international cluster Randomized Controlled Trial (cRCT) will be performed in Belgium, Italy, Ireland and Portugal.,Based on the power analysis, a sample of 40 hospital teams and 398 patients will be included in the study.,In the control arm of the study, usual care will be provided.,The experimental teams will implement a CP as complex intervention which will include three active components: a formative evaluation of the quality and organization of care, a set of evidence based key interventions, and support on the development and implementation of the CP.,The main outcome will be six-month readmission rate.,As a secondary endpoint a set of clinical outcome and performance indicators (including care process evaluation and team functioning indicators) will be measured in both groups.,The EQCP study is the first international cRCT on care pathways.,The design of the EQCP project is both a research study and a quality improvement project and will include a realistic evaluation framework including process analysis to further understand why and when CP can really work.,NCT00962468

Administering maintenance COPD therapy with a combination of multiple inhalers may increase inhaler errors.,This study evaluated the potential benefits of using a single Ellipta dry powder inhaler (DPI) compared with two combinations of DPIs commonly used to deliver triple maintenance therapy.,Patients receiving inhaled COPD medication were enrolled in this multicenter, randomized, open-label, placebo-device, crossover study with a 2×2 complete block design (NCT0298218), which comprised two substudies: Ellipta vs Diskus + HandiHaler (substudy 1) or Turbuhaler + HandiHaler (substudy 2).,Patients demonstrated inhaler use after reading the relevant patient information leaflet (PIL).,A trained investigator assessed user errors (critical errors [errors likely to result in no or significantly reduced medication being inhaled] and overall errors).,The primary endpoint was the proportion of patients making ≥1 critical error after reading the PIL.,The secondary endpoints included error rates during ≤2 reassessments following investigator instruction (if required), instruction time, and patient preference.,After reading the PIL, significantly fewer patients made critical errors with Ellipta compared with Diskus + HandiHaler (9% [7/80] vs 75% [60/80], respectively; P<0.001) or Turbuhaler + HandiHaler (9% [7/79] vs 73% [58/79], respectively; P<0.001).,The number of patients making overall errors was also lower with Ellipta vs tested inhaler combinations (P<0.001 for each substudy).,The median instruction time needed for error-free use was shorter with Ellipta in substudies 1 and 2 (2.7 and 2.6 minutes, respectively) vs either combination (10.6 [Diskus + HandiHaler] and 11.3 minutes [Turbuhaler + HandiHaler], respectively).,Significantly more patients preferred Ellipta over Diskus + HandiHaler or Turbuhaler + HandiHaler overall for taking their COPD medication (81% vs 9% and 84% vs 4%, respectively) and per the number of steps for taking their COPD medication (89% vs 8% and 91% vs 5%, respectively).,Fewer patients with COPD made critical errors with the single DPI, and patients required less instruction time, compared with each dual DPI combination.

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.

Public health is a priority for the Chinese Government.,Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance.,This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level.,We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017.,We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk.,We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI).,Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017.,Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017.,Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017.,Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs.,All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88.,The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain.,The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4).,China has made substantial progress in reducing the burden of many diseases and disabilities.,Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system.,China National Key Research and Development Program and Bill & Melinda Gates Foundation.

Traditional Chinese medicine (TCM) is commonly used to combine with pharmacotherapy for stable chronic obstructive pulmonary disease (COPD) in China and other Asian countries such as South Korea and Japan.,The objective of this systematic review is to evaluate the efficacy and safety of tonifying kidney therapy (Bushen, TK) for stable COPD.,Randomized controlled trials (RCTs) of TK for stable COPD were searched from 4 databases including Pubmed, the Cochrane library, CBM (China Biology Medicine disc, CBMdisc), CNKI (China National Knowledge Infrastructure) from inception to December 2017.,Two reviewers independently screened the literature, extracted the data and assessed the risk of bias in included studies.,RevMan 5.3 software was used for meta-analysis.,The primary outcomes analyzed in this meta-analysis were effectiveness, TCM Syndrome Score, dyspnea (modified Medical Research Council questionnaire [mMRC]), COPD health status (COPD Assessment Test [CAT]), exercise capacity (6-min walk distance in meters [6mWD]), and respiratory-specific quality of life (St George's Respiratory Questionnaire [SGRQ]).,Second outcomes analyzed for this meta-analysis were lung function (forced expiratory volume in 1 second [FEV1], FEV1%, forced vital capacity [FVC], FEV1/FVC), the frequency of acute exacerbation, T-lymphocyte subsets (CD4, CD8, CD4/CD8), and immunoglobulin (IgA, IgG, and IgM).,The summary results will be pooled using the random-effects model or fixed-effects model according to the heterogeneity of the included studies.,This systematic review will provide an evidence of TK for stable COPD, and will submit to a peer-reviewed journal for publication.,The conclusion of this systematic review will provide evidence to judge whether TK is an effective intervention for stable COPD patients.,PROSPERO CRD 42018090328.

Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD.

Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD.,We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease.,Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans.,Emphysema was quantified by the percent of lung with attenuation < −950HU on inspiratory CT.,Four gas trapping measures were defined: (1) Exp−856, the percent of lung < −856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC856-950, the difference between expiratory and inspiratory lung volumes with attenuation between −856 and −950 HU; and (4) Residuals from the regression of Exp−856 on percent emphysema.,In 8517 subjects with complete data, Exp−856 was highly correlated with emphysema.,The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema.,Exp−856, E/I MLA and RVC856-950 were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema.,In subjects with severe emphysema, E/I MLA and RVC856-950 showed the highest correlations with clinical variables.,Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence.,Its underdiagnosis and hence under-treatment is a general feature across all countries.,This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease.,A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms.,Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV1% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV1 ≥80% predicted.,In recent years, an elegant series of studies has shown that “exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment”.,In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation.,Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy.,This is an essential issue in COPD.,In fact, on one hand, airflow limitation, even mild, can unduly limit the patient’s physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease.,Therefore, we thought that it was worthwhile to analyze further and discuss this stage of “mild COPD”.,To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with “mild” airflow limitation.,The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind “mild” COPD.,Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system.

Clinical guidelines for management of patients with chronic obstructive pulmonary disease (COPD) include recommendations based on high levels of evidence, but gaps exist in their implementation.,The aim of this study was to examine the perspectives of medical practitioners regarding implementation of six high-evidence recommendations for the management of people with COPD.,Semi-structured interviews were conducted with medical practitioners involved with care of COPD patients in hospital and general practice.,Interviews sought medical practitioners’ experience regarding implementation of smoking cessation, influenza vaccination, pulmonary rehabilitation, guideline-based medications, long-term oxygen therapy for hypoxemia and plan and advice for future exacerbations.,Interviews were audiotaped, transcribed verbatim and analyzed using content analysis.,Nine hospital-based medical practitioners and seven general practitioners participated.,Four major categories were identified which impacted on implementation of the target recommendations in the care of patients with COPD: (1) role clarity of the medical practitioner; (2) persuasive communication with the patient; (3) complexity of behavioral change required; (4) awareness and support available at multiple levels.,For some recommendations, strength in all four categories provided significant enablers supporting implementation.,However, with regard to pulmonary rehabilitation and plans and advice for future exacerbations, all identified categories that presented barriers to implementation.,This study of medical practitioner perspectives has indicated areas where significant barriers to the implementation of key evidence-based recommendations in COPD management persist.,Developing strategies to target the identified categories provides an opportunity to achieve greater implementation of those high-evidence recommendations in the care of people with COPD.

The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003

COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment.,Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation.,We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens.,COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015.,Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured.,Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality.,Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed.,Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined.,A total of 62 COPD patients were enrolled.,These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively.,Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria.,Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively.,Influenza was the most commonly detected viral pathogen.,Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar.,Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation.,Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035).,Increased serum PCT is associated with longer LOS in COPD exacerbation.,However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.

The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.

Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients.

