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Corticosteroids (CS) have limited efficacy in the treatment of chronic obstructive pulmonary disease (COPD). p38 mitogen-activated protein kinase (MAPK) activation is increased in lung macrophages of COPD.,We investigated whether p38 MAPK inhibition can modulate CS insensitivity of peripheral blood mononuclear cells (PBMCs) from patients with COPD.,PBMCs from patients with COPD (n=8) or healthy smokers (n=8) were exposed to lipopolysaccharide (LPS) with a selective p38 MAPK inhibitor (GW856553; 10−10-10−6 M), with dexamethasone (10−10-10−6 M), or with both.,Phosphorylated glucocorticoid receptor (GR) was measured by Western blot.,Baseline (P<0.01) and LPS-induced (P<0.05) CXCL8 release was greater in PBMCs from COPD compared to healthy smokers.,Inhibition of LPS-induced CXCL8 release by dexamethasone (10−6 M) was reduced, and baseline and LPS-induced p38 MAPK activation increased in PBMCs of COPD.,GW856553 (10−9 and 10−10 M) synergistically increased the inhibitory effect of dexamethasone (10−8 and 10−6 M) on LPS-induced CXCL8 release in COPD.,Similar results were obtained for IL-6 release.,GW856553 inhibited dexamethasone- and LPS-activated phosphorylation of serine 211 on GR.,CS insensitivity in COPD PBMCs is reversed by inhibition of p38 MAPK activity, partly by preventing phosphorylation of GR at serine 211.,p38 MAPK inhibition may be beneficial in COPD by restoring CS sensitivity. | There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown.,This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure.,In acute and chronic CS exposure, the activation and expression of p38 MAPK in the lungs, as well as lung inflammation and injury (proteinase production, apoptosis, and oxidative DNA damage), were compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW (emphysema-resistant).,The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was administrated intra-peritoneally to C57BL/6 mice, to examine whether it ameliorated cigarette smoke-induced lung inflammation and injury.,Acute CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was significantly activated and up-regulated by both acute and chronic CS exposure in C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW mice.,SB203580 significantly attenuated lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2, protein levels of KC, MIP-1α, IL-1β, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA damage, and apoptosis caused by acute CS exposure.,Cigarette smoke activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced emphysema.,Its selective inhibition ameliorated lung inflammation and injury in a murine model of cigarette smoke exposure. p38 MAPK pathways are a possible molecular target for the treatment of chronic obstructive pulmonary disease. | 1 |
Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung.,The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation.,A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007.,Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication.,Multivariable negative binomial regression was performed with adjustment for potential confounding factors.,The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations.,We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications.,COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group.,In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81-0.92).,Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD. | Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers.,The utility of these clinical subtypes is unclear.,However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant.,The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.,Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis.,Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%.,Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%).,Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized.,Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St.,George’s Respiratory Questionnaire score 43 vs 31, p < 0.0001).,Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use.,The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study.,Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes.,COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa.,Clinicaltrials.gov identifiers: COPDGene NCT00608764, ECLIPSE NCT00292552.,The online version of this article (doi:10.1186/1471-2466-14-164) contains supplementary material, which is available to authorized users. | 1 |
Small airway fibrosis is the main contributor in airflow obstruction in chronic obstructive pulmonary disease.,Epithelial mesenchymal transition (EMT) has been implicated in this process, and in large airways, is associated with angiogenesis, ie, Type-3, which is classically promalignant.,In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways in subjects with chronic airflow limitation (CAL) and what type of EMT is present on the basis of vascularity.,We evaluated epithelial activation, reticular basement membrane fragmentation (core structural EMT marker) and EMT-related mesenchymal biomarkers in small and large airways from resected lung tissue from 18 lung cancer patients with CAL and 9 normal controls.,Tissues were immunostained for epidermal growth factor receptor (EGFR; epithelial activation marker), vimentin (mesenchymal marker), and S100A4 (fibroblast epitope).,Type-IV collagen was stained to demonstrate vessels.,There was increased expression of EMT-related markers in CAL small airways compared to controls: EGFR (P<0.001), vimentin (P<0.001), S100A4 (P<0.001), and fragmentation (P<0.001), but this was less than that in large airways.,Notably, there was no hypervascularity in small airway reticular basement membrane as in large airways.,Epithelial activation and S100A4 expression were related to airflow obstruction.,EMT is active in small airways, but less so than in large airways in CAL, and may be relevant to the key pathologies of chronic obstructive pulmonary disease, small airway fibrosis, and airway cancers. | 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. | 1 |
The aim of the study was to characterize pharmacokinetics of tiotropium solution 5 µg compared to powder 18 µg and assess dose-dependency of tiotropium solution pharmacodynamics in comparison to placebo.,In total 154 patients with chronic obstructive pulmonary disease (COPD) were included in this multicenter, randomized, double-blind within-solution (1.25, 2.5, 5 µg, and placebo), and open-label powder 18 µg, crossover study, including 4-week treatment periods.,Primary end points were peak plasma concentration (Cmax,ss), and area under the plasma concentration-time profile (AUC0-6h,ss), both at steady state.,The pharmacodynamic response was assessed by serial spirometry (forced expiratory volume in 1 second/forced vital capacity).,Safety was evaluated as adverse events and by electrocardiogram/Holter.,Tiotropium was rapidly absorbed with a median tmax,ss of 5-7 minutes postdosing for both devices.,The gMean ratio of solution 5 µg over powder 18 µg was 81% (90% confidence interval, 73-89%) for Cmax,ss and 76% (70-82%) for AUC0-6h,ss, indicating that bioequivalence was not established.,Dose ordering for bronchodilation was observed.,Powder 18 µg and solution 5 µg were most effective, providing comparable bronchodilation.,All treatments were well tolerated with no apparent relation to dose or device.,Comparable bronchodilator efficacy to powder18 µg at lower systemic exposure supports tiotropium solution 5 µg for maintenance treatment of COPD. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven. | 1 |
Lung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling.,Abnormal repair and remodeling has been observed in lung diseases like COPD.,As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function.,We investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays.,TGF-β1-induced miRNA expression changes were validated and replicated in an independent set of lung fibroblasts composted of 10 controls and 15 COPD patients using qRT-PCR.,Ago2-immunoprecipitation followed by mRNA expression profiling was used to identify the miRNA-targetomes of unstimulated and TGF-β1-stimulated primary lung fibroblasts (n = 2).,The genes affected by TGF-β1-modulated miRNAs were identified by comparing the miRNA targetomes of unstimulated and TGF-β1-stimulated fibroblasts.,Twenty-nine miRNAs were significantly differentially expressed after TGF-β1 stimulation (FDR<0.05).,The TGF-β1-induced miR-455-3p and miR-21-3p expression changes were validated and replicated, with in addition, lower miR-455-3p levels in COPD (p<0.05).,We identified 964 and 945 genes in the miRNA-targetomes of unstimulated and TGF-β1-stimulated lung fibroblasts, respectively.,The TGF-β and Wnt pathways were significantly enriched among the Ago2-IP enriched and predicted targets of miR-455-3p and miR-21-3p.,The miR-455-3p target genes HN1, NGF, STRADB, DLD and ANO3 and the miR-21-3p target genes HHEX, CHORDC1 and ZBTB49 were consistently more enriched after TGF-β1 stimulation.,Two miRNAs, miR-455-3p and miR-21-3p, were induced by TGF-β1 in lung fibroblasts.,The significant Ago2-IP enrichment of targets of these miRNAs related to the TGF-β and/or Wnt pathways (NGF, DLD, HHEX) in TGF-β1-stimulated fibroblasts suggest a role for these miRNAs in lung diseases by affecting lung fibroblast function. | Inflammatory airway diseases are a significant health problems requiring new approaches to the existing therapies and addressing fundamental issues.,Difficulties in developing effective therapeutic strategies might be caused by lack of understanding of their exact molecular mechanism.,MicroRNAs (miRNAs) are a class of regulators that already revolutionized the view of gene expression regulation.,A cumulating number of investigations show a pivotal role of miRNAs in the pathogenesis of asthma, chronic obstructive pulmonary disease (COPD), or airway remodeling through the regulation of many pathways involved in their pathogenesis.,Expression changes of several miRNAs have also been found to play a role in the development and/or improvement in asthma or COPD.,Still, relatively little is known about the role of miRNAs in inflammatory disorders.,The microRNA profiles may differ depending on the cell type or antigen-presenting cell.,Based on the newest literature, this review discusses the current knowledge concerning miRNA contribution and influence on lung inflammation and chosen inflammatory airway diseases: asthma and COPD. | 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 a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage.,Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking.,Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years.,We performed nucleic acid detection for 20 respiratory viruses and 16S ribosomal RNA gene sequencing to evaluate the bacterial microbiota in 1179 sputum samples collected at stable, acute exacerbation and follow-up visits.,Similar viral and bacterial taxa were found in patients from the USA compared to Bulgaria and Czech Republic but their microbiome diversity was significantly different (P < 0.001) and did not impact exacerbation rates.,Virus infection was strongly associated with exacerbation events (P < 5E-20).,Human rhinovirus (13.1%), coronavirus (5.1%) and influenza virus (3.6%) constitute the top viral pathogens in triggering exacerbation.,Moraxella and Haemophilus were 5-fold and 1.6-fold more likely to be the dominating microbiota during an exacerbation event.,Presence of Proteobacteria such as Pseudomonas or Staphylococcus amongst others, were associated with exacerbation events (OR > 0.17; P < 0.02) but more strongly associated with exacerbation frequency (OR > 0.39; P < 4E-10), as confirmed by longitudinal variations and biotyping of the bacterial microbiota, and suggesting a role of the microbiota in sensitizing the lung.,This study highlights bacterial taxa in lung sensitization and viral triggers in COPD exacerbations.,It provides a global overview of the diverse targets for drug development and explores new microbiome analysis methods to guide future patient management applications. | 1 |
Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management.,The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories.,This study will also evaluate COPD real-life patient care in the Czech Republic.,The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients.,This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤60%).,Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study.,Patient recruitment is done on the basis of signed informed consent.,The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic.,The objective of this paper was to outline the methodology of this study.,The establishment of the database is a useful step in improving care for COPD subjects.,Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients.,Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic. | Recent literature has suggested that emphysema and chronic bronchitis, traditionally considered to be entities overlapping within chronic obstructive pulmonary disease (COPD), may be distinct disorders.,Few studies have examined the differences in patient characteristics and health outcomes between these conditions.,This study examined whether COPD phenotypes represent distinct patient populations, in a large nationally representative US sample.,Data were obtained from the 2010 US National Health and Wellness Survey (NHWS).,NHWS respondents (n = 75,000) were categorized as a COPD phenotype based on their self-reported diagnosis of COPD only (n = 970), emphysema only (n = 399), or chronic bronchitis only (n = 2071).,Phenotypes were compared on demographics, health characteristics, treatment patterns, health outcomes, work productivity, and resource use.,Variables were compared using Chi-square and analysis of variance tests for categorical and continuous outcomes, respectively.,Health outcomes were also examined using regression modeling, controlling for demographic and health characteristic covariates.,Patients with chronic bronchitis were significantly younger (51.38 years versus 63.24 years for COPD versus 63.30 years for emphysema, P < 0.05) and more likely to be employed (46.98% versus 23.81% for COPD versus 28.33% for emphysema, P < 0.05).,Relative to the other phenotypes, patients with chronic bronchitis were also significantly more likely to be female, nonwhite, and to exercise currently (all P < 0.05), and were significantly less likely to be a current or former smoker (P < 0.05).,Controlling for demographic and health characteristics, patients self-identified as having COPD only reported significantly worse physical quality of life (adjusted mean 36.69) and health utilities (adjusted mean 0.65) and significantly more absenteeism (adjusted mean 7.08%), presenteeism (adjusted mean 30.73%), overall work impairment (adjusted mean 34.06%), and activity impairment (adjusted mean 46.59%) than the other phenotypes (all P < 0.05).,These results suggest considerable heterogeneity among different COPD phenotypes with respect to demographics, health characteristics, disease characteristics, treatment patterns, and health outcomes.,Research aimed at understanding the differences in patient characteristics and disease presentation of these phenotypes could be used to guide treatment recommendations. | 1 |
Severe exacerbations and mortality are major outcomes in COPD, and risk factors for these events are actively searched for.,Several predictors of mortality have been identified in COPD.,The inspiratory capacity/total lung capacity (IC/TLC) ratio has been shown to be a strong predictor of all cause and respiratory mortality in patients with COPD.,The major objectives of this study were to analyze which clinical parameters, including lung volumes, were the best predictors of the 5-year cumulative risk of hospital admissions or death and the 5-year risk of exacerbations, in stable COPD patients.,This study retrospectively reviewed data from 98 stable COPD patients, consecutively recruited in 2012.,Forced expiratory volume in 1 s (FEV1), modified Medical Research Council dyspnea scale, exacerbation history (ExH), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 groups, and lung volumes were reviewed.,Five years later, this population was evaluated for cumulative exacerbations, hospital admissions, and mortality.,All the population, and GOLD group D separately, were analyzed.,The cumulative 5-year combined risk of hospital admission or death was significantly predicted by the ExH and the IC/TLC ratio.,Analyzing separately group D, FEV1 was the only predictor of this outcome.,The frequency of exacerbations in the previous year was the best predictor of future cumulative 5-year risk of subsequent exacerbations, both for the total population and the GOLD D group.,ExH and IC/TLC ratio were the best predictors of the most severe outcomes in COPD (admissions or mortality), independently of COPD severity.,FEV1 was the only predictor of the cumulative 5-year combined risk of hospital admission or death in the GOLD D group.,ExH was the best predictor of 5-year cumulative future risk of exacerbations.,Besides FEV1 and ExH, the IC/TLC ratio can be a useful predictor of severe outcomes in COPD. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
Background: COPD pathology involves not only the lungs but also extrapulmonary abnormalities.,Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function.,COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids.,Some of these factors have been shown to deteriorate with COPD exacerbations.,We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations.,Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated.,Methods: Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited.,During follow-up, exacerbations had been prospectively recorded.,Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated.,The change was compared between patients with and without a history of exacerbations.,Results: The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ABMD mg/ml year: −3.78 versus −0.30, p = 0.02).,Moreover, multivariate regression analysis showed that exacerbations and baseline Pa02 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation.,Conclusions: This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression.,Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations. | Osteoporosis is one of the systemic features of COPD.,A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear.,Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema.,The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis.,Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.,Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires.,Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA).,Twenty age-matched healthy volunteers were recruited as controls.,Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD.,Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05).,The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001).,Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables.,The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance.,The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05).,The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.,Radiographic emphysema is correlated with low BMD in current and former smokers with COPD.,IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD. | 1 |
Current pharmacological treatments for chronic obstructive pulmonary disease (COPD) are mostly limited to inhaled bronchodilators and corticosteroids.,Azithromycin can contribute to exacerbation prevention.,Roflumilast, a phosphodiesterase (PDE) 4 inhibitor administered orally, also prevents exacerbations in selected patients with chronic bronchitis, recurrent exacerbations, severe airflow limitation and concomitant therapy with long-acting inhaled bronchodilators.,This outcome likely results from anti-inflammatory effects since PDE4 is expressed by all inflammatory cell types involved in COPD.,The use of this agent is, however, limited by side-effects, particularly nausea and diarrhea.,To address remaining unmet needs and enrich therapeutic options for patients with COPD, inhaled dual PDE3/4 inhibitors have been developed, with the aim of enhancing bronchodilation through PDE3 inhibition and modulating inflammation and mucus production though PDE4 inhibition, thus producing a potentially synergistic effect on airway calibre.,Experimental preclinical data confirmed these effects in vitro and in animal models.,At present, RPL554/ensifentrine is the only agent of this family in clinical development.,It decreases sputum markers of both neutrophilic and eosinophilic inflammation in patients with COPD.,Clinical Phase II trials confirmed its bronchodilator effect and demonstrated clinically meaningful symptom relief and quality of life improvements in these patients.,The safety profile appears satisfactory, with less effects on heart rate and blood pressure than salbutamol and no other side effect.,Altogether, these data suggest that ensifentrine could have a role in COPD management, especially in addition to inhaled long-acting bronchodilators with or without corticosteroids since experimental studies suggest potentiation of ensifentrine effects by these agents.,However, results from ongoing and future Phase III studies are needed to confirm both beneficial effects and favourable safety profile on a larger scale and assess other outcomes including exacerbations, lung function decline, comorbidities and mortality. | Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).,To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.,In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg).,Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.,In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD.,Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients.,In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals −46, 315mL) with a probability that the true treatment ratio was >0% (Pr(θ>0)) of 93% was observed in AECOPD.,However, FRI endpoints remained unchanged.,We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group.,We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD. | 1 |
Self-management support for chronic obstructive pulmonary disease (COPD) patients is recommended by UK national guidelines, but extent of implementation is unknown.,We aimed to describe self-management behaviour and support among COPD patients and explore behaviour associated with having a self-management plan.,We undertook cross-sectional analysis of self-reported data from diagnosed COPD patients in the Birmingham COPD Cohort study.,Questionnaire items relevant to self-management behaviour, knowledge of COPD, receipt of self-management plans and advice from healthcare professionals were examined.,Multiple regression models were used to identify behaviour associated with having a self-management plan.,One-thousand seventy-eight participants (676 males, 62.7%, mean age 69.8 (standard deviation 9.0) years) were included.,The majority reported taking medications as instructed (940, 94.0%) and receiving annual influenza vaccinations (962, 89.2%).,Only 400 (40.4%) participants had self-management plans, 538 (49.9%) reported never having received advice on diet/exercise and 110 (42.7%) current smokers had been offered practical help to stop smoking in the previous year.,General knowledge about COPD was moderate (mean total Bristol COPD Knowledge Questionnaire score: 31.5 (standard deviation 10.7); max score 65), corresponding to 48.5% of questions answered correctly.,Having a self-management plan was positively associated with self-reported adherence to medication (odds ratio 3.10, 95% confidence interval 1.43 to 6.72), attendance at a training course (odds ratio 2.72, 95% confidence interval 1.81 to 4.12), attendance at a support group (odds ratio 6.28, 95% confidence interval 2.96 to 13.35) and better disease knowledge (mean difference 4.87, 95% confidence interval 3.16 to 6.58).,Primary care healthcare professionals should ensure more widespread implementation of individualised self-management plans for all patients and improve the lifestyle advice provided.,Health professionals should ensure all patients with chronic lung disease receive individualized self-management plans and lifestyle advice.,UK national guidelines state that patients with chronic obstructive pulmonary disease (COPD) should receive personalized self-management plans and comprehensive support to help them manage their disease.,Ainee Khan and colleagues at the University of Birmingham analyzed patient questionnaire data gathered during the Birmingham COPD Cohort study to explore self-management behavior, receipt of self-management plans and advice, and patient knowledge of COPD.,Of 1,078 participants, only 400 had self-management plans, and less than half reported receiving lifestyle advice or support.,Those with plans were more likely to adhere to medication, had greater knowledge about COPD and were more likely to attend support groups and training courses.,The authors recommend carefully-planned, wider implementation of COPD self-management plans and associated support. | Physical inactivity is associated with poor outcomes in COPD, and as a result, interventions to improve physical activity (PA) are a current research focus.,However, many trials have been small and inconclusive.,The aim of this systematic review and meta-analysis was to study the effects of randomized controlled trials (RCTs) targeting PA in COPD.,Databases (Physiotherapy Evidence Database [PEDro], Embase, MEDLINE, CINAHL and the Cochrane Central Register for Controlled Trials) were searched using the following keywords: “COPD”, “intervention” and “physical activity” from inception to May 20, 2016; published RCTs that aimed to increase PA in individuals with COPD were included.,The PEDro scale was used to rate study quality.,Standardized mean differences (effect sizes, ESs) with 95% confidence intervals (CIs) were determined.,Effects of included interventions were also measured according to the minimal important difference (MID) in daily steps for COPD (599 daily steps).,A total of 37 RCTs with 4,314 participants (mean forced expiratory volume in one second (FEV1) % predicted 50.5 [SD=10.4]) were identified.,Interventions including exercise training (ET; n=3 studies, 103 participants) significantly increased PA levels in COPD compared to standard care (ES [95% CI]; 0.84 [0.44-1.25]).,The addition of activity counseling to pulmonary rehabilitation (PR; n=4 studies, 140 participants) showed important effects on PA levels compared to PR alone (0.47 [0.02-0.92]), achieving significant increases that exceeded the MID for daily steps in COPD (mean difference [95% CI], 1,452 daily steps [549-2,356]).,Reporting of methodological quality was poor in most included RCTs.,Interventions that included ET and PA counseling during PR were effective strategies to improve PA in COPD. | 1 |
