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Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required. | Randomized controlled trials have confirmed the evidence and helped to define when and where non invasive mechanical ventilation (NIV) should be the first line treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Noninvasive ventilation has its best indication in moderate-to-severe respiratory acidosis in patients with AECOPD.,For this indication, studies conducted in ICU, in wards and in accident and emergency departments confirmed its effectiveness in preventing endotracheal intubation and reducing mortality.,The skill of the health care team promotes proper NIV utilization and improves the patient outcome.,Patients with severe acidosis or with altered levels of consciousness due to hypercapnic acute respiratory failure are exposed to high risk of NIV failure.,In these patients a NIV trial may be attempted in closely monitored clinical settings where prompt endotracheal intubation may be assured. | 1 |
Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD).,The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease.,(i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks.,One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS).,(i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission.,Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured.,All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients.,Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment.,There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014.,ID is common in COPD patients but is rarely looked for or treated.,Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea. | Introduction.,Chronic obstructive pulmonary disease (COPD) is associated with comorbidities such as cardiovascular disease, metabolic disease, osteoporosis, and anxiety and/or depression.,Although pulmonary rehabilitation programs are proven to be beneficial in patients with COPD, it is unclear whether comorbidities influence pulmonary rehabilitation outcomes.,The aim of the present review was to investigate to what extent the presence of comorbidities can affect pulmonary rehabilitation outcomes.,Methods.,The systematic literature search (Pubmed, EMBASE, and PEDro) resulted in 4 articles meeting the inclusion criteria.,The odds ratios (95% confidence intervals) of the logistic regression analyses, with comorbidities as independent variables and pulmonary rehabilitation outcomes (dyspnea, functional exercise capacity, and quality of life) as dependent variables, were used for data extraction.,Results.,Patients with anxiety and/or depression less likely improve in dyspnea.,Osteoporosis is associated with less improvements in functional exercise capacity, while cardiovascular disease does not seem to negatively impact on this outcome.,Patients with cardiovascular comorbidity will experience less positive changes in quality of life.,Conclusion.,Evidence from literature suggests that comorbidities can have a negative influence on pulmonary rehabilitation outcomes.,Screening for comorbidities in pulmonary rehabilitation settings seems useful to readdress the right patients for individually tailored pulmonary rehabilitation. | 1 |
Increased prescribing of inhaled long-acting anti-muscarinic (LAMA) and combined inhaled long-acting β2-agonist and corticosteroid (LABA+ICS) drugs for the treatment of chronic obstructive pulmonary disease (COPD) has led to hopes of reduced hospital admissions from this disease.,To investigate the impact of rising primary care prescribing of LAMA and LABA+ICS drugs on COPD admissions.,This retrospective cohort study of general practice COPD admission and prescribing data between 2007 and 2010 comprised a representative group of 806 English general practices (population 5,264,506).,Outcome measures were practice rates of COPD patient admissions and prescription costs of LAMA and LABA+ICS.,General practice characteristics were based on the UK quality and outcomes framework.,Rates of COPD admissions remained stable from 2001 to 2010.,Practice-prescribing volumes of LAMA per practice patient and LABA+ICS per practice patient increased by 61 and 26%, respectively, between 2007 and 2010.,Correlation between costs of LAMA and those of LABA+ICS increased year on year, and was the highest in 2010 (Pearson’s r=0.68; 95% confidence interval (CI), 0.64-0.72).,Practice COPD admission rates were positively predicted by practice-prescribing volumes of LAMA (2010: B=1.23, 95% CI, 0.61-1.85) and of LABA+ICS (2010: B=0.32, 95% CI, 0.12-0.52) when controlling for practice list size, COPD prevalence and deprivation.,The increase in the prescribing of LAMA and LABA+ICS inhalers was not associated with the predicted fall in hospital admission rates for COPD patients.,The positive correlation between high practice COPD prescribing and high practice COPD admissions was not explained. | To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS).,The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007.,The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS.,Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data.,We examined the baseline characteristics of these patients along with their healthcare resource utilization.,Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines.,A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results.,The adherent subgroup received COPD medications consistent with current GOLD guidelines.,Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines.,In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines.,In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines.,GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts.,Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD.,Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers. | 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. | Inhaled corticosteroids (ICSs) are recommended for patients with frequent exacerbation of chronic obstructive pulmonary disease (COPD).,However, accumulating evidence has indicated the risk of pneumonia from the use of ICS.,This study aimed to investigate the association between ICS and pneumonia in the real-world clinical setting.,A retrospective cohort study was performed using nationwide population data from the Korea National Health Insurance Service.,Subjects who had a new diagnosis of COPD and who received inhaled bronchodilators without a diagnosis of pneumonia before the initiation of bronchodilators were identified.,Subjects were followed up until their first diagnosis of pneumonia.,The risk of pneumonia in ICS users was compared to that in non-ICS users.,A total of 87,594 subjects were identified and 1:1 matched to 22,161 ICS users and non-ICS users.,More ICS users were diagnosed with pneumonia compared to non-ICS users (33.73% versus 24.51%, P<0.0001).,The incidence rate per 100,000 person-years was 8904.98 for ICS users and 6206.79 for non-ICS users.,The hazard ratio (HR) of pneumonia for ICS users was 1.62 (95% CI 1.54-1.70).,The HR of subjects prescribed with the lowest ICS cumulative dose was 1.35 (1.27-1.43).,The HR increased to 1.51 (1.42-1.60), 1.96 (1.85-2.09), and 2.03 (1.89-2.18) as the cumulative dose increased.,Pneumonia was strongly associated with fluticasone propionate (1.79 (1.70-1.89)) and fluticasone furoate (1.80 (1.61-2.01)) use, compared to the use of other types of ICS.,ICS increases the risk of pneumonia in patients with COPD.,Hence, ICS should be carefully prescribed in patients with risk factors for pneumonia while considering the cumulative doses and subtypes of ICS. | 1 |
To investigate the association between living near dense traffic and lung function in a cohort of adults from a single urban region.,Cross-sectional results from a cohort study.,The adult-onset asthma and exhaled nitric oxide (ADONIX) cohort, sampled during 2001-2008 in Gothenburg, Sweden.,Exposure was expressed as the distance from participants’ residential address to the nearest road with dense traffic (>10 000 vehicles per day) or very dense traffic (>30 000 vehicles per day).,The exposure categories were: low (>500 m; reference), medium (75-500 m) or high (<75 m).,The source population was a population-based cohort of adults (n=6153).,The study population included 5441 participants of European descent with good quality spirometry and information about all outcomes and covariates.,Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at a clinical examination.,The association with exposure was examined using linear regression adjusting for age, gender, body mass index, smoking status and education in all participants and stratified by sex, smoking status and respiratory health status.,We identified a significant dose-response trend between exposure category and FEV1 (p=0.03) and borderline significant trend for FVC (p=0.06) after adjusting for covariates.,High exposure was associated with lower FEV1 (−1.0%, 95% CI −2.5% to 0.5%) and lower FVC (−0.9%, 95% CI −2.2% to 0.4%).,The effect appeared to be stronger in women.,In highly exposed individuals with current asthma or chronic obstructive pulmonary disease, FVC was lower (−4.5%, 95% CI −8.8% to −0.1%).,High traffic exposure at the residential address was associated with lower than predicted FEV1 and FVC lung function compared with living further away in a large general population cohort.,There were particular effects on women and individuals with obstructive disease. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases.,This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population.,We aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS.,The UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS.,Poisson regression was used to compare the frequency of respiratory adverse events.,At entry, the groups were well matched apart from a higher FEV1% predicted (38 vs.,41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs.,36%; ICS vs. no ICS, respectively).,Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs.,0.056 respectively; p = 0.012).,When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs.,0.058, respectively; p < 0.001).,COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs.,0.84 respectively; p = 0.013).,ICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown.,In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation.,The online version of this article (doi:10.1007/s00408-017-9990-8) contains supplementary material, which is available to authorized users. | The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium.,Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations.,We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged.,Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression.,We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease.,Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts.,Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein.,The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS.,Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect.,The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression.,Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens. | 1 |
Thrombocytosis has been associated with COPD prevalence and increased all-cause mortality in patients with acute exacerbation of COPD (AECOPD); but whether it is associated with morbidity in stable COPD is unknown.,This study aims to determine the association of thrombocytosis with COPD morbidity including reported AECOPD, respiratory symptoms and exercise capacity.,Participants with COPD were included from two multi-center observational studies (SPIROMICS and COPDGene).,Cross-sectional associations of thrombocytosis (platelet count ≥350 × 109/L) with AECOPD during prior year (none vs. any), exertional dyspnea (modified Medical Research Council (mMRC) score ≥ 2), COPD Assessment Test (CAT) score ≥ 10, six-minute-walk distance (6MWD), and St.,George Respiratory questionnaire (SGRQ) were modeled using multivariable logistic or linear regression.,A pooled effect estimate for thrombocytosis was produced using meta-analysis of data from both studies.,Thrombocytosis was present in 124/1820 (6.8%) SPIROMICS participants and 111/2185 (5.1%) COPDGene participants.,In meta-analysis thrombocytosis was associated with any AECOPD (adjusted odds ratio [aOR] 1.5; 95% confidence interval [95% CI]: 1.1-2.0), severe AECOPD (aOR 1.5; 95% CI: 1.1-2.2), dyspnea (mMRC ≥ 2 aOR 1.4; 95% CI: 1.0-1.9), respiratory symptoms (CAT ≥ 10 aOR 1.6; 95% CI: 1.1-2.4), and higher SGRQ score (β 2.7; 95% CI: 0.5, 5).,Thrombocytosis was also associated with classification into Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D (aOR 1.7 95% CI: 1.2-2.4).,Thrombocytosis was associated with higher likelihood of prior exacerbation and worse symptoms.,Platelet count, a commonly measured clinical assay, may be a biomarker for moderate-severe COPD symptoms, guide disease classification and intensity of treatment.,Future longitudinal studies investigating the role of platelets in COPD progression may be warranted.,ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). | Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD.,Fibroblast-derived WNT-5A inhibits canonical WNT-β-catenin-driven alveolar epithelial cell-mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.,Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide.,One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined.,Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated.,Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis.,We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens.,WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence.,Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro.,Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo.,Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD.,We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy. | 1 |
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | 1 |
Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population. | Breathlessness is a primary clinical feature of chronic obstructive pulmonary disease (COPD).,We aimed to describe the frequency of and factors associated with breathlessness in a cohort of COPD patients identified from the Clinical Practice Research Datalink (CPRD), a general practice electronic medical records database.,Patients with a record of COPD diagnosis after January 1 2008 were identified in the CPRD.,Breathlessness was assessed using the Medical Research Council (MRC) dyspnoea scale, with scoring ranging from 1-5, which has been routinely administered as a part of the regular assessment of patients with COPD in the general practice since April 2009.,Stepwise multivariate logistic regression estimated independent associations with dyspnoea.,Negative binomial regression evaluated a relationship between breathlessness and exacerbation rate during follow-up.,The total cohort comprised 49,438 patients diagnosed with COPD; 40,425 (82%) had any MRC dyspnoea grade recorded.,Of those, 22,770 (46%) had moderate-to-severe dyspnoea (MRC≥3).,Breathlessness increased with increasing airflow limitation; however, moderate-to-severe dyspnoea was also observed in 32% of patients with mild airflow obstruction.,Other factors associated with increased dyspnoea grade included female gender, older age (≥70 years), obesity (BMI ≥30), history of moderate-to-severe COPD exacerbations, and frequent visits to the general practitioner.,Patients with worse breathlessness were at higher risk of COPD exacerbations during follow-up.,Moderate-to-severe dyspnoea was reported by >40% of patients diagnosed with COPD in primary care.,Presence of dyspnoea, including even a perception of mild dyspnoea (MRC = 2), was associated with increased disease severity and a higher risk of COPD exacerbations during follow-up. | 1 |
Singing for lung health (SLH) is a popular arts-in-health activity for people with long-term respiratory conditions.,Participants report biopsychosocial benefits, however, research on impact is limited.,The ‘SLH: Improving Experiences of Lung Disease trial’, a randomised controlled, single (assessor) blind, trial of 12 weeks SLH versus usual care for people with chronic obstructive pulmonary disease (COPD) (n=120) was setup to help to address this.,The first group (n=18, nine singing and nine controls) started face-to-face (five sessions) before changing to online delivery (seven sessions) due to COVID-19-related physical distancing measures.,As such, the experience of this group is here reported as a pilot study to inform further research in this area.,We conducted semistructured interviews and thematic analysis regarding barriers, facilitators and key considerations for transitioning from face-to-face to online delivery.,Pilot quantitative outcomes include attendance, premeasures and postmeasures of quality of life and disease impact (Short Form 36 Health Survey, COPD Assessment Test score), breathlessness (Medical Research Council breathlessness scale, Dyspnoea-12), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalised Anxiety Disorder-7), balance confidence (Activity specific Balance Confidence, ABC scale) and physical activity (clinical visit PROactive physical activity in COPD tool, combining subjective rating and actigraphy).,Attendance was 69% overall, (90% of the face-to-face sessions, 53% online sessions).,Analysis of semistructured interviews identified three themes regarding participation in SLH delivered face to face and online, these where (1) perceived benefits; (2) digital barriers (online) and (3) digital facilitators (online).,Findings were summarised into key considerations for optimising transitioning singing groups from face-to-face to online delivery.,Pilot quantitative data suggested possible improvements in depression (treatment effect −4.78 PHQ-9 points, p<0.05, MCID 5) and balance confidence (treatment effect +17.21 ABC scale points, p=0.04, MCID 14.2).,This study identifies key considerations regarding the adaptation of SLH from face-to-face to online delivery.,Pilot data suggest online group singing for people with COPD may deliver benefits related to reducing depression and improved balance confidence. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely.,We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.,Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included.,The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression.,A total 175 participants were included.,No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79).,The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant.,However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline.,There was no significant difference in lung function decline rates according to the GOLD groups.,Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. | 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 |
Breathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (“over-perception”).,Pulmonary rehabilitation profoundly affects breathlessness, without influencing lung function.,Learned associations influence brain mechanisms of sensory perception.,We hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations.,In 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during a breathlessness-related word-cue task (using functional magnetic resonance imaging), and clinical and psychological measures of breathlessness.,Changes in ratings of breathlessness word cues positively correlated with changes in activity in the insula and anterior cingulate cortex.,Changes in ratings of breathlessness-anxiety negatively correlated with activations in attention regulation and motor networks.,Baseline activity in the insula, anterior cingulate cortex and prefrontal cortex correlated with improvements in breathlessness and breathlessness-anxiety.,Pulmonary rehabilitation is associated with altered neural responses related to learned breathlessness associations, which can ultimately influence breathlessness perception.,These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.,Pulmonary rehabilitation improves breathlessness by recalibrating the brain's sensory perception networkshttp://ow.ly/crhy30cQerx | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
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. | The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk).,Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping.,The previous system was solely based on airflow obstruction.,Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations.,The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.,Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates.,A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage.,Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history.,Lung function decline was analysed in a repeated measures model.,Mortality increased from A to D, but there was no difference between B and C.,For the previous GOLD stages 2-4, survival curves were clearly separated.,Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D.,Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D.,With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations.,Distinguishing between the sub-stages of high-risk led to substantial improvements.,The new classification system is a modest step towards a phenotype approach.,It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.,ClinicalTrials.gov NCT00144339 (September 2, 2005).,The online version of this article (doi:10.1186/1471-2466-14-163) contains supplementary material, which is available to authorized users. | 1 |
Symptomatic patients with chronic obstructive pulmonary disease (COPD) and low exacerbation risk still have disease instability, which can be improved with better bronchodilation.,We evaluated two long-acting bronchodilators individually and in combination on reducing exacerbation risk and the potential impact of concurrent medication in these patients.,Integrated post hoc intent-to-treat (ITT) analysis of data from two large 24-week, randomized placebo (PBO)-controlled trials (NCT01313637, NCT01313650).,Symptomatic patients with moderate-to-very-severe COPD with/without an exacerbation history were randomized (2:3:3:3) to once-daily: PBO, umeclidinium/vilanterol (UMEC/VI 62.5/25 μg [NCT01313650] or 125/25 μg [NCT01313637]), UMEC (62.5 [NCT01313650] or 125 μg [NCT01313637]) or VI (25 μg) via the ELLIPTA inhaler.,Medication subgroups were segmented by treatment status at screening: a) maintenance-naïve or on maintenance medications, b) inhaled corticosteroid [ICS]-free or ICS-treated, c) low or high albuterol use based on median run-in use (< 3.6 or ≥ 3.6 puffs/day).,Time to first moderate/severe exacerbation (Cox proportional hazard model) and change from baseline in trough forced expiratory volume in 1 s (FEV1; mixed model repeated measures) were analyzed.,Safety was also assessed.,Of 3021 patients (ITT population; UMEC/VI: n = 816; UMEC: n = 825; VI: n = 825; PBO: n = 555), 36% had a recent exacerbation history, 33% were maintenance-naïve, 51% were ICS-free.,Mean baseline albuterol use was 5.1 puffs/day.,In the ITT population, UMEC/VI, UMEC, and VI reduced the risk of a first exacerbation versus PBO by 58, 44, and 39%, respectively (all p < 0.05).,UMEC/VI provided significant risk reductions versus PBO in all subgroups.,VI had no benefit versus PBO in maintenance-naïve, ICS-free, and low rescue use patients and was significantly less effective than UMEC/VI in these subgroups.,UMEC had no significant benefit versus PBO in maintenance-naïve and ICS-free patients.,All bronchodilators improved FEV1 versus PBO, and UMEC/VI significantly improved FEV1 versus both monotherapies across all populations studied (p < 0.05).,All bronchodilators were similarly well tolerated.,Results suggest that UMEC/VI reduces exacerbation risk versus PBO more consistently across medication subgroups than UMEC or VI, particularly in patients with no/low concurrent medication use.,Confirmed prospectively, these findings may support first-line use of dual bronchodilation therapy in symptomatic low-risk patients.,The online version of this article (10.1186/s12931-019-1027-9) contains supplementary material, which is available to authorized users. | Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis.,We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD.,The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.,This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations.,Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.,In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%).,The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001).,In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%).,UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).,This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods.,UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy. | 1 |
