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Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | To date, clinico-physiologic indices have not been compared with quantitative CT imaging indices in determining the risk of chronic obstructive pulmonary disease (COPD) exacerbation.,We therefore compared clinico-physiologic and CT imaging indices as risk factors for COPD exacerbation in patients with COPD.,We retrospectively analyzed 260 COPD patients from pulmonary clinics at 11 hospitals in Korea from June 2005 to November 2009 and followed-up for at least one year.,At the time of enrollment, none of these patients had COPD exacerbations for at least 2 months.,All underwent clinico-physiologic and radiological evaluation for risk factors of COPD exacerbation.,After 1 yr, 106 of the 260 patients had at least one exacerbation of COPD.,Multiple logistic regression analysis showed that old age, high Charlson Index, and low FEV1 were significant in a clinico-physiologic model, with C-statistics of 0.69, and that increased age and emphysema index were significant in a radiologic model, with C-statistics of 0.64.,The difference between the two models was statistically significant (P = 0.04 by bootstrap analysis).,Combinations of clinico-physiologic risk factors may be better than those of imaging risk factors in predicting COPD exacerbation. | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | 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 |
A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression.,Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time.,33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects.,A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months.,In COPD, compared to no-COPD, we found a faster lung function decline at follow-up.,Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced.,Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD.,The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001).,Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = − 0.587, p < 0.01) and with baseline smoking history (r = − 0.39, p < 0.03).,No correlation was found between ΔFEV1, ΔCRP and ΔWBCs.,By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance.,Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression.,Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease. | COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. | 1 |
The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD) is complicated by the presence of comorbidities.,The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data.,This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES), 1999-2008.,COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded.,Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment.,Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs.,36.9%), depression (20.6% vs.,12.5%), osteoporosis (16.9% vs.,8.5%), cancer (16.5% vs.,9.9%), coronary heart disease (12.7% vs.,6.1%), congestive heart failure (12.1% vs.,3.9%), and stroke (8.9% vs.,4.6%).,Subjects with COPD were also more likely to report mobility difficulty (55.6% vs.,32.5%), use of >4 prescription medications (51.8% vs.,32.1), dizziness/balance problems (41.1% vs.,23.8%), urinary incontinence (34.9% vs.,27.3%), memory problems (18.5% vs.,8.8%), low glomerular filtration rate (16.2% vs.,10.5%), and visual impairment (14.0% vs.,9.6%).,All reported comparisons have p < 0.05.,Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities.,This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed), a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity. | 1 |
Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes.,Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment).,Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF25-75).,Measures of symptom burden (COPD Assessment Test) and functional impairment (six-minute walk distance) also associate with disparate lung microbiota composition.,Drivers of these relationships include members of the Streptococcus, Prevotella, Veillonella, Staphylococcus, and Pseudomonas genera.,Thus, lung microbiota differences may contribute to airway dysfunction and airway disease in milder COPD. | The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity. | 1 |
Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD).,CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality.,The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.,Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade.,But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population.,The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.,In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence.,We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD.,While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years.,Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. | Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | 1 |
Ventilation/perfusion (V/P) single-photon emission computed tomography (SPECT) is recognized as a diagnostic method with potential beyond the diagnosis of pulmonary embolism.,V/P SPECT identifies functional impairment in diseases such as heart failure (HF), pneumonia, and chronic obstructive pulmonary disease (COPD).,The development of hybrid SPECT/computed tomography (CT) systems, combining functional with morphological imaging through the addition of low-dose CT (LDCT), may be useful in COPD, as these patients are prone to lung cancer and other comorbidities.,The aim of this study was to investigate the added value of LDCT among healthy smokers and patients with stable COPD, when examined with V/P SPECT/CT hybrid imaging.,Sixty-nine subjects, 55 with COPD (GOLD I-IV) and 14 apparently healthy smokers, were examined with V/P SPECT and LDCT hybrid imaging.,Spirometry was used to verify COPD grade.,Only one apparently healthy smoker and three COPD patients had a normal or nearly normal V/P SPECT.,All other patients showed various degrees of airway obstruction, even when spirometry was normal.,The same interpretation was reached on both modalities in 39% of the patients.,LDCT made V/P SPECT interpretation more certain in 9% of the patients and, in 52%, LDCT provided additional diagnoses.,LDCT better characterized the type of emphysema in 12 patients.,In 19 cases, tumor-suspected changes were reported.,Three of these 19 patients (ie, 4.3% of all subjects) were in the end confirmed to have lung cancer.,The majority of LDCT findings were not regarded as clinically significant.,V/P SPECT identified perfusion patterns consistent with decompensated left ventricular HF in 14 COPD patients.,In 16 patients (23%), perfusion defects were observed.,HF and perfusion defects were not recognized with LDCT.,In COPD patients and long-time smokers, hybrid imaging had added value compared to V/P SPECT alone, by identifying patients with lung malignancy and more clearly identifying emphysema.,V/P SPECT visualizes comorbidities to COPD not seen with LDCT, such as pulmonary embolism and left ventricular HF. | Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease.,We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease.,Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control).,Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration.,Mean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm).,Emphysema mice lost body weight, controls gained weight.,Running distance was shorter in emphysema than in controls.,Diaphragm muscle length was shorter in controls compared to emphysema.,Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms.,Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls.,Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length.,The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation.,The model may deepen our understanding of systemic aspects of COPD. | 1 |
Dysregulation of circRNAs has been reported to be functionally associated with chronic obstructive pulmonary disease (COPD).,The present investigation elucidated the potential role of CircRNA0001859 in regulating chronic obstructive pulmonary disease acute (COPD) and Acute Exacerbation of COPD (AECOPD).,Mice model of COPD was established to screen and verify the dysregulated expression of CircRNA0001859.,Fluorescence in situ hybridization (FISH) and quantitative real-time PCR (qRT-PCR) were carried out to detect the expression of CircRNA0001859. 38 stable COPD patients, 24 AECOPD patients, 57 COPD with lung cancer patients and 28 healthy person with age and sex matched to total patients were used for the present investigation.,circRNA0001859 was downregulated in the lung tissue of mice after the three kinds of treatments (Cigarette smoke (CS)/NK alone or CS + NNK) for inducing COPD.,FISH assay verified the downregulation of circRNA0001859 both in the mice lung and human bronchial epithelial cell of COPD model.,Furthermore,, the level of circRNA0001859 was also downregulated in the peripheral blood of COPD and lung cancer patients.,CircRNA0001859 might act as a diagnostic and prognostic biomarker for the treatment of in COPD and AECOPD with Are under the receiver operating characteristic curve (ROC curve) (AUC) of 0.7433 and 0.8717, respectively.,We explored a novel circRNA0001859, which might act as a potential therapeutic biomarker for the treatment of COPD and AECOPD. | MiR‐148 is a negative regulator of autophagy 16‐like 1 (ATG16L1), a gene implicated in the pathogenesis of ventilator‐associated pneumonia (VAP).,Therefore, the role of miR‐148 polymorphism in the pathogenesis of VAP was studied here.,The expression of miR‐148, ATG16L1, Beclin‐I, LC3‐II, TNF‐α and IL‐6 in serum and peripheral blood mononuclear cells (PBMCs) of VAP patients was detected to study their relationship in the pathogenesis of VAP.,Chronic obstructive pulmonary disease patients carrying the AA/AG genotypes of miR‐148 rs4719839 single nucleotide polymorphism (SNP) were more prone to VAP due to the higher expression of miR‐148, TNF‐α and IL‐6 along with suppressed expression of ATG16L1, Beclin‐I and LC3‐II in their serum and PBMCs.,Transfection of miR‐148 mimics to primary PBMCs genotyped as GG and AA decreased the expression of ATG16L1, Beclin‐I and LC3‐II.,Finally, cells carrying the AA genotype of rs4719839 SNP were more sensitive to the role of LPS stimulation in suppressing ATG16L1, Beclin‐I and LC3‐II expression while activating TNF‐α and IL‐6 expression.,Our work presented detailed evidence, suggesting that the rs4719839 polymorphism can affect the risk of VAP. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible.,The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations.,Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD.,Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective.,Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations.,This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD. | 1 |
