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To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting.,A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009.,Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed.,Treatment classes included long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations.,At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up.,A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis.,At diagnosis (0-3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%).,Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months.,Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months.,Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months.,Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline.,The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state.

Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms.

Pulmonary rehabilitation (PR) is a key treatment of chronic obstructive pulmonary disease (COPD) but studies are still needed to identify the most pertinent criteria to personalize this intervention and improve its efficacy.,This real-life retrospective study compared the effects of home-based PR on exercise tolerance, anxiety, depression, and health-related quality of life (HRQoL) in COPD patients, according to their medical equipment.,Exercise tolerance, anxiety, depression, and HRQoL were evaluated in 109 patients equipped with long-term oxygen therapy (LTOT), 84 patients with noninvasive ventilation (NIV), 25 patients with continuous positive airway pressure (CPAP), and 80 patients with no equipment (NE), before, just after, and 6 and 12 months after PR.,At baseline, the body mass index in the CPAP and NIV groups was higher (p<0.05) than in the other two groups, and the forced expiratory volume in 1 second was lower in the LTOT and NIV groups (p<0.001).,All parameters improved after PR in the four groups (p<0.05), but for exercise tolerance, only the 6-minute stepper test showed maintained improvement after 6 and 12 months, whereas the 10 times sit-to-stand and timed up-and-go tests were only improved just after PR.,At every time point, exercise tolerance was lower in the LTOT group (p<0.05), with a similar trend in the NIV group.,Despite differences in the medical equipment to treat COPD, home-based PR showed comparable feasibility, safety, and efficacy in all equipment-based groups.,Medical equipment should therefore not be a barrier to home-based PR.

Personalized, global pulmonary rehabilitation (PR) management of patients with COPD is effective, regardless of the place in which this rehabilitation is provided.,The objective of this retrospective observational study was to study the long-term outcome of exercise capacity and quality of life during management of patients with COPD treated by home-based PR.,Home-based PR was administered to 211 patients with COPD (mean age, 62.3±11.1 years; mean forced expiratory volume in 1 second, 41.5%±17.7%).,Home-based PR was chosen because of the distance of the patient’s home from the PR center and the patient’s preference.,Each patient was individually managed by a team member once a week for 8 weeks with unsupervised continuation of physical exercises on the other days of the week according to an individual action plan.,Exercise conditioning, therapeutic patient education, and self-management were included in the PR program.,The home assessment comprised evaluation of the patient’s exercise capacity by a 6-minute stepper test, Timed Up and Go test, ten times sit-to-stand test, Hospital Anxiety and Depression score, and quality of life (Visual Simplified Respiratory Questionnaire, VQ11, Maugeri Respiratory Failure 28).,No incidents or accidents were observed during the course of home-based PR.,The 6-minute stepper test was significantly improved after completion of the program, at 6 months and 12 months, whereas the Timed Up and Go and ten times sit-to-stand test were improved after PR and at 6 months but not at 12 months.,Hospital Anxiety and Depression and quality of life scores improved after PR, and this improvement persisted at 6 months and 12 months.,Home-based PR for unselected patients with COPD is effective in the short term, and this effectiveness is maintained in the medium term (6 months) and long term (12 months).,Home-based PR is an alternative to outpatient management provided all activities, such as exercise conditioning, therapeutic education, and self-management are performed.

Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19).,Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown.,We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection.,We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects.,ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090).,ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049).,Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of -0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively.,However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051).,Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES.,Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD.,However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively).,This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung.,Further studies to understand the impact on clinical course of disease are now required.,The online version contains supplementary material available at 10.1186/s12931-021-01755-3.

Telemonitoring of symptoms and physiological signs has been suggested as a means of early detection of chronic obstructive pulmonary disease (COPD) exacerbations, with a view to instituting timely treatment.,However, algorithms to identify exacerbations result in frequent false-positive results and increased workload.,Machine learning, when applied to predictive modelling, can determine patterns of risk factors useful for improving prediction quality.,Our objectives were to (1) establish whether machine learning techniques applied to telemonitoring datasets improve prediction of hospital admissions and decisions to start corticosteroids, and (2) determine whether the addition of weather data further improves such predictions.,We used daily symptoms, physiological measures, and medication data, with baseline demography, COPD severity, quality of life, and hospital admissions from a pilot and large randomized controlled trial of telemonitoring in COPD.,We linked weather data from the United Kingdom meteorological service.,We used feature selection and extraction techniques for time series to construct up to 153 predictive patterns (features) from symptom, medication, and physiological measurements.,We used the resulting variables to construct predictive models fitted to training sets of patients and compared them with common symptom-counting algorithms.,We had a mean 363 days of telemonitoring data from 135 patients.,The two most practical traditional score-counting algorithms, restricted to cases with complete data, resulted in area under the receiver operating characteristic curve (AUC) estimates of 0.60 (95% CI 0.51-0.69) and 0.58 (95% CI 0.50-0.67) for predicting admissions based on a single day’s readings.,However, in a real-world scenario allowing for missing data, with greater numbers of patient daily data and hospitalizations (N=57,150, N+=55, respectively), the performance of all the traditional algorithms fell, including those based on 2 days’ data.,One of the most frequently used algorithms performed no better than chance.,All considered machine learning models demonstrated significant improvements; the best machine learning algorithm based on 57,150 episodes resulted in an aggregated AUC of 0.74 (95% CI 0.67-0.80).,Adding weather data measurements did not improve the predictive performance of the best model (AUC 0.74, 95% CI 0.69-0.79).,To achieve an 80% true-positive rate (sensitivity), the traditional algorithms were associated with an 80% false-positive rate: our algorithm halved this rate to approximately 40% (specificity approximately 60%).,The machine learning algorithm was moderately superior to the best symptom-counting algorithm (AUC 0.77, 95% CI 0.74-0.79 vs AUC 0.66, 95% CI 0.63-0.68) at predicting the need for corticosteroids.,Early detection and management of COPD remains an important goal given its huge personal and economic costs.,Machine learning approaches, which can be tailored to an individual’s baseline profile and can learn from experience of the individual patient, are superior to existing predictive algorithms and show promise in achieving this goal.,International Standard Randomized Controlled Trial Number ISRCTN96634935; http://www.isrctn.com/ISRCTN96634935 (Archived by WebCite at http://www.webcitation.org/722YkuhAz)

In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases.,In the discovery cohort, the gene expression level of 84 lncRNAs were measured in the blood of 24 adult patients including healthy controls and patients with asthma and COPD.,In the replication cohort the expression of 6 selected lncRNAs were measured in 163 subjects including healthy controls and adults with allergic rhinitis, asthma, COPD and children with asthma.,It was evaluated whether these lncRNAs can be used as diagnostic biomarkers for any studied disease.,With systems biology analysis the biological functions of the selected lncRNAs were predicted.,In the discovery cohort, the mean expression of 27 lncRNAs showed nominally significant differences in at least one comparison.,OIP5-AS1, HNRNPU, RP11-325K4.3, JPX, RP11-282O18.3, MZF1-AS1 were selected for measurement in the replication cohort.,Three lncRNAs (HNRNPU, RP11-325K4.3, JPX) expressed significantly higher in healthy children than in adult controls.,All the mean expression level of the 6 lncRNAs differed significantly between adult allergic rhinitis patients and controls.,RP11-325K4.3, HNRNPU and OIP5-AS1 expressed higher in allergic asthma than in non-allergic asthma.,COPD and asthma differed in the expression of RP11-325K4.3 from each other.,In examining of the lncRNAs as biomarkers the weighted accuracy (WA) values were especially high in the comparison of healthy controls and patients with allergic rhinitis.,OIP5-AS1 and JPX achieved 0.98 and 0.9 WA values, respectively, and the combination of the selected lncRNAs also resulted in a high performance (WA = 0.98).,Altogether, OIP5-AS1 had the highest discriminative power in case of three out of six comparisons.,Differences were detected in the expression of circulating lncRNAs in chronic respiratory diseases.,Some of these differences might be utilized as biomarkers and also suggest a possible role of these lncRNAs in the pathomechanism of these diseases.,The lncRNAs and the associated pathways are potential therapeutic targets in these diseases, but naturally additional studies are needed for the confirmation of these results.

The aim of the study was to determine the expression profile of long noncoding RNAs (lncRNAs) in CD4+ T cells from COPD patients and explore the clinical value of the lncRNAs.,First, microarray analysis was performed.,Differentially expressed lncRNAs were validated by quantitative real-time reverse transcription-PCR (qRT-PCR) in samples from 56 patients with acute exacerbations of COPD (AECOPD), 56 patients with stable COPD, and 35 healthy controls.,Meanwhile, the clinical value was tested by receiver operating characteristic curve analysis.,The functions of lncRNAs were analyzed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database.,The potential target genes that might be regulated by NR-026690 and ENST00000447867 were identified by the lncRNA-mRNA network and competing endogenous RNA network.,The transcriptional expression level of rap guanine nucleotide exchange factor 3 (RAPGEF3) was tested by qRT-PCR.,The correlation of the expression between NR-026690, ENST00000447867, and RAPGEF3 was analyzed by Spearman’s correlation test.,We found that the relative expression levels of ENST00000447867 and NR-026690 in the CD4+ T cells of AECOPD patients were significantly higher than in the stable COPD patients and control subjects by microarray and qRT-PCR validation.,The transcriptional expression level of RAPGEF3 in the CD4+ T cells was significantly higher in the AECOPD group compared to the control group (P<0.01) and the stable COPD group (P<0.05).,RAPGEF3 expression was positively associated with NR-026690 (r=0.4925, P<0.01) and ENST00000447867 (r=0.4065, P<0.01).,NR-026690 and ENST00000447867 might be potential biomarkers for COPD.,They might affect RAPGEF3 as miRNA sponges to regulate COPD development.

Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality.

Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients.

Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19).,This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients.,A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea.,The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model.,Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively.,The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs.,45.2%, P < 0.001) and male (52.5% vs.,36.6%, P < 0.001) patients than the non-COPD group.,Relatively greater proportions of patients with COPD received intensive critical care (7.1% vs.,3.7%, P = 0.041) and mechanical ventilation (5.7% vs.,2.4%, P = 0.015).,Multivariate analyses showed that COPD was not a risk factor for respiratory failure but was a significant independent risk factor for all-cause mortality (OR = 1.80, 95% CI 1.11-2.93) after adjustment for age, sex, and Charlson Comorbidity Index score.,Among COVID-19 patients, relatively greater proportions of patients with COPD received mechanical ventilation and intensive critical care.,COPD is an independent risk factor for all-cause mortality in COVID-19 patients in Korea.

Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD).,The major objective of the management of these patients is the prevention and effective treatment of exacerbations.,Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy.,It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens.,In some patients, systemic corticosteroids are also indicated to improve symptoms.,In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence.,It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy.,Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition.,Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations.,Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations.,There is a need to design long-term studies to evaluate these interventions in the natural history of the disease.,The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions.