We aimed to compare impulse oscillation system (IOS) and traditional pulmonary function tests (PFTs) for the assessment of the severity of chronic obstructive pulmonary disease (COPD), and to assess the use of IOS parameters to identify patients who were forced expiratory volume in 1 second (FEV1)%pred < 50%.,Patients with COPD (n = 215) were enrolled at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,All patients were assessed by traditional PFT and IOS.,Diagnostic performance of IOS parameters to determine indication for patients of FEV1%pred < 50% was assessed on receiver-operating characteristics (ROC) curve analysis.,Out of 215 patients, 18, 83, 78, and 36 patients were classified as grade 1, 2, 3, and 4, respectively, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity grading.,On Spearman correlation analysis, FEV1%pred, MMEF 75%-25%, and residual volume/total lung capacity (RV/TLC) correlated with total respiratory impedance (Z5)%pred, resistance at 5 Hz (R5)-resistance at 20 Hz (R20), R5-R20% R5, R5, R5%pred, frequency response (Fres), reactance area (Ax), and reactance at 5 Hz (X5).,On ROC curve analysis, the area under the curve (AUC) of X5 absolute value, Fres, Ax, Z5%pred, R5-R20, and R5-R20% R5 were 0.748, 0.755, 0.760, 0.705, 0.715, and 0.735, respectively, for COPD patients who required inhalational glucocorticoid therapy.,IOS parameters showed a good correlation with traditional pulmonary function parameters; reactance parameters showed a stronger correlation than that of the resistance parameters.,IOS can be used as an alternative method for pulmonary function assessment in patients with COPD with FEV1%pred < 50% who need inhalational glucocorticoid therapy.,Clinical trial registration number: ChiCTR-OCH-14004904. | Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear.,This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD.,Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers.,Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay.,Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test.,Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD.,First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007).,Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), FEV1/Pre (justified r=−0.308, P<0.001; justified r=−0.295, P=0.001, respectively) and SAO indicators such as FEV3/FVC, MMEF25-75/Pre (justified r=−0.289, P=0.001; justified r=−0.273, P=0.002, respectively), but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively).,Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1.,Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD. | 1 |
MicroRNAs (miRNAs) are a family of small noncoding RNAs and are essential in the regulation of gene expression.,Their impacts on gene expression have been reported in various diseases.,The role of hypoxia‐inducible factor 1 alpha (HIF‐1α) in the development and progression of chronic obstructive pulmonary disease (COPD) has also been demonstrated.,However, the role of microRNA‐186 (miR‐186) in relation to HIF in COPD is unknown.,Cell culture experiments were performed using human lung fibroblast cells (MRC‐5).,Cell viability was determined by MTT and flow cytometry assays.,Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blot analysis were used to assess the expression levels of HIF‐1α and inflammatory cytokines.,Dual‐luciferase reporter assays were used to reveal the correlation between miR‐186 and HIF‐1α.,After miR‐186 transfection, the cell lines showed reduced proliferation and increased apoptosis.,After overexpression of miR‐186, we found that the HIF‐1α expression level was reduced in MRC‐5 cells.,We found that miR‐186 can affect apoptosis of inflammatory fibroblasts through the regulation of HIF‐1α and affect the downstream signaling pathways.,These data suggested that miR‐186 contributes to the pathogenesis of COPD and that miRNA‐186 may also affect the HIF‐1α‐dependent lung structure maintenance program. | Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease.,Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD.,However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD.,miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR.,Degeneration of lung tissue, necrosis, infiltration and neutrophil cells were assessed with H&E and flow cytometry.,Interleukin (IL)-6 and IL-8 levels were determined by an enzyme-linked immunosorbent assay and qRT-PCR.,Luciferase reporter assay and correlation analyses were used to confirm and measure the levels between miR-181c and its target CCN1.,We showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked (p < 0.01).,We also observed a down-regulation of miR-181c in HBECs and a mouse model after cigarette smoke (CS) exposure.,Functional assays demonstrated that miR-181c over-expression decreased the inflammatory response, neutrophil infiltration, reactive oxygen species (ROS) generation, and inflammatory cytokines induced by CS, while its down-regulation produced the opposite effects.,Subsequent investigation found that CCN1 was a direct target of miR-181c.,CCN1 expression was increased in lung tissues of COPD patients, and was negatively correlated with miR-181c expression in human COPD samples (p < 0.01).,Taken together, our data suggest the critical roles of miR-181c and its target CCN1 in COPD development, and provide potential therapeutic targets for COPD treatment. | 1 |
Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD).,We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD.,Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients.,Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models.,Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells.,None of the TLR4 SNPs was associated with FEV1 level.,Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time.,This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD. | Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear.,Induced sputum was obtained from adults with COPD (n = 22), and healthy controls (n = 29) and was processed for differential cell counts.,The sputum supernatant was assayed for innate immune mediators using ELISA, whilst sputum gene expression was measured using real-time PCR.,Peripheral blood neutrophils were isolated and their response to lipopolysaccaride (LPS) stimulation was assessed in a subgroup of participants with COPD (n = 13) and healthy controls (n = 21).,Participants with COPD had significantly higher protein levels of interleukin (IL)-8, and neutrophil elastase (NE) and detection of oncostatin M (OSM) compared to healthy controls.,Gene expression for toll-like receptor (TLR) 2, IL-8 and OSM were also significantly higher in COPD participants.,The level of IL-1β, surfactant protein (SP)-A, matrix metalloproteinase (MMP)-9 and TLR4 mRNA was not significantly different between groups.,The level of innate immune response markers were highly associated with the presence of sputum neutrophils, each other and the degree of airflow limitation (FEV1/FVC).,Peripheral blood neutrophils from participants with COPD had an increased response to stimulation by LPS; with a greater fold increase in the production of IL-8 and MMP-9 protein, and gene expression of IL-8, TLR2 and TLR4.,The innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis. | 1 |
Acute exacerbations are a leading cause of worsening COPD in terms of lung function decline, quality of life, and survival.,They also have a relevant economic burden on the health care system.,Determining the risk factors for acute exacerbation and early relapse could be a crucial element for a better management of COPD patients.,This review analyzes the current knowledge and underlines the main risk factors for recurrent acute exacerbations.,Comprehensive evaluation of COPD patients during stable phase and exacerbation could contribute to prevent treatment failure and relapses. | Chronic obstructive pulmonary disease (COPD) can greatly impact the quality of life by limiting patients’ activities.,However, data on impact of symptomatic burden on the health care resource utilization (HCRU) and employment in COPD are lacking.,We examined the association between COPD Assessment Test (CAT) score and direct/indirect costs associated with HCRU and work productivity.,Data from >2,100 patients with COPD consulting for routine care were derived from respiratory disease-specific programs in Europe, the USA and China.,Questionnaires, including CAT and Work Productivity and Activity Impairment (WPAI), were used to collect the past and current disease status data and HCRU characteristics from physicians (general practitioners/specialists) and patients.,A regression approach was used to quantify the association of CAT with HCRU and WPAI variables.,CAT score was modeled as a continuous independent variable (range: 0-40).,Ninety percent of patients with COPD had a CAT score ≥10.,Short-acting therapy and maintenance bronchodilator monotherapy, respectively, were currently prescribed to patients with CAT scores of 10-19 (5.8% and 27.6%), 20-29 (5.1% and 13.1%) and 30-40 (2.8% and 6.6%).,Prescribing of maintenance bronchodilator dual therapy was low across the CAT score groups (0-9, 7.8%; 10-19, 6.4%; 20-29, 5.9%; 30-40, 4.4%), whereas maintenance triple combination therapy was prescribed more commonly in patients with higher CAT scores (0-9, 16.1%; 10-19, 23.2%; 20-29, 25.9%; 30-40, 35.5%).,Increasing CAT scores were significantly associated with a higher frequency of primary care physician visits (P<0.001), pulmonologist visits (P=0.007), exacerbations requiring hospitalization (P<0.001) and WPAI scores (P<0.001).,Most patients with COPD presented with high symptom levels, despite being treated for COPD.,Increasing symptom burden was associated with increasing HCRU and had a detrimental impact on work productivity. | 1 |
Serum D-dimer is elevated in respiratory disease.,The objective of our study was to investigate the effect of D-dimer on in-hospital and 1-year mortality after acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Upon admission, we measured 343 AECOPD patients’ serum D-dimer levels and arterial blood gas analysis, and recorded their clinical characteristics.,The level of D-dimer that discriminated survivors and non-survivors was determined using a receiver operator curve (ROC).,The risk factors for in-hospital mortality were identified through univariate analysis and multiple logistic regression analyses.,To evaluate the predictive role of D-dimer for 1-year mortality, univariate and multivariate Cox regression analyses were performed.,In all, 28 patients died, and 315 patients survived in the in-hospital period.,The group of dead patients had lower pH levels (7.35±0.11 vs 7.39±0.05, P<0.0001), higher D-dimer, arterial carbon dioxide tension (PaCO2), C-reactive protein (CRP), and blood urea nitrogen (BUN) levels (D-dimer 2,244.9±2,310.7 vs 768.2±1,078.4 µg/L, P<0.0001; PaCO2: 58.8±29.7 vs 46.1±27.0 mmHg, P=0.018; CRP: 81.5±66, P=0.001; BUN: 10.20±6.87 vs 6.15±3.15 mmol/L, P<0.0001), and lower hemoglobin levels (118.6±29.4 vs 128.3±18.2 g/L, P=0.001).,The areas under the ROC curves of D-dimer for in-hospital death were 0.748 (95% confidence interval (CI): 0.641-0.854).,D-dimer ≥985 ng/L was a risk factor for in-hospital mortality (relative risk =6.51; 95% CI 3.06-13.83).,Multivariate logistic regression analysis also showed that D-dimer ≥985 ng/L and heart failure were independent risk factors for in-hospital mortality.,Both univariate and multivariate Cox regression analyses showed that D-dimer ≥985 ng/L was an independent risk factor for 1-year death (hazard ratio (HR) 3.48, 95% CI 2.07-5.85 for the univariate analysis; and HR 1.96, 95% CI 1.05-3.65 for the multivariate analysis).,D-dimer was a strong and independent risk factor for in-hospital and 1-year death for AECOPD patients. | Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high.,The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care.,We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools.,The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014.,Consecutive admissions were identified by screening admissions and searching coding records.,Admission clinical data, including DECAF indices, and mortality were recorded.,The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve.,In the internal and external validation cohorts, 880 and 845 patients were recruited.,Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted.,Overall mortality was 7.7%.,The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality.,DECAF is a robust predictor of mortality, using indices routinely available on admission.,Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0-1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3-6) for escalation planning or appropriate early palliation.,UKCRN ID 14214. | 1 |
Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD).,This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone.,This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2).,A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George’s Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation.,Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy.,Adverse events (AEs) were also assessed.,Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818).,Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001).,Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population.,No significant reduction in risk of a SGRQ CID was observed.,AE incidence was similar between treatment groups.,Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations.,Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.,GlaxoSmithKline (study number: 202067).,Plain language summary available for this article.,The online version of this article (10.1007/s12325-018-0771-4) contains supplementary material, which is available to authorized users. | Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases with high morbidity and mortality.,It has become the fifth most burdened and the third most deadly disease in the global economy and increases year by year.,The prevention and treatment of COPD are urgent.,Smoking is the main and most common risk factor for COPD.,Cigarette smoke (CS) contains a large number of toxic substances, can cause a series of changes in the trachea, lung tissue, pulmonary blood vessels, and promotes the occurrence and development of COPD.,In recent years, the development of epigenetics and molecular biology have provided new guidance for revealing the pathogenesis, diagnosis, and treatment of diseases.,The latest research indicates that pulmonary vascular endothelial cell apoptosis initiates and participates in the pathogenesis of COPD.,In this review, we summarize the current research on the epigenetic mechanisms and molecular biology of CS-induced pulmonary vascular endothelial cell apoptosis in COPD, providing a new research direction for pathogenesis of COPD and a new target for the diagnosis, treatment, and prevention of COPD. | This study aimed to explore the relation between lymphocyte to high-density lipoprotein ratio (LHR) and pulmonary function of chronic obstructive pulmonary disease (COPD) patients compared with neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR).,In total, 154 participants (n = 77 with COPD and n = 77 without COPD) were recruited.,LHR, NLR, PLR, lung function and other data were collected and compared.,Pearson’s correlation test and the receiver operating characteristics curves were used to compare the utility of LHR, NLR and PLR.,Besides, univariate and multivariate logistic regression analyses were conducted.,COPD patients with poorer lung function had a lower LHR level (P < 0.001).,In low LHR group, more patients underwent greater airflow limitation than the other group (P = 0.006).,LHR positively correlated with forced expiratory volume in 1 second in percent of the predicted value (FEV1%) (r = 0.333, P = 0.003).,At a cut-off value of 2.08, the sensitivity and specificity of LHR in predicting FEV1% < 50 were 93.2% and 55.6%, respectively, with an AUC of 0.770 (P = 0.001) better than NLR and PLR.,Based on logistic regression analyses, it was proved that LHR was associated with decreased risk of FEV1 <50% predicted in COPD patients (odds ratio = 0.198, 95% CI: 0.048-0.811, P = 0.024).,In contrast with NLR and PLR, LHR has higher accuracy for predicting pulmonary function in COPD; lower LHR level is independently associated with poorer pulmonary function. | 1 |
Case finding of patients at risk of COPD by community pharmacists could identify a substantial number of people with undiagnosed COPD, but little is known about the feasibility and effectiveness of pharmacy-based COPD case finding using microspirometry.,The objective of this study was to assess the feasibility and effectiveness of COPD case-finding service provided by community pharmacists, utilizing a combination of risk assessment questionnaire and microspirometry.,A 6-month service was conducted in 21 community pharmacies in Australia.,Pharmacists trained in COPD case finding, including lung function test (LFT), invited their patients aged ≥35 years with a history of smoking and/or respiratory symptoms to participate.,High-risk patients were identified via a COPD risk assessment questionnaire (Initial Screening Questionnaire [ISQ]) and underwent LFT.,Pharmacists referred patients with a forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio <0.75 to their general practitioner (GP) for further assessment and diagnosis.,In all, 91 of 167 (54%) patients had an ISQ score >3 indicating high COPD risk.,Of the 157 patients who were able to complete LFT, 61 (39%) had an FEV1/FEV6 ratio of <0.75 and were referred to their GP.,Patients with high ISQ symptoms scores (>3) were at a significantly higher risk of an FEV1/FEV6 ratio of <0.75, compared to patients with fewer COPD symptoms.,A total of 15 (10%) patients were diagnosed with COPD by their GP.,Another eight (5%) patients were diagnosed with other medical conditions and 87% of these were initiated on treatment.,Although only half of all screened patients lived in regional areas, 93% of those diagnosed with COPD were from regional areas.,A brief community pharmacy-based COPD case-finding service utilizing the ISQ, LFT and GP referral is feasible and may lead to identification and diagnosis of a substantial number of people with COPD.,This might be an important strategy for reducing the burden of COPD, particularly for those living in rural locations. | The disease burden is increasing for chronic obstructive pulmonary disease (COPD) due to increasing of the growth rate of prevalence and mortality.,But the empirical researches are a little for COPD that studied the association between continuity of care and death and about predictors effect on mortality.,To investigate the association between continuity of care (COC) and chronic obstructive pulmonary disease (COPD) mortality and to identify other mortality-related factors in COPD patients.,We conducted a longitudinal, population-based retrospective cohort study in adult patients with COPD from 2002 to 2012 using a nationwide health insurance claims database.,The study sample included individuals aged 40 years and over who developed COPD in 2005 and survived until 2006.,We performed a Cox proportional hazard regression analysis with COC analyzed as a time-dependent covariate.,Of the 3,090 participants, 60.8% died before the end of study (N = 1,879).,The median years of survival for individuals with high COC (COC index≥0.75) was 3.92, and that for patients with low COC (COC index<0.75) was 2.58 in a Kaplan Meier analysis.,In a multivariate, time-dependent analysis, low COC was associated with a 22% increased risk of all-cause mortality (HR, 1.22; 95% CI, 1.09-1.36).,Not receiving oxygen therapy at home was associated with a 23% increased risk of all-cause mortality (HR, 1.23; 95% CI, 1.01-1.49).,Moreover, the risk of all-cause mortality for individuals who admitted one time increased 38% (HR, 1.38; 95% CI, 1.21-1.59), two times was 63% (HR, 1.63; 95% CI, 1.34-1.99) and 3+ times was 96% (HR, 1.96; 95% CI, 1.63-2.36) relative to the reference group (no admission).,High COC was associated with a decreased risk of all-cause mortality.,In addition, home oxygen therapy and number of hospital admissions may predict mortality in patients with COPD. | 1 |
Extracellular matrix (ECM) creates the tissue microenvironment and serves a role in airway wall remodeling in chronic obstructive pulmonary disease (COPD).,However, the biological function of ECM in COPD remains to be elucidated.,In the present study, 24 healthy Sprague Dawley rats were randomized to normal and COPD groups.,COPD was established by intratracheal injection with lipopolysaccharide over 30 days.,Subsequently, airway smooth muscle cells (ASMCs) were isolated from rats and served as a model to assess the effects of three ECM components, including collagen type I, laminin and collagen type III (COL-3).,Functional analysis in vitro, using cell counting kit-8, flow cytometry, wound healing and cell adhesion assays indicated that the ECM components could promote cell proliferation, cell cycle progression, migration and adhesion ability, respectively.,Furthermore, as demonstrated by ELISA, treatment with ECM components increased levels of C-X-C motif chemokine ligand 1 (CXCL1), CXCL8 and interleukin-6 in ASMCs.,Expression of transforming growth factor β1 (TGFβ1), fibroblast growth factor-1 (FGF-1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was increased, and expression of matrix metalloproteinase-9 (MMP-9) was decreased following treatment with ECM components, as demonstrated by reverse transcription-quantitative polymerase chain reaction and western blot analysis.,Additionally, specific activation of phosphoinositide 3-kinase (PI3K) signaling, using insulin-like growth factor-1 (IGF-1), promoted cell proliferation and cell cycle progression, increased expression of TGFβ1, FGF-1, PI3K, AKT, phospho-AKT, serine/threonine-protein kinase mTOR (mTOR), phospho-mTOR and TIMP1, promoted cell migration capacity and reduced the expression level of MMP-9 in cells from COPD rats.,Consistently, PI3K inhibitor LY294002 exerted the opposite effect to IGF-1.,In conclusion, ECM proteins promoted proliferation, migration and adhesion of ASMCs form rat models of COPD through activation of the PI3K/AKT signaling pathway. | Individuals with severe Z α1-antitrypsin (AAT) deficiency have a considerably increased risk of developing chronic obstructive lung disease (COPD).,It has been hypothesized that compensatory increases in levels of other protease inhibitors mitigate the effects of this AAT deficiency.,We analysed plasma levels of AAT, α1-antichymotrypsin (ACT) and secretory leukocyte protease inhibitor (SLPI) in healthy (asymptomatic) and COPD subjects with and without AAT deficiency.,Studied groups included: 71 asymptomatic AAT-deficient subjects (ZZ, n = 48 and SZ, n = 23, age 31 ± 0.5) identified during Swedish neonatal screening for AAT deficiency between 1972 and 1974; age-matched controls (MM, n = 57, age 30.7 ± 0.6); older asymptomatic ZZ (n = 10); healthy MM (n = 20, age 53 ± 9.6); and COPD patients (ZZ, n = 10, age 47.4 ± 11 and MM, n = 10, age 59.4 ± 6.7).,Plasma levels of SLPI, AAT and ACT were analysed using ELISA and immunoelectrophoresis.,No significant difference was found in plasma ACT and SLPI levels between the healthy MM and the ZZ or SZ subjects in the studied groups.,Independent of the genetic variant, subjects with COPD (n = 19) had elevated plasma levels of SLPI and ACT relative to controls (n = 153) (49.5 ± 7.2 vs 40.7 ± 9.1 ng/ml, p < 0.001 and 0.52 ± 0.19 vs 0.40 ± 0.1 mg/ml, p < 0.05, respectively).,Our findings show that plasma levels of ACT and SLPI are not elevated in subjects with genetic AAT deficiency compared MM controls and do not appear to compensate for the deficiency of plasma AAT. | 1 |
Autoimmunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD).,Studies have identified disease-specific autoantibodies (DSAAbs) in COPD patients, but natural autoantibodies (NAAbs) may also play a role.,Previous studies have concentrated on circulating autoantibodies, but lung-associated autoantibodies may be most important.,Our aim was to investigate NAAbs and DSAAbs in the circulation and lungs of COPD smoking (CS) patients compared to smokers (S) without airway obstruction and subjects who have never smoked (NS).,Immunoglobulin (Ig)G antibodies that bind to lung tissue components were significantly lower in the circulation of CS patients than NS (with intermediate levels in S), as detected by enzyme-linked immunosorbent assay (ELISA).,The levels of antibodies to collagen-1 (the major lung collagen) detected by ELISA were also reduced significantly in CS patients’ sera compared to NS.,The detection of these antibodies in NS subjects indicates that they are NAAbs.,The occurrence of DSAAbs in some CS patients and S subjects was indicated by high levels of serum IgG antibodies to cytokeratin-18 and collagen-5; furthermore, antibodies to collagen-5 eluted from homogenized lung tissue exposed to low pH (0·1 M glycine, pH 2·8) were raised significantly in CS compared to S and NS.,Thus, this study supports a role in COPD for both NAAbs and DSAAbs. | Chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases of mucosal tissues that affect the respiratory and gastrointestinal tracts, respectively.,They share many similarities in epidemiological and clinical characteristics as well as inflammatory pathologies.,Importantly, both conditions are accompanied by systemic co-morbidities that are largely overlooked in both basic and clinical research.,Therefore, consideration of these complications may maximise the efficacy of prevention and treatment approaches.,Here, we examine both the intestinal involvement in COPD and the pulmonary manifestations of IBD.,We also review the evidence for inflammatory organ cross-talk that may drive these associations, and discuss the current frontiers of research into these issues. | 1 |
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases.,The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid.,An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid).,The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population.,Patients were deemed to have COPD if this diagnosis appeared on their clinical histories.,Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated.,Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%).,After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity.,Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs. | 1 |
The increasing prevalence of chronic diseases requires changes in health care delivery.,In COPD, telemedicine appears to be a useful tool.,Our objective was to evaluate the efficacy (in improving health care-resource use and clinical outcomes) of a telemonitoring-based program (telEPOC) in COPD patients with frequent hospitalizations.,We conducted a nonrandomized observational study in an intervention cohort of 119 patients (Galdakao-Usansolo Hospital) and a control cohort of 78 patients (Cruces Hospital), followed up for 2 years (ClinicalTrials.gov identifier: NCT02528370).,The inclusion criteria were two or more hospital admissions in the previous year or three or more admissions in the previous 2 years.,The intervention group received telemonitoring plus education and controls usual care.,Most participants were men (13% women), and the sample had a mean age of 70 years, forced expiratory volume in 1 second of 45%, Charlson comorbidity index score of 3.5, and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index score of 4.1.,In multivariate analysis, the intervention was independently related to lower rates of hospital admission (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.27-0.54; P<0.0001), emergency department attendance (OR 0.56, 95% CI 0.35-0.92; P<0.02), and 30-day readmission (OR 0.46, 95% CI 0.29-0.74; P<0.001), as well as cumulative length of stay (OR 0.58, 95% CI 0.46-0.73; P<0.0001).,The intervention was independently related to changes in several clinical variables during the 2-year follow-up.,An intervention including telemonitoring and education was able to reduce the health care-resource use and stabilize the clinical condition of frequently admitted COPD patients. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