People with chronic obstructive pulmonary disease (COPD) sometimes experience anxiety, depression and comorbid cognitive deficits.,Rather than being merely a consequence of symptom-related physical impairments these additional problems may be part of the clinical course of the condition.,The relationship between the physical and psychological aspects of the condition is illustrated by the patterns of use of non-invasive ventilation (NIV); NIV is often rejected or used inappropriately, resulting in clinical deterioration and an increase in health care costs.,The study aims to analyse the effects of psychological support on the acceptance of, and adherence to, NIV.,The primary outcome will be a latent variable related to indices of use of NIV equipment and adherence to treatment regime; while survival rates and psychological variables will constitute the secondary outcomes.,A two-arm randomised controlled trial will be conducted.,We aim to recruit 150 COPD patients for whom NIV is indicated.,The experimental group will receive a brief course of psychological support that will include counselling, relaxation and mindfulness-based exercises.,In some cases, it will also include neuropsychological rehabilitation exercises.,Support will be delivered via four to eight meetings at the HD Respiratory Rehabilitation Unit, at home or via telemedicine.,Controls will receive standard care and watch educational videos related to the management of their disease.,This investigation will gain insight about the role of a psychological intervention as part of a treatment plan during the process of adaptation to NIV in COPD patients.,ClinicalTrials.gov, ID: NCT02499653.,Registered on 14 July 2015.,The online version of this article (doi:10.1186/s13063-017-1802-1) contains supplementary material, which is available to authorized users. | Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | 1 |
The quest for the right combination of bronchodilators with different mechanisms of action such as long-acting muscarinic antagonists and long-acting β-agonists in the management of stable moderate-to-severe chronic obstructive pulmonary disease (COPD) is a topic of intense research activity currently, given the rising morbidity and mortality due to this disease.,The fixed-dose combination of aclidinium bromide and formoterol fumarate in a single inhaler seems to offer superior advantages over either drugs given alone or as separate inhalers concurrently.,Since the fixed-dose combination needs to be given twice daily, it is likely to achieve control of symptoms most crucial to the quality of life in COPD, namely, the morning hours.,This is reflected in significant trough FEV1 (forced expiratory volume in 1 second) improvements after the dose.,This paper reviews the various studies related to this combination put in the perspective of its safety and efficacy and potential benefits over other therapeutic options.,However, there is a dearth of data on the long-term safety and efficacy in terms of improvement in lung function.,This combination could emerge as an excellent option in the management of stable COPD if data on exacerbation rates and patient-reported outcomes become available from longer-term studies.,Moreover, we need some more studies to define the ideal phenotype of COPD best suited for the use of this combination. | 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 |
An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease.,Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema.,We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers.,Emphysema was measured using a morphometric measure of the lungs’ surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema.,There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p < 0.0001, p < 0.0001, and p = 0.0003, respectively).,The extent of staining of type II pneumocytes and airways for matrix metalloproteinase-1 was significantly related to the extent of smoking (p = 0.012 and p = 0.013, respectively).,In addition, the extent of matrix metalloproteinase-1 staining of alveolar macrophages was related to the lung surface area/volume ratio and to qualitative estimates of emphysema on CT.,These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells.,Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.,The online version of this article (doi:10.1007/s00408-014-9585-6) contains supplementary material, which is available to authorized users. | Toll-like receptors (TLRs) on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD) is unknown.,Lung tissue collected from clinically-indicated resections (n = 34) was used either: (a) to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b) to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands.,We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants.,All the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD.,In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells.,Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists.,Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD.,These data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1. | 1 |
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD).,New-user observational cohort designs may minimize biases associated with previous case-control designs.,To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.,Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.,Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010).,New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.,Outcomes: severe pneumonia (primary) and any pneumonia (secondary).,Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83).,Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively.,Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use.,There was an apparent dose-related effect, with greater risk at higher daily doses of ICS.,There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.,The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time.,This risk must be weighed against the benefits when prescribing ICS to patients with COPD. | 1 |
Even with the dissemination of several clinical guidelines, chronic obstructive pulmonary disease (COPD) remains underdiagnosed and mismanaged by many primary care physicians (PCPs).,The objective of this study was to elucidate barriers to consistent implementation of COPD guidelines.,A cross-sectional study implemented in July 2008 was designed to assess attitudes and barriers to COPD guideline usage.,Five hundred US PCPs (309 family medicine physicians, 191 internists) were included in the analysis.,Overall, 23.6% of the surveyed PCPs reported adherence to spirometry guidelines over 90% of the time; 25.8% reported adherence to guidelines related to long-acting bronchodilator (LABD) use in COPD patients.,In general, physicians were only somewhat familiar with COPD guidelines, and internal medicine physicians were significantly more familiar than family physicians (P < 0.05).,In a multivariate model controlling for demographics and barriers to guideline adherence, we found significant associations with two tested guideline components.,Adherence to spirometry guidelines was associated with agreement with guidelines, confidence in interpreting data, ambivalence to outcome expectancy, and ability to incorporate spirometry into patient flow.,Adherence to LABD therapy guidelines was associated with agreement with guidelines and confidence in gauging pharmacologic response.,Adherence to guideline recommendations of spirometry use was predicted by agreement with the recommendations, self-efficacy, perceived outcome expectancy if recommendations were adhered to, and resource availability.,Adherence to recommendations of LABD use was predicted by agreement with guideline recommendations and self-efficacy.,Increasing guideline familiarity alone may have limited patient outcomes, as other barriers, such as low confidence and outcome expectancy, are more likely to impact guideline adherence. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell.,Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants.,If however, this balance is disturbed a situation called oxidative stress occurs.,Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer.,Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease.,Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress.,In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression.,In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings. | Chronic obstructive pulmonary disease (COPD) has significant systemic effects that substantially impact quality of life and survival.,The purpose of this study was to assess and compare peripheral muscle strength and endurance, exercise capacity, fatigue perception and quality of life between patients with COPD and healthy subjects.,Twenty COPD patients (mean FEV1 49.3 ± 19.2%) and 20 healthy subjects were included in the study.,Pulmonary function testing and six-minute walk test (6MWT) were performed.,Peripheral muscle strength was measured with a hand-held dynamometer, peripheral muscle endurance was evaluated with sit-ups, squats and modified push-ups tests.,Fatigue perception was assessed using the Fatigue Impact Scale (FIS) and Fatigue Severity Scale (FSS).,General quality of life was determined with the Nottingham Health Profile (NHP), and cough-specific quality of life was evaluated with the Leicester Cough Questionnaire (LCQ).,Pulmonary functions, strength of shoulder abductor and flexor muscles, numbers of sit-ups and squats, 6MWT distance and 6MWT% were significantly lower in COPD patients than in healthy subjects (p < 0.05).,FIS psychosocial sub-dimension and total scores, NHP scores for all sub-dimensions except pain sub-dimension of the COPD group were significantly higher than those of healthy subjects (p < 0.05).,The LCQ physical, psychological and social sub-dimensions and total scores were significantly lower in COPD patients than in healthy subjects (p < 0.05).,Pulmonary functions, peripheral muscle strength and endurance, exercise capacity and quality of life were adversely affected in patients with COPD.,There are greater effect of fatigue on psychosocial functioning and general daily life activities and effect of cough on the quality of life in patients with COPD.,This study supports the idea that COPD patients must be evaluated in a comprehensive manner for planning pulmonary rehabilitation programs. | 1 |
Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions.,Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis.,Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity.,Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells.,NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment.,CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD.,These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD.,Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases.,Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD. | The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | 1 |
It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 1 |
Our starting point is that relatively new findings into the pathogenesis and pathophysiology of airway disease in smokers that lead to chronic obstructive pulmonary disease (COPD) need to be reassessed as a whole and integrated into “mainstream” thinking along with traditional concepts which have stood the test of time.,Such a refining of the accepted disease paradigm is urgently needed as thinking on therapeutic targets is currently under active reconsideration.,We feel that generalised airway wall “inflammation” is unduly over-emphasised, and highlight the patchy and variable nature of the pathology (with the core being airway remodelling).,In addition, we present evidence for airway wall disease in smokers/COPD as including a hypocellular, hypovascular, destructive, fibrotic pathology, with a likely spectrum of epithelial-mesenchymal transition states as significant drivers of this remodelling.,Furthermore, we present data from a number of research modalities and integrate this with the aetiology of lung cancer, the role of chronic airway luminal colonisation/infection by a specific group of “respiratory” bacteria in smokers (which results in luminal inflammation) and the central role for oxidative stress on the epithelium.,We suggest translation of these insights into more focus on asymptomatic smokers and early COPD, with the potential for fresh preventive and therapeutic approaches.,We discuss the pathogenesis and pathophysiology of COPD, emphasising their need to be reassessed as a whole and integrated with traditional concepts to refine the disease paradigm.,This is urgently needed to open-up thinking about therapeutic targets.https://bit.ly/3pTyrsi | The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls.,The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers.,To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients.,Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392).,Of the total cohort, 19,894 patients were included in the study.,Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population.,In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41-0.71), while the risk of lung cancer increased with increasing age.,A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37-0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15-2.16).,In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk.,The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies. | 1 |
Patients with COPD have an increased risk of cardiovascular disease.,Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated.,We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.,Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment.,In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined.,These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.,On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar.,The IL-6 was also increased (p < 0.05).,Twenty-two patients completed study assessments.,In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01).,Total cholesterol and ISWT also improved (p < 0.05).,On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.,Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD. | Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD).,We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls.,This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.,To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.,Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable.,The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects.,Rbm fragmentation correlated with smoking history in COPD but not with age.,There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05).,The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004).,In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).,Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall.,Rbm fragmentation was also present to as great an extent in ex-smokers with COPD.,These characteristics may have potential physiological consequences. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation and is associated with a chronic inflammatory response in both airways and lungs. microRNAs (miRNAs) are often highly conserved between species and have an intricate role within homeostatic conditions and immune responses.,Also, miRNAs are dysregulated in smoking-associated diseases.,We investigated the miRNA profile of 523 miRNAs by stem-loop RT-qPCR in lung tissue and cell-free bronchoalveolar lavage (BAL) supernatant of mice exposed to air or cigarette smoke (CS) for 4 or 24 weeks.,After 24 weeks of CS exposure, 31 miRNAs were differentially expressed in lung tissue and 78 in BAL supernatant.,Next, we correlated the miRNA profiling data to inflammation in BAL and lung, obtained by flow cytometry or ELISA.,In addition, we surveyed for overlap with newly assessed miRNA profiles in bronchial biopsies and with previously assessed miRNA profiles in lung tissue and induced sputum supernatant of smokers with COPD.,Several miRNAs showed concordant differential expression between both species including miR-31*, miR-155, miR-218 and let-7c.,Thus, investigating miRNA profiling data in different compartments and both species provided accumulating insights in miRNAs that may be relevant in CS-induced inflammation and the pathogenesis of COPD. | On-going airway inflammation is characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD).,However, the key factors determining the decrease in lung function, an important clinical parameter of COPD, are not clear.,Genome-wide linkage analyses provide evidence for significant linkage to airway obstruction susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster.,Moreover, a genetic variation in the defensin beta 1 (DEFB1) gene was found to be associated with COPD.,Therefore, we hypothesized that DEFB1 is differently regulated and expressed in human lungs during COPD progression.,Gene expression of DEFB1 was assessed in bronchial epithelium and BAL fluid cells of healthy controls and patients with COPD and using bisulfite sequencing and ChIP analysis, the epigenetic control of DEFB1 mRNA expression was investigated.,We can demonstrate that DEFB1 mRNA expression was significantly increased in bronchopulmonary specimen of patients with COPD (n = 34) vs. healthy controls (n = 10) (p<0.0001).,Furthermore, a significant correlation could be detected between DEFB1 and functional parameters such as FEV1 (p = 0.0024) and the FEV1/VC ratio (p = 0.0005).,Upregulation of DEFB1 mRNA was paralleled by changes in HDAC1-3, HDAC5 and HDAC8 mRNA expression.,Whereas bisulfite sequencing revealed no differences in the methylation state of DEFB1 promoter between patients with COPD and controls, ChIP analysis showed that enhanced DEFB1 mRNA expression was associated with the establishment of an active histone code.,Thus, expression of human DEFB1 is upregulated and related to the decrease in pulmonary function in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) patients often show skeletal muscle dysfunction that has a prominent negative impact on prognosis.,The study aims to further explore underlying mechanisms of skeletal muscle dysfunction as a characteristic systemic effect of COPD, potentially modifiable with preventive interventions (i.e. muscle training).,The research analyzes network module associated pathways and evaluates the findings using independent measurements.,We characterized the transcriptionally active network modules of interacting proteins in the vastus lateralis of COPD patients (n = 15, FEV1 46 ± 12% pred, age 68 ± 7 years) and healthy sedentary controls (n = 12, age 65 ± 9 years), at rest and after an 8-week