With increasing availability of different treatments for chronic obstructive pulmonary disease (COPD), we sought to understand patient preferences for COPD treatment in the UK, USA, and Germany using a discrete choice experiment (DCE).,Qualitative research identified six attributes associated with COPD maintenance treatments: ease of inhaler use, exacerbation frequency, frequency of inhaler use, number of different inhalers used, side effect frequency, and out-of-pocket costs.,A DCE using these attributes, with three levels each, was designed and tested through cognitive interviews and piloting.,It comprised 18 choice sets, selected using a D-efficient experimental design.,Demographics and disease history were collected and the final DCE survey was completed online by participants recruited from panels in the UK, USA and Germany.,Responses were analyzed using mixed logit models, with results expressed as odds ratios (ORs).,Overall, 450 participants (150 per country) completed the DCE; most (UK and Germany, 97.3%; USA, 98.0%) were included in the final analysis.,Based on relative attribute importance, avoidance of side effects was found to be most important (UK: OR 11.65; USA: OR 7.17; Germany: OR 11.45; all p<0.0001), followed by the likelihood of fewer exacerbations (UK: OR 2.22; USA: OR 1.63; Germany: OR 2.54; all p<0.0001) and increased ease of use (UK: OR 1.84; USA: OR 1.84; Germany: OR 1.60; all p<0.0001).,Number of inhalers, out-of-pocket costs, and frequency of inhaler use were found to be less important.,Preferences were relatively consistent across the three countries.,All participants required a reduction in exacerbations to accept more frequent inhaler use or use of more inhalers.,When selecting COPD treatment, individuals assigned the highest value to the avoidance of side effects, experiencing fewer exacerbations, and ease of inhaler use.,Ensuring that patients’ preferences are considered may encourage treatment compliance.

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.

Assessments of lung function, exacerbations and health status are common measures of chronic obstructive pulmonary disease (COPD) progression and treatment response in clinical trials.,We hypothesised that a composite endpoint could more holistically assess clinically important deterioration (CID) in a COPD clinical trial setting.,A composite endpoint was tested in a post hoc analysis of 5652 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2-4 COPD from the 4-year UPLIFT study.,Patients received tiotropium 18 μg or placebo.,The composite endpoint included time to first confirmed decrease in trough forced expiratory volume in 1 s (FEV1) ≥100 mL, confirmed increase in St.,George’s Respiratory Questionnaire (SGRQ) total score ≥ 4 units, or moderate/severe exacerbation.,Most patients (> 80%) experienced CID, with similar incidence among GOLD subgroups.,Most confirmed trough FEV1 (74.6-81.6%) and SGRQ (72.3-78.1%) deteriorations were sustained across the study and in all GOLD subgroups.,Patients with CID more frequently experienced subsequent exacerbation (hazard ratio [HR] 1.79; 95% confidence interval [CI] 1.67, 1.92) or death (HR 1.21; 95% CI 1.06, 1.39) by Month 6.,CID was responsive to bronchodilator treatment.,Composite endpoints provide additional information on COPD progression and treatment effects in clinical trials.,ClinicalTrials.gov NCT00144339.

The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.

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.

Polypharmacy of respiratory medications is commonly observed in patients with chronic obstructive pulmonary disease (COPD).,The aims of this study were to investigate determinants of polypharmacy and to study the consistency of actual respiratory drug use with current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in pulmonary rehabilitation candidates with COPD.,Data were extracted from the records of all patients with a diagnosis of COPD referred for pulmonary rehabilitation to CIRO+ between 2005 and 2009.,Use of respiratory medications, self-reported COPD exacerbations, lung function, blood gases, exercise capacity, Medical Research Council (MRC) dyspnea grade, and St George’s Respiratory Questionnaire (SGRQ) were recorded as part of assessment of health status.,In total, 1859 COPD patients of mean age (± standard deviation) 64.3 ± 9.7 years and with a forced expiratory volume in one second (FEV1) of 44.7% ± 18.2% were included.,On average, patients used 3.5 ± 1.5 respiratory medications; this number increased with increasing GOLD stage, MRC score, and SGRQ scores.,FEV1 (% predicted), SGRQ, and number of recent exacerbations were independent determinants of polypharmacy.,Use of long-acting bronchodilators and inhaled corticosteroids was substantial and comparable in all GOLD stages.,Use of corticosteroids was not restricted to patients with frequent exacerbations.,Polypharmacy of respiratory medications is common in COPD patients with persistent symptoms.,In addition to severity of disease, health status is an independent predictor of polypharmacy.,Actual drug use in COPD patients referred for pulmonary rehabilitation is partially inconsistent with current GOLD guidelines.

Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers.,The utility of these clinical subtypes is unclear.,However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant.,The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.,Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis.,Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%.,Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%).,Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized.,Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St.,George’s Respiratory Questionnaire score 43 vs 31, p < 0.0001).,Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use.,The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study.,Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes.,COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa.,Clinicaltrials.gov identifiers: COPDGene NCT00608764, ECLIPSE NCT00292552.,The online version of this article (doi:10.1186/1471-2466-14-164) contains supplementary material, which is available to authorized users.

Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD).,However, limited data are available regarding the longitudinal change in dyspnea, and it remains unknown which of relevant measurements might be used for following dyspnea.,We previously consecutively recruited 137 male outpatients with moderate to very severe COPD, and followed them every 6 months for 5 years.,We then reviewed and reanalyzed the data focusing on the relationships between the change in dyspnea and the changes in other clinical measurements of lung function, exercise tolerance tests and psychological status.,Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ) and the St.,George’s Respiratory Questionnaire (SGRQ) were also used.,Dyspnea at the end of exercise tolerance tests was measured using the Borg scale.,The mMRC, CRQ dyspnea and SGRQ activity significantly worsened over time (p < 0.001), but the OCD did not (p = 0.097).,Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV1) (correlation of determination (r2) = 0.05-0.19), diffusing capacity for carbon monoxide (r2 = 0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r2 = 0.14-0.17), although these correlations were weak.,Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements.,Dyspnea worsened over time in patients with COPD.,However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements.,Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status.,Changes in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements.

Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD).,However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD.,We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.,Eligible participants (n = 170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months.,COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.,After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41 ± 3.56 and 11.08 ± 3.05, p < 0.0001).,The changes of CAT (p = 0.028) and mMRC scores (p = 0.049) between the two groups differed after 1 month of treatment.,In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF25% pred) was significantly improved after 3 months (4.84 ± 8.73%, p < 0.0001) and 6 months (6.21 ± 8.65%, p < 0.0001).,There was a significant difference in small airway function tests (MEF50% pred, MEF25% pred, and MMEF% pred) between the two groups after 6 month of treatment (p = 0.003, p < 0.0001, and p = 0.021, respectively).,Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up.,Additionally, this therapy also improved the indicators of small airway function.,Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).,The online version of this article (10.1007/s12325-018-0831-9) contains supplementary material, which is available to authorized users.

To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD.,We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo.,A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George’s Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24.,Inconsistency models were not statistically significant for all outcomes.,LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24.,All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1.,Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant.,LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement.,Similar trends were observed for the transition dyspnea index and St George’s Respiratory Questionnaire outcomes.,There were no significant differences in the incidences of adverse events among all treatment options.,LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement.,There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes.

In chronic obstructive pulmonary disease (COPD), both the time needed for patients to gain symptom improvement with long-acting bronchodilator therapy and whether an early response is predictive of a sustained response is unknown.,This study aimed to investigate how quickly meaningful symptom responses are seen in patients with COPD with bronchodilator therapy and whether these responses are sustained.,Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a 24-week, double-blind, double-dummy, parallel-group trial that randomised patients to umeclidinium/vilanterol (UMEC/VI), umeclidinium or salmeterol.,Daily Evaluating Respiratory Symptoms in COPD (E-RS:COPD) score and rescue salbutamol use were captured via an electronic diary and analysed initially in 4-weekly periods.,Post hoc analyses assessed change from baseline in daily E-RS:COPD score and rescue medication use weekly (Weeks 1-8), and association between E-RS:COPD responder status at Weeks 1-4 and later time points.,In the intent-to-treat population (n = 2425), reductions from baseline in E-RS:COPD scores and rescue medication use were apparent from Day 2 with all treatments.,Treatment differences for UMEC/VI versus either monotherapy plateaued by Week 4-8 and were sustained at Weeks 21-24; improvements were consistently greater with UMEC/VI.,For all treatments, most patients (60-85%) retained their Weeks 1-4 E-RS:COPD responder/non-responder status at Weeks 21−24.,Among patients receiving UMEC/VI who were E-RS:COPD responders at Weeks 1-4, 70% were responders at Weeks 21-24.,Patients with symptomatic COPD had greater potential for early symptom improvements with UMEC/VI versus either monotherapy.,This benefit was generally maintained for 24 weeks.,Early monitoring of treatment response can provide clinicians with an early indication of a patient’s likely longer-term response to prescribed bronchodilator treatment and will facilitate appropriate early adjustments in care.,NCT03034915, 2016-002513-22 (EudraCT Number).,The reviews of this paper are available via the supplemental material section.

Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users.

Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users.

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease.

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.

Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction.,We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain.,We interviewed 576 subjects of both sexes aged 20-70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire.,Forced spirometry was performed by 497 subjects according to ATS normative.,Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women).,Textile industry was the most frequently reported job in relation to these exposures (39%).,Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3).,Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits.,Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV1 -80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV1/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed.,Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry.,Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking.

The common comorbidities associated with COPD include, among others, anxiety, depression, and insomnia, for which the typical treatment involves the use of benzodiazepines (BZD).,However, these medicines should be used with extra caution among COPD patients, since treatment with traditional BZD may compromise respiratory function.,This study investigated the use of BZD among persons suffering from COPD by analyzing three relevant indicators: 1) the sum of defined daily doses (DDD); 2) the number of prescribers involved; and 3) the number of different types of BZD used.,The study builds on a linkage of national prescription data and patient-administrative data, which includes all Norwegian drug prescriptions to persons hospitalized with a COPD diagnosis during 2009, amounting to a total of 5,380 observations.,Regression techniques were used to identify the patients and the clinical characteristics associated with BZD use.,Of the 5,380 COPD patients treated in hospital during 2009, 3,707 (69%) were dispensed BZD during the following 12 months.,Moreover, they were dispensed on average 197.08 DDD, had 1.22 prescribers, and used 0.98 types of BZD during the year.,Women are more likely to use BZD for all levels of BZD use.,Overnight planned care not only increases the risk of BZD use (DDD), but also the number of prescribers and the types of BZD in use.,In light of the high levels of BZD prescription found in this study, especially among women, it is recommended that general practitioners, hospital specialists, and others treating COPD patients should aim to acquire a complete picture of their patients’ BZD medication before more is prescribed in order to keep the use to a minimum.

Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).,Design Population based longitudinal consecutive cohort study.,Setting Centres prescribing long term oxygen therapy in Sweden.,Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register.,Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs.,Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation.,No patient was lost to follow-up.,Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively.,Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend.,Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44).,Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99).,Associations were not modified by being naive to the drugs or by hypercapnia.,Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.

COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users.

Counseling has been suggested as a promising approach for facilitating changes in health behavior.,The aim of this systematic review of counseling interventions for people with COPD was to describe: 1) counseling definitions, 2) targeted health behaviors, 3) counseling techniques and 4) whether commonalities in counseling techniques were associated with improved health behaviors.,Ten databases were searched for original randomized controlled trials which included adults with COPD, used the term “counseling” as a sole or component of a multifaceted intervention and were published in the previous 10 years.,Data extraction, study appraisal and coding for behavior change techniques (BCTs) were completed by two independent reviewers.,Data were synthesized descriptively, with meta-analysis conducted where possible.,Of the 182 studies reviewed as full-text, 22 were included.,A single study provided a definition for counseling.,Two key behaviors were the main foci of counseling: physical activity (n=9) and smoking cessation (n=8).,Six studies (27%) reported underlying models and/or theoretical frameworks.,Counseling was the sole intervention in 10 studies and part of a multicomponent intervention in 12.,Interventions targeting physical activity included a mean of 6.3 (±3.1) BCTs, smoking cessation 4.9 (±2.9) BCTs and other behaviors 6.5 (±3.9) BCTs.,The most frequent BCTs were social support unspecified (n=22; 100%), goal setting behavior (n=11), problem-solving (n=11) and instructions on how to perform the behavior (n=10).,No studies shared identical BCT profiles.,Counseling had a significant positive effect for smoking cessation and positive but not significant effect for physical activity.,Counseling for health behavior change was rarely defined and effectiveness varied by target behavior.,Provision of specific details when reporting studies of counseling interventions (definition, BCTs, dosage) would allow clarification of the effectiveness of counseling as an approach to health behavior change in people with COPD.

Chronic obstructive pulmonary disease (COPD) is a costly long-term condition associated with frequent Accident and Emergency (A&E) and hospital admissions.,Psychological difficulties and inadequate self-management can amplify this picture.,To compare a cognitive-behavioural manual versus information booklets (IB) on health service use, mood and health status.,Two hundred and twenty-two COPD patients were randomly allocated to receive either the COPD breathlessness manual (CM) or IB.,They were instructed to work through their programme at home, over 5 weeks.,Guidance from a facilitator was provided at an initial home visit plus two telephone call follow-ups.,After 12 months, total A&E visits had reduced by 42% in the CM group, compared with a 16% rise in the IB group.,The odds of people in the IB group attending A&E 12 months post-intervention was 1.9 times higher than for the CM group (CI 1.05-3.53).,Reduction in hospital admissions and bed days were greatest in the CM group.,At 6 months, there were significantly greater improvements in anxiety (F (2,198)=5.612, P=0.004), depression (F (1.8,176.1)=10.697, P⩽0.001) and dyspnoea (F (2,198)=18.170, P⩽0.001) in the CM group.,Estimated savings at 12 months were greatest in the CM group, amounting to £30k or £270 per participant.,The COPD manual, which addresses physical and mental health, is a straightforward cost-effective intervention that is worth offering to COPD patients within primary or secondary care.

High blood urea nitrogen (BUN) is associated with an elevated risk of mortality in various diseases, such as heart failure and pneumonia.,Heart failure and pneumonia are common comorbidities of acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,However, data on the relationship of BUN levels with mortality in patients with AECOPD are sparse.,The purpose of this study was to evaluate the correlation between BUN level and in-hospital mortality in a cohort of patients with AECOPD who presented at the emergency department (ED).,A total of 842 patients with AECOPD were enrolled in the retrospective observational study from January 2018 to September 2020.,The outcome was all-cause in-hospital mortality.,Receiver operating characteristic (ROC) curve analysis and logistic regression models were performed to evaluate the association of BUN levels with in-hospital mortality in patients with AECOPD.,Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics, and logistic regression models were also performed in the propensity score matching cohort.,During hospitalization, 26 patients (3.09%) died from all causes, 142 patients (16.86%) needed invasive ventilation, and 190 patients (22.57%) were admitted to the ICU.,The mean level of blood urea nitrogen was 7.5 ± 4.5 mmol/L.,Patients in the hospital non-survivor group had higher BUN levels (13.48 ± 9.62 mmol/L vs.,7.35 ± 4.14 mmol/L, p < 0.001) than those in the survivor group.,The area under the curve (AUC) was 0.76 (95% CI 0.73-0.79, p < 0.001), and the optimal BUN level cutoff was 7.63 mmol/L for hospital mortality.,As a continuous variable, BUN level was associated with hospital mortality after adjusting respiratory rate, level of consciousness, pH, PCO2, lactic acid, albumin, glucose, CRP, hemoglobin, platelet distribution width, D-dimer, and pro-B-type natriuretic peptide (OR 1.10, 95% CI 1.03-1.17, p=0.005).,The OR of hospital mortality was significantly higher in the BUN level ≥7.63 mmol/L group than in the BUN level <7.63 mmol/L group in adjusted model (OR 3.29, 95% CI 1.05-10.29, p=0.041).,Similar results were found after multiple imputation and in the propensity score matching cohort.,Increased BUN level at ED admission is associated with hospital mortality in patients with AECOPD who present at the ED.,The level of 7.63 mmol/L can be used as a cutoff value for critical stratification.

Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of their disease, sometimes requiring hospital admission and being associated with increased mortality.,Although previous studies have reported mortality from exacerbations of COPD, there is limited information about prediction of individual in-hospital mortality.,We therefore aimed to use data from a nationwide inpatient database in Japan to generate a nomogram for predicting in-hospital mortality from patients’ characteristics on admission.,We retrospectively collected data on patients with COPD who had been admitted for exacerbations and been discharged between July 1, 2010 and March 31, 2013.,We performed multivariable logistic regression analysis to examine factors associated with in-hospital mortality and thereafter used these factors to develop a nomogram for predicting in-hospital prognosis.,The study comprised 3,064 eligible patients.,In-hospital death occurred in 209 patients (6.8%).,Higher mortality was associated with older age, being male, lower body mass index, disturbance of consciousness, severe dyspnea, history of mechanical ventilation, pneumonia, and having no asthma on admission.,We developed a nomogram based on these variables to predict in-hospital mortality.,The concordance index of the nomogram was 0.775.,Internal validation was performed by a bootstrap method with 50 resamples, and calibration plots were found to be well fitted to predict in-hospital mortality.,We developed a nomogram for predicting in-hospital mortality of exacerbations of COPD.,This nomogram could help clinicians to predict risk of in-hospital mortality in individual patients with COPD exacerbation.

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.

COPD, characterized by chronic inflammation and airway remodeling, has significant pathological alterations in composition and deposition of the extracellular matrix.,The expression of procollagen 1 C-terminal peptide (PICP) and collagen type 1 C-terminal telopeptide (ICTP), two major by-products in the synthesis and degradation of collagen, was shown to be positively correlated with inflammatory mediator levels in previous studies.,In this study, we investigated whether the serum concentrations of PICP and ICTP were associated with the inflammation level for patients with stable COPD.,We collected serum samples from 25 control subjects and 20 patients with stable COPD from December 2011 to October 2012 in Shanghai Zhongshan Hospital and Shanghai Dahua Hospital.,We determined concentrations of PICP, ICTP, C-reactive protein (CRP), IL-6, IL-8, and tumor necrosis factor (TNF)-α by using enzyme-linked immunosorbent assay methods.,Demographic characteristics were comparable between the two groups.,In patients with stable COPD, serum levels of CRP, IL-6, IL-8, and TNF-α were all elevated compared to control subjects, but only changes of IL-6 achieved statistical significance.,Serum concentration of PICP was significantly elevated in patients with COPD, and level of ICTP was slightly decreased.,Moreover, serum concentrations of PICP were positively correlated with the levels of both IL-6 and IL-8.,The increased levels of serum PICP in COPD might indicate the condition of airway remodeling, and IL-6 and/or IL-8 might play an important role in stimulating collagen synthesis.

Background: Glycopyrrolate administered by a novel, investigational eFlow® Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes.,Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.,Methods: The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time.,Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time.,Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile.,Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.,Results: The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL).,Delivered dose was 88% of the nominal dose for both formulation strengths.,The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL.,Nebulization times were 1-2.5 minutes with no apparent increasing trend with use over a 60-day period.,The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1-0.2 μm) after 60-day simulated use.,Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.,Conclusion: The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition.,The unit dose vial mitigates medication misuse and ensures dose uniformity.,Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD.

COPD is a progressive disease characterized by exacerbations and a decline in health status and lung function.,Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy.,This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting β2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID.,CRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings.,Three definitions of CID (D1-D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV1), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD).,In D1 and D2, either TDI or CCQ was evaluated along with FEV1 and AECOPD, whereas in D3, all 4 parameters were included.,ClinicalTrials.gov number: NCT01985334.,Of the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments.,The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30-0.55]; D2: OR 0.41 [95% CI: 0.31-0.55]; D3: OR 0.39 [95% CI: 0.29-0.52]).,Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56-1.02]; D2: OR 0.75 [95% CI: 0.56-1.00]; D3: OR 0.67 [95% CI: 0.51-0.89]).,In this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice.

We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations.

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.

Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy.,We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population.,In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190- -30 HU; skeletal muscle -29-150 HU.,Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03).,Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength.,Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72-0.95).,Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes.,CT-based skeletal muscle adiposity markers reflect muscle quality in COPD and help identify patients with fibre shifthttp://ow.ly/xolWA

There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease (COPD).,It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation.,Patients were randomised to either singing classes or a film club for eight weeks.,Response was assessed quantitatively through health status questionnaires, measures of breathing control, exercise capacity and physical activity and qualitatively, through structured interviews with a clinical psychologist.,The singing group (n=13 mean(SD) FEV1 44.4(14.4)% predicted) and film group (n=11 FEV1 63.5(25.5)%predicted) did not differ significantly at baseline.,There was a significant difference between the response of the physical component score of the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but no difference in response of the mental component score of the SF-36, breathing control measures, exercise capacity or daily physical activity.,In the qualitative element, positive effects on physical well-being were reported in the singing group but not the film group.,Singing classes have an impact on health status distinct from that achieved simply by taking part in a group activity.,Registration Current Controlled Trials - ISRCTN17544114

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity stage classifies Chronic Obstructive Pulmonary Disease (COPD) into groups based on symptoms, exacerbations and forced expiratory volume in one second (FEV1).,This allows patients to change to less severe COPD stages, a novel aspect of assessment not previously evaluated.,We aimed to investigate the association between temporal changes in GOLD severity stage and outcomes in COPD patients.,This was a record-linkage study using patients registered with a Scottish regional COPD network 2000-2015.,Annual spirometry & symptoms were recorded and linked to healthcare records to identify exacerbations, hospitalisations and mortality.,Spirometry, modified Medical Research Council (mMRC) dyspnoea scale and acute exacerbations over the previous year were used to assign GOLD severity at each visit.,A time-dependent Cox model was used to model time to death.,Secondary outcomes were respiratory specific mortality and hospitalisations.,Effect sizes are expressed as Hazard Ratios HR (95%CI).,Four thousand, eight hundred and eighty-five patients (mean age 67.3 years; 51.3% female) with 21,348 visits were included.,During a median 6.6 years follow-up there were 1530 deaths.,For the secondary outcomes there were 712 respiratory deaths and 1629 first hospitalisations.,Across 16,463 visit-pairs, improvement in COPD severity was seen in 2308 (14%), no change in 11,010 (66.9%) and worsening in 3145 (19.1).,Compared to patients staying in GOLD stage A, those worsening had a stepwise increased mortality and hospitalisations.,Improving COPD severity classification was associated with reduced mortality and worsening COPD severity was associated with increased mortality and hospitalisations.,Change in GOLD group has potential as monitoring tool and outcome measure in clinical trials.,The online version of this article (10.1186/s12931-018-0960-3) contains supplementary material, which is available to authorized users.

Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users.

Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis.,In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release.,Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined.,The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD.,Primary adult lung fibroblasts were isolated from patients with or without COPD.,MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without inflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α.,MiR-503 expression was decreased in COPD lung fibroblasts.,The expression of miR-503 was positively correlated with %FVC, %FEV1, and %DLco as well as IL-6, -8, PGE2, HGF, KGF, and VEGF in the absence or presence of IL-1ß/TNF-α.,In addition, IL-8 and VEGF release from COPD lung fibroblasts were increased compared to those from control.,Exogenous miR-503 inhibited VEGF release from primary adult and fetal lung fibroblasts but not IL-8 release.,As expected, COPD fibroblasts proliferated more slowly than control fibroblasts.,MiR-503 did not affect proliferation of either control or COPD lung fibroblasts.,MiR-503 inhibition of VEGF protein production and mRNA was mediated by direct binding to the 3’ untranslated region of VEGF mRNA.,Endogenous miR-503 was differently regulated by exogenous stimulants associated with COPD pathogenesis, including IL-1ß/TNF-α, TGF-ß1 and PGE2.,Endogenous miR-503 inhibition augmented VEGF release by IL-1ß/TNF-α and TGF-ß1 but not by PGE2, demonstrating selectivity of miR-503 regulation of VEGF.,In conclusions, reduced miR-503 augments VEGF release from lung fibroblasts from patients with COPD.,Since VEGF contributes to disturbed vasculature in COPD, altered miR-503 production might play a role in modulating fibroblast-mediated vascular homeostasis in COPD.

Chronic obstructive pulmonary disease (COPD) patients are at higher risk of developing lung cancer and its metastasis, but no suitable biomarker has been reported for differential diagnosis of these patients.,Levels of serum biomarkers (VEGF, IL-8, MMP-9 and MMP-2) were analyzed in these patients, which were compared with healthy donors (HD).,Levels of VEGF (P < 0.005) and MMP-9 (P < 0.05) were significantly higher in COPD patients than HD.,Compared to HD, a decrease in IL-8 (~8.1 folds; P < 0.0001) but an increase in MMP-9 (~1.6 folds; P < 0.05) levels were observed in the lung cancer patients.,Cancer patients showed significantly (P < 0.005) lower levels of serum VEGF (1.9 folds) and IL-8 (~9 folds) than the COPD patients.,VEGF level was significantly higher (2.6 folds; P < 0.0005) in metastatic than non-metastatic cancer patients.,However, MMP-2 didn’t show significant variation in these patients.,The Youden’s index (YI) values for lung cancer diagnosis in HD using IL-8 was 0.55 with 83.3% overall accuracy.,VEGF was able to diagnose COPD in HD with better YI (0.38) and overall accuracy (70.6%).,IL-8 was able to diagnose cancer in COPD patients and HD with YI values of 0.35, 0.55 with 71% and 83.3% overall accuracy, respectively.

To determine the characteristics of undiagnosed chronic obstructive pulmonary disease (COPD) in a senior community center.,We performed a cross-sectional, observational study with the following procedures: questionnaire to record demographic and health status data, anthropometry, questionnaire about COPD risk factors and symptoms, spirometry, and socioeconomic evaluation.,Simple logistic regression and multiple analyses were carried out to assess associations.,The studied variables were tested for associations with previous COPD diagnosis.,Three hundred and thirty-five subjects aged 50 years or older were recruited and 318 completed the protocol.,Seventy-one (22%) had presumptive COPD.,Among them, 57 (80%) did not have a previous physician-made diagnosis of COPD.,We found no associations between previous diagnosis and socioeconomic status, anthropometric data, or risk factors.,Regarding respiratory symptoms, there was an association between previous COPD diagnosis and wheezing (P=0.011).,FEV1 and FVC values were lower in the previous diagnosis group compared to the group without a previous diagnosis (P<0.001, Student’s t-test).,We found an association of lower FEV1 (<50% predicted value) with a previous diagnosis (P=0.028).,Our results showed a high prevalence of undiagnosed obstructive ventilatory defects in a senior community center.,Previous COPD diagnosis was associated with more severe disease and more frequent wheezing.,This study highlights the potential of these centers to increase COPD diagnosis and to reduce its risks.

The aim of this study was to measure dynamic lung hyperinflation and its influence on dyspnea perception in moderate and severe chronic obstructive pulmonary disease patients after performing activities of daily living.,We measured inspiratory capacity, sensation of dyspnea, peripheral oxygen saturation, heart rate and respiratory rate in 19 chronic obstructive pulmonary disease patients.,These measurements were taken at rest and after performing activities of daily living (e.g., going up and down a set of stairs, going up and down a ramp and sweeping and mopping a room).,The inspiratory capacity of patients at rest was significantly decreased compared to the capacity of patients after performing activities.,The change in inspiratory capacity was -0.67 L after going up and down a ramp, -0.46 L after sweeping and mopping a room, and -0.55 L after climbing up and down a set of stairs.,Dyspnea perception increased significantly between rest, sweeping and mopping, and going up and down a set of stairs.,Dyspnea perception correlated positively with inspiratory capacity variation (r = 0.85) and respiratory rate (r = 0.37) and negatively with peripheral oxygen saturation (r = -0.28).,Chronic obstructive pulmonary disease patients exhibited reductions in inspiratory capacity and increases in dyspnea perception during commonly performed activities of daily living, which may limit physical performance in these patients.

Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases.,The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of smokers or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis.,Computational analyses of omics technologies are expected as one of the solutions to resolve such complexities.,We obtained transcriptomic data by in vitro testing with exposures of human bronchial epithelial cells to the inducers for early events of COPD to identify the potential descriptive marker genes.,With the identified genes, the machine learning technique was employed with the publicly available transcriptome data obtained from the lung specimens of COPD and non-COPD patients to develop the model that can reflect the risk continuum across smoking and COPD.,The expression levels of 15 genes were commonly altered among in vitro tissues exposed to known inducible factors for earlier events of COPD (exposure to cigarette smoke, DNA damage, oxidative stress, and inflammation), and 10 of these genes and their corresponding proteins have not previously reported as COPD biomarkers.,Although these genes were able to predict each group with 65% accuracy, the accuracy with which they were able to discriminate COPD subjects from smokers was only 29%.,Furthermore, logistic regression enabled the conversion of gene expression levels to a numerical index, which we named the “potential risk factor (PRF)” index.,The highest significant index value was recorded in COPD subjects (0.56 at the median), followed by smokers (0.30) and non-smokers (0.02).,In vitro tissues exposed to cigarette smoke displayed dose-dependent increases of PRF, suggesting its utility for prospective risk estimation of tobacco products.,Our experimental-based transcriptomic analysis identified novel genes associated with COPD, and the 15 genes could distinguish smokers and COPD subjects from non-smokers via machine-learning classification with remarkable accuracy.,We also suggested a PRF index that can quantitatively reflect the risk continuum across smoking and COPD pathogenesis, and we believe it will provide an improved understanding of smoking effects and new insights into COPD.

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.

Eighty percent of COPD patients experience dyspnea during activities of daily life (ADL).,To the best of our knowledge, the Modified Medical Research Council (MMRC) dyspnea scale is the only validated scale designed to quantify dyspnea during ADL available in the French language.,Two other instruments are only available in English versions: the London Chest Activity of Daily Living (LCADL) scale that allows a specific evaluation of dyspnea during ADL and the Dyspnea-12 questionnaire that evaluates the affective (emotional) and sensory components of dyspnea in daily life.,The aim of this study was to translate and validate French versions of both LCADL and Dyspnea-12 questionnaires and to determine the reliability of these versions for the evaluation of dyspnea in severe to very severe COPD patients.,Both translation and cultural adaptation were based on Beaton’s recommendations.,Fifty consecutive patients completed the French version of LCADL and Dyspnea-12 and other questionnaires (MMRC, Saint George’s Respiratory Questionnaire [SGRQ], Hospital Anxiety and Depression [HAD]), at a 2-week interval.,Internal consistency, validity, and reliability of LCADL and Dyspnea-12 were evaluated.,The French version of LCADL and Dyspnea-12 demonstrated good internal consistency with Cronbach’s α of, respectively, 0.84 and 0.91.,LCADL was correlated significantly with item activity of SGRQ (ρ=0.55, p<0.001), total score of SGRQ (ρ=0.63, p<0.001), item impact of SGRQ (ρ=0.57, p<0.001), and HAD-depression (HAD-D) (ρ=0.47, p=0.001); and Dyspnea-12 was correlated significantly with MMRC (ρ=0.39, p<0.001), HAD-anxiety (ρ=0.64, p<0.001), and HAD-D (ρ=0.64, p<0.001).,The French version of LCADL and Dyspnea-12 demonstrated good test-retest reliability with, respectively, intraclass coefficient =0.84 (p<0.001) and 0.91 (p<0.001).,The French versions of LCADL and Dyspnea-12 questionnaires are promising tools to evaluate dyspnea in severe to very severe COPD patients.

Upper-extremity exercise is for pulmonary rehabilitation.,The 6-minute pegboard and ring test (6PBRT) was developed to evaluate arm exercise capacity in patients with chronic obstructive pulmonary disease (COPD).,The purpose of this study was to characterize the 6PBRT and evaluate its relationship with upper-extremity activities of daily living (ADLs) in COPD patients.,Twenty outpatients with mild to very severe COPD underwent the 6PBRT and spirometry, and their maximal inspiratory and expiratory pressures and grip strength were measured.,For the 6PBRT, subjects were asked to move as many rings as possible in 6 minutes, and the score was the number of moved rings during the 6-minute period.,Upper-extremity ADLs were evaluated with the upper extremity activities subdomain of the modified Pulmonary Functional Status and Dyspnea Questionnaire.,Upper-extremity ADLs were also measured objectively by using a wrist accelerometer every day for 1 week.,There was a positive correlation between 6PBRT score and inspiratory capacity (r = 0.71, P , 0.001), inspiratory capacity/total lung capacity predicted (r = 0.68, P , 0.01), and forced vial capacity (r = 0.57, P , 0.01).,There was also a positive correlation between 6PBRT score and accelerometer count (r = 0.54, P , 0.05) and a negative correlation between 6PBRT score and arm activity score (ρ = −0.49, P , 0.05).,The 6PBRT may be a predictive test to maintain and improve upper-extremity ADL during pulmonary rehabilitation in patients with COPD.

