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Tiotropium bromide is an anticholinergic agent that has gained worldwide acceptance as a first-line, once daily maintenance therapy for patients with moderate-to-severe chronic obstructive pulmonary disease.,The purpose of this review is to synthesize the evidence base in the past 10 years on the development of tiotropium and its efficacy compared to other able interventions such as long-acting beta agonists (LABAs), as well as to assess its safety profile and its effects on health-related outcomes in patients with COPD.,Treatment with tiotropium bromide has generally improved patients’ health-related quality of life, reduced the number of patients suffering from acute exacerbations, decreased the number of hospitalizations, improved dyspnea, and reduced adverse events compared to placebo.,In the past decade, several studies have examined the safety and efficacy of tiotropium in comparison to placebo and to LABAs (salmeterol, formoterol, and indacaterol) over periods ranging from 3 months to 48 months of follow-up.,Head-to-head comparisons of tiotropium 18 μg (once daily) with salmeterol 50 μg (twice daily) in well-controlled trials demonstrated that tiotropium was superior in reducing acute exacerbation events and in improving quality of life.,In a few short-term studies, indacaterol was comparable to tiotropium in its efficacy in improving health-related outcomes.,Although the safety record of tiotropium has been exemplary in comparison to placebo, anticholinergic events such as dry mouth can be encountered in some patients.,While the long-term safety of tiotropium when delivered in the HandiHaler® has been well documented, its delivery using the Respimat® Soft Mist Inhaler™ was associated with an elevated risk of cardiovascular complications, including increased mortality when compared to placebo.,The exact mechanism for this is not known but is being investigated in a large multinational study that will evaluate the long-term safety of different doses of tiotropium delivered by the Respimat® soft mist inhaler versus the HandiHaler®.,Further studies are required to investigate the efficacy and safety of tiotropium in comparison with novel LABAs such as indacaterol and vilanterol, and with other emerging novel anticholinergic agents such as aclidinium bromide and NVA237 (glycopyrronium bromide). | Data on differences in clinical characteristics and management of COPD in different countries and settings are limited.,We aimed to characterize the profile of patients with COPD in a number of countries and their treatment in order to evaluate adherence to recommendations of international guidelines.,This was an observational, international, cross-sectional study on patients with physician-diagnosed COPD.,Demographic and clinical characteristics, risk factors, and treatment were collected by their physician via an internet web-based questionnaire developed for the study.,A total of 77 investigators from 17 countries provided data on 833 patients.,The countries with the highest number of patients included were: Argentina (128), Ecuador (134), Spain (162), and Hong Kong (153).,Overall, 79.3% were men and 81% former smokers, with a mean FEV1 = 42.7%, ranging from 34.3% in Hong Kong to 58.8% in Ecuador.,Patients reported a mean of 1.6 exacerbations the previous year, with this frequency being significantly and negatively correlated with FEV1(%) (r = −0.256; p < 0.0001).,Treatment with short-acting bronchodilators and theophyllines was more frequent in Ecuador and Hong Kong compared with Spain and Argentina, and in patients belonging to lower socioeconomic levels (p < 0.0001 for all comparisons).,Inadequacy of treatment with inhaled corticosteroids and theophyllines was high, with significant differences among countries.,Differences in the clinical characteristics and management of COPD were significant across countries.,Adherence to international guidelines appears to be low.,Efforts should be made to disseminate and adapt guidelines to the socioeconomic reality of different settings. | 1 |
Using data from the Continuing to Confront COPD International Physician and Patient Surveys, this paper describes physicians’ attitudes and beliefs regarding chronic obstructive pulmonary disease (COPD) prognosis, and compares physician and patient perceptions with respect to COPD.,In 12 countries worldwide, 4,343 patients with COPD were identified through systematic screening of population samples, and 1,307 physicians who regularly saw patients with COPD were sampled from in-country professional databases.,Both patients and physicians completed surveys about their COPD knowledge, beliefs, and perceptions; physicians answered further questions about diagnostic methods and treatment choices for COPD.,Most physicians (79%) responded that the long-term health outlook for patients with COPD has improved over the past decade, largely attributed to the introduction of better medications.,However, patient access to medication remains an issue in many countries, and some physicians (39%) and patients (46%) agreed/strongly agreed with the statement “there are no truly effective treatments for COPD”.,There was strong concordance between physicians and patients regarding COPD management practices, including the use of spirometry (86% of physicians and 76% of patients reporting they used/had undergone a spirometry test) and smoking cessation counseling (76% of physicians reported they counseled their smoking patients at every clinic visit, and 71% of smoking patients stated that they had received counseling in the past year).,However, the groups differed in their perception about the role of smoking in COPD, with 78% of physicians versus 38% of patients strongly agreeing with the statement “smoking is the cause of most cases of COPD”.,The Continuing to Confront COPD International Surveys demonstrate that while physicians and patients largely agreed about COPD management practices and the need for more effective treatments for COPD, a gap exists about the causal role of smoking in COPD. | This study aimed to characterize and differentiate the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy 2011 cut points through the modified Medical Research Council dyspnea scale (mMRC) and chronic obstructive pulmonary disease (COPD) assessment test (CAT).,Analysis of COPD patient data from the 2012 Adelphi Respiratory Disease Specific Program was conducted in Europe and US.,Matched data from physicians and patients included CAT and mMRC scores.,Receiver operating characteristic curves and kappa analysis determined a cut point for CAT and mMRC alignment and thus defined patient movement (“movers”) within GOLD groups A-D, depending on the tool used.,Logistic regression analysis, with a number of physician- and patient-reported covariates, characterized those movers.,Comparing GOLD-defined high-symptom patients using mMRC and CAT cut points (≥2 and ≥10, respectively), there were 890 (53.65%) movers; 887 of them (99.66%) moved from less symptomatic GOLD groups A and C (using mMRC) to more symptomatic groups B and D (using CAT).,For receiver operating characteristic (area under the curve: 0.82, P<0.001) and kappa (maximized: 0.45) recommended CAT cut points of ≥24 and ≥26, movers reduced to 429 and 403 patients, respectively.,Logistic regression analysis showed variables significantly associated with movers were related to impact on normal life, age, cough, and sleep (all P<0.05).,Within movers, direction of movement was significantly associated with the same variables (all P<0.05).,Use of current mMRC or CAT cut points leads to inconsistencies for COPD assessment classification.,It is recommended that cut points are aligned and both tools administered simultaneously for optimal patient care and to allow for closer management of movers.,Our research may suggest an opportunity to investigate a combined score approach to patient management based on the worst result of mMRC and CAT.,The reduced number of remaining movers may then identify patients who have greater impact of disease and may require a more personalized treatment plan. | 1 |
Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life.,Despite this, COPD treatment and its management are mainly based on lung function assessments.,There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives.,Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD.,Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice.,In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases worldwide.,Episodes of acute exacerbations of COPD (AECOPD) are associated with disease severity and progression.,Although substantial progress has been made in understanding the dynamics of AECOPD, little is known about the sputum microbiome of AECOPD in the Chinese population.,In this study, we characterized the sputum microbiomes from sputum specimens collected from healthy controls (n = 10), stable (n = 4), AECOPD (n = 36), and recovery (n = 18) stages by sequencing the V3-V4 region of the 16S rRNA gene with a HiSeq sequencer.,Streptococcus was the most dominant genus among all the different types of sputum.,A random forest model was developed to identify bacterial taxa that differentiate AECOPD samples from others.,Most of the top predictors, except Pseudomonas, were less abundant in AECOPD samples.,We also developed random forest models to differentiate subtypes of AECOPD based on blood eosinophil counts, the frequency of AECOPD, and sputum eosinophils.,Bacterial taxa associated with Pasteurellaceae, Fusobacterium, Solobacterium, Haemophilus, Atopobium, Corynebacterium and Streptococcus, were enriched in the sputum microbiomes of eosinophilic AECOPD.,Random forest models also demonstrate that a total of 2 bacterial OTUs were needed to differentiate frequent from non-frequent AECOPDs, and 23 OTUs were enough to accurately predict sputum-eosinophilic (sputum eosinophilic concentration ≥ 3%) AECOPD.,This study expanded our understanding of the sputum microbiome associated with different subtypes and clinical status of patients with AECOPD in a Chinese cohort, which provides insights into novel and more targeted management of the different subtypes of AECOPD. | Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD).,However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.,We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.,In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera.,Haemophilus formed only 3% of the healthy microbiome.,In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively.,There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history.,Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).,The healthy and COPD sputum microbiomes are distinct and independent of smoking history.,Our results underline the important role for Gammaproteobacteria in COPD. | 1 |
Several new fixed-dose combination bronchodilators have been recently launched, and assessing their efficacy relative to each other, and with open dual combinations is desirable.,This network meta-analysis (NMA) assessed the efficacy of umeclidinium and vilanterol (UMEC/VI) with that of available dual bronchodilators in single/separate inhalers.,A systematic literature review identified randomized controlled trials of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years), assessing the efficacy of combination bronchodilators in single or separate inhalers.,Comparative assessment was conducted on change from baseline in trough forced expiratory volume in 1 second (FEV1), St George’s Respiratory Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores, and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian framework.,A systematic literature review identified 77 articles of 26 trials comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus tiotropium (TIO) 18 μg, salmeterol plus TIO, or indacaterol plus TIO, with TIO and placebo as common comparators at 12 weeks and approximately 24 weeks.,The NMA showed that at 24 weeks, efficacy of UMEC/VI was not significantly different compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: −14.2, 42.3]), SGRQ total score (0.18 [−1.28, 1.63]), TDI focal score (−0.30 [−0.73, 0.13]), and rescue medication use (0.02 [−0.27, 0.32]); compared with salmeterol plus TIO on trough FEV1 (67.4 mL [−25.3, 159.4]), SGRQ total score (−0.11 [−1.84, 1.61]), and TDI focal score (0.58 [−0.33, 1.50]); and compared with formoterol plus TIO 18 μg on SGRQ total score (−0.68 [−1.77, 0.39]).,Results at week 12 were consistent with week 24 outcomes.,Due to lack of availability of evidence, no comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks.,UMEC/VI has comparable efficacy to other dual-bronchodilator combinations on available efficacy endpoints. | Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA) indicated for maintenance bronchodilator treatment of chronic obstructive pulmonary disease (COPD).,The efficacy of aclidinium was compared with tiotropium and glycopyrronium, using a network meta-analysis (NMA) of randomized controlled trials (RCTs) in moderate-to-severe COPD patients.,A systematic review was performed to identify RCTs evaluating aclidinium 400 μg twice daily (BID), glycopyrronium 50 μg once daily (OD), tiotropium 18 μg OD, or tiotropium 5 μg OD in adults with moderate-to-severe COPD.,The outcomes of interest were: trough forced expiratory volume in 1 second (FEV1); St George’s Respiratory Questionnaire (SGRQ) total score and proportion of patients achieving ≥4 unit change; Transition Dyspnea Index (TDI) focal score and proportion of patients achieving ≥1 point change.,The results were synthesized by means of a Bayesian NMA.,Twenty-one studies (22,542 patients) were included: aclidinium 400 μg BID (three studies); tiotropium 5 μg OD (three studies); tiotropium 18 μg OD (13 studies); and glycopyrronium 50 μg OD (two studies).,Regarding trough FEV1 at 24 weeks, aclidinium demonstrated comparable efficacy to tiotropium 5 μg (difference in change from baseline [CFB]), (0.02 L [95% credible interval CrI −0.05, 0.09]); tiotropium 18 μg (0.02 L [95% CrI −0.05, 0.08]); and glycopyrronium (0.00 L [95% CrI −0.07, 0.07]).,Aclidinium resulted in higher improvement in SGRQ score at 24 weeks, compared to tiotropium 5 μg (difference in CFB, −2.44 [95% CrI −4.82, −0.05]); and comparable results to tiotropium 18 μg (−1.80 [95% CrI −4.52, 0.14]) and glycopyrronium (−1.52 [95% CrI −4.08, 1.03]).,Improvements in TDI score were comparable for all treatments.,Maintenance treatment with aclidinium 400 μg BID is expected to produce similar improvements in lung function, health-related quality of life, and dyspnea compared to tiotropium 5 μg OD; tiotropium 18 μg OD; and glycopyrronium 50 μg OD. | 1 |
COPD exacerbations and hospitalizations have been associated with poor prognosis for the COPD patient.,To evaluate the frequency and risk factors of COPD exacerbations, hospitalizations, and admissions to intensive care units (ICUs) in Greece by a nationwide cross-sectional study.,A nationwide observational, multicenter, cross-sectional study was conducted in the clinical practice setting of respiratory medicine physicians over a 6 month-period (October 2010 to March 2011).,A total of 6,125 COPD patients were recruited by 199 respiratory physicians.,Participants had a median age of 68.0 years, 71.3% were males, and 71.8% suffered from comorbidities.,The median disease duration was 10.0 years.,Of the patients, 45.3% were classified as having GOLD (Global initiative for chronic Obstructive Lung Disease) stage III or IV COPD.,Patients with four or more comorbidities had 78.5% and threefold-higher than expected number of exacerbations and hospitalizations, respectively, as well as fivefold-higher risk of admission to the ICU compared to those with no comorbidities.,Obese patients had 6.2% fewer expected exacerbations compared to those with a normal body mass index.,Patients with GOLD stage IV had 74.5% and fivefold-higher expected number of exacerbations and hospitalizations, respectively, and nearly threefold-higher risk of admission to the ICU compared to stage I patients.,An additional risk factor for exacerbations and hospitalizations was low compliance with treatment: 45% of patients reported forgetting to take their medication, and 81% reported a preference for a treatment with a lower dosing frequency.,Comorbidities, disease severity, and compliance with treatment were identified as the most notable risk factors for exacerbations, hospitalizations, and ICU admissions.,The results point to the need for a multifactorial approach for the COPD patient and for the development of strategies that can increase patient compliance with treatment. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT).,Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database.,MITT was defined as subjects with ≥1 overlapping days’ supply of three COPD medications (ICS, LABA, and LAMA).,Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up.,In addition, analyses were stratified by number of inhalers.,In total, 14,635 MITT users were identified (mean age, 62 years).,Mean PDC for MITT at 12 months was 0.37%.,Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively.,The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT.,Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up.,Patients with COPD had low adherence to and persistence with MITT in a real-world setting.,Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT.,Reducing the number of inhalers may improve overall adherence to intended triple therapy. | It is not known if the medicines and services for COPD are used in Australia according to the COPD-X guideline.,This study examined the use of medicines and health services for COPD among an Australian cohort to determine if they were consistent with recommendations.,The administrative claims data from the Australian Government Department of Veterans’ Affairs were used and included persons aged ≥50 years who were using medicines for COPD in April 2016.,Use of medicines was identified using the Anatomical, Therapeutic and Chemical Classification and Pharmaceutical Benefits Scheme.,Use of services was identified using the Medicare Benefits Schedule and Australian Government Department of Veterans’ Affairs Fee Schedule.,Of the 143,261 persons aged ≥50 years, 12,623 (8.8%) were on medicines for COPD.,Of the total COPD population, 42% were managed on monotherapy, 36% on dual therapy, 21% on triple therapy, and 1.5% on more than three COPD medicines.,Monotherapy comprised tiotropium (80%) predominantly.,Services to practitioners who may provide pulmonary rehabilitation service showed less than 10% of the cohort had a claim for a visit to an exercise physiologist and less than a third had a claim for a physiotherapist visit in the prior 12 months.,Services to assist with care coordination in the form of general practitioner management plans were only claimed by half of the cohort, while services supporting appropriate medicine use were claimed by less than one in six cases, despite high levels of inhaler use and multiple inhaler use.,More than three-quarters of COPD persons aged 50 years and above were managed on either monotherapy or dual therapy, consistent with the guideline recommendations.,Almost one-quarter was on three or more therapies, which will create challenges for multiple device management.,Many services that may benefit persons with COPD appear to be underutilized. | 1 |
p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators.,COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations.,These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD.,The principal hypothesis was that decreasing lung inflammation via inhibition of p38α would reduce exacerbations and improve quality of life for COPD patients at high risk for acute exacerbations.,The p38 isoform most relevant to lung inflammation was assessed using an in situ proximity ligation assay in severe COPD patients and donor controls.,Volunteers aged 18-55 years were randomized into the lipopolysaccharide (LPS) challenge study, which investigated the effect of a single dose of AZD7624 vs placebo on inflammatory biomarkers.,The Proof of Principle study randomized patients aged 40-85 years with a diagnosis of COPD for >1 year to AZD7624 or placebo to assess the effect of p38 inhibition in decreasing the rate of exacerbations.,The p38 isoform most relevant to lung inflammation was p38α, and AZD7624 specifically inhibited p38α and p38β isoforms in human alveolar macrophages.,Thirty volunteers were randomized in the LPS challenge study.,AZD7624 reduced the increase from baseline in sputum neutrophils and TNF-α by 56.6% and 85.4%, respectively (p<0.001).,In the 213 patients randomized into the Proof of Principle study, there was no statistically significant difference between AZD7624 and placebo when comparing the number of days to the first moderate or severe exacerbation or early dropout.,Although p38α is upregulated in the lungs of COPD patients, AZD7624, an isoform-specific inhaled p38 MAPK inhibitor, failed to show any benefit in patients with COPD. | Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations.,It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation.,To provide a cell-by-cell overview of the inflammatory processes during COPD exacerbations.,To evaluate cell activation, and cytokine production, cellular interactions, damaging effects of inflammatory mediators to tissue, and the relation to symptoms at the onset of COPD exacerbations.,To speculate on future therapeutic options to modify inflammation during COPD exacerbations.,During COPD exacerbations, there is increased airway wall inflammation, with pathophysiological influx of eosinophils, neutrophils, and lymphocytes.,Although links have been suggested between the increase in eosinophils and lymphocytes and a viral etiology of the exacerbation, and between the increase in neutrophils and a bacterial aetiology, these increases in both inflammatory cell types are not limited to the respective aetiologies and the underlying mechanisms remain elusive.,Further research is required to fully understand the inflammatory mechanisms in the onset and development of COPD exacerbations.,This might make inflammatory pathway-specific intervention possible, resulting in a more effective treatment of COPD exacerbations with fewer side effects. | 1 |
Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis.,Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer’s and Parkinson’s diseases, but little is known about iron accumulation in COPD.,We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction.,Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects.,Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay.,Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)).,The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues.,Futhermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity.,The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively).,In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction.,These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress. | Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD).,The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease.,(i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks.,One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS).,(i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission.,Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured.,All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients.,Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment.,There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014.,ID is common in COPD patients but is rarely looked for or treated.,Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea. | 1 |
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. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
In symptomatic patients with COPD, the decision whether to initiate maintenance treatment with a single agent or a combination of long-acting bronchodilators remains unclear.,To investigate whether baseline symptomatic status influences response to tiotropium/olodaterol treatment.,Post hoc analysis of the randomized OTEMTO® studies (NCT01964352; NCT02006732), in which patients with moderate-to-severe COPD received placebo, tiotropium 5 µg, tiotropium/olodaterol 2.5/5 µg, or tiotropium/olodaterol 5/5 µg once daily for 12 weeks via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany).,Impact of baseline symptomatic status (modified Medical Research Council [mMRC] score) on response to treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg, or placebo at Week 12 was assessed by St George’s Respiratory Questionnaire (SGRQ) total score and response rate, transition dyspnea index (TDI) focal score and response rate, and trough forced expiratory volume in 1 second response.,Tiotropium/olodaterol improved SGRQ total scores and response rates compared with placebo and tiotropium for patients with baseline mMRC scores 0-1 and ≥2.,For tiotropium/olodaterol vs tiotropium, greater improvements were observed for patients with mMRC ≥2 (SGRQ score adjusted mean treatment difference −3.44 [95% CI: −5.43, −1.46]; P=0.0007; SGRQ response rate ORs 2.09 [95% CI: 1.41, 3.10]; P=0.0002).,Dyspnea, measured by TDI score, was consistently improved with tiotropium/olodaterol vs placebo for patients with mMRC scores 0-1 and ≥2 (adjusted mean treatment difference 1.63 [95% CI: 1.06, 2.20]; P<0.0001 and 1.60 [95% CI: 1.09, 2.10]; P<0.0001, respectively).,In patients with mMRC scores 0-1 and ≥2, tiotropium/olodaterol consistently improved TDI response rate and lung function vs placebo and tiotropium.,Patients with COPD with more severe baseline dyspnea appear to derive greater health status benefit with tiotropium/olodaterol compared with tiotropium alone. | 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. | 1 |