Emphysema is a progressive disease characterized by irreversible airspace enlargement followed by a decline in lung function.,It also causes extrapulmonary effects, such as loss of body mass and cor pulmonale, which are associated with shorter survival and worse clinical outcomes.,Ghrelin, a growth-hormone secretagogue, stimulates muscle anabolism, has anti-inflammatory effects, promotes vasodilation, and improves cardiac performance.,Therefore, we hypothesized that ghrelin might reduce lung inflammation and remodelling as well as improve lung mechanics and cardiac function in experimental emphysema.,Forty female C57BL/6 mice were randomly assigned into two main groups: control (C) and emphysema (ELA).,In the ELA group (n=20), animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals.,C animals (n=20) received saline alone (50 μL) using the same protocol.,Two weeks after the last instillation of saline or PPE, C and ELA animals received ghrelin or saline (n=10/group) intraperitoneally (i.p.) daily, during 3 weeks.,Dual-energy X-ray absorptiometry (DEXA), echocardiography, lung mechanics, histology, and molecular biology were analysed.,In elastase-induced emphysema, ghrelin treatment decreased alveolar hyperinflation and mean linear intercept, neutrophil infiltration, and collagen fibre content in the alveolar septa and pulmonary vessel wall; increased elastic fibre content; reduced M1-macrophage populations and increased M2 polarization; decreased levels of keratinocyte-derived chemokine (KC, a mouse analogue of interleukin-8), tumour necrosis factor-α, and transforming growth factor-β, but increased interleukin-10 in lung tissue; augmented static lung elastance; reduced arterial pulmonary hypertension and right ventricular hypertrophy on echocardiography; and increased lean mass.,In the elastase-induced emphysema model used herein, ghrelin not only reduced lung damage but also improved cardiac function and increased lean mass.,These findings should prompt further studies to evaluate ghrelin as a potential therapy for emphysema.,The online version of this article (10.1186/s12931-017-0668-9) contains supplementary material, which is available to authorized users. | The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1).,However, asingle measurement of FEV1 cannot reliably predict subsequent decline.,Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD.,We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease.,Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT.,The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months.,Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11).,Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines.,Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04).,In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03).,In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05).,These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients.,Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD.,COPD patients have a variety of comorbidities, but little is known about their impact on quality of life.,This study was designed to investigate comorbid factors that may contribute to high CAT scores.,An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects.,Health status was assessed by the CAT, the St.,Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health.,Comorbidities were identified based on patients’ reports, physicians’ records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale.,Dual X-ray absorptiometry measurements of bone mineral density were performed.,The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36.,The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients.,Symptomatic COPD patients have a high prevalence of comorbidities.,A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized.,Clinical trial registered with UMIN (UMIN000003470). | 1 |
This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St.,George’s Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations.,A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations.,These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance.,Sixty-seven trials were included in the analysis.,Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024).,Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant.,The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations.,Even in cases of non-significant relationships, results were in the expected direction with few exceptions.,The results of this analysis offer health care providers and payers a broader picture of the relationship between exacerbations and mean change in FEV1 as well as SGRQ score, and will help inform clinical and formulary-making decisions while stimulating new research questions for future prospective studies. | Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources.,Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients.,This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD.,This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China.,We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D).,The final sample comprised 135 patients.,Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period.,The median (interquartile) time to readmission was 78 days (42-178 days).,Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively).,The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C.,Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination. | 1 |
Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
A core feature of chronic obstructive pulmonary disease (COPD) is the accelerated decline in forced expiratory volume in one second (FEV1).,The recent Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD) study suggested that particular phenotypes of COPD benefit from fluticasone±salmeterol by reducing the rate of FEV1 decline, yet the underlying mechanisms are unknown.,Whole-genome gene expression profiling using the Affymetrix Gene ST array (V.1.0) was performed on 221 bronchial biopsies available from 89 COPD patients at baseline and after 6 and 30 months of fluticasone±salmeterol and placebo treatment in GLUCOLD.,Linear mixed effects modelling revealed that the expression of 138 genes decreased, whereas the expression of 140 genes significantly upregulated after both 6 and 30 months of treatment with fluticasone±salmeterol versus placebo.,A more pronounced treatment-induced change in the expression of 50 and 55 of these 278 genes was associated with a lower rate of decline in FEV1 and Saint George Respiratory Questionnaire, respectively.,Genes decreasing with treatment were involved in pathways related to cell cycle, oxidative phosphorylation, epithelial cell signalling, p53 signalling and T cell signalling.,Genes increasing with treatment were involved in pathways related to focal adhesion, gap junction and extracellular matrix deposition.,Finally, the fluticasone-induced gene expression changes were enriched among genes that change in the airway epithelium in smokers with versus without COPD in an independent data set.,The present study suggests that gene expression in biological pathways of COPD is dynamic with treatment and reflects disease activity.,This study opens the gate to targeted and molecular phenotype-driven therapy of COPD. | Whether inhaled corticosteroids suppress airway inflammation in chronic obstructive pulmonary disease (COPD) remains controversial.,We sought to determine the effects of inhaled corticosteroids on sputum indices of inflammation in stable COPD.,We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Databases for randomized, controlled clinical trials that used induced sputum to evaluate the effect of inhaled corticosteroids in stable COPD.,For each chosen study, we calculated the mean differences in the concentrations of sputum cells before and after treatment in both intervention and control groups.,These values were then converted into standardized mean differences to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across original studies.,If significant heterogeneity was present (p < 0.10), then a random effects model was used to pool the original data.,In the absence of significant heterogeneity, a fixed effects model was used.,We identified six original studies that met the inclusion criteria (N = 162 participants).,In studies with higher cumulative dose (≥ 60 mg) or longer duration of therapy (≥ 6 weeks), inhaled corticosteroids were uniformly effective in reducing the total cell, neutrophil, and lymphocyte counts.,In contrast, studies with lower cumulative dose (< 60 mg) or shorter duration of therapy (< 6 weeks) did not demonstrate a favorable effect of inhaled corticosteroids on these sputum indices.,Our study suggests that prolonged therapy with inhaled corticosteroids is effective in reducing airway inflammation in stable COPD. | 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. | Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | 1 |
Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation.,The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure.,This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1] 30%-60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators.,The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year.,Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life.,Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up.,A total of 15 patients (47% male, age 63.2±4.0 years) underwent TLD with a total procedure time of 89±16 min, and the total fluoroscopy time was 2.5±2.7 min.,Primary safety end point of freedom from worsening of COPD was 100%.,There were no procedural complications reported.,Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD.,Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy.,TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years. | Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction.,Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms.,To evaluate ‘targeted lung denervation’ (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD.,This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%-60% predicted).,Patients underwent staged TLD at 20 watts (W) or 15 W following baseline assessment off bronchodilators.,Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365 days after TLD.,The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year.,Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life.,Twenty-two patients were included (n=12 at 20 W, n=10 at 15 W).,The procedures were technically feasible 93% of the time.,Primary safety endpoint was achieved in 95%.,Asymptomatic bronchial wall effects were observed in 3 patients at 20 W.,The clinical safety profiles were similar between the two energy doses.,At 1 year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8 min±12.8 vs 2.6 min±8.7, p=0.277), and St George's Respiratory Questionnaire (−11.1 points ±9.1 vs −0.9 points ±8.6, p=0.044).,Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated.,Further investigation of this novel therapy is warranted.,NCT01483534. | 1 |
Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | 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 |
In cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear.,Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae, a key COPD pathogen.,We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD.,Patients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality.,A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota, through 16S rRNA PCR and sequencing, or airway inflammation during stable and exacerbated COPD.,Patients with MBL deficiency with COPD were significantly less likely to have severe exacerbations (incidence rate ratio (IRR) 0.66, 95% CI 0.48 to 0.90, p=0.009), or to have moderate or severe exacerbations (IRR 0.77, 95% CI 0.60 to 0.99, p=0.047).,MBL deficiency did not affect rate of FEV1 decline or mortality.,In the subcohort, patients with MBL deficiency had a more diverse lung microbiota (p=0.008), and were less likely to be colonised with Haemophilus spp.,There were lower levels of airway inflammation in patients with MBL deficiency.,Patients with MBL deficient genotype with COPD have a lower risk of exacerbations and a more diverse lung microbiota.,This is the first study to identify a genetic association with the lung microbiota in COPD. | Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.,To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.,3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array.,An analysis of risk of COPD was carried out using ever smoking controls (n=4784).,Associations with %predicted FEV1 were tested in cases.,We followed-up signals of interest (p<10−5) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.,Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10−6, preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10−6).,In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10−6).,We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5.,No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10−7).,This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study. | 1 |
Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD).,We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.,We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers.,We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population.,We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1.,We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease.,We set genome-wide significance at p<5 × 10−8.,UK Biobank participants were recruited from March 15, 2006, to July 7, 2010.,Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012.,We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups.,We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10−16) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10−11).,We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2).,These variants also showed association with COPD, including in individuals with no history of smoking.,The number of copies of a 150 kb region containing the 5′ end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1.,We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.,By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour.,These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.,Medical Research Council. | New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences.,There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema).,The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD). | 1 |
The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research.,The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls.,Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups.,Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV1, FEV1/FVC and DLCO.,Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values.,To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile.,While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV1 related parameters.,Associations of Fibrinogen with DLCO and MPO with FEV1/FVC were stronger in patients without metabolic syndrome (r = −0.52, p = 0.005 and r = −0.61, p = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r = −0.25, p = 0.47 and r = −0.15, p = 0.96, respectively), and may be driving overall associations in the general cohort.,In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV1, FEV1/FVC and DLCO.,These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD. | The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1).,However, asingle measurement of FEV1 cannot reliably predict subsequent decline.,Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD.,We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease.,Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT.,The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months.,Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11).,Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines.,Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04).,In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03).,In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05).,These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients.,Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression. | 1 |
Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ. | Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication.,In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.,This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 μg via the HandiHaler® in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]).,Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting β-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment).,Treatment effects were determined using non-parametric analysis.,At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102).,The improvement was consistent across baseline treatment and COPD severity.,Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001).,The percentage of patients with ≥1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity.,Rescue medication usage was significantly reduced in the tiotropium group compared with placebo.,Adverse event profile was consistent with previous studies.,Tiotropium provides additional benefits to usual primary care management in a representative COPD population.,The identifier is: NCT00274079. | 1 |
Genetic studies have shown an association between single-nucleotide polymorphisms on chromosome 15q25 and smoking-related traits and diseases, such as quantity of smoking, lung cancer and chronic obstructive pulmonary disease (COPD).,A discussion has centred on the variants and their effects being directly disease related or indirect via nicotine addiction.,To address these discrepancies, we genotyped the single-nucleotide polymorphism rs16969968 in the CHRNA5/A3/B4 gene cluster at chromosome 15q25, in 56 307 individuals from a large homogenous population-based cohort, the North Trøndelag Health Study (HUNT) in Norway.,The variant was examined in relation to four different outcomes: lung cancer, loss of lung function equivalent to that of COPD, smoking behaviour and the use of smokeless tobacco (snus).,Novel associations were found between rs16969968 and the motivational factor for starting to use snus, and the quantity of snus used.,Our results also confirm and extend previous findings for associations between rs16969968 and lung cancer, loss of lung function equivalent to that of COPD, and smoking quantity.,Our data suggest a role for rs16969968 in nicotine addiction, and the novel association with snus strengthens this observation. | Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior.,This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers.,Current smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study.,Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND).,Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained.,Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes.,Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence.,Subjects with high nicotine dependence had greater cumulative and current amounts of smoking.,However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008).,Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases.,Both CHRNA3/5 SNPs were associated with FTND in current smokers.,An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers.,Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers.,Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.,ClinicalTrials (NCT): NCT00608764 | 1 |
The use of solid biomass as cooking fuel could be a potential risk factor for chronic bronchitis (CB) and airflow obstruction (AFO) among never-smoking women.,The disease burden in India among women is generally underestimated due to limited population-based epidemiological investigations.,The aim of the study was to determine the prevalence of CB and AFO among never-smoking women, and its association with household cooking fuel use.,We conducted a community-based cross-sectional study with a representative study sample (N = 1120) in Odisha, India during 2013-14.,Study participants, never-smoking women aged 18-49 years, were recruited randomly from the population census.,Trained community health volunteers administered a validated questionnaire that aligned with the standards of the Burden of Obstructive Lung Disease (BOLD) initiative and conducted spirometry.,Prevalence estimates of CB (defined as “cough with productive of sputum for at least 3 months of the year for at least 2 years”) and AFO (pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7) was estimated.,Indoor PM2.5 exposure data were collected from a subset of 130 of the total 1120 homes in the study settings.,Multivariable regression models were used to estimate the associated risk factors.,Prevalence of CB and AFO were 7.3 and 22.4% respectively among the study participants.,Of the study participants, 31% used exclusive liquefied petroleum gas, 18% used mixed fuel and 51% exclusively used solid biomass fuel for household cooking.,In adjusted analysis, both CB (odds ratio 1·96, 95% CI: 1.06-3.64; p = 0·031) and AFO (OR 5.55, 95% CI: 3.51-8.78; p < 0·001) were found to be associated with cooking with solid biomass fuel.,Interquartile range increases in PM2.5 was associated with significantly lower FEV1/FVC ratio.,The study highlights that the estimates of population burden of CB and AFO are much higher than shown in previous epidemiological studies, and that cooking fuel type and time spent on cooking were associated with increased chronic bronchitis as well as decreased lung function as measured by FEV1/FCV ratios.,To most accurately understand the current burden of disease and most effectively prevent an escalation in the future disease burden, further epidemiological investigations are warranted. | Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | 1 |
Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD.,Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported.,Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).,To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.,In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly).,Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline.,The primary analysis was based on the intention-to-treat principle.,The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised.,The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)).,More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).,PTR was not superior to conventional PR on the 6MWD and we found no differences between groups.,As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.,Trial registration number,ClinicalTrials.gov (NCT02667171), 28 January 2016. | Arterial stiffness is an important predictor of cardiovascular risk besides classic cardiovascular risk factors.,Previous studies showed that arterial stiffness is increased in patients with COPD compared to healthy controls and exercise training may reduce arterial stiffness.,Since physical inactivity is frequently observed in patients with COPD and exercise training may improve arterial stiffness, we hypothesized that low daily physical activity may be associated with increased arterial stiffness.,In 123 patients with COPD (72% men; mean [standard deviation] age: 62 [7.5] years; median [quartile] forced expiratory volume in 1 second 35 [27/65] %predicted), arterial stiffness was assessed by augmentation index (AI).,Daily physical activity level (PAL) was measured by an activity monitor (SenseWear Pro™) >1 week.,The association between AI and PAL was investigated by univariate and multivariate regression analysis, taking into account disease-specific characteristics and comorbidities.,Patients suffered from moderate (35%), severe (32%), and very severe (33%) COPD, and 22% were active smokers.,Median (quartile) PAL was 1.4 (1.3/1.5) and mean (standard deviation) AI 26% (9.2%).,PAL showed a negative association with AI (B=−9.32, P=0.017) independent of age, sex, blood pressure, and airflow limitation.,In COPD patients, a higher PAL seems to favorably influence arterial stiffness and therefore may reduce cardiovascular risk.,http://www.ClinicalTrials.gov, NCT01527773 | 1 |
Administering maintenance COPD therapy with a combination of multiple inhalers may increase inhaler errors.,This study evaluated the potential benefits of using a single Ellipta dry powder inhaler (DPI) compared with two combinations of DPIs commonly used to deliver triple maintenance therapy.,Patients receiving inhaled COPD medication were enrolled in this multicenter, randomized, open-label, placebo-device, crossover study with a 2×2 complete block design (NCT0298218), which comprised two substudies: Ellipta vs Diskus + HandiHaler (substudy 1) or Turbuhaler + HandiHaler (substudy 2).,Patients demonstrated inhaler use after reading the relevant patient information leaflet (PIL).,A trained investigator assessed user errors (critical errors [errors likely to result in no or significantly reduced medication being inhaled] and overall errors).,The primary endpoint was the proportion of patients making ≥1 critical error after reading the PIL.,The secondary endpoints included error rates during ≤2 reassessments following investigator instruction (if required), instruction time, and patient preference.,After reading the PIL, significantly fewer patients made critical errors with Ellipta compared with Diskus + HandiHaler (9% [7/80] vs 75% [60/80], respectively; P<0.001) or Turbuhaler + HandiHaler (9% [7/79] vs 73% [58/79], respectively; P<0.001).,The number of patients making overall errors was also lower with Ellipta vs tested inhaler combinations (P<0.001 for each substudy).,The median instruction time needed for error-free use was shorter with Ellipta in substudies 1 and 2 (2.7 and 2.6 minutes, respectively) vs either combination (10.6 [Diskus + HandiHaler] and 11.3 minutes [Turbuhaler + HandiHaler], respectively).,Significantly more patients preferred Ellipta over Diskus + HandiHaler or Turbuhaler + HandiHaler overall for taking their COPD medication (81% vs 9% and 84% vs 4%, respectively) and per the number of steps for taking their COPD medication (89% vs 8% and 91% vs 5%, respectively).,Fewer patients with COPD made critical errors with the single DPI, and patients required less instruction time, compared with each dual DPI combination. | The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD).,To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use.,Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication.,The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire).,Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device.,Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years).,Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs.,27.3%; P<0.001).,Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs.,5.3, respectively; P<0.001).,After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs.,3.3%, respectively).,Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler.,The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler. | 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. | Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy.,Respimat® Soft Mist™ Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices.,The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs.,This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy.,In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI.,In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases.,Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD. | 1 |