Combined pulmonary fibrosis and emphysema (CPFE) is increasingly acknowledged as a separate syndrome with distinct clinical, physiological and radiological characteristics.,We sought to identify physiologic and radiographic indices that predict mortality in CPFE.,Data on clinical characteristics, pulmonary function, high-resolution computed tomography (HRCT) and treatment were compared between patients with usual interstitial pneumonia (UIP) plus emphysema (CPFE group) and those with IPF alone (IPF group).,Composite physiologic index (CPI) and HRCT scores at diagnosis and during follow-up were assessed.,CPFE group (N = 87) was characterized by the predominance of males and smokers, who were less likely to have viral infection prior to the diagnosis, and display basal crackles, finger clubbing and wheeze, as compared to that in the IPF group (N = 105).,HRCT and CPI scores increased over time in both groups.,Moreover, CPFE group had a poorer prognosis, lower 5-year survival rate (43.42 % vs.,65.56 %; P < 0.05), and higher mortality (39.47 % vs.,23.33 %; P < 0.05) as compared to that in the IPF group.,All CPFE patients received oxygen therapy, antibiotics and oral N-acetylcysteine; > 50 % received bronchodilators, 40 % received corticosteroids and 14 % needed noninvasive mechanical ventilation.,On survival analyses, pulmonary arterial hypertension (PAH) and ≥ 5-point increase in CPI score per year were predictors of mortality in the CPFE group (hazard ratio [HR]: 10.29, 95 % Confidence Interval [CI]: 2.69-39.42 and HR: 21.60, 95 % CI: 7.28-64.16, respectively).,Patients with CPFE were predominantly male and smokers and exhibited distinct clinical, physiological and radiographic characteristics.,They had a poorer prognosis than IPF.,PAH and ≥ 5-point increase in CPI score per year were predictors of mortality in these patients.,Future studies are needed to identify the optimal treatment approach to CPFE.

The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is a recently described entity associating upper-lobe emphysema and lower-lobe fibrosis.,We sought to evaluate differences in pulmonary function between CPFE patients with and without airflow obstruction.,Thirty-one CPFE patients were divided into two groups according to the presence or absence of irreversible airflow obstruction based on spirometry (forced expiratory volume in 1 second/forced vital capacity <70% following inhalation of a β2-agonist) as follows: CPFE patients with airflow obstruction (CPFE OB+ group, n=11), and CPFE patients without airflow obstruction (CPFE OB− group, n=20).,Pulmonary function, including respiratory impedance evaluated using impulse oscillometry and dynamic hyperinflation following metronome-paced incremental hyperventilation, was retrospectively analyzed in comparison with that observed in 49 chronic obstructive pulmonary disease (COPD) patients (n=49).,In imaging findings, low-attenuation-area scores on chest high-resolution computed tomography, representing the degree of emphysema, were significantly lower in the CPFE OB− group than in the CPFE OB+ and COPD groups.,In contrast, the severity of pulmonary fibrosis was greater in the CPFE OB− group than in the CPFE OB+ group.,In pulmonary function, lung hyperinflation was not apparent in the CPFE OB− group.,Impairment of diffusion capacity was severe in both the CPFE OB− and CPFE OB+ groups.,Impulse oscillometry showed that respiratory resistance was not apparent in the CPFE OB− group compared with the COPD group, and that easy collapsibility of small airways during expiration of tidal breath was not apparent in the CPFE OB+ group compared with the COPD group.,Dynamic hyperinflation following metronome-paced incremental hyperventilation was significantly greater in the COPD group than in the CPFE OB− group, and also tended to be greater in the CPFE OB+ group than in the CPFE OB− group.,The mechanisms underlying impairment of physiological function may differ among CPFE OB+ patients, CPFE OB− patients, and COPD patients.,CPFE is a heterogeneous disease, and may have distinct phenotypes physiologically and radiologically.

The high incidence of cognition disorders in chronic obstructive pulmonary disease (COPD) patients represents a main focus in public health field recently.,Thus, we tried to explore relationship between cognitive function and arterial partial pressure O2 (PaO2) in patients with COPD as assessed by Mini-mental State Examination (MMSE) and/or Montreal Cognitive Assessment (MoCA).,Medical and scientific literature databases, such as Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database, were searched independently by 2 reviewers until February 2016.,Correlation coefficient (r or rs) values were obtained from each study, and 95% confidence intervals (CIs) were calculated using STATA12.0 software.,A total of 2049 studies were produced, and 9 of which were analyzed (714 participants) in the meta-analysis.,The pooled r observed medium relationship for all selected studies (r = 0.405, 95% CI 0.31-0.55), and notable heterogeneity was also tested between studies (χ2 = 17.72, P = .023; I2 = 54.9%).,After the sensitivity and subgroup analysis, the heterogeneity significantly decreased.,Subgroup analysis showed that MMSE score was stronger correlation between PaO2 and cognitive function than MoCA score in the COPD patients.,Begg test did not indicate potential risk of publication bias.,There was a negative correlation between cognitive function and anoxia in patients with COPD, so it may be extremely essential to predict and improve the status of hypoxia in COPD patients.

During our medical training, we learned that oxygen administration in patients with chronic obstructive pulmonary disease (COPD) induces hypercapnia through the 'hypoxic drive' mechanism and can be dangerous.,This mindset frequently results in the reluctance of clinicians to administer oxygen to hypoxemic patients with COPD.,However, this fear is not based on evidence in the literature.,Here, we will review the impact and pathophysiology of oxygen-induced hypercapnia in patients with acute exacerbation of COPD and recommend a titrated oxygen management.

Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide.,Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown.,Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell-cell communication tools.,They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases.,Recently, EVs have attracted considerable attention in pulmonary research.,In this review, we summarize the recent findings of EV-mediated COPD pathogenesis.,We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD.

Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD).,Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism.,We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages.,In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks.,Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages.,In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK.,Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways.,This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism.

The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function.

αB-crystallin (HspB5) is a chaperone whose role as a marker of innate immunity activation as well as its therapeutic potential have recently been investigated in several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain-Barré syndrome.,The aim of this study is to determine the role of αB-crystallin in chronic obstructive pulmonary disease (COPD) pathogenesis and inflammation.,Plasma levels of αB-crystallin were studied in 163 patients: 52 healthy non-COPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-II; 43 COPD smokers in GOLD stages III-IV.,Forty-eight patients were diagnosed with acute inflammatory respiratory disease.,The plasma levels of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay (Calbiochem), and were confirmed with Western blotting.,Tissue expression of the protein was compared in three different groups of patients: COPD smokers, COPD nonsmokers, and in patients with age-related emphysema.,The mean level of anti-αB-crystallin antibodies in non-COPD smokers was 0.291nm.,In COPD smokers it was 0.352 nm and, in patients with inflammatory lung diseases, 0.433 nm.,There was a statistically significant difference between COPD smokers and healthy non-COPD smokers (P = 0.010).,The same could be observed comparing the group of patients with acute inflammation and non-COPD healthy smokers (P = 0.007).,There was no statistically significant difference between patients with mild/moderate inflammation and those with severe COPD.,Tissue detection of the protein showed that it was significantly overexpressed in COPD smokers in comparison to COPD nonsmokers and was only slightly expressed in patients with age-related emphysema.,αB-crystallin is increased in patients with inflammatory lung diseases.,Though unspecific, it could be used in a panel of markers discerning COPD smokers from healthy nonsmokers.,As αB-crystallin is a regulator of innate immunity and a therapeutic anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be explored further.

Smoking cessation is the only effective intervention to slow down the accelerated decline in lung function in smokers with chronic obstructive pulmonary disease.,Nevertheless, physicians often do not routinely provide evidence-based smoking cessation treatment to their patients.,To understand underlying reasons, we explored how physicians engage in smoking cessation treatment in their chronic obstructive pulmonary disease patients.,In total, 21 focus group discussions were held with general practitioners and pulmonologists in seven different countries in Europe and Asia.,We generated three themes, whereby some of the issues concerned smokers in general: first, ‘physicians’ frustration with chronic obstructive pulmonary disease patients who smoke’.,These frustrations interfered with the provision of evidence-based treatment and could result in this group of patients being treated unequally.,Second: ‘physicians’ limited knowledge of, and negative beliefs about, smoking cessation treatment’.,This hindered treating smokers effectively.,Third: ‘healthcare organisational factors that influence the use of smoking cessation treatments’.,Money and time issues, as well as the failure to regard smoking as a disease, influenced how physicians engaged in smoking cessation treatment.,Our results indicate that there is a number of barriers to the provision of effective smoking cessation treatment in patients with chronic obstructive pulmonary disease and smokers in general.,Introducing an informative smoking cessation programme, including communication skills and ethical issues, in the vocational and postgraduate medical training may help to address these barriers.,This is important in order to increase engagement with smoking cessation treatment and to improve quality of chronic obstructive pulmonary disease care.,Doctors should be given careful, ethically-informed guidance during medical training to help them to support patients to quit smoking.,The most important part of treatment for patients with chronic obstructive pulmonary disease (COPD) is help to stop smoking.,However, there is evidence to suggest that doctors don’t always motivate COPD patients to quit.,Eva Anne Marije van Eerd at Maastrict University, The Netherlands, together with an international team of scientists, conducted focus group interviews with doctors in seven different countries to assess barriers to smoking cessation.,They found that doctors’ frustration with and negative attitudes towards patients who continued to smoke contributed to poor cessation management and treatment inequalities in some cases.,Many doctors also cited a lack of experience with smoking cessation techniques alongside time and money issues as barriers to effective treatment.

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.