To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors.,We conducted a random cross-sectional national survey of adults older than 40 years in Taiwan.,Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health.,Subjects with diagnosed COPD were subdivided by smoking status.,Subjects who fulfilled the case definition of COPD and smoked were designated as “possible COPD”.,Participants who did not fit the case definition of COPD were asked only about their personal circumstances and smoking habits.,Data from these groups were analyzed and compared.,Of the 6,600 participants who completed the survey, 404 (6.1%) fulfilled the epidemiological case definition of COPD: 137 with diagnosed COPD and 267 possible COPD.,The most common comorbidities of COPD were hypertension or cardiovascular diseases (36.1%).,Subjects with definite COPD had significantly higher COPD Assessment Test scores than the possible COPD group (14.6±8.32 vs 12.6±6.49, P=0.01) and significantly more comorbid illnesses (P=0.01).,The main risk factors contributing to health care utilization in each COPD cohort were higher COPD Assessment Test scores (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.26), higher modified Medical Research Council Breathlessness Scale scores (OR 1.97, 95% CI 1.11-3.51), and having more than one comorbidity (OR 5.19, 95% CI 1.05-25.61).,With estimated prevalence of 6.1% in the general population, COPD in Taiwan has been underdiagnosed.,Symptoms and comorbidities were independent risk factors for health care utilization in subjects with definite or possible COPD.,There is an urgent need to raise awareness of the importance of early evaluation and prompt treatment for subjects with chronic airway symptoms. | Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear.,We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.,Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007).,COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal.,Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry.,Model performance was assessed using standard criteria.,4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70.,The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76).,Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78).,The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).,Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD.,Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD. | 1 |
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most common reason for the hospitalization and death of pulmonary patients.,The use of antibiotics as adjuvant therapy for AECOPD, however, is still a matter of debate.,In this study, we searched the PubMed, EmBase, and Cochrane databases for randomized controlled trials published until September 2016 that evaluated the use of antibiotics for AECOPD treatment.,The major outcome variables were clinical cure rate and adverse effects.,The microbiological response rate, relapse of exacerbation, and mortality were also analysed.,A random-effect network was used to assess the effectiveness and tolerance of each antibiotic used for AECOPD treatment.,In this meta-analysis, we included 19 articles that assessed 17 types of antibiotics used in 5906 AECOPD patients.,The cluster ranking showed that dirithromycin had a high clinical cure rate with a low rate of adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole had high clinical cure rates with median rates of adverse effects.,In terms of the microbiological response rate, only doxycycline was significantly better than placebo (odds ratio (OR), 3.84; 95% confidence interval (CI), 1.96-7.54; p < 0.001).,There were no other significant results with respect to the frequency of recurrence or mortality.,Our study indicated that dirithromycin is adequate for improving the clinical cure rate of patients with AECOPD with few adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole are also recommended for disease treatment.,However, caution should still be exercised when using antibiotics to treat AECOPD.,Trial Registration Not applicable.,The online version of this article (doi: 10.1186/s12890-017-0541-0) contains supplementary material, which is available to authorized users. | Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality.,Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties.,Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.,We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs.,The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.,Nine RCTs comprising 1666 patients met the inclusion criteria.,Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01).,Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective.,Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates.,The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups.,A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).,Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD.,However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance.,A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages. | 1 |
The efficacy of long-term noninvasive positive pressure ventilation (NPPV) in stable hypercapnic COPD patients with respiratory failure remains unclear.,The aim of this meta-analysis was to critically assess the efficacy of long-term NPPV on mortality, acute exacerbation, exercise capacity, symptoms and significant physiological parameters (lung function, respiratory muscle function and gas exchange).,We performed an electronic literature search using the PubMed, Cochrane Library, Embase, OVID and Chinese Biomedical Literature Database in May 2017.,Studies comparing treatment effects of NPPV with oxygen therapy in stable hypercapnic COPD patients with respiratory failure were conducted, and at least one of the following parameters were reviewed: frequency of acute exacerbation, mortality, lung function, respiratory muscle function, gas exchange, exercise capacity.,Seven studies with 810 subjects were identified.,The partial pressure of arterial carbon dioxide (PaCO2) significantly decreased in patients who received long-term NPPV (weighted mean difference [WMD] −3.73, 95% CI: −5.83 to −1.64, P=0.0005).,No significant difference was found in mortality, partial pressure of arterial oxygen (PaO2), frequency of acute exacerbation, lung function, respiratory muscle function and exercise capacity.,The subgroup analysis showed that NPPV significantly improved the survival of patients when it was targeted at greatly reducing hypercapnia (WMD 0.35, 95% CI: 0.19 to 0.64, P=0.0006).,The results indicate that long-term NPPV decreases the PaCO2 of stable hypercapnic COPD patients with respiratory failure and improves mortality with the aim of reducing PaCO2. | Telemedicine may increase accessibility to pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD), thus enhancing long-term exercise maintenance.,We aimed to explore COPD patients’ adherence and experiences in long-term telerehabilitation to understand factors affecting satisfaction and potential for service improvements.,A two-year pilot study with 10 patients with COPD was conducted.,The intervention included treadmill exercise training at home and a webpage for telemonitoring and self-management combined with weekly videoconferencing sessions with a physiotherapist.,We conducted four separate series of data collection.,Adherence was measured in terms of frequency of registrations on the webpage.,Factors affecting satisfaction and adherence, together with potential for service improvements, were explored through two semi-structured focus groups and an individual open-ended questionnaire.,Qualitative data were analysed by systematic text condensation.,User friendliness was measured by the means of a usability questionnaire.,On average, participants registered 3.0 symptom reports/week in a web-based diary and 1.7 training sessions/week.,Adherence rate decreased during the second year.,Four major themes regarding factors affecting satisfaction, adherence and potential improvements of the intervention emerged: (i) experienced health benefits; (ii) increased self-efficacy and independence; and (iii) emotional safety due to regular meetings and access to special competence; (iv) maintenance of motivation.,Participants were generally highly satisfied with the technical components of the telerehabilitation intervention.,Long-term adherence to telerehabilitation in COPD was maintained for a two-year period.,Satisfaction was supported by experienced health benefits, self-efficacy, and emotional safety.,Maintenance of motivation was a challenge and might have affected long-term adherence.,Four key factors of potential improvements in long-term telerehabilitation were identified: (i) adherence to different components of the telerehabilitation intervention is dependent on the level of focus provided by the health personnel involved; (ii) the potential for regularity that lies within the technology should be exploited to avoid relapses after vacation; (iii) motivation might be increased by tailoring individual consultations to support experiences of good health and meet individual goals and motivational strategies; (iv) interactive functionalities or gaming tools might provide peer-support, peer-modelling and enhance motivation. | 1 |
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. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are linked to several mitochondrial alterations.,Cigarette smoke (CS) alters the structure and function of mitochondria.,OPA1 is the main inner mitochondrial GTPase responsible for the fusion events.,OPA1 undergoes proteolytic cleavage from long to short forms during acute stress and mitophagy.,However, the exact role of OPA1 isoforms and related proteins during CS-induced mitophagy and COPD is not clear.,Lung tissues from non-smokers, smokers, COPD and IPF were used to determine the relative expression of OPA1 and related proteins.,Additionally, we used mouse lungs from chronic (6 months) CS exposure to evaluate the status of OPA1.,Primary lung fibroblasts from normal and COPD patients and naked mole rat (NMR) lung fibroblasts, human fetal lung fibroblast (HFL1), mouse embryonic fibroblast from wild type (WT), OPA1−/−, MFN1 and MFN2−/− were used to determine the effect of CS on OPA1 isoforms.,Various mitochondrial fusion promoters/activators (BGP-15, leflunomide, M1) and fission inhibitor (DRP1) were used to determine their effect on OPA1 status and cigarette smoke extract (CSE)-induced lung epithelial (BEAS2B) cell damage, respectively.,Seahorse flux analyzer was used to determine the effect of these compounds in BEAS2B cells with and without CSE exposure.,Short OPA1 isoforms were predominantly detected and significantly increased in COPD subjects.,Acute CSE treatment in various cell lines except NMR was found to increase the conversion of long to short OPA1 isoforms.,CSE treatment significantly increased mitochondrial stress-related protein SLP2 in all the cells used.,OPA1 interacting partners like prohibitins (PHB1 and 2) were also altered depending on the CS exposure.,Finally, BGP-15 and leflunomide treatment were able to preserve the long OPA1 isoform in cells treated with CSE.,The long OPA1 isoform along with SLP2 and prohibitins play a crucial role in CS-induced lung damage, causing mitophagy/mitochondrial dysfunction in COPD, which may be used as a novel therapeutic target in COPD.,Image 1,•Smoking is the main causative factor for Chronic Obstructive Pulmonary Disease (COPD) which is associated with mitochondrial dysfunction and altered mitophagy.,•Various strategies and models ranging from human samples, mouse models and naked mole rat fibroblasts were used to determine the behavior of the OPA1 forms by cigarette smoke and in COPD.,•Cigarette smoke exposure and in patients with COPD the lung cellular levels of S-OPA1 are significantly increased, along with SLP-2 levels with altered prohibitins.,•Compounds like BGP-15 and leflunomide promoted/maintained the L-OPA1 levels.,•Long OPA1 isoforms along with SLP2 and prohibitins play a crucial role in tobacco smoke-induced lung damage during mitophagy/mitochondrial dysfunction in COPD, which can be a therapeutic target in COPD.,Smoking is the main causative factor for Chronic Obstructive Pulmonary Disease (COPD) which is associated with mitochondrial dysfunction and altered mitophagy.,Various strategies and models ranging from human samples, mouse models and naked mole rat fibroblasts were used to determine the behavior of the OPA1 forms by cigarette smoke and in COPD.,Cigarette smoke exposure and in patients with COPD the lung cellular levels of S-OPA1 are significantly increased, along with SLP-2 levels with altered prohibitins.,Compounds like BGP-15 and leflunomide promoted/maintained the L-OPA1 levels.,Long OPA1 isoforms along with SLP2 and prohibitins play a crucial role in tobacco smoke-induced lung damage during mitophagy/mitochondrial dysfunction in COPD, which can be a therapeutic target in COPD. | Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown.,The aim of the present study was to investigate the effect of Sirt3 on airway epithelial mitochondria in cigarette smoke-induced COPD.,Our present study has shown serious airway inflammation, alveolar space enlargement, and mitochondrial damage of the airway epithelium in COPD rats.,Compared to the control rats, Sirt3 protein expression was significantly decreased in the airway epithelium and lung tissue homogenate from COPD rats.,In airway epithelial cells (BEAS-2B), cigarette smoke extract (CSE) treatment significantly decreased mRNA and protein expression of Sirt3 and manganese superoxide dismutase (MnSOD), as well as MnSOD activity in a concentration and time-dependent manner.,Sirt3 siRNA further significantly intensified the decreases in MnSOD expression and activity and aggravated mitochondrial oxidative stress and cell injury when airway epithelial cells were treated with 7.5% CSE.,In contrast, Sirt3 overexpression significantly prevented the decrease of MnSOD expression and activity and improved mitochondrial oxidative stress and cell injury in CSE-treated airway epithelial cells.,These data suggest that Sirt3 inhibits airway epithelial mitochondrial oxidative stress possibly through the regulation of MnSOD, thereby contributing to the pathogenesis of COPD. | 1 |
Nonadherence to inhalation therapy is very common in patients with chronic obstructive pulmonary disease (COPD).,Few data are available to support the role of community pharmacists in optimizing inhalation therapy in COPD patients.,Since 2007, the Kitano Hospital and the Kita-ku Pharmaceutical Association have provided a network system for delivering correct inhalation techniques through certified community pharmacists.,The effects of this network system on clinical outcomes in COPD patients were examined.,A total of 88 consecutive outpatients with COPD at baseline and 82 of those 4 years later were recruited from the respiratory clinic of Kitano Hospital Medical Research Institute.,Measurements included the frequency of COPD exacerbations, patients’ adherence to inhalation therapy using a five-point Likert scale questionnaire, and patients’ health status both prior to this system and 4 years later.,Usable information was obtained from 55 patients with COPD at baseline, and from 51 patients 4 years later.,Compared with baseline values, a significant decrease was observed in the frequency of COPD exacerbations (1.5 ± 1.6 versus 0.8 ± 1.4 times/year, P = 0.017).,Adherence to the inhalation regimen increased significantly (4.1 ± 0.7 versus 4.4 ± 0.8, P = 0.024), but health status was unchanged.,At 4 years, of 51 COPD patients, 39 (76%) patients who visited the certified pharmacies showed significantly higher medication adherence than those who did not (4.6 ± 0.6 versus 3.9 ± 1.0, P = 0.022).,The network system may improve COPD control and adherence to inhalation regimens. | To review published evidence regarding the cost effectiveness of multi-component COPD programs and to illustrate how potentially cost effective programs can be identified.,Systematic search of Medline and Cochrane databases for evaluations of multi-component disease management or chronic care programs for adults with COPD, describing process, intermediate, and end results of care.,Data were independently extracted by two reviewers and descriptively summarized.,Twenty articles describing 17 unique COPD programs were included.,There is little evidence for significant improvements in process and intermediate outcomes, except for increased provision of patient self-management education and improved disease-specific knowledge.,Overall, the COPD programs generate end results equivalent to usual care, but programs containing ≥3 components show lower relative risks for hospitalization.,There is limited scope for programs to break-even or save money.,Identifying cost effective multi-component COPD programs remains a challenge due to scarce methodologically sound studies that demonstrate significant improvements on process, intermediate and end results of care.,Estimations of potential cost effectiveness of specific programs illustrated in this paper can, in the absence of ‘perfect data’, support timely decision-making regarding these programs.,Nevertheless, well-designed health economic studies are needed to decrease the current decision uncertainty. | 1 |
The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment.,The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial.,Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients.,A total of 404 patients received treatment, with 165 participating in the ESWT substudy.,A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% (p = 0.02)] but not with tiotropium/olodaterol 2.5/5 µg [9% (p = 0.14)] versus placebo.,In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 µg [21% (p = 0.055)] and tiotropium/olodaterol 2.5/5 µg [21% (p = 0.056)] versus placebo.,Tiotropium/olodaterol 5/5 µg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time.,[ClinicalTrials.gov identifier: NCT01525615.] | Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality.,Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance.,However, none of these studies were designed with physical activity as primary outcome.,This study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 μg once daily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with moderate-to-severe COPD.,In this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received IND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods).,Eligible patients were ≥40 years of age, current or ex-smokers (smoking history ≥10 pack-years), with post-salbutamol forced expiratory volume in 1 s (FEV1) 40-80 % predicted, and FEV1:forced vital capacity <0.70.,The co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure.,Key secondary endpoints were average number of steps per day and the duration of at least moderate activity per day.,Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.,A total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 % predicted), with 183 (94.3 %) completing the study.,Compared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001), activity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day (difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity (difference 4.4 min, p = 0.264).,IND/GLY was associated with statistically significant improvements versus placebo in peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days.,The incidence of treatment-emergent adverse events was 22.8 % with IND/GLY and 22.9 % with placebo.,In this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient education or lifestyle advice, improved daily physical activity levels.,This suggests that IND/GLY has the potential to impact two of the main clinical concerns in the care of patients with COPD.,ClinicalTrials.gov number: NCT01996319.,The online version of this article (doi:10.1186/s12890-016-0256-7) contains supplementary material, which is available to authorized users. | 1 |
Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD).,Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.,Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors.,Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.,236 COPD patients from five European centres were included.,Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”.,After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14.,Both demonstrated good model fit (person separation index >0.7).,Confirmatory factor analysis supported the bidimensional structure.,Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.,Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.,Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patientshttp://ow.ly/LJqP8 | The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | 1 |
Epigenetics changes have been shown to be affected by cigarette smoking.,Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD).,We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers.,We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina’s Infinium HumanMethylation450 BeadChip.,Our data revealed that the differentially methylated genes were related to top canonical pathways (e.g., G beta gamma signaling, mechanisms of cancer, and nNOS signaling in neurons), disease and disorders (organismal injury and abnormalities, cancer, and respiratory disease), and molecular and cellular functions (cell death and survival, cellular assembly and organization, cellular function and maintenance) in patients with COPD.,The genome-wide DNA methylation analysis identified suggestive genes, such as NOS1AP, TNFAIP2, BID, GABRB1, ATXN7, and THOC7 with DNA methylation changes in COPD lung tissues that were further validated by pyrosequencing.,Pyrosequencing validation confirmed hyper-methylation in smokers and patients with COPD as compared to non-smokers.,However, we did not detect significant differences in DNA methylation for TNFAIP2, ATXN7, and THOC7 genes in smokers and COPD groups despite the changes observed in the genome-wide analysis.,Our study suggests that DNA methylation in suggestive genes, such as NOS1AP, BID, and GABRB1 may be used as epigenetic signatures in smokers and patients with COPD if the same is validated in a larger cohort.,Future studies are required to correlate DNA methylation status with transcriptomics of selective genes identified in this study and elucidate their role and involvement in the progression of COPD and its exacerbations.,The online version of this article (doi:10.1186/s13148-017-0335-5) contains supplementary material, which is available to authorized users. | Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance.,Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels.,Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids.,ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations.,Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations.,To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis.,Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation.,Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs.,When exposed to ATP the EVs release IL-1β/IL-18 via a P2X7/caspase-dependent mechanism.,Furthermore ATP challenge can cause a P2X7 dependent increase in LPS-driven neutrophilia.,This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area. | 1 |
Biomarkers for the progression of lung function in COPD are currently scarce.,Plasma fetuin-B (FETUB) was identified by iTRAQ-based proteomics and was verified by ELISA in another group.,Information regarding acute exacerbation (AE) was collected in a one-year follow-up programme.,FETUB concentrations (1652 ± 427 ng/ml) were greater in COPD patients than in controls (1237 ± 77 ng/ml).,The concentrations of FETUB in GOLD II (1762 ± 427 ng/ml), III (1650 ± 375 ng/ml) and IV (1800 ± 451 ng/ml) groups were greater than those in the controls (1257 ± 414 ng/ml) and the GOLD I (1345 ± 391 ng/ml) group.,ROCs indicated that FETUB distinguished COPD patients from controls (AUC 0.747, 95% CI: 0.642-0.834) and also GOLD II, III and IV from GOLD I COPD patients (AUC: 0.770, 95% CI: 0.634-0.874).,The combination of FETUB and fibrinogen performed better (AUC: 0.804, 95% CI: 0.705-0.881).,FETUB also predicted the occurrence of AE (AUC: 0.707, 95% CI: 0.566-0.824) or frequent AE (AUC: 0.727, 95% CI: 0.587-0.840).,FETUB concentrations were negatively correlated with FEV1%pred (r = −0.446, p = 0.000) and positively correlated with RV%pred (r = 0.317, p = 0.004), RV/TLC% (r = 0.360, p = 0.004), CT emphysema% (r = 0.322, p = 0.008) and grades of lung function (r = 0.437, p = 0.000).,In conclusion, FETUB is likely to assist the diagnosis and management of COPD as a complement for other markers. | The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported.,However, CRP is a systemic inflammatory biomarker that is related to many other diseases.,The objective of this study is to discover a diagnostic biomarker for COPD.,Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study.,Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected.,CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects.,Receiver operating characteristic values of CRP and the identified biomarkers were determined.,A validation COPD cohort was used to reexamine the identified biomarker.,Correlation of the biomarker with 1-year lung function decline was determined.,Proteoglycan 4 (PRG4) was identified as a biomarker in COPD.,The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05).,PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency.,There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R2=0.91, P=0.013).,PRG4 may be a biomarker for identification of severity in COPD.,It was related to the 1-year forced vital capacity decline in COPD patients. | 1 |
The introduction of microCT has made it possible to show that the terminal bronchioles are narrowed and destroyed before the onset of emphysematous destruction in COPD.,This report extends those observations to the cellular and molecular level in the centrilobular phenotype of emphysematous destruction in lungs donated by persons with very severe COPD (n = 4) treated by lung transplantation with unused donor lungs (n = 4) serving as controls.,These lung specimens provided companion samples to those previously examined by microCT (n = 61) that we examined using quantitative histology (n = 61) and gene expression profiling (n = 48).,The histological analysis showed that remodeling and destruction of the bronchiolar and alveolar tissue is associated with macrophage, CD4, CD8, and B cell infiltration with increased formation of tertiary lymphoid organs.,Moreover, gene set enrichment analysis showed that genes known to be expressed by natural killer (NK), lymphoid tissue inducer (LTi), and innate lymphoid cell 1 (ILC1) cells, but not ILC2 or ILC3 cells, were enriched in the expression profiles associated with CD4, CD8, and B cell infiltration.,Based on these findings, we postulate that the centrilobular phenotype of emphysematous destruction COPD is driven by a Th1 response activated by infiltrating ILC1, NK, and LTi cells. | In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction.,In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown.,We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function.,Lung tissue sections from 19 COPD patients (median [interquartile range] FEV1% predicted 56 [23-75]) and 10 controls were stained for tryptase and chymase.,Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.,COPD patients had lower MC-T numbers in the subepithelial area of central airways than controls.,In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02).,Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups.,More MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients.,It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered. | 1 |