endurance training program.,Network modules were functionally evaluated using experimental data derived from the same study groups.,At baseline, we identified four COPD specific network modules indicating abnormalities in creatinine metabolism, calcium homeostasis, oxidative stress and inflammatory responses, showing statistically significant associations with exercise capacity (VO2 peak, Watts peak, BODE index and blood lactate levels) (P < 0.05 each), but not with lung function (FEV1).,Training-induced network modules displayed marked differences between COPD and controls.,Healthy subjects specific training adaptations were significantly associated with cell bioenergetics (P < 0.05) which, in turn, showed strong relationships with training-induced plasma metabolomic changes; whereas, effects of training in COPD were constrained to muscle remodeling.,In summary, altered muscle bioenergetics appears as the most striking finding, potentially driving other abnormal skeletal muscle responses.,Trial registration The study was based on a retrospectively registered trial (May 2017), ClinicalTrials.gov identifier: NCT03169270,The online version of this article (10.1186/s12967-018-1405-y) contains supplementary material, which is available to authorized users. | Chronic bronchitis (CB) is one of the classic phenotypes of COPD.,The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population.,We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE).,CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years.,CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry.,Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls.,Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis.,For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A.,In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7).,We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6).,This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD.,ClinicalTrials.gov NCT00608764, NCT00292552,The online version of this article (doi:10.1186/s12931-014-0113-2) contains supplementary material, which is available to authorized users. | 1 |
Fatigue is the second most common symptom in patients with chronic obstructive pulmonary disease (COPD).,Despite its high prevalence, fatigue is often ignored in daily practice.,For this reason, little is known about the underlying determinants of fatigue in patients with COPD.,The primary objectives of this study are to chart the course of fatigue in patients with COPD, to identify the physical, systemic, psychological and behavioural factors that precipitate and perpetuate fatigue in patients with COPD, to evaluate the impact of exacerbation-related hospitalisations on fatigue and to better understand the association between fatigue and 2-year all-cause hospitalisation and mortality in patients with COPD.,The secondary aim is to identify diurnal differences in fatigue by using ecological momentary assessment (EMA).,This manuscript describes the protocol of the FAntasTIGUE study and gives an overview of the possible strengths, weaknesses and clinical implications.,A 2-year longitudinal, observational study, enrolling 400 patients with clinically stable COPD has been designed.,Fatigue, the primary outcome, will be measured by the subjective fatigue subscale of the Checklist Individual Strength (CIS-Fatigue).,The secondary outcome is the day-to-day/diurnal fatigue, registered in a subsample (n=60) by EMA.,CIS-Fatigue and EMA will be evaluated at baseline, and at 4, 8 and 12 months.,The precipitating and perpetuating factors of fatigue (physical, psychological, behavioural and systemic) will be assessed at baseline and at 12 months.,Additional assessments will be conducted following hospitalisation due to an exacerbation of COPD that occurs between baseline and 12 months.,Finally, at 18 and 24 months the participants will be followed up on their fatigue, number of exacerbations, exacerbation-related hospitalisation and survival.,This protocol was approved by the Medical research Ethics Committees United, Nieuwegein, the Netherlands (NL60484.100.17).,NTR6933; Pre-results. | A previous Phase IIIb study (NCT01462929) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo.,This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study.,Symptomatic patients (defined as those with Evaluating Respiratory Symptoms [E-RS™] in COPD baseline score ≥10 units) received aclidinium bromide 400 μg twice daily (BID), tiotropium 18 μg once daily (QD), or placebo, for 6 weeks.,Lung function, COPD respiratory symptoms, and incidence of adverse events (AEs) were assessed.,In all, 277 symptomatic patients were included in this post hoc analysis.,Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second (FEV1) from baseline to week 6 at all time points over 24 hours versus placebo.,In addition, improvements in FEV1 from baseline during the nighttime period were observed for aclidinium versus tiotropium on day 1 (aclidinium 157 mL, tiotropium 67 mL; P<0.001) and week 6 (aclidinium 153 mL, tiotropium 90 mL; P<0.05).,Aclidinium improved trough FEV1 from baseline versus placebo and tiotropium at day 1 (aclidinium 136 mL, tiotropium 68 mL; P<0.05) and week 6 (aclidinium 137 mL, tiotropium 71 mL; P<0.05).,Aclidinium also improved early-morning and nighttime symptom severity, limitation of early-morning activities, and E-RS Total and domain scores versus tiotropium (except E-RS Chest Symptoms) and placebo over 6 weeks.,Tolerability showed similar incidence of AEs in each arm.,In this post hoc analysis of symptomatic patients with moderate to severe COPD, aclidinium 400 μg BID provided additional improvements compared with tiotropium 18 μg QD in: 1) bronchodilation, particularly during the nighttime, 2) daily COPD symptoms (E-RS), 3) early-morning and nighttime symptoms, and 4) early-morning limitation of activity. | 1 |
Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk.,Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors.,AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo).,Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study.,Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820).,Maximum exposure to treatment was 48 months.,The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36).,The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively.,Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively.,For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38).,This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments.,However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs. | Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide.,The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results.,Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease.,The bacterial metagenomes within sputum samples from eight COPD patients and ten ‘healthy’ smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus.,The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations.,Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism.,This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity. | Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. | 1 |
Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain.,This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema.,Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects.,In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period.,Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort.,Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects.,In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups.,Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline.,MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression.,Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. | Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status. | 1 |
Chronic obstructive pulmonary disease (COPD) is predicted to become a major cause of death worldwide.,Studies on the variability in the estimates of key epidemiological parameters of COPD may contribute to better assessment of the burden of this disease and to helpful guidance for future research and public policies.,In the present study, we examined differences in the main epidemiological characteristics of COPD derived from studies across countries of the European Union, focusing on prevalence, severity, frequency of exacerbations and mortality, as well as on differences between the studies' methods.,This systematic review was based on a search for the relevant literature in the Science Citation Index database via the Web of Science and on COPD mortality rates issued from national statistics.,Analysis was finally based on 65 articles and Eurostat COPD mortality data for 21 European countries.,Epidemiological characteristics of COPD varied widely from country to country.,For example, prevalence estimates ranged between 2.1% and 26.1%, depending on the country, the age group and the methods used.,Likewise, COPD mortality rates ranged from 7.2 to 36.1 per 105 inhabitants.,The methods used to estimate these epidemiological parameters were highly variable in terms of the definition of COPD, severity scales, methods of investigation and target populations.,Nevertheless, to a large extent, several recent international guidelines or research initiatives, such as GOLD, BOLD or PLATINO, have boosted a substantial standardization of methodology in data collection and have resulted in the availability of more comparable epidemiological estimates across countries.,On the basis of such standardization, severity estimates as well as prevalence estimates present much less variation across countries.,The contribution of these recent guidelines and initiatives is outlined, as are the problems remaining in arriving at more accurate COPD epidemiological estimates across European countries.,The accuracy of COPD epidemiological parameters is important for guiding decision making with regard to preventive measures, interventions and patient management in various health care systems.,Therefore, the recent initiatives for standardizing data collection should be enhanced to result in COPD epidemiological estimates of improved quality.,Moreover, establishing international guidelines for reporting research on COPD may also constitute a major contribution. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