Readmission rates following hospitalisation for COPD exacerbations are unacceptably high, and the contributing factors are poorly understood.,Our objective was to summarise and evaluate the factors associated with 30- and 90-day all-cause readmission following hospitalisation for an exacerbation of COPD.,We systematically searched electronic databases from inception to 5 November 2019.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesised a narrative from eligible studies and conducted a meta-analysis where this was possible using a random-effects model.,In total, 3533 abstracts were screened and 208 full-text manuscripts were reviewed.,A total of 32 papers met the inclusion criteria, and 14 studies were included in the meta-analysis.,The readmission rate ranged from 8.8-26.0% at 30 days and from 17.5-39.0% at 90 days.,Our narrative synthesis showed that comorbidities, previous exacerbations and hospitalisations, and increased length of initial hospital stay were the major risk factors for readmission at 30 and 90 days.,Pooled adjusted odds ratios (95% confidence intervals) revealed that heart failure (1.29 (1.22-1.37)), renal failure (1.26 (1.19-1.33)), depression (1.19 (1.05-1.34)) and alcohol use (1.11 (1.07-1.16)) were all associated with an increased risk of 30-day all-cause readmission, whereas being female was a protective factor (0.91 (0.88-0.94)).,Comorbidities, previous exacerbations and hospitalisation, and increased length of stay were significant risk factors for 30- and 90-day all-cause readmission after an index hospitalisation with an exacerbation of COPD.,Clinicians need to take a holistic approach including attention to comorbidities in the pre-discharge care of patients with COPD exacerbations to reduce the potential risk of readmission.http://bit.ly/2sucXKV

Pulmonary rehabilitation is a highly effective treatment for people with chronic lung disease but remains underused across the world.,Recent years have seen the emergence of new program models that aim to improve access and uptake, including telerehabilitation and low-cost, home-based models.,This workshop was convened to achieve consensus on the essential components of pulmonary rehabilitation and to identify requirements for successful implementation of emerging program models.,A Delphi process involving experts from across the world identified 13 essential components of pulmonary rehabilitation that must be delivered in any program model, encompassing patient assessment, program content, method of delivery, and quality assurance, as well as 27 desirable components.,Only those models of pulmonary rehabilitation that have been tested in clinical trials are currently considered as ready for implementation.,The characteristics of patients most likely to succeed in each program model are not yet known, and research is needed in this area.,Health professionals should use clinical judgment to determine those patients who are best served by a center-based, multidisciplinary rehabilitation program.,A comprehensive patient assessment is critical for personalization of pulmonary rehabilitation and for effectively addressing individual patient goals.,Robust quality-assurance processes are important to ensure that any pulmonary rehabilitation service delivers optimal outcomes for patients and health services.,Workforce capacity-building and training should consider the skills necessary for emerging models, many of which are delivered remotely.,The success of all pulmonary rehabilitation models will be judged on whether the essential components are delivered and on whether the expected patient outcomes, including improved exercise capacity, reduced dyspnea, enhanced health-related quality of life, and reduced hospital admissions, are achieved.

Limited accessibility to health care may be a barrier to obtaining good care.,Few studies have investigated the association between access-to-care factors and COPD hospitalizations.,The objective of this study is to estimate the association between access-to-care factors and health care utilization including hospital/emergency department (ED) visits and primary care physician (PCP) office visits among adults with COPD utilizing a nationally representative survey data.,We conducted a pooled cross-sectional analysis based upon a bivariate probit model, utilizing datasets from the 2011-2012 Behavioral Risk Factor Surveillance System linked with the 2014 Area Health Resource Files among adults with COPD.,Dichotomous outcomes were hospital/ED visits and PCP office visits.,Key covariates were county-level access-to-care factors, including the population-weighted numbers of pulmonary care specialists, PCPs, hospitals, rural health centers, and federally qualified health centers.,Among a total of 9,332 observations, proportions of hospital/ED visits and PCP office visits were 16.2% and 44.2%, respectively.,Results demonstrated that access-to-care factors were closely associated with hospital/ED visits.,An additional pulmonary care specialist per 100,000 persons serves to reduce the likelihood of a hospital/ED visit by 0.4 percentage points (pp) (P=0.028).,In contrast, an additional hospital per 100,000 persons increases the likelihood of hospital/ED visit by 0.8 pp (P=0.008).,However, safety net facilities were not related to hospital utilizations.,PCP office visits were not related to access-to-care factors.,Pulmonary care specialist availability was a key factor in reducing hospital utilization among adults with COPD.,The findings of our study implied that an increase in the availability of pulmonary care specialists may reduce hospital utilizations in counties with little or no access to pulmonary care specialists and that since availability of hospitals increases hospital utilization, directing patients with COPD to pulmonary care specialists may decrease hospital utilizations.

Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke.,We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population.,Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed.,We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status.,Some 63.8% of women and 62.2% of men reported ≥1 ACE.,COPD was reported by 4.9% of women and 4.0% of men.,In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs.,Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only.,ACEs are related to COPD, especially among women.,These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD.,This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions.,A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.,Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort.,Biomarker repeatability was assessed using baseline and 3-month samples.,Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.,Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls.,Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period.,Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit.,CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.,Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD).,Further analysis of more promising biomarkers may reveal utility in subsets of patients.,Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.,SCO104960, clinicaltrials.gov identifier NCT00292552

Reticular basement membrane (RBM) thickening has been variably associated with asthma and chronic obstructive pulmonary disease (COPD).,Even if RBM thickness is similar in both diseases, its composition might still differ.,To assess whether RBM thickness and composition differ between asthma and COPD.,We investigated 24 allergic asthmatics (forced expiratory volume in one second [FEV1] 92% predicted), and 17 nonallergic COPD patients (FEV1 60% predicted), and for each group a control group of similar age and smoking habits (12 and 10 persons, respectively).,Snap-frozen sections of bronchial biopsies were stained with hematoxylin/eosin and for collagen I, III, IV, V, laminin and tenascin.,RBM thickening was assessed by digital image analysis.,Relative staining intensity of each matrix component was determined.,Mean (SD) RBM thickness was not significantly different between asthma and COPD 5.5 (1.3) vs 6.0 (1.8) μm, but significantly larger than in their healthy counterparts, ie, 4.7 (0.9) and 4.8 (1.2) μm, respectively.,Collagen I and laminin stained significantly stronger in asthma than in COPD.,Tenascin stained stronger in asthma than in healthy controls of similar age, and stronger in COPD controls than in asthma controls (p < 0.05).,RBM thickening occurs both in asthma and COPD.,We provide supportive evidence that its composition differs in asthma and COPD.

Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8.

The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established.,Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades.,To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells.,Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months.,Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot.,Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression.,Exposure to nicotine-free e-cigarettes did not affect these lung parameters.,NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1.,Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion.,Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction.,These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties.,Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use.

Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials.,Little is known on the correspondence between the two methods.,Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO.,Dyspnea was assessed by the mMRC scale and the BDI.,Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George’s Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained.,Correlations between mMRC and BDI scores were assessed using Spearman’s correlation coefficient.,An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores.,Data are given as median (interquartile ranges, [IQR]).,Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]).,The mMRC grade and BDI score were, respectively, 1 [1-3] and 6 [4-8].,Both BDI and mMRC scores were significantly correlated at the group level (rho =−0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade.,In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio.,The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index.,Dyspnea is a complex symptom with multiple determinants in COPD patients.,Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable.

The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.

The 6-minute pegboard and ring test (6-PBRT) is a useful test for assessing the functional capacity of upper limbs in patients with stable COPD.,Although 6-PBRT has been validated in stable patients, the possibility of a high floor effect could compromise the validity of the test in the hospital setting.,The aim of this study was to verify the convergent validity of 6-PBRT in hospitalized patients with acute exacerbation of COPD (AECOPD).,A cross-sectional study was conducted in a tertiary hospital.,Patients who were hospitalized due to AECOPD and healthy elderly participants, voluntarily recruited from the community, were considered for inclusion.,All participants underwent a 6-PBRT.,Isokinetic evaluation to measure the strength and endurance of elbow flexors and extensors, handgrip strength (HGS), spirometry testing, the modified Pulmonary Functional Status Dyspnea Questionnaire (PFSDQ-M), the COPD assessment test (CAT), and symptoms of dyspnea and fatigue were all measured as comparisons for convergent validity.,Good convergent validity was considered if >75% of these hypotheses could be confirmed (correlation coefficient>0.50).,A total of 17 patients with AECOPD (70.9±5.1 years and forced expiratory volume in 1 second [FEV1] of 41.8%±17.9% of predicted) and 11 healthy elderly subjects were included.,The HGS showed a significant strong correlation with 6-PBRT performance (r=0.70; p=0.002).,The performance in 6-PBRT presented a significant moderate correlation with elbow flexor torque peak (r=0.52; p=0.03) and elbow extensor torque peak (r=0.61; p=0.01).,The total muscular work of the 15 isokinetic contractions of the elbow flexor and extensor muscles showed a significant moderate correlation with the performance in 6-PBRT (r=0.59; p=0.01 and r=0.57; p=0.02, respectively).,Concerning the endurance of elbow flexors and extensors, there was a significant moderate correlation with 6-PBRT performance (r=−0.50; p=0.04 and r=−0.51; p=0.03, respectively).,In relation to the upper-extremity physical activities of daily living (ADLs) assessed by means of PFSDQ-M, there was a significant moderate correlation of 6-PBRT with three domains: influence of dyspnea on ADLs (r=−0.66; p<0.001), influence of fatigue on ADLs (r=−0.60; p=0.01), and change in ADLs in relation to the period before the disease onset (r=−0.51; p=0.03).,The CAT was also correlated with 6-PBRT (r=−0.51; p=0.03).,Finally, the performance in 6-PBRT showed a significant moderate correlation with the increase in dyspnea (r=−0.63; p=0.01) and a strong correlation with the increase in fatigue of upper limbs (r=−0.76; p<0.001) in patients with AECOPD.,Convergent validity was considered adequate, since 81% from 16 predefined hypotheses were confirmed.,There was no correlation between 6-PBRT and patients’ height.,The performance in 6-PBRT was worse in patients with AECOPD compared to healthy elderly individuals (248.7±63.0 vs 361.6±49.9 number of moved rings; p<0.001).,The 6-PBRT is valid for the evaluation of functional capacity of upper limbs in hospitalized patients with AECOPD.