An increasing body of evidence suggests that the long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination appears to play an important role in maximizing bronchodilation, with studies to date indicating that combining different classes of bronchodilators may result in significantly greater improvements in lung function compared to the use of a single drug, and that these combinations are well tolerated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,An inhaled, fixed-dose combination of two 24-hour bronchodilators, the LAMA umeclidinium and the LABA vilanterol, is under development as a once-daily treatment for COPD.,The efficacy of both mono-components has already been demonstrated.,The information currently available suggests that umeclidinium/vilanterol is an effective once-daily dual bronchodilator fixed-dose combination in the treatment of COPD.,However, it remains to be seen if it compares favorably with current therapies.,Moreover, the question remains whether umeclidinium/vilanterol fixed-dose combination, which significantly improves FEV1, is also associated with improvements in other outcome measures that are important to COPD patients. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
The objective of the FAVOR study was to evaluate the effect of indacaterol/glycopyrronium (IND/GLY) versus tiotropium on peak forced expiratory volume in 1 s (FEV1) and also to investigate patient satisfaction and treatment preference.,Patients with moderate-to-severe airflow limitation (FEV1/forced vital capacity ratio of <0.70), those with a COPD assessment test score of ≥10, and those who were maintained on tiotropium HandiHaler® therapy prior to enrollment were recruited for the study, and randomized (1:1) to receive either 4 weeks open-label IND/GLY (110/50 μg) once daily followed by 4 weeks of tiotropium (18 μg) once daily or vice versa.,The primary endpoint was FEV1 1 h post-inhalation after 4 weeks of treatment.,Other endpoints included patient’s and physician’s preference for treatment, patient’s satisfaction evaluated using a study-specific questionnaire and the abbreviated Treatment Satisfaction Questionnaire for Medication, and safety and tolerability.,Eighty-seven out of 88 randomized patients completed the study and showed significantly higher FEV1 1 h post-inhalation after 4 weeks of treatment with IND/GLY versus tiotropium (treatment difference =0.081 L; p=0.0017).,IND/GLY was preferred over tiotropium among the patients (69.4% versus 30.6%, p=0.0004) and the physicians (81.6% versus 18.4%, p<0.0001).,A higher proportion of the patients stated they were very satisfied or satisfied with IND/GLY versus tiotropium with regard to dyspnea reduction (79.3% versus 58.0%, respectively) and reduction of dyspnea on exertion (72.4% versus 43.2%, respectively).,Patients treated with IND/GLY showed significant improvement in Treatment Satisfaction Questionnaire for Medication domain scores versus tiotropium.,IND/GLY demonstrated a good safety and tolerability profile.,This study indicated that, beyond FEV1, important patient-reported outcomes improved with the open-label dual bronchodilator IND/GLY when compared with tiotropium.,This study suggests that individual patients felt the lung function benefits with IND/GLY compared with tiotropium, which, in turn, may also have contributed to the preference for IND/GLY. | NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients. | 1 |
The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms.,The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.,In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.,The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.,Overall, 676 patients completed the study.,The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met.,QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001).,QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001).,QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use.,However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC.,Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%).,The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).,These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year. | The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD.,COPD patients have a variety of comorbidities, but little is known about their impact on quality of life.,This study was designed to investigate comorbid factors that may contribute to high CAT scores.,An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects.,Health status was assessed by the CAT, the St.,Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health.,Comorbidities were identified based on patients’ reports, physicians’ records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale.,Dual X-ray absorptiometry measurements of bone mineral density were performed.,The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36.,The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients.,Symptomatic COPD patients have a high prevalence of comorbidities.,A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized.,Clinical trial registered with UMIN (UMIN000003470). | 1 |
It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD).,The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD.,National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008.,Comorbidities were obtained from the Swedish Hospital Discharge Register.,Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion.,The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, PaO2 breathing air, FEV1, smoking history and year of inclusion.,In total, 8,712 patients (55% women) were included and 6,729 patients died during the study period.,No patient was lost to follow-up.,Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P<0.05 for all odds ratios).,Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes.,Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95% confidence interval, 0.68-0.77; P<0.001).,Comorbidity is different in men and women, but does not explain the sex-related difference in mortality in oxygen-dependent COPD. | The influence of gender on the expression of COPD has received limited attention.,Quality of Life (QoL) has become an important outcome in COPD patients.,The aim of our study was to explore factors contributing to gender differences in Quality of Life of COPD patients.,In 146 men and women with COPD from a pulmonary clinic we measured: Saint George's Respiratory Questionnaire (SGRQ), age, smoking history, PaO2, PaCO2, FEV1, FVC, IC/TLC, FRC, body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC), degree of comorbidity (Charlson index) and exacerbations in the previous year.,We explored differences between genders using Mann-Whitney U-rank test.,To investigate the main determinants of QoL, a multiple lineal regression analysis was performed using backward Wald's criteria, with those variables that significantly correlated with SGRQ total scores.,Compared with men, women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01, symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p = 0.01).,SGRQ total scores correlated in men with: FEV1% (-0.378, p < 0.001), IC/TLC (-0.368, p = 0.002), PaO2 (-0.379, p = 0.001), PaCO2 (0.256, p = 0.05), 6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index (0.380, p = 0.001) and MMRC (0.654, p < 0.001).,In women, the scores correlated only with FEV1% (-0.293, p = 0.013) PaO2 (-0.315, p = 0.007), exacerbations (0.290, p = 0.013) and MMRC (0.628, p < 0.001).,Regression analysis (B, 95% CI) showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8), IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women manifested the highest independent associations with SGRQ scores.,In moderate to severe COPD patients attending a pulmonary clinic, there are gender differences in health status scores.,In turn, the clinical and physiological variables independently associated with those scores differed in men and women.,Attention should be paid to the determinants of QoL scores in women with COPD. | 1 |
The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components.,Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown.,The aim of this study was to assess the cost-utility and budget impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.,A cost-utility study was performed, using an individual-level Markov model.,To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium-olodaterol TOnado trial.,In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium-olodaterol FDC was compared with tiotropium.,Cost-utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis.,The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%).,Both univariate and probabilistic sensitivity analyses were performed.,Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.,As a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY.,Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY.,Results were robust in univariate and probabilistic sensitivity analyses.,Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence.,Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.,Tiotropium-olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds. | Introduction: Inhaled corticosteroids (ICS) (in fixed combinations with long-acting β2-agonists [LABAs]) are frequently prescribed for patients with chronic obstructive pulmonary disease (COPD), outside their labeled indications and recommended treatment strategies and guidelines, despite having the potential to cause significant side effects.,Areas covered: Although the existence of asthma in patients with asthma-COPD overlap syndrome (ACOS) clearly supports the use of anti-inflammatory treatment (typically an ICS/LABA combination, as ICS monotherapy is usually not indicated for COPD), the current level of ICS/LABA use is not consistent with the prevalence of ACOS in the COPD population.,Data have recently become available showing the comparative efficacy of fixed bronchodilator combinations (long-acting muscarinic antagonist [LAMA]/LABA with ICS/LABA combinations).,Additionally, new information has emerged on ICS withdrawal without increased risk of exacerbations, under cover of effective bronchodilation.,Expert opinion: For patients with COPD who do not have ACOS, a LAMA/LABA combination may be an appropriate starting therapy, apart from those with mild disease who can be managed with a single long-acting bronchodilator.,Patients who remain symptomatic or present with exacerbations despite effectively delivered LAMA/LABA treatment may require additional drug therapy, such as ICS or phosphodiesterase-4 inhibitors.,When prescribing an ICS/LABA, the risk:benefit ratio should be considered in individual patients. | 1 |
To determine whether visually assessed patterns of emphysema at CT might provide a simple assessment of mortality risk among cigarette smokers.,Of the first 4000 cigarette smokers consecutively enrolled between 2007 and 2011 in this COPDGene study, 3171 had data available for both visual emphysema CT scores and survival.,Each CT scan was retrospectively visually scored by two analysts using the Fleischner Society classification system.,Severity of emphysema was also evaluated quantitatively by using percentage lung volume occupied by low-attenuation areas (voxels with attenuation of −950 HU or less) (LAA-950).,Median duration of follow-up was 7.4 years.,Regression analysis for the relationship between imaging patterns and survival was based on the Cox proportional hazards model, with adjustment for age, race, sex, height, weight, pack-years of cigarette smoking, current smoking status, educational level, LAA-950, and (in a second model) forced expiratory volume in 1 second (FEV1).,Observer agreement in visual scoring was good (weighted κ values, 0.71-0.80).,There were 519 deaths in the study cohort.,Compared with subjects who did not have visible emphysema, mortality was greater in those with any grade of emphysema beyond trace (adjusted hazard ratios, 1.7, 2.5, 5.0, and 4.1, respectively, for mild centrilobular emphysema, moderate centrilobular emphysema, confluent emphysema, and advanced destructive emphysema, P < .001).,This increased mortality generally persisted after adjusting for LAA-950.,The visual presence and severity of emphysema is associated with significantly increased mortality risk, independent of the quantitative severity of emphysema.,Online supplemental material is available for this article. | Parametric response mapping (PRM) of paired CT lung images has been shown to improve the phenotyping of COPD by allowing for the visualization and quantification of non-emphysematous air trapping component, referred to as functional small airways disease (fSAD).,Although promising, large variability in the standard method for analyzing PRMfSAD has been observed.,We postulate that representing the 3D PRMfSAD data as a single scalar quantity (relative volume of PRMfSAD) oversimplifies the original 3D data, limiting its potential to detect the subtle progression of COPD as well as varying subtypes.,In this study, we propose a new approach to analyze PRM.,Based on topological techniques, we generate 3D maps of local topological features from 3D PRMfSAD classification maps.,We found that the surface area of fSAD (SfSAD) was the most robust and significant independent indicator of clinically meaningful measures of COPD.,We also confirmed by micro-CT of human lung specimens that structural differences are associated with unique SfSAD patterns, and demonstrated longitudinal feature alterations occurred with worsening pulmonary function independent of an increase in disease extent.,These findings suggest that our technique captures additional COPD characteristics, which may provide important opportunities for improved diagnosis of COPD patients. | 1 |
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. | Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation.,Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown.,To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD.,Subjects with asthma and COPD (n = 54 and n = 49) were studied.,Clinical characteristics and sputum were collected at entry into the study.,A 2-step sputum processing method was performed for supernatant and cytospin preparation.,Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels.,Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17.,There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02].,In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes.,However, these phenotypes were unrelated to the diagnosis of asthma or COPD.,Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique.,Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease.,Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated. | 1 |
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients.,In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally.,Demographics, anthropometrics, lung function and clinical data were assessed.,Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband.,Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters.,Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns.,Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data.,Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all).,Daily physical activity measures and hourly patterns are heterogeneous in COPD.,Clusters of patients were identified solely based on physical activity data.,These findings may be useful to develop interventions aiming to promote physical activity in COPD. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
Patient preference is an important factor when choosing an inhaler device for asthma or chronic obstructive pulmonary disease (COPD).,To identify characteristics of patients with asthma or COPD who prefer a once-daily controller medication regimen.,This retrospective observational study used electronic patient records and linked outcomes from patient-completed questionnaires in a primary care database.,We compared the characteristics of patients indicating a preference for once-daily therapy with those who were unsure or indicating no preference.,Of 3,731 patients with asthma, 2,174 (58%) were women; the mean age was 46 years (range 2-94).,Of 2,138 patients with COPD, 980 (46%) were women; the mean age was 70 years (range 35-98).,Approximately half of the patients in each cohort indicated once-daily preference, one-quarter were unsure, and one-quarter did not prefer once-daily therapy.,In patients with asthma or COPD, the preference for once-daily controller medication was significantly associated with poor adherence and higher concerns about medication.,In asthma, good control and low self-perceived controller medication need were associated with once-daily preference.,By contrast, in COPD, a high self-perceived need for controller medication was associated with once-daily preference.,There was no significant relationship between once-daily preference and age, sex, disease severity, or exacerbation history.,Understanding patient preferences may help prescribers to individualise therapy better for asthma and COPD. | Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users. | 1 |
Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations.,Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of “clinically important deterioration” (CID) has therefore been developed.,We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies.,The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE).,All studies recruited patients with symptomatic COPD, FEV1 <50%, and an exacerbation history.,We measured the time to first CID and to sustained CID, an endpoint combining FEV1, St George’s Respiratory Questionnaire (SGRQ), moderate-to-severe exacerbations, and death.,The time to first CID was based on the first occurrence of any of the following: a decrease of ≥100 mL from baseline in FEV1, an increase of ≥4 units from baseline in SGRQ total score, the occurrence of a moderate/severe COPD exacerbation, or death.,The time to sustained CID was defined as: a CID in FEV1 and/or SGRQ total score maintained at all subsequent visits, an exacerbation, or death.,Extrafine BDP/FF/G significantly extended the time to first CID vs BDP/FF (HR 0.61, P<0.001), tiotropium (0.72, P<0.001), and IND/GLY (0.82, P<0.001), and significantly extended the time to sustained CID vs BDP/FF (HR 0.64, P<0.001) and tiotropium (0.80, P<0.001), with a numerical extension vs IND/GLY.,In patients with symptomatic COPD, FEV1 <50%, and an exacerbation history, extrafine BDP/FF/G delayed disease deterioration compared with BDP/FF, tiotropium, and IND/GLY.,The studies are registered in ClinicalTrials.gov: TRILOGY, NCT01917331; TRINITY, NCT01911364; TRIBUTE, NCT02579850. | 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. | 1 |
COPD has been associated with a high number of comorbidities and a relatively high level of health care resource utilization.,This study aimed to estimate the social economic impact of COPD in the autonomous community of Extremadura (Spain) in 2015.,This is a retrospective observational study carried out using a representative sample of patients diagnosed with COPD in Extremadura.,Sociodemographic data, data on health care resource utilization, formal and informal care received by the patients, and loss of labor productivity in the last 12 months were collected through an electronic data collection platform.,Direct health care costs were estimated using the bottom-up approach, costs of informal care were assessed using the substitution method, and labor productivity losses were calculated using the human capital method.,A sample of 386 patients was obtained (mean age: 71.8±10.3 years, males: 76.2%).,The results show an average annual cost per patient of 3,077 euros.,Direct health care costs represented 43.8% (1,645 euros), direct non-health care costs amounted to 38.3% (1,440 euros), and labor productivity losses represented 17.9% (672 euros) of the average annual cost.,The total annual cost of patients with COPD in Extremadura reached 36.2 million euros in 2015.,COPD poses a significant burden for the health care system and the society of Extremadura.,The implementation of preventive and control measures could result in a substantial reduction in the economic impact. | To determine generic utilities for Spanish chronic obstructive pulmonary disease (COPD) patients stratified by different classifications: GOLD 2007, GOLD 2013, GesEPOC 2012 and BODEx index.,Multicentre, observational, cross-sectional study.,Patients were aged ≥40 years, with spirometrically confirmed COPD.,Utility values were derived from EQ-5D-3 L.,Means, standard deviations (SD), medians and interquartile ranges (IQR) were computed based on the different classifications.,Differences in median utilities between groups were assessed by non-parametric tests.,346 patients were included, of which 85.5% were male with a mean age of 67.9 (SD = 9.7) years and a mean duration of COPD of 7.6 (SD = 5.8) years; 80.3% were ex-smokers and the mean smoking history was 54.2 (SD = 33.2) pack-years.,Median utilities (IQR) by GOLD 2007 were 0.87 (0.22) for moderate; 0.80 (0.26) for severe and 0.67 (0.42) for very-severe patients (p < 0.001 for all comparisons).,Median utilities by GOLD 2013 were group A: 1.0 (0.09); group B: 0.87 (0.13); group C: 1.0 (0.16); group D: 0.74 (0.29); comparisons were statistically significant (p < 0.001) except A vs C.,Median utilities by GesEPOC phenotypes were 0.84 (0.33) for non exacerbator; 0.80 (0.26) for COPD-asthma overlap; 0.71 (0.62) for exacerbator with emphysema; 0.72 (0.57) for exacerbator with chronic bronchitis (p < 0.001).,Comparisons between patients with or without exacerbations and between patients with COPD-asthma overlap and exacerbator with chronic bronchitis were statistically-significant (p < 0.001).,Median utilities by BODEx index were: group 0-2: 0.89 (0.20); group 3-4: 0.80 (0.27); group 5-6: 0.67 (0.29); group 7-9: 0.41 (0.31).,All comparisons were significant (p < 0.001) except between groups 3-4 and 5-6.,Irrespective of the classification used utilities were associated to disease severity.,Some clinical phenotypes were associated with worse utilities, probably related to a higher frequency of exacerbations.,GOLD 2007 guidelines and BODEx index better discriminated patients with a worse health status than GOLD 2013 guidelines, while GOLD 2013 guidelines were better able to identify a smaller group of patients with the best health. | 1 |
A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear.,Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable.,To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases.,We recruited 59 outpatients with MetS and 76 outpatients with COPD.,After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29).,A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%.,More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease.,MetS+COPD patients exhibited significantly higher C-peptide levels.,We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers.,Finally, a negative association emerged between smoking and vitamin D.,We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance.,Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development. | Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier.,Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity.,In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling.,The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.,Patients scheduled for lung resection were prospectively recruited.,Demographic, clinical data and pulmonary function tests results were recorded.,Emphysema was visually scored and histological remodeling features were noted.,Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay.,We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding.,In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.,13 COPD and 7 non COPD patients were included.,The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [−0.77;-0.03] respectively).,Cell proliferation index was decreased in COPD patients (19 ± 6% in COPD vs 27 ± 3% in non COPD, p = 0.04).,The severity of COPD was associated with a lower level of MMP-2 (7.8 ± 2 105 AU in COPD GOLD D vs 12.8 ± 0.13 105 AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]).,Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI [0.09;0.87] respectively).,Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels.,Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).,Our results showed an abnormal bronchial epithelial wound closure process in severe COPD.,Further studies are needed to elucidate the contribution and the regulation of this mechanism in the complex pathophysiology of COPD.,The online version of this article (doi:10.1186/s12931-014-0151-9) contains supplementary material, which is available to authorized users. | 1 |
To characterize the distribution of BMI in a population-based sample of COPD patients and to evaluate the impact of obesity on their health status, exercise tolerance, systemic inflammation and comorbidity.,A population-based sample of 3,797 subjects aged 40-80 years from the EPI-SCAN study was selected.,Subjects were categorized according their body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) or obese (BMI≥30.0 kg/m2).,Subjects were evaluated with post-bronchodilator spirometry and 6-minute walk tests.,Smoking habits, respiratory symptoms, generic and specific quality of life, daily physical activities, comorbidities and systemic inflammatory biomarkers were recorded.,The prevalence of obesity or being overweight was higher in the 382 COPD patients than in the subjects without airflow limitation (29.4%, 95%CI 24.8-33.9% vs.,24.3, 95%CI 22.9-25.8; and 44.7%, 95%CI 39.7-49.6% vs.,43.0%, 95%CI 41.3-44.6, respectively; p = 0.020).,In the COPD subgroup, obese subjects presented more dyspnea and less chronic cough, chronic bronchitis or chronic phlegm than normal-weight patients, as well as a worse health status.,Moreover, reduced exercise tolerance and higher plasmatic C-reactive protein levels were found in the obese patients, who also presented a greater prevalence of cardiovascular disease (adjusted odds ratio 4.796, 95%CI 1.806-12.736, p = 0.002).,In a population-based sample, obesity is more prevalent in COPD patients than in subjects without airflow limitation.,Furthermore, obesity affects the clinical manifestations, quality of life and exercise tolerance of COPD patients, and it may contribute to a phenotype characterized by increased systemic inflammation and greater frequency of cardiovascular comorbidity. | New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences.,There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema).,The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD). | 1 |