To assess and compare the prevalence of comorbidities and risk factors for cardiovascular disease (CVD) in COPD patients according to disease severity.,The study included 25 patients with mild-to-moderate COPD (68% male; mean age, 65 ± 8 years; mean FEV1, 73 ± 15% of predicted) and 25 with severe-to-very severe COPD (males, 56%; mean age, 69 ± 9 years; mean FEV1, 40 ± 18% of predicted).,Comorbidities were recorded on the basis of data obtained from medical charts and clinical evaluations.,Comorbidities were registered on the basis of data obtained from medical charts and clinical evaluations.,The Charlson comorbidity index was calculated, and the Hospital Anxiety and Depression Scale (HADS) score was determined.,Of the 50 patients evaluated, 38 (76%) had been diagnosed with at least one comorbidity, 21 (42%) having been diagnosed with at least one CVD.,Twenty-four patients (48%) had more than one CVD.,Eighteen (36%) of the patients were current smokers, 10 (20%) had depression, 7 (14%) had dyslipidemia, and 7 (14%) had diabetes mellitus.,Current smoking, depression, and dyslipidemia were more prevalent among the patients with mild-to-moderate COPD than among those with severe-to-very severe COPD (p < 0.001, p = 0.008, and p = 0.02, respectively).,The prevalence of high blood pressure, diabetes mellitus, alcoholism, ischemic heart disease, and chronic heart failure was comparable between the two groups.,The Charlson comorbidity index and HADS scores did not differ between the groups.,Comorbidities are highly prevalent in COPD, regardless of its severity.,Certain risk factors for CVD, themselves classified as diseases (including smoking, dyslipidemia, and depression), appear to be more prevalent in patients with mild-to-moderate COPD. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
Reducing the need for hospitalisation in patients with chronic obstructive pulmonary disease (COPD) is an important goal in COPD management.,The aim of this study was to evaluate re-hospitalisation, treatment, comorbidities and mortality in patients with COPD who were hospitalised for the first time due to a COPD exacerbation.,This was a retrospective, population-based observational cohort study of Swedish patients using linked data from three mandatory national health registries to assess re-hospitalisation rates, medication use and mortality.,Rate of hospitalisation was calculated using the number of events divided by the number of person-years at risk; risk of all-cause and COPD-related mortality were assessed using Cox proportional hazard models.,In total, 51,247 patients were identified over 10 years; 35% of patients were not using inhaled corticosteroid, long-acting muscarinic antagonist or long-acting β2-agonist treatment prior to hospitalisation, 38% of whom continued without treatment after being discharged.,Re-hospitalisation due to a second severe exacerbation occurred in 11.5%, 17.8% and 24% of the patients within 30, 90 and 365 days, respectively.,Furthermore, 24% died during the first year following hospitalisation and risk of all-cause and COPD-related mortality increased with every subsequent re-hospitalisation.,Comorbidities, including ischaemic heart disease, heart failure and pneumonia, were more common amongst patients who were re-hospitalised than those who were not.,Following hospitalisation for first severe COPD exacerbation, many patients did not collect the treatment recommended by current guidelines.,Risk of mortality increased with every subsequent re-hospitalisation.,Patients with concurrent comorbidities had an increased risk of being re-hospitalised.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use:,https://youtu.be/11uPtnnXGTQ | 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 |
We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.,This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy.,Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa.,The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population.,The incidence of adverse events was also assessed.,In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population.,UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28-77 mL); p < 0.001].,Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34-3.14).,Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.,In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD.,Both treatments had similar safety profiles.,These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.,ClinicalTrials.gov identifier NCT02799784.,GlaxoSmithKline.,The online version of this article (doi:10.1007/s12325-017-0626-4) contains supplementary material, which is available to authorized users. | Tiotropium-olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA), commercialized under the name of Spiolto or Stiolto.,The efficacy of tiotropium-olodaterol 5-5 μg once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration.,Tiotropium-olodaterol 5-5 μg not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance.,Improvements exceeded the minimal clinically important difference (MCID) for forced expiratory volume in 1 second (FEV1), dyspnea, and quality of life.,Differences between tiotropium-olodaterol 5-5 μg and the respective monocomponents were statistically significant for FEV1, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID.,However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life.,Moreover, tiotropium-olodaterol 5-5 μg was significantly more effective than salmeterol-fluticasone (FDC) twice daily at improving pulmonary function.,Differences between tiotropium-olodaterol and other LAMA/LABA FDCs were not observed for FEV1 or other efficacy markers.,Therefore, tiotropium-olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation.,We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations.,Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia.,Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis.,The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated.,Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year).,A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators.,A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male.,The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9).,One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators.,Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001).,In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators.,Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD. | 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. | 1 |
Chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) are known risk factors for mortality.,In this study, we examined the overlap of CKD and airflow limitation (AFL) that characterises COPD and its effect on 10-year mortality in a community-based population.,This study included 1,233 health check-up participants (mean age, 63.7 years; 46.7% men).,We defined serum creatinine-based CKD (CKDcr) and serum cystatin C-based CKD (CKDcys) as glomerular filtration rate <60 mL/min/1.73 m2, estimated using serum creatinine or cystatin C, and/or dipstick proteinuria ≥1+.,AFL was defined as forced expiratory volume in 1 s to forced vital capacity ratio <70% on spirometry.,Compared with subjects without AFL, those with AFL showed a significantly higher prevalence of CKDcys but not of CKDcr.,Cox proportional hazard analysis adjusted for confounders showed that the hazard ratio (95% confidence interval) for all-cause mortality was 1.45 (0.77-2.63) in subjects with CKDcys alone, 1.29 (0.60-2.54) in those with AFL alone, and 2.94 (1.33-6.12) in those with both CKDcys and AFL, with subjects without both AFL and CKD as the reference.,This study showed that AFL and CKDcys are strongly associated and that their overlap is a significant risk factor for mortality in community-based populations. | Serum uric acid (sUA) levels were previously found to be correlated with hypoxic states.,We aimed to determine the levels of sUA and sUA/creatinine ratios in stable COPD patients and to evaluate whether sUA level and sUA/creatinine ratio can be used as predictors of exacerbation risk and disease severity.,This cross-sectional study included stable COPD patients and healthy controls.,The sUA levels and sUA/creatinine ratios in each group were evaluated and their correlations with the study parameters were investigated.,ROC analyses for exacerbation risk and disease severity were reported.,The study included 110 stable COPD patients and 52 healthy controls.,The mean sUA levels and sUA/creatinine ratios were significantly higher in patients with COPD compared to healthy controls.,The most common comorbidities in COPD patients were hypertension, diabetes, and coronary artery disease.,While sUA levels were significantly higher in patients with hypertension (p=0.002) and malignancy (p=0.033), sUA/creatinine ratios was higher in patients with malignancy (p=0.004).,The ROC analyses indicated that sUA/creatinine ratios can be more useful than sUA levels in predicting exacerbation risk (AUC, 0.586 vs.,0.426) and disease severity (AUC, 0.560 vs.,0.475) especially at higher cut-off values, but with low specificity.,Our study suggested that sUA levels and sUA/creatinine ratios increased in patients with stable COPD, especially among patients with certain comorbidities compared to healthy controls.,At higher cut-off values, sUA levels and especially sUA/creatinine ratios, might be useful in predicting COPD exacerbation risk and disease severity.,Also, their association with comorbidities, especially with malignancy and hypertension, may benefit from further investigation. | 1 |
Recent telehealth studies have demonstrated minor impact on patients affected by long-term conditions.,The use of technology does not guarantee the compliance required for sustained collection of high-quality symptom and physiological data.,Remote monitoring alone is not sufficient for successful disease management.,A patient-centred design approach is needed in order to allow the personalisation of interventions and encourage the completion of daily self-management tasks.,A digital health system was designed to support patients suffering from chronic obstructive pulmonary disease in self-managing their condition.,The system includes a mobile application running on a consumer tablet personal computer and a secure backend server accessible to the health professionals in charge of patient management.,The patient daily routine included the completion of an adaptive, electronic symptom diary on the tablet, and the measurement of oxygen saturation via a wireless pulse oximeter.,The design of the system was based on a patient-centred design approach, informed by patient workshops.,One hundred and ten patients in the intervention arm of a randomised controlled trial were subsequently given the tablet computer and pulse oximeter for a 12-month period.,Patients were encouraged, but not mandated, to use the digital health system daily.,The average used was 6.0 times a week by all those who participated in the full trial.,Three months after enrolment, patients were able to complete their symptom diary and oxygen saturation measurement in less than 1 m 40s (96% of symptom diaries).,Custom algorithms, based on the self-monitoring data collected during the first 50 days of use, were developed to personalise alert thresholds.,Strategies and tools aimed at refining a digital health intervention require iterative use to enable convergence on an optimal, usable design.,‘Continuous improvement’ allowed feedback from users to have an immediate impact on the design of the system (e.g., collection of quality data), resulting in high compliance with self-monitoring over a prolonged period of time (12-month).,Health professionals were prompted by prioritisation algorithms to review patient data, which led to their regular use of the remote monitoring website throughout the trial.,Trial registration: ISRCTN40367841.,Registered 17/10/2012. | Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden.,Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure.,The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood.,We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the ‘MIOTIC study’ to investigate the influence of mIoT among stable COPD patients.,In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management.,Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year.,Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management. | 1 |
Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies.,Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.,Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts.,A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients.,Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.,Odds ratios (ORs) were pooled by random effects models.,Fourteen observational studies were eligible for the study.,Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29-3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16-7.82), severe airway obstruction (1.31, 95% CI, 1.09-1.58) and mortality (1.96, 95% CI, 1.04-3.70).,The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. | COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function.,CT imaging is emerging as an important, noninvasive tool in phenotyping COPD.,However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known.,Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation.,Airway physiology and health status were also determined.,The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively.,The presence of EM was associated with lower lung function (mean difference % FEV1, −20%; 95% CI, −28 to −11; P < .001).,There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM.,The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96).,Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE.,The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD. | 1 |
Small airway fibrosis is the main contributor to physiological airway dysfunction in COPD.,One potential mechanism contributing to small airway fibrosis is epithelial mesenchymal transition (EMT).,When associated with angiogenesis (so called EMT-Type-3) it may well also be the link with the development of airway epithelial cancer, which is closely associated with COPD and predominantly in large airways.,In a recent study published in Respiratory Research, Reimann and colleagues, showed increased expression of S100A4 in vasculature of human COPD and murine lungs.,It is quite possible that the process of endothelial to mesenchymal transition (EndMT) is active in COPD lungs which we wish to comment on. | The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a).,The genetic ablation of p66Shc (p66Shc-/-) renders mice resistant to oxidative stress and p53-dependent apoptosis.,We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure.,No differences between wild type (WT) and p66Shc-/- mice were observed in terms of inflammation and oxidant burden after acute CS exposure; however,p66Shc ablation modifies specific features of chronic inflammation induced by repeated exposure to CS.,Unlike WT mice, p66Shc-/- mice did not develop emphysema, showing protection toward oxidative damage to DNA and apoptosis as revealed by a trivial 8-hydroxyguanosine staining and faint TUNEL and caspase-3 positivity on alveolar epithelial cells.,Unexpectedly, CS exposure in p66Shc-/- mice resulted in respiratory bronchiolitis with fibrosis in surrounded alveoli.,Respiratory bronchiolitis was characterized by peribronchiolar infiltrates of lymphocytes and histiocytes, accumulation of ageing pigmented macrophages within and around bronchioles, and peribronchiolar fibrosis.,The blockage of apoptosis interferes with the macrophage “clearance” from alveolar spaces, favouring the accumulation of aging macrophages into alveoli and the progressive accumulation of iron pigment in long-lived senescent cells.,The presence of areas of interstitial and alveolar fibrosis in peripheral parenchyma often accompanied the bronchiolar changes.,Macrophages from smoking p66Shc-/- mice elaborate M2 cytokines (i.e., IL-4 and IL-13) and enzymes (i.e., chitinase and arginase I), which can promote TGF-beta expression, collagen deposition, and fibrosis in the surrounding areas.,We demonstrate here that resistance to oxidative stress and p53-dependent apoptosis can modify tissue responses to CS caused by chronic inflammation without influencing early inflammatory response to CS exposure. | 1 |
In COPD, the course of the disease including morbidity and mortality is strongly associated with severe exacerbations.,The current GOLD recommendations emphasize blood eosinophil counts as a marker for responsiveness to inhaled corticosteroids (ICS).,Retrospective analyses from randomized clinical trials indicate a favorable response to systemic corticosteroids in exacerbated COPD patients with blood eosinophils > 2%, however data outside clinical trials are scarce.,We retrospectively evaluated data from 1007 cases of patients who were admitted to the University Medical Center Marburg between 01/2013 and 12/2018.,All patients had been diagnosed with an acute exacerbation of COPD (ICD-10 J44.0/J44.1).,Our analysis was based on a subgroup of 417 patients in whom a full blood cell count was obtained at the day of admission.,Patients were predominantly male (63.3%), had a median age of 74 years (IQR 65 years - 83 years) and a median FEV1 of 1.03 l (42.6% predicted).,We compared the hospital length of stay and other outcome parameters using established thresholds for the eosinophil blood cell count (100 and 300 eosinophils/μl and 2%).,Patients with low eosinophils (< 2%, <100 cells/μl) had a longer median time in hospital (length of hospital stay - LOS) as compared to patients with high eosinophils (< 2%: 9.31 vs. ≥2%:7 days, and < 100/μl: 10 vs. 100-300/μl: 8 vs. > 300/μl: 7 days).,The median CRP was higher in patients with low eosinophils as compared to the other groups (< 2%: 22.7 vs. ≥2%: 9 mg/dl and < 100: 25 vs.,100-300: 13.5 vs.,> 300: 7.1 mg/dl).,Time to re-hospitalization or time to death did not differ between strata of eosinophils.,Sensitivity analysis in a subgroup of patients in which pneumonia was excluded by chest x-ray did not significantly alter the results.,The results support the hypothesis that patients with severe COPD exacerbations and elevated blood eosinophil counts respond better to systemic corticosteroid treatment than patients with a non-eosinophilic exacerbation. | Numerous studies have investigated the association between eosinophilia and clinical outcome of patients with chronic obstructive pulmonary disease (COPD) but the evidence is conflicting.,We conducted a pooled analysis of outcome measures comparing eosinophilic and non-eosinophilic COPD patients.,We searched articles indexed in four databases using Medical Subject Heading or Title and Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from inception to December 2016.,Observational studies and randomized controlled trials with parallel groups comparing COPD patients with and without eosinophilia were included.,Comparing to the non-eosinophilic group, those with eosinophilic COPD had a similar risk for exacerbation in 12 months [Odds ratio = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55] and in-hospital mortality [OR = 0.52, 95% CI 0.25-1.07].,Eosinophilia was associated with reduced length of hospital stay (P = 0.04).,Subsequent to therapeutic interventions, eosinophilic outpatients performed better in pulmonary function tests [Mean Difference = 1.64, 95% CI 0.05-3.23, P < 0.001].,Inclusion of hospitalized patients nullified the effect.,Improvement of quality of life was observed in eosinophilic subjects [Standardized Mean Difference = 1.83, 95% CI 0.02-3.64, P = 0.05], independent of hospitalization status.,In conclusion, blood eosinophilia may be predictive of favorable response to steroidal and bronchodilator therapies in patients with stable COPD. | 1 |
Self-management is recognised as an essential criteria for the provision of high quality care for chronic obstructive pulmonary disease (COPD).,The management of COPD is usually delivered by a wide range of healthcare practitioners.,This study aimed to understand the factors affecting self-management of COPD from the perspectives of the different multidisciplinary healthcare teams involved in COPD care.,Semi-structured interviews were conducted with participants from primary care, specialist respiratory and pulmonary rehabilitation (PR) teams.,Purposive sampling and snowballing were employed in participant recruitment.,All interviews were audio-recorded and transcribed verbatim and data were analysed thematically.,A total of 20 participants (eight primary care practitioners, seven respiratory specialists and five PR practitioners) were interviewed until data saturation was reached.,Participants identified a range of complex and interrelated factors affecting COPD self-management that were grouped into three broad categories-patient, practitioner and organisational/system-level factors.,Patient-level factors were predominantly considered as barriers, with COPD knowledge and understanding, and the individual patients’ life circumstances/context being the most prominent issues.,Practitioner-level factors identified were practitioners’ speciality, interest and experience in respiratory conditions as the overarching factor that influenced how self-management was understood and practiced.,A number of organisational/system-level factors were identified by all practitioners, including inconsistency of referral pathways and the wide variations of different self-management planning tools.,Factors affecting self-management of COPD across these three levels need to be tackled equally in order to improve the effectiveness of interventions and to embed and integrate self-management support approaches into routine practice.,Better co-ordination between healthcare services, practitioners and patients may help improve self-management for chronic lung disease.,Self-management is crucial for patients with chronic obstructive pulmonary disease (COPD), but it can be difficult for healthcare workers to monitor and support patient progress.,Oladapo Ogunbayo at Newcastle University, UK, and co-workers conducted interviews with healthcare practitioners to explore perceived barriers to successful self-management of COPD.,Three distinct categories emerged; those at patient level, practitioner level and organisational level, the needs of which should be carefully balanced to improved self-management.,Patient knowledge and understanding of COPD, alongside individual life circumstances, were often barriers to effective self-care.,Those practitioners with specialist respiratory knowledge took a more holistic approach to self-management than their primary care counterparts.,A lack of continuity between services and across self-management planning tools presented further barriers. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
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 | Few studies have evaluated the associations between respiratory parameters and pain in chronic obstructive pulmonary disease (COPD).,The purpose of this study is to evaluate the differences in respiratory parameters between COPD patients who did and did not have pain.,In this cross-sectional study respiratory parameters were measured by spirometry and the St Georges Respiratory Questionnaire.,Patients responded to a single question that asked if they were generally bothered by pain.,Of the 100 patients, 45% reported that they were generally bothered by pain.,Patients who had pain reported a higher number of comorbidities (P < 0.001) and higher breathlessness scores (P = 0.003).,Physical dimensions of breathlessness were significantly associated with pain (P ≤ 0.03).,The results of logistic regression analysis determined that a higher number of comorbidities (OR = 0.28; P = 0.026) and higher breathlessness scores (OR = 1.03; P = 0.003) made significant unique contributions to the prediction of pain group membership.,Comorbidity and breathlessness were risk factors for pain and the physical dimensions of breathlessness were associated with pain. | 1 |