In recent years, the pleiotropic roles of vitamin D have been highlighted in various diseases.,However, the association between serum vitamin D and COPD is not well studied.,This updated systematic review and meta-analysis aimed to assess the relationship between vitamin D and the risk, severity, and exacerbation of COPD.,A systematic literature search was conducted in PubMed, Medline, EMBASE, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases.,The pooled risk estimates were standardized mean difference (SMD) with 95% confidence interval (CI) for vitamin D levels and odds ratio (OR) with 95% CI for vitamin D deficiency.,Meta-regression and subgroup analyses were performed on latitude, body mass index, and assay method.,A total of 21 studies, including 4,818 COPD patients and 7,175 controls, were included.,Meta-analysis showed that lower serum vitamin D levels were found in COPD patients than in controls (SMD: −0.69, 95% CI: −1.00, −0.38, P<0.001), especially in severe COPD (SMD: −0.87, 95% CI: −1.51, −0.22, P=0.001) and COPD exacerbation (SMD: −0.43, 95% CI: −0.70, −0.15, P=0.002).,Vitamin D deficiency was associated with increased risk of COPD (OR: 1.77, 95% CI: 1.18, 2.64, P=0.006) and with COPD severity (OR: 2.83, 95% CI: 2.00, 4.00, P<0.001) but not with COPD exacerbation (OR: 1.17, 95% CI: 0.86, 1.59, P=0.326).,Assay methods had significant influence on the heterogeneity of vitamin D deficiency and COPD risk.,Serum vitamin D levels were inversely associated with COPD risk, severity, and exacerbation.,Vitamin D deficiency is associated with increased risk of COPD and severe COPD but not with COPD exacerbation.,It is worth considering assay methods in the heterogeneity sources analysis of association between vitamin D deficiency and COPD. | Exacerbations are a leading cause of morbidity in COPD.,The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD).,We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls.,Individual metabolites were measured via selective reaction monitoring with mass spectrometry.,We used a mixed-effect model to compare metabolite levels in cases compared to controls and a paired t-test to test for differences between days 0 and 30 in the AECOPD group.,We identified 377 analytes at a false discovery rate of 5% that differed between cases (day 0) and controls, and 31 analytes that differed in the AECOPD cases between day 0 and day 30 (false discovery rate: 5%).,Tryptophan was decreased at day 0 of AECOPD compared to controls corresponding to an increase in indoleamine 2,3-dioxygenase activity.,Patients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consistent with an increase in indoleamine 2,3-dioxygenase activity. | 1 |
Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs.,Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet.,We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade.,Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke.,The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied.,However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between.,Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively.,Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. | There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients.,We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.,We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.,Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.,Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively).,Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05).,Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads.,Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs.,No association was observed between inflammation and health status (p > 0.05).,Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique.,The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae.,However, discordance between inflammation and health status was observed.,The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. | 1 |
Heme oxygenase 1 (HMOX1) plays an important role in the development of chronic obstructive pulmonary disease (COPD).,However, the association of HMOX1 length polymorphism in promoter region to the risk and severity of COPD has not been well studied.,In this study, we searched the databases including PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) and extracted the information from related articles.,Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to study the effect of HMOX1 polymorphism on the risk and severity of COPD.,As a result, nine studies were included for this meta‐analysis.,Higher frequencies of L allele and type I genotype (containing at least one L allele) were found in patients with COPD (for L allele, OR 2.02, 95% CI: 1.32-3.11, P = 0.001; for type I genotype, OR 1.82, 95% CI: 1.28-2.61, P = 0.001), especially in Asian population (for L allele, OR 2.23, 95% CI: 1.68-2.95, P < 0.001; for type I genotype, OR 2.02, 95% CI: 1.51-2.70, P < 0.001).,Genotyping method, source of control subjects, literature quality and language also affected the results to some extent.,However, there was little difference in HMOX1 genotypes distribution in patients with COPD with different severity.,Our study indicated L allele and type I genotype were related to the susceptibility but not the severity of COPD. | Chronic bronchitis (CB) is one of the classic phenotypes of COPD.,The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population.,We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE).,CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years.,CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry.,Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls.,Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis.,For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A.,In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7).,We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6).,This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD.,ClinicalTrials.gov NCT00608764, NCT00292552,The online version of this article (doi:10.1186/s12931-014-0113-2) contains supplementary material, which is available to authorized users. | 1 |
COPD exacerbations have negative impact on patients’ survival.,Several risk factors for grave outcomes of such exacerbations have been descried.,Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival.,Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival.,This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation.,Included were 232 consecutive COPD exacerbation patients.,The median time of follow-up was 34.9 months (IQR 23.13-41.73 months).,During this period 104 (44.8%) patients died.,All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)).,The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached.,For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p < 0.001 for comparison of lower quartile with upper three quartiles).,The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6-3.5).,This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08-3.1, p < 0.05).,Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation. | 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. | 1 |
Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.,The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III.,Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months.,The primary outcome was the number of acute exacerbations during the study.,In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus.,1.13 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.002).,No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group.,Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023).,Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.,In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations.,The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.,RESTORE study: erdosteine reduces both rate and duration of COPD exacerbations with a placebo-like safety profilehttp://ow.ly/BbGI30dRdEt | 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 |
Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer.,Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD.,Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer.,However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.,The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms.,Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD.,We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers.,RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT.,Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers.,Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group.,Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro.,The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells.,Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression.,Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling.,In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-catenin signaling.,These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.,The online version contains supplementary material available at 10.1186/s12931-021-01881-y. | Disease-specific alterations of the cell-free DNA methylation status are frequently found in serum samples and are currently considered to be suitable biomarkers.,Candidate markers were identified by bisulfite conversion-based genome-wide methylation screening of lung tissue from lung cancer, fibrotic ILD, and COPD. cfDNA from 400 μl serum (n = 204) served to test the diagnostic performance of these markers.,Following methylation-sensitive restriction enzyme digestion and enrichment of methylated DNA via targeted amplification (multiplexed MSRE enrichment), a total of 96 markers were addressed by highly parallel qPCR.,Lung cancer was efficiently separated from non-cancer and controls with a sensitivity of 87.8%, (95%CI: 0.67-0.97) and specificity 90.2%, (95%CI: 0.65-0.98).,Cancer was distinguished from ILD with a specificity of 88%, (95%CI: 0.57-1), and COPD from cancer with a specificity of 88% (95%CI: 0.64-0.97).,Separation of ILD from COPD and controls was possible with a sensitivity of 63.1% (95%CI: 0.4-0.78) and a specificity of 70% (95%CI: 0.54-0.81).,The results were confirmed using an independent sample set (n = 46) by use of the four top markers discovered in the study (HOXD10, PAX9, PTPRN2, and STAG3) yielding an AUC of 0.85 (95%CI: 0.72-0.95).,This technique was capable of distinguishing interrelated complex pulmonary diseases suggesting that multiplexed MSRE enrichment might be useful for simple and reliable diagnosis of diverse multifactorial disease states.,•The multiplexed MSRE enrichment strategy allowed a highly parallel assessment the cfDNA methylation status based on 400 μl of patient serum.,•The multivariate classification of the discovered biomarkers, thus, stabilized the prediction and allowed for differential diagnosis.,•This method including the biomarker set may be used to monitor the lung cancer risk in COPD and fibrotic ILD patients.,The multiplexed MSRE enrichment strategy allowed a highly parallel assessment the cfDNA methylation status based on 400 μl of patient serum.,The multivariate classification of the discovered biomarkers, thus, stabilized the prediction and allowed for differential diagnosis.,This method including the biomarker set may be used to monitor the lung cancer risk in COPD and fibrotic ILD patients.,We developed a multiplexed DNA methylation profiling strategy to track disease specific DNA methylation changes prevailing in 400 μl serum of lung cancer, fibrotic ILD and COPD patients.,Plasma or serum samples, often referred to as ‘liquid biopsies’ have several advantages over tissue sampling: (a) they are easily accessible, (b) are not subject to biopsy bias and (c) can be repeatedly drawn from the same patient.,The differential diagnosis attempt performed in the study on patients suffering from different lung diseases suggests that multiplexed cfDNA methylation profiling allows for the capture of these interconnected disease phenotypes, stabilizes the prediction and enhances diagnostic accuracy. | 1 |
Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD) has been controversial.,Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD.,We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD.,Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies.,Publication bias was assessed using a funnel plot.,Our search identified nine retrospective cohort studies that met the study inclusion criteria.,The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%).,The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality.,Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded.,The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials. | Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD).,Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.,A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000-2001.,Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained.,Information on long-term mortality was obtained from national registries in each of the Nordic countries.,In total, 202 patients (79%) died during the follow up period, whereas 54 (21%) were still alive.,Primary cause of death was respiratory (n = 116), cardiovascular (n = 43), malignancy (n = 28), other (n = 10), or unknown (n = 5).,Mortality was related to older age, with a hazard risk ratio (HRR) of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1) (HRR 0.80), body mass index (BMI) <20 kg/m2 (HRR 3.21), and diabetes (HRR 3.02).,Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality.,An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.,Almost four out of five patients died within 9 years following an admission for COPD exacerbation.,Increased mortality was associated with older age, lower lung function, low BMI, and diabetes, and these factors should be taken into account when making clinical decisions about patients who have been admitted to hospital for a COPD exacerbation. | 1 |
Chronic obstructive pulmonary disease (COPD) is among the leading causes of morbidity and mortality worldwide, but longitudinal studies of the economic consequences of COPD are scarce.,This Danish study evaluated for the first time ever the economic consequences of COPD of an entire nation before and after the diagnosis.,Records from the Danish National Patient Registry (1998-2010), direct and indirect costs, including frequency of primary and secondary sector contacts and procedures, medication, unemployment benefits and social transfer payments were extracted from national databases.,131 811 patients with COPD were identified and compared with 131 811 randomly selected controls matched for age, gender, educational level, residence and marital status.,Direct and indirect economic and health consequences of COPD in Denmark in the time period 1998-2010.,Patients with COPD had a poor survival.,The average (95% CI) 12-year survival rate was 0.364 (0.364 to 0.368) compared with 0.686 among controls (0.682 to 0.690).,COPD was associated with significantly higher rates of health-related contacts, medication use and higher socioeconomic costs.,The employment and the income rates of employed patients with COPD were significantly lower compared with controls.,The annual net costs, including social transfers were €8572 for patients with COPD.,These consequences were present up to 11 years before first-time diagnosis in the secondary healthcare sector and became more pronounced with disease advancement.,This study provides unique national data on direct and indirect costs before and after initial diagnosis with COPD in Denmark as well as mortality, health and economic consequences for the individual and for society.,It could be speculated that early identification and intervention might contribute to the solution. | Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system. | 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. | 1 |
Neutrophil elastase, metalloproteinases, and their inhibitors play an important role in the development of chronic obstructive pulmonary disease (COPD), resulting in extensive tissue damage and malfunctioning of the airways.,Nearly fifty years after the protease-antiprotease imbalance hypothesis has been suggested for the cause of emphysema, it is still appealing, but it does not explain the considerable variation in the clinical expressions of emphysema.,However, there are many recent research findings to support the imbalance hypothesis as will be shown in this review.,Although limited, there might be openings for the treatment of the disease. | The incidence and severity of chronic lung diseases is growing and affects between 100 and 150 million people worldwide and is associated with a significant rate of mortality.,Unfortunately, the initial cause that triggers most chronic lung diseases remains unknown and current available therapies only ameliorate, but do not cure the disease.,Thus, there is a need for identification of new targets and development of novel therapies especially for those most severely affected.,IL-6, like other inflammatory cytokines, has been shown to be elevated in different lung diseases, but it was considered a byproduct of ongoing inflammation in the lung.,However, recent studies support a dissociation of IL-6 from inflammation in the lung and suggest that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD.,IL-6 may therefore be a germane target for treatment of these and other chronic lung disease.,Here, we provide an overview of the studies in mouse models and human patients that provide support for the involvement of IL-6 in lung diseases. | 1 |
The relationship between chronic obstructive pulmonary disease (COPD) and diabetes remains incompletely understood.,This study evaluated diabetes risk and post-diabetes outcomes in COPD patients with and without exacerbations.,We identified 4671 adults newly diagnosed with COPD exacerbations and 9342 adults newly diagnosed with COPD without exacerbations during 2000-2008 using Taiwan’s National Health Insurance Research Database.,A comparison cohort of 18684 adults without COPD, matched by age and sex, was randomly selected from the same dataset for the control group.,Diabetes events during 2000-2013 were ascertained from medical claims during the follow-up period.,Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes associated with COPD with or without exacerbations were calculated.,We conducted another nested cohort study of 395516 patients with diabetes hospitalization during 2002-2013 and calculated adjusted odds ratios (ORs) and 95% CIs of histories of COPD and COPD exacerbations associated with adverse events after diabetes admission.,During the follow-up period, the incidences of diabetes for patients without COPD and for patients with COPD without or with exacerbations were 3.4, 4.1 and 7.4 per 1000 person-years, respectively (P < 0.0001).,Increased risk of diabetes for patients with COPD without exacerbations (HR 1.09, 95% CI 1.02-1.17) and COPD with exacerbations (HR 2.18, 95% CI 1.88-2.52) was noted.,Post-diabetes pneumonia (OR 3.28, 95% CI 3.13-3.43), intensive care admission (OR 1.32, 95% CI 1.26-1.39) and mortality (OR 2.06, 95% CI 1.88-2.25) were associated with COPD exacerbations.,Prevention and intervention strategies for diabetes and post-diabetes outcomes are needed for this susceptible population. | Chronic obstructive pulmonary disease (COPD) is a chronic, irreversible disease and a leading cause of worldwide morbidity and mortality.,In Canada, COPD is the fourth leading cause of death.,This systematic review was undertaken to update healthcare professionals and decision makers regarding the recent clinical, humanistic and economic burden evidence in Canada.,A systematic literature search was conducted in PubMed, EMBASE, and Cochrane databases to identify original research published January 2000 through December 2012 on the burden of COPD in Canada.,Each search was conducted using controlled vocabulary and key words, with “COPD” as the main search concept and limited to Canadian studies, written in English and involving human subjects.,Selected studies included randomized controlled trials, observational studies and systematic reviews/meta-analyses that reported healthcare resource utilization, quality of life and/or healthcare costs.,Of the 972 articles identified through the literature searches, 70 studies were included in this review.,These studies were determined to have an overall good quality based on the quality assessment.,COPD patients were found to average 0-4 annual emergency department visits, 0.3-1.5 annual hospital visits, and 0.7-5 annual physician visits.,Self-care management was found to lessen the overall risk of emergency department (ED) visits, hospitalization and unscheduled physician visits.,Additionally, integrated care decreased the mean number of hospitalizations and telephone support reduced the number of annual physician visits.,Overall, 60-68 % of COPD patients were found to be inactive and 60-72 % reported activity restriction.,Pain was found to negatively correlate with physical activity while breathing difficulties resulted in an inability to leave home and reduced the ability to handle activities of daily living.,Evidence indicated that treating COPD improved patients’ overall quality of life.,The average total cost per patient ranged between CAN $2444-4391 from a patient perspective to CAN $3910-6693 from a societal perspective.,Furthermore, evidence indicated that COPD exacerbations lead to higher costs.,The clinical, humanistic and economic burden of COPD in Canada is substantial.,Use of self-care management programs, telephone support, and integrated care may reduce the overall burden to Canadian patients and society. | 1 |
Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries.,However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown.,This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE.,The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE.,Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks.,Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded.,The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494.,The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications.,Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries.,There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD.,The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE. | We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. | 1 |
Little is known regarding the relationship between balance impairments and physical activity in COPD.,There has been no study investigating the relationship between balance and objectively measured physical activity.,Here we investigated the association between balance and physical activity measured by an activity monitor in elderly COPD patients.,Twenty-two outpatients with COPD (mean age, 72±7 years; forced expiratory volume in 1 second, 53%±21% predicted) and 13 age-matched healthy control subjects (mean age, 72±6 years) participated in the study.,We assessed all 35 subjects’ balance (one-leg standing test [OLST] times, Short Physical Performance Battery total scores, standing balance test scores, 4 m gait speed, and five-times sit-to-stand test [5STST]) and physical activity (daily steps and time spent in moderate-to-vigorous physical activity per day [MV-PA]).,Possible confounders were assessed in the COPD group.,The between-group differences in balance test scores and physical activity were analyzed.,A correlation analysis and multivariate regression analysis were conducted in the COPD group.,The COPD patients exhibited significant reductions in OLST times (P=0.033), Short Physical Performance Battery scores (P=0.013), 4 m gait speed (P<0.001), five-times sit-to-stand times (P=0.002), daily steps (P=0.003), and MV-PA (P=0.022) compared to the controls; the exception was the standing balance test scores.,The correlation and multivariate regression analyses revealed significant independent associations between OLST times and daily steps (P<0.001) and between OLST times and MV-PA (P=0.014) in the COPD group after adjusting for possible confounding factors.,Impairments in balance and reductions in physical activity were observed in the COPD group.,Deficits in balance are independently associated with physical inactivity. | Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction.,Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies.,Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD.,Participants were recruited from all 48 contiguous U.S. states by random digit dialing.,Lifetime ETS exposure was ascertained by structured telephone interview.,We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD.,Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD.,The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21).,The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84).,The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure.,ETS exposure may be an important cause of COPD.,Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure. | 1 |
Long-acting muscarinic antagonist/long-acting β2-agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy.,We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI).,This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD (NCT01085045).,Treatments included GFF MDI twice daily (BID) (GP/FF 72/9.6 μg or 36/9.6 μg), GP MDI 36 μg BID, FF MDI 7.2 and 9.6 μg BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 μg BID or tiotropium DPI 18 μg once daily.,The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12) on Day 7 relative to baseline FEV1.,Secondary endpoints included pharmacokinetics and safety.,GFF MDI 72/9.6 μg or 36/9.6 μg led to statistically significant improvements in FEV1 AUC0-12 after 7 days’ treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p ≤ 0.0002).,GFF MDI 36/9.6 μg was non-inferior to GFF MDI 72/9.6 μg and monocomponent MDIs were non-inferior to open-label comparators.,Pharmacokinetic results showed glycopyrrolate and formoterol exposure were decreased following administration via fixed-dose combination versus monocomponent MDIs; however, this was not clinically meaningful.,GFF MDI was well tolerated.,GFF MDI 72/9.6 μg and 36/9.6 μg BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD.,ClinicalTrials.gov NCT01085045.,Registered 9 March 2010.,The online version of this article (doi:10.1186/s12931-016-0491-8) contains supplementary material, which is available to authorized users. | Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler. | 1 |