According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting β2 agonist therapy is recommended in patients with moderate-to-severe disease and an increased risk of exacerbations.,However, ICS are largely overprescribed in clinical practice, and most patients are unlikely to benefit from long-term ICS therapy.,Evidence from recent randomized-controlled trials supports the hypothesis that ICS can be safely and effectively discontinued in patients with stable COPD and in whom ICS therapy may not be indicated, without detrimental effects on lung function, health status, or risk of exacerbations.,This article summarizes the evidence supporting the discontinuation of ICS therapy, and proposes an algorithm for the implementation of ICS withdrawal in patients with COPD in clinical practice.,Given the increased risk of potentially serious adverse effects and complications with ICS therapy (including pneumonia), the use of ICS should be limited to the minority of patients in whom the treatment effects outweigh the risks. | 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. | 1 |
Acute exacerbations are the major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD).,Rhinovirus, which causes acute exacerbations may also accelerate progression of lung disease in these patients.,Current therapies reduces the respiratory symptoms and does not treat the root cause of exacerbations effectively.,We hypothesized that quercetin, a potent antioxidant and anti-inflammatory agent with antiviral properties may be useful in treating rhinovirus-induced changes in COPD.,Mice with COPD phenotype maintained on control or quercetin diet and normal mice were infected with sham or rhinovirus, and after 14 days mice were examined for changes in lung mechanics and lung inflammation.,Rhinovirus-infected normal mice showed no changes in lung mechanics or histology.,In contrast, rhinovirus-infected mice with COPD phenotype showed reduction in elastic recoiling and increase in lung inflammation, goblet cell metaplasia, and airways cholinergic responsiveness compared to sham-infected mice.,Interestingly, rhinovirus-infected mice with COPD phenotype also showed accumulation of neutrophils, CD11b+/CD11c+ macrophages and CD8+ T cells in the lungs.,Quercetin supplementation attenuated rhinovirus-induced all the pathologic changes in mice with COPD phenotype.,Together these results indicate that quercetin effectively mitigates rhinovirus-induced progression of lung disease in a mouse model of COPD.,Therefore, quercetin may be beneficial in the treatment of rhinovirus-associated exacerbations and preventing progression of lung disease in COPD. | Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare.,One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi]) infection.,However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood.,As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1).,Recombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE.,To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells.,The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi.,We found that: (1) HNE directly increased NTHi load in human airway epithelial cells; (2) HNE degraded human SPLUNC1 protein; (3) Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4) NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5) SPLUNC1 was reduced in lungs of COPD patients.,Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections.,SPLUNC1 therapy likely attenuates bacterial infections during AECOPD. | 1 |
Asthma and chronic obstructive pulmonary disease are inflammatory lung disorders responsible for significant morbidity and mortality worldwide.,While the importance of allergic responses in asthma is well known, respiratory viral and bacterial infections and pollutants especially cigarette smoke are important factors in the pathogenesis of both diseases.,Corticosteroid treatment remains the first preference of treatment in either disease, however these therapies are not always completely effective, and are associated with side effects and steroid resistance.,Due to such limitations, development of new treatments represents a major goal for both the pharmaceutical industry and academic researchers.,There are now excellent reasons to promote NF-κB signalling intermediates and Rel family proteins as potential therapeutic targets for both asthma and chronic obstructive pulmonary disease.,This notion is supported by the fact that much of the underlying inflammation of both diseases independent of stimuli, is mediated at least in part, by NF-κB mediated signalling events in several cell types.,Also, a range of inhibitors of NF-κB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-κB decoy sequences, small molecule inhibitors such as IKK-β inhibitors, and proteasome inhibitors affecting NF-κB signalling, that have either shown promise in animal models or have begun clinical trials in other disorders.,This review will focus on the role of NF-κB in both diseases, will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-κB as a therapeutic target in these two important inflammatory lung diseases. | In this review we consider the therapeutic potential of targeting Akt for the treatment of COPD.,Akt is a serine/threonine protein kinase that functions as a signaling intermediate linked to multiple signaling programs involved in survival, inflammation, and growth.,Akt is closely associated with key membrane-bound receptors and represents a convergent integration point for multiple stimuli implicated in COPD pathogenesis.,Persistent activation of Akt secondary to somatic mutations in regulatory oncogenes, such as PTEN, may explain why inflammation in COPD does not resolve when smoking is ceased.,Akt is also implicated in the systemic manifestations of COPD such as skeletal muscle wasting and metabolic disturbances.,Furthermore, targeting Akt may provide a useful means of limiting the severity and duration of disease exacerbations in COPD.,As such, Akt represents a particularly attractive therapeutic target for the treatment of COPD.,Interestingly, current knowledge suggests that both inhibitors and activators of Akt may be useful for treating different clinical subpopulations of COPD patients. | 1 |
Rationale: Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches.,Objectives: To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations.,Methods: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts.,The microbiome was analyzed using COPDMAP and AERIS as a discovery data set and BEAT-COPD as a validation data set.,Measurements and Main Results: The airway microbiome in neutrophilic COPD was heterogeneous, with two primary community types differentiated by the predominance of Haemophilus.,The Haemophilus-predominant subgroup had elevated sputum IL-1β and TNFα (tumor necrosis factor α) and was relatively stable over time.,The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic.,Patients in this state at stability were susceptible to the greatest microbiome shifts during exacerbations.,This subgroup can temporally switch to both neutrophilic Haemophilus-predominant and eosinophilic states that were otherwise mutually exclusive.,Time-series analysis on the microbiome showed that the temporal trajectories of Campylobacter and Granulicatella were indicative of intrapatient switches from neutrophilic to eosinophilic inflammation, in track with patient sputum eosinophilia over time.,Network analysis revealed distinct host-microbiome interaction patterns among neutrophilic Haemophilus-predominant, neutrophilic balanced microbiome, and eosinophilic subgroups.,Conclusions: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies.,Neutrophilic and eosinophilic COPD are interchangeable in some patients.,Monitoring temporal variability of the airway microbiome may track patient inflammatory status over time. | We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD.,We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects.,Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages.,Multiplex ELISA measured BAL cytokines.,Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles.,We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups.,However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects.,BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs.,The mouse-model of COPD showed similar increase in mRNA for M2 markers.,Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance.,There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | This report updates surveillance results for COPD in the United States.,For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed.,In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD.,From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019).,In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD.,From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001).,In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD.,Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033).,There were 133,575 deaths (63.1 per 100,000) from COPD in 2010.,The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163).,Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001).,Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed.,Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States. | 1 |
Pulmonary rehabilitation (PR) is an important treatment option for chronic obstructive pulmonary disease (COPD) patients and might contribute to a reduction in exacerbation and exacerbation-related hospitalization rate.,In this prospective study, all COPD patients that completed a comprehensive pulmonary rehabilitation program (PRP) between June 2006 and December 2012 were included.,Self-reported exacerbation and hospitalization frequency 1 year before PR was retrospectively recorded.,During the year following PR, exacerbation and hospitalization frequency was recorded with questionnaires.,For 343 patients, complete information on exacerbation and hospitalization rate was obtained.,The mean number of exacerbations decreased significantly after participating in a PRP by 1.37 exacerbations/year (95% confidence interval 1.029 to 1.717) from 4.56±3.26 exacerbations in the year preceding PR to 3.18±2.53 in the year following PR (P<0.0005).,The number of hospitalizations due to exacerbations decreased significantly by 0.68 hospitalizations/year (95% confidence interval 0.467 to 0.903) from 1.48±1.84 in the year preceding PR to 0.80±1.31 hospitalizations/year in the year following PR (P<0.0005).,The proportion of patients with a frequent exacerbation type (more than two exacerbations/year) was reduced by 24%.,Multivariate regression analysis to explore determinants that might predict reduction in exacerbation frequency or change in exacerbation pattern did not reveal clinically useful predictors, although patients with more exacerbations before PR had the highest potential for reduction.,In a large population of severely impaired COPD patients with high exacerbation rates, a significant reduction in exacerbation and hospitalization frequency was observed after participation in a comprehensive PRP. | Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa.,The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined.,To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients.,A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year.,High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients.,P. aeruginosa isolates were genotyped by PFGE.,Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis.,P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%).,Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization.,In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation.,Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75).,In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients.,The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics.,Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis. | 1 |
Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity.,Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians.,The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids.,There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting.,Patients’ comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use.,This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques.,Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD. | COPD remains under-recognized and under-treated.,Much of early COPD care is given by primary care physicians but only when COPD is recognized.,This survey explores the attitudes, beliefs, and knowledge related to COPD recognition, diagnosis, and treatment from family physicians and nurse practitioners (NPs) and physician assistants (PAs) working in primary care.,We completed a survey of family physicians, and NPs/PAs attending one of three CME programs on five common chronic conditions including COPD.,Return rate was 62% (n = 284) including 178 physicians and 100 NPs/PAs.,Fewer than half of the respondents reported knowledge of or use of COPD guidelines.,The barriers to recognition and diagnosis of COPD they reported included the multiple morbidities of most COPD patients, failure of patients to report COPD symptoms, as well as lack of knowledge and inadequate training in COPD diagnosis and management.,Three quarters (74%) of respondents reported use of spirometry to diagnose COPD but only 32% said they included reversibility assessment.,COPD was incorrectly assessed as a disease primarily of men (78% of respondents) that appeared after age 60 (61%).,Few respondents reported that they believed COPD treatment was useful or very useful for improving symptoms (15%) or decreasing exacerbations (3%) or that pulmonary rehabilitation was helpful (3%), but 13% reported they thought COPD treatment could extend longevity.,Primary care physicians and NPs/PAs working in primary care continue to report lack of awareness and use of COPD guidelines, as well as correct information related to COPD epidemiology or potential benefits of available treatments including pulmonary rehabilitation.,It is unlikely that diagnosis and management of COPD will improve in primary care until these knowledge gaps and discrepancies with published efficacy of therapy issues are addressed. | 1 |
We studied if pre-bronchodilator FEV1/FEV6 determinations with microspirometers by GPs improve the diagnostic process for COPD in a 6-8 month clustered randomised controlled trial in Dutch general practices (http://www.trialregister.nl: NTR4041).,GPs allocated to microspirometry (MI) used COPD-6® microspirometers in patients ≥50 years old with a smoking history and respiratory complaints that could indicate undiagnosed COPD and ask to refer patients for full spirometry if MI was positive (FEV1/FEV6 <0.73).,Introduction of the COPD-6® was postponed in the usual care (UC) group.,GPs of both study arms were asked to list all patients that fulfilled study criteria and at the end of the study we screened the electronic medical record system for number of patients that fulfilled study criteria and visited their GP within the study period.,Main end point was a documented diagnostic conclusion of COPD within 3 months after the patient’s visit.,We used multilevel logistic regression with correction for relevant covariates.,Next, we described the process of care. 21 practices (88 GPs) participated and 416 possible undiagnosed COPD patient visited these practices in the study period. 78 (of 192 visiting) subjects were listed by MI GPs and diagnostic conclusions were documented in 77%, compared to 61 listed (of 224 visiting) subjects and 44% with documented diagnostic conclusions by UC GPs (Odds Ratio: OR: 4.3, 95%CI: 1.6-11.5).,Microspirometry improved the diagnostic process for possible underlying COPD in patients who consulted their GP with respiratory symptoms, but the majority of possible undiagnosed COPD patients remained unrecognised by GPs.,A quick, simple test that can be used by family doctors may help identify patients suffering from chronic obstructive pulmonary disease (COPD).,The small, inexpensive microspirometry (MI) kit enables doctors conducting routine appointments to measure the volume of air expelled from patients’ lungs.,Lisette van den Bemt at Radboud University Medical Center, the Netherlands, and co-workers worked with two groups of doctors in local practices.,Both groups were asked to identify patients over 50 with a smoking history, respiratory problems and no diagnose of asthma and COPD, and start a diagnostic process for COPD.,One group was given microspirometers to aid diagnoses.,Of 192 patients visiting the MI doctors, 78 were identified and 77 per cent were later listed as COPD or COPD was ruled out.,In the other group, 61 out of 224 patients were identified with only 44 per cent listed. | Chronic obstructive pulmonary disease (COPD) is common but largely underdiagnosed.,Case-finding initiatives have been evaluated in primary care, but few studies have explored the views of service providers on implementing them in practice.,To explore the views of primary health care providers on case finding for COPD.,A total of 20 semi-structured interviews were conducted from March 2014 to September 2014 among general practitioners, nurses, and managers from practices participating in a large COPD case-finding trial based in primary care in the West Midlands, UK.,Participants’ views were sought to explore perceived benefits, harms, barriers, and facilitators to implementing COPD case finding in practice.,Interviews were transcribed and analyzed using the framework method.,Participants felt that case finding improves patient care but also acknowledged potential harms to providers (increase in workload) and to patients (overdiagnosis).,Insufficient resources, poor knowledge of COPD, and limited access to diagnostic services were viewed as barriers to diagnosis, while provision of community respiratory services, including COPD specialist nurses, and support from secondary care were thought to be facilitators.,Participants also expressed a need for more education on COPD for both patients and clinicians.,Care providers believe that early detection of COPD improves patient care but also has accompanying harms.,Barriers to diagnosing COPD, such as insufficient expertise in primary care and limited access to diagnostic services in the community, should be explored and addressed.,The knowledge and attitudes of the public about COPD and its symptoms should also be investigated to inform future education and awareness-raising strategies. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular events.,This study evaluated the association between high-sensitivity cardiac troponin I concentration and cardiovascular events in patients with COPD and heightened cardiovascular risk.,In a double-blind randomized controlled trial, 16,485 patients with COPD and cardiovascular disease or risk factors were randomized to once daily inhaled placebo, fluticasone furoate (100 μg), vilanterol (25 μg), or their combination.,Plasma high-sensitivity cardiac troponin I concentrations were measured in a subgroup of 1,599 patients.,Outcomes were on-treatment cardiovascular events and COPD exacerbations over a median of 18 months, and cardiovascular death over a median of 27 months.,Baseline plasma cardiac troponin I concentrations were above the limit of detection (1.2 ng/l) in 1,542 (96%) patients.,Concentrations were unaffected by inhaled therapies at 3 months (p > 0.05).,Compared with the lowest quintile (cardiac troponin <2.3 ng/l), patients in the highest quintile (≥7.7 ng/l) were at greater risk of cardiovascular events (hazard ratio [HR] 3.7; 95% confidence interval [CI]: 1.3 to 10.1; p = 0.012) and cardiovascular death (HR: 20.1; 95% CI: 2.4 to 165.2; p = 0.005) after adjustment for risk factors.,By contrast, there were no differences in exacerbations between quintiles (HR: 1.1; 95% CI: 0.8 to 1.5; p = 0.548).,In patients with COPD and heightened cardiovascular risk, plasma cardiac troponin I concentrations are a specific and major indicator of future cardiovascular events and cardiovascular death.,Inhaled therapies did not affect cardiac troponin I concentrations consistent with their neutral effect on mortality and cardiovascular outcomes.,(Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease [SUMMIT]; NCT01313676) | To assess the distribution of high-sensitivity cardiac troponin T (hs-cTnT) concentrations in stable chronic obstructive pulmonary disease (COPD), and whether hs-cTnT is associated with pulmonary function.,Prospectively designed, cross-sectional study.,Outpatient clinic of Norwegian teaching hospital and community-based setting.,Sample of 101 stable COPD patients from the hospital's outpatient clinic and 120 individuals derived from a random general population sample.,Ratio of hs-cTnT in stable COPD patients compared with references from the general population.,Change in ratio of hs-cTnT per unit increase of relevant covariables.,The crude geometric means of circulating hs-cTnT in the cases and the references were 7.75 and 3.01 ng/l, respectively (p <0.001); that is, a relative ratio of 2.57 (95% CI 2.05 to 3.23).,After adjustment for relevant confounders, this ratio was moderately attenuated to 1.65 (1.31-2.08).,In the total study cohort, as well as among stable COPD patients, we found a significant positive association between hs-cTnT and interleukin-6 concentrations (p <0.001) and the presence of pathologic Q waves (p=0.023).,Among stable COPD patients, one quartile increase in forced expiratory volume 1 was associated with a 39% decrease in hs-cTnT and patient category (Global Initiative of Obstructive Lung Disease classification 2011) was positively associated with hs-cTnT (p trend <0.001) after multivariate adjustment.,Stable COPD is independently associated with higher hs-cTnT compared with randomly drawn subjects from the general population.,In patients with stable COPD, higher hs-cTnT seems to be associated with immune activation and the severity of the disease. | 1 |
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. | Stem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration.,However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury.,In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche.,We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats.,The MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson’s trichrome staining, immunohistochemistry, and real-time PCR.,The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay.,rAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats.,HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection.,Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions.,Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats.,MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling. | 1 |
Health-related quality of life (HRQoL) should be seen as a tool that provides an overall view of the general clinical condition of a COPD patient.,The aims of this study were to identify variables associated with HRQoL and whether they continue to have an influence in the medium term, during follow-up.,Overall, 543 patients with COPD were included in this prospective observational longitudinal study.,At all four visits during a 5-year follow-up, the patients completed the Saint George’s Respiratory Questionnaire (SGRQ), pulmonary function tests, the 6-min walk test (6MWT), and a physical activity (PA) questionnaire, among others measurements.,Data on hospitalization for COPD exacerbations and comorbidities were retrieved from the personal electronic clinical record of each patient at every visit.,The best fit to the data of the cohort was obtained with a beta-binomial distribution.,The following variables were related over time to SGRQ components: age, inhaled medication, smoking habit, forced expiratory volume in one second, handgrip strength, 6MWT distance, body mass index, residual volume, diffusing capacity of the lung for carbon monoxide, PA (depending on level, 13 to 35% better HRQoL, in activity and impacts components), and hospitalizations (5 to 45% poorer HRQoL, depending on the component).,Among COPD patients, HRQoL was associated with the same variables throughout the study period (5-year follow-up), and the variables with the strongest influence were PA and hospitalizations. | Little is known about the relationship between hemoglobin concentrations, functional status and health related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD).,Our aim was to investigate the prevalence of anemia and the association of hemoglobin with shortness of breath, exercise capacity, muscle strength and HRQL, in COPD patients.,A total of 105 COPD patients (77 males, 71.6 ± 9.2 years) were studied.,Patients were classified as anemic and non anemic using the WHO criteria.,We used the Medical Research Council Dyspnoea scale (MRCs) to measure shortness of breath.,Exercise capacity was assessed using the six minute walking distance (6MWD) and the peak of VO2 during the maximal cycle ergometer test (VO2max).,We used the Quadriceps and Handgrip strength assessment to determine muscle strength.,The Saint George Respiratory Questionnaire was used to investigate HRQL.,The physiological/functional characteristics of the two groups were compared.,Regression models adjusting for confounders examined the independent association of anemia and of hemoglobin levels with clinical and functional outcomes.,Anemic patients (12.3%) showed a significantly higher MRCs, a lower 6MWD, VO2max, and a worse quality of life.,On the contrary, there was no difference in muscle strength between the two groups.,In the regression models, hemoglobin was independently associated with reduced exercise capacity and HRQL.,Anemia in COPD was a risk factor for poorer exercise capacity and quality of life, and these outcomes were linearly associated with hemoglobin.,Our results should stimulate further research into exploring whether increasing hemoglobin has a beneficial effect on the outcomes in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer.,Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls.,Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers.,We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type.,From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history.,Genome-wide miRNA profiles were generated and evaluated using machine learning techniques.,For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family.,The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5).,We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis.,For selected miRNAs, qRT-PCR analysis was applied to validate the results.,In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.,Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day.,Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658).,Daily data for atmospheric PM10 and ozone (O3) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases.,Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.,Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001).,Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001).,After allowance for these effects, higher O3 levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032).,Whilst, during the week PM10 reduced activity (p = 0.018) but not during the weekend.,Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends.,This study also provides evidence of an independent effect of atmospheric pollution at high levels.,The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users. | To assess associations among chronic obstructive pulmonary disease (COPD), disability as measured by activities of daily living (ADL) and instrumental ADL (IADL), engagement in social activities, and death among elderly noninstitutionalized US residents.,A nationally representative sample of 9,415 adults who were aged ≥70 years and responded to the Second Supplement on Aging survey in 1994-1996 and mortality follow-up study through 2006 were assessed.,Multiple logistic regression analyses were performed to assess the risk of all-cause mortality in participants with COPD after accounting for age, sex, race/ethnicity, and smoking status.,At baseline, approximately 9.6% of study participants reported having COPD.,Compared with participants without COPD, those with COPD were significantly more likely (P<0.05) to have difficulty with at least one ADL (44.3% versus [vs] 27.5%) and with at least one IADL (59.9% vs 40.2%), significantly less likely to be engaged in social activities (32.6% vs 26.3%), and significantly more likely to die by 2006 (70.7% vs 60.4%; adjusted risk ratio 1.15, P<0.05).,The association between COPD and risk for death was moderately attenuated by disability status.,COPD is positively associated with disability and mortality risk among US adults aged ≥70 years.,The significant relationship between COPD and mortality risk was moderately attenuated, but was not completely explained by stages of ADL and IADL limitations and social activities. | 1 |
Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD.,Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported.,Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).,To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.,In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly).,Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline.,The primary analysis was based on the intention-to-treat principle.,The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised.,The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)).,More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).,PTR was not superior to conventional PR on the 6MWD and we found no differences between groups.,As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.,Trial registration number,ClinicalTrials.gov (NCT02667171), 28 January 2016. | Despite optimal pharmacological therapy and pulmonary rehabilitation, patients with COPD continue to be breathless.,There is a need to develop additional strategies to alleviate symptoms.,Learning to sing requires control of breathing and posture and might have benefits that translate into daily life.,To test this hypothesis we performed a randomised controlled trial, comparing a six week course of twice weekly singing classes to usual care, in 28 COPD patients.,The experience of singing was assessed in a qualitative fashion, through interviews with a psychologist.,In addition, we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops.,In the RCT, the physical component score of the SF36 improved in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. -3.8(8.4) p = 0.02.,Singers also had a significant fall in HAD anxiety score; -1.1(2.7) vs.,+0.8(1.7) p = 0.03.,Singing did not improve single breath counting, breath hold time or shuttle walk distance.,In the qualitative element, 8 patients from the singing group were interviewed.,Positive effects on physical sensation, general well-being, community/social support and achievement/efficacy emerged as common themes. 150 participants in open workshops completed a questionnaire. 96% rated the workshops as "very enjoyable" and 98% thought the workshop had taught them something about breathing in a different way. 81% of attendees felt a "marked physical difference" after the workshop.,Singing classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease; no adverse consequences of participation were observed.,Current Controlled Trials - ISRCTN17544114. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide.,Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations.,Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation.,Long-acting β2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD.,The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects.,Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe.,Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA.,Several other agents are in the late stages of development, most of which offer once-daily dosing.,The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations.,These evolving treatments will provide new opportunities and challenges in the management of COPD. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli.,More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs).,LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management.,Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres.,Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD.,The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings.,The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs.,This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings.,We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2).,To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2.,We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry.,We will report ROC areas, sensitivity and specificity.,Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs.,The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers.,The control group will receive COPD education and standard of care treatment provided by local health providers.,Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St.,George’s Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year.,The primary endpoint is SGRQ at 12 months.,Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated.,We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD.,This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings.,NCT03359915 (GECo1).,Registered on 2 December 2017 and NCT03365713 (GECo2).,Registered on 7 December 2017.,Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2).,The online version of this article (10.1186/s13063-018-2909-8) contains supplementary material, which is available to authorized users. | Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge.,The prognostic significance of early readmission is not fully understood.,The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients.,The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge.,Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years.,Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity.,Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51-4.05) was the only variable independently associated with 30-day readmission.,The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10-5.59).,In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5).,In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) carries a considerable economic burden, both for individuals and societies.,This study aimed to assess direct and indirect costs associated with COPD, and how costs vary across disease severity.,This was a nationwide, population-based cohort study utilizing Danish health registries.,Patients; ≥40 years of age, with an in- and/or outpatient diagnosis of COPD (ICD-10 J44) in 2008-2016, were identified in the nationwide Danish COPD Registry.,Included patients were matched 1:4 to a population-based non-COPD reference population of 196,623 individuals by sex, year of birth, co-habitation status, and municipality.,Patients were grouped by disease severity according to different characteristics including GOLD groups A-D, based on moderate (short-term oral corticosteroid use), presence of severe exacerbations (emergency visit or hospitalization) and symptom score.,Index was the date of the first outpatient visit with a symptom score registration.,The costs were calculated during a 12 months post-index follow-up.,In all, 49,826 patients with COPD (mean age 69.2 years, 52% females) were included.,Total annual costs, including direct costs, costs for elderly care, and costs for retirement home, were higher for patients with COPD (€28,969) compared with the reference population (€10,6913).,In GOLD groups A-D, the total direct costs were A: €8,766, B: €13,060, C: €11,113, and D: €17,749, respectively.,A major driver of direct costs was severe exacerbations.,The mean costs per moderate and severe exacerbation were €888 and €7,091, respectively, during 28 days of follow-up.,The costs for non-COPD-related Health Care Resource Utilization were higher than the COPD-related costs in GOLD groups A-C, but not in GOLD group D.,In this nationwide real-world study, total direct costs were three-fold higher among patients with COPD compared with the reference population.,Severe exacerbations were a major driver of the direct costs.,The costs increased with increasing disease severity. | Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world.,Although smoking is the main risk factor for this disease, only a minority of smokers develop COPD.,Why this happens is largely unknown.,Recent discoveries by the human microbiome project have shed new light on the importance and richness of the bacterial microbiota at different body sites in human beings.,The microbiota plays a particularly important role in the development and functional integrity of the immune system.,Shifts or perturbations in the microbiota can lead to disease.,COPD is in part mediated by dysregulated immune responses to cigarette smoke and other environmental insults.,Although traditionally the lung has been viewed as a sterile organ, by using highly sensitive genomic techniques, recent reports have identified diverse bacterial communities in the human lung that may change in COPD.,This review summarizes the current knowledge concerning the lung microbiota in COPD and its potential implications for pathogenesis of the disease. | 1 |
Interactions between spirometry and patient-reported outcomes in COPD are not well understood.,This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy.,Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations.,Mean and standard deviations of treatment effects were extracted for each arm of each study.,Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling.,The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score.,Thirty-six studies (≥3 months) were included.,Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data.,Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ.,The correlation strengthened with increasing study duration from 3 to 12 months.,Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1.,The association between change in FEV1 and other patient-reported outcomes was generally weak.,Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common cause of morbidity and mortality worldwide.,It is often undiagnosed and insufficiently managed.,Effective forms of continuing medical education (CME) for primary care physicians (PCPs) are necessary to ensure the implementation of guidelines in clinical practice and, thus, improve patients’ health.,In this study, we will measure the effects of CME by Case Method and compare them against those of traditional lectures and no CME at all through an unblinded, cluster randomised controlled trial (CRCT).,Thirty-three primary health care centres (PHCCs) in Stockholm, Sweden, with a total of 180 PCPs will be involved.,Twenty-two primary PHCCs, will be cluster-randomised into: an intervention group who will receive CME by Case Method (n = 11) and a control group who will receive traditional lectures (n = 11).,The remaining PHCCs (n = 11) will be a reference group and will receive no CME.,From the intervention and control groups, 460 randomly selected patients with COPD in GOLD stages 2 and 3 will participate, while no patients will be recruited from the reference group.,For the patients, smoking status, actual treatment and urgent visits to a health provider due to airway problems will be registered.,For the PCPs, professional competence (i.e. knowledge and management skills) in COPD, will be measured using a questionnaire based on current guidelines and guideline implementation problems in clinical practice which has previously been described by the authors.,Data will be collected at baseline and at follow-up, which will be after 1.5 years for the patients, and 1 year for the PCPs.,Statistical methods for individual-level and cluster-level analyses will be used.,COPD is considered a particularly complex clinical challenge involving managing multimorbidity, symptom adaptation, and lifestyle problematisation.,Case Method in CME for PCPs may contribute to a better understanding of the impact of COPD on patients’ lives and, thus, improve their management of it.,The present study is expected to contribute scientific knowledge about indicators for an effective CME in COPD that is tailor-made to primary care physicians.,ClinicalTrials.gov, identifier: NCT02213809.,Registered on 10 August 2014.,Protocol version: Issue date: May 2014.,The online version of this article (doi:10.1186/s13063-017-1889-4) contains supplementary material, which is available to authorized users. | To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden.,Primary health care centres (PHCCs) in Stockholm, Sweden.,A total of 59 PCPs.,Semi-structured individual and focus-group interviews between 2012 and 2014.,Data were analysed inspired by grounded theory methods (GTM).,Time-pressured patient-doctor consultations lead to deprioritization of COPD.,During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients.,The reasons PCPs gave for deprioritizing COPD are: “Not becoming aware of COPD”, “Not becoming concerned due to clinical features”, “Insufficient local routines for COPD care”, “Negative personal attitudes and views about COPD”, “Managing diagnoses one at a time”, and “Perceiving a patient’s motivation as low’’.,De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi-morbidity.,A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines.,Key pointsUnder-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.,Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.,Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD. | 1 |
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations.,The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract.,The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations.,In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD.,In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes.,This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. | Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction.,Recently, sweat evaporimetry has been shown to efficiently measure β-adrenergic sweat rate and specifically quantify CFTR function in the secretory coil of the sweat gland.,To evaluate the presence and severity of systemic CFTR dysfunction in smoking-related lung disease using sweat evaporimetry to determine CFTR-dependent sweat rate.,We recruited a cohort of patients consisting of healthy never smokers (N = 18), healthy smokers (12), COPD smokers (25), and COPD former smokers (12) and measured β-adrenergic sweat secretion rate with evaporative water loss, sweat chloride, and clinical data (spirometry and symptom questionnaires).,β-adrenergic sweat rate was reduced in COPD smokers (41.9 ± 3.4, P < 0.05, ± SEM) and COPD former smokers (39.0 ± 5.4, P < 0.05) compared to healthy controls (53.6 ± 3.4).,Similarly, sweat chloride was significantly greater in COPD smokers (32.8 ± 3.3, P < 0.01) and COPD former smokers (37.8 ± 6.0, P < 0.01) vs. healthy controls (19.1 ± 2.5).,Univariate analysis revealed a significant association between β-adrenergic sweat rate and female gender (β = 0.26), age (−0.28), FEV1% (0.35), dyspnea (−0.3), and history of smoking (−0.27; each P < 0.05).,Stepwise multivariate regression included gender (0.39) and COPD (−0.43) in the final model (R2 = 0.266, P < 0.0001).,β-adrenergic sweat rate was significantly reduced in COPD patients, regardless of smoking status, reflecting acquired CFTR dysfunction and abnormal gland secretion in the skin that can persist despite smoking cessation. β-adrenergic sweat rate and sweat chloride are associated with COPD severity and clinical symptoms, supporting the hypothesis that CFTR decrements have a causative role in COPD pathogenesis. | 1 |
Past research has suggested significant relationships between symptoms and health outcomes among patients with COPD.,However, these studies have generally focused on a broad COPD sample and may have included those not receiving proper treatment.,As a result, the aim of this study was to document the burden of COPD symptoms among those who are currently treated with the standard-of-care (SOC) medications in both the US and Western Europe.,Data from the 2013 US (N=75,000) and 2011 (N=57,512)/2013 (N=62,000) European (France, Germany, Italy, Spain, and UK; 5EU) National Health and Wellness Survey (NHWS) were used.,The NHWS is a health survey administered to a demographically representative sample of the adult population in each country.,A total of 1,666 and 2,006 patients with self-reported physician diagnosis of COPD in the 5EU and US, respectively, were being treated with the appropriate SOC (based on self-reported medication use) and were included in the analyses.,Symptoms (eg, dyspnea, coughing, wheezing) were reported descriptively and summed to create a symptom score (with higher score indicating more frequent symptoms).,The relationships between the symptom score and patient outcomes (eg, health status using the Short Form-36 version 2 [SF-36v2], work productivity and activity impairment [WPAI], and self-reported health care resource use) were explored using regression modeling.,Nearly all patients (99.7% and 99.8% in the 5EU and US, respectively) reported experiencing symptoms and >80% reported experiencing at least one symptom “often”.,Increasing symptom scores were associated with poorer health status (unstandardized beta [b] =−0.87 and −0.78 for mental component summary and physical component summary, respectively, in the US and b =−0.67 and −0.79 in the 5EU, respectively; all P<0.05).,Increasing symptom scores were also associated with greater work impairment (b =0.09 and 0.06 for the US and 5EU, respectively), activity impairment (b =0.05 and 0.06, respectively), and health care resource utilization (eg, hospitalizations: b =0.05 and 0.06, respectively) (all P<0.05).,Approximately 70% of patients reported some level of non-adherence.,Greater non-adherence was significantly associated with more frequent symptoms, poorer health status, and greater work impairment and health care resource use (all P<0.05).,Patients with COPD who are using the appropriate SOC still experience symptoms, which have a significant effect on both humanistic and economic outcomes. | Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | 1 |
Antibiotic and oral corticosteroid prescribing rate in patients suffering from acute exacerbations of chronic obstructive pulmonary disease (COPD) or asthma in general practice are only sparsely described.,Our aim was to identify predictors for such prescribing when results from CRP testing, spirometry, and pulse oximetry are available.,Patients aged 40 years or more diagnosed with asthma, COPD or both, the previous five years from seven general practice offices in Norway, were invited to a baseline examination and asked to visit their GPs during exacerbations the following 12 months.,At all visits, symptoms, chest findings, and results from spirometry, pulse oximetry and CRP testing were registered.,Out of the 376 who took part in baseline examination, 95 patients with an exacerbation were included in the analysis.,Based on the diagnosis made by GPs, 46 patients (48.4%) were only registered with asthma, and 49 (51.6%) with COPD (or both diagnosis). 11 patients had taken antibiotics and 16 had taken systemic corticosteroids prior to their visit to their GPs.,After excluding those already treated, antibiotics were prescribed in 34.9% and systemic corticosteroids in 42.5% of patients diagnosed with COPD compared to 14.6% and 30.8% respectively in patients only diagnosed with asthma (P = 0.02, P = 0.2).,In the COPD group, antibiotic prescribing was not significantly associated with purulence or other respiratory symptoms, but increased phlegm was a significant predictor of antibiotic prescribing in the whole sample (P = 0.04).,Prolonged expiration, wheezes and diminished breath sounds also predicted the prescribing of both antibiotics and systemic corticosteroids in the whole sample with P values < 0.01.,The prescribing rate of antibiotics and systemic corticosteroids also increased with increasing CRP value (P = 0.001 and P = 0.01, respectively) and with decreasing oxygen saturation (P = 0.01 and P = 0.003, respectively).,FEV1/FVC < 0.7 at baseline was as significant predictor in patients with COPD and in the whole sample of patients regarding treatment with antibiotics (P = 0.004 and P = 0.001, respectively) and treatment with systemic corticosteroids (P = 0.004 and P = 0.001, respectively).,Chest findings, raised CRP value and decreased oxygen saturation were stronger predictors of prescribing of antibiotics and systemic corticosteroids than were respiratory symptoms.,Further evaluation of the importance of these findings to guide treatment of asthma and COPD exacerbations is warranted. | Objective To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients’ management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice.,Design 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial.,Setting 15 general practices in the eastern part of the Netherlands.,Participants Patients with COPD confirmed by spirometry and treated in general practice.,Patients with very severe COPD or treated by a respiratory physician were excluded.,Interventions A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients’ own initiative).,Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score.,Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale.,Results 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55).,At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant.,Secondary outcomes did not differ, except for exacerbation management.,Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58).,Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice.,Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group.,Trial registration Clinical trials NCT00128765. | 1 |
Previous studies suggest that gender differences exist in COPD diagnosis and symptoms; these differences may be more pronounced in younger adults.,Our objective was to explore age-associated gender differences across a range of COPD severities.,A total of 4,484 current and former smokers with COPD from the Genetic Epidemiology of COPD cohort were investigated using regression modeling to explore the association between gender, age, disease severity, and the contributing elements of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (symptoms, exacerbation risk, airflow limitation).,The age-gender interaction was observed across multiple age categories.,Compared to men with COPD, younger women with COPD had a greater likelihood of more severe dyspnea, airflow limitation, greater risk for exacerbations, and categorization in GOLD groups B and D.,These differences were less pronounced in older women with COPD.,However, older women remained more likely to experience severe dyspnea and to manifest more severe COPD (B vs A) than older men, despite lower pack-years of smoking.,These data demonstrate the significant symptom burden of COPD in women, especially younger women.,More research is needed to understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted clinical assessment and management approaches to improve outcomes for women and men with COPD at all ages. | Eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with more frequent exacerbations, lower lung function, and corticosteroid responsiveness.,We hypothesized increased eosinophils are associated with a severe COPD phenotype, including exacerbation frequency, and tested whether blood eosinophils reliably predict sputum eosinophils.,Comprehensive baseline data on SPIROMICS subjects, recruited for a range of COPD severity for smokers with ≥20 pack year history, included demographics, questionnaires, clinical assessments, quantitative computed tomography (QCT), blood and induced sputum.,Significantly, stratification by mean sputum eosinophils ≥1·25% (N=827) was associated with reduced FEV1 % predicted (differences: 10% pre-bronchodilator, 4·7% post-bronchodilator), QCT density measures for emphysema and air trapping, and exacerbations treated with corticosteroids (p=0·002).,In contrast, stratification by mean blood eosinophils ≥200/µL (N=2499) showed that FEV1 % predicted was significant between low and high blood subgroups, but less than observed between sputum subgroups (blood eosinophil group differences: 4·2% pre-bronchodilator, 2·7% post-bronchodilator), slightly increased airway wall thickness (0·02 mm, p=0·032), greater symptoms (p=0·037), and wheezing (p=0·018), but no evidence of association with COPD exacerbations or other indices of severity.,Blood eosinophils showed weak although significant association with sputum eosinophils (ROC AUC=0·64, p<0·001), but with a high false discovery rate (72%).,Elevated sputum eosinophils, with or without blood eosinophils, were associated with lower lung function.,Elevated blood eosinophils only in combination with elevated sputum eosinophils were associated with COPD exacerbations.,Stratification of SPIROMICS subjects by blood eosinophils alone showed minimal clinical differences and no association with exacerbations, whereas stratification by sputum eosinophils was associated with larger phenotypic differences and COPD exacerbations.,Importantly, increased blood eosinophils did not reliably predict airway eosinophils in induced sputum. | 1 |