Care coordination is defined as good communication between professionals to enable access to services based on need.,To explore patients' experience of care coordination in order to inform current debates on how best to coordinate care and deliver services in end-of-life for patients with lung cancer and those with chronic obstructive pulmonary disease (COPD).,A qualitative study involving serial interviews was performed in 18 patients recruited from three hospital outpatient clinics situated in a hospital.,Interviews were transcribed verbatim and data were analysed thematically.,Data comprised 38 interviews.,Patients experiencing services related to lung cancer reported good access enabled by the involvement of a keyworker.,This contrasted with COPD patients' experiences of services.,The keyworker coordinated care between and within clinical settings, referred patients to community palliative care services, helped them with financial issues, and provided support.,For patients with lung cancer, the keyworker's role augmented access to various services and enabled care based on their needs.,The experiences of patients with COPD highlight the importance of providing a keyworker for this group of patients in both secondary and primary care. | Despite a well-recognised burden of disabling physical symptoms compounded by co-morbidities, psychological distress and social isolation, the needs of people with severe chronic obstructive pulmonary disease (COPD) are typically poorly addressed.,To assess the effectiveness of interventions designed to deliver holistic care for people with severe COPD.,We searched 11 biomedical databases, three trial repositories (January 1990-March 2012; no language restrictions) and contacted international experts to locate published, unpublished and in-progress randomised controlled trials (RCTs), quasi-RCTs and controlled clinical trials (CCTs) that investigated holistic interventions to support patients with severe COPD in any healthcare context.,The primary outcome was health-related quality of life (HRQoL).,Quality assessment and data extraction followed Cochrane Collaboration methodology.,We used a piloted data extraction sheet and undertook narrative synthesis.,From 2,866 potentially relevant papers, we identified three trials: two RCTs (from United States and Australia), and one CCT (from Thailand): total 216 patients.,Risk of bias was assessed as moderate in two studies and high in the third.,All the interventions were led by nurses acting in a co-ordinating role (e.g. facilitating community support in Thailand, providing case-management in the USA, or co-ordinating inpatient care in Australia).,HRQoL improved significantly in the Thai CCT compared to the (very limited) usual care (p<0.001), in two sub-domains in the American trial, but showed no significant changes in the Australian trial.,Exercise tolerance, dyspnoea, and satisfaction with care also improved in the Thai trial.,Some 15 years after reports first highlighted the unmet needs of people with severe COPD, we have been unable to find robust trial evidence about interventions that can address those needs.,There is an urgent need to develop and evaluate holistic care interventions designed improve HRQoL for people with severe COPD.,PROSPERO (CRD42012002430). | 1 |
Human lung single-cell atlas reveals the complexity and diversity of aberrant cellular populations in pulmonary fibrosis.,We provide a single-cell atlas of idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease, by profiling 312,928 cells from 32 IPF, 28 smoker and nonsmoker controls, and 18 chronic obstructive pulmonary disease (COPD) lungs.,Among epithelial cells enriched in IPF, we identify a previously unidentified population of aberrant basaloid cells that coexpress basal epithelial, mesenchymal, senescence, and developmental markers and are located at the edge of myofibroblast foci in the IPF lung.,Among vascular endothelial cells, we identify an ectopically expanded cell population transcriptomically identical to bronchial restricted vascular endothelial cells in IPF.,We confirm the presence of both populations by immunohistochemistry and independent datasets.,Among stromal cells, we identify IPF myofibroblasts and invasive fibroblasts with partially overlapping cells in control and COPD lungs.,Last, we confirm previous findings of profibrotic macrophage populations in the IPF lung.,Our comprehensive catalog reveals the complexity and diversity of aberrant cellular populations in IPF. | Previous studies have identified lung, sputum or blood transcriptomic biomarkers associated with the severity of airflow limitation in COPD.,Yet, it is not clear whether the lung pathobiology is mirrored by these surrogate tissues.,The aim of this study was to explore this question.,We used Weighted Gene Co-expression Network Analysis (WGCNA) to identify shared pathological mechanisms across four COPD gene-expression datasets: two sets of lung tissues (L1 n = 70; L2 n = 124), and one each of induced sputum (S; n = 121) and peripheral blood (B; n = 121).,WGCNA analysis identified twenty-one gene co-expression modules in L1.,A robust module preservation between the two L datasets was observed (86%), with less preservation in S (33%) and even less in B (23%).,Three modules preserved across lung tissues and sputum (not blood) were associated with the severity of airflow limitation.,Ontology enrichment analysis showed that these modules included genes related to mitochondrial function, ion-homeostasis, T cells and RNA processing.,These findings were largely reproduced using the consensus WGCNA network approach.,These observations indicate that major differences in lung tissue transcriptomics in patients with COPD are poorly mirrored in sputum and are unrelated to those determined in blood, suggesting that the systemic component in COPD is independently regulated.,Finally, the fact that one of the preserved modules associated with FEV1 was enriched in mitochondria-related genes supports a role for mitochondrial dysfunction in the pathobiology of COPD.,The online version of this article (10.1186/s12931-018-0965-y) contains supplementary material, which is available to authorized users. | 1 |
In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP).,In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients.,CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP.,Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera.,Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p < 0.05), whereas no significant differences were found with IFN-γ (Th1) and IL-17A (Th17).,Among COPD patients, two subpopulations were observed based on the percentage of IL-4 (Th2) producing CD4+ T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7).,Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p < 0.05), but not in controls.,The VGVAPG-induced increase in IL-4 was inhibited in the presence of analogous peptide antagonizing VGVAPG/elastin receptor (S-gal) interactions.,The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD.,Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients. | Chronic obstructive pulmonary disease (COPD) and lung cancer are devastating pulmonary diseases that commonly coexist and present a number of clinical challenges.,COPD confers a higher risk for lung cancer development, but available chemopreventive measures remain rudimentary.,Current studies have shown a marked benefit of cancer screening in the COPD population, although challenges remain, including the common underdiagnosis of COPD.,COPD-associated lung cancer presents distinct clinical features.,Treatment for lung cancer coexisting with COPD is challenging as COPD may increase postoperative morbidities and decrease survival.,In this review, we outline current progress in the understanding of the clinical association between COPD and lung cancer, and suggest possible cancer prevention strategies in this patient population. | 1 |
COPD self-management reduces hospital admissions and improves health-related quality of life (HRQoL).,However, whilst most patients are managed in primary care, the majority of self-management trials have recruited participants with more severe disease from secondary care.,We report the findings of a systematic review of the effectiveness of community-based self-management interventions in primary care patients with COPD.,We systematically searched eleven electronic databases and identified 12 eligible randomised controlled trials with seven included in meta-analyses for HRQoL, anxiety and depression.,We report no difference in HRQoL at final follow-up (St George’s Respiratory Questionnaire total score −0.29; 95%CI −2.09, 1.51; I2 0%), nor any difference in anxiety or depression.,In conclusion, supported self-management interventions delivered in the community to patients from primary care do not appear to be effective.,Further research is recommended to identify effective self-management interventions suitable for primary care populations, particularly those with milder disease.,Further work is needed to ensure that self-management of chronic lung disease in primary care settings actively improves patients’ quality of life.,While self-management is beneficial to patients in secondary care with severe chronic obstructive pulmonary disease (COPD), few studies have examined self-management effectiveness in primary care patients with milder COPD.,Kate Jolly at the University of Birmingham, UK, and co-workers identified only 12 studies out of over 12,500 that specifically examined self-management in primary care.,Of these, seven were suitable for metanalysis.,The team found that community-based interventions to support self-management did not make a significant difference to patients’ perceived quality of life, or in reducing anxiety and depression.,They call for further research to identify specific support that will help patients with mild to moderate COPD cope and adapt to the progressive condition. | Objective To evaluate the effects of a community based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China.,Design Cluster randomised controlled trial.,Setting Eight healthcare units in two communities.,Participants Of 1062 people aged 40-89, 872 (101 with COPD and 771 without COPD) who fulfilled the inclusion and exclusion criteria were allocated to the intervention or the usual care programmes.,Intervention Participants randomly assigned to integrated intervention (systematic health education, intensive and individualised intervention, treatment, and rehabilitation) or usual care.,Main outcome measures Annual rate of decline in forced expiratory rate in one second (FEV1) before use of bronchodilator.,Results Annual rate of decline in FEV1 was significantly lower in the intervention community than the control community, with an adjusted difference of 19 ml/year (95% confidence interval 3 to 36) and 0.9% (0.1% to 1.8%) of predicted values (all P<0.05), as well as a lower annual rate of decline in FEV1/FVC (forced vital capacity) ratio (adjusted difference 0.6% (0.1% to 1.2%) P=0.029).,There were also higher rates of smoking cessation (21% v 8%, P<0.004) and lower cumulative death rates from all causes (1% v 3%, P<0.009) in the intervention community than in the control community during the four year follow-up.,Improvements in knowledge of COPD and smoking hazards, outdoor air quality, environmental tobacco smoke, and working conditions were also achieved (all P<0.05).,The difference in cumulative incidence rate of COPD (both around 4%) and cumulative death rate from COPD (2% v 11%) did not reach significance between the two communities.,Conclusions A community based integrated intervention can have a significant impact on the prevention and management of COPD, mainly reflected in the annual rate of decline in FEV1.,Trial registration Chinese Clinical Trials Registration (ChiCTR-TRC-00000532). | 1 |
T cells and B cells participate in the pathogenesis of COPD.,Currently, NK cells and NKT cells have gained increasing attention.,In the present study, 19 COPD patients and 12 healthy nonsmokers (HNS) were recruited, and their pulmonary function was assessed.,The frequencies of CD3+ T, CD4+ T, CD8+ T, B, NK, and NKT-like cells were determined using flow cytometry.,The frequencies of spontaneous and inducible IFN-γ + or CD107a+ NK and NKT-like cells as well as activating or inhibitory receptors were also detected.,The potential association of lymphocyte subsets with disease severity was further analyzed.,Significantly decreased numbers of CD3+ and CD4+ T cells, and the CD4+/CD8+ ratio, but increased numbers of CD3−CD56+ NK and CD3+CD56+ NKT-like cells were observed in COPD patients compared to HNS.,The frequencies of inducible IFN-γ-secreting NK and NKT-like cells were less in COPD patients.,The frequencies of CD158a and CD158b on NK cells and CD158b on NKT-like cells were greater.,The frequency of CD158b+ NK cells was negatively correlated with FEV1% prediction and FEV1/FVC.,Our data indicate that COPD patients have immune dysfunction, and higher frequencies of inhibitory NK cells and NKT-like cells may participate in the pathogenesis of COPD. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
This multicenter, prospective, observational study aimed to supplement real-world evidence on the effects of aclidinium bromide on the quality of life (QoL), symptoms, and activity impairment of patients with COPD.,Eligible patients were ≥40 years of age, newly initiated on aclidinium bromide as monotherapy or add-on therapy according to the product’s approved label.,Patient-reported COPD assessment test (CAT), the severity of symptoms and their impact on daily activities, and the features of the Genuair® inhaler device were assessed at enrollment and at 12 weeks post-treatment onset.,Between 13 March 2015 and 29 January 2016, 285 eligible consenting patients (76.3% males; median age: 69.0 years; 26.0% newly diagnosed with COPD) were enrolled by 15 hospital-based respiratory medicine specialists in Greece.,Aclidinium bromide was initiated as add-on therapy to other inhaled maintenance medications in 73.1% of evaluable patients.,The median (interquartile range [IQR]) baseline CAT score decreased from 14.0 (9.0-20.0) to 10.0 (6.0-15.0) points (p<0.001) after 12 weeks of treatment, with 76.5% of the patients achieving a ≥2-point decrease.,The severity of night-time and early-morning symptoms, assessed using a 5-point Likert-type scale, decreased from a median (IQR) of 1.0 (0.0-2.0) to 0.0 (0.0-1.0), and from 2.0 (1.0-2.0) to 1.0 (1.0-2.0), respectively (p<0.001 for both).,In patients with paired data, the prevalence of at least moderate night-time symptoms, early-morning symptoms, and daily activity impairment decreased from 28.2% to 19.1%, from 63.6% to 34.2%, and from 59.5% to 38.7%, respectively (p<0.001 for all).,Inhaler device features were assessed as “very good”/“good” by more than 90% of the patients.,The adverse drug reaction rate was 1.4%.,The study provides real-world evidence on the beneficial effects of aclidinium bromide on the patients’ QoL, symptom severity, and daily activity impairment, which are complemented by a favorable safety profile and high patient satisfaction with the inhaler device. | Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life.,This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status.,Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]).,These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7.,Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate.,Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male).,In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05).,Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients.,Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05).,Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001).,In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05).,The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients.,Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used.,Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms. | 1 |
Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium.,Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations.,We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged.,Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression.,We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease.,Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts.,Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein.,The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS.,Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect.,The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression.,Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens. | 1 |
It has recently been shown that chronic noninvasive ventilation (NIV) improves a number of outcomes including survival, in patients with stable hypercapnic COPD.,However, the mechanisms responsible for these improved outcomes are still unknown.,The aim of the present study was to identify parameters associated with: 1) an improved arterial partial pressure of carbon dioxide (PaCO2) and 2) survival, in a cohort of hypercapnic COPD patients treated with chronic NIV.,Data from 240 COPD patients treated with chronic NIV were analyzed.,Predictors for the change in PaCO2 and survival were investigated using multivariate linear and Cox regression models, respectively.,A higher level of bicarbonate before NIV initiation, the use of higher inspiratory ventilator pressures, the presence of anxiety symptoms, and NIV initiated following an exacerbation compared to NIV initiated in stable disease were associated with a larger reduction in PaCO2.,A higher body mass index, a higher FEV1, a lower bicarbonate before NIV initiation, and younger age and NIV initiation in stable condition were independently associated with better survival.,The change in PaCO2 was not associated with survival, neither in a subgroup of patients with a PaCO2 >7.0 kPa before the initiation of NIV.,Patients with anxiety symptoms and a high bicarbonate level at NIV initiation are potentially good responders in terms of an improvement in hypercapnia.,Also, higher inspiratory ventilator pressures are associated with a larger reduction in PaCO2.,However, the improvement in hypercapnia does not seem to be associated with an improved survival and emphasizes the need to look beyond PaCO2 when considering NIV initiation. | High-intensity (high-pressure and high backup rate) noninvasive ventilation has recently been advocated for the management of stable hypercapnic chronic obstructive pulmonary disease (COPD).,However, the relative contributions of high inspiratory pressure and high backup rate to ventilator adherence and physiological outcome have not been investigated.,Patients with stable hypercapnic COPD (daytime PaCO2 > 6 kPa) and nocturnal hypoventilation were enrolled.,Patients were randomly allocated to high-pressure and high backup rate (high-intensity) and high-pressure and low backup rate (high-pressure) for a 6-week period.,At the end of the first treatment period, patients were switched to the alternative treatment.,The primary outcome measure was mean nightly ventilator usage.,Twelve patients were recruited, with seven completing the 12-week trial protocol.,The mean patient age was 71 ± 8 years, with a forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of 50% ± 13% and FEV1 of 32% ± 12%.,The baseline PaCO2 and PaO2 were 8.6 ± 1.7 kPa and 7.3 ± 1.4 kPa, respectively.,There was no significant difference demonstrated in mean nightly ventilator usage between the high-intensity and high-pressure groups (difference of 4 minutes; 95% confidence interval −45 to 53; P = 0.9).,Furthermore, there were no differences in any of the secondary endpoints, with the exception of the respiratory domain of the Severe Respiratory Insufficiency questionnaire, which was lower in the high-intensity arm than in the high-pressure arm (57 ± 11 versus 69 ± 16; P < 0.05).,There was no additional benefit, in terms of night-time ventilator adherence or any of the other measured parameters, demonstrated by addition of a high backup rate to high-pressure noninvasive ventilation.,These data suggest that it is the high-pressure component of the high-intensity noninvasive ventilation approach that plays the important therapeutic role in the management of hypercapnic respiratory failure in COPD patients. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression.,However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established.,Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema.,We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms.,Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity.,Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice.,Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice.,Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression.,Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS.,Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated.,Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1.,Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression.,Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation. | ► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress.,Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation.,However, no data on the possible relationship between COPD and ox-LDL are available.,This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress.,Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits.,Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62 ± 7.56 versus 12.57 ± 5.90 mU/L, P < 0.05).,Serum levels of CRP and ROS were also significantly higher in COPD patients.,Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r = −0.347, P = 0.016), while they correlated positively with CRP and ROS levels.,These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD.,Future studies are needed to determine whether and how ox-LDL plays a role in COPD. | Early preclinical diagnosis of COPD is urgent.,We proposed that fatty acid composition of red blood cells may serve as a prognostic test for the complications in the chronic respiratory diseases.,Fatty acid composition of the erythrocyte membranes in patients with chronic respiratory diseases (chronic bronchitis, CB, and stable chronic obstructive pulmonary disease, COPD) was studied.,It was established that modification of the fatty acid composition in the erythrocyte membranes was unidirectional in both groups of patients.,Patients with CB and stable COPD (group A, GOLD 1) (15 subjects in each group) were studied in clinic.,The activity of the inflammatory process was evaluated by the phagocytic activity of neutrophils, cytokine levels and cytokine receptors in the blood serum (TNFα, sTNF-RI, bFGF, TGF-β, IL-8).,Fatty acid (FA) composition of the erythrocyte membranes was analyzed by gas liquid chromatography.,Statistical data processing was performed by the methods of descriptive statistics with Statistica 6.0.,In both groups (CB and COPD), a significant accumulation of the saturated FAs (14:0, 15:0, 18:0) was established.,The amount of the arachidonic acid (20:4n-6) was increased by 13% (р < 0.05) in CB patients and by 41% (р < 0.001) in COPD patients, as compared with healthy persons.,The elevated level of the PUFA n-6 in the erythrocytes membranes in patients with chronic respiratory diseases confirms that proinflammatory (leukotriene B4) and bronchospasm (prostaglandin D2) mediator substrates is increased.,The level of the eicosapentaenoic acid (20:5n-3) was decreased by 32% (р < 0.05) in CB patients and 2-fold (р < 0.001) in COPD patients.,The observed increase in the 20:4n-6/20:5n-3 ratio - 1.5-fold (р < 0.001) in CB patients and 3-fold in COPD patients - can be a specific marker of the adverse course of the respiratory pathology and the chronic inflammatory development.,Chronic respiratory disease development is associated with the disturbance of the fatty acid composition in erythrocyte membranes and disbalance of the ratio between precursor of pro- and antiinflammatory eicosanoids. | 1 |
Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations.,It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation.,To provide a cell-by-cell overview of the inflammatory processes during COPD exacerbations.,To evaluate cell activation, and cytokine production, cellular interactions, damaging effects of inflammatory mediators to tissue, and the relation to symptoms at the onset of COPD exacerbations.,To speculate on future therapeutic options to modify inflammation during COPD exacerbations.,During COPD exacerbations, there is increased airway wall inflammation, with pathophysiological influx of eosinophils, neutrophils, and lymphocytes.,Although links have been suggested between the increase in eosinophils and lymphocytes and a viral etiology of the exacerbation, and between the increase in neutrophils and a bacterial aetiology, these increases in both inflammatory cell types are not limited to the respective aetiologies and the underlying mechanisms remain elusive.,Further research is required to fully understand the inflammatory mechanisms in the onset and development of COPD exacerbations.,This might make inflammatory pathway-specific intervention possible, resulting in a more effective treatment of COPD exacerbations with fewer side effects. | 1 |
Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination.,This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).,In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks.,Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT).,Safety evaluations included adverse events (AEs).,Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001).,Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2-0.0]; P≤0.05).,More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01).,Improvements in SGRQ and CAT scores were similar between treatments.,The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).,UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US.,Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies.,Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality.,Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009.,Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD.,Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation.,Estimates of restricted activity days range from 27-63 days per year.,Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days.,Estimates of bed confinement range from 13-32 days per year.,Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs.,In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied.,COPD is associated with substantial indirect costs.,The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability.,Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD. | Subjective health status is the result of an interaction between physiological and psychosocial factors in patients with chronic obstructive pulmonary disease (COPD).,However, there is little understanding of multivariate explanations of subjective health status in COPD.,The purpose of this study was to explore what determines subjective health status in COPD by evaluating the relationships between background variables such as age and sex, predicted FEV1%, oxygen saturation, breathlessness, anxiety and depression, exercise capacity, and physical and mental health.,This study had a cross-sectional design, and included 100 COPD patients (51% men, mean age 66.1 years).,Lung function was assessed by predicted FEV1%, oxygen saturation by transcutaneous pulse oximeter, symptoms with the St George Respiratory Questionnaire and the Hospital Anxiety and Depression Scale, physical function with the Incremental Shuttle Walking Test, and subjective health status with the SF-36 health survey.,Linear regression analysis was used.,Older patients reported less breathlessness and women reported more anxiety (p < 0.050).,Women, older patients, those with lower predicted FEV1%, and those with greater depression had lower physical function (p < 0.050).,Patients with higher predicted FEV1%, those with more breathlessness, and those with more anxiety or depression reported lower subjective health status (p < 0.050).,Symptoms explained the greatest variance in subjective health status (35%-51%).,Symptoms are more important for the subjective health status of patients with COPD than demographics, physiological variables, or physical function.,These findings should be considered in the treatment and care of these patients. | 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. | 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. | 1 |
Recently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases.,Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases.,Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer.,Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations.,We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I.,= 1.14-1.54) and lung cancer (OR = 1.57; 95% CI = 1.31-1.87), respectively.,The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13-1.75).,The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles.,However, none of these effects were found for another SNP, rs1051730G>A.,The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer. | Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease.,Recent studies suggested an association between COPD and polymorphisms in CHRNA coding subunits of nicotinic acetylcholine receptor.,Herein, we performed a meta-analysis to clarify the impact of CHRNA variants on COPD.,We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on CHRNA.,Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.,Among seven reported variants in CHRNA, rs1051730 was finally analyzed with sufficient studies.,Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed.,A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10-5).,At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10-5).,Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).,Our findings suggest that rs1051730 in CHRNA is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction. | 1 |
The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 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 |
Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | Proteases have been shown to degrade airway mucin proteins and to damage the epithelium impairing mucociliary clearance.,There are increased proteases in the COPD airway but changes in protease-antiprotease balance and mucin degradation have not been investigated during the course of a COPD exacerbation.,We hypothesized that increased protease levels would lead to mucin degradation in acute COPD exacerbations.,We measured neutrophil elastase (NE) and alpha 1 protease inhibitor (A1-PI) levels using immunoblotting, and conducted protease inhibitor studies, zymograms, elastin substrate assays and cigarette smoke condensate experiments to evaluate the stability of the gel-forming mucins, MUC5AC and MUC5B, before and 5-6 weeks after an acute pulmonary exacerbation of COPD (n = 9 subjects).,Unexpectedly, mucin concentration and mucin stability were highest at the start of the exacerbation and restored to baseline after 6 weeks.,Consistent with these data, immunoblots and zymograms confirmed decreased NE concentration and activity and increased A1-PI at the start of the exacerbation.,After recovery there was an increase in NE activity and a decrease in A1-PI levels.,In vitro, protease inhibitor studies demonstrated that serine proteases played a key role in mucin degradation.,Mucin stability was further enhanced upon treating with cigarette smoke condensate (CSC).,There appears to be rapid consumption of secreted proteases due to an increase in antiproteases, at the start of a COPD exacerbation.,This leads to increased mucin gel stability which may be important in trapping and clearing infectious and inflammatory mediators, but this may also contribute acutely to mucus retention. | 1 |
The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events.,Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes.,Smoking is associated with mood disorders, including depression and anxiety.,Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function.,Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses.,Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders.,Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus.,Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD.,We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD.,Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice.,Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT.,As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD.,Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD.,Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD. | Chronic obstructive pulmonary disease (COPD) progresses very slowly and the majority of patients are therefore elderly.,COPD is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli and there are increasing evidences for a close relationship between premature aging and chronic inflammatory diseases.,Thus, COPD is considered to be a disease of an accelerating aging.,In this review, we collected the evidence for roles of aging on pathogenesis of COPD and considered future therapeutic strategy for COPD based on this senescence hypothesis.,Since calorie restriction has been proved to extend lifespan, many efforts were made to clarify the molecular mechanism of aging.,Aging is defined as the progressive decline of homeostasis that occurs after the reproductive phase of life is complete, leading to an increasing risk of disease or death due to impaired DNA repair after damage by oxidative stress or telomere shortening as a result of repeated cell division.,During aging, pulmonary function progressively deteriorates; innate immunity is impaired and pulmonary inflammation increases, accompanied by structural changes, such as an enlargement of airspaces.,Noxious environmental gases, such as cigarette smoke, may worsen these aging-related events in the lung or accelerate aging of the lung due to reduction in anti-aging molecules and/or stimulation of aging molecules.,Aging signaling are complex but conserved in divert species, such as worm, fruit fry, rodent and humans.,Especially the insulin like growth factor (IGF-1) signaling was well documented.,Geroprotectors are therapeutics that affect the root cause of aging and age-related diseases, and thus prolong the life-span of animals.,Most of geroprotectors such as melatonin, metformin, rapamycin and resveratrol are anti-oxidant or anti-aging molecule regulators.,Therefore, geroprotection for the lung might be an attractive approach for the treatment of COPD by preventing premature aging of lung. | 1 |
Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by inflammation-induced airflow limitation and parenchymal destruction.,In addition to pulmonary manifestations, patients with COPD develop systemic problems, including skeletal muscle and other organ-specific dysfunctions, nutritional abnormalities, weight loss, and adverse psychological responses.,Patients with COPD often complain of dyspnea on exertion, reduced exercise capacity, and develop a progressive decline in lung function with increasing age.,These symptoms have been attributed to increases in the work of breathing and in impairments in gas exchange that result from airflow limitation and dynamic hyperinflation.,However, there is mounting evidence to suggest that skeletal muscle dysfunction, independent of lung function, contributes significantly to reduced exercise capacity and poor quality of life in these patients.,Limb and ventilatory skeletal muscle dysfunction in COPD patients has been attributed to a myriad of factors, including the presence of low grade systemic inflammatory processes, nutritional depletion, corticosteroid medications, chronic inactivity, age, hypoxemia, smoking, oxidative and nitrosative stresses, protein degradation and changes in vascular density.,This review briefly summarizes the contribution of these factors to overall skeletal muscle dysfunction in patients with COPD, with particular attention paid to the latest advances in the field. | Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development.,We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year.,64 patients with stable COPD (FEV1 mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart.,Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation.,QMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04).,The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment.,Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001).,Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs.,+1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs.,+0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026).,Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations.,Factors predicting progression of quadriceps weakness could not be identified from the present cohort. | 1 |
Chronic obstructive pulmonary disease (COPD) is predominantly associated with neutrophilic inflammation.,Active neutrophil elastase (NE) is a serine proteinase, secreted by neutrophils, in response to inflammation and pathogen invasion.,We sought to investigate if NE could be used as a biomarker for bacterial infection in patients with COPD.,NE was quantified using ProteaseTag® Active NE Immunoassay (ProAxsis, Belfast) from the sputum of COPD subjects at stable state, exacerbation and 2 weeks post treatment visit.,NE was measured in 90 samples from 30 COPD subjects (18 males) with a mean (range) age of 65 (45-81) years and mean (SD) FEV1 of 47% (18).,The geometric mean (95%CI) of NE at stable state was 2454 ng/mL (1460 to 4125 ng/mL).,There was a significant increase in NE levels at an exacerbation (p = 0.003), and NE levels were higher in a bacterial-associated exacerbation (NE log difference 3.873, 95% CI of log difference 1.396 to 10.740, p = 0.011).,NE was an accurate predictor of a bacteria-associated exacerbation (area (95%CI) under the receiver operator characteristic curve 0.812 (0.657 to 0.968).,NE is elevated during exacerbations of COPD.,NE may be a viable biomarker for distinguishing a bacterial exacerbation in patients with COPD.,Leicestershire, Northamptonshire and Rutland ethics committee (reference number: 07/H0406/157). | This systematic review evaluated the effects of Chinese herbal medicine (CHM) plus routine pharmacotherapy (RP) on the objective outcome measures BODE index, 6-minute walk test (6MWT), and 6-minute walk distance (6MWD) in individuals with stable chronic obstructive pulmonary disease (COPD).,Searches were conducted of six English and Chinese databases (PubMed, EMBASE, CENTRAL, CINAHL, CNKI and CQVIP) from their inceptions until 18th November 2013 for randomized controlled trials involving oral administration of CHM plus RP compared to the same RP, with BODE Index and/or 6MWT/D as outcomes.,Twenty-five studies were identified.,BODE Index was used in nine studies and 6MWT/D was used in 22 studies.,Methodological quality was assessed using the Cochrane Risk of Bias tool.,Weaknesses were identified in most studies.,Six studies were judged as ‘low’ risk of bias for randomisation sequence generation.,Twenty-two studies involving 1,834 participants were included in the meta-analyses.,The main meta-analysis results showed relative benefits for BODE Index in nine studies (mean difference [MD] −0.71, 95% confidence interval [CI] −0.94, −0.47) and 6MWT/D in 17 studies (MD 54.61 meters, 95%CI 33.30, 75.92) in favour of the CHM plus RP groups.,The principal plants used were Astragalus membranaceus, Panax ginseng and Cordyceps sinensis.,A. membranaceus was used in combination with other herbs in 18 formulae in 16 studies.,Detailed sub-group and sensitivity analyses were conducted.,Clinically meaningful benefits for BODE Index and 6MWT were found in multiple studies.,These therapeutic effects were promising but need to be interpreted with caution due to variations in the CHMs and RPs used and methodological weakness in the studies.,These issues should be addressed in future trials. | 1 |
Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often coexist.,We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at heightened CVD risk.,The SUMMIT (Study to Understand Mortality and MorbidITy) was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 16 485 patients with moderate COPD who had or were at high risk of CVD.,Here, we assessed the prespecified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD adverse events across the four groups: once-daily inhaled placebo (n=4111), long-acting beta2-agonist (vilanterol (VI) 25 µg; n=4118), corticosteroid (fluticasone furoate (FF) 100 µg; n=4135) and combination therapy (FF/VI; n=4121).,Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with overt CVD (66%).,The composite CVD endpoint occurred in 688 patients (first event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%), and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI 0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93, 95% CI 0.75 to 1.14).,Outcomes were similar among all subgroups.,Adverse events, including palpitations and arrhythmias, did not differ by treatment.,In patients with COPD with moderate airflow limitation and heightened CVD risk, treatment with inhaled VI, FF or their combination has an excellent safety profile and does not impact CVD outcomes.,NCT01313676. | Objectives To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use.,Design Population based cohort study in England.,Setting UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11.,Participants Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record.,Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London.,Main outcome measure Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct.,Results Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years).,Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001).,Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers.,With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02).,Conclusions The use of β blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD.,Registration NCT01335672. | 1 |
Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile.,Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.,Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks.,Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks.,Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.,Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively.,In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo.,Secondary end points supported the efficacy of olodaterol.,These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. | Aerosols delivered by Respimat® Soft Mist™ Inhaler (SMI) are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs), improving the efficiency of pulmonary drug delivery to patients.,In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD) and with poor pMDI technique received radiolabelled Berodual® (fenoterol hydrobromide 50 μg/ipratropium bromide 20 μg) via Respimat® SMI or hydrofluoroalkane (HFA)-MDI (randomized order) on test days 1 and 2, with no inhaler technique training.,The procedure was repeated on test days 3 and 4 after training.,Deposition was measured by gamma scintigraphy.,All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted) inhaled too fast at screening (peak inspiratory flow rate [IF]: 69-161 L/min).,Whole lung deposition was higher with Respimat® SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose) and trained patients (53% of delivered vs 21% of metered dose) (pSign-Test].15; pANOVA < = 0.05).,Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time).,Drug delivery to the lungs with Respimat® SMI is more efficient than with pMDI, even with poor inhaler technique.,Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat® SMI. | 1 |
The latest chronic obstructive pulmonary disease (COPD) epidemiology survey in China estimated that there were 99 million potential COPD patients in the country, the majority of whom are undiagnosed.,Screening for COPD in primary care settings is of vital importance for China, but it is not known which strategy would be the most suitable for adoption in primary care.,Studies have been conducted to test the accuracy of questionnaires, expiratory peak flow meters and microspirometers to screen for COPD, but no study has directly evaluated and compared the effectiveness and cost-effectiveness of these methods in the Chinese setting.,We present the protocol for a multicentre cross-sectional study, to be conducted in eight community hospitals from four cities among Chinese adults aged 40 years or older to investigate the effectiveness and cost-effectiveness of different case-finding methods for COPD, and determine the test performance of individual and combinations of screening tests and strategies in comparison with quality diagnostic spirometry.,Index tests are screening questionnaires (COPD Diagnostic Questionnaire (CDQ), COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk Questionnaire (CAPTURE), symptom-based questionnaire, COPD Screening Questionnaire (COPD-SQ)), microspirometer and peak flow.,Each participant will complete all of these tests in one assessment.,The primary analysis will compare the performance of a screening questionnaire with a handheld device.,Secondary analyses will include the comparative performance of each index test, as well as a comparison of strategies where we use a screening questionnaire and a handheld device.,Approximately 2000 participants will be recruited over 9 to 12 months.,The study has been approved by Peking University Hospital and University of Birmingham.,All study participants will provide written informed consent.,Study results will be published in appropriate journal and presented at national and international conferences, as well as relevant social media and various community/stakeholder engagement activities.,ISRCTN13357135. | Acknowledgement of COPD underdiagnosis and misdiagnosis in primary care can contribute to improved disease diagnosis.,PUMA is an international primary care study in Argentina, Colombia, Venezuela and Uruguay.,To assess COPD underdiagnosis and misdiagnosis in primary care and identify factors associated with COPD underdiagnosis in this setting.,COPD was defined as post-bronchodilator (post-BD) forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.70 and the lower limit of normal (LLN).,Prior diagnosis was self-reported physician diagnosis of emphysema, chronic bronchitis, or COPD.,Those patients with spirometric COPD were considered to have correct prior diagnosis, while those without spirometric criteria had misdiagnosis.,Individuals with spirometric criteria without previous diagnosis were considered as underdiagnosed.,1,743 patients were interviewed, 1,540 completed spirometry, 309 (post-BD FEV1/FVC <0.70) and 226 (LLN) had COPD.,Underdiagnosis using post-BD FEV1/FVC <0.70 was 77% and 73% by LLN.,Overall, 102 patients had a prior COPD diagnosis, 71/102 patients (69.6%) had a prior correct diagnosis and 31/102 (30.4%) had a misdiagnosis defined by post-BD FEV1/FVC ≥0.70.,Underdiagnosis was associated with higher body mass index (≥30 kg/m2), milder airway obstruction (GOLD I-II), black skin color, absence of dyspnea, wheezing, no history of exacerbations or hospitalizations in the past-year.,Those not visiting a doctor in the last year or only visiting a GP had more risk of underdiagnosis.,COPD underdiagnosis (65.8%) and misdiagnosis (26.4%) were less prevalent in those with previous spirometry.,COPD underdiagnosis is a major problem in primary care.,Availability of spirometry should be a priority in this setting. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries.,Recent studies investigated the impact of comorbidities on the survival in COPD, but most of them lacked a referent group of comorbidity-matched, nonobstructed individuals.,We examined the 10-year mortality in a sample of 200 COPD patients and 201 nonobstructed controls.,They were part of a larger cohort enrolled in a European case-control study aimed at assessing genetic susceptibility to COPD.,By design, the COPD group included patients with a forced expiratory volume in 1 second (FEV1) ≤70% predicted.,Cases and controls were matched on age, sex, and cumulative smoking history, and shared a nearly identical prevalence of cardiovascular and metabolic disorders.,We estimated the hazard of death with Cox regression and percentiles of survival with Laplace regression.,COPD was the main exposure variable of interest.,Five comorbidities (hypertension, coronary artery disease, prior myocardial infarction, chronic heart failure, and diabetes) were included as covariates in multiple regression models.,The all-cause mortality rate was significantly higher in cases than in controls (43% vs 16%, P < 0.001).,The unadjusted hazard of death for COPD was 3-fold higher than the referent category (P < 0.001), and remained nearly unchanged after introducing the 5 comorbidities in multiple regression.,Patients with COPD had significantly shorter survival percentiles than comorbidity-matched controls (P < 0.001).,Notably, 15% of the nonobstructed controls died by 10.3 years into the study; the same proportion of COPD patients had died some 6 years earlier, at 4.6 years.,In a separate analysis, we split the whole sample into 2 groups based on the lower tertile of FEV1 and carbon monoxide lung diffusing capacity (DLCO).,The hazard of death for COPD patients with low FEV1 and DLCO was nearly 3.5-fold higher than in all the others (P < 0.001), and decreased only slightly after introducing age and chronic heart failure as relevant covariates.,COPD is a strong predictor of reduced survival independently of coexisting cardiovascular and metabolic disorders.,Efforts should be made to identify patients at risk and to ensure adherence to prescribed therapeutic regimens. | Patients with myocardial infarction (MI) and concomitant chronic obstructive pulmonary disease (COPD) constitute a high‐risk group with increased mortality. β‐Blocker therapy has been shown to reduce mortality, prevent arrhythmias, and delay heart failure development after an MI in broad populations.,However, the effect of β‐blockers in COPD patients is less well established and they may also be less treated due to fear of adverse reactions.,We investigated β‐blocker prescription at discharge in patients with COPD after MI.,Patients hospitalized for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry.,Patients with COPD who were alive and discharged after an MI were selected as the study population.,In this cohort, patients who were discharged with β‐blockers were compared to patients not discharged with β‐blockers.,The primary end point was all‐cause mortality.,A total of 4858 patients were included, of which 4086 (84.1%) were discharged with a β‐blocker while 772 (15.9%) were not.,After adjusting for potential confounders including baseline characteristics, comorbidities, and in‐hospital characteristics, patients discharged with a β‐blocker had lower all‐cause mortality (hazard ratio 0.87, 95% CI 0.78 to 0.98) during the total follow‐up time (maximum 7.2 years).,In the subgroup of patients with a history of heart failure, the corresponding hazard ratio was 0.77 (95% CI 0.63 to 0.95).,Patients with COPD discharged with β‐blockers after an MI had a lower all‐cause mortality compared to patients not prescribed β‐blockers.,The results indicate that MI patients with COPD may benefit from β‐blockers. | 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 Spanish COPD guideline (GesEPOC) classifies COPD into four clinical phenotypes based on the exacerbation frequency and dominant clinical manifestations.,In this study, we compared the disease-specific health-related quality of life (HRQoL) of patients with different clinical phenotypes.,This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018.,Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George’s Respiratory Questionnaire for COPD (SGRQ-c).,Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS).,The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes (P<0.001).,Patients who were AE CB had significantly higher total CAT score than those with ACOS (P=0.033), AE NON-CB (P=0.001), and NON-AE (P<0.001).,Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB (P=0.001) and NON-AE (P<0.001).,However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS (P=0.187).,There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them.,Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components.,Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components. | 1 |