To validate a Portuguese-language version of the COPD assessment test (CAT) for use in Brazil and to assess the reproducibility of this version.,This was multicenter study involving patients with stable COPD at two teaching hospitals in the city of Fortaleza, Brazil.,Two independent observers (twice in one day) administered the Portuguese-language version of the CAT to 50 patients with COPD.,One of those observers again administered the scale to the same patients one week later.,At baseline, the patients were submitted to pulmonary function testing and the six-minute walk test (6MWT), as well as completing the previously validated Portuguese-language versions of the Saint George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (MMRC) dyspnea scale, and hospital anxiety and depression scale (HADS).,Inter-rater and intra-rater reliability was excellent (intraclass correlation coefficient [ICC] = 0.96; 95% CI: 0.93-0.97; p < 0.001; and ICC = 0.98; 95% CI: 0.96-0.98; p < 0.001, respectively).,Bland Altman plots showed good test-retest reliability.,The CAT total score correlated significantly with spirometry results, 6MWT distance, SGRQ scores, MMRC dyspnea scale scores, and HADS-depression scores.,The Portuguese-language version of the CAT is a valid, reproducible, and reliable instrument for evaluating patients with COPD in Brazil.,Realizar a validação e verificar a reprodutibilidade da versão em português do Brasil do COPD Assessment Test (CAT).,Estudo multicêntrico, no qual foram selecionados pacientes com DPOC estável em dois hospitais de ensino na cidade de Fortaleza, CE.,A versão do CAT foi aplicada duas vezes a 50 pacientes com DPOC por dois observadores independentes no mesmo dia.,Após uma semana, esse mesmo questionário foi aplicado novamente aos mesmos pacientes por um dos observadores.,No primeiro dia, os pacientes foram submetidos à prova de função pulmonar e ao teste de caminhada de seis minutos (TC6) e responderam as versões validadas de qualidade de vida relacionada à saúde (QVRS).,(SGRQ), escala de dispneia Modified Medical Research Council (MMRC) e hospital anxiety and depression scale (HADS).,As reprodutibilidades interobservador e intraobservador foram excelentes (coeficiente de correlação intraclasse [CCI] = 0,96; IC95%: 0,93-0,97; p < 0,001; e CCI = 0,98; IC95%: 0,96-0,98; p < 0,001, respectivamente).,As disposições gráficas de Bland Altman demonstraram boa confiabilidade teste-reteste.,Houve correlações significativas do escore total do CAT com os resultados de espirometria, TC6, SGRQ, escala de dispneia MMRC e HADS-depressão.,A versão brasileira do CAT é um instrumento válido, reprodutível e confiável para a avaliação dos pacientes com DPOC na população brasileira.

The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice.,The aim of this study was to explore the factors associated with the use of ICS in these patients.,The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan.,Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients.,Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively).,The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients.,Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14-4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24-2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40-2.96; P<0.001).,The COPD assessment test score was also associated with an ICS prescription in group B (OR, 1.04; 95% CI, 1.00-1.07; P=0.038).,About one-third of the GOLD group A and B patients with COPD in Taiwan are prescribed ICS.,Our findings suggest that wheezing and COPD assessment test score are related to the prescription of ICS in these patients.

Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven.

The treatment of COPD has become increasingly effective.,Measures that range from behavioral changes, reduction in exposure to risk factors, education about the disease and its course, rehabilitation, oxygen therapy, management of comorbidities, and surgical and pharmacological treatments to end-of-life care allow health professionals to provide a personalized and effective therapy.,The pharmacological treatment of COPD is one of the cornerstones of COPD management, and there have been many advances in this area in recent years.,Given the greater availability of drugs and therapeutic combinations, it has become increasingly challenging to know the indications for, limitations of, and potential risks and benefits of each treatment modality.,In order to critically evaluate recent evidence and systematize the major questions regarding the pharmacological treatment of COPD, 24 specialists from all over Brazil gathered to develop the present recommendations.,A visual guide was developed for the classification and treatment of COPD, both of which were adapted to fit the situation in Brazil.,Ten questions were selected on the basis of their relevance in clinical practice.,They address the classification, definitions, treatment, and evidence available for each drug or drug combination.,Each question was answered by two specialists, and then the answers were consolidated in two phases: review and consensus by all participants.,The questions answered are practical questions and help select from among the many options the best treatment for each patient and his/her peculiarities.

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality.,Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD.,For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function.,Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects.,Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile.,The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone.,Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects.,The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

Chronic obstructive pulmonary disease (COPD) and lung cancer are devastating pulmonary diseases that commonly coexist and present a number of clinical challenges.,COPD confers a higher risk for lung cancer development, but available chemopreventive measures remain rudimentary.,Current studies have shown a marked benefit of cancer screening in the COPD population, although challenges remain, including the common underdiagnosis of COPD.,COPD-associated lung cancer presents distinct clinical features.,Treatment for lung cancer coexisting with COPD is challenging as COPD may increase postoperative morbidities and decrease survival.,In this review, we outline current progress in the understanding of the clinical association between COPD and lung cancer, and suggest possible cancer prevention strategies in this patient population.

The aim of this study was to determine the relationship between lobar severity of emphysema and lung cancer using automated lobe segmentation and emphysema quantification methods.,This study included 78 patients (74 males and 4 females; mean age of 72 years) with the following conditions: pathologically proven lung cancer, available chest computed tomographic (CT) scans for lobe segmentation, and quantitative scoring of emphysema.,The relationship between emphysema and lung cancer was analyzed using quantitative emphysema scoring of each pulmonary lobe.,The most common location of cancer was the left upper lobe (LUL) (n = 28), followed by the right upper lobe (RUL) (n = 27), left lower lobe (LLL) (n = 13), right lower lobe (RLL) (n = 9), and right middle lobe (RML) (n = 1).,Emphysema ratio was the highest in LUL, followed by that in RUL, LLL, RML, and RLL.,Multivariate logistic regression analysis revealed that upper lobes (odds ratio: 1.77; 95% confidence interval: 1.01-3.11, P = 0.048) and lobes with emphysema ratio ranked the 1st or the 2nd (odds ratio: 2.48; 95% confidence interval: 1.48-4.15, P < 0.001) were significantly and independently associated with lung cancer development.,In emphysema patients, lung cancer has a tendency to develop in lobes with more severe emphysema.

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.

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.

Multimorbidity has already become common in primary care and will be a challenge in the future.,Primary care in Sweden participates to a great extent in the care of patients with two severe, chronic conditions: chronic obstructive pulmonary disease (COPD) and heart failure.,Both conditions are characterized by high mortality and often coexist.,Age, sex, heart failure and other comorbidities are considered to be the major predictors of mortality in patients with COPD.,We aimed to study the impact of heart failure, other comorbidities, age and sex on mortality in patients with COPD.,A register-based, prospective cohort study conducted in Blekinge County in Sweden with about 150,000 inhabitants.,The study population was comprised of people aged ≥35 years.,The data about diagnoses of COPD and heart failure came from the 2007 health care register, in which we found 984 individuals with a diagnosis of COPD.,Date of death was collected from January 1st, 2008 -August 31st, 2015.,The diagnosis-based Adjusted Clinical Groups (ACG) Case-Mix System 7.1 was used to describe comorbidity.,Each individual was assigned one of six comorbidity levels called resource utilization bands (RUB) graded from 0 to 5.,Estimated eight year mortality in patients with COPD and coexisting heart failure was seven times higher than in patients with COPD alone - odds ratio 7.06 (95% CI 3.88-12.84).,Adjusting for age and male sex resulted in odds ratio 3.75 (95% CI 1.97-7.15).,Further adjusting for other comorbidities resulted in odds ratio 3.26 (95% CI 1.70-6.25).,The mortality was strongly associated with the highest comorbidity level - RUB 5 where the odds ratio was 5.19 (95% CI 2.59-10.38).,Heart failure has an important impact on mortality in patients with COPD.,The mortality in patients with COPD and coexisting heart failure was strongly associated with age, male sex and other comorbidities.,Of those three predictors, only other comorbidities can be influenced.,Heart failure and other comorbidities should be recognized early and properly treated in order to improve survival in patients with coexisting COPD and heart failure.

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.

Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals.,However, clinical relevance of CT abnormalities is uncertain in the general population.,We evaluated data from 1361 participants aged ≥40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans.,CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B).,Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up.,About 11% of life-time never-smokers demonstrated emphysema on CT scans.,Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively.,Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score≥10(OR,2.17; 95%CI,1.42-3.30) and risk of ≥2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0).,Burden of thoracic CT abnormalities is high among Canadians ≥40 years of age, including never-smokers and smokers with normal lung function.,Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function.

Exacerbations of COPD represent an important medical and health care problem.,Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis.,The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease.,However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients.,In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care.,This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations.

During the last decade, many articles have been published, including reviews on fractional exhaled nitric oxide (FeNO) use and utility in clinical practice and for monitoring and identifying eosinophilic airway inflammation, especially in asthma, and evaluating corticosteroid responsiveness.,However, the exact role of FeNO in patients with chronic obstructive pulmonary disease (COPD) and its ability to distinguish patients with COPD and those having concomitant asthma, that is, asthma-COPD overlap (ACO) is still unclear and needs to be defined.,Due to the broad topics of FeNO in chronic airway disease, we undertook a scoping review.,The present article describes the protocol of a scoping review of peer-reviewed published literature specific to FeNO in COPD/ACO over the last decade.,We used Joanna Briggs Institute Reviewers’ Manual scoping review methodology as well as Levac et al’s and Arksey et al’s framework as guides.,We searched a variety of databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and BioSciences Information Service (BIOSIS) on 29 June 2016.,Additional studies will be recognised by exploring the reference list of identified eligible studies.,Screening of eligible studies will be independently performed by two reviewers and any disagreement will be solved by the third reviewer.,We will analyse the gathered data from article bibliographies and abstracts.,To investigate the body of published studies regarding the role of FeNO in patients with COPD and its usefulness in the clinical setting, a scoping review can be used as a modern and pioneer model, which does not need ethics approval.,By this review, new insights for conducting new research specific to FeNO in COPD/ACO population will emerge.,The results of this study will be reported in the scientific meetings and conferences, which aim to provide information to the clinicians, primary care providers and basic science researchers.

Fractional exhaled nitric oxide (FeNO) is an easy, sensitive, reproducible, and noninvasive marker of eosinophilic airway inflammation.,Accordingly, FeNO is extensively used to diagnose and manage asthma.,Patients with COPD who share some of the features of asthma have a condition called asthma-COPD overlap syndrome (ACOS).,The feasibility of using FeNO to differentiate ACOS patients from asthma and COPD patients remains unclear.,From February 2013 to May 2016, patients suspected with asthma and COPD through physician’s opinion were subjected to FeNO measurement, pulmonary function test (PFT), and bronchial hyperresponsiveness or bronchodilator test.,Patients were divided into asthma alone group, COPD alone group, and ACOS group according to a clinical history, PFT values, and bronchial hyperresponsiveness or bronchodilator test.,Receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in diagnosing ACOS.,The optimal operating point was also determined.,A total of 689 patients were enrolled in this study: 500 had asthma, 132 had COPD, and 57 had ACOS.,The FeNO value in patients with ACOS was 27 (21.5) parts per billion (ppb; median [interquartile range]), which was significantly higher than that in the COPD group (18 [11] ppb).,The area under the ROC curve was estimated to be 0.783 for FeNO.,Results also revealed an optimal cutoff value of >22.5 ppb FeNO for differentiating ACOS from COPD patients (sensitivity 70%, specificity 75%).,FeNO measurement is an easy, noninvasive, and sensitive method for differentiating ACOS from COPD.,This technique is a new perspective for the management of COPD patients.