This systematic review aimed to identify the most effective components of interventions to facilitate self-management of health care behaviors for patients with COPD.,PROSPERO registration number CRD42011001588.,We used standard review methods with a systematic search to May 2012 for randomized controlled trials of self-management interventions reporting hospital admissions or health-related quality of life (HRQoL).,Mean differences (MD), hazard ratios, and 95% confidence intervals (CIs) were calculated and pooled using random-effects meta-analyses.,Effects among different subgroups of interventions were explored including single/multiple components and multicomponent interventions with/without exercise.,One hundred and seventy-three randomized controlled trials were identified.,Self-management interventions had a minimal effect on hospital admission rates.,Multicomponent interventions improved HRQoL (studies with follow-up >6 months St George’s Respiratory Questionnaire (MD 2.40, 95% CI 0.75-4.04, I2 57.9).,Exercise was an effective individual component (St George’s Respiratory Questionnaire at 3 months MD 4.87, 95% CI 3.96-5.79, I2 0%).,While many self-management interventions increased HRQoL, little effect was seen on hospital admissions.,More trials should report admissions and follow-up participants beyond the end of the intervention.

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a

Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users.

Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes.,Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown.,We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome.,This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations.,Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo.,The primary end point was mean in-hospital blood glucose concentration.,Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool.,52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo).,All were included in the primary end point analysis.,The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273).,No significant between-group differences were observed on any of the secondary end points.,Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants.,Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes.,ISRCTN66148745 and NCT01247870.

Cardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge.,The factors associated with cTnT elevation in COPD are not known.,From our hospital's database, all patients admitted with COPD exacerbation in 2000-03 were identified. 441 had measurement of cTnT performed.,Levels of cTnT ≥ 0.04 μg/l were considered elevated.,Clinical and historical data were retrieved from patient records, hospital and laboratory databases.,Odds ratios for cTnT elevation were calculated using logistic regression.,120 patients (27%) had elevated cTnT levels.,The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration.,The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20-1.94) for a 5 × 106/ml increase in neutrophils, 1.21 (1.12-1.32) for a 10 μmol/l increase in creatinine, 0.80 (0.69-0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09-1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15-1.82) for a 10 point increase in CIIS.,Multiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD.,The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury.

Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11).

The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a

Severe exacerbations and mortality are major outcomes in COPD, and risk factors for these events are actively searched for.,Several predictors of mortality have been identified in COPD.,The inspiratory capacity/total lung capacity (IC/TLC) ratio has been shown to be a strong predictor of all cause and respiratory mortality in patients with COPD.,The major objectives of this study were to analyze which clinical parameters, including lung volumes, were the best predictors of the 5-year cumulative risk of hospital admissions or death and the 5-year risk of exacerbations, in stable COPD patients.,This study retrospectively reviewed data from 98 stable COPD patients, consecutively recruited in 2012.,Forced expiratory volume in 1 s (FEV1), modified Medical Research Council dyspnea scale, exacerbation history (ExH), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 groups, and lung volumes were reviewed.,Five years later, this population was evaluated for cumulative exacerbations, hospital admissions, and mortality.,All the population, and GOLD group D separately, were analyzed.,The cumulative 5-year combined risk of hospital admission or death was significantly predicted by the ExH and the IC/TLC ratio.,Analyzing separately group D, FEV1 was the only predictor of this outcome.,The frequency of exacerbations in the previous year was the best predictor of future cumulative 5-year risk of subsequent exacerbations, both for the total population and the GOLD D group.,ExH and IC/TLC ratio were the best predictors of the most severe outcomes in COPD (admissions or mortality), independently of COPD severity.,FEV1 was the only predictor of the cumulative 5-year combined risk of hospital admission or death in the GOLD D group.,ExH was the best predictor of 5-year cumulative future risk of exacerbations.,Besides FEV1 and ExH, the IC/TLC ratio can be a useful predictor of severe outcomes in COPD.