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. | The potential role of growth factors in chronic obstructive pulmonary disease (COPD) has begun to be addressed only recently and is still poorly understood.,For this study, we investigated potential abnormalities of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in patients with COPD.,To this end, we compared the levels of HGF and KGF, measured by enzyme-linked immunosorbent assay (ELISA), in bronchoalveolar lavage (BAL) fluid and in serum in 18 patients with COPD (62 ± 9 yrs, forced expiratory volume in one second [FEV1] 57 ± 12% ref, X ± standard deviation of mean), 18 smokers with normal lung function (58 ± 8 yrs, FEV1 90 ± 6% ref) and 8 never smokers (67 ± 9 yrs, 94 ± 14% ref).,We found that in BAL, HGF levels were higher in patients with COPD than in the other two groups whereas, in serum, HGF concentration was highest in smokers with normal lung function (p < 0.01).,KGF levels were not significantly different between groups, neither in blood nor in BAL (most values were below the detection limit).,These results highlight a different response of HGF in BAL and serum in smokers with and without COPD that may be relevant for tissue repair in COPD. | 1 |
Fatigue is one of the most common symptoms among subjects with chronic obstructive pulmonary disease (COPD), but is rarely identified in clinical practice.,The aim of this study was to evaluate the association between fatigue and health-related quality of life (HRQoL) assessed with clinically useful instruments, both among subjects with and without COPD.,Further, to investigate the association between fatigue and the COPD Assessment Test (CAT)-energy question.,Data were collected in 2014 within the population-based OLIN COPD study.,Subjects with (n = 367) and without (n = 428) COPD participated in clinical examinations including spirometry and completed questionnaires about fatigue (FACIT-Fatigue, clinically relevant fatigue ⩽43), and HRQoL (EQ-5D-VAS, lower score = worse health; CAT, lower score = fewer symptoms/better health).,Subjects with clinically relevant fatigue had worse HRQoL measured with EQ-5D-VAS, regardless of having COPD or not.,Decreasing EQ-5D-VAS scores, any respiratory symptoms and anxiety/depression were associated with clinically relevant fatigue also when adjusted for confounders.,Among subjects with COPD, clinically relevant fatigue was associated with increasing total CAT score, and CAT score ⩾10.,The proportion of subjects with clinically relevant fatigue increased significantly, with a higher score on the CAT-energy question, and nearly 50% of those with a score of 2, and 70% of those with a score of ⩾3, had clinically relevant fatigue.,Fatigue was associated with respiratory symptoms, anxiety/depression and worse HRQoL when using the clinically useful instruments EQ-5D-VAS and CAT.,The CAT-energy question can be used to screen for fatigue in clinical practice, using a cut-off of ⩾2. | Cough is a prevalent symptom that impacts quality of life in COPD.,The aim of this study was to assess the relationship between cough-specific quality of life, abdominal muscle endurance, fatigue, and depression in stable patients with COPD.,Twenty-eight patients with COPD (mean age 60.6±8.7 years) referred for pulmonary rehabilitation participated in this cross-sectional study.,Sit-ups test was used for assessing abdominal muscle endurance.,Leicester Cough Questionnare (LCQ) was used to evaluate symptom-specific quality of life.,Fatigue perception was evaluated with Fatigue Impact Scale (FIS).,Beck Depression Inventory (BDI) was used for assessing depression level.,The LCQ total score was significantly associated with number of sit-ups; BDI score; FIS total; physical, cognitive, and psychosocial scores (P<0.05).,Scores of the LCQ physical, social, and psychological domains were also significantly related with number of sit-ups, FIS total score, and BDI score (P<0.05).,FIS total score and number of sit-ups explained 58% of the variance in LCQ total score (r=0.76, r2=0.577, F(2-20)=12.296, P<0.001).,Chronic cough may adversely affect performance in daily life due to its negative effect on fatigue and decrease abdominal muscle endurance in patients with COPD.,Decreased cough-related quality of life is related with increased level of depression in COPD patients.,Effects of increased abdominal muscle endurance and decreased fatigue in COPD patients with chronic cough need further investigation. | 1 |
The causal association between depression, anxiety, and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) is unclear.,We therefore conducted a systematic review of prospective cohort studies that measured depression, anxiety, and HRQoL in COPD.,Electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature [CINAHL], British Nursing Index and Archive, PsycINFO and Cochrane database) were searched from inception to June 18, 2013.,Studies were eligible for inclusion if they: used a nonexperimental prospective cohort design; included patients with a diagnosis of COPD confirmed by spirometry; and used validated measures of depression, anxiety, and HRQoL.,Data were extracted and pooled using random effects models.,Six studies were included in the systematic review; of these, three were included in the meta-analysis for depression and two were included for the meta-analysis for anxiety.,Depression was significantly correlated with HRQoL at 1-year follow-up (pooled r=0.48, 95% confidence interval 0.37-0.57, P<0.001).,Anxiety was also significantly correlated with HRQoL at 1-year follow-up (pooled r=0.36, 95% confidence interval 0.23-0.48, P<0.001).,Anxiety and depression predict HRQoL in COPD.,However, this longitudinal analysis does not show cause and effect relationships between depression and anxiety and future HRQoL.,Future studies should identify psychological predictors of poor HRQoL in well designed prospective cohorts with a view to isolating the mediating role played by anxiety disorder and depression. | Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality.,Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions.,However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known.,We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD.,We then determined what types of psychological and lifestyle interventions are most effective.,Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety.,CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012.,Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety.,Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis.,Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09).,Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18).,Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD.,Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population. | 1 |
Urban particulate matter (UPM) is an important trigger of airway inflammation.,The cross-talk between the external and internal matrix in the respiratory tract occurs due to the transepithelial network of macrophages/dendritic cells.,This study characterized the immune processes induced by the epithelium after UPM exposure in special regard to interactions with monocyte-derived dendritic cells (moDCs) and monocyte-derived macrophages (moMφs) in obstructive lung diseases.,A triple-cell co-culture model (8 controls, 10 asthma, and 8 patients with COPD) utilized nasal epithelial cells, along with moMφs, and moDCs was exposed to UPM for 24 h.,The inflammatory response of nasal epithelial cells to UPM stimulation is affected differently by cell-cell interactions in healthy people, asthma or COPD patients of which the interactions with DCs had the strongest impact on the inflammatory reaction of epithelial cells after UPM exposure.,The epithelial remodeling and DCs dysfunction might accelerate the inflammation after air pollution exposure in asthma and COPD. | Small-airway remodelling is one of the most remarkable pathological features of chronic obstructive pulmonary disease (COPD), in which angiogenesis plays a critical role that contributes to disease progression.,The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF), as well as its receptors, VEGFR1, VEGFR2, are thought to be the major mediators of pathological angiogenesis, and sunitinib exhibits anti-angiogenesis property through VEGF blockage and has been widely used to treat various cancers.,In our study, Sprague-Dawley rats were subjected to lipopolysaccharide (LPS) injection and cigarette smoke (CS) inhalation to induce COPD, following sunitinib administration was conducted.,Haematoxylin-eosin, Masson staining and immunostaining analysis were used to evaluate the pathological changes; quantitative real-time PCR and enzyme-linked immunosorbent assay were performed to provide more compelling data on the function of VEGF, VEGFR1, VEGFR2 in angiogenesis.,Sunitinib treatment was associated with less angiogenesis in small-airway remodelling with a slightly disordered lung architecture, and lower expression level of VEGF, VEGFR1, VEGFR2.,Overall, our results indicate that VEGF is a vital important factor that contributes to the small-airway remodelling in a rat model of COPD through promoting angiogenesis, which mainly depend on the specific binding between VEGF and VEGFR1 and can be effectively attenuated by sunitinib. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) has significant systemic effects beyond the lungs amongst which muscle wasting is a prominent contributor to exercise limitation and an independent predictor of morbidity and mortality.,The molecular mechanisms leading to skeletal muscle dysfunction/wasting are not fully understood and are likely to be multi-factorial.,The need to develop therapeutic strategies aimed at improving skeletal muscle dysfunction/wasting requires a better understanding of the molecular mechanisms responsible for these abnormalities.,Microarrays are powerful tools that allow the investigation of the expression of thousands of genes, virtually the whole genome, simultaneously.,We aim at identifying genes and molecular pathways involved in skeletal muscle wasting in COPD.,We assessed and compared the vastus lateralis transcriptome of COPD patients with low fat free mass index (FFMI) as a surrogate of muscle mass (COPDL) (FEV1 30 ± 3.6%pred, FFMI 15 ± 0.2 Kg.m−2) with patients with COPD and normal FFMI (COPDN) (FEV1 44 ± 5.8%pred, FFMI 19 ± 0.5 Kg.m−2) and a group of age and sex matched healthy controls (C) (FEV1 95 ± 3.9%pred, FFMI 20 ± 0.8 Kg.m−2) using Agilent Human Whole Genome 4x44K microarrays.,The altered expression of several of these genes was confirmed by real time TaqMan PCR.,Protein levels of P21 were assessed by immunoblotting.,A subset of 42 genes was differentially expressed in COPDL in comparison to both COPDN and C (PFP < 0.05; −1.5 ≥ FC ≥ 1.5).,The altered expression of several of these genes was confirmed by real time TaqMan PCR and correlated with different functional and structural muscle parameters.,Five of these genes (CDKN1A, GADD45A, PMP22, BEX2, CGREF1, CYR61), were associated with cell cycle arrest and growth regulation and had been previously identified in studies relating muscle wasting and ageing.,Protein levels of CDKN1A, a recognized marker of premature ageing/cell cycle arrest, were also found to be increased in COPDL.,This study provides evidence of differentially expressed genes in peripheral muscle in COPD patients corresponding to relevant biological processes associated with skeletal muscle wasting and provides potential targets for future therapeutic interventions to prevent loss of muscle function and mass in COPD.,The online version of this article (doi:10.1186/s12931-014-0139-5) contains supplementary material, which is available to authorized users. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Some COPD patients are more susceptible to exacerbations than others.,Mechanisms underlying these differences in susceptibility are not well understood.,We hypothesized that altered cell mediated immune responses may underlie a propensity to suffer from frequent exacerbations in COPD.,Peripheral blood mononuclear cells (PBMCs) were obtained from 24 stable COPD patients, eight frequent exacerbators (≥3 diary-card exacerbations/year) and 16 infrequent exacerbators (< 3 diary-card exacerbations/year).,Detailed multi-parameter flow cytometry was used to study differences in innate and adaptive systemic immune function between frequent and infrequently exacerbating COPD patients.,The 24 COPD patients had a mean (SD) age of 76.3 (9.4) years and FEV1 1.43 (0.60)L, 53.3 (18.3)% predicted.,PBMCs of frequent exacerbators (FE) contained lower frequencies of CD4+ T central memory cells (CD4+ Tcm) compared to infrequent exacerbators (IE) (FE = 18.7 %; IE = 23.9 %; p = 0.035).,This observation was also apparent in absolute numbers of CD4+ Tcm cells (FE = 0.17 × 10^6/mL; IE = 0.25 × 10^6/mL; p = 0.035).,PBMCs of FE contained a lower frequency of CD8+ T effector memory cells expressing HLA-DR (Human Leukocyte Antigen - D Related) compared to IE COPD patients (FE = 22.7 %; IE = 31.5 %; p = 0.007).,Differences in the adaptive systemic immune system might associate with exacerbation susceptibility in the ‘frequent exacerbator’ COPD phenotype.,These differences include fewer CD4+ T central memory cells and CD8+ T effector memory cells.,Not applicable. | To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | 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 | Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible disease responsible for the deaths of 3 million people worldwide in 2005, and predicted to be the third leading cause of death worldwide by 2030.,Many COPD models developed to date have followed a Markov structure, in which patients or populations can move between defined health states over successive time periods or cycles.,In COPD, health states are typically based on disease severity defined solely by lung function, as described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,These current modelling methods may restrict the ability to reflect the disease progression/clinical pathway or clinical practice.,Given these limitations in previous COPD models, the authors aimed to develop a more flexible model that could improve on the description of the clinical disease pathway.,The overall objective of this model was to inform the development of policies, guidelines or cost-effectiveness analyses.,A second objective was to validate the model in relation to existing epidemiology studies of COPD.,A patient simulation model was developed in Microsoft Excel™.,The predictability of the model was tested by populating it with data from natural history of disease studies as well as with clinical trial data.,Each patient moves through the model with demographic characteristics randomly generated from a set distribution.,These characteristics determine the risk of clinical events occurring in the model.,The validation with these studies found the model to have generally good predictive ability, yielding in this way a good degree of external validity.,The micro-simulation model is a flexible approach for modelling COPD that allows consideration of complex COPD treatment pathways.,The model was found to be generally robust in terms of predicting clinical outcomes of published studies when tested against other studies.,It has significant potential as a tool for supporting future COPD treatment positioning decisions as well as to inform the development of policies, guidelines or cost-effectiveness analyses. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is defined as a disease characterized by persistent, progressive airflow limitation.,Recent studies have underlined that COPD is correlated to many systemic manifestations, probably due to an underlying pattern of systemic inflammation.,In COPD fractional exhaled Nitric Oxide (FeNO) levels are related to smoking habits and disease severity, showing a positive relationship with respiratory functional parameters.,Moreover FeNO is increased in patients with COPD exacerbation, compared with stable ones.,In alpha-1 antitrypsin deficiency, a possible cause of COPD, FeNO levels may be monitored to early detect a disease progression.,FeNO measurements may be useful in clinical setting to identify the level of airway inflammation, per se and in relation to comorbidities, such as pulmonary arterial hypertension and cardiovascular diseases, either in basal conditions or during treatment.,Finally, some systemic inflammatory diseases, such as psoriasis, have been associated with higher FeNO levels and potentially with an increased risk of developing COPD.,In these systemic inflammatory diseases, FeNO monitoring may be a useful biomarker for early diagnosis of COPD development. | Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation.,Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood.,Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists.,We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients.,We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II).,Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage.,All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage.,These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1.,There were no severe exacerbations or other adverse events.,Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation. | 1 |
Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | 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 |
Remote patient monitoring should reduce mortality rates, improve care, and reduce costs.,We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers.,Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field.,We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain.,Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO2) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients.,We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise.,We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters.,The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems.,Graphical abstractᅟ,ᅟ | Telehealth programs to promote early identification and timely self-management of acute exacerbations of chronic obstructive pulmonary diseases (AECOPDs) have yielded disappointing results, in part, because parameters monitored (symptoms, pulse oximetry, and spirometry) are weak predictors of exacerbations.,Breathing rate (BR) rises during AECOPD and may be a promising predictor.,Devices suitable for home use to measure BR have recently become available, but their accuracy, acceptability, and ability to detect changes in people with COPD is not known.,We compared five BR monitors, which used different monitoring technologies, with a gold standard (Oxycon Mobile®; CareFusion®, a subsidiary of Becton Dickinson, San Diego, CA, USA).,The monitors were validated in 21 stable COPD patients during a 57-min “activities of daily living protocol” in a laboratory setting.,The two best performing monitors were then tested in a 14-day trial in a home setting in 23 stable COPD patients to determine patient acceptability and reliability of signal.,Acceptability was explored in qualitative interviews.,The better performing monitor was then given to 18 patients recruited during an AECOPD who wore the monitor to observe BR during the recovery phase of an AECOPD.,While two monitors demonstrated acceptable accuracy compared with the gold standard, some participants found them intrusive particularly when ill with an exacerbation, limiting their potential utility in acute situations.,A reduction in resting BR during the recovery from an AECOPD was observed in some, but not in all participants and there was considerable day-to-day individual variation.,Resting BR shows some promise in identifying exacerbations; however, further prospective study to assess this is required. | 1 |