Self-management support is one mechanism by which telehealth interventions have been proposed to facilitate management of long-term conditions.,The objectives of this metareview were to (1) assess the impact of telehealth interventions to support self-management on disease control and health care utilization, and (2) identify components of telehealth support and their impact on disease control and the process of self-management.,Our goal was to synthesise evidence for telehealth-supported self-management of diabetes (types 1 and 2), heart failure, asthma, chronic obstructive pulmonary disease (COPD) and cancer to identify components of effective self-management support.,We performed a metareview (a systematic review of systematic reviews) of randomized controlled trials (RCTs) of telehealth interventions to support self-management in 6 exemplar long-term conditions.,We searched 7 databases for reviews published from January 2000 to May 2016 and screened identified studies against eligibility criteria.,We weighted reviews by quality (revised A Measurement Tool to Assess Systematic Reviews), size, and relevance.,We then combined our results in a narrative synthesis and using harvest plots.,We included 53 systematic reviews, comprising 232 unique RCTs.,Reviews concerned diabetes (type 1: n=6; type 2, n=11; mixed, n=19), heart failure (n=9), asthma (n=8), COPD (n=8), and cancer (n=3).,Findings varied between and within disease areas.,The highest-weighted reviews showed that blood glucose telemonitoring with feedback and some educational and lifestyle interventions improved glycemic control in type 2, but not type 1, diabetes, and that telemonitoring and telephone interventions reduced mortality and hospital admissions in heart failure, but these findings were not consistent in all reviews.,Results for the other conditions were mixed, although no reviews showed evidence of harm.,Analysis of the mediating role of self-management, and of components of successful interventions, was limited and inconclusive.,More intensive and multifaceted interventions were associated with greater improvements in diabetes, heart failure, and asthma.,While telehealth-mediated self-management was not consistently superior to usual care, none of the reviews reported any negative effects, suggesting that telehealth is a safe option for delivery of self-management support, particularly in conditions such as heart failure and type 2 diabetes, where the evidence base is more developed.,Larger-scale trials of telehealth-supported self-management, based on explicit self-management theory, are needed before the extent to which telehealth technologies may be harnessed to support self-management can be established. | 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 |
Pulmonary hypertension (PH) is a common complication of chronic respiratory disease.,Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae.,However, the association between DM and PH in chronic respiratory disease remains unclear.,In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease.,We prospectively analyzed 386 patients in our hospital with chronic respiratory disease.,An echocardiographic pressure gradient between the right atrium and the right ventricle of ≥ 40 mmHg was defined as PH.,We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH.,Of the 386 patients, 42 (10.9%) were diagnosed as having PH.,The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group.,Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients.,DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease. | Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions.,They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.,To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles.,Combined, they provide important information on development, progression and the end-stage disease.,In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance.,Comprehensive overview of compartment-specific microarray studies of material from pulmonary hypertension patientshttp://ow.ly/YEFO2 | 1 |
CD4+ T cells in the lung are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), although CD4+ T cell subsets and the direct effect of smoking on these cells, especially the expression of MRs, have not been comprehensively examined.,First, circulating CD4+ T cell subsets in healthy nonsmokers, patients with SCOPD and patients with AECOPD were evaluated by flow cytometry.,Then, differentiation experiments were carried out using RT-PCR, and Ki-67/Annexin V antibodies were used to measure proliferation and apoptosis.,We also explored the impact of CSE on the differentiation and survival of CD4+Th/Tregs and examined the expression of MRs in healthy nonsmokers and patients with SCOPD.,We found the percentages of circulating Th1 and Th17 cells were increased in patients with AECOPD, while the percentage of Th2 cells was decreased in patients with SCOPD.,The percentages of Th10 cells were decreased in both patients with SCOPD and patients with AECOPD, while the percentages of Tregs were increased.,In addition, the percentages of CD4+α-7+ T cells were decreased in patients with SCOPD and patients with AECOPD.,However, only the decrease observed in patients with AECOPD was significant.,In vitro studies also revealed MR expression affected the polarization of T cells, with different CD4+ T cell subtypes acquiring different MR expression profiles.,The addition of CSE facilitated CD4+ T cell polarization towards pro-inflammatory subsets (Th1 and Th17) and affected the survival of CD4+ T cells and Treg cells by up-regulating the expression of MR3 and 5, resulting in an imbalance of CD4+ T cell subsets.,Our findings suggest an imbalance of circulating CD4+ T cell subsets is involved in COPD pathogenesis in smokers.,Cigarette smoking may contribute to this imbalance by affecting the polarization and survival of Th/Tregs through the up-regulation of MR3 and MR5. | Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema.,In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations.,Six unused donor lungs served as controls.,Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1).,The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate.,The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09).,The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1).,An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05).,TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05).,A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r2 = 0.8).,A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r2 = 0.99),Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease.,The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease.,Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types. | 1 |
The use of information and communication technologies to manage chronic diseases allows the application of integrated care pathways, and the optimization and standardization of care processes.,Decision support tools can assist in the adherence to best-practice medicine in critical decision points during the execution of a care pathway.,The objectives are to design, develop, and assess a clinical decision support system (CDSS) offering a suite of services for the early detection and assessment of chronic obstructive pulmonary disease (COPD), which can be easily integrated into a healthcare providers' work-flow.,The software architecture model for the CDSS, interoperable clinical-knowledge representation, and inference engine were designed and implemented to form a base CDSS framework.,The CDSS functionalities were iteratively developed through requirement-adjustment/development/validation cycles using enterprise-grade software-engineering methodologies and technologies.,Within each cycle, clinical-knowledge acquisition was performed by a health-informatics engineer and a clinical-expert team.,A suite of decision-support web services for (i) COPD early detection and diagnosis, (ii) spirometry quality-control support, (iii) patient stratification, was deployed in a secured environment on-line.,The CDSS diagnostic performance was assessed using a validation set of 323 cases with 90% specificity, and 96% sensitivity.,Web services were integrated in existing health information system platforms.,Specialized decision support can be offered as a complementary service to existing policies of integrated care for chronic-disease management.,The CDSS was able to issue recommendations that have a high degree of accuracy to support COPD case-finding.,Integration into healthcare providers' work-flow can be achieved seamlessly through the use of a modular design and service-oriented architecture that connect to existing health information systems. | To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined.,Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature.,Existing knowledge such as genotype - phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data.,Different approaches to this challenge exist but so far none has proven entirely satisfactory.,To address this challenge we previously developed a generic knowledge management framework, BioXM™, which allows the dynamic, graphic generation of domain specific knowledge representation models based on specific objects and their relations supporting annotations and ontologies.,Here we demonstrate the utility of BioXM for knowledge management in systems biology as part of the EU FP6 BioBridge project on translational approaches to chronic diseases.,From clinical and experimental data, text-mining results and public databases we generate a chronic obstructive pulmonary disease (COPD) knowledge base and demonstrate its use by mining specific molecular networks together with integrated clinical and experimental data.,We generate the first semantically integrated COPD specific public knowledge base and find that for the integration of clinical and experimental data with pre-existing knowledge the configuration based set-up enabled by BioXM reduced implementation time and effort for the knowledge base compared to similar systems implemented as classical software development projects.,The knowledgebase enables the retrieval of sub-networks including protein-protein interaction, pathway, gene - disease and gene - compound data which are used for subsequent data analysis, modelling and simulation.,Pre-structured queries and reports enhance usability; establishing their use in everyday clinical settings requires further simplification with a browser based interface which is currently under development. | 1 |
Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. | This study was conducted to determine COPD severity at the time of diagnosis as confirmed by spirometry in patients treated in a US managed care setting.,All patients with one or more inpatient stays, one or more emergency department visits, or two or more outpatient visits with diagnosis codes for COPD during 1994-2006 were identified from the Lovelace Patient Database.,From this group, a subset of continuously enrolled patients with evidence in claims of a first available pulmonary function test or pulmonary clinic visit and a confirmatory claim for a COPD diagnosis was selected.,Medical chart abstraction was undertaken for this subset to gather information for diagnosis and severity staging of each patient based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD.,Of the 12,491 patients with a primary or secondary COPD diagnosis between 1994 and 2006, there were 1520 continuously enrolled patients who comprised the study cohort.,Among the 648 eligible records from patients with evidence of a pulmonary function test, 366 were identified by spirometry as having COPD of GOLD stage I or higher (average percentage of predicted forced expiratory volume in 1 second: 60%): 19% were diagnosed at the stage of mild disease (GOLD stage I); 50% at moderate disease (GOLD stage II); and 31% at severe or very severe disease (GOLD stage III or IV, respectively).,The majority of patients in these groups were not receiving maintenance treatment.,The results demonstrate a very low incidence of early-stage diagnosis, confirmed by a pulmonary function test, of COPD in a large US sample and support calls for increased screening for COPD and treatment upon diagnosis. | 1 |
Low adherence to Global initiative for chronic Obstructive Lung Disease (GOLD) guideline recommendations has been reported worldwide.,There has been no study on the adherence to GOLD guidelines for COPD treatment in Turkey.,To investigate the rates of adherence to GOLD 2010 guidelines for COPD treatment among pulmonologists.,A multi-center, cross-sectional, observational study was carried out in eleven pulmonary outpatient clinics across Turkey.,Adherence to GOLD was evaluated through hospital records.,Demographic and clinical data were recorded.,Study included 719 patients (mean age: 62.9±9.7 years; males 85.4%) of whom 16 was classified as GOLD Stage I, 238 as II, 346 as III, and 119 as IV, and only 59.5% received appropriate treatment.,Rates of guideline adherence varied across GOLD stages (I, 6.3%; II, 14.7%; III, 84.4%; and IV, 84%).,Causes of inappropriate therapies were overtreatment (Stage I, 100% and Stage II, 91.1%), undertreatment (Stage III, 3.3% and Stage IV, 10.9%) and lack of treatment (Stage II, 3.8%; Stage III, 2.3%; and Stage IV, 5.9%).,The most preferred regimen (43.4%) was long-acting β2-agonist-inhaled corticosteroid-long-acting muscarinic antagonist.,Overall, 614 patients (89%) received treatment containing inhaled corticosteroid.,Pulmonologists in Turkey have low rates of adherence to GOLD guidelines in COPD treatment.,Inappropriateness of therapies was due to overtreatment in early stages and excessive use of inhaled corticosteroid (ICS) in all disease stages. | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined.,We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function.,NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome.,Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation.,Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001).,This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002).,Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01).,Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes.,Consistent results were observed regardless of the method of quantifying sputum NETs.,Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD.,NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity. | Patients with COPD have an increased risk of cardiovascular disease.,Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated.,We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.,Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment.,In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined.,These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.,On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar.,The IL-6 was also increased (p < 0.05).,Twenty-two patients completed study assessments.,In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01).,Total cholesterol and ISWT also improved (p < 0.05).,On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.,Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD. | 1 |
Patients with high grade chronic pulmonary obstructive disease (COPD) account for much of the COPD-related mortality and incur excessive financial burdens and medical care utilization.,We aimed to determine the characteristics and medical care use of such patients using nationwide data from the Korean Health Insurance Review and Assessment Service in 2009.,Patients with COPD were identified by searching with the International Classification of Diseases-10th Revision for those using medication.,Patients with high grade COPD were selected based on their patterns of tertiary institute visits and medication use.,The numbers of patients with high grade COPD increased rapidly in Korea during the study period, and they showed a high prevalence of comorbid disease.,The total medical costs were over three times higher in patients with high grade COPD compared with those without it ($3,744 versus $1,183; P < 0.001).,Medication costs comprised the largest portion of medical cost, but most impact came from hospitalization and exacerbation in both groups of patients.,COPD grade and hospitalization in the previous year were the major factors affecting medical costs and days of utilizing health care resources.,Patients with high grade COPD impose a high economic burden on the health care system in Korea.,Prevention of progression to high grade COPD is important, both clinically and economically. | 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 |
Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood.,Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD).,The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood.,We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort.,Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13.,The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of β = −0.068 g/L per minor allele (P = 1.20*10−12).,But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1-5%) variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z) variants.,Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001), as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57).,Extending the analysis to lung function revealed a more complex situation.,Only in individuals with severely compromised pulmonary health (N = 397), associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants.,Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood.,As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression.,Here we show that polymeric immunoglobulin receptor-deficient (pIgR−/−) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age.,Progressive airway wall remodelling and emphysema in pIgR−/− mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase.,Re-derivation of pIgR−/− mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling.,These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema.,The mechanisms driving lung inflammation and remodelling in chronic obstructive pulmonary disease (COPD) are incompletely understood.,Here the authors show that lack of secretory IgA promotes bacterial invasion in small airways, resulting in leukocyte recruitment and a COPD-like phenotype. | Nontypeable Haemophilus influenzae (NTHi) is the most common cause for bacterial exacerbations in chronic obstructive pulmonary disease (COPD).,Recent investigations suggest the participation of the inflammasome in the pathomechanism of airway inflammation.,The inflammasome is a cytosolic protein complex important for early inflammatory responses, by processing Interleukin-1β (IL-1β) to its active form.,Since inflammasome activation has been described for a variety of inflammatory diseases, we investigated whether this pathway plays a role in NTHi infection of the airways.,A murine macrophage cell line (RAW 264.7), human alveolar macrophages and human lung tissue (HLT) were stimulated with viable or non-viable NTHi and/or nigericin, a potassium ionophore.,Secreted cytokines were measured with ELISA and participating proteins detected via Western Blot or immunohistochemistry.,Western Blot analysis of cells and immunohistochemistry of lung tissue detected the inflammasome key components NLRP3 and caspase-1 after stimulation, leading to a significant induction of IL-1β expression (RAW: control at the lower detection limit vs.,NTHi 505±111pg/ml, p<0.01).,Inhibition of caspase-1 in human lung tissue led to a significant reduction of IL-1β and IL-18 levels (IL-1β: NTHi 24 h 17423±3198pg/ml vs.,NTHi+Z-YVAD-FMK 6961±1751pg/ml, p<0.01).,Our data demonstrate the upregulation of the NRLP3-inflammasome during NTHi-induced inflammation in respiratory cells and tissues.,Our findings concerning caspase-1 dependent IL-1β release suggest a role for the inflammasome in respiratory tract infections with NTHi which may be relevant for the pathogenesis of bacterial exacerbations in COPD. | 1 |
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged ≥40 years), and pooled study results are presented herein.,Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo.,After the 26-week treatment period, placebo subjects completed the trial and 75% of subjects on active treatment entered a 26-week safety extension.,Coprimary efficacy variables were mean changes in forced expiratory volume in one second (FEV1), area under the curve from 0 to 12 hours postdose (AUC0-12 h), and morning predose/trough FEV1 from baseline to the week 13 endpoint.,Key secondary efficacy variables were St George’s Respiratory Questionnaire scores, symptom-free nights, time-to-first exacerbation, and partly stable COPD at the week 26 endpoint.,In the 26-week treatment period, significantly greater increases in FEV1 AUC0-12 h occurred with MF/F 400/10 versus MF 400 and placebo at the week 13 and week 26 endpoints (P ≤ 0.032).,These increases were over three-fold greater with MF/F 400/10 than with MF 400.,Also, significantly greater increases in morning predose/trough FEV1 occurred with MF/F 400/10 versus F 10 and placebo at the week 13 endpoint (P < 0.05).,The increase was four-fold greater with MF/F 400/10 than with F 10.,All active treatment groups achieved minimum clinically important differences from baseline (>4 units) in St George’s Respiratory Questionnaire scores at week 26.,Symptom-free nights increased by ≥14% in the MF/F 400/10, MF 400, and F 10 groups (P ≤ 0.033 versus placebo).,The incidence of exacerbations was lower in the MF/F groups (≤33.3%) than it was in the MF, formoterol, and placebo groups (≥33.8%) over the 26-week treatment period.,The incidence of adverse events was similar in the active-treated and placebo-treated subjects across 26 weeks of treatment.,Over the 1-year study period, there were no notable differences in the incidence or types of adverse events between the MF/F 400/10 and MF/F 200/10 groups compared with the MF or formoterol groups.,Differences in rates of individual treatment-emergent adverse events were <3% between treatment groups.,Rates of pneumonia were low (≤2%) across all treatment groups.,Patients treated with MF/F demonstrated significant improvements in lung function, health status, and exacerbation rates.,Although significant improvements were seen with both doses, a trend showing a dose-response effect was observed in the lung function measurements. | 1 |
Chronic obstructive pulmonary disease (COPD) is a debilitating heterogeneous disease characterised by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance.,In COPD, the relationship between the neutrophil serine protease, neutrophil elastase, and its endogenous inhibitor, alpha-1-antitrypsin (AAT) is the best characterised.,AAT belongs to a superfamily of serine protease inhibitors known as serpins.,Advances in screening technologies have, however, resulted in many members of the serpin superfamily being identified as having differential expression across a multitude of chronic lung diseases compared to healthy individuals.,Serpins exhibit a unique suicide-substrate mechanism of inhibition during which they undergo a dramatic conformational change to a more stable form.,A limitation is that this also renders them susceptible to disease-causing mutations.,Identification of the extent of their physiological/pathological role in the airways would allow further expansion of knowledge regarding the complexity of protease regulation in the lung and may provide wider opportunity for their use as therapeutics to aid the management of COPD and other chronic airways diseases. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive, chronic respiratory disease with a significant socioeconomic burden.,Exacerbations, the sudden and sustained worsening of symptoms, can lead to hospitalization and reduce quality of life.,Major limitations of previous telemonitoring interventions for COPD include low compliance, lack of consensus on what constitutes an exacerbation, limited numbers of patients, and short monitoring periods.,We developed a telemonitoring system based on a digital health platform that was used to collect data from the 1-year EDGE (Self Management and Support Programme) COPD clinical trial aiming at daily monitoring in a heterogeneous group of patients with moderate to severe COPD.,The objectives of the study were as follows: first, to develop a systematic and reproducible approach to exacerbation identification and to track the progression of patient condition during remote monitoring; and second, to develop a robust algorithm able to predict COPD exacerbation, based on vital signs acquired from a pulse oximeter.,We used data from 110 patients, with a combined monitoring period of more than 35,000 days.,We propose a finite-state machine-based approach for modeling COPD exacerbation to gain a deeper insight into COPD patient condition during home monitoring to take account of the time course of symptoms.,A robust algorithm based on short-period trend analysis and logistic regression using vital signs derived from a pulse oximeter is also developed to predict exacerbations.,On the basis of 27,260 sessions recorded during the clinical trial (average usage of 5.3 times per week for 12 months), there were 361 exacerbation events.,There was considerable variation in the length of exacerbation events, with a mean length of 8.8 days.,The mean value of oxygen saturation was lower, and both the pulse rate and respiratory rate were higher before an impending exacerbation episode, compared with stable periods.,On the basis of the classifier developed in this work, prediction of COPD exacerbation episodes with 60%-80% sensitivity will result in 68%-36% specificity.,All 3 vital signs acquired from a pulse oximeter (pulse rate, oxygen saturation, and respiratory rate) are predictive of COPD exacerbation events, with oxygen saturation being the most predictive, followed by respiratory rate and pulse rate.,Combination of these vital signs with a robust algorithm based on machine learning leads to further improvement in positive predictive accuracy.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6olpMWNpc) | 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 |
People with chronic obstructive pulmonary disease (COPD) have balance impairments and an increased risk of falls.,The psychometric properties of short balance tests to inform fall risk assessment in COPD are unknown.,Our objective was to determine the validity (concurrent, convergent, and known-groups) of short balance and mobility tests for fall risk screening.,Participants with COPD aged ≥ 60 years attended a single assessment.,Correlation coefficients described the relationships between the Brief Balance Evaluation Systems Test (Brief BESTest), Single-Leg Stance (SLS), Timed Up and Go (TUG), and Timed Up and Go Dual-Task (TUG-DT) tests, with the comprehensive Berg Balance Scale (BBS), chair-stand test, and measures of exercise tolerance, functional limitation, disability, and prognosis.,Independent t-tests or Mann-Whitney U tests were used to examine differences between groups with respect to fall risk.,Receiver operating characteristic curves examined the ability of the screening tests to identify individuals with previous falls.,A total of 86 patients with COPD completed the study (72.9 ± 6.8 years; forced expiratory volume in 1 second: 47.3 ± 20.3% predicted).,The Brief BESTest identified individuals who reported a previous fall (area under the curve (AUC) = 0.715, p = 0.001), and the SLS showed borderline acceptable accuracy in identifying individuals with a fall history (AUC = 0.684, p = 0.004).,The strongest correlations were found for the Brief BESTest and SLS with the BBS (r = 0.80 and r = 0.72, respectively) and between the TUG and TUG-DT with the chair-stands test (r = 0.73 and r = 0.70, respectively).,The Brief BESTest and SLS show the most promise as balance screening tools for fall risk assessment in older adults with COPD.,These tests should be further evaluated prospectively. | Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in progressive airflow limitation and respiratory distress.,Physiopathological features of COPD suggest that people who suffer from this disease have many risk factors for falls that have been identified in older individuals.,The aim of the study was to compare and quantify functional balance between COPD patients and healthy subjects; to investigate the risk of falls in acute stages of the disease and to identify risk factors that could lead to falls.,We studied 46 patients with moderate-severe COPD (29 stable and 17 in acute exacerbation - AECOPD) and 17 healthy subjects (control group) having similar demographic data.,We analyzed the difference in Berg Balance Scale (BBS), Single Leg Stance (SLS) and Timed Up and Go test (TUG) between these three groups and the correlation of these scores with a number of incriminatory factors.,The presence of COPD was associated with significant worsening of balance tests: BBS (55 control, vs.,53 COPD, vs.,44 AECOPD points p<0.001), TUG (8.6 control vs.,12.3 COPD vs.,15.9 AECOPD seconds. p<0.001), SLS (31.1 control vs.,17.7 COPD vs.,7.2 AECOPD seconds p<0.001) which may be associated with an increased risk of falls.,Anxiety and depression were significantly associated with decreased balance test scores; anxiety (2 control vs.,6 COPD vs.,9 AECOPD points p<0.001) depression (2 control vs.,7 COPD vs.,12 AECOPD points p<0.001).,According to our results COPD patients in moderate-severe stages and especially those in exacerbation have a high risk of falls. | 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. | Genome-wide association studies (GWAS) and candidate gene studies have identified a number of risk loci associated with the smoking-related disease COPD, a disorder that originates in the airway epithelium.,Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome, enriched, in part, at known GWAS/candidate gene loci.,Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n = 10) and healthy smokers (n = 7).,The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS to confer risk for COPD.,Smoker BC have 676 genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation.,Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10−4 compared to chance), including 4 genes (NFKBIB, LTBP4, EGLN2 and TGFB1) associated with risk for COPD.,These observations provide the first direct connection between known genetic risks for smoking-related lung disease and airway BC, the population of lung cells that undergo the earliest changes associated with smoking. | 1 |