COPD symptoms show a diurnal variability.,However, morning and night variability has generally not been taken into consideration in disease management plans.,The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status.,A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology.,We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service.,Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1).,A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0).,Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers (P<0.0001).,Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect.,Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%).,Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors (n=346, OR:4.13, CI: 2.45−6.95, P<0.000).,Morning symptoms increased the odds of poor health status at follow-up (n=346, OR:12.22, CI:4.76−31.39, P<0.000).,Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations.,Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ.,Severe morning symptoms predicted worsening of COPD health status. | Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms.,While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood.,Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011.,Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week.,Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met.,Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures.,Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels.,Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom.,Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms.,Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without.,Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is now the fourth leading cause of death in the world, and it continues to increase in developing countries.,The World Health Organization expects COPD to be the third most common cause of death in the world by 2020.,Effective and continuous postdischarge care can help patients to maintain good health.,The use of electronic health records (EHRs) as an element of community health care is new technology in China.,The aim of this study was to develop and evaluate a Web-based coaching program using EHRs for physical function and health-related quality of life for patients with COPD in China.,A randomized controlled trial was conducted from 2008 to 2015 at two hospitals.,The control group received routine care and the intervention group received routine care with the addition of the Web-based coaching program using EHRs.,These were used to manage patients’ demographic and clinical variables, publish relevant information, and have communication between patients and health care providers.,Participants were not blinded to group assignment.,The effects of the intervention were evaluated by lung function, including percent of forced expiratory volume in 1 second (FEV1%), percent of forced vital capacity (FVC%), peak expiratory flow (PEF), maximum midexpiratory flow; St George’s Respiratory Questionnaire (SGRQ); Modified Medical Research Council Dyspnea Scale (MMRC); and 6-Minute Walk Test (6MWT).,Data were collected before the program, and at 1, 3, 6, and 12 months after the program.,Of the 130 participants, 120 (92.3%) completed the 12-month follow-up program.,There were statistically significant differences in lung function (FEV1%: F1,4=5.47, P=.002; FVC%: F1,4=3.06, P=.02; PEF: F1,4=12.49, P<.001), the total score of SGRQ (F1,4=23.30, P<.001), symptoms of SGRQ (F1,4=12.38, P<.001), the activity of SGRQ (F1,4=8.35, P<.001), the impact of SGRQ (F1,4=12.26, P<.001), MMRC (F1,4=47.94, P<.001), and 6MWT (F1,4=35.54, P<.001) between the two groups with the variation of time tendency.,The Web-based coaching program using EHRs in China appears to be useful for patients with COPD when they are discharged from hospital into the community.,It promotes the sharing of patients’ medical information by hospital and community nurses, and achieves dynamic management and follow-up analysis for patients’ disease.,In addition, this program can postpone the decreasing rate of lung function, improve quality of life, decrease dyspnea, and increase physical capacity. | Regular physical activity (PA) is recommended for persons with chronic obstructive pulmonary disease (COPD).,Interventions that promote PA and sustain long-term adherence to PA are needed.,We examined the effects of an Internet-mediated, pedometer-based walking intervention, called Taking Healthy Steps, at 12 months.,Veterans with COPD (N=239) were randomized in a 2:1 ratio to the intervention or wait-list control.,During the first 4 months, participants in the intervention group were instructed to wear the pedometer every day, upload daily step counts at least once a week, and were provided access to a website with four key components: individualized goal setting, iterative feedback, educational and motivational content, and an online community forum.,The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content.,Participants randomized to the wait-list control group were instructed to wear the pedometer, but they did not receive step-count goals or instructions to increase PA.,The primary outcome was health-related quality of life (HRQL) assessed by the St George’s Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome was daily step count.,Linear mixed-effect models assessed the effect of intervention over time.,One participant was excluded from the analysis because he was an outlier.,Within the intervention group, we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data, number of log-ins to the website each month, use of the online community forum, and responses to a structured survey.,Participants were 93.7% male (223/238) with a mean age of 67 (SD 9) years.,At 12 months, there were no significant between-group differences in SGRQ-TS or daily step count.,Between-group difference in daily step count was maximal and statistically significant at month 4 (P<.001), but approached zero in months 8-12.,Within the intervention group, mean 76.7% (SD 29.5) of 366 days had valid step-count data, which decreased over the months of study (P<.001).,Mean number of log-ins to the website each month also significantly decreased over the months of study (P<.001).,The online community forum was used at least once during the study by 83.8% (129/154) of participants.,Responses to questions assessing participants’ goal commitment and intervention engagement were not significantly different at 12 months compared to 4 months.,An Internet-mediated, pedometer-based PA intervention, although efficacious at 4 months, does not maintain improvements in HRQL and daily step counts at 12 months.,Waning pedometer adherence and website engagement by the intervention group were observed.,Future efforts should focus on improving features of PA interventions to promote long-term behavior change and sustain engagement in PA.,Clinicaltrials.gov NCT01102777; https://clinicaltrials.gov/ct2/show/NCT01102777 (Archived by WebCite at http://www.webcitation.org/6iyNP9KUC) | 1 |
Quantifying physical activity in chronic obstructive pulmonary disease (COPD) is important as physical inactivity is related to poor health outcomes.,This study analyzed the relationship between patients’ self-reported daily walking time and relevant characteristics related to COPD severity.,Pooled analysis was performed on data from four observational studies on which daily walking time was gathered from a personal interview.,Patients were classified as physically inactive if walking time was <30 min/day.,Walking times were described and compared according to several markers of disease severity.,The mean daily walking time of 5,969 patients was 66 (standard deviation [SD] 47) min/day; 893 (15%) patients were inactive.,A linear dose-response relationship was observed between walking time and the modified Medical Research Council (mMRC) dyspnea score, admissions, COPD assessment test (CAT), body mass index, airway obstruction, dyspnea, exacerbation (BODEx) index, and Charlson index (P<0.001).,Daily walking times were lower in patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B and D (P<0.001).,Often, inactive patients had mMRC or Charlson index >3, post-bronchodilator forced expiratory volume in the first second <30% predicted, at least one hospitalization for COPD, classified as GOLD B or D, BODEx >4, and CAT score >30.,Lower self-reported walking times are related to worse markers of disease severity in COPD. | 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 |
There are no validated measures of disease activity in COPD.,Since “active” disease is expected to have worse outcomes (e.g. mortality), we explored potential markers of disease activity in patients enrolled in the ECLIPSE cohort in relation to 8-year all-cause mortality.,We investigated 1) how changes in relevant clinical variables over time (1 or 3 years) relate to 8-year mortality; 2) whether these variables inter-relate; and 3) if any clinical, imaging and/or biological marker measured cross-sectionally at baseline relates to any activity component.,Results showed that 1) after 1 year, hospitalisation for COPD, exacerbation frequency, worsening of body mass index, airflow obstruction, dyspnoea and exercise (BODE) index or health status (St George's Respiratory Questionnaire (SGRQ)) and persistence of systemic inflammation were significantly associated with 8-year mortality; 2) at 3 years, the same markers, plus forced expiratory volume in 1 s (FEV1) decline and to a lesser degree computed tomography (CT) emphysema, showed association, thus qualifying as markers of disease activity; 3) changes in FEV1, inflammatory cytokines and CT emphysema were not inter-related, while the multidimensional indices (BODE and SGRQ) showed modest correlations; and 4) changes in these markers could not be predicted by any baseline cross-sectional measure.,In COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores and FEV1 decline are independent markers of disease activity associated with 8-year all-cause mortality.,These disease activity markers are generally independent and not predictable from baseline measurements.,In patients with COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores, and FEV1 decline, are independent markers of disease activity associated with 8-year all-cause mortalityhttps://bit.ly/2CyifcN | Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution.,The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.,This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age).,Subjects with any other condition associated with an inflammatory process were excluded.,COPD was defined as a post-bronchodilator FEV1/FVC < 0.70.,The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication.,Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests.,Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.,We compared 324 COPD patients and 110 reference subjects.,After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs.,0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs.,10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs.,3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs.,1.36 ± 0.02 log nmol/l; p = 0.048) than controls.,In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.,Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. | 1 |
The aim of this study was to describe peoples’ experiences and expectations of support when living with chronic obstructive pulmonary disease.,We conducted and analysed face‐to‐face or telephone interviews with 17 individuals (aged 44-77 years) diagnosed with chronic obstructive pulmonary disease.,The interviewer asked open‐ended questions aimed at encouraging further narration, and we analysed the participants’ narratives using a phenomenological hermeneutical approach.,This report adheres to the COREQ guidelines.,The overall theme suggests that people with chronic obstructive pulmonary disease describe support as shared knowledge and experiences, based on the following subthemes; similar experiences, the need of genuine professional knowledge, self‐reliance versus self‐blame, and the Internet - feeling safe but uncertain.,People with chronic obstructive pulmonary disease find their strength through shared knowledge and dialogical support with others who have similar experiences and with professionals.,A person‐centred eHealth approach may be suitable for this group as it offers both collaboration and support.,There is a demand for access to genuine professional knowledge as additional support to patients’ own capabilities and needs.,Patient associations were assessed as reliable sources of information and to some extent also support, but the importance of access to professional sources was also stressed. | Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | 1 |
This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.,Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied.,The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls.,Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001].,The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.,The characteristics of Rbm remodelling are quite different in asthma and COPD. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
The 2018 Global Initiative for Chronic Obstructive Lung Disease Report reveals that the blood eosinophil count could forecast the risk of flare-ups.,This study explored the correlations of blood eosinophils with fractional exhaled nitric oxide (FeNO) and pulmonary function parameters in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,The data of patients with AECOPD at our hospital admitted between July 2018 and June 2019 were retrospectively analyzed.,All patients were stratified into an eosinophilic group (≥2%) or a noneosinophilic group (<2%) based on the peripheral eosinophil count per centum.,Cross-sectional analysis was performed to compare clinical characteristics, percentage of eosinophils, FeNO, and pulmonary function between the 2 groups.,After applying the inclusion/exclusion criteria, 247 patients were included.,FeNO values were higher in eosinophilic group (n=97) than in noneosinophilic group (n=150) (P=0.005).,The forced expiratory volume in 1 second% predicted (FEV1% predicted), FEV1, and forced vital capacity (FVC) were higher in the eosinophilic group than in the noneosinophilic group (P=0.043; P=0.040; and P=0.011, respectively).,Blood eosinophilia showed positive correlations with FeNO (P=0.004) and spirometry variables (FEV1 [% predicted], P=0.003; FEV1, P<0.001; and FVC, P<0.001).,An FeNO level of 22.5 ppb was the best cutoff value to predict blood eosinophilia (P=0.000).,Blood eosinophil count is a likely biomarker that can predict positive relationship with FeNO values and pulmonary function parameters. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
To investigate the association between inhaled corticosteroid (ICS) exposure patterns and the risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients, we performed a nested case-control study.,Between 1998 and 2010, 51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849 control subjects selected from a cohort of COPD patients using ICSs via risk-set sampling of the database constructed by the National Health Research Institutes of Taiwan.,After adjusting for covariates, the current use of ICSs was associated with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.25, 95% confidence interval [CI] =1.20-1.30), and there was an increase in the OR with increase in the average daily dosage.,Additionally, users of fluticasone/salmeterol, fluticasone, and either fluticasone/salmeterol or fluticasone were more likely to be at a higher risk of pneumonia (OR =1.35, 95% CI =1.28-1.41; OR =1.22, 95% CI =1.10-1.35; and OR =1.33, 95% CI =1.27-1.39, respectively).,In contrast, there were no statistically significant associations between the risk of pneumonia and the use of budesonide/formoterol, budesonide, or either budesonide/formoterol or budesonide.,In conclusion, ICSs are significantly associated with an increased risk of pneumonia in COPD patients.,The effect is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs. | Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function.,This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol.,This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study.,Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4-14-day washout period.,ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients.,The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects.,Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point).,In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 μM versus 0.09 μM).,The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006).,Both treatments were well tolerated.,The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar.,In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide.,Trial registration number NCT00379028 | 1 |
No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD).,Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.,Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors.,Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.,236 COPD patients from five European centres were included.,Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”.,After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14.,Both demonstrated good model fit (person separation index >0.7).,Confirmatory factor analysis supported the bidimensional structure.,Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.,Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.,Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patientshttp://ow.ly/LJqP8 | Indacaterol is a long-acting beta-2 agonist for once-daily treatment of COPD.,We evaluated the effects of indacaterol 150 μg on lung hyperinflation compared with placebo and open-label tiotropium 18 μg.,We measured physical activity during treatment with indacaterol 150 μg and matched placebo.,We performed a randomized, three-period, cross-over study (21 days of treatment separated by two wash-out periods of 13 days) with indacaterol 150 μg or matching placebo and tiotropium 18 μg.,Lung function was assessed by body plethysmography and spirometry.,Physical activity was measured for one week by a multisensory armband at the end of both treatment periods with indacaterol/matched placebo.,The primary endpoint was peak inspiratory capacity at the end of each treatment period.,129 patients (mean age, 61 years; mean post-bronchodilator FEV1, 64%), were randomized and 110 patients completed the study.,Peak inspiratory capacity was 0.22 L greater with Indacaterol at day 21 compared to placebo (p < 0.001).,Similar results were observed for tiotropium.,Both bronchodilators also significantly improved other parameters of lung hyperinflation compared with placebo.,All parameters of physical activity were significantly increased during treatment with indacaterol versus placebo.,Indacaterol 150 μg improved lung hyperinflation in patients with moderate COPD, which was associated with an increase of physical activity.,ClinicalTrials.gov registration number: NCT01012765. | 1 |
Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity.,Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes.,Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support.,We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study.,PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler.,Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity.,To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps.,This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies.,The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations.,The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations.,NCT02085161. | Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations.,We hypothesized that short-acting β2-agonist (SABA) reliever use would predict short- and long-term exacerbation risk in COPD patients.,We performed a retrospective analysis of data from a study (ClinicalTrials.gov registration: NCT00419744) comparing budesonide/formoterol 320/9 μg with formoterol 9 μg (both twice daily) in patients with moderate-to-very-severe COPD; reliever salbutamol 90 μg was provided.,First occurrence of reliever use >4 (low), >10 (medium), and >20 (high) inhalations/day was assessed as a predictor of short-term (3-week) exacerbation risk.,Mean daily reliever use in the week preceding the 2-month visit was investigated as a predictor of the long-term (10-month) exacerbation risk, using intervals of 2-5, 6-9, and ≥10 inhalations/day.,Overall, 810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator forced expiratory volume in 1 s 37.7 % of predicted).,First occurrence of low, medium, or high reliever use was predictive of an exacerbation within the following 3 weeks; exacerbation risk increased significantly with increasing reliever use.,Mean reliever use over 1 week was predictive of long-term exacerbation risk.,Patients with mean use of 2-5, 6-9, and ≥10 inhalations/day exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the following 10 months, compared with <2 inhalations/day.,Budesonide/formoterol was associated with lower short- and long-term exacerbation risk than formoterol in all reliever-use groups.,SABA reliever use is a predictor of short- and long-term exacerbation risk in moderate-to-very-severe COPD patients with a history of exacerbations receiving budesonide/formoterol or formoterol. | 1 |
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms.,Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections.,Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.,Exogenous interferon-β reverses these effects.,FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways.,Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection.,This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production.,Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.,Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia.,Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ. | To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD).,We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups.,The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture.,LOS and CAT as well as demographic information were recorded.,Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both.,Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus.,Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae.,The longest LOS and the highest CAT score were detected in coinfection group.,CAT score was positively correlated with LOS.,Respiratory infection is a common causative agent of exacerbations in COPD.,Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS.,CAT score may be a predictor of longer LOS in AECOPD. | 1 |
The rate of obesity is increasing in Asia, but the clinical impact of body mass index (BMI) on the outcome of chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to assess this impact while focusing on the risk of exacerbation, health-care utilization, and medical costs.,We examined 43,864 subjects registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to National Health Insurance (NHI) data.,COPD was confirmed by spirometry.,BMI was used to stratify patients into four categories: underweight (BMI <18.5 kg/m2), normal range (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (≥25 kg/m2).,Of the 1,320 patients with COPD with mild to moderate airflow obstruction, 27.8% had a BMI ≥25 kg/m2.,Compared with normal-weight patients, obese patients tended to experience fewer exacerbations (incidence rate ratio [IRR] 0.88; 95% CI 0.77-0.99; P = 0.04), although this association was not significant in a multivariable analysis.,COPD-related health-care utilization and medical expenses were higher among underweight patients than the other groups.,After adjustment, the risk of COPD-related hospitalization was highest among underweight and higher among overweight patients vs normal-weight patients (adjusted IRRs: 7.12, 1.00, 1.26, and 1.02 for underweight, normal, overweight, and obese groups, respectively; P = 0.01).,Decreased weight tends to negatively influence prognosis of COPD with mild to moderate airflow obstruction, whereas higher BMI was not significantly related to worse outcomes. | A low body mass index (BMI) is associated with increased mortality and low health-related quality of life in patients with COPD.,The Asia-Pacific classification of BMI has a lower cutoff for overweight and obese categories compared to the World Health Organization (WHO) classification.,The present study assessed patients with COPD among different BMI categories according to two BMI classification systems: WHO and Asia-Pacific.,Patients with COPD aged 40 years or older from the Korean COPD Subtype Study cohort were selected for evaluation.,We enrolled 1,462 patients.,Medical history including age, sex, St George’s Respiratory Questionnaire (SGRQ-C), the modified Medical Research Council (mMRC) dyspnea scale, and post-bronchodilator forced expiratory volume in 1 second (FEV1) were evaluated.,Patients were categorized into different BMI groups according to the two BMI classification systems.,FEV1 and the diffusing capacity of the lung for carbon monoxide (DLCO) percentage revealed an inverse “U”-shaped pattern as the BMI groups changed from underweight to obese when WHO cutoffs were applied.,When Asia-Pacific cutoffs were applied, FEV1 and DLCO (%) exhibited a linearly ascending relationship as the BMI increased, and the percentage of patients in the overweight and obese groups linearly decreased with increasing severity of the Global Initiative for Chronic Obstructive Lung Disease criteria.,From the underweight to the overweight groups, SGRQ-C and mMRC had a decreasing relationship in both the WHO and Asia-Pacific classifications.,The prevalence of comorbidities in the different BMI groups showed similar trends in both BMI classifications systems.,The present study demonstrated that patients with COPD who have a high BMI have better pulmonary function and health-related quality of life and reduced dyspnea symptoms.,Furthermore, the Asia-Pacific BMI classification more appropriately reflects the correlation of obesity and disease manifestation in Asian COPD patients than the WHO classification. | 1 |