Decreased airway lumen size and increased lung volume are major structural changes in chronic obstructive pulmonary disease (COPD).,However, even though the outer wall of the airways is connected with lung parenchyma and the mechanical properties of the parenchyma affect the behaviour of the airways, little is known about the interactions between airway and lung sizes on lung function and symptoms.,The present study examined these effects by establishing a novel computed tomography (CT) index, namely, airway volume percent (AWV%), which was defined as a percentage ratio of the airway tree to lung volume.,Inspiratory chest CT, pulmonary function, and COPD Assessment Tests (CAT) were analysed in 147 stable males with COPD.,The whole airway tree was automatically segmented, and the percentage ratio of the airway tree volume in the right upper and middle-lower lobes to right lung volume was calculated as the AWV% for right lung.,Low attenuation volume % (LAV%), total airway count (TAC), luminal area (Ai), and wall area percent (WA%) were also measured.,AWV% decreased as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grade increased (p < 0.0001).,AWV% was lower in symptomatic (CAT score ≥ 10) subjects than in non-symptomatic subjects (p = 0.036).,AWV% was more closely correlated with forced expiratory volume in 1 s (FEV1) and ratio of residual volume to total lung capacity (RV/TLC) than Ai, Ai to lung volume ratio, and volume of either the lung or the airway tree.,Multivariate analyses showed that lower AWV% was associated with lower FEV1 and higher RV/TLC, independent of LAV%, WA%, and TAC.,A disproportionally small airway tree with a relatively large lung could lead to airflow obstruction and gas trapping in COPD.,AWV% is an easily measured CT biomarker that may elucidate the clinical impacts of the airway-lung interaction in COPD.,The online version of this article (10.1186/s12931-019-1047-5) contains supplementary material, which is available to authorized users.

Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD).,It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD).,However, little is known about which phenotypes of COPD are associated with increased EAT.,One hundred and eighty smokers who were referred to the clinic were consecutively enrolled.,A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT.,These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively.,The same measurements were made on 225 Vietnamese COPD patients to replicate the results.,Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70.,The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients.,The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001).,These results were replicated in the Vietnamese population.,The EAT area is independently associated with airway wall thickness.,Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD.

Biomarkers for the management of chronic obstructive pulmonary disease (COPD) are limited.,The aim of this study was to explore new plasma biomarkers in patients with COPD.,Thyroxine-binding globulin (THBG) was initially identified by proteomics in a discovery panel and subsequently verified by enzyme-linked immunosorbent assay in another verification panel with a 1-year follow-up.,THBG levels were elevated in patients with COPD (9.2±2.3 μg/mL) compared to those of the controls (6.6±2.0 μg/mL).,Receiver operating characteristic curves suggested that THBG was able to slightly differentiate between patients with COPD and controls (area under the curve [AUC]: 0.814) and performed better if combined with fibrinogen (AUC: 0.858).,THBG was more capable of distinguishing Global Initiative for Obstructive Lung Disease stages I-III and IV (AUC: 0.851) compared with fibrinogen (AUC 0.582).,THBG levels were negatively associated with predicted percentage forced expiratory volume in 1 s and positively related to predicted percentage residual volume, RV/percentage total lung capacity, and percentage low-attenuation area.,COPD patients with higher baseline THBG levels had a greater risk of acute exacerbation (AE) than those with lower THBG levels (P=0.014, by Kaplan-Meier curve; hazard ratio: 4.229, by Cox proportional hazards model).,In summary, THBG is a potential plasma biomarker of COPD and can assist in the management of stable stage and AEs in COPD patients.

Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with systemic inflammation and balance impairment.,The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD]) phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation.,We enrolled 41 patients with COPD (22 stable and 19 in AECOPD) and 20 healthy subjects (control group), having no significant differences regarding the anthropometric data.,We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I) questionnaire, Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Single Leg Stance (SLS), 6-minute walking distance (6MWD), isometric knee extension (IKE) between these groups, and also the correlation between these scores and inflammatory biomarkers.,The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001), 6MWD (P<0.001), SLS (P<0.001), and BBS (P<0.001), at the same time noting a significant increase in median TUG score across the studied groups (P<0.001).,The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP) levels (10.60 vs 4.01; P=0.003) and decrease in PaO2 (70.1 vs 59.1; P<0.001).,We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes.,In both COPD groups, we observed that fibrinogen reversely and significantly correlated with the 6MWD, and FES-I questionnaire is correlated positively with TUG test.,Hs-CRP correlated reversely with the walking test and SLS test, while correlating positively with TUG test and FES-I questionnaire.,According to this study, COPD in advanced and acute stages is associated with an increased history of falls, systemic inflammation, balance impairment, and lower extremity muscle weakness.