Drugs for inhalation are the cornerstone of therapy in obstructive lung disease.,We have observed that up to 75 % of patients do not perform a correct inhalation technique.,The inability of patients to correctly use their inhaler device may be a direct consequence of insufficient or poor inhaler technique instruction.,The objective of this study is to test the efficacy of two educational interventions to improve the inhalation techniques in patients with Chronic Obstructive Pulmonary Disease (COPD).,This study uses both a multicenter patients´ preference trial and a comprehensive cohort design with 495 COPD-diagnosed patients selected by a non-probabilistic method of sampling from seven Primary Care Centers.,The participants will be divided into two groups and five arms.,The two groups are: 1) the patients´ preference group with two arms and 2) the randomized group with three arms.,In the preference group, the two arms correspond to the two educational interventions (Intervention A and Intervention B) designed for this study.,In the randomized group the three arms comprise: intervention A, intervention B and a control arm.,Intervention A is written information (a leaflet describing the correct inhalation techniques).,Intervention B is written information about inhalation techniques plus training by an instructor.,Every patient in each group will be visited six times during the year of the study at health care center.,Our hypothesis is that the application of two educational interventions in patients with COPD who are treated with inhaled therapy will increase the number of patients who perform a correct inhalation technique by at least 25 %.,We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, considering that it will be adequate and feasible within the context of clinical practice.,Current Controlled Trials ISRTCTN15106246 | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven. | 1 |
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.,The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression.,Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.,Among these new drugs, we focussed on thioredoxin (Trx).,Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways.,The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.,In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF).,Taken together, these findings suggest that Trx may be the ideal drug for treating COPD. | Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models.,Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice.,Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of chronic obstructive pulmonary disease (COPD) patients.,These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways.,Poly I:C induced increased numbers of neutrophils and natural killer cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively.,Using gene set variation analysis on representative clinical data sets, gene sets defined by poly I:C-induced differentially expressed genes were enriched in the molecular profiles of COPD but not idiopathic pulmonary fibrosis patients.,Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients. | 1 |
Background and objective: There are few data on the short‐term natural history of airway inflammation during severe episodes of acute exacerbation of COPD (AECOPD).,An observational study was performed to determine how rapidly conventional treatment improves airway inflammation in patients admitted to hospital with AECOPD.,Methods: Twenty‐four consecutive patients with AECOPD were recruited and changes in sputum inflammatory indices were assessed after 2 and 4 days of treatment.,The primary end‐points included presence of bacteria and viruses, changes in sputum total cell counts (TCC) and polymorphonuclear leukocyte (PMN) differential counts, and levels of secretory leukocyte protease inhibitor (SLPI), IL‐8 and TNF‐α.,Results: All patients received oral corticosteroids and 17 (71%) were also treated with oral antibiotics.,A bacterial or viral pathogen was isolated from 12 patients (50%), and Aspergillus fumigatus was isolated from one.,A positive bacterial culture was associated with increased sputum TCC and PMN count (P < 0.05), as well as higher levels of IL‐8 and TNF‐α (P < 0.05), and a trend towards lower sputum SLPI levels (P = 0.06).,Sputum PMN numbers fell by 70% within the first 48 h of admission (P < 0.05), accompanied by an increase in sputum SLPI (P < 0.001) and reductions in the levels of TNF‐α (P < 0.005) and IL‐8 (P = 0.06), with no further significant change at 4 days.,Conclusions: Conventional treatment for severe AECOPD is associated with rapid reduction of neutrophilic inflammation and improvement in anti‐protease defences. | COPD exacerbations are associated with neutrophilic airway inflammation.,Adhesion molecules on the surface of neutrophils may play a key role in their movement from blood to the airways.,We analysed adhesion molecule expression on blood and sputum neutrophils from COPD subjects and non-obstructed smokers during experimental rhinovirus infections.,Blood and sputum were collected from 9 COPD subjects and 10 smoking and age-matched control subjects at baseline, and neutrophil expression of the adhesion molecules and activation markers measured using flow cytometry.,The markers examined were CD62L and CD162 (mediating initial steps of neutrophil rolling and capture), CD11a and CD11b (required for firm neutrophil adhesion), CD31 and CD54 (involved in neutrophil transmigration through the endothelial monolayer) and CD63 and CD66b (neutrophil activation markers).,Subjects were then experimentally infected with rhinovirus-16 and repeat samples collected for neutrophil analysis at post-infection time points.,At baseline there were no differences in adhesion molecule expression between the COPD and non-COPD subjects.,Expression of CD11a, CD31, CD62L and CD162 was reduced on sputum neutrophils compared to blood neutrophils.,Following rhinovirus infection expression of CD11a expression on blood neutrophils was significantly reduced in both subject groups.,CD11b, CD62L and CD162 expression was significantly reduced only in the COPD subjects.,Blood neutrophil CD11b expression correlated inversely with inflammatory markers and symptom scores in COPD subjects.,Following rhinovirus infection neutrophils with higher surface expression of adhesion molecules are likely preferentially recruited to the lungs.,CD11b may be a key molecule involved in neutrophil trafficking in COPD exacerbations. | 1 |
In patients with COPD, self-management skills are important to reduce the impact of exacerbations.,However, both detection and adequate response to exacerbations appear to be difficult for some patients.,Little is known about the underlying process of exacerbation-related self-management.,Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior.,A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated.,Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015.,Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed.,Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management.,Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms.,Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions.,This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients.,The conceptual model can be used as a framework for health care professionals providing self-management support.,In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account. | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | Little information is available regarding the vulnerability of patients with chronic obstructive pulmonary disease (COPD) in China.,We aimed to assess this according to patient gender.,A cross-sectional study was conducted in the rural area of Xuzhou in China.,We interviewed and administered questionnaires to 2825 male and 2825 female patients with COPD and subjected the data generated to statistical analysis.,We compared differences between proportions of male and female patients using the χ2 test.,The rate of current smoking in men was 30.1%, whereas that in women was 10.9%, and 31.5% of men had a history of using biomass fuel compared with 75.3% of women.,Further, 26.0% of the male patients and 16.4% of the female patients did not take theophylline regularly when their disease was stable.,During acute exacerbations, 65.8% of the male patients and 39.7% of the female patients took theophylline or similar drugs.,The average potential shortening of life expectancy was 1.76 years for men and 1.18 years for women.,The average indirect economic burden was 11158.4 yuan for men and 7481.2 yuan for women.,The quality of life was worse in female patients than in male patients.,We found that patients with COPD were vulnerable and that factors determining vulnerability were different for men than for women.,Therefore, we recommend adopting different measures for men and women when attempting to prevent, control, and treat COPD, rehabilitate these patients, and improve their quality of life. | 1 |
The Spanish Guidelines for COPD (GesEPOC) describe four clinical phenotypes: non-exacerbator (NE), asthma-COPD overlap syndrome (ACO), frequent exacerbator with emphysema (EE), and exacerbator with chronic bronchitis (ECB).,The objective of this study was to determine the frequency of COPD phenotypes, their clinical characteristics, and the availability of diagnostic tools to classify COPD phenotypes in clinical practice.,This study was an epidemiological, cross-sectional, and multi-centered study.,Patients ≥40 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of <0.7 and who were smokers or former smokers (with at least 10 pack-years) were included.,The availability of diagnostic tools to classify COPD phenotypes was assessed by an ad hoc questionnaire.,A total of 647 patients (294 primary care [PC], 353 pulmonology centers) were included.,Most patients were male (80.8%), with a mean age (SD) of 68.2 (9.2) years, mean post-bronchodilator FEV1 was 53.2% (18.9%) and they suffered a mean of 2.2 (2.1) exacerbations in the last year.,NE was the most frequent phenotype (47.5%) found, followed by ECB (29.1%), EE (17.0%), and ACO (6.5%).,Significant differences between the four phenotypes were found regarding age; sex; body mass index; FEV1; body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE)/body mass index, airflow obstruction, dyspnea and exacerbations (BODEx) index; modified Medical Research Council dyspnea scale; respiratory symptoms; comorbidi-ties; hospitalizations; and exacerbations in the last year.,Physicians considered that >80% of the diagnostic tools needed to classify COPD phenotypes were available, with the exception of computed tomography (26.9%) and carbon monoxide transfer test (13.5%) in PC, and sputum eosinophilia count in PC and pulmonology centers (40.4% and 49.4%, respectively).,In Spanish clinical practice, almost half of the patients with COPD presented with NE phenotype.,The prevalence of ACO according to the Spanish consensus definition was very low.,In general, physicians indicated that they had the necessary tools for diagnosing COPD phenotypes. | Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease.,We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up.,This was a multicenter, prospective, observational study.,Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]).,Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first.,A total of 497 patients were included in the study.,The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%).,A total of 303 (61%) patients experienced a composite event.,Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048).,In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event.,A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829-0.899; P=0.001).,The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire.,However, previous history of exacerbations was the strongest predictor of the composite event. | 1 |
After the development of the COPD Strategy of the National Health Service in Spain, all scientific societies, patient organisations, and central and regional governments formed a partnership to enhance care and research in COPD.,At the same time, the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) took the initiative to convene the various scientific societies involved in the National COPD Strategy and invited them to participate in the development of the new Spanish guidelines for COPD (Guía Española de la EPOC; GesEPOC).,Probably the more innovative approach of GesEPOC is to base treatment of stable COPD on clinical phenotypes, a term which has become increasingly used in recent years to refer to the different clinical forms of COPD with different prognostic implications.,The proposed phenotypes are: (A) infrequent exacerbators with either chronic bronchitis or emphysema; (B) overlap COPD-asthma; (C) frequent exacerbators with emphysema predominant; and (D) frequent exacerbators with chronic bronchitis predominant.,The assessment of severity has also been updated with the incorporation of multidimensional indices.,The severity of the obstruction, as measured by forced expiratory volume in 1 second, is essential but not sufficient.,Multidimensional indices such as the BODE index have shown excellent prognostic value.,If the 6-minute walking test is not performed routinely, its substitution by the frequency of exacerbations (BODEx index) provides similar prognostic properties.,This proposal aims to achieve a more personalised management of COPD according to the clinical characteristics and multidimensional assessment of severity. | The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU.,They are not indicated for the treatment of asthma.,In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo.,Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms.,COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.,The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%).,Headache was the most common AE in each treatment group (8-11%).,AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups.,No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo.,The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo.,With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day).,Both active treatments improved lung function versus placebo.,UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD. | 1 |
To quantify the extent of squamous metaplasia in bronchial biopsies and relate it to the presence of chronic obstructive pulmonary disease (COPD), a smoking-related pathology.,Bronchial biopsies (n = 15 in each group) from smokers with COPD GOLD stage1 and GOLD stage2, smokers without COPD and healthy non-smokers were stained immunohistochemically with a panel of antibodies that facilitated the identification of pseudostratified epithelium and distinction of squamous metaplasia and squamous epithelium from tangentially cut epithelium.,The percentage length of each of these epithelial phenotypes was measured as a percent of total epithelial length using computerised image analysis.,Sections were also stained for carcinoembryonic antigen and p53, early markers of carcinogenesis, and Ki67, and the percentage epithelial expression measured.,The extent of squamous metaplasia was significantly increased in both COPD1 and COPD2 compared to healthy smokers and healthy non-smokers.,The amount of fully differentiated squamous epithelium was also increased in COPD1 and COPD2 compared to healthy non-smokers, as was the expression of carcinoembryonic antigen.,These features correlated with one other.,In subjects with COPD there is a loss of pseudostratified epithelium accompanied by an increase in squamous metaplasia with transition into a fully squamous epithelium and expression of early markers of carcinogenesis. | Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease.,A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS).,Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants.,The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice.,Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h.,GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues.,GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL) activity in lung and liver tissue.,GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged.,Next, the time course of rebound in GSH levels after the CS exposure was examined.,CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months.,Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis.,Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels.,CS exposures evoke a powerful GSH adaptive response in the lung and systemically.,These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels.,Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD. | 1 |
Diabetes damages major organ systems through disrupted glycemic control and increased inflammation.,The effects of diabetes on the lung have been of interest for decades, but the modest reduction in pulmonary function and its nonprogressive nature have limited its investigation.,A recent systematic review found that diabetes was associated with reductions in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide of the lung and increased FEV1/FVC.,They reported pooled results including few smokers.,This study will examine measures of pulmonary function in participants with extensive smoking exposure.,We examined pulmonary function in participants with a >10-pack-year history of smoking with and without diabetes with and without chronic obstructive pulmonary disease (COPD).,We measured pulmonary function, exercise capacity, and pulmonary-related quality of life in 10,129 participants in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study.,Participants with diabetes were observed to have reduced pulmonary function after controlling for known risk factors and also significant reductions in exercise capacity and quality of life across functional stages of COPD.,Pulmonary function in patients with ≥10 pack-years of smoking and diabetes is reduced, and this decrease is associated with significant reductions in activity-related quality of life and exercise capacity. | Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year.,Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.,1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly.,Exacerbations were defined by health care utilisation.,Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.,Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE.,More severe disease was associated with changing from IE to FE and less severe disease from FE to IE.,Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.,No parameter clearly predicts an imminent change in exacerbation frequency category.,SCO104960, clinicaltrials.gov identifier NCT00292552 | 1 |
Objectives.,A detailed understanding of the intricate relationships between different acute phase reactants (APRs) in chronic obstructive pulmonary disease (COPD) can shed new light on its clinical course.,In this case-control study, we sought to identify the interaction networks of a number of plasma APRs in COPD, with a special focus on their association with disease severity.,Methods.,COPD cases and healthy smoking controls (3:1 ratio) were recruited in our outpatient pulmonary clinic.,Cardiopulmonary exercise testing was used to rule out the presence of ischemic heart disease.,All subjects were males as per protocol.,Multiple plasma APRs - including α-2-macroglobulin, C-reactive protein (CRP), ferritin, fibrinogen, haptoglobin, procalcitonin (PCT), serum amyloid A (SAA), serum amyloid P, and tissue plasminogen activator (tPA) - were measured using commercial Acute Phase Bio-Plex Pro Assays and analyzed on the Bio-Plex manager software.,Correlations between different APRs were investigated using a heat map.,Network visualization and analyses were performed with the Cytoscape software platform.,Results.,A total of 96 COPD cases and 33 controls were included in the study.,Plasma A2M, CRP, and SAP levels were higher in COPD patients than in controls.,Circulating concentrations of haptoglobin and tPA were found to increase in parallel with the severity of the disease.,Increasing disease severity was associated with distinct intricate networks of APRs, which were especially evident in advanced stages.,Conclusions.,We identified different networks of APRs in COPD, which were significantly associated with disease severity. | 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 |
Inhalation therapy is the main treatment for asthma and chronic obstructive pulmonary disease (COPD) patients.,Owing to the poor inhaler technique in using inhalers, we assessed the effect of a multidimensional pharmaceutical care on inhalation technique in patients with asthma and COPD.,A 3-month controlled parallel-group study was undertaken in asthma and COPD patients using dry powder inhalers (DPIs).,Patients in the intervention group received multidimensional pharmaceutical care, including establishment of a special dispensing window, face-to-face demonstration and education, brochure education, videos education, online consultation and education, and follow-up reeducation.,Patients in the control group received usual pharmaceutical care.,The inhaler technique score, correctness of inhaler usage, beliefs about medicines questionnaire (BMQ) score, asthma control test (ACT), and COPD assessment test (CAT) were measured pre- and postintervention.,Quality of life improvement evaluated according to score changes of ACT in asthma and CAT in COPD and patient satisfaction were measured postintervention.,259 patients finished the study with 133 in the intervention group and 126 in the control group.,Compared to preintervention and control group postintervention, the inhaler technique score, correctness of inhaler usage, and ACT score significantly increased in the intervention group postintervention, while the BMQ score and CAT score decreased significantly (P < 0.05).,Significant improvements in quality of life and patient satisfaction were found (P < 0.05).,This study showed the multidimensional pharmaceutical care for asthma and COPD patients were effective in improving inhalation technique.,By providing pharmaceutical care, pharmacists might help asthma and COPD patients to acquire better quality of life. | The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management.,A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD.,The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management.,Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation.,Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD.,Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations.,Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD.,In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence.,Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration. | 1 |
Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema.,The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects.,Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways.,20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks.,Bronchoalveolar lavage (BAL) was performed at baseline and after treatment.,Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites.,The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed.,Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens.,Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-α, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid.,Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-α, IL-13 and IL-12p40.,AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects.,NCT02557958. | Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase.,The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations.,Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months.,The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction.,Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase.,These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients.,In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results.,Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients.,The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations.,Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients. | 1 |
Fibrosis in peripheral airways is responsible for airflow limitation in chronic obstructive pulmonary disease (COPD).,Annexin A1 modulates several key biological events during inflammation.,However, little is known about its role in airway fibrosis in COPD.,We investigated whether levels of Annexin A1 were upregulated in patients with COPD, and whether it promoted airway fibrosis.,We quantified serum Annexin A1 levels in never-smokers (n=12), smokers without COPD (n=11), and smokers with COPD (n=22).,Correlations between Annexin A1 expression and clinical indicators (eg, lung function) were assessed.,In vitro, human bronchial epithelial (HBE) cells were exposed to cigarette smoke extract (CSE) and Annexin A1 expression was assessed.,Primary human lung fibroblasts were isolated from patients with COPD and effects of Annexin A1 on fibrotic deposition of lung fibroblasts were evaluated.,Serum Annexin A1 was significantly higher in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines stage III or IV than in those with GOLD stages I or II (12.8±0.8 ng/mL versus 9.8±0.7 ng/mL; p=0.016).,Annexin A1 expression was negatively associated with airflow obstruction (forced expiratory volume in one second % predicted; r=−0.72, p<0.001).,In vitro, Annexin A1 was significantly increased in CSE-exposed HBE cells in a time- and concentration-dependent manner.,Annexin A1 promoted lung fibroblasts proliferation, migration, differentiation, and collagen deposition via the ERK1/2 and p38 mitogen-activated protein kinase pathways.,Annexin A1 expression is upregulated in patients with COPD and affects lung fibroblast function.,However, more studies are needed to clarify the role of Annexin A1 in airway fibrosis of COPD. | Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | 1 |