AMPLIFY assessed the efficacy and safety of aclidinium bromide/formoterol fumarate (AB/FF) vs its monocomponents and tiotropium (TIO) in patients with moderate-to-very severe symptomatic COPD (NCT02796677).,In this 24-week, Phase III, double-dummy, active-controlled study, symptomatic patients (COPD Assessment Test score ≥10) were randomized to twice-daily AB/FF 400/12 µg, AB 400 µg, or FF 12 µg, or once-daily TIO 18 µg.,Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEV1 (AB/FF vs AB) and in pre-dose (trough) FEV1 (AB/FF vs FF).,Non-inferiority of AB vs TIO in pre-dose FEV1 was also an objective.,Normalized area under the curve (AUC)0-3/3 h FEV1 and nighttime and early morning symptoms were also assessed.,A subgroup participated in a 24-hour serial spirometry sub-study.,A total of 1,594 patients were randomized; 566 entered the sub-study.,At week 24, 1-hour post-dose FEV1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P<0.0001).,AB/FF significantly improved trough FEV1 vs FF (55 mL, P<0.001) and AB was non-inferior to TIO.,AB/FF significantly improved AUC0-3/3 h FEV1 vs all comparators (P<0.0001) and provided significant improvements in early morning symptoms vs TIO.,The 24-hour spirometry demonstrated significantly greater improvements with AB/FF in AUC12-24/12 h vs all comparators, and in AUC0-24/24 h vs FF or TIO at week 24.,In patients with moderate-to-very severe symptomatic COPD, twice-daily AB/FF significantly improved lung function vs monocomponents and TIO, and early morning symptom control vs TIO. | To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD.,We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo.,A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George’s Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24.,Inconsistency models were not statistically significant for all outcomes.,LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24.,All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1.,Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant.,LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement.,Similar trends were observed for the transition dyspnea index and St George’s Respiratory Questionnaire outcomes.,There were no significant differences in the incidences of adverse events among all treatment options.,LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement.,There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes. | 1 |
Long-term maintenance therapy for COPD is evolving rapidly.,Dual bronchodilation with new long-acting muscarinic antagonist and long-acting beta-agonist (LAMA/LABA) fixed dose combination inhalers were introduced over the past 2 years.,In clinical trials, these inhalers significantly improved lung function (trough forced expiratory volume in 1 second), patient-reported outcomes, and quality of life measures compared with placebo, their respective monocomponents, and tiotropium.,The recorded adverse events of these new inhalers were also similar to those of their monocomponents or placebo.,There are concerns regarding long-term complications (weight gain, osteoporosis, cataract) and increased risk of community-acquired pneumonia with the use of inhaled corticosteroids (ICS).,The new LAMA/LABA inhalers could potentially reduce the use of ICS as part and parcel of maintenance therapy in COPD.,Recent studies compared these LAMA/LABA inhalers with ICS/LABA combination inhalers in moderate-to-severe COPD.,The results are promising and favor the LAMA/LABA inhalers, especially in the longer duration trials.,Furthermore, there is a clearer picture emerging as to the subgroup of COPD patients who may be able to successfully switch from their current ICS/LABA therapy to these new LAMA/LABA inhalers. | 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. | 1 |
The gold standard for the diagnosis of chronic obstructive pulmonary disease (COPD) is spirometry, but there are barriers to its use in primary care.,To externally validate the COPD Diagnostic Questionnaire (CDQ) as a diagnostic tool in patients at increased risk in Australian general practice and to compare its performance with other CDQ validation studies.,Patients were recruited from 36 general practices in Sydney, Australia.,Former or current smokers aged 40-85 years with no prior COPD diagnosis were invited to a case-finding appointment with the practice nurse.,The CDQ was collected and pre- and postbronchodilator spirometry was performed.,Cases for whom complete CDQ data were present and the spirometry met quality standards were analysed.,Of 1,631 patients who attended case-finding recruitment, 1,054 (65%) could be analysed.,Spirometry showed 13% had COPD.,The ability of the CDQ to discriminate between patients with and without COPD was fair, represented by the area under the receiver operating characteristic curve of 0.713.,With a CDQ cut-off point value of 16.5 the sensitivity was 80% and specificity 47% and, at a cut-off point value of 19.5, the sensitivity was 63% and specificity 70%.,The CDQ did not discriminate between patients with and without COPD accurately enough to use as a diagnostic tool in patients at increased risk of COPD in Australian general practice.,Further research is needed on the value of the CDQ as a tool for selecting patients for spirometry. | COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated.,We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD.,COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5).,A national survey of 697 patients was conducted at 12 practitioner sites.,Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%).,ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity.,Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations.,For known-groups validation, COPD-PS differences between clinical groups were tested.,Test-retest reliability was evaluated in a 20% sample.,Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO.,Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age.,COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91).,Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3).,Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems.,With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%.,The COPD-PS accurately classified physician-reported COPD (AUC = 0.89).,The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD. | 1 |
A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions.,To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending.,A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD).,Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants.,Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier.,In addition, we identified determinants associated with low activation for self-management using logistic regression analysis.,We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients.,Mean age was 69.6±10.9.,Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%.,All associations, except for social support, were disease transcending.,This study explored factors associated with varying levels of activation for self-management.,These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management.,Increased scientific efforts are needed to explain the greater part of the factors that contribute to the complex nature of patient activation for self-management. | The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care.,The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation.,Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care).,Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care.,The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32).,The program was accessed on 86% of the treatment days, especially the diary.,Patient adherence with the exercise scheme was low (21%).,Health care providers seem to play an important role in patients’ adherence to telehealth in usual care.,Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence. | 1 |
To assess the effects of a home-based telehealth intervention on the use of secondary healthcare and mortality.,Observational study of a mainstream telehealth service, using person-level administrative data.,Time to event analysis (Cox regression) was performed comparing telehealth patients with controls who were matched using a machine-learning algorithm.,A predominantly rural region of England (North Yorkshire).,716 telehealth patients were recruited from community, general practice and specialist acute care, between June 2010 and March 2013.,Patients had chronic obstructive pulmonary disease, congestive heart failure or diabetes, and a history of associated inpatient admission.,Patients were matched 1:1 to control patients, also selected from North Yorkshire, with respect to demographics, diagnoses of health conditions, previous hospital use and predictive risk score.,Telehealth involved the remote exchange of medical data between patients and healthcare professionals as part of the ongoing management of the patient's health condition.,Monitoring centre staff alerted healthcare professionals if the telemonitored data exceeded preset thresholds.,Control patients received usual care, without telehealth.,Time to the first emergency (unplanned) hospital admission or death.,Secondary metrics included time to death and time to first admission, outpatient attendance and emergency department visit.,Matched controls and telehealth patients were similar at baseline.,Following enrolment, telehealth patients were more likely than matched controls to experience emergency admission or death (adjusted HR 1.34, 95% CI 1.16 to 1.56, p<0.001).,They were also more likely to have outpatient attendances (adjusted HR=1.25, 1.11 to 1.40, p<0.001), but mortality rates were similar between groups.,Sensitivity analyses showed that we were unlikely to have missed reductions in the likelihood of an emergency admission or death because of unobserved baseline differences between patient groups.,Telehealth was not associated with a reduction in secondary care utilisation. | Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc. | 1 |
Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD.,In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety.,Moreover, the anticipation of dyspnea itself can have a significant effect on patients’ emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD.,Dyspnea is, therefore, a key target for COPD treatments.,Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients’ increased inspiratory neural drive to breathe.,However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea.,Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes.,Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention. | Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | 1 |
Cycle ergometer training (CET) has been shown to improve exercise performance of the quadriceps muscles in patients with COPD, and inspiratory muscle training (IMT) may improve the pressure-generating capacity of the inspiratory muscles.,However, the effects of combined CET and IMT remain unclear and there is a lack of comprehensive assessment.,Eighty-one patients with COPD were randomly allocated to three groups: 28 received 8 weeks of CET + IMT (combined training group), 27 received 8 weeks of CET alone (CET group), and 26 only received 8 weeks of free walking (control group).,Comprehensive assessment including respiratory muscle strength, exercise capacity, pulmonary function, dyspnea, quality of life, emotional status, nutritional status, and body mass index, airflow obstruction, and exercise capacity index were measured before and after the pulmonary rehabilitation program.,Respiratory muscle strength, exercise capacity, inspiratory capacity, dyspnea, quality of life, depression and anxiety, and nutritional status were all improved in the combined training and CET groups when compared with that in the control group (P<0.05) after pulmonary rehabilitation program.,Inspiratory muscle strength increased significantly in the combined training group when compared with that in the CET group (ΔPImax [maximal inspiratory pressure] 5.20±0.89 cmH2O vs 1.32±0.91 cmH2O; P<0.05).,However, there were no significant differences in the other indices between the two groups (P>0.05).,Patients with weakened respiratory muscles in the combined training group derived no greater benefit than those without respiratory muscle weakness (P>0.05).,There were no significant differences in these indices between the patients with malnutrition and normal nutrition after pulmonary rehabilitation program (P>0.05).,Combined training is more effective than CET alone for increasing inspiratory muscle strength.,IMT may not be useful when combined with CET in patients with weakened inspiratory muscles.,Nutritional status had slight impact on the effects of pulmonary rehabilitation.,A comprehensive assessment approach can be more objective to evaluate the effects of combined CET and IMT. | This paper reviews evidence and quality of Systematic Reviews (SRs) on the effects of breathing control exercises (BCEs) and respiratory muscle training (RMT) on breathlessness/dyspnea and other symptoms, and quality of life (QOL) for individuals with chronic obstructive pulmonary disease (COPD).,A search for BCE and RMT literature in COPD published between January 1, 2002 and December 31, 2013 was performed in the following databases: PubMed, Ovid, CINAHL, PsycINFO, AMED, Cochrane and PEDro.,The AMSTAR criteria were used to evaluate quality.,After reviewing 642 reports, seven SRs were identified on RMT and BCEs.,Three SRs were of high quality, three were of moderate quality, and one was of low quality.,Two high-quality SRs reported significantly beneficial effects of RMT on dyspnea, and one reported significant effects on disease-specific QOL and fatigue.,In these SRs, pooled data analyses were performed with three to fourteen single randomised control trials (RCTs) included in the analysis.,In one of the SRs the quality of the single RCTs were rated by the authors to be between 5-7 (with10 best) and in the other one the quality of the single RCTs were rated to be between 30-83% of the maximum score.,One high-quality SR found a significant positive effect of BCE based on pooled data analysis with two single RCTs in regard to pursed-lip breathing (PLB) on breathlessness.,In this SR, one single RCT on diaphragmatic breathing (DB) and another one on yoga breathing (YB) showed effect on disease-specific QOL.,The single RCTs included in the SR were rated by the authors in the SRs to be of low and moderate quality.,Based on three high-quality SRs performing pooled data analyses, there is evidence that RMT has effect on breathlessness, fatigue and disease-specific QOL and PLB on breathlessness.,There is also evidence that single studies on DB and YB has effect on disease-specific QOL.,Few RCTs are available and the variable quality of the single RCTs in the SRs, seem to require more RCTs in particular for BCEs, but also RMT before conclusions regarding effects and high quality SRs can be written.,The online version of this article (doi:10.1186/1471-2466-14-184) contains supplementary material, which is available to authorized users. | 1 |
We built a decision-analytic model to compare the cost-effectiveness of using portable spirometer and questionnaire to screen chronic obstructive pulmonary diseases (COPD) with no screening (i.e. usual care) among chronic bronchitis patient in China.,A lifetime horizon and a payer perspective were adopted.,Cost data of health services including spirometry screening and treatment costs covered both maintenance and exacerbation.,The result indicated that portable spirometer screening was cost-saving compared with questionnaire screening and no screening, with an incremental cost-effectiveness ratio (ICER) of −5026 and −1766 per QALY, respectively.,Sensitivity analyses confirmed the robustness of the results.,In summary, portable spirometer screening is likely the optimal option for COPD screening among chronic bronchitis patients China. | The underdiagnosis of chronic obstructive pulmonary disease (COPD) could be improved through screening using portable devices simpler than conventional spirometers in specific healthcare settings to reach a higher percentage of the at-risk population.,This study was designed to assess the validity and reliability of the COPD-6 portable device to screen for COPD in non-specialized healthcare settings.,Prospective cohort study to validate a diagnostic test.,Three cohorts were recruited: primary care (PC), emergency services (ES) and community pharmacies (CPh).,Study population: individuals with risk factors for COPD (>40 years, smoking >10 pack-years, with respiratory symptoms).,The values measured using the COPD-6 were FEV1, FEV6 and the FEV1/FEV6 ratio.,Subsequently, participants underwent conventional spirometry at hospital, using a post-bronchodilator FEV1/FVC value <0.7 as the gold standard criterion for the COPD diagnosis.,437 participants were included, 362 were valid for the analysis.,COPD was diagnosed in 114 patients (31.5%).,The area under the ROC curve for the COPD-6 for COPD screening was 0.8.,The best cut-off point for the FEV1/FEV6 ratio was 0.8 (sensitivity, 92.1%) using spirometry with the bronchodilator test as the gold standard.,There were practically no differences in the COPD-6 performancein the different settings and also regarding age, gender and smoking status.,The COPD-6 device is a valid tool for COPD screening in non-specialized healthcare settings.,In this context, the best cut-off point for the FEV1/FEV6 ratio is 0.8. | 1 |
Triple inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) combination therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations/symptoms on dual LAMA/LABA or ICS/LABA therapy.,The relative efficacy of budesonide/glycopyrronium/formoterol fumarate metered dose inhaler 320/18/9.6 µg (BGF MDI) in COPD was compared with other ICS/LAMA/LABA fixed-dose and open combination therapies in a network meta-analysis (NMA).,A systematic literature review was conducted to identify randomized controlled trials of at least 10-week duration, including at least one fixed-dose or open combination triple therapy arm, in patients with moderate to very severe COPD.,Studies were assessed for methodological quality and risk of bias.,A three-level hierarchical Bayesian NMA model was used to determine the exacerbation rate per patient per year as well as the following outcomes at week 24: changes from baseline in pre-dose trough forced expiratory volume in 1 s (FEV1), post-dose peak FEV1, and St.,George’s Respiratory Questionnaire (SGRQ) total score; proportion of SGRQ responders; and Transition Dyspnea Index focal score.,Change from baseline in rescue medication use over weeks 12-24 was also analyzed.,Meta-regression and sensitivity analyses were used to assess heterogeneity across studies.,Eighteen studies (n = 29,232 patients) contributed to the NMA.,ICS/LABA dual combinations were combined as a single treatment group to create a connected network.,Across all outcomes, there were no statistically significant differences between BGF MDI and other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium/formoterol fumarate) and open combinations with data available within the network.,Results from sensitivity analyses and meta-regression were consistent with the base-case scenario.,This NMA suggested that BGF MDI has comparable efficacy to other ICS/LAMA/LABA fixed-dose and open triple combination therapies in reducing exacerbations and improving lung function and symptoms in patients with moderate to very severe COPD.,Further research is warranted as additional evidence regarding triple therapies, especially fixed-dose combinations, becomes available.,The online version of this article (10.1007/s12325-020-01311-3) contains supplementary material, which is available to authorized users. | The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively.,We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD.,207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 μg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 μg via HandiHaler.,Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1) < 50% predicted, or FEV1 < 80% predicted and ≥ 2 moderate or 1 severe exacerbations in the prior year.,The primary endpoint in both trials was weighted mean change from baseline (wmCFB) in 0-24-h FEV1 at Week 12.,Secondary endpoints included CFB in trough FEV1 at Day 84 and 85.,Other endpoints included serial FEV1 and health status outcomes at Week 12.,Safety was evaluated descriptively.,The modified per-protocol population included 720 and 711 patients in studies 207608 and 207609 (intent-to-treat population: 728 and 732).,FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 (Study 207608 treatment difference [95% confidence interval]: 15 mL [− 13, 43]; Study 207609: 11 mL [− 20, 41]).,FF/UMEC/VI improved trough FEV1 CFB versus BUD/FOR+TIO at Day 84 and 85 (Day 85 treatment difference: Study 207608: 38 mL [10, 66]; Study 207609: 51 mL [21, 82]) and FEV1 at 12 and 24 h post-morning dose at Week 12 in both studies.,No treatment differences were seen in health status outcomes.,Safety profiles were similar between treatments; pneumonia occurred in 7 (< 1%) patients with FF/UMEC/VI and 9 (1%) patients with BUD/FOR+TIO, across both studies.,FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 in patients with COPD.,Greater improvements in trough and serial FEV1 measurements at Week 12 with FF/UMEC/VI versus BUD/FOR+TIO, together with similar health status improvements and safety outcomes including the incidence of pneumonia, suggest that once-daily single-inhaler FF/UMEC/VI triple therapy is a viable option for patients looking to simplify their treatment regimen.,GSK (207608/207609; NCT03478683/NCT03478696). | 1 |
Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy.,Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo.,Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George’s Respiratory Questionnaire.,Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment.,Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol.,Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo.,Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo.,St George’s Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo.,No safety signals were identified from adverse-event or other safety data.,Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile. | 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 |
Asthma and COPD have overlapping characteristics.,As there are limited data on whether asthma-COPD overlap (ACO) represents a distinct condition, this study aimed to determine the similarities and differences of ACO with asthma and COPD.,US population-based, cross-sectional study using National Health and Nutrition Examination Survey data (2009-2012) compared participants with ACO vs those with asthma or COPD, each as mutually exclusive disease states.,Demographics, health status, disability/limitations, health care resource utilization, clinical characteristics, and peripheral blood eosinophil counts were analyzed.,A total of 1,609, 479, and 299 participants with asthma, COPD, and ACO, respectively, were included.,An age-matched asthma subgroup included 299 participants from the asthma group.,Compared with asthma and COPD, participants with ACO had worse health status, increased disease burden, and more comorbid conditions.,The ACO, vs age-matched asthma subgroup, had lower percent predicted prebronchodilator forced expiratory volume in 1 second (82.1% vs 88.0%; P=0.017).,The ACO group had significantly more asthma attacks in the past year than the age-matched asthma subgroup (49.8% vs 38.4%; P<0.001).,The ACO group had more participants with postbronchodilator forced expiratory volume in 1 second <80% predicted (52.1%) vs COPD (30.8%; P=0.003) and more participants with blood eosinophil counts ≥400 cells/µL (16.9%) vs COPD (9.5%; P=0.007) and the asthma subgroup (6.7%; P=0.014).,The ACO group represents an important subset of patients with chronic respiratory disease with an increased burden of disease over asthma and COPD individually.,Early identification of this population will enable appropriate therapeutic interventions in a timely manner. | Interleukin (IL)-33 promotes T helper (Th)2 immunity and systemic inflammation.,The role of IL-33 in asthma has been widely investigated.,IL-33 has also been suggested to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,This study investigated the clinical significance and usefulness of plasma IL-33 level in patients with COPD.,A total of 307 patients with stable COPD from 15 centers, who were in the Korean Obstructive Lung Disease cohort, were enrolled in this study.,Plasma IL-33 levels were measured by enzyme-linked immunosorbent assay.,We analyzed the association between IL-33 level and other clinical characteristics related to COPD.,We also examined the features of patients with COPD who exhibited high IL-33 levels.,IL-33 levels varied, but were very low in most patients.,Eosinophil count was significantly correlated with a plasma IL-33 level.,In addition, old age and current smoking were related to a low IL-33 level.,Significantly more patients with a higher IL-33 level had chronic bronchitis compared with those with a low IL-33 level.,Plasma IL-33 level in patients with stable COPD was related to eosinophil count and chronic bronchitis phenotype.,Further studies are needed to identify the precise mechanisms of IL-33/ST2 pathway in patients with COPD. | 1 |