The ability of circulating monocytes to develop into lung macrophages and promote lung tissue damage depends upon their phenotypic pattern of differentiation and activation.,Whether this phenotypic pattern varies with COPD severity is unknown.,Here we characterize the activation and differentiation status of circulating monocytes in patients with moderate vs. severe COPD.,Blood monocytes were isolated from normal non-smokers (14), current smokers (13), patients with moderate (9), and severe COPD (11).,These cells were subjected to analysis by flow cytometry to characterize the expression of activation markers, chemoattractant receptors, and surface markers characteristic of either M1- or M2-type macrophages.,Patients with severe COPD had increased numbers of total circulating monocytes and non-classical patrolling monocytes, compared to normal subjects and patients with moderate COPD.,In addition, while the percentage of circulating monocytes that expressed an M2-like phenotype was reduced in patients with either moderate or severe disease, the levels of expression of M2 markers on this subpopulation of monocytes in severe COPD was significantly elevated.,This was particularly evident for the expression of the chemoattractant receptor CCR5.,Blood monocytes in severe COPD patients undergo unexpected pre-differentiation that is largely characteristic of M2-macrophage polarization, leading to the emergence of an unusual M2-like monocyte population with very high levels of CCR5.,These results show that circulating monocytes in patients with severe COPD possess a cellular phenotype which may permit greater mobilization to the lung, with a pre-existing bias toward a potentially destructive inflammatory phenotype.,The online version of this article (10.1186/s12890-018-0664-y) contains supplementary material, which is available to authorized users.

Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors.,Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility.,Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.,Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study.,Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.,Individual genes were not found to be significantly associated with the number of exacerbations.,However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association.,A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection.,Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections.,The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.,A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness.,While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.,The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users.

Over the past two decades, there have been significant changes in the pharmacological management of COPD, due to an explosion of inhaler trials, and timely updation of national and international guidelines.,We sought to describe temporal changes in prescribing practices in the United Kingdom, and some of the factors that may have influenced them.,COPD patients were identified from UK primary care nationally representative electronic healthcare records (Clinical Practice Research Datalink), between 2000 and 2016.,Prescription data were described by the three maintenance inhaled medication classes used, inhaled corticosteroids (ICS), long-acting beta agonist (LABA), long-acting muscarinic antagonist (LAMA), and their combinations, dual LABA-ICS, dual LAMA-LABA, or triple therapy LABA-ICS-LAMA.,Differing patient characteristics across the six different therapy regimens were measured in 2016.,COPD patients were identified: 187,588 prevalent and incident inhaler users and 169,511 incident inhaler users.,Since 2002, LAMA showed increasing popularity, while ICS alone exhibited an inverse trend.,Triple therapy prescriptions rapidly increased as the first-line therapy until 2014 when LAMA-LABA prescriptions started to increase.,By 2014, 41% of all COPD patients were maintained on triple therapy, and 13% were maintained on LAMA only.,Characterizing the patients in 2016 revealed that those on triple therapy were more likely to have more severe disease, yet, over a third of patients on triple therapy had only mild disease.,UK prescribing practices were not in keeping with national guidelines but did appear to align with evidence from major drug trials and updated international guidelines.,There has been a huge upsurge in triple therapy but incident data show this trend is beginning to reverse for initial management.

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.

Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD).,We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.,This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months.,Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2-12.,Responders were defined by ≥100 mL improvement in prebronchodilator FEV1 and ≥4-point decrease in SGRQ total score.,Overall, 2,331 and 1,799 patients were included in the 0-2- and 0-12-month responder analyses, respectively, and 2,360 patients in the 2-12-month exacerbation rate analysis.,At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders.,The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters.,Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14-7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83-5.31).,Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk.,Early FEV1 and SGRQ treatment responses relate to their changes at 12 months.,FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients.,This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required.

Inhaled corticosteroids (ICS) reduce exacerbation rates and improve health status but can increase the risk of pneumonia in COPD.,The GLUCOLD study, investigating patients with mild-to-moderate COPD, has shown that long-term (2.5-year) ICS therapy induces anti-inflammatory effects.,The literature suggests that cigarette smoking causes ICS insensitivity.,The aim of this study is to compare anti-inflammatory effects of ICS in persistent smokers and persistent ex-smokers in a post-hoc analysis of the GLUCOLD study.,Persistent smokers (n = 41) and persistent ex-smokers (n = 31) from the GLUCOLD cohort were investigated.,Effects of ICS treatment compared with placebo were estimated by analysing changes in lung function, hyperresponsiveness, and inflammatory cells in sputum and bronchial biopsies during short-term (0-6 months) and long-term (6-30 months) treatment using multiple regression analyses.,Bronchial mast cells were reduced by short-term and long-term ICS treatment in both smokers and ex-smokers.,In contrast, CD3+, CD4+, and CD8+ cells were reduced by short-term ICS treatment in smokers only.,In addition, sputum neutrophils and lymphocytes, and bronchial CD8+ cells were reduced after long-term treatment in ex-smokers only.,No significant interactions existed between smoking and ICS treatment.,Even in the presence of smoking, long-term ICS treatment may lead to anti-inflammatory effects in the lung.,Some anti-inflammatory ICS effects are comparable in smokers and ex-smokers with COPD, other effects are cell-specific.,The clinical relevance of these findings, however, are uncertain.

The aim of this study was to extend previous findings and determine the value of prompt initiation of maintenance treatment (MT) following COPD exacerbations requiring hospitalization or an emergency department (ED) visit.,Administrative claims data (collected between January 1, 2009 and June 30, 2012) from an employer-sponsored commercially insured population were retrospectively used to identify patients with a COPD exacerbation resulting in hospitalization or an ED visit.,Patients initiating approved MT for COPD within 30 days of discharge/diagnosis (prompt) were compared with those initiating MT within 31-180 days (delayed).,COPD-related total, medical, and prescription drug costs during a 1-year follow-up period were evaluated using semilog ordinary least square regressions, controlling for baseline characteristics plus COPD-related costs from the previous year.,The odds and number of subsequent COPD-related exacerbations during the follow-up were compared between the prompt and delayed cohorts using logistic regression and zero-inflated negative binomial models, respectively.,A total of 6,521 patients with a COPD-related hospitalization or an ED visit were included, of whom 4,555 received prompt MT and 1,966 received delayed MT.,Adjusted COPD-related total and medical costs were significantly lower for the prompt MT than the delayed MT cohorts (US$3,931 vs US$4,857 and US$2,327 vs US$3,087, respectively; both P<0.010), as were COPD-related prescription costs (US$1,526 vs US$1,683, P<0.010) during the 1-year follow-up period.,Patients receiving delayed MT were 68% more likely to have a subsequent exacerbation requiring hospitalization and 80% more likely to have an exacerbation requiring an ED visit.,Prompt initiation of MT following a COPD-related hospitalization or an ED visit was associated with a significant reduction in COPD-related costs and odds of exacerbation in the following year compared with delayed initiation.

There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population.,The study examined COPD patients with moderate COPD exacerbations.,COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation.,This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation.,A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period.,A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs.,COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009).,COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution.,21,524 patients with a moderate COPD exacerbation were identified.,Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation.,Annual costs averaged $594 per patient.,A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis.,The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04).,After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91).,The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort.,However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05).,Total monthly COPD-related costs, as a result, did not differ between cohorts.,Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy.,Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC.

Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD.,This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of “fixed triple” (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form “open triple” combinations.,Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium.,Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio.,Furthermore, triple therapy showed a promising signal in terms of improved survival.,The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia.,Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap.

COPD is a treatable disease with increasing prevalence worldwide.,Treatment aims to stop disease progression, to improve quality of life, and to reduce exacerbations.,We aimed to evaluate the association of the stage of COPD on adherence to inhaled therapy and the relationship between adherence and COPD exacerbations.,A retrospective analysis of patients hospitalized for acute exacerbation of COPD in a tertiary care hospital in Upper Austria and discharged with a guideline conform inhaled therapy was performed.,Follow-up data on medical utilization was recorded for the subsequent 24 months.,Adherence to inhaled therapy was defined according to the percentage of prescribed inhalers dispensed to the patient and classified as complete (> 80%), partial (50-80%) or low (< 50%).,Out of 357 patients, 65.8% were male with a mean age of 66.5 years and a mean FEV1 of 55.0%pred.,Overall, 35.3% were current smokers, and only 3.9% were never-smokers.,In 77.0% inhaled triple therapy (LAMA + LABA + ICS) was prescribed.,33.6% showed complete adherence to their therapy (33.2% in men, 34.4% in women), with a mean age of 67.0 years.,Mean medication possession ratio by GOLD spirometry class I - IV were 0.486, 0.534, 0.609 and 0.755, respectively (p = 0.002).,Hence, subjects with complete adherence to therapy had a significantly lower FEV1 compared to those with low adherence (49.2%pred. vs 59.2%pred., respectively; p < 0.001).,The risk of exacerbations leading to hospitalization was 10-fold higher in GOLD spirometry class IV compared to GOLD spirometry class I, which was even more evident in multivariate analysis (OR 13.62).,Complete adherence to inhaled therapy was only seen in 33.6% and was higher among those with more severe COPD.,Not applicable.

Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms.,While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood.,Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011.,Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week.,Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met.,Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures.,Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels.,Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom.,Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms.,Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without.,Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD.

Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms.

Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population.

Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium.,Previous studies have compared glycopyrronium with open-label tiotropium.,In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.,In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily.,The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL).,Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.,657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study.,Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL).,Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001).,FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12.,Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant).,Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).,Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).,In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.,ClinicalTrial.gov, NCT01613326

COPD is a highly heterogeneous disease.,Potential biomarkers to identify patients with COPD who will derive the greatest benefit from inhaled corticosteroid (ICS) treatment are needed.,Blood eosinophil count can serve as a predictive biomarker for the efficacy of ICS treatment.,The aim of this systematic review and meta-analysis was to assess whether a blood eosinophil count of ≥2% in patients undergoing ICS therapy was associated with a greater reduction in COPD exacerbation rate and pneumonia incidence.,An electronic search was performed using the keywords “COPD”, “eosinophil”, and “clinical trial” in the PubMed and EMBASE databases to retrieve articles, up to 2017, relevant to our focus.,Data were extracted, and a meta-analysis was conducted using RevMan 5 (version 5.3.5).,Five studies comprising 12,496 patients with moderate-to-very severe COPD were included.,At baseline, 60% of the patients had ≥2% blood eosinophils.,Our meta-analysis showed a 17% reduction in exacerbation of moderate/severe COPD in patients with ≥2% blood eosinophils undergoing ICS therapy compared to the non-ICS/ICS withdrawal/placebo group.,The difference between the two types of treatment was significant (risk ratio [RR], 0.816; 95% CI, 0.67-0.99; P=0.03).,Furthermore, the risk of pneumonia-related events was significantly increased in the subgroup with eosinophil count ≥2% undergoing ICS-containing treatments (RR, 1.969; 95% CI, 1.369-2.833; P<0.001).,There was no significant difference in the subgroup with eosinophil count <2% (RR, 1.29; 95% CI, 0.888-1.879; P<0.181).,The results of our meta-analysis suggest that the 2% threshold for blood eosinophils could accurately predict ICS treatment response in patients with COPD, but increased the risk of pneumonia.

Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users.