As only some smokers develop COPD with emphysema, we explored the molecular pathogenesis of early-stage COPD with emphysema using gene expression profiling of human lung tissues.,First, 110 subjects who had smoked more than ten pack-years were classified into three groups: COPD with emphysema, COPD without emphysema, and healthy smokers.,COPD and emphysema were confirmed by post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.7 and by chest computed tomography.,Lung tissues obtained surgically from the 110 subjects were processed and used for RNA-Seq analysis.,Among the 110 subjects, 29 had COPD with emphysema, 21 had COPD without emphysema, and 60 were healthy smokers; their mean post-bronchodilator forced expiratory volume in 1 second values were 78%, 80%, and 94%, respectively.,Using RNA-Seq, we evaluated 16,676 genes expressed in lung tissues.,Among them, 1,226 genes in the COPD with emphysema group and 434 genes in the COPD without emphysema group were differentially expressed genes compared to the expression in healthy smokers.,In the COPD with emphysema group, ACER2 and LMAN2L were markedly increased and decreased, respectively.,In the COPD without emphysema group, the CHRM3 gene, previously reported to be associated with COPD, and HDAC10 were markedly increased and decreased, respectively.,Our study identified differences in gene expression in subjects with COPD according to emphysema status using RNA-Seq transcriptome analysis.,These findings may have mechanistic implications in COPD. | There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis.,We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD.,To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0.7, FEV1% < 80%), and 30 non-COPD controls.,Targeted next generation sequencing was used to measure total and allele-specific expression of 35 genes in genome maintenance (GM) genes pathways linked to COPD pathogenesis, including seven TP53 and CEBP transcription factor family members.,Shrinkage linear discriminant analysis (SLDA) was used to identify COPD-classification models.,COPD GWAS were queried for putative cis-regulatory SNPs in the targeted genes.,On a network basis, TP53 and CEBP transcription factor pathway gene pair network connections, including key DNA repair gene ERCC5, were significantly different in COPD subjects (e.g., Wilcoxon rank sum test for closeness, p-value = 5.0E-11).,ERCC5 SNP rs4150275 association with chronic bronchitis was identified in a set of Lung Health Study (LHS) COPD GWAS SNPs restricted to those in putative regulatory regions within the targeted genes, and this association was validated in the COPDgene non-hispanic white (NHW) GWAS.,ERCC5 SNP rs4150275 is linked (D’ = 1) to ERCC5 SNP rs17655 which displayed differential allelic expression (DAE) in BEC and is an expression quantitative trait locus (eQTL) in lung tissue (p = 3.2E-7).,SNPs in linkage (D’ = 1) with rs17655 were predicted to alter miRNA binding (rs873601).,A classifier model that comprised gene features CAT, CEBPG, GPX1, KEAP1, TP73, and XPA had pooled 10-fold cross-validation receiver operator characteristic area under the curve of 75.4% (95% CI: 66.3%-89.3%).,The prevalence of DAE was higher than expected (p = 0.0023) in the classifier genes.,GM genes comprised by COPD-associated BEC expression patterns were enriched for SNPs with cis-regulatory function, including a putative cis-rSNP in ERCC5 that was associated with COPD risk.,These findings support additional total and allele-specific expression analysis of gene pathways with high prior likelihood for involvement in COPD pathogenesis.,The online version of this article (10.1186/s12890-018-0603-y) 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. | Chronic obstructive pulmonary disease (COPD) is a progressive disease affecting 3 million people in the UK, in which patients exhibit airflow obstruction that is not fully reversible.,COPD treatment guidelines are largely informed by randomised controlled trial results, but it is unclear if these findings apply to large patient populations not studied in trials.,Non-interventional studies could be used to study patient groups excluded from trials, but the use of these studies to estimate treatment effectiveness is in its infancy.,In this study, we will use individual trial data to validate non-interventional methods for assessing COPD treatment effectiveness, before applying these methods to the analysis of treatment effectiveness within people excluded from, or under-represented in COPD trials.,Using individual patient data from the landmark COPD Towards a Revolution in COPD Health (TORCH) trial and validated methods for detecting COPD and exacerbations in routinely collected primary care data, we will assemble a cohort in the UK Clinical Practice Research Datalink (selecting people between 1 January 2004 and 1 January 2017) with similar characteristics to TORCH participants and test whether non-interventional data can generate comparable results to trials, using cohort methodology with propensity score techniques to adjust for potential confounding.,We will then use the methodological template we have developed to determine risks and benefits of COPD treatments in people excluded from TORCH.,Outcomes are pneumonia, COPD exacerbation, mortality and time to treatment change.,Groups to be studied include the elderly (>80 years), people with substantial comorbidity, people with and without underlying cardiovascular disease and people with mild COPD.,Ethical approval has been granted by the London School of Hygiene & Tropical Medicine Ethics Committee (Ref: 11997).,The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency (protocol no.,17_114R).,An application to use the TORCH trial data made to clinicalstudydatarequest.com has been approved.,In addition to scientific publications, dissemination methods will be developed based on discussions with patient groups with COPD. | 1 |
Symptoms, particularly dyspnea, and activity limitation, have an impact on the health status and the ability to function normally in patients with chronic obstructive pulmonary disease (COPD).,To develop an electronic patient diary (eDiary), qualitative patient interviews were conducted from 2009 to 2010 to identify relevant symptoms and degree of bother due to symptoms.,The eDiary was completed by a subset of 209 patients with moderate-to-severe COPD in the 26-week QVA149 SHINE study.,Two morning assessments (since awakening and since the last assessment) and one evening assessment were made each day.,Assessments covered five symptoms (“shortness of breath,” “phlegm/mucus,” “chest tightness,” “wheezing,” and “coughing”) and two impact items (“bothered by COPD” and “difficulty with activities”) and were scored on a 10-point numeric scale.,Patient compliance with the eDiary was 90.4% at baseline and 81.3% at week 26.,Correlations between shortness of breath and impact items were >0.95.,Regression analysis showed that shortness of breath was a highly significant (P<0.0001) predictor of impact items.,Exploratory factor analysis gave a single factor comprising all eDiary items, including both symptoms and impact items.,Shortness of breath, the total score (including five symptoms and two impact items), and the five-item symptom score from the eDiary performed well, with good consistency and reliability.,The eDiary showed good sensitivity to change, with a 0.6 points reduction in the symptoms scores (on a 0-10 point scale) representing a meaningful change.,The eDiary was found to be valid, reliable, and responsive.,The high correlations obtained between “shortness of breath” and the ratings of “bother” and “difficulty with activities” confirmed the relevance of this symptom in patients with COPD.,Future studies will be required to explore further psychometric properties and their ability to differentiate between COPD treatments. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
Many patients with chronic obstructive pulmonary disease (COPD) suffer from poor sleep quality.,We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients.,This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment.,Sleep quality was measured using the Pittsburgh Sleep Quality Index.,Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire.,Outcomes included time to first exacerbation and exacerbation rate.,Sleep quality was “poor” (Pittsburgh Sleep Quality Index >5) in 53% of participants but was not related to age or severity of airflow obstruction.,Quality of life scores were worse in “poor” sleepers than in “good” sleepers.,Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the “poor” sleepers.,Unadjusted time to first exacerbation was shorter (190 versus 239 days) and exacerbation rate (1.7 versus 1.37 per year) was greater in the poor sleepers, but no differences were observed after adjusting for medications and comorbid conditions associated with poor sleep.,Poor sleepers had greater exacerbation rates than did good sleepers.,This appeared to be due largely to them having more, or more severe, concomitant medical conditions and taking more medications. | The aim of this study was to analyse mortality and associated risk factors, with special emphasis on health status, medications and co-morbidity, in patients with chronic obstructive pulmonary disease (COPD) that had been hospitalized for acute exacerbation.,This prospective study included 416 patients from each of the five Nordic countries that were followed for 24 months.,The St.,George's Respiratory Questionnaire (SGRQ) was administered.,Information on treatment and co-morbidity was obtained.,During the follow-up 122 (29.3%) of the 416 patients died.,Patients with diabetes had an increased mortality rate [HR = 2.25 (1.28-3.95)].,Other risk factors were advanced age, low FEV1 and lower health status.,Patients treated with inhaled corticosteroids and/or long-acting beta-2-agonists had a lower risk of death than patients using neither of these types of treatment.,Mortality was high after COPD admission, with older age, decreased lung function, lower health status and diabetes the most important risk factors.,Treatment with inhaled corticosteroids and long-acting bronchodilators may be associated with lower mortality in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is recognized as a multisystemic inflammatory disease associated with extrapulmonary comorbidities, including respiratory muscle weakness and cardiovascular and cardiac autonomic regulation disorders.,We investigated whether alterations in respiratory muscle strength (RMS) would affect cardiac autonomic modulation in COPD patients.,This study was a cross-sectional study done in ten COPD patients affected by moderate to very severe disease.,The heart rate variability (HRV) signal was recorded using a Polar cardiofrequencimeter at rest in the sitting position (10 minutes) and during a respiratory sinus arrhythmia maneuver (RSA-M; 4 minutes).,Linear analysis in the time and frequency domains and nonlinear analysis were performed on the recorded signals.,RMS was assessed using a digital manometer, which provided the maximum inspiratory pressure (PImax) and the maximum expiratory pressure (PEmax).,During the RSA-M, patients presented an HRV power increase in the low-frequency band (LFnu) (46.9±23.7 vs 75.8±27.2; P=0.01) and a decrease in the high-frequency band (HFnu) (52.8±23.5 vs 24.0±27.0; P=0.01) when compared to the resting condition.,Significant associations were found between RMS and HRV spectral indices: PImax and LFnu (r=−0.74; P=0.01); PImax and HFnu (r=0.74; P=0.01); PEmax and LFnu (r=−0.66; P=0.01); PEmax and HFnu (r=0.66; P=0.03); between PEmax and sample entropy (r=0.83; P<0.01) and between PEmax and approximate entropy (r=0.74; P=0.01).,Using a linear regression model, we found that PImax explained 44% of LFnu behavior during the RSA-M.,COPD patients with impaired RMS presented altered cardiac autonomic control, characterized by marked sympathetic modulation and a reduced parasympathetic response; reduced HRV complexity was observed during the RSA-M. | In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses.,We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD.,Sixteen sedentary males with COPD were enrolled in this study.,Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured.,The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA).,Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated.,HF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio.,Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=−0.53 (P<0.05).,Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=−0.77, r2=0.43, P<0.05).,Responses of HRV indices were more prominent during M-RSA in moderate to severe COPD.,Moreover, greater lung function impairment was related to poorer heart rate dynamics.,Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients. | 1 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear.,We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.,Sputum was collected from 174 stable COPD subjects longitudinally over 12 months.,Microbial sampling using culture and qPCR was performed.,Spirometry and sputum measures of airway inflammation were assessed.,Sputum was qPCR-positive (>106 copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]).,Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >106 copies/mL.,Samples that had qPCR copy numbers >106/mL, whether culture-positive or not, had increased sputum neutrophil counts.,H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P<0.001), were repeatable within subjects, and were >106/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive.,Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life.,qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods. | 1 |
Previous studies have reported that anemia increased mortality in patients with COPD.,However, it is unclear whether anemia is associated with increased COPD mortality in the general population.,The purpose of our study is to identify whether anemia is related to long-term mortality in COPD using a large population-based database.,Using the National Health Insurance Service-Health Screening Cohort, we identified COPD patients with available hemoglobin level.,We analyzed mortality among patients with COPD from 2003 to 2013 according to hemoglobin level.,A total of 7,114 patients with COPD were identified.,Mean age was 65.0±9.3 years, and 62.9% were male.,Anemia was present in 469 patients (6.6%).,The overall mortality rate was 46.5% in anemia and 32.1% in non-anemia groups (p<0.001).,The hazard ratio of anemia for mortality was 1.31 (95% CI, 1.11-1.54).,Among patients with anemia, the hemoglobin level correlated well with mortality.,Anemia was associated with increased long-term mortality of COPD, and even mild anemia was related to a significantly increased risk. | Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality.,We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.,Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death.,Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits.,Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.,In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.,COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.,The online version of this article (10.1186/s12890-018-0573-0) contains supplementary material, which is available to authorized users. | 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. | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Health professionals tasked with advising patients with asthma and chronic obstructive pulmonary disease (COPD) how to use inhaler devices properly and what to do about unwanted effects will be aware of a variety of commonly held precepts.,The evidence for many of these is, however, lacking or old and therefore in need of re-examination.,Few would disagree that facilitating and encouraging regular and proper use of inhaler devices for the treatment of asthma and COPD is critical for successful outcomes.,It seems logical that the abandonment of unnecessary or ill-founded practices forms an integral part of this process: the use of inhalers is bewildering enough, particularly with regular introduction of new drugs, devices and ancillary equipment, without unnecessary and pointless adages.,We review the evidence, or lack thereof, underlying ten items of inhaler ‘lore’ commonly passed on by health professionals to each other and thence to patients.,The exercise is intended as a pragmatic, evidence-informed review by a group of clinicians with appropriate experience.,It is not intended to be an exhaustive review of the literature; rather, we aim to stimulate debate, and to encourage researchers to challenge some of these ideas and to provide new, updated evidence on which to base relevant, meaningful advice in the future.,The discussion on each item is followed by a formal, expert opinion by members of the ADMIT Working Group. | 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. | 1 |
Supplemental Digital Content is available in the text,Nowadays, there is growing recognition that chronic obstructive pulmonary disease (COPD) may have influence on lung cancer.,However, coexisted COPD related to prognosis of lung cancer is still elusive.,We conducted this meta-analysis to examine the association between COPD and 5-year overall survival (OS) and postoperative pulmonary complications of patients with lung cancer.,A comprehensive computer-based online search was conducted using PubMed, Embase, Medline, and the Cochrane Library for articles published before September 30, 2017.,We identified 29 eligible studies, which included 70,111 patients in the related literature.,Twenty-two of the 29 studies provided hazard ratio for OS (1.18, 95% confidence interval: 1.11-1.25; P < .001), it suggested that the presence of COPD indicated poor survival for the patients with lung cancer.,In subgroup analysis, the relationship between COPD and OS occurrence remained statistically prominent in the subgroups stratified by study designs, COPD diagnosis timing, lung cancer surgery, cancer stage, and origins of patients.,The presence of COPD increased the risk of bronchopleural fistula, pneumonia, prolonged air leakage, and prolonged mechanical ventilation.,The present meta-analysis suggested that coexisting COPD is associated with poor survival outcomes in patients with lung cancer and higher rates of postoperative pulmonary complications. | COPD is an important comorbidity of lung cancer, but the impact of COPD on the outcomes of lung cancer remains uncertain.,Because both COPD and lung cancer are heterogeneous diseases, we evaluated the link between COPD phenotypes and the prognosis of different histological subtypes of lung cancer.,In this retrospective study, subjects with a newly and pathologically confirmed diagnosis of lung cancer were enrolled from patients preparing for lung cancer surgery.,All participants underwent pulmonary function test (PFT).,The diagnosis of COPD was based on GOLD criteria.,Lung cancer subtypes and COPD phenotypes were categorized by WHO classification of lung tumors and computer quantitative analysis of PFT.,The HRs were estimated by Cox regression analysis.,Among 2,222 lung cancer patients, 32.6% coexisted with COPD.,After adjustment for age, sex, body mass index (BMI), smoking status, and therapy method, COPD was significantly associated with the decreased overall survival (OS) of lung cancer (HR 1.28, 95% CI 1.05-1.57).,With the increased severity of COPD, the OS of lung cancer was gradually worsened (HR 1.23, 95% CI 1.08-1.39).,But surgical treatment and high BMI were independent prognostic protective factors (HR 0.46, 95% CI 0.37-0.56; HR 0.96, 95% CI 0.94-0.99).,Moreover, in terms of disease heterogeneity, emphysema-predominant phenotype of COPD was an independent prognostic risk factor for squamous carcinoma (HR 2.53, 95% CI 1.49-4.30).,No significant relationship between COPD phenotype and lung cancer prognosis was observed among adenocarcinoma, small cell lung cancer, large cell lung cancer, and other subtype patients.,These findings suggest that COPD, especially emphysema-predominant phenotype, is an independent prognostic risk factor for squamous carcinoma only. | 1 |
Specialized proresolving mediators (SPMs) are endogenous lipid metabolites of long‐chain polyunsaturated fatty acids that are involved in promoting the resolution of inflammation.,Many disease conditions characterized by excessive inflammation have impaired or altered SPM biosynthesis, which may lead to chronic, unresolved inflammation.,Exogenous administration of SPMs in infectious conditions has been shown to be effective at improving infection clearance and survival in preclinical models.,SPMs have also shown tremendous promise in the context of inflammatory lung conditions, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease, mostly in preclinical settings.,To date, SPMs have not been studied in the context of the novel Coronavirus, severe acute respiratory syndrome Coronavirus‐2 (SARS‐CoV‐2), however their preclinical efficacy in combatting infections and improving acute respiratory distress suggest they may be a valuable resource in the fight against Coronavirus disease‐19 (COVID‐19).,Overall, while the research on SPMs is still evolving, they may offer a novel therapeutic option for inflammatory conditions. | The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | 1 |
The direct relationship between pulmonary structural changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) is unclear.,We investigated AHR in relation to airway and parenchymal structural changes in a guinea pig model of COPD and in COPD patients.,Precision-cut lung slices (PCLS) were prepared from guinea pigs challenged with lipopolysaccharide or saline two times weekly for 12 wk.,Peripheral PCLS were obtained from patients with mild to moderate COPD and non-COPD controls.,AHR to methacholine was measured in large and small airways using video-assisted microscopy.,Airway smooth muscle mass and alveolar airspace size were determined in the same slices.,A mathematical model was used to identify potential changes in biomechanical properties underlying AHR.,In guinea pigs, lipopolysaccharide increased the sensitivity of large (>150 μm) airways toward methacholine by 4.4-fold and the maximal constriction of small airways (<150 μm) by 1.5-fold.,Similarly increased small airway responsiveness was found in COPD patients.,In both lipopolysaccharide-challenged guinea pigs and patients, airway smooth muscle mass was unaltered, whereas increased alveolar airspace correlated with small airway hyperresponsiveness in guinea pigs.,Fitting the parameters of the model indicated that COPD weakens matrix mechanical properties and enhances stiffness differences between the airway and the parenchyma, in both species.,In conclusion, this study demonstrates small airway hyperresponsiveness in PCLS from COPD patients.,These changes may be related to reduced parenchymal retraction forces and biomechanical changes in the airway wall.,PCLS from lipopolysaccharide-exposed guinea pigs may be useful to study mechanisms of small airway hyperresponsiveness in COPD. | It is increasingly acknowledged that delays in the diagnosis of chronic inflammatory lung conditions have hampered our understanding of pathogenesis and thus our ability to design efficacious therapies.,This is particularly true for COPD, where most patients are diagnosed with moderate-to-severe airflow obstruction and little is known about the inflammatory processes present in early disease.,There is great interest in developing screening tests that can identify those most at risk of developing COPD before airflow obstruction has developed for the purpose of research and clinical care.,Landmark pathology studies have suggested that damage to the small airways precedes the development of airflow obstruction and emphysema and, thus, presents an opportunity to identify those at risk of COPD.,However, despite a number of physiological tests being available to assess small airways function, none have been adopted into routine care in COPD.,The reasons that tests of small airways have not been utilized widely include variability in test results and a lack of validated reference ranges from which to compare results for some methodologies.,Furthermore, population studies have not consistently demonstrated their ability to diagnose disease.,However, the landscape may be changing.,As the equipment that delivers tests of small airways become more widely available, reference ranges are emerging and newer methodologies specifically seek to address variability and difficulty in test performance.,Moreover, there is evidence that while tests of small airways may not be helpful across the full range of established disease severity, there may be specific groups (particularly those with early disease) where they might be informative.,In this review, commonly utilized tests of small airways are critically appraised to highlight why these tests may be important, how they can be used and what knowledge gaps remain for their use in COPD. | 1 |
Mesenchymal cells are an essential cell type because of their role in tissue support, their multilineage differentiation capacities and their potential clinical applications.,They play a crucial role during lung development by interacting with airway epithelium, and also during lung regeneration and remodeling after injury.,However, much less is known about their function in lung disease.,In this review, we discuss the origins of mesenchymal cells during lung development, their crosstalk with the epithelium, and their role in lung diseases, particularly in chronic obstructive pulmonary disease. | One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients.,However, local inflammation may result and can contribute to worsening of clinical status in these patients.,We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients.,This initial study sought to investigate the safety of this approach.,For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used.,Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs.,Patients were evaluated 1, 7, 30, and 90 days after therapy.,All patients completed the study protocol and 90‐day follow‐up.,MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death.,No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease.,Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes.,However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV.,EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores.,Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy.,Stem Cells Translational Medicine 2017;6:962-969 | 1 |