This study is an analysis of a pilot COPD clinical audit that evaluated adherence to guidelines for patients with COPD in a stable disease phase during a routine visit in specialized secondary care outpatient clinics in order to identify the variables associated with the decision to step-up or step-down pharmacological treatment.,This study was a pilot clinical audit performed at hospital outpatient respiratory clinics in the region of Andalusia, Spain (eight provinces with over eight million inhabitants), in which 20% of centers in the area (catchment population 3,143,086 inhabitants) were invited to participate.,Treatment changes were evaluated in terms of the number of prescribed medications and were classified as step-up, step-down, or no change.,Three backward stepwise binominal multivariate logistic regression analyses were conducted to evaluate variables associated with stepping up, stepping down, and inhaled corticosteroids discontinuation.,The present analysis evaluated 565 clinical records (91%) of the complete audit.,Of those records, 366 (64.8%) cases saw no change in pharmacological treatment, while 99 patients (17.5%) had an increase in the number of drugs, 55 (9.7%) had a decrease in the number of drugs, and 45 (8.0%) noted a change to other medication for a similar therapeutic scheme.,Exacerbations were the main factor in stepping up treatment, as were the symptoms themselves.,In contrast, rather than symptoms, doctors used forced expiratory volume in 1 second and previous treatment with long-term antibiotics or inhaled corticosteroids as the key determinants to stepping down treatment.,The majority of doctors did not change the prescription.,When changes were made, a number of related factors were noted.,Future trials must evaluate whether these therapeutic changes impact clinically relevant outcomes at follow-up. | Excluding the tropics, exacerbations of chronic obstructive pulmonary disease (COPD) are more frequent in winter.,However, studies that directly relate hospitalizations for exacerbation of COPD to ambient temperature are lacking.,The aim of this study was to assess the influence of temperature on the number of hospitalizations for COPD.,This was a population-based study in a metropolitan area.,All hospital discharges for acute exacerbation of COPD during 2009 in Barcelona and its metropolitan area were analyzed.,The relationship between the number of hospitalizations for COPD and the mean, minimum, and maximum temperatures alongside comorbidity, humidity, influenza rate, and environmental pollution were studied.,A total of 9,804 hospitalization discharges coded with COPD exacerbation as a primary diagnosis were included; 75.4% of cases were male with a mean age of 74.9±10.5 years and an average length of stay of 6.5±6.1 days.,The highest number of admissions (3,644 [37.2%]) occurred during winter, followed by autumn with 2,367 (24.1%), spring with 2,347 (23.9%), and summer with 1,446 (14.7%; P<0.001).,The maximum, minimum, and mean temperatures were associated similarly with the number of hospitalizations.,On average, we found that for each degree Celsius decrease in mean weekly temperature, hospital admissions increased by 5.04% (r2=0.591; P<0.001).,After adjustment for humidity, comorbidity, air pollution, and influenza-like illness, only mean temperatures retained statistical significance, with a mean increase of 4.7% in weekly admissions for each degree Celsius of temperature (r2=0.599, P<0.001).,Mean temperatures are closely and independently related to the number of hospitalizations for COPD. | 1 |
The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms.,The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.,In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.,The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.,Overall, 676 patients completed the study.,The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met.,QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001).,QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001).,QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use.,However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC.,Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%).,The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).,These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
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. | Early descriptions of patients admitted to hospital during the COVID-19 pandemic showed a lower prevalence of asthma and chronic obstructive pulmonary disease (COPD) than would be expected for an acute respiratory disease like COVID-19, leading to speculation that inhaled corticosteroids (ICSs) might protect against infection with severe acute respiratory syndrome coronavirus 2 or the development of serious sequelae.,We assessed the association between ICS and COVID-19-related death among people with COPD or asthma using linked electronic health records (EHRs) in England, UK.,In this observational study, we analysed patient-level data for people with COPD or asthma from primary care EHRs linked with death data from the Office of National Statistics using the OpenSAFELY platform.,The index date (start of follow-up) for both cohorts was March 1, 2020; follow-up lasted until May 6, 2020.,For the COPD cohort, individuals were eligible if they were aged 35 years or older, had COPD, were a current or former smoker, and were prescribed an ICS or long-acting β agonist plus long-acting muscarinic antagonist (LABA-LAMA) as combination therapy within the 4 months before the index date.,For the asthma cohort, individuals were eligible if they were aged 18 years or older, had been diagnosed with asthma within 3 years of the index date, and were prescribed an ICS or short-acting β agonist (SABA) only within the 4 months before the index date.,We compared the outcome of COVID-19-related death between people prescribed an ICS and those prescribed alternative respiratory medications: ICSs versus LABA-LAMA for the COPD cohort, and low-dose or medium-dose and high-dose ICSs versus SABAs only in the asthma cohort.,We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the association between exposure categories and the outcome in each population, adjusted for age, sex, and all other prespecified covariates.,We calculated e-values to quantify the effect of unmeasured confounding on our results.,We identified 148 557 people with COPD and 818 490 people with asthma who were given relevant respiratory medications in the 4 months before the index date.,People with COPD who were prescribed ICSs were at increased risk of COVID-19-related death compared with those prescribed LABA-LAMA combinations (adjusted HR 1·39 [95% CI 1·10-1·76]).,Compared with those prescribed SABAs only, people with asthma who were prescribed high-dose ICS were at an increased risk of death (1·55 [1·10-2·18]), whereas those given a low or medium dose were not (1·14 [0·85-1·54]).,Sensitivity analyses showed that the apparent harmful association we observed could be explained by relatively small health differences between people prescribed ICS and those not prescribed ICS that were not recorded in the database (e value lower 95% CI 1·43).,Our results do not support a major role for regular ICS use in protecting against COVID-19-related death among people with asthma or COPD.,Observed increased risks of COVID-19-related death can be plausibly explained by unmeasured confounding due to disease severity.,UK Medical Research Council. | 1 |
COPD affects millions of people worldwide.,Poor treatment adherence contributes to increased symptom severity, morbidity and mortality.,This study was designed to investigate adherence to COPD treatment in Turkey and Saudi Arabia.,An observational, cross-sectional study in adult COPD patients in Turkey and Saudi Arabia.,Through physician-led interviews, data were collected on sociodemographics and disease history, including the impact of COPD on health status using the COPD Assessment Test (CAT); quality of life, using the EuroQol Five-Dimension questionnaire (EQ-5D); and anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).,Treatment adherence was measured using the 8-item Morisky Medication Adherence Scale (MMAS-8).,Multivariate logistic regression analysis examined the predictors of non-adherence and the impact of adherence on symptom severity.,Four hundred and five COPD patients participated: 199 in Turkey and 206 in Saudi Arabia.,Overall, 49.2% reported low adherence (MMAS-8 <6).,Of those, 74.7% reported high disease impact (CAT >15) compared to 58.4% reporting medium/high adherence (p=0.0008).,Patients with low adherence reported a lower mean 3-level EQ-5D utility value (0.54±0.35) compared to those with medium/high adherence (0.64±0.30; p<0.0001).,Depression with HADS score 8-10 or >10 was associated with lower adherence (OR 2.50 [95% CI: 1.43-4.39] and 2.43 [95% CI: 1.39-4.25], respectively; p=0.0008).,Being a high school/college graduate was associated with better adherence compared with no high school (OR 0.57 [95% CI: 0.33-0.98] and 0.38 [95% CI: 0.15-1.00], respectively; p=0.0310).,After adjusting for age, gender, and country, a significant association between treatment adherence (MMAS-8 score ≥6) and lower disease impact (CAT ≤15) was observed (OR 0.56 [95% CI: 0.33-0.95]; p=0.0314).,Adherence to COPD treatment is poor in Turkey and Saudi Arabia.,Non-adherence to treatment is associated with higher disease impact and reduced quality of life.,Depression, age, and level of education were independent determinants of adherence. | Low therapeutic adherence to medication is very common.,Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment.,The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies.,The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence.,Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients.,A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling.,Subjects will be randomly allocated into two groups, using the block randomization technique.,Every patient in each group will be visited four times during the year of the study.,Intervention: Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training.,Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group.,Adherence to a prescribed treatment involves a behavioural change.,Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice.,Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group.,We will evaluate the effectiveness of this multifactor intervention on patient adherence to inhaled drugs considering that it will be right and feasible to the clinical practice context.,Current Controlled Trials ISCTN18841601 | 1 |
Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | 1 |
Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often coexist.,We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at heightened CVD risk.,The SUMMIT (Study to Understand Mortality and MorbidITy) was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 16 485 patients with moderate COPD who had or were at high risk of CVD.,Here, we assessed the prespecified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD adverse events across the four groups: once-daily inhaled placebo (n=4111), long-acting beta2-agonist (vilanterol (VI) 25 µg; n=4118), corticosteroid (fluticasone furoate (FF) 100 µg; n=4135) and combination therapy (FF/VI; n=4121).,Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with overt CVD (66%).,The composite CVD endpoint occurred in 688 patients (first event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%), and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI 0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93, 95% CI 0.75 to 1.14).,Outcomes were similar among all subgroups.,Adverse events, including palpitations and arrhythmias, did not differ by treatment.,In patients with COPD with moderate airflow limitation and heightened CVD risk, treatment with inhaled VI, FF or their combination has an excellent safety profile and does not impact CVD outcomes.,NCT01313676. | Whether the use of inhaled corticosteroids (ICSs) in patients with COPD can protect from osteoporosis remains undetermined.,The aim of this study is to assess the incidence of osteoporosis in patients with COPD with ICS use and without.,This is a retrospective cohort and population-based study in which we extracted newly diagnosed female patients with COPD between 1997 and 2009 from Taiwan’s National Health Insurance (TNHI) database between 1996 and 2011 (International Classification of Diseases, Ninth Revision - Clinical Modification [ICD-9-CM] 491, 492, 496).,The patients with COPD were defined by the presence of two or more diagnostic codes for COPD within 12 months on either inpatient or outpatient service claims submitted to TNHI.,Patients were excluded if they were younger than 40 years or if osteoporosis had been diagnosed prior to the diagnosis of COPD and cases of asthma (ICD-9 CM code 493.,X) before the index date.,These enrolled patients were followed up till 2011, and the incidence of osteoporosis was determined.,The Cox proportional hazards regression model was also used to estimate hazard ratios (HRs) for incidences of lung cancer.,Totally, 10,723 patients with COPD, including ICS users (n=812) and nonusers (n=9,911), were enrolled.,The incidence rate of osteoporosis per 100,000 person years is 4,395 in nonusers and 2,709 in ICS users (HR: 0.73, 95% confidence interval [CI]: 0.63-084).,The higher ICS dose is associated with lower risk of osteoporosis (0 mg to ≤20 mg, HR: 0.84, 95% CI: 0.69-1.04; >20 mg to ≤60 mg, HR: 0.78, 95% CI: 0.59-1.04; and >60 mg, HR: 0.72, 95% CI: 0.55-0.96; P for trend =0.0023) after adjusting for age, income, and medications.,The cumulative osteoporosis probability significantly decreased among the ICS users when compared with the nonusers (P<0.001).,Female patients with COPD using ICS have a dose-response protective effect for osteoporosis. | 1 |
Protein and mRNA expression are in most cases poorly correlated, which suggests that the posttranscriptional regulatory program of a cell is an important component of gene expression.,This regulatory network is still poorly understood, including how RNA structure quantitatively contributes to translational control.,We present here a series of structural and functional experiments that together allow us to derive a quantitative, structure-dependent model of translation that accurately predicts translation efficiency in reporter assays and primary human tissue for a complex and medically important protein, α-1-antitrypsin.,Our model demonstrates the importance of accurate, experimentally derived RNA structural models partnered with Kozak sequence information to explain protein expression and suggests a strategy by which α-1-antitrypsin expression may be increased in diseased individuals.,Chronic obstructive pulmonary disease (COPD) affects over 65 million individuals worldwide, where α-1-antitrypsin deficiency is a major genetic cause of the disease.,The α-1-antitrypsin gene, SERPINA1, expresses an exceptional number of mRNA isoforms generated entirely by alternative splicing in the 5′-untranslated region (5′-UTR).,Although all SERPINA1 mRNAs encode exactly the same protein, expression levels of the individual mRNAs vary substantially in different human tissues.,We hypothesize that these transcripts behave unequally due to a posttranscriptional regulatory program governed by their distinct 5′-UTRs and that this regulation ultimately determines α-1-antitrypsin expression.,Using whole-transcript selective 2′-hydroxyl acylation by primer extension (SHAPE) chemical probing, we show that splicing yields distinct local 5′-UTR secondary structures in SERPINA1 transcripts.,Splicing in the 5′-UTR also changes the inclusion of long upstream ORFs (uORFs).,We demonstrate that disrupting the uORFs results in markedly increased translation efficiencies in luciferase reporter assays.,These uORF-dependent changes suggest that α-1-antitrypsin protein expression levels are controlled at the posttranscriptional level.,A leaky-scanning model of translation based on Kozak translation initiation sequences alone does not adequately explain our quantitative expression data.,However, when we incorporate the experimentally derived RNA structure data, the model accurately predicts translation efficiencies in reporter assays and improves α-1-antitrypsin expression prediction in primary human tissues.,Our results reveal that RNA structure governs a complex posttranscriptional regulatory program of α-1-antitrypsin expression.,Crucially, these findings describe a mechanism by which genetic alterations in noncoding gene regions may result in α-1-antitrypsin deficiency. | Genome-wide association studies aim to correlate genotype with phenotype.,Many common diseases including Type II diabetes, Alzheimer’s, Parkinson’s and Chronic Obstructive Pulmonary Disease (COPD) are complex genetic traits with hundreds of different loci that are associated with varied disease risk.,Identifying common features in the genes associated with each disease remains a challenge.,Furthermore, the role of post-transcriptional regulation, and in particular alternative splicing, is still poorly understood in most multigenic diseases.,We therefore compiled comprehensive lists of genes associated with Type II diabetes, Alzheimer’s, Parkinson’s and COPD in an attempt to identify common features of their corresponding mRNA transcripts within each gene set.,The SERPINA1 gene is a well-recognized genetic risk factor of COPD and it produces 11 transcript variants, which is exceptional for a human gene.,This led us to hypothesize that other genes associated with COPD, and complex disorders in general, are highly transcriptionally diverse.,We found that COPD-associated genes have a statistically significant enrichment in transcript complexity stemming from a disproportionately high level of alternative splicing, however, Type II Diabetes, Alzheimer’s and Parkinson’s disease genes were not significantly enriched.,We also identified a subset of transcriptionally complex COPD-associated genes (~40%) that are differentially expressed between mild, moderate and severe COPD.,Although the genes associated with other lung diseases are not extensively documented, we found preliminary data that idiopathic pulmonary disease genes, but not cystic fibrosis modulators, are also more transcriptionally complex.,Interestingly, complex COPD transcripts are more often the product of alternative acceptor site usage.,To verify the biological importance of these alternative transcripts, we used RNA-sequencing analyses to determine that COPD-associated genes are frequently expressed in lung and liver tissues and are regulated in a tissue-specific manner.,Additionally, many complex COPD-associated genes are spliced differently between COPD and non-COPD patients.,Our analysis therefore suggests that post-transcriptional regulation, particularly alternative splicing, is an important feature specific to COPD disease etiology that warrants further investigation. | 1 |
There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD).,The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population.,The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.,A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.,We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2.,Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc.,Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation.,The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days.,The overall ICU mortality was 25%.,Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01).,The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute exacerbation of severe COPD were lower than those with other etiologies of acute respiratory failure.,A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated with a 45% decrease in ICU survival (P < .001).,A discharge home at the time of index admission was associated an increased overall survival compared with any other discharge location (P < .001).,We report good early outcomes, but significant long-term morbidity in patients with severe COPD requiring invasive mechanical ventilation for acute respiratory failure.,A higher APACHE score and presence of active malignancy are associated with a decrease in ICU survival, whereas a discharge home is associated with an increase in the overall survival. | Noninvasive ventilation (NIV) is used in critically ill patients with acute respiratory failure (ARF) to avoid endotracheal intubation.,However, the impact of NIV use on ARF patient’s outcomes is still unclear.,Our objectives were to evaluate the rate of NIV failure in hypoxemic patients with an arterial carbon dioxide partial pressure (PaCO2) < 45 mmHg or ≥ 45 mmHg at ICU admission, the predictors of NIV failure, ICU and hospital length of stay and 28-day mortality.,Prospective single center cohort study.,All consecutive patients admitted to a mixed ICU during a three-month period who received NIV, except for palliative care purposes, were included in this study.,Demographic data, APACHE II score, cause of ARF, number of patients that received NIV, incidence of NIV failure, length of ICU, hospital stay and mortality rate were compared between NIV failure and success groups.,Eighty-five from 462 patients (18.4 %) received NIV and 26/85 (30.6 %) required invasive mechanical ventilation.,NIV failure patients were comparatively younger (67 ± 21 vs. 77 ± 14 years; p = 0.031), had lower arterial bicarbonate (p = 0.005), lower PaCO2 levels (p = 0.032), higher arterial lactate levels (p = 0.046) and APACHE II score (p = 0.034) compared to NIV success patients.,NIV failure occurred in 25.0 % of patients with PaCO2 ≥ 45 mmHg and in 33.3 % of patients with PaCO2 < 45 mmHg (p = 0.435).,NIV failure was associated with an increased risk of in-hospital death (OR 4.64, 95 % CI 1.52 to 14.18; p = 0.007) and length [median (IQR)] of ICU [12 days (8-31) vs. 2 days (1-4); p < 0.001] and hospital [30 (19-42) vs. 15 (9-33) days; p = 0.010] stay.,Predictors of NIV failure included age (OR 0.96, 95 % CI 0.93 to 0.99; p = 0.007) and APACHE II score (OR 1.13, 95 % CI 1.02 to 1.25; p = 0.018).,NIV failure was associated with an increased risk of in-hospital death, ICU and hospital stay and was not affected by baseline PaCO2 levels.,Patients that failed were comparatively younger and had higher APACHE II score, suggesting the need for a careful selection of patients that might benefit from NIV.,A well-designed study on the impact of a short monitored NIV trial on outcomes is needed. | 1 |
To evaluate the association among chronic obstructive pulmonary disease (COPD) with asthma, steroid use, and pneumonia in the general population.,Using Taiwan’s National Health Insurance Research Database to identify patients with incident pneumonia, we established a COPD with asthma cohort of 12,538 patients and a COPD cohort of 25,069 patients.,In both cohorts, the risk of incident pneumonia was assessed using multivariable Cox proportional hazards models.,The adjusted hazard ratio (aHR) with 95% confidence interval (CI) for incident pneumonia was 2.38 (2.14, 2.66) in the COPD with asthma cohort, regardless of age, sex, comorbidities, and drug use.,COPD cohort without inhaled corticosteroids (ICSs) use served as a reference.,The aHR (95% CI) for COPD cohort with ICSs use was 1.34 (0.98, 1.83); that for COPD with asthma cohort without ICSs use was 2.46 (2.20, 2.76); and that for COPD with asthma cohort with ICSs use was 2.32 (1.99, 2.72).,COPD cohort without oral steroids (OSs) use served as a reference; the aHR (95% CI) for COPD with asthma cohort without OSs use and with OSs use was 3.25 (2.72, 3.89) and 2.38 (2.07, 2.74), respectively.,The COPD with asthma cohort had a higher risk of incident pneumonia, regardless of age, sex, comorbidities, and ICSs or OSs use.,COPD cohort with ICSs use did not have a notable risk of incident pneumonia.,The COPD with asthma cohort had a higher risk of incident pneumonia, even without ICSs/OSs use. | COPD patients with community-acquired pneumonia (CAP) have worse clinical outcomes, as compared to those without COPD.,Cardiovascular disease (CVD) is a common comorbidity for COPD patients.,Whether COPD with comorbid CVD will increase the risk of CAP is not well investigated.,The incidence and factors associated with CAP in COPD patients with and without CVD were analyzed.,The medical records of patients with newly diagnosed COPD between 2007 and 2010 were reviewed.,The patients’ characteristics, medical history of CVD, occurrence of CAP, and type of medication were recorded.,Kaplan-Meier curves were used to assess the differences in cumulative incidence of CAP.,Cox’s proportional hazards regression model was used to determine the adjusted hazard ratios with 95% confidence intervals in relation to factors associated with CAP in COPD patients with and without CVD.,Among 2,440 patients, 475 patients (19.5%) developed CAP during the follow-up period.,COPD patients who developed CAP were significantly older, had lower forced expiratory volume in 1 second, frequent severe exacerbation and comorbid CVD, as well as received inhaled corticosteroid (ICS)-containing therapy than those without CAP.,The cumulative incidence of CAP was higher in COPD patients with CVD compared to those without CVD.,Patients who received ICS-containing therapy had significantly increased risk of developing CAP compared to those who did not.,For patients with COPD, comorbid CVD is an independent risk factor for developing CAP.,ICS-containing therapy may increase the risk of CAP among COPD patients. | 1 |
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