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. | Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality.,Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions.,However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known.,We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD.,We then determined what types of psychological and lifestyle interventions are most effective.,Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety.,CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012.,Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety.,Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis.,Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09).,Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18).,Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD.,Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population. | 1 |
Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD.,Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported.,Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).,To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.,In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly).,Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline.,The primary analysis was based on the intention-to-treat principle.,The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised.,The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)).,More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).,PTR was not superior to conventional PR on the 6MWD and we found no differences between groups.,As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.,Trial registration number,ClinicalTrials.gov (NCT02667171), 28 January 2016. | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression.,To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100™).,105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects.,The reliability coefficient and the coefficient of variation (CV) were calculated.,The performance of each analyte and mean analyte levels were evaluated across sample types.,20% of analytes were not consistently detectable in any sample type.,Higher reliability and/or smaller CV were determined for 12 analytes in EDTA plasma compared to serum, and for 11 analytes in serum compared to EDTA plasma.,While reliability measures were similar for EDTA plasma and P100 plasma for a majority of analytes, CV was modestly increased in P100 plasma for eight analytes.,Each analyte within a multiplex produced independent measurement characteristics, complicating selection of sample type for individual multiplexes.,There were notable detectability and measurability differences between serum and plasma.,Multiplexing may not be ideal if large reliability differences exist across analytes measured within the multiplex, especially if values differ based on sample type.,For some analytes, the large CV should be considered during experimental design, and the use of duplicate and/or triplicate samples may be necessary.,These results should prove useful for studies evaluating selection of samples for evaluation of potential blood biomarkers. | The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.,Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included.,Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162).,Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).,Expression of CD11b was increased on circulating neutrophils from smokers with COPD.,It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.,Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05).,In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).,Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation.,Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment.,Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process.,Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions.,This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD. | 1 |
Handheld inhalers are used to deliver treatment for COPD.,Incorrect usage leads to suboptimal disease control.,Complex treatment regimens and use of multiple inhalers may reduce patient compliance.,The Anoro Ellipta™ dry powder inhaler (DPI) simultaneously delivers umeclidinium bromide (UMEC) and vilanterol (VI) without coformulation being required.,To assess the correct usage and ease of use of the Ellipta™ DPI administering UMEC/VI and to compare patient preference for Ellipta™ with the HandiHaler® through exploratory analyses of patient and observer questionnaires in five Phase III studies.,Two Phase III, 3-month double-blind, placebo-controlled studies assessed the correct usage of the Ellipta™ DPI at Day 1 and after 6 weeks, and ease of use of the Ellipta™ DPI using a nonvalidated patient questionnaire after 6 weeks or early withdrawal.,In three 6-month, blinded double-dummy, active comparator studies (two Phase IIIa and one Phase IIIb), patients completed a COPD device preference questionnaire between the Ellipta™ DPI and the Handi-Haler® at Day 168 (Week 24) or early withdrawal.,In the 3-month placebo-controlled studies, ≥98% of patients used the Ellipta™ DPI correctly and 99% of patients found the inhaler easy/very easy-to-use and the dose counter easy/very easy to read.,Across the two Phase IIIa active comparator studies, patients consistently stated a preference for the Ellipta™ DPI over HandiHaler® regarding the number of steps to use (59% vs 17%), time taken to use (62% vs 14%), and ease of use (63% vs 15%) regardless of which inhaler contained active drug.,Results were consistent in the Phase IIIb active comparator study.,Delivery of UMEC/VI via the Ellipta™ DPI was considered easy-to-use, and patients with COPD demonstrated clear preference for this inhaler compared with HandiHaler®. | This study aims to (i) evaluate the association between anxiety and depressive symptoms and health-related quality of life (HRQoL); and (ii) identify the effect modifiers of this relationship in patients with chronic obstructive pulmonary disease (COPD).,A total of 337 clinically stable COPD patients answered the St.,George's Respiratory Questionnaire (SGRQ) (assessing HRQoL) and the Hospital Anxiety and Depression Scale (HADS).,Socio-demographic information, lung function, and other clinical data were collected.,Most patients (93%) were male; they had a mean (SD) age of 68 (9) years and mild to very severe COPD (post-bronchodilator FEV1 52 (16)% predicted).,Multivariate analyses showed that anxiety, depression, or both conditions were associated with poor HRQoL (for all SGRQ domains).,The association between anxiety and total HRQoL score was 6.7 points higher (indicating a worse HRQoL) in current workers than in retired individuals.,Estimates for patients with "both anxiety and depression" were 5.8 points lower in stage I-II than in stage III-IV COPD, and 10.2 points higher in patients with other comorbidities than in those with only COPD.,This study shows a significant association between anxiety, depression, or both conditions and impaired HRQoL.,Clinically relevant factors affecting the magnitude of this association include work status, COPD severity, and the presence of comorbidities. | 1 |
Chronic obstructive pulmonary disease (COPD) is influenced by genetic and environmental factors.,A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD.,Here, we examined the relationship between circulating serpina3g, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1 and -2, respectively) and severity of COPD.,We included 150 stable COPD patients and 35 control subjects in the study.,The COPD patients were classified into four groups (I, II, III, and IV), according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines based on the severity of symptoms and the exacerbation risk.,Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in the all patients than in control subjects.,Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in groups III and IV than in groups I and II.,A negative correlation between serpina3g, MMP-9, and TIMP-1 and -2 levels and the forced expiratory volume in 1 s (FEV1) was observed.,MMP-9 concentration and the MMP-9/TIMP-1 ratio were higher in patients with emphysema than in other phenotypes (both with p < 0.01).,The findings of this study suggest that circulating serpina3g, MMP-9, and TIMP-1 and -2 levels may play an important role in airway remodeling in COPD pathogenesis.,Disrupted protease-antiprotease imbalance in patients with COPD is related to the presence of airway injury.,MMP-9 concentration and the MMP-9/TIMP-1 ratio are the best predictors of emphysema in COPD patients. | Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death worldwide in 2015.,Current treatments for patients ease discomfort and help decrease disease progression; however, none improve lung function or change mortality.,COPD is heterogeneous in its molecular and clinical presentation, making it difficult to understand disease aetiology and define robust therapeutic strategies.,Given the complexity of the disease we propose a precision medicine approach to understanding and better treating COPD.,It is possible that multiOMICs can be used as a tool to integrate data from multiple fields.,Moreover, analysis of electronic medical records could aid in the treatment of patients and in the predictions of outcomes.,The Precision Medicine Initiative created in 2015 has made precision medicine approaches to treat disease a reality; one of these diseases being COPD. | 1 |
Smoking is the major etiologic factor in COPD, yet the exact underlying pathogenetic mechanisms have not been elucidated.,Since a few years, there is mounting evidence that a specific immune response, partly present as an autoimmune response, contributes to the pathogenesis of COPD.,Increased levels of anti-Hep-2 epithelial cell and anti-elastin autoantibodies as well as antibodies against airway epithelial and endothelial cells have been observed in COPD patients.,Whether the presence of these autoantibodies contributes to the pathogenesis of COPD is unclear.,To test whether induction of autoantibodies against lung matrix proteins can augment the smoke-induced inflammatory response, we immunized mice with a mixture of the lung extracellular matrix (ECM) proteins elastin, collagen, and decorin and exposed them to cigarette smoke for 3 or 6 months.,To evaluate whether the immunization was successful, the presence of specific antibodies was assessed in serum, and presence of specific antibody producing cells in spleen and lung homogenates.,In addition, the presence of inflammatory cells and cytokines was assessed in lung tissue and emphysema development was evaluated by measuring the mean linear intercept.,We demonstrated that both ECM immunization and smoke exposure induced a humoral immune response against ECM proteins and that ECM immunization itself resulted in increased macrophage numbers in the lung.,The specific immune response against ECM proteins did not augment the smoke-induced inflammatory response in our model.,By demonstrating that smoke exposure itself can result in a specific immune response and that presence of this specific immune response is accompanied by an influx of macrophages, we provide support for the involvement of a specific immune response in the smoke-induced inflammatory response as can be seen in patients with COPD. | Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease.,We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease.,Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control).,Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration.,Mean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm).,Emphysema mice lost body weight, controls gained weight.,Running distance was shorter in emphysema than in controls.,Diaphragm muscle length was shorter in controls compared to emphysema.,Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms.,Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls.,Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length.,The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation.,The model may deepen our understanding of systemic aspects of COPD. | 1 |
Transforming growth factor β (TGF-β), signaling induced by cigarette smoke (CS), plays an important role in the progression of airway diseases, like chronic bronchitis associated with chronic obstructive pulmonary disease (COPD), and in smokers.,Chronic bronchitis is characterized by reduced mucociliary clearance (MCC).,Cystic fibrosis transmembrane conductance regulator (CFTR) plays an important role in normal MCC.,TGF-β and CS (via TGF-β) promote acquired CFTR dysfunction by suppressing CFTR biogenesis and function.,Understanding the mechanism by which CS promotes CFTR dysfunction can identify therapeutic leads to reverse CFTR suppression and rescue MCC.,TGF-β alters the microRNAome of primary human bronchial epithelium.,TGF-β and CS upregulate miR-145-5p expression to suppress CFTR and the CFTR modifier, SLC26A9. miR-145-5p upregulation with a concomitant CFTR and SLC26A9 suppression was validated in CS-exposed mouse models.,While miR-145-5p antagonism rescued the effects of TGF-β in bronchial epithelial cells following transfection, an aptamer to block TGF-β signaling rescues CS- and TGF-β-mediated suppression of CFTR biogenesis and function in the absence of any transfection reagent.,These results demonstrate that miR-145-5p plays a significant role in acquired CFTR dysfunction by CS, and they validate a clinically feasible strategy for delivery by inhalation to locally modulate TGF-β signaling in the airway and rescue CFTR biogenesis and function.,The authors demonstrate that TGF-β and cigarette smoke upregulate miR-145-5p to suppress CFTR biogenesis.,This is also the first report of microRNA-mediated regulation of SLC26A9, an important CFTR-modifying gene, and the authors demonstrate that miR-145-5p is also involved in TGF-β- and cigarette smoke-mediated suppression of SLC26A9. | Chronic Obstructive Pulmonary Disease (COPD) is often caused by smoking and other stressors.,This causes oxidative stress, which induces numerous changes on both the transcriptome and proteome of the cell.,We aimed to examine if the endomembrane pathway, including the endoplasmic reticulum (ER), Golgi, and lysosomes, was disrupted in fibroblasts from COPD patients as opposed to healthy ever‐smokers or never‐smokers, and if the response to stress differed.,Different cellular compartments involved in the endomembrane pathway, as well as mRNA expression and apoptosis, were examined before and after the addition of stress in lung fibroblasts from never‐smokers, ever‐smokers, and patients with COPD.,We found that the ER, Golgi, and lysosomes were disorganized in fibroblasts from COPD patients under baseline conditions.,After a time course with ER stress inducing chemicals, changes to the phenotypes of cellular compartments in COPD patient fibroblasts were observed, and the expression of the ER stress‐induced gene ERP72 was upregulated more in the COPD patient's cells compared to ever‐smokers or never‐smokers.,Lastly, a tendency of increased active Caspase‐3 was observed in COPD fibroblasts.,Our results show that COPD patients have phenotypic changes in the lung fibroblasts endomembrane pathway, and respond differently to stress.,Furthermore, these fibroblasts were cultured for several weeks outside the body, but they were not able to regain proper ER structure, indicating that the internal changes to the endomembrane system are permanent in smokers.,This vulnerability to cellular stress might be a cause as to why some smokers develop COPD. | 1 |
The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.,While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model.,Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage.,Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT.,Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data.,Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included.,A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.,Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC.,The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium.,Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.,Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. | Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are central to the pharmacological management of COPD.,Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 μg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD.,The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 μg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD.,A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411).,Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs.,Costs are presented in US dollars based on 2015 prices.,The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs).,Costs and outcomes were discounted at a 3% annual rate.,Incremental cost-effectiveness ratios were calculated.,One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results.,UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751).,Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment.,UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses.,Sensitivity analyses confirmed that the results were robust.,The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD. | 1 |
In Denmark, the treatment of COPD is mainly managed by general practitioners (GPs).,Pulmonary rehabilitation (PR) is available to patients with COPD in the local community by GP referral, but in practice, many patients do not participate in rehabilitation.,The aim of our study was to explore 1) GPs’ perceptions of their role and responsibility in the rehabilitation of patients with COPD, and 2) GPs’ perceptions of how patients manage their COPD.,The study was based on a qualitative design with semi-structured key-informant interviews with GPs.,Investigator triangulation was applied during data generation, and analysis was done using thematic analysis methodology.,Our main findings were that GPs relied on patients themselves to take the initiative to make clinic appointments and on professionals at health centers to provide the PR including consultations on lifestyle changes.,The GPs experienced that patients chose to come to the clinic when they were in distress and that patients either declined or had poor adherence to rehabilitation when offered.,The GPs were relieved that the health centers had taken over the responsibility of rehabilitation as GPs lacked the resources to discuss rehabilitation and follow up on individual plans.,Our study suggested a potential self-reinforcing problem with the treatment of COPD being mainly focused on medication rather than on PR.,Neither GPs nor patients used a proactive approach.,Further, GPs were not fully committed to discuss non-pharmacological treatment and perceived the patients as unmotivated for PR.,As such, there is a need for optimizing non-pharmacological treatment of COPD and in particular the referral process to PR. | More than one third of individuals with chronic obstructive pulmonary disease (COPD) experience comorbid symptoms of depression and anxiety.,This review aims to provide an overview of the burden of depression and anxiety in those with COPD and to outline the contemporary advances and challenges in the management of depression and anxiety in COPD.,Symptoms of depression and anxiety in COPD lead to worse health outcomes, including impaired health-related quality of life and increased mortality risk.,Depression and anxiety also increase health care utilization rates and costs.,Although the quality of the data varies considerably, the cumulative evidence shows that complex interventions consisting of pulmonary rehabilitation interventions with or without psychological components improve symptoms of depression and anxiety in COPD.,Cognitive behavioral therapy is also an effective intervention for managing depression in COPD, but treatment effects are small.,Cognitive behavioral therapy could potentially lead to greater benefits in depression and anxiety in people with COPD if embedded in multidisciplinary collaborative care frameworks, but this hypothesis has not yet been empirically assessed.,Mindfulness-based treatments are an alternative option for the management of depression and anxiety in people with long-term conditions, but their efficacy is unproven in COPD.,Beyond pulmonary rehabilitation, the evidence about optimal approaches for managing depression and anxiety in COPD remains unclear and largely speculative.,Future research to evaluate the effectiveness of novel and integrated care approaches for the management of depression and anxiety in COPD is warranted. | 1 |
Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients.,However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index.,For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.,In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation.,The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months.,The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index.,Mortality was assessed using Kaplan-Meier survival and Cox Regression.,Performance of models was compared using C-statistics.,Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively.,Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function.,The CODE index predicted mortality slightly more accurately than the BODE and WODE indices.,Cachexia is associated with increased mortality among COPD patients.,Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.,The online version of this article (10.1186/s12931-019-1073-3) contains supplementary material, which is available to authorized users. | Asthma-COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease.,However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized.,To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected.,This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma.,The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS.,Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90) of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135).,The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves.,Only sputum NGAL levels could differentiate ACOS from asthma (P<0.001 and P<0.001) and COPD (P<0.05 and P=0.002) in the discovery and replication cohorts, respectively.,Sputum NGAL levels were independently correlated with the percentage of pre-bronchodilator forced expiratory volume in 1 second predicted in multivariate analysis in the discovery and replication cohorts (P=0.001 and P=0.002, respectively).,In conclusion, sputum biomarkers reflecting both airway inflammation and remodeling of the tissue show potential in differentiation between asthma, COPD, and ACOS. | 1 |
A new quinolone, zabofloxacin, has now been developed; hence, a non-inferiority trial is needed to compare this new compound with another widely used quinolone to examine its efficacy and safety for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations.,This was a prospective, multicenter, double-blind, double-dummy, randomized, controlled, parallel-group, Phase III, non-inferiority clinical trial designed to compare oral zabofloxacin (367 mg once daily for 5 days) with moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation.,In all, 345 COPD patients with a moderate COPD exacerbation were enrolled in the study via the outpatient clinics at 31 university hospitals.,Clinical per protocol analysis revealed that the clinical cure rate for zabofloxacin was 86.7% and that for moxifloxacin was 86.3% (the rate difference, 0.4%; 95% confidence interval, −7.7%-8.6%).,Intention-to-treat analysis revealed clinical cure rates of 77.1% and 77.3% (difference, −0.2%; 95% confidence interval, −9.0%-8.8%), respectively.,These results confirm that zabofloxacin is not inferior to moxifloxacin.,The favorable microbiological response rate for zabofloxacin was 67.4% and that for moxifloxacin was 79.5% (P=0.22).,Patients in the zabofloxacin group showed better patient-oriented outcomes, as measured by EXAcerbations of Chronic Pulmonary Disease Tool-Patient-Reported Outcome and the COPD assessment test scores, than patients in the moxifloxacin group.,Adverse drug reactions related to zabofloxacin occurred in 9.7% of cases and those related to moxifloxacin occurred in 9.6% of cases (P=0.97).,The dropout rate due to adverse events was 0% (0/175) in the zabofloxacin group and 1.8% (3/167) in the moxifloxacin group (P=0.12).,Oral zabofloxacin (367 mg once daily for 5 days) was not inferior to oral moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. | Respiratory infection is the most common cause for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD).,The aim of this work was to study the etiology of the respiratory infection in order to assess the usefulness of the clinical and analytical parameters used for COPD identification.,We included 132 patients over a period of 2 years.,The etiology of the respiratory infection was studied by conventional sputum, paired serology tests for atypical bacteria, and viral diagnostic techniques (immunochromatography, immunofluorescence, cell culture, and molecular biology techniques).,We grouped the patients into four groups based on the pathogens isolated (bacterial versus. viral, known etiology versus unknown etiology) and compared the groups.,A pathogen was identified in 48 patients.,The pathogen was identified through sputum culture in 34 patients, seroconversion in three patients, and a positive result from viral techniques in 14 patients.,No significant differences in identifying etiology were observed in the clinical and analytical parameters within the different groups.,The most cost-effective tests were the sputum test and the polymerase chain reaction.,Based on our experience, clinical and analytical parameters are not useful for the etiological identification of COPD exacerbations.,Diagnosing COPD exacerbation is difficult, with the conventional sputum test for bacterial etiology and molecular biology techniques for viral etiology providing the most profitability.,Further studies are necessary to identify respiratory syndromes or analytical parameters that can be used to identify the etiology of new AE-COPD cases without the laborious diagnostic techniques. | 1 |