Patients with chronic obstructive pulmonary disease (COPD) often have coagulation abnormalities.,However, the factors that lead to coagulation dysfunction in acute exacerbation of COPD (AECOPD) remain insufficiently explored.,This study aimed to investigate the factors affecting coagulation status in patients with COPD and their influence on thrombosis.,Data of COPD patients, including 135 cases in acute exacerbation stage and 44 cases in stable stage from Nov 2016 to Nov 2019 in our hospital, were collected.,Healthy people (n = 135) were enrolled as the controls.,The coagulation parameters, blood gas indexes and blood routine examination results were collected and analyzed.,White blood count (WBC), neutrophil count, neutrophil percentage (N%), platelet (PLT), prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), and activated partial thromboplastin time (APTT) increased, plasma thrombin time (TT) decreased in AECOPD group compared with the control group.,In AECOPD group, PT, APTT, and FIB were positively correlated with neutrophils and C‐reaction protein levels.,PT was positively correlated with PCO2 and negatively with pH.,Thrombosis was observed in five acute exacerbation and three stable stage COPD patients.,Patients with AECOPD presented abnormal coagulation status, which was correlated to infection and hypercapnia and might be potentially the risk factor of thrombosis.,Patients with AECOPD often have coagulation abnormalities.,In this study, some factors such as infection and hypercapnia were found to be related to the coagulation abnormality and thrombosis in those patients | Previous studies suggested that the prevalence of chronic respiratory disease in patients hospitalised with COVID-19 was lower than its prevalence in the general population.,The aim of this study was to assess whether chronic lung disease or use of inhaled corticosteroids (ICS) affects the risk of contracting severe COVID-19.,In this population cohort study, records from 1205 general practices in England that contribute to the QResearch database were linked to Public Health England's database of SARS-CoV-2 testing and English hospital admissions, intensive care unit (ICU) admissions, and deaths for COVID-19.,All patients aged 20 years and older who were registered with one of the 1205 general practices on Jan 24, 2020, were included in this study.,With Cox regression, we examined the risks of COVID-19-related hospitalisation, admission to ICU, and death in relation to respiratory disease and use of ICS, adjusting for demographic and socioeconomic status and comorbidities associated with severe COVID-19.,Between Jan 24 and April 30, 2020, 8 256 161 people were included in the cohort and observed, of whom 14 479 (0·2%) were admitted to hospital with COVID-19, 1542 (<0·1%) were admitted to ICU, and 5956 (0·1%) died.,People with some respiratory diseases were at an increased risk of hospitalisation (chronic obstructive pulmonary disease [COPD] hazard ratio [HR] 1·54 [95% CI 1·45-1·63], asthma 1·18 [1·13-1·24], severe asthma 1·29 [1·22-1·37; people on three or more current asthma medications], bronchiectasis 1·34 [1·20-1·50], sarcoidosis 1·36 [1·10-1·68], extrinsic allergic alveolitis 1·35 [0·82-2·21], idiopathic pulmonary fibrosis 1·59 [1·30-1·95], other interstitial lung disease 1·66 [1·30-2·12], and lung cancer 2·24 [1·89-2·65]) and death (COPD 1·54 [1·42-1·67], asthma 0·99 [0·91-1·07], severe asthma 1·08 [0·98-1·19], bronchiectasis 1·12 [0·94-1·33], sarcoidosis 1·41 [0·99-1·99), extrinsic allergic alveolitis 1·56 [0·78-3·13], idiopathic pulmonary fibrosis 1·47 [1·12-1·92], other interstitial lung disease 2·05 [1·49-2·81], and lung cancer 1·77 [1·37-2·29]) due to COVID-19 compared with those without these diseases.,Admission to ICU was rare, but the HR for people with asthma was 1·08 (0·93-1·25) and severe asthma was 1·30 (1·08-1·58).,In a post-hoc analysis, relative risks of severe COVID-19 in people with respiratory disease were similar before and after shielding was introduced on March 23, 2020.,In another post-hoc analysis, people with two or more prescriptions for ICS in the 150 days before study start were at a slightly higher risk of severe COVID-19 compared with all other individuals (ie, no or one ICS prescription): HR 1·13 (1·03-1·23) for hospitalisation, 1·63 (1·18-2·24) for ICU admission, and 1·15 (1·01-1·31) for death.,The risk of severe COVID-19 in people with asthma is relatively small.,People with COPD and interstitial lung disease appear to have a modestly increased risk of severe disease, but their risk of death from COVID-19 at the height of the epidemic was mostly far lower than the ordinary risk of death from any cause.,Use of inhaled steroids might be associated with a modestly increased risk of severe COVID-19.,National Institute for Health Research Oxford Biomedical Research Centre and the Wellcome Trust. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | Patients with COPD experience exacerbations that may require hospitalization.,Patients do not always feel supported upon discharge and frequently get readmitted.,A Self-management Program of Activity, Coping, and Education for COPD (SPACE for COPD), a brief self-management program, may help address this issue.,To investigate if SPACE for COPD employed upon hospital discharge would reduce readmission rates at 3 months, compared with usual care.,This is a prospective, single-blinded, two-center trial (ISRCTN84599369) with participants admitted for an exacerbation, randomized to usual care or SPACE for COPD.,Measures, including health-related quality of life and exercise capacity, were taken at baseline (hospital discharge) and at 3 months.,The primary outcome measure was respiratory readmission at 3 months.,Seventy-eight patients were recruited (n=39 to both groups).,No differences were found in readmission rates or mortality at 3 months between the groups.,Ten control patients were readmitted within 30 days compared to five patients in the intervention group (P>0.05).,Both groups significantly improved their exercise tolerance and Chronic Respiratory Questionnaire (CRQ-SR) results, with between-group differences approaching statistical significance for CRQ-dyspnea and CRQ-emotion, in favor of the intervention.,The “Ready for Home” survey revealed that patients receiving the intervention reported feeling better able to arrange their life to cope with COPD, knew when to seek help about feeling unwell, and more often took their medications as prescribed, compared to usual care (P<0.05).,SPACE for COPD did not reduce readmission rates at 3 months above that of usual care.,However, encouraging results were seen in secondary outcomes for those receiving the intervention.,Importantly, SPACE for COPD appears to be safe and may help prevent readmission with 30 days. | 1 |
To establish the dose−response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulized formulation of the long acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebulizer in patients with chronic obstructive pulmonary disease (COPD).,Patients with moderate to severe COPD (GOLD II/III), with reversible lung function, were enrolled into this randomized, double-blind, placebo-controlled, six period crossover study (n = 42).,Patients received single doses of EP-101 (12.5-400 μg) and placebo via a high efficiency nebulizer (eFlow® PARI nebulizer), with washout between treatments.,Plasma pharmacokinetics were assessed in a subset of patients (n = 11).,All treatments were well tolerated with similar adverse event rates reported with placebo and at all doses.,There were no clinically relevant changes in heart rate, systolic and diastolic blood pressure or in ECG parameters including QTc interval.,Following treatment with EP-101 at all doses there was a rapid bronchodilator response within 5 min.,Significant improvements in mean change from baseline FEV1 at 24 h were reported at doses ≥50 μg compared with placebo, with a clear dose−response relationship.,Mean changes in FEV1 were 0.10 l (95% CI 0.06, 0.14) and 0.12 l (95% CI 0.08, 0.16) for 100 μg and 200 μg, respectively.,Single doses of EP-101 ranging from 12.5 μg to 400 μg were well tolerated.,EP-101 delivered by high efficiency nebulizer device produced a rapid onset of bronchodilatation with clinically meaningful improvements in lung function maintained over a 24 h period at all doses >50 μg. | 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. | 1 |
There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD.,It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.,We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013.,Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline.,Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.,We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria.,The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%-45.8% (RCTs) and 13.7-42.1% (observational studies).,The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%-40.0% vs 40.1%-60.6%), other ischemic heart disease (12.3%-14.2% vs 12.5%-41.0%), diabetes (10.3%-10.9% vs 4.0%-38.9%), depression (8.5%-9.5% vs 17.0%-20.6%), and cardiac arrhythmia (7.8%-11.4% vs 11.3%-15.8%).,The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for “real-life patients.”,The tiotropium RCTs tended to include patients with more severe disease than the observational studies. | This was a multicenter, randomized, double-blind within device, parallel-group, dose-ranging study.,COPD patients (n = 202; 86% male; mean age: 61 years) were randomized to receive tiotropium 1.25 μg, 2.5 μg, 5 μg, 10 μg, or 20 μg Respimat® SMI (a novel, propellant-free device); tiotropium 18 μg HandiHaler®; placebo Respimat®; or placebo HandiHaler® for 3 weeks.,The primary endpoint was trough FEV1 on Day 21.,Other assessments included FVC, PEFR, rescue medication use, safety, and pharmacokinetics.,In general, all active treatments improved the primary and secondary endpoints on Day 21 (steady state) compared with placebo.,Tiotropium 5 μg Respimat®, 20 μg Respimat®, and tiotropium 18 μg HandiHaler® were statistically significantly higher than placebo for the primary endpoint (mean change in trough FEV1 was 150 mL (both Respimat® doses) versus 20 mL (placebo Respimat®); p < 0.05; and 230 mL (HandiHaler®) versus −90 mL (placebo HandiHaler®); p ≤ 0.001).,The urinary excretion (up to 2 hours post-dose) of tiotropium 5-10 μg Respimat® was comparable with tiotropium 18 μg HandiHaler®; the overall incidence of adverse events was comparable across treatment groups.,Tiotropium 5 and 10 μg Respimat® improve lung function in COPD patients and appear to be comparable with tiotropium 18 μg HandiHaler®. | 1 |
Intergenerational associations in chronic obstructive pulmonary disease (COPD) have been well recognized and may result from genetic, gene environment, or exposure to life course factors.,Consequently, adult offspring of parents with COPD may be at a greater risk of developing COPD.,The aim of this study was to review the prevalence of co-occurrence of COPD in adult offspring with one or both parents having COPD independent of specific genetic variations.,In total, five databases were searched for original studies in which prevalence of COPD was reported in both offspring (children) and one or both parents.,Studies were excluded if COPD was not clearly defined, COPD was linked to specific genetic variations, COPD was combined with other chronic respiratory conditions, or estimates included other first-degree relatives.,Data extraction (ie, sample characteristics, prevalence of COPD, and odds ratio [OR] if reported) was completed by two independent reviewers.,A meta-analysis of prevalence and OR was conducted, where possible.,Of the 3,382 citations, 129 full texts were reviewed to include eight studies (six case-control, one cross-sectional, and one cohort) reflecting either prevalence of COPD in offspring of parents with COPD (descendent approach, n=3), which ranged from 0% to 17.3%, or prevalence of people with COPD reporting positive parental history of COPD (antecedent approach, n=5), for which the pooled prevalence was 28.6%.,Offspring of people with COPD had 1.57 times greater odds (95% confidence interval =1.29-1.93; P<0.001) of having COPD compared with people not having a parental history of COPD.,The prevalence of COPD in adult offspring of people with COPD is greater than population-based estimates, and the ORs indicate a higher risk in this group.,This offers clinicians a potential strategy for opportunistic screening, early identification, and intervention in this at-risk group. | Although β-blockers are an established therapy in heart failure (HF) guidelines, including for patients with chronic obstructive pulmonary disease (COPD), there remain concerns regarding bronchoconstriction even with cardioselective β-blockers.,We wished to assess the real-life use of β-blockers for patients with HF and comorbid COPD.,We evaluated data from the Optimum Patient Care Research Database over a period of 1 year for co-prescribing of β-blockers with either an ACE inhibitor (ACEI) or angiotensin-2 receptor blocker (ARB) in patients with HF alone versus HF+COPD.,Association with inhaler therapy was also evaluated.,We identified 89 861 patients with COPD, 24 237 with HF and 10 853 with both conditions.,In patients with HF+COPD, the mean age was 79 years; 60% were male, and 27% had prior myocardial infarction.,Of patients with HF+COPD, 22% were taking a β-blocker in conjunction with either ACEI/ARB (n=2416) compared with 41% of patients with HF only (n=10 002) (adjusted OR 0.54, 95% CI 0.51 to 0.58, p<0.001).,Among HF+COPD patients taking inhaled corticosteroid (ICS) with long-acting β-agonist (LABA) and long-acting muscarinic antagonist, 27% of patients were taking an ACEI/ARB with β-blockers (n=778) versus 46% taking an ACEI/ARB without β-blockers (n=1316).,Corresponding figures for those patients taking ICS/LABA were 20% (n=583) versus 48% (n=1367), respectively.,These data indicate a substantial unmet need for patients with COPD who should be prescribed β-blockers more often for concomitant HF. | 1 |
The population with multiple chronic conditions is growing.,Prior studies indicate that patients with comorbidities are frequently excluded from trials but do not address whether information is available in trials to draw conclusions about treatment effects for these patients.,We conducted a literature survey of trials from 11 Cochrane Reviews for four chronic diseases (diabetes, heart failure, chronic obstructive pulmonary disease, and stroke).,The Cochrane Reviews systematically identified and summarized trials on the effectiveness of diuretics, metformin, anticoagulants, longacting beta-agonists alone or in combination with inhaled corticosteroids, lipid lowering agents, exercise and diet.,Eligible studies were reports of trials included in the Cochrane reviews and additional papers that described the methods of these trials.,We assessed the exclusion and inclusion of people with comorbidities, the reporting of comorbidities, and whether comorbidities were considered as potential modifiers of treatment effects.,Overall, the replicability of both the inclusion criteria (mean [standard deviation (SD)]: 6.0 (2.1), range (min-max): 1-9.5) and exclusion criteria(mean(SD): 5.3 (2.1), range: 1-9.5) was only moderate.,Trials excluded patients with many common comorbidities.,The proportion of exclusions for comorbidities ranged from 0-42 percent for heart failure, 0-55 percent for COPD, 0-44 percent for diabetes, and 0-39 percent for stroke.,Seventy of the 161 trials (43.5%) described the prevalence of any comorbidity among participants with the index disease.,The reporting of comorbidities in trials was very limited, in terms of reporting an operational definition and method of ascertainment for the presence of comorbidity and treatments for the comorbidity.,It was even less common that the trials assessed whether comorbidities were potential modifiers of treatment effects.,Comorbidities receive little attention in chronic disease trials.,Given the public health importance of people with multiple chronic conditions, trials should better report on comorbidities and assess the effect comorbidities have on treatment outcomes. | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Glycopyrronium is a once-daily, inhaled long-acting muscarinic antagonist (LAMA) demonstrating similar efficacy to inhaled tiotropium in patients with moderate-to-severe COPD; however, the benefit of LAMAs on COPD symptoms has been variable.,COPD is a progressive disease in which many patients develop an acute or sustained deterioration.,Data on the prevention of clinically important deteriorations (CID) using LAMAs are limited.,A pooled analysis was performed on four Phase III trials (n = 2936) that compared the efficacy of glycopyrronium (n = 1859) with tiotropium (n = 1077).,The primary endpoint was significant delay and/or reduction in the occurrence of CID.,CID was defined as any of the following: ≥100 mL decrease from baseline in pre-dose forced expiratory volume in 1 second (FEV1), ≥4 point increase in St George’s Respiratory Questionnaire score or a moderate-to-severe COPD exacerbation occurring after the first dose of study medication.,A sustained CID was a CID occurring on ≥2 consecutive visits 4 weeks apart or for ≥50% of all available subsequent visits.,Baseline characteristics for the overall population were similar.,Patients had moderate (62%) or severe (38%) COPD.,Mean post-bronchodilator FEV1 was approximately 55% predicted, and mean FEV1 reversibility was 16.7 and 18.6% in the glycopyrronium and tiotropium groups, respectively.,Both glycopyrronium and tiotropium significantly reduced time to CID and sustained CID versus placebo (p < 0.001).,No statistically significant differences were found between the glycopyrronium and tiotropium treatment groups in time to CID or sustained CID.,Glycopyrronium is effective in delaying time to clinically important deteriorations, with similar efficacy to tiotropium.,A novel inhaled drug shows promise in treating moderate to severe chronic lung disease.,Guidelines recommend long-term treatment of chronic obstructive pulmonary disease (COPD) with long-acting muscarinic antagonist (LAMA) inhalers.,Tiotropium is a common COPD LAMA.,Now, Anthony D’Urzo at the University of Toronto, Canada, together with an international research team, have carried out a pooled analysis of results from four clinical trials to compare the efficacy of a novel LAMA, glycopyrronium, with tiotropium.,In these trials, 2936 patients were treated with either glycopyrronium or tiotropium, and the health status of patients using glycopyrronium was also compared with those given a placebo.,Glycopyrronium was as effective as tiotropium in delaying or preventing clinically important deteriorations in patient health.,The risk of deteriorations was significantly lower in the glycopyrronium group than the placebo group. | Chronic obstructive pulmonary disease (COPD) is a debilitating condition characterized by airflow limitation that is not fully reversible.,It is a major cause of morbidity and mortality and represents substantial economic and social burden throughout the world.,A range of interventions has been developed that decrease symptoms and address complications associated with COPD.,However, to date few interventions have been unequivocally demonstrated to modify disease progression.,Assessment of the potential for interventions to modify disease progression is complicated by the lack of a clear definition of disease modification and disagreement over appropriate markers by which modification should be evaluated.,To clarify these issues, a working group of physicians and scientists from the USA, Canada and Europe was convened.,The proposed working definition of disease modification resulting from the group discussions was “an improvement in, or stabilization of, structural or functional parameters as a result of reduction in the rate of progression of these parameters which occurs whilst an intervention is applied and may persist even if the intervention is withdrawn”.,According to this definition, pharmacologic interventions may be considered disease-modifying if they provide consistent and sustained improvements in structural and functional parameters.,Smoking cessation and lung volume reduction surgery would both qualify as disease-modifying interventions. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lungs associated with progressive disability.,Although general practitioners (GPs) should play an important role in the COPD management, critical issues have been documented in the primary care setting.,The aim of this study was to evaluate the effectiveness of an educational program for the improvement of the COPD management in a Sicilian general practice setting.,The effectiveness of the program, was evaluated by comparing 15 quality-of-care indicators developed from data extracted by 33 GPs, at baseline vs. 12 and 24 months, and compared with data from a national primary care database (HSD).,Moreover, data on COPD-related and all-cause hospitalizations over time of COPD patients, was measured.,Overall, 1,465 patients (3.2%) had a registered diagnosis of COPD at baseline vs.,1,395 (3.0%) and 1,388 (3.0%) over time (vs.,3.0% in HSD).,COPD patients with one spirometry registered increased from 59.7% at baseline to 73.0% after 2 years (vs.,64.8% in HSD).,Instead, some quality of care indicators where not modified such as proportion of COPD patients treated with ICS in monotherapy that was almost stable during the study period: 9.6% (baseline) vs.,9.9% (after 2 years), vs.,7.7% in HSD.,COPD-related and all-cause hospitalizations of patients affected by COPD decreased during the two observation years (from 6.9% vs.,4.0%; from 23.0% vs.,18.9%, respectively).,Our study showed that educational program involving specialists, clinical pharmacologists and GPs based on training events and clinical audit may contribute to partly improve both diagnostic and therapeutic management of COPD in primary care setting, despite this effect may vary across GPs and indicators of COPD quality of care.,An education program for doctors covering chronic lung disease diagnosis and management improves elements of patient care in Italy.,Gianluca Trifirò at the University of Messina, Italy, and co-workers followed a cohort of 33 family doctors and 1,465 patients with chronic obstructive pulmonary disease (COPD) in Sicilian primary care for two years, comparing quality of care for patients before and after implementing the education program.,The training, led by lung specialists and clinical pharmacologists, updated doctors with the latest information on COPD diagnosis, medication and disease management, and trained them in spirometry test interpretation.,The team assessed the value of the program using quality-of-care indicators and asked each doctor to re-evaluate patients’ COPD diagnosis.,Their results showed improvement in some areas, including spirometry testing, alongside a reduction in hospital admissions over the two-year period. | Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | 1 |
As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l | Bodyweight and fat distribution may be related to COPD risk.,Limited prospective evidence linked COPD to abdominal adiposity.,We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.,The China Kadoorie Biobank recruited participants aged 30-79 years from 10 areas across China.,Anthropometric indexes were objectively measured at the baseline survey during 2004-2008.,After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016.,We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.,Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported.,Compared with subjects with normal BMI (18.5-<24.0 kg·m−2), underweight (BMI <18.5 kg·m−2) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66-1.89).,Overweight (BMI 24.0-<28.0 kg·m−2) and obesity (BMI ≥28.0 kg·m−2) were not associated with an increased risk after adjustment for waist circumference.,A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI.,Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.http://bit.ly/36To4fk | 1 |
α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT.,Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD.,Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression.,Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice.,The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ.,AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease.,Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear.,There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments.,AATD is a hereditary disorder associated with a high risk for the development of several lung diseases.,There is a need to answer different questions about epidemiology, genetics, pathophysiology, clinical management and prognosis of these lung diseases.http://bit.ly/2IHQGOp | Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD).,AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism.,However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema.,Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury.,To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM).,Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C.,AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence.,Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells.,Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice.,This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement.,Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs.,In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema. | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | Caveolae are vesicular invaginations of the plasma membrane.,Caveolin-1 is the structural protein component of caveolae.,Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signaling molecules within caveolar membranes.,Cigarette smoke, a source of oxidants, is an environmental hazard that causes pulmonary emphysema.,Recently, we reported that the development of cigarette smoking-induced pulmonary emphysema was inhibited in caveolin-1 null mice, which do not express caveolin-1.,We demonstrated that lack of caveolin-1 expression in lung fibroblasts dramatically inhibited premature senescence induced by oxidants contained in cigarette smoke.,Mechanistically, we uncovered that premature senescence of lung fibroblasts induced by oxidative stress occurred through activation of an ataxia telangiectasia-mutated (ATM)/p53-depedent pathway following sequestration of the catalytic subunit of protein phosphatase 2A (PP2A-C), an inhibitor of ATM, by caveolin-1 into caveolar membranes.,We propose caveolin-1 as a key player of a novel signaling pathway that links cigarette smoke to premature senescence of lung fibroblasts and development of pulmonary emphysema. | 1 |
Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been studied in relation to the susceptibility to COPD and COPD with pulmonary hypertension (PH) with inconclusive results.,We performed the first comprehensive meta-analysis to evaluate accurately the association between the ACE gene polymorphism and the risk of COPD.,Data were analyzed using odds ratios (ORs) and the corresponding 95% CIs to measure the strength of the models.,Subgroup analyses were conducted by ethnicity and complication which referred to PH.,In total, 15 studies (2,635 participants) were included in our study, of which four studies (288 participants) were for PH subgroup.,The overall analysis results indicated that the ACE gene polymorphism was not associated with COPD susceptibility in all gene models.,However, the ethnic subgroup analysis results indicated that ACE gene polymorphism was associated with Asians’ susceptibility to COPD (DD+DI vs II, OR=1.47, P=0.019, 95% CI: 1.07-2.02).,Further, the overall results of the present study detected no statistical significance between ACE gene polymorphism and the risk of COPD with PH, but the homozygote variant (DD) increased the risk of PH in Asian COPD patients (DD vs ID+II, OR=2.05, P=0.05, 95% CI: 1.00-4.19).,The current study suggests that ACE polymorphism, particularly the homozygote variant (DD), might contribute to the risk of COPD and COPD with PH among Asians.,Further studies with larger sample size and more ethnicities are expected to be conducted in the future to validate the results. | The interleukin-1 (IL-1) gene polymorphisms have been implicated in chronic obstructive pulmonary disease (COPD) risk, but results are controversial.,We aimed to conduct a meta-analysis to address this issue.,Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association.,The meta-analysis revealed no association between the IL1B (−511), (−31), (+3954) polymorphisms and COPD risk.,However, stratification by ethnicity indicated that the T allele carriers of the IL1B (−511) polymorphism and the C allele carriers of the IL1B (−31) variant were associated with an increased risk for developing COPD in East Asians (OR = 1.61, 95% CI: 1.13-2.31, Pz = 0.009 and OR = 1.55, 95% CI: 1.14-2.11, Pz = 0.006, respectively).,The meta-analysis revealed a significant association between the IL1RN (VNTR) polymorphism and COPD risk in all study subjects and East Asians under homozygote model (22 vs.,LL: OR = 3.16, 95% CI: 1.23-8.13, Pz = 0.017 and OR = 3.20, 95% CI: 1.13-9.12, Pz = 0.029, respectively).,Our meta-analysis suggests that the IL1B (−511), (−31) and IL1RN (VNTR) polymorphisms are associated with COPD risk in East Asians.,There is no association between the IL1B (+3954) polymorphism and COPD risk.,Further studies should be performed in other ethnic groups besides East Asians. | 1 |
Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD).,We conducted a population-based case-control study to evaluate the effects of hypnotics on the risk of adverse respiratory events in patients with COPD.,The case-control study was investigated using data retrieved from the Taiwan National Health Insurance Research Database.,Patients with newly diagnosed adverse respiratory events (pneumonia, COPD with acute exacerbation, acute respiratory failure, and cardiopulmonary arrest) were included in the case group.,Patients with COPD and no history of adverse respiratory events were randomly selected for the control group, which was frequency-matched with the case group according to index date, age (per 10 years), and sex.,Patients who had used hypnotics within 1 month meant active users.,The odds ratios (ORs) and 95% confidence intervals (CIs) of were calculated using univariable and multivariable logistic regression models.,Most of the study participants were male (71.6%), and the mean ages of the participants in the case and control groups were 69.2 (±12.4) and 67.5 (±12.3) years, respectively.,After potential confounding factors were adjusting for, the adjusted ORs of adverse respiratory events were 12.0 for active users of benzodiazepines (95% CI, 8.11-17.6) and 10.5 for active users of nonbenzodiazepines (95% CI, 7.68-14.2) compared with the adjusted ORs of those who never used hypnotics.,The results of this epidemiological study suggested that hypnotics increased the risk of adverse respiratory events in patients with COPD. | Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcoholic Fatty Liver Disease (NAFLD) both independently increase cardiovascular risk.,We hypothesized that NAFLD might increase the incidence of cardiovascular disease and death in COPD patients.,The relationship between NAFLD, incident cardiovascular events, and death was assessed in a prospective cohort of COPD patients with 5-year follow-up.,Noninvasive algorithms combining biological parameters (FibroMax®) were used to evaluate steatosis, non-alcoholic steatohepatitis (NASH) and liver fibrosis.,Univariate and multivariate Cox regression models were used to assess the hazard for composite outcome at the endpoint (death or cardiovascular event) for each liver pathology.,In 111 COPD patients, 75% exhibited liver damage with a prevalence of steatosis, NASH and fibrosis of 41%, 37% and 61%, respectively.,During 5-year follow-up, 31 experienced at least one cardiovascular event and 7 died.,In univariate analysis, patients with liver fibrosis had more cardiovascular events and higher mortality (Hazard ratio [95% CI]: 2.75 [1.26; 6.03]) than those with no fibrosis; this remained significant in multivariate analysis (Hazard ratio [95% CI]: 2.94 [1.18; 7.33]).,We also found that steatosis and NASH were not associated with increased cardiovascular events or mortality.,To conclude, early assessment of liver damage might participate to improve cardiovascular outcomes in COPD patients. | 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 |
In chronic obstructive pulmonary disease (COPD), the problem of poor patient participation in studies of self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as COPD support programmes) is established.,Understanding this problem beyond the previously reported socio-demographics and clinical factors is critical.,The aim of this study was to explore factors that explain patient participation in studies of COPD support programmes.,Thematic ‘framework’ synthesis was conducted on literature published from 1984 to 1 February 2015.,Emergent themes and subthemes were mapped onto the adapted ‘attitude-social influence-external barriers’ and the ‘self-regulation’ models to produce analytical themes.,Ten out of 12 studies were included: PR (n=9) and SM (n=1).,Three descriptive themes with 38 subthemes were mapped onto the models' constructs, and it generated four analytical themes: ‘attitude’, ‘social influences’ and ‘illness’ and ‘intervention representations’.,The following factors influenced (1) attendance-helping oneself through health improvements, perceived control of worsening condition, perceived benefits and positive past experience of the programme, as well as perceived positive influence of professionals; (2) non-attendance-perceived negative effects and negative past experience of the programme, perceived physical/practical concerns related to attendance, perceived severity of condition/symptoms and perceived negative influence of professionals/friends; (3) dropout-no health improvements perceived after attending a few sessions of the programme, perceived severity of the condition and perceived physical/practical concerns related to attendance.,Psychosocial factors including perceived practical/physical concerns related to attendance influenced patients’ participation in COPD support programmes.,Addressing the negative beliefs/perceptions via behaviour change interventions may help improve participation in COPD support programmes and, ultimately, patient outcomes. | Home telehealth has the potential to benefit heart failure (HF) and chronic obstructive pulmonary disease (COPD) patients, however large-scale deployment is yet to be achieved.,The aim of this review was to assess levels of uptake of home telehealth by patients with HF and COPD and the factors that determine whether patients do or do not accept and continue to use telehealth.,This research performs a narrative synthesis of the results from included studies.,Thirty-seven studies met the inclusion criteria.,Studies that reported rates of refusal and/or withdrawal found that almost one third of patients who were offered telehealth refused and one fifth of participants who did accept later abandoned telehealth.,Seven barriers to, and nine facilitators of, home telehealth use were identified.,Research reports need to provide more details regarding telehealth refusal and abandonment, in order to understand the reasons why patients decide not to use telehealth.,The online version of this article (doi:10.1007/s12160-014-9607-x) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common cause of suffering and death.,Evidence-based management of COPD by general practitioners (GPs) is crucial for decreasing the impact of the disease.,Efficient strategies include early diagnosis, smoking cessation and multimodal treatment.,To describe knowledge about and skills for managing COPD in GPs in Sweden.,Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers (PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice and free-text questions about COPD.,Their knowledge and practical management skills were assessed by assigned points that were analyzed with non-parametric tests.,Overall, 250 GPs at 34 PHCCs replied (89% response rate).,Total mean score was 9.9 (maximum 26).,Scores were highest on ‘management of smoking cessation’, ‘follow-up after exacerbation’ and ‘diagnostic procedures’.,Spirometry was used frequently, although interpretation skills were suboptimal.,‘Management of maintenance therapy’, ‘management of multimorbidity’ and ‘interprofessional cooperation’ had mediocre scores.,Scores were unrelated to whether there was a nurse-led asthma/COPD clinic at the PHCC.,Swedish GPs’ knowledge of COPD and adherence to current guidelines seem insufficient.,A nurse-led asthma/COPD clinic at the PHCC does not correlate with sufficient COPD skills in the GPs.,The relevance of this study to participants’ actual clinical practice and usefulness of easy-to-access clinical guides are interesting topics for future investigation.,To identify problem areas, we suggest using questionnaires prior to educational interventions.,General practitioners (GPs) play a crucial role in providing evidence-based care for patients with chronic obstructive pulmonary disease (COPD) who are treated in primary care.,Swedish GPs’ knowledge about COPD and adherence to current guidelines seem insufficient.,Areas in greatest need of improvement are spirometry interpretation, management of maintenance therapy, management of multimorbidity in patients with COPD and interprofessional cooperation. | The use of adequate self-management strategies for people with chronic obstructive pulmonary disease (COPD) reduces healthcare use, improves health-related quality of life (HRQoL) and recovery after acute exacerbations.,However, not many people with COPD receive support that promotes the use of such strategies and therefore new methods to facilitate and promote the use of self-management strategies are highly warranted.,This pilot trial aims to evaluate the feasibility of the study design and study procedures considering effectiveness of the novel intervention, the COPD-web.,The overall design is a pragmatic controlled pilot trial with preassessments and postassessments and a parallel process evaluation.,Patients with the diagnosis of COPD will be eligible for the study.,The intervention group will be recruited when visiting one of the six participating primary care units in Sweden.,The control group will be identified from the unit's computerised registers.,The intervention, the COPD-web, is an interactive web page with two sections; one directed at people with COPD and one at healthcare professionals.,The sections aim to support patients’ self-management skills-and to facilitate the provision of support for self-management strategies, respectively.,Effectiveness with regard to patients’ symptoms, HRQoL, knowledge of and readiness for COPD-related self-management, health literacy, self-efficacy for physical activity and time spent in physical activity and time being sedentary, and further, healthcare professionals’ knowledge of and readiness to support COPD-related self-management strategies will be assessed using questionnaires at 3 and 12 months.,The process evaluation will include observations and interviews.,Ethical approval has been obtained.,Findings will be presented at conferences, submitted for publication in peer-reviewed publications and presented to the involved healthcare professionals, patients and to patient organisations.,ClinicalTrials.gov: NCT02696187 | 1 |
This systematic review aimed to systematise the different designs used to deliver pulmonary rehabilitation during acute exacerbations of COPD (AECOPD) and explore which ones are the most effective.,PubMed, Scopus, Web of Science, EBSCO and Cochrane were searched.,Randomised controlled trials comparing pulmonary rehabilitation or at least one of its components with usual care or comparing different components of pulmonary rehabilitation were included.,Network meta-analysis was conducted in MetaXL 5.3 using a generalised pairwise modelling framework.,Pooled effects compared each treatment to usual care.,42 studies were included.,Most studies were conducted in an inpatient setting (57%) and started the intervention 24-48 h after hospital admission (24%).,Exercise training (71%), education and psychosocial support (57%) and breathing techniques (55%) were the most used components.,Studies combining exercise with breathing techniques presented the larger effects on exercise capacity (weighted mean difference (WMD) −41.06, 95% CI −131.70-49.58) and health-related quality of life (WMD 14.64, 95% CI 8.73-20.54), and breathing techniques presented the larger effects on dyspnoea (WMD 1.90, 95% CI 0.53-3.27) and length of hospitalisation (effect size =0.15, 95% CI −0.28-0.57).,A few minor adverse events were found.,Pulmonary rehabilitation is a safe intervention during AECOPD.,Exercise, breathing techniques, and education and psychosocial support seem to be the core components for implementing pulmonary rehabilitation during AECOPD.,Studies may now focus on comparisons of optimal timings to start the intervention, total duration of the intervention, duration and frequency of sessions, and intensity for exercise prescription.,Combination of exercise training, breathing techniques and education and psychosocial support is the most effective design to deliver pulmonary rehabilitation during acute exacerbations of COPDhttps://bit.ly/2TAh2aP | Pulmonary rehabilitation (PR) is able to improve dyspnea, endurance capacity, and health-related quality of life in chronic obstructive pulmonary disease (COPD) patients, but it is rarely used in China.,This study aimed to assess the effectiveness and safety of PR after exacerbation of COPD.,Patients admitted to hospital due to an exacerbation of COPD were randomized to receive either PR or routine care (control group).,The PR program was performed from the second day of admission until discharge.,The pre-post changes in 6-minute walk distance (6MWD), self-reported quality of life (QOL) assessed by CAT score and CRQ-SAS score, and activity of daily life assessed by ADL-D score were determined.,The perceived end-effort dyspnea (Borg scale) was measured throughout the study.,A total of 101 patients were enrolled, of whom 7 withdrew after randomization, and 94 completed this study.,There were 66 patients in the PR group and 28 in the control group.,The 6MWD, resting SpO2, and exercise Borg dyspnea score were significantly improved in the PR group.,In addition, the PR group had greater improvement in the total CRQ-SAS score and had a lower CAT score.,Significant improvements were also found in the ADL-D and BODE index in the PR group.,No adverse events were recorded during exercise.,Our study provides evidence that it is safe and feasible to apply an early PR in patients with acute exacerbation of COPD. | 1 |
There is growing evidence that home telemonitoring can be advantageous in societies with increasing prevalence of chronic diseases.,The main objective of this study is to evaluate the effect of a primary care-based telemonitoring intervention on the number and length of hospital admissions.,A randomised controlled trial was carried out across 20 health centres in Bilbao (Basque Country, Spain) to assess the impact of home telemonitoring on in-home chronic patients compared with standard care.,The study lasted for one year.,Fifty-eight in-home patients, diagnosed with heart failure (HF) and/or chronic lung disease (CLD), aged 14 or above and with two or more hospital admissions in the previous year were recruited.,The intervention consisted of daily patient self-measurements of respiratory-rate, heart-rate, blood pressure, oxygen saturation, weight, body temperature and the completion of a health status questionnaire using PDAs.,Alerts were generated when pre-established thresholds were crossed.,The control group (CG) received usual care.,The primary outcome measure was the number of hospital admissions that occurred at 12 months post-randomisation.,The impact of telemonitoring on the length of hospital stay, use of other healthcare resources and mortality was also explored.,The intervention group (IG) included 28 patients and the CG 30.,Patient baseline characteristics were similar in both groups.,Of the 21 intervention patients followed-up for a year, 12 had some admissions (57.1%), compared to 19 of 22 controls (86.4%), being the difference statistically significant (p = 0.033, RR 0.66; 95%CI 0.44 to 0.99).,The mean hospital stay was overall 9 days (SD 4.3) in the IG versus 10.7 (SD 11.2) among controls, and for cause-specific admissions 9 (SD 4.5) vs.,11.2 (SD 11.8) days, both without statistical significance (p = 0.891 and 0.927, respectively).,Four patients need to be telemonitored for a year to prevent one admission (NNT).,There were more telephone contacts in the IG than in the CG (22.6 -SD 16.1- vs.,8.6 -SD 7.2-, p = 0.001), but fewer home nursing visits (15.3 -SD 11.6- vs.,25.4 -SD 26.3-, respectively), though the difference was not statistically significant (p = 0.3603).,This study shows that telemonitoring of in-home patients with HF and/or CLD notably increases the percentage of patients with no hospital admissions and indicates a trend to reduce total and cause-specific hospitalisations and hospital stay.,Home telemonitoring can constitute a beneficial alternative mode of healthcare provision for medically unstable elderly patients.,Current Controlled Trials ISRCTN89041993 | The ability to objectively differentiate exacerbations of chronic obstructive pulmonary disease (COPD) from day-to-day symptom variations would be an important development in clinical practice and research.,We assessed the ability of domiciliary pulse oximetry to achieve this.,40 patients with moderate-severe COPD collected daily data on changes in symptoms, heart-rate (HR), oxygen saturation (SpO2) and peak-expiratory flow (PEF) over a total of 2705 days. 31 patients had data suitable for baseline analysis, and 13 patients experienced an exacerbation.,Data were expressed as multiples of the standard deviation (SD) observed from each patient when stable.,In stable COPD, the SD for HR, SpO2 and PEF were approximately 5 min-1, 1% and 10l min-1.,There were detectable changes in all three variables just prior to exacerbation onset, greatest 2-3 days following symptom onset.,A composite Oximetry Score (mean magnitude of SpO2 fall and HR rise) distinguished exacerbation onset from symptom variation (area under receiver-operating characteristic curve, AUC = 0.832, 95%CI 0.735-0.929, p = 0.003).,In the presence of symptoms, a change in Score of ≥1 (average of ≥1SD change in both HR and SpO2) was 71% sensitive and 74% specific for exacerbation onset.,We have defined normal variation of pulse oximetry variables in a small sample of patients with COPD.,A composite HR and SpO2 score distinguished exacerbation onset from symptom variation, potentially facilitating prompt therapy and providing validation of such events in clinical trials. | 1 |
Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management.,Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease.,Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics.,To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management.,To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction.,An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people).,Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena.,(1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering.,The results indicate the high potential of a systems approach to address COPD heterogeneity.,Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD. | The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined.,Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation.,COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa.,Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing.,Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa.,Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364).,In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations.,An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples.,These increases were not identified by culture in 5 out of 13 participants (38.5 %).,Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions.,Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.,The online version of this article (doi:10.1007/s10096-013-2044-0) contains supplementary material, which is available to authorized users. | 1 |
The present paper is a narrative review focusing on the psychological impact, identification of protective factors, and interventions minimizing the psychological burdens of chronic obstructive pulmonary disease (COPD).,The research reviews studies on neurocognitive functions, personality, emotional problems, and health-related quality of life.,This is done with regard to resources as well as activities enabling or enhancing a patient’s adaptation.,PubMed and PsychArticles databases were searched for relevant medical (eg, CODP, emphysema), psychopathology (eg, depression), and psychological (eg, personality) keywords, followed by hand search.,After application of the inclusion and exclusion criteria, the search resulted in 82 articles and book chapters.,The choice was based on evidence accepted by evidence-based medicine, although at different levels of strength.,Psychological experiencing of COPD appears to be very unequally represented with scientific research on emotional problems and functioning decrease significantly outnumbering those addressing resources or effective interventions.,As our initial literature search called for an urgent need for further exploration, we have carefully pointed out numerous areas where the knowledge on how to protect or restore psychological well-being among COPD patients should be broadened. | “Physical inactivity” and “sedentary lifestyles” are phrases often used when describing lifestyles of people with chronic obstructive pulmonary disease (COPD).,Evidence suggests activity types, independent of energy expenditure, influence health outcomes, so understanding patterns of time use is important, particularly in chronic disease.,We aimed to identify reports of time use in people with COPD.,Predefined search strategies were used with six electronic databases to identify individual activity reports (including frequencies and/or durations) in which community-dwelling people with COPD engaged.,Eligible studies were assessed independently against predefined criteria and data were extracted by two reviewers.,Data synthesis was achieved by aggregating activity reports into activity domains (sports/exercise, screen time, transport, quiet time, self-care, sociocultural, work/study, chores, and sleep).,Twenty-six publications reported 37 specific daily activities.,People with COPD were found to spend extended periods in sedentary behaviors (eg, standing [194 min/day]; sitting [359 min/day]; lying [88 min/day]), have limited engagement in physical activity (eg, walking [51 min/day]; exercising [1.2 episodes per week {ep/w}, 13 min/day]), have high health care needs (medical appointments [1.0 ep/w]), and experience difficulties associated with activities of daily living (eg, showering [2.5 ep/w, 60 minutes per episode]; preparing meals [4.7 ep/w]).,Little data could be found describing how people with COPD use their time, and data synthesis was problematic because of variations in methodologies, population differences, and research emphases.,Identified data largely referred to posture and were skewed according to country, assessment methods, and disease severity.,Comparisons with age-matched population data showed people with COPD spent less time engaged in personal-care activities (self-care and sleeping) and chores than people in similar age groups.,The incorporation of time-use outcomes in future research designs should be encouraged.,Ideally, these tools should use consistent frameworks and comparable outcome measures in order to provide clearer descriptions of time use in chronic disease. | 1 |
Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression.,We aimed to assess this in a prospective observational study.,The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD).,Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline.,Effect modification by blood eosinophils was studied through interaction terms.,Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS.,In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001).,This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS.,Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS.,More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function. | The severity of chronic obstructive pulmonary disease (COPD) should not be based on the level of airflow limitation alone.,A multicomponent index such as the DOSE index (dyspnoea score (D), level of airflow obstruction (O), current smoking status (S), and exacerbations (E)) has the potential to predict important future outcomes in patients with COPD more effectively than the forced expiratory volume in one second.,Health status deterioration should be prevented in COPD patients.,To investigate whether the DOSE index can predict which patients are at risk of a clinically relevant change in health status.,A prospective cohort study was performed using data from primary and secondary care.,The DOSE score was determined at baseline and the 2-year change in the Clinical COPD Questionnaire (CCQ) score was calculated.,Linear regression analysis was performed for the effect of a high DOSE score (≥4) on the change in CCQ score.,The study population consisted of 209 patients (112 patients from primary care).,Overall, a high DOSE score was a significant predictor of a change in CCQ score after 2 years (0.41, 95% CI 0.13 to 0.70), particularly in primary care patients.,A DOSE score of ≥4 has the ability to identify COPD patients with a greater risk of future worsening in health status. | 1 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | GOLD guidelines classify COPD patients into A-D groups based on health status as assessed by COPD Assessment Test (CAT) or mMRC tools and exacerbations and recommend single or dual long-acting bronchodilators as maintenance therapy, with additional inhaled corticosteroids (ICS) if the disease remains uncontrolled.,We aimed to classify primary care COPD patients into A-D groups, assess usual treatment and adherence to guidelines, potential mismatches between CAT-and mMRC-based classification and described symptoms within groups.,A total of 257 primary care COPD patients were enrolled between 2015 and 2016 in Greece.,Physicians used structured interviews to collect cross-sectional data including demographics, symptoms, CAT, mMRC scores, and medications.,Patients were classified into A-D groups based on CAT and mMRC, and prevalence of symptoms and medication was estimated within A-D groups.,Interviews with physicians were also performed to explore additional issues about treatment and adherence to guidelines.,Mean (SD) age was 65 (12.3) years with 79% males.,The majority of patients reported uncontrolled symptoms (91% and 61% with ≥10 CAT or ≥2 mMRC scores, respectively).,Thirty-seven percentage had $2 exacerbations in the past year.,Group B was the largest followed by Groups D, A, and C.,Patients were classified as more severe by CAT than by mMRC.,In all groups, the majority were treated with combined long-acting beta agonist/ICS (> 50%).,When patients were asked to report their main symptoms, dyspnea and cough were the most important symptoms mentioned, and there was a great variation between the A-D groups.,However, Groups A-C reported mainly morning symptoms, whereas Group D suffered symptoms all day.,Physicians reported a significant number of barriers to implementing guidelines, eg, frequent lack of guideline updates, access to diagnostic procedures, and prescription-reimbursement issues.,Our study confirms poor adherence to guidelines regarding treatment with an overuse of ICS and important barriers to implementation.,A mismatch in classification occurs depending on the tool used, which can mislead clinicians in their choice of treatment. | 1 |
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