Identifying those patients who underperform in the 6-minute walk test (6MWT <350 m), and the reasons for their poor performance, is a major concern in the management of chronic obstructive pulmonary disease.,To explore the accuracy and relevance of the 4-m gait-speed (4MGS) test, and the 5-repetition sit-to-stand (5STS) test, as diagnostic markers, and clinical determinants, of poor performance in the 6MWT.,We recruited 137 patients with stable chronic obstructive pulmonary disease to participate in our cross-sectional study.,Patients completed the 4MGS and 5STS tests, with quantitative (in seconds) and qualitative ordinal data collected; the latter were categorized using a scale of 0 to 4.,The following potential covariates and clinical determinants of poor 6MWT were collated: age, quadriceps muscle-strength (QMS), health status, dyspnea, depression, and airflow limitation.,Area under the receiver-operating characteristic curve data (AUC) was used to assess accuracy, with logistic regression used to explore relevance as clinical determinants.,The AUCs generated using the 4MGS and 5STS tests were comparable, at 0.719 (95% confidence interval [CI] 0.629-0.809) and 0.711 (95% CI 0.613-0.809), respectively.,With ordinal data, the 5STS test was most accurate (AUC of 0.732; 95% CI 0.645-0.819); the 4MGS test showed poor discriminatory power (AUC <0.7), although accuracy improved (0.726, 95% CI 0.637-0.816) when covariates were included.,Unlike the 4MGS test, the 5STS test provided a significant clinical determinant of a poor 6MWT (odds ratio 1.23, 95% CI 1.05-1.44).,The 5STS test reliably predicts a poor 6MWT, especially when using ordinal data.,Used alone, the 4MGS test is reliable when measured with continuous data. | High-level activities are typically not performed by patients with chronic obstructive pulmonary disease (COPD), which results in reduced functional performance; however, the physiological parameters that contribute to this reduced performance are unknown.,The aim of this study was to determine the relationships between high-level functional performance, leg muscle strength/power, aerobic power, and anaerobic power.,Thirteen patients with COPD underwent an incremental maximal cardiopulmonary exercise test, quadriceps isokinetic dynamometry (isometric peak torque and rate of torque development; concentric isokinetic peak torque at 90°/sec, 180°/sec, and 270°/sec; and eccentric peak torque at 90°/sec), a steep ramp anaerobic test (SRAT) (increments of 25 watts every 10 seconds), and three functional measures (timed up and go [TUG], timed stair climb power [SCPT], and 30-second sit-to-stand test [STS]).,TUG time correlated strongly (P < 0.05) with all muscle strength variables and with the SRAT.,Isometric peak torque was the strongest determinant of TUG time (r = −0.92).,SCPT and STS each correlated with all muscle strength variables except concentric at 270°/sec and with the SRAT.,The SRAT was the strongest determinant of SCPT (r = 0.91), and eccentric peak torque at 90°/sec was most significantly associated with STS (r = 0.81).,Performance on the SRAT (anaerobic power); slower-velocity concentric, eccentric, and isometric contractions; and rate of torque development are reflected in all functional tests, whereas cardiopulmonary exercise test performance (aerobic power) was not associated with any of the functional or muscle tests.,High-level functional performance in patients with COPD is associated with physiological parameters that require high levels of muscle force and anaerobic work rates. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with major healthcare and socioeconomic burdens.,International consortia recommend a personalized approach to treatment and management that aims to reduce both symptom burden and the risk of exacerbations.,Recent clinical trials have investigated single-inhaler triple therapy (SITT) with a long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA), and inhaled corticosteroid (ICS) for patients with symptomatic COPD.,Here, we review evidence from randomized controlled trials showing the benefits of SITT and weigh these against the reported risk of pneumonia with ICS use.,We highlight the challenges associated with cross-trial comparisons of benefit/risk, discuss blood eosinophils as a marker of ICS responsiveness, and summarize current treatment recommendations and the position of SITT in the management of COPD, including potential advantages in terms of improving patient adherence.,Evidence from trials of SITT versus dual therapies in symptomatic patients with moderate to very severe airflow limitation and increased risk of exacerbations shows benefits in lung function and patient-reported outcomes.,Moreover, the key benefits reported with SITT are significant reductions in exacerbations and hospitalizations, with data also suggesting reduced all-cause mortality.,These benefits outweigh the ICS-class effect of higher incidence of study-reported pneumonia compared with LAMA/LABA.,Important differences in trial design, baseline population characteristics, such as exacerbation history, and assessment of outcomes, have significant implications for interpreting data from cross-trial comparisons.,Current understanding interprets the blood eosinophil count as a continuum that can help predict response to ICS and has utility alongside other clinical factors to aid treatment decision-making.,We conclude that treatment decisions in COPD should be guided by an approach that considers benefit versus risk, with early optimization of treatment essential for maximizing long-term benefits and patient outcomes. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality.,Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD.,The effects of once-daily inhaled fluticasone furoate/vilanterol (FF/VI) 100/25 µg, VI 25 µg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial.,Eligible patients were ≥40 years old, with ≥10 pack-year smoking history, forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70, and post-bronchodilator FEV1 ≤70% of predicted.,Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded.,Primary endpoint is change from baseline in aPWV after 24 weeks of treatment.,Safety analyses included adverse events (AEs).,The intent-to-treat population included 430 patients: FF/VI (n=135), VI (n=154), and placebo (n=141).,Patients were predominantly male (79%) and Asian or White (each 48%), with a mean age of 68.5 years (standard deviation [SD] =7.9), percentage predicted post-bronchodilator FEV1 50.1% (SD =13.3), and aPWV 13.26 m/s (SD =2.22) at screening.,At 24 weeks, mean (standard error [SE]) changes from baseline in aPWV were −1.75 m/s (SE =0.26, FF/VI), −1.95 m/s (SE =0.24, VI), and −1.97 m/s (SE =0.28, placebo).,AEs occurred in 57% (FF/VI), 51% (VI), and 41% (placebo) of patients.,No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo. | Tiotropium bromide is an effective therapy for COPD patients.,Comparing across programs tiotropium Respimat® Soft Mist™ inhaler was at least as efficacious as tiotropium HandiHaler®, however, concerns have been raised about tiotropium’s safety when given via Respimat®.,The TIOSPIR® trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat® 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler® 18 μ once daily (marketed).,The hypotheses to be tested are 1). that tiotropium Respimat® 5 μg once daily and Respimat® 2.5 μg once daily are non-inferior to HandiHaler® in terms of all-cause mortality, and 2). that tiotropium Respimat® 5 μg once daily is superior to HandiHaler® in terms of time to first exacerbation.,A spirometry substudy evaluates the bronchodilator efficacy.,The trial is a randomized, double-blind, double dummy, event-driven, parallel group study.,Participants can use any background treatment for COPD except inhaled anticholinergic agents.,The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included.,Clinical sites are international and include both primary care as well as specialists.,To date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2-3 years.,TIOSPIR® will provide precise estimates of the relative safety and efficacy of the Respimat® and HandiHaler® formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort. | 1 |
The tissue turnover of unperturbed adult lung is remarkably slow.,However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration.,Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction.,Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis.,Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development.,Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors.,Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs.,With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality.,In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. | Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD.,Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD.,Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”.,These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation.,In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells.,Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs).,Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD.,This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD. | 1 |
The purpose of the current study was to determine the association between sedentary time and physical activity with clinically relevant health outcomes among adults with impaired spirometry and those with or without self-reported obstructive lung disease (asthma or COPD).,Data from participants of the Canadian Longitudinal Study on Aging were used for analysis (n = 4156).,Lung function was assessed using spirometry.,Adults were said to have impaired spirometry if their Forced Expiratory Volume in 1 s was <5th percentile lower limit of normal (LLN).,A modified version of the Physical Activity Scale for the Elderly was used to assess sitting time and physical activity levels.,Healthcare use and quality of life outcomes were assessed using self report.,Among those with asthma, participating in strengthening activities was associated with lower odds of reporting poor perceived health (OR = 0.65, CI: 0.53, 0.79), poor perceived mental-health (OR = 0.73, CI: 0.60, 0.88), unhealthy aging (OR = 0.68, CI: 0.56, 0.83), and reporting an emergency department visit in the past 12 months (OR = 0.76, CI: 0.60, 0.95).,Among those with COPD, those who reported highest weekly sedentary time had higher odds of reporting poor perceived health (OR = 2.70, CI: 1.72, 4.24), poor perceived mental-health (OR = 1.99, CI: 1.29, 3.06), and unhealthy aging (OR = 3.04, CI: 1.96, 4.72).,Among those below the LLN, sitting time (OR = 2.57, CI: 1.40, 4.72) and moderate intensity physical activity (OR = 0.23, CI: 0.09, 0.63) were associated with overnight hospital stays.,Higher physical activity levels and lower sedentary time may be associated with lower healthcare use and better quality of life.,This research may have implications related to the use of physical activity for improving health outcomes and quality of life among adults with obstructive lung disease or impaired spirometry.,The online version of this article (10.1186/s12890-018-0659-8) contains supplementary material, which is available to authorized users. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD).,The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD.,This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD.,It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers.,The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report.,This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations.,The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient.,The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma-COPD overlap syndrome (ACOS).,These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions.,For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol-ipratropium) is recommended in patients with less symptoms.,If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended.,For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide-formoterol, beclomethasone dipropionate-formoterol, fluticasone propionate-salmeterol or fluticasone furoate-vilanterol) is recommended as a first choice.,Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium-indacaterol or umeclidinium-vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic.,If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast.,ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD.,Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD.,Thus, evidence-based recommendation of treatment cannot be given.,The treatment should cover both diseases.,Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both). | 1 |
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. | A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use.,Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice.,We performed a systematic literature search in both Pubmed and Embase up to September 2010.,Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only.,Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies.,Of 7,028 articles screened, 13 studies comprising 15 indices were included.,Only 1 index had been explored for its application in daily practice.,We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation.,Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea.,The quality of the studies underlying the indices varied between fairly poor and good.,Statistical methods to assess the predictive abilities of the indices were heterogenic.,They generally revealed moderate to good discrimination, when measured.,Limitations: We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity.,We identified 15 prognostic COPD indices.,Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation.,Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide.,The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.,Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.,Pathway analyses revealed that several altered metabolites are involved in oxidative stress.,Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7).,Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4).,Significantly altered metabolites were confirmed quantitatively using targeted metabolomics.,Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10).,The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.,These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin-lysoPA axis, are associated with disease mechanisms and/or prevalence.,Oxidative stress and the autotaxin-lysoPA axis evidence sex-associated metabotypes in the serum of COPD patientshttp://ow.ly/kAeE309MpdI | Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema.,Environmental exposure, primarily cigarette smoking, can cause high oxidative stress and is the main factor of COPD development.,Cigarette smoke also contributes to the imbalance of oxidant/antioxidant due to exogenous reactive oxygen species (ROS).,Moreover, endogenously released ROS during the inflammatory process and mitochondrial dysfunction may contribute to this disease progression.,ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such as DNA, proteins, and lipids leading to epithelial cell injury and death.,Various detoxifying enzymes and antioxidant defense systems can be involved in ROS removal.,In this review, we summarize the main findings regarding the biological role of ROS, which may contribute to COPD development, and cytoprotective mechanisms against this disease progression. | 1 |
Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD).,CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality.,The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.,Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade.,But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population.,The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.,In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence.,We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD.,While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years.,Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. | Objectives To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use.,Design Population based cohort study in England.,Setting UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11.,Participants Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record.,Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London.,Main outcome measure Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct.,Results Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years).,Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001).,Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers.,With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02).,Conclusions The use of β blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD.,Registration NCT01335672. | 1 |
Pulmonary rehabilitation (PR) improves exercise capacity and health status in patients with COPD, but many patients assessed for PR do not complete therapy.,It is unknown whether socioeconomic deprivation associates with rates of completion of PR or the magnitude of clinical benefits bequeathed by PR.,PR services across England and Wales enrolled patients to the National PR audit in 2015.,Deprivation was assessed using Index of Multiple Deprivation (IMD) derived from postcodes.,Study outcomes were completion of therapy and change in measures of exercise performance and health status.,Univariate and multivariate analyses investigated associations between IMD and these outcomes.,210 PR programmes enrolled 7413 patients.,Compared with the general population, the PR sample lived in relatively deprived neighbourhoods.,There was a statistically significant association between rates of completion of PR and quintile of deprivation (70% in the least and 50% in the most deprived quintiles).,After baseline adjustments, the risk ratio (95% CI) for patients in the most deprived relative to the least deprived quintile was 0.79 (0.73 to 0.85), p<0.001.,After baseline adjustments, IMD was not significantly associated with improvements in exercise performance and health status.,In a large national dataset, we have shown that patients living in more deprived areas are less likely to complete PR.,However, deprivation was not associated with clinical outcomes in patients who complete therapy.,Interventions targeted at enhancing referral, uptake and completion of PR among patients living in deprived areas could reduce morbidity and healthcare costs in such hard-to-reach populations. | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
An incremental approach using open-triple therapy may improve outcomes in patients with chronic obstructive pulmonary disease (COPD).,However, there is little sufficient, real-world evidence available identifying time to open-triple initiation.,This retrospective study of patients with COPD, newly initiated on long-acting muscarinic antagonist (LAMA) monotherapy or inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination therapy, assessed baseline demographics, clinical characteristics, and exacerbations during 12 months prior to first LAMA or ICS/LABA use.,Time to initiation of open-triple therapy was assessed for 12 months post-index date.,Post hoc analyses were performed to assess the subsets of patients with pulmonary-function test (PFT) information and patients with and without comorbid asthma.,Demographics and clinical characteristics were similar between cohorts in the pre-specified and post hoc analyses.,In total, 283 (19.3%) and 160 (10.9%) patients had moderate and severe exacerbations at baseline, respectively, in the LAMA cohort, compared with 482 (21.3%) and 289 (12.8%) patients in the ICS/LABA cohort.,Significantly more patients initiated open-triple therapy in the LAMA cohort compared with the ICS/LABA cohort (226 [15.4%] versus 174 [7.7%]; P<0.001); results were similar in the post hoc analyses.,Mean (standard deviation) time to open-triple therapy was 79.8 (89.0) days in the LAMA cohort and 122.9 (105.4) days in the ICS/LABA cohort (P<0.001).,This trend was also observed in the post hoc analyses, though the difference between cohorts was nonsignificant in the subset of patients with PFT information.,In this population, patients with COPD are more likely to initiate open-triple therapy following LAMA therapy, compared with ICS/LABA therapy.,Further research is required to identify factors associated with the need for treatment augmentation among patients with COPD. | Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines.,This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD.,Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis.,Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997-2001; (2) 2002-2006; and (3) 2007-2010.,Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression.,The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment.,Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis.,Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors.,In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens.,Predictors of initial therapy were identified. | 1 |
Frailty is a state of increased risk of unfavorable outcomes when exposed to stressors, and COPD is one of the several chronic illnesses associated with the condition.,However, few studies have been conducted regarding the prevalence of COPD and its related factors in Southeast Asia.,The objectives of this study were to determine the prevalence of frailty in COPD patients and to identify the associated factors in these populations.,A cross-sectional study of COPD patients who attended a COPD clinic was conducted from May 2015 to December 2016.,Baseline characteristics were collected, and the diagnosis of frailty was based on the FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale.,Descriptive statistics were used to analyze baseline data.,Factors associated with frailty were analyzed using univariate and multivariate regression analyses.,The results showed that the prevalence rates of frailty and pre-frailty were 6.6% (eight out of 121 cases) and 41.3% (50 out of 121 cases), respectively, among COPD patients.,Fatigue was the most common component of the FRAIL scale that was found more frequently in frail patients than in non-frail patients (odds ratio [OR] 91.9).,Factors associated with frailty according to multivariate analyses were comorbid cancer (adjusted OR [AOR] 45.8), at least two instances of nonelective admission over the past 12 months (AOR 112.5), high waist circumference (WC) (AOR 1.3), and presence of sarcopenia (AOR 29.5).,In conclusion, frailty affected 6.6% of stable COPD patients.,Cancer, two or more instances of nonelective hospitalization over the past 12 months, high WC, and presence of sarcopenia were associated with frailty.,Early identification and intervention in high-risk patients is recommended to prevent or delay the adverse outcomes of frailty. | Impaired physical performance is common in chronic obstructive pulmonary disease (COPD), but its assessment can be difficult in routine clinical practice.,We compared the timed up and go (TUG) test and other easily applied assessments of physical performance with the 6-minute walk distance (6MWD).,In a longitudinal study of comorbidities in COPD, submaximal physical performance was determined in 520 patients and 150 controls using the TUG test and 6MWD.,Spirometry, body composition, handgrip strength, the COPD assessment test, St George’s Respiratory Questionnaire (SGRQ), and the modified Medical Research Council dyspnoea scale were also determined.,Patients and controls were similar in age, body mass index, and sex proportions.,The TUG in the patients was greater than that in the control group, P=0.001, and was inversely related to 6MWD (r=−0.71, P<0.001) and forced expiratory volume in one second predicted (r=−0.19, P<0.01) and was directly related to the SGRQ activity (r=0.39, P<0.001), SGRQ total (r=0.37, P<0.001), and total COPD assessment test scores (r=0.37, P<0.001).,The TUG identified the difference in physical performance between patients and controls.,The TUG test and validated questionnaires provide a measure of physical performance, which is rapid and could be used in clinical practice. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world.,It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD.,The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected.,The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors.,In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity.,In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke.,We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with changes in the composition and function of peripheral and respiratory muscles, which can negatively impact quality of life.,Ultrasonography can provide a non-invasive evaluation of the integrity of both peripheral muscles and diaphragm, but its use in patients with COPD is still being investigated.,We aimed at evaluating the relationship between quadriceps size, using ultrasonography and symptoms, lung function and diaphragm contractility in a cohort of patients with COPD.,COPD patients were prospectively recruited and ultrasonography of the dominant quadriceps and of the diaphragm was performed.,Quadriceps size was evaluated using three measurements: 1) cross-sectional area of the rectus femoris (Qcsa), 2) thickness (Qthick) and 3) contractile index (Qci), defined as the ratio of quadriceps thickness/total anterior thigh thickness.,Diaphragm contractility was evaluated using thickening fraction (TFdi).,Clinical characteristics and number of moderate-to-severe exacerbations in the previous year were retrieved from medical files.,Dyspnea (mMRC scale) and disease impact on health status (COPD Assessment Test (CAT)) were measured at inclusion.,Fat-free mass index (FFMI) was assessed using bioelectrical impedance.,Forty patients were recruited (20 males, mean age and FEV1 66±6 years and 49±17%predicted, respectively).,Mean Qcsa, Qthick and Qci were 336±145 mm2, 1.55±0.53 cm and 64±16%, respectively, and mean TFdi was 91±36%.,Qci was significantly correlated with FFMI (rho=0.59, p=0.001), TFdi (rho=0.41, p=0.008), FEV1 (rho=0.43, p=0.001) but not with age (rho=0.18, p=0.28).,Qci was significantly correlated to CAT score (rho=−0.47, p=0.002), even when controlled for FEV1, and was lower in patients with an mMRC score ≥2 (55±15 vs 70±14%, p=0.002).,Qcsa and Qci were significantly lower in patients with frequent exacerbations.,In a multiple linear regression analysis that included age, gender, FFMI, FEV1 and TFdi, only FFMI and TFdi were found to be significantly related to lower Qci values.,In patients with COPD, ultrasound evaluation of the quadriceps contractile index is feasible and related to disease severity, clinical symptoms, exacerbation history and diaphragm contractility.,As such, it may provide a novel tool for the evaluation of the severity and burden of the disease in this population.,Further studies are required to better delineate its potential role as a prognostic marker in this population. | Quantifying the improvements in lower limb or quadriceps muscle mass following resistance training (RT), is an important outcome measure in COPD.,Ultrasound is a portable, radiation free imaging technique that can measure the size of superficial muscles belonging to the quadriceps group such as the rectus femoris, but has not been previously used in COPD patients following RT.,We compared the responsiveness of ultrasound derived measures of quadriceps mass against dual energy x-ray absorptiometry (DEXA), in patients with COPD and healthy controls following a programme of high intensity knee extensor RT.,Portable ultrasound was used to assess the size of the dominant quadriceps in 45 COPD patients and 19 healthy controls-before, during, and after 8 weeks of bilateral high intensity isokinetic knee extensor RT.,Scanning was performed at the mid-thigh region, and 2 indices of quadriceps mass were measured-rectus femoris cross-sectional area (RFcsa) and quadriceps muscle thickness (Qt).,Thigh lean mass (Tdexa) was determined by DEXA.,Training resulted in a significant increase in Tdexa, RFcsa and Qt in COPD patients [5.7%, 21.8%, 12.1% respectively] and healthy controls [5.4%, 19.5%, 10.9 respectively].,The effect size for the changes in RFcsa (COPD= 0.77; Healthy=0.83) and Qt (COPD=0.36; Healthy=0.78) were greater than the changes in Tdexa (COPD=0.19; Healthy=0.26) following RT.,Serial ultrasound measurements of the quadriceps can detect changes in muscle mass in response to RT in COPD.,The technique has good reproducibility, and may be more sensitive to changes in muscle mass when compared to DEXA.,http://www.controlled-trials.com (Identifier: ISRCTN22764439) | 1 |
Chronic obstructive pulmonary disease (COPD), one of the most common chronic diseases and a leading cause of death, has historically been considered a disease of men.,However, there has been a rapid increase in the prevalence, morbidity, and mortality of COPD in women over the last two decades.,This has largely been attributed to historical increases in tobacco consumption among women.,But the influence of sex on COPD is complex and involves several other factors, including differential susceptibility to the effects of tobacco, anatomic, hormonal, and behavioral differences, and differential response to therapy.,Interestingly, nonsmokers with COPD are more likely to be women.,In addition, women with COPD are more likely to have a chronic bronchitis phenotype, suffer from less cardiovascular comorbidity, have more concomitant depression and osteoporosis, and have a better outcome with acute exacerbations.,Women historically have had lower mortality with COPD, but this is changing as well.,There are also differences in how men and women respond to different therapies.,Despite the changing face of COPD, care providers continue to harbor a sex bias, leading to underdiagnosis and delayed diagnosis of COPD in women.,In this review, we present the current knowledge on the influence of sex on COPD risk factors, epidemiology, diagnosis, comorbidities, treatment, and outcomes, and how this knowledge may be applied to improve clinical practices and advance research. | A 6-second spirometry test is easier than full exhalations.,We compared the reliability of the ratio of the Forced expiratory volume in 1 second/Forced expiratory volume in 6 seconds (FEV1/FEV6) to the ratio of the FEV1/Forced vital capacity (FEV1/FVC) for the detection of airway obstruction.,The PLATINO population-based survey in individuals aged 40 years and over designed to estimate the prevalence of post-Bronchodilator airway obstruction repeated for the same study participants after 5-9 years in three Latin-American cities.,Using the FEV1/FVC<Lower limit of normal (LLN) index, COPD prevalence apparently changed from 9.8 to 13.2% in Montevideo, from 9.7 to 6.0% in São Paulo and from 8.5 to 6.6% in Santiago, despite only slight declines in smoking prevalence (from 30.8% to 24.3%).,These changes were associated with differences in Forced expiratory time (FET) between the two surveys.,In contrast, by using the FEV1/FEV6 to define airway obstruction, the changes in prevalence were smaller: 9.7 to 10.6% in Montevideo, 8.6 to 9.0% in São Paulo, and 7.5 to 7.9% in Santiago.,Changes in the prevalence of COPD with criteria based on FEV1/FVC correlated strongly with changes in the FET of the tests (R2 0.92) unlike the prevalence based on a low FEV1/FEV6 (R2 = 0.40).,The FEV1/FEV6 is a more reliable index than FEV1/FVC because FVC varies with the duration of the forced exhalation.,Reporting FET and FEV1/FEV6<LLN helps to understand differences in prevalence of COPD obtained from FEV1/FVC-derived indices. | 1 |
Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD).,However, their relationship remains uncertain.,A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.,Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks.,Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured.,In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.,After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]).,UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]).,Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC.,UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005).,There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.,Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance. | Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD.,Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents.,Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent.,The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations.,Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes.,In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs.,Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results.,In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily).,Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments.,Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed.,Overall, the safety profiles of the FDCs were similar to placebo.,Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA-LAMA combinations. | 1 |
Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use. | Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide.,Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease.,We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors.,Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103).,We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions.,We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice.,HRVs are isolated from nasal and lung fluid from subjects with AE-COPD.,Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection.,HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells.,Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells.,Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD.,HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD.,Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD. | 1 |
Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD.,Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry.,Setting Tayside, Scotland (2001-2010),Population 5977 patients aged >50 years with a diagnosis of COPD.,Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates.,Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective.,There was a 22% overall reduction in all cause mortality with β blocker use.,Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD.,Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker.,There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent,Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function. | Statins have anti-inflammatory and immunomodulating properties which could possibly influence inflammatory airways disease.,We assessed evidence for disease modifying effects of statin treatment in patients with chronic obstructive pulmonary disease (COPD).,A systematic review was conducted of studies which reported effects of statin treatment in COPD.,Data sources searched included MEDLINE, EMBASE and reference lists.,Eight papers reporting nine original studies met the selection criteria.,One was a randomized controlled trial (RCT), one a retrospective nested case-control study, five were retrospective cohort studies of which one was linked with a case-control study, and one was a retrospective population-based analysis.,Outcomes associated with treatment with statins included decreased all-cause mortality in three out of four studies (OR/HR 0.48-0.67 in three studies, OR 0.99 in one study), decreased COPD-related mortality (OR 0.19-0.29), reduction in incidence of respiratory-related urgent care (OR 0.74), fewer COPD exacerbations (OR 0.43), fewer intubations for COPD exacerbations (OR 0.1) and attenuated decline in pulmonary function.,The RCT reported improvement in exercise capacity and dyspnea after exercise associated with decreased levels of C-reactive protein and Interleukin-6 in statin users, but no improvement of lung function.,There is evidence from observational studies and one RCT that statins may reduce morbidity and/or mortality in COPD patients.,Further interventional studies are required to confirm these findings. | 1 |
Exercise intolerance is a common development in patients with chronic obstructive pulmonary disease (COPD).,There is little data on the use of an isolated program using vibration platform training on functional capacity in these patients, which is an area that deserves investigation.,To investigate the effect of training on a vibrating platform (whole-body vibration [WBV]) on functional performance and quality of life of subjects with COPD.,A randomized controlled crossover pilot study with eleven subjects with COPD (forced expiratory volume in 1 second [FEV1]% predicted =14.63±11.14; forced vital capacity [FVC]% predicted =48.84±15.21; FEV1/FVC =47.39±11.63) underwent a 12-week WBV training program.,Participants were randomized into the intervention group (IG) undergoing three sessions per week for a total of 12 weeks and control group (CG) without intervention.,We evaluated the 6-minute walk test (6MWT), distance walked (DW), duration of the walk (TW), and index of perceived exertion (IPE), quality of life using St George’s Respiratory Questionnaire (SGRQ) and developed a 12-week program of training on a vibrating platform.,The mean age was 62.91±8.82 years old (72.7% male).,The DW increased at the end of training with a difference between groups of 75 m; all domains of the SGRQ improved at the end of training.,The effect size Cohen’s d ranged from small to large for all the measured results.,These preliminary results suggest that WBV may potentially be a safe and feasible way to improve functional capacity in the 6MWT of patients with COPD undergoing a training program on the vibrating platform as well as in all domains of the SGRQ quality of life.,However, further studies with a larger number of patients are needed to establish the long-term effect on functional capacity and quality of life in these patients. | Benefits of community-based whole-body vibration (WBV) as a mode of exercise training for people with chronic obstructive pulmonary disease (COPD) have not been investigated.,The low skill demand of WBV may enhance habitual sustainability to physical activity by people with COPD, provided efficacy of WBV can be established.,The purpose of this trial was to compare a community-based WBV intervention with a sham WBV (SWBV) intervention and monitor exacerbations, exercise tolerance, and functional performance of the lower limbs of people with COPD.,Community-dwelling adults with a GOLD clinical diagnosis of COPD were recruited to the trial.,This was a Phase II efficacy trial with crossover to sham intervention interspersed with two-week washout.,Each six-week intervention consisted of two sessions per week of either WBV or SWBV.,The interventions were completed in the home of each participant under supervision.,The outcome measures were selected psychological (perceived dyspnoea) and physiological (heart rate and oxygen saturation) responses to exercise, simulated activities of daily living (timed-up-and got test and 5-chair stands test), and selected kinematic variables of gait across the 14-week trial.,Sixteen adults with stable COPD were recruited to the trial.,No exacerbations were reported during the WBV or SWBV interventions.,After WBV, performance of activities of daily living (ADLs) and gait improved (p ≤ 0.05), while there was no change after SWBV (p > 0.05).,Despite five withdrawals during the washout period, a 100% compliance to each six-week intervention was noted.,Results showed that WBV did not exacerbate symptoms of COPD that can be associated with physical inactivity.,The WBV intervention improved tests to simulate ADLs such as rising from a chair, turning, and walking gait with greater effect than a SWBV intervention.,If a placebo effect was systemic to the WBV intervention, the effect was negligible.,As a standalone community-based intervention, WBV was an efficacious mode of exercise training for people with stable COPD that did not negatively effect exercise tolerance or exacerbate the disease, while concurrently improving functional performance of the lower limbs.,Australian and New Zealand Clinical Trials Registry ACTRN12612000508875. | 1 |
Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).,We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.,Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.,Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD.,While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella.,Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.,Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations.,These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.,The online version of this article (10.1186/s12931-019-1085-z) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction.,Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations.,Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome.,The role of the lung microbiome in the pathogenesis of COPD remains unknown.,The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora.,Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients.,The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid.,Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats.,Our results showed a significant increase in microbial diversity with the development of COPD.,The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria.,Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity.,However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators.,Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. | 1 |
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. | The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation.,We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.,Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits.,Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays.,Low-dose CT scans evaluated emphysema.,Sputum neutrophil % increased with GOLD stage.,There was a weak association between % sputum neutrophils and FEV1 % predicted (univariate r2 = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression).,Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre.,There were no associations between neutrophils and exacerbation rates or emphysema.,Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak.,The mean change over 1 year in neutrophil % was an increase of 3.5%.,Sputum neutrophil measurements in COPD are associated weakly with FEV1 % predicted and health status.,Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation. | 1 |
Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | 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. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | 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. | 1 |
COPD is the third leading cause of death in the world and its global burden is predicted to increase further.,Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner.,In a prospective population-based cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV1/FVC < 0.70).,In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician.,Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk.,In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones.,The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4.,The IR was higher in males and in smokers.,The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males.,The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers.,The proportion of never-smokers among female COPD cases is substantial.,The online version of this article (doi:10.1007/s10654-016-0132-z) contains supplementary material, which is available to authorized users. | Waste management, namely, collection, transport, sorting and processing, and disposal, is an issue of social concern owing to its environmental impact and effects on public health.,In fact, waste management activities are carried out according to procedures that can have various negative effects on the environment and, potentially, on human health.,The aim of our study was to assess the potential effects on respiratory health of this exposure in workers in the waste management and disposal field, as compared with a group of workers with no occupational exposure to outdoor pollutants.,The sample consisted of a total of 124 subjects, 63 waste collectors, and 61 office clerks.,Informed consent was obtained from all subjects before inclusion in the study.,The entire study population underwent pulmonary function assessments with spirometry and completed two validated questionnaires for the diagnosis of rhinitis and chronic bronchitis.,Statistical analyses were performed using STATA 13.,Spirometry showed a statistically significant reduction in the mean Tiffenau Index values in the exposed workers, as compared with the controls, after adjusting for the confounding factors of age, BMI, and smoking habit.,Similarly, the mean FEV1 values were lower in the exposed workers than in the controls, this difference being again statistically significant.,The FVC differences measured in the two groups were not found to be statistically significant.,We ran a cross-sectional study to investigate the respiratory health of a group of workers in the solid waste collection and disposal field as compared with a group of office workers.,In agreement with most of the data in the literature, our findings support the existence of a prevalence of respiratory deficits in waste disposal workers.,Our data suggest the importance of adopting preventive measures, such as wearing specific individual protection devices, to protect this particular category of workers from adverse effects on respiratory health. | 1 |
In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality.,Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin.,A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included.,All patients underwent coronary angiography within 72 hours after hospitalization.,Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed.,Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention.,Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history.,Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, P=0.01) and a significantly more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01).,Neither additional laboratory parameters for inflammation and myocardial injury nor lung functional measurements differed significantly between the groups.,Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin.,In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value. | Objectives.,To investigate the effect of the cause of acute respiratory failure and the role of comorbidities both acute and chronic on the outcome of COPD patients admitted to Respiratory Intensive Care Unit (RICU) with acute respiratory failure and treated with NIV.,Design.,Observational prospective study.,Patients and Methods.,176 COPD patients consecutively admitted to our RICU over a period of 3 years and treated with NIV were evaluated.,In all patients demographic, clinical, and functional parameters were recorded including the cause of acute respiratory failure, SAPS II score, Charlson comorbidity index, and further comorbidities not listed in the Charlson index.,NIV success was defined as clinical improvement leading to discharge to regular ward, while exitus or need for endotracheal intubation was considered failure.,Results.,NIV outcome was successful in 134 patients while 42 underwent failure.,Univariate analysis showed significantly higher SAP II score, Charlson index, prevalence of pneumonia, and lower serum albumin level in the failure group.,Multivariate analysis confirmed a significant predictive value for pneumonia and albumin.,Conclusions.,The most important determinants of NIV outcome in COPD patients are the presence of pneumonia and the level of serum albumin as an indicator of the patient nutritional status. | 1 |
We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB).,We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB.,Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations.,We characterized cytokine protein concentrations in blood and bacterial growth in sputum.,Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups.,During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations.,Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora.,During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner.,In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways.,Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts. | Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity.,Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD.,The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells), and CD1a+ cells (Langerhans cells).,The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues.,To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE), and dendritic cells extracted from mice chronically exposed to cigarette smoke.,In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue.,Human monocyte-derived dendritic cells exposed to CSE (0.1-2%) exhibited enhanced survival in vitro when compared with control dendritic cells.,Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice.,Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1), and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through oxidative stress.,Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not impaired.,These data indicate that COPD is associated with increased numbers of cells bearing markers associated with Langerhans cells and mature dendritic cells, and that cigarette smoke promotes survival signals and augments survival of dendritic cells.,Although CSE suppressed dendritic cell CCR7 expression, migration towards a CCR7 ligand was not diminished, suggesting that reduced CCR7-dependent migration is unlikely to be an important mechanism for dendritic cell retention in the lungs of smokers with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | The chronic obstructive pulmonary disease (COPD) assessment test (CAT) was recently introduced for use in assessing disease-specific quality of life and follow-up of patients with COPD.,The purpose of this study was to evaluate the effect of the dyspnea on disease-specific quality of life detected by CAT score in patients with COPD.,In this study, 90 stable patients with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were included.,The level of dyspnea was assessed with the Medical Research Council (MRC) dyspnea scale, and disease-specific quality of life was assessed with CAT score.,The mean±SD age was 68.5±10.9 (range 41-97) years.,A significant relationship was established between CAT score, MRC dyspnea scale score and GOLD stage in patients with COPD.,There was also a positive correlation between dyspnea scale scores and GOLD stage in the patients (p<0.001), as well as positive correlation between CAT score and dyspnea scale score (p<0.001).,CAT score showed a significant correlation with hospitalization and exacerbations (p<0.05).,Dyspnea is an important symptom that may impact quality of life in patients with COPD.,CAT was shown to be a simple, fast and intelligible measurement of disease-specific quality of life, and was correlated with levels of dyspnea in patients with COPD. | 1 |
Oxidative stress induced by smoking is considered to be important in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD).,Heme oxygenase-1 (HMOX1) is an essential enzyme in heme catabolism that is induced by oxidative stress and may play a protective role as an antioxidant in the lung.,We determined whether HMOX1 polymorphisms were associated with lung function in COPD patients and whether the variants had functional effects.,We genotyped five single nucleotide polymorphisms (SNPs) in the HMOX1 gene in Caucasians who had the fastest (n = 278) and the slowest (n = 304) decline of FEV1 % predicted, selected from smokers in the NHLBI Lung Health Study.,These SNPs were also studied in Caucasians with the lowest (n = 535) or the highest (n = 533) baseline lung function.,Reporter genes were constructed containing three HMOX1 promoter polymorphisms and the effect of these polymorphisms on H2O2 and hemin-stimulated gene expression was determined.,The effect of the HMOX1 rs2071749 SNP on gene expression in alveolar macrophages was investigated.,We found a nominal association (p = 0.015) between one intronic HMOX1 SNP (rs2071749) and lung function decline but this did not survive correction for multiple comparisons.,This SNP was in perfect linkage disequilibrium with rs3761439, located in the promoter of HMOX1.,We tested rs3761439 and two other putatively functional polymorphisms (rs2071746 and the (GT)n polymorphism) in reporter gene assays but no significant effects on gene expression were found.,There was also no effect of rs2071749 on HMOX1 gene expression in alveolar macrophages.,We found no association of the five HMOX1 tag SNPs with lung function decline and no evidence that the three promoter polymorphisms affected the regulation of the HMOX1 gene. | Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood.,Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease.,Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2.,A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility.,We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls.,Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene.,Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated.,The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre.,Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053.,No significant associations were identified for TGFbeta1.,These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis. | 1 |
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