Among patients with chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) is a common comorbidity and is probably associated with increased systemic inflammation and worse prognosis.,Metformin, with its pleiotropic anti-inflammatory and antioxidant actions, may offer theoretical benefits in COPD patients with DM.,Thus, this study aimed to investigate the effects of DM and metformin use on mortality in the clinical trajectory of COPD.,This was a retrospective cohort study comprising patients with spirometry-confirmed COPD and an age of ≥40 years from 2008 to 2014.,The primary outcome of interest was all-cause mortality.,We evaluated the effects of DM on mortality through the clinical course of COPD and we also assessed the impact of metformin use on survival of the COPD population.,Among 4231 COPD patients, 556 (13%) had DM, and these patients had 1.62 times higher hazards of 2-year mortality than those without DM (95% confidence interval [CI], 1.15-2.28) after adjusting for age, gender, COPD stage, comorbidities and prior COPD hospitalization.,Over a 2-year period, metformin users had a significantly lower risk of death (hazard ratio, 0.46; 95% CI, 0.23-0.92) compared with non-metformin users in patients with coexistent COPD and DM.,Moreover, metformin users had similar survival to COPD patients without DM.,This study shows that DM is associated with an increased risk of death in COPD patients and metformin use seems to mitigate the hazard.,Our findings suggest a potential role of metformin in the management of DM in COPD.,The online version of this article (10.1186/s12931-019-1035-9) contains supplementary material, which is available to authorized users. | Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD).,Mitochondrial oxidative stress might be involved in driving the oxidative stress-induced pathology.,We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.,Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined.,Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD.,Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.,Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression.,Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR.,ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased.,Healthy smokers were intermediate between healthy nonsmokers and patients with COPD.,Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects.,MitoQ and Tiron inhibited TGF-β-induced ASM cell proliferation and CXCL8 release.,Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation.,Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD. | 1 |
Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD).,New-user observational cohort designs may minimize biases associated with previous case-control designs.,To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.,Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.,Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010).,New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.,Outcomes: severe pneumonia (primary) and any pneumonia (secondary).,Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83).,Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively.,Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use.,There was an apparent dose-related effect, with greater risk at higher daily doses of ICS.,There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.,The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time.,This risk must be weighed against the benefits when prescribing ICS to patients with COPD. | 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 |
Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results.,Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear.,Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years.,Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years.,Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB−) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB+).,CB+ subjects were older, more frequently current smokers and had more pack-years than CB− subjects.,During a median 6.5 years of follow-up, CB+ subjects had greater decline in lung function (−38 mL·year−1, 95% CI −61.7-−14.6; p=0.024).,CB+ subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7-5.9; p<0.001).,In females, survival was significantly worse in CB+ subjects compared to CB− subjects.,Regarding cause-specific mortality, CB+ subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12-4.17; p=0.002).,COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.,Chronic bronchitis increases the risk of exacerbations and mortality among patients with COPDhttp://ow.ly/o1fq30bFf9Q | Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1.,However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients.,The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%.,We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center.,The inclusion criteria were as follows: age ≥40 years, postbron-chodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year.,Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist.,The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug.,Of the 587 patients enrolled in the study, 257 took tiotropium.,Following propensity score matching, 404 patients were included in the analysis.,The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively.,Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13).,Therefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%. | 1 |
To assess tracheobronchial angles and their changes on combined inspiratory and expiratory thoracic computed tomography (CT) scans and to determine correlations between tracheobronchial angles and several indices of chronic obstructive pulmonary disease (COPD).,A total of 80 smokers underwent combined inspiratory and expiratory CT scans.,Of these, 65 subjects also performed spirometry and 55 patients were diagnosed with COPD.,On CT scans, 3-dimensinal tracheobronchial angles (trachea-right main bronchus [RMB], trachea-left main bronchus [LMB], and RMB-LMB) were automatically measured by software.,Lung volumes at inspiration and expiration were also automatically calculated.,Changes in tracheobronchial angles between inspiration and expiration were assessed by the Mann-Whitney test.,Correlations of the angles with lung volume, airflow limitation, and CT-based emphysema index were evaluated by Spearman rank correlation.,The trachea-LMB angle was significantly smaller and the RMB-LMB angle was significantly larger at expiration than inspiration (P<0.0001).,The trachea-LMB and RMB-LMB angles were significantly correlated with lung volume, particularly at expiration.,The RMB-LMB angle was significantly correlated with airflow limitation and CT emphysema index (P<0.001-0.05) at inspiration and expiration, suggesting that narrowed RMB-LMB angle indicates more severe airflow limitation and larger extent of emphysema.,Tracheobronchial angles change during respiration and are correlated with severity of COPD and emphysema. | A substantial proportion of patients with chronic obstructive pulmonary disease (COPD) develops various degree of intrathoracic tracheal collapsibility.,We studied whether the magnitude of intrathoracic tracheal collapsibility could be different across clinical phenotypes and sex in COPD.,Intrathoracic tracheal collapsibility measured at paired inspiratory-expiratory low dose computed tomography (CT) and its correlation with clinical, functional, and CT-densitometric data were investigated in 69 patients with COPD according to their predominant conductive airway or emphysema phenotypes and according to sex.,Intrathoracic tracheal collapsibility was higher in patients with predominant conductive airway disease (n=28) and in females (n=27).,Women with a predominant conductive airway phenotype (n=10) showed a significantly greater degree of collapsibility than women with predominant emphysema (28.9%±4% versus 11.6%±2%; P<0.001).,Intrathoracic tracheal collapsibility was directly correlated with inspiratory-expiratory volume variation at CT and with forced expiratory volume (1 second), and inversely correlated with reduced CT lung density and functional residual capacity.,Intrathoracic tracheal collapsibility was not correlated with cough and wheezing; however, intrathoracic tracheal collapsibility and clinical phenotypes of COPD are closely correlated.,In patients with a predominant emphysematous phenotype, a reduced collapsibility may reflect the mechanical properties of the stiff hyperinflated emphysematous lung.,The high collapsibility in patients with predominant airway disease, mild airway obstruction, and in women with this phenotype may reflect chronic airway inflammation.,The lack of relationship with such symptoms as wheezing, cough, and dyspnea could indicate that intrathoracic tracheal collapsibility itself should be considered neither an abnormal feature of COPD nor a relevant clinical finding. | 1 |
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 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. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | 1 |
Introduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD.,Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.,Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017.,Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.,Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events).,In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively).,In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107-2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081-3.984; P=0.028] were higher in the group with eosinophil count less than 2%.,Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events.,Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment. | Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from acute exacerbations (AECOPD) and display varying disease severity.,However, there is no available biomarker for the classification of AECOPD.,This study is aimed at investigating the sputum cellular profiles to classify patients with AECOPD.,A total of 83 patients with AECOPD and 26 healthy controls were recruited.,Their demographic and clinical characteristics were recorded, and their lung function was examined.,The phenotypes of sputum inflammatory cells were characterised, and the concentrations of sputum and serum amyloid-A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) were measured.,Based on the sputum inflammatory cell profiles, individual patients were categorized into one of the four subgroups with inflammatory eosinophilic, neutrophilic, paucigranulocytic, and mixed granulocytic AECOPD.,Most AECOPD patients were reevaluated within 12-14 months after discharge.,There were 10 (12%) eosinophilic, 36 (43%) neutrophilic, 5 (6%) mixed granulocytic, and 32 (39%) paucigranulocytic AECOPD patients.,The patients with mixed granulocytic or neutrophilic AECOPD had a higher BODE score, more sputum inflammatory cells, lower lung function, and longer hospital stay, accompanied by higher concentrations of sputum MMP-9, IL-6 and CRP, and serum SAA, IL-6 and CRP.,Notably, 83% of patients with neutrophilic AECOPD displayed evidence of bacterial infection and many of them responded poorly to standard therapies.,In addition, patients with mixed granulocytic or neutrophilic stable COPD remained at lower lung functions and higher levels of inflammation.,Patients with AECOPD display heterogeneous inflammation, and the profiles of sputum inflammatory cells may be used as valuable biomarkers for the classification of AECOPD patients. | 1 |
The term Asthma and COPD Overlap (ACO) describes a condition where asthma and COPD overlap.,We aimed to investigate associations between ACO and insomnia and respiratory symptoms, and to investigate the prevalence of ACO and the characteristics of subjects with ACO in two Northern European population studies.,The study comprised 25 429 subjects aged ≥ 40 years who participated in one of two Northern European general population surveys.,Both surveys included questions on asthma, COPD, respiratory and sleep-related symptoms, including difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening, and excessive daytime sleepiness.,ACO was defined as having both self-reported asthma and COPD.,The prevalence of ACO was 1.0%.,The group with ACO had a higher prevalence of both insomnia and respiratory symptoms than subjects with only asthma or COPD.,Having ACO was independently associated with a 2-3 times higher probability of having sleep-related symptoms as compared with the group without asthma or COPD, after adjustment for age, sex, BMI, smoking history and educational level (adjusted odds ratio 2.14-3.36, 95% CI).,Subjects with ACO have a high prevalence of insomnia and respiratory symptoms.,To our knowledge, this is the first study to assess the association between sleep-related symptoms and ACO. | 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 |
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. | Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems.,Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity.,To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses.,Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings.,We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation.,Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality.,We pooled the results using fixed effects models where statistically significant heterogeneity (p ≤ 0.1) was absent.,We identified six trials including 230 patients.,Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12-0.54]) and mortality (0.45 [0.22-0.91]).,Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13-1.61) for the fatigue domain, 1.36 (0.94-1.77) for emotional function and 1.88 (1.67-2.09) for mastery.,Weighted mean differences for the St.,Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7).,In all trials, rehabilitation improved exercise capacity (64-215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48-115).,Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation.,Larger trials, however, are needed to further investigate the role of respiratory rehabilitation after acute exacerbation and its potential to reduce costs caused by COPD. | 1 |
Studies report high in-hospital mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) especially for those requiring admission to an intensive care unit.,Recognizing factors associated with mortality in these patients could reduce health care costs and improve end-of-life care.,This retrospective study included AECOPD patients admitted to the respiratory intensive care unit of a tertiary hospital in Beijing from Jan 1, 2011 to Dec 31, 2018.,Patients demographic characteristics, blood test results and comorbidities were extracted from the electronic medical record system and compared between survivors and non-survivors.,We finally enrolled 384 AECOPD patients: 44 (11.5%) patients died in hospital and 340 (88.5%) were discharged.,The most common comorbidity was respiratory failure (294 (76.6%)), followed by hypertension (214 (55.7%)), coronary heart disease (115 (29.9%)) and chronic heart failure (76 (19.8%)).,Multiple logistic regression analysis revealed that independent risk factors associated with in-hospital mortality included lymphocytopenia, leukopenia, chronic heart failure and requirement for invasive mechanical ventilation.,The in-hospital mortality of patients with acute COPD exacerbation requiring RICU admission is high.,Lymphocytes < 0.8 × 109/L, leukopenia, requirement for invasive mechanical ventilation, and chronic heart failure were identified as risk factors associated with increased mortality rates. | Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide.,Patients with COPD frequently have systemic comorbidities that often require unscheduled hospitalization for exacerbation and deterioration of physical conditions, and can have a poor prognosis.,We verified factors affecting patients’ short-term mortality, using a national inpatient database in Japan.,We retrospectively collected data for COPD patients (age: >40 years) with emergency admission between July 2010 and March 2013, using the Diagnosis Procedure Combination database.,We performed multivariate logistic analyses fitted with a generalized estimating equation to assess factors associated with all-cause in-hospital mortality.,A total of 177,207 patients (mean age: 77.5 years; males: 72.9%) were identified.,All-cause in-hospital death occurred in 23,614 patients (13.7%).,Higher mortality was associated with older age, male sex, lower body mass index, more severe dyspnea, lower level of consciousness, and worse activities of daily life.,Higher mortality was also associated with comorbid conditions, including bacterial pneumonia, aspiration pneumonia, interstitial pneumonitis, pulmonary embolism, respiratory failure, lung cancer, heart failure, cerebral infarction, liver cirrhosis, and chronic renal failure.,Our study demonstrated that all-cause in-hospital mortality in patients with COPD who required emergency hospitalization was associated with deteriorated general conditions and comorbidities at admission.,Physicians should take into account these prognostic factors to choose better treatment options for COPD patients. | 1 |
Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
Acute Exacerbations of COPD (AECOPD) identified from electronic healthcare records (EHR) are important for research, public health and to inform healthcare utilisation and service provision.,However, there is no standardised method of identifying AECOPD in UK EHR.,We aimed to validate the recording of AECOPD in UK EHR.,We randomly selected 1385 patients with COPD from the Clinical Practice Research Datalink.,We selected dates of possible AECOPD based on 15 different algorithms between January 2004 and August 2013.,Questionnaires were sent to GPs asking for confirmation of their patients’ AECOPD on the dates identified and for any additional relevant information.,Responses were reviewed independently by two respiratory physicians.,Positive predictive value (PPV) and sensitivity were calculated.,The response rate was 71.3%.,AECOPD diagnostic codes, lower respiratory tract infection (LRTI) codes, and prescriptions of antibiotics and oral corticosteroids (OCS) together for 5-14 days had a high PPV (>75%) for identifying AECOPD.,Symptom-based algorithms and prescription of antibiotics or OCS alone had lower PPVs (60-75%).,A combined strategy of antibiotic and OCS prescriptions for 5-14 days, or LRTI or AECOPD code resulted in a PPV of 85.5% (95% CI, 82.7-88.3%) and a sensitivity of 62.9% (55.4-70.4%).,Using a combination of diagnostic and therapy codes, the validity of AECOPD identified from EHR can be high.,These strategies are useful for understanding health-care utilisation for AECOPD, informing service provision and for researchers.,These results highlight the need for common coding strategies to be adopted in primary care to allow easy and accurate identification of events. | We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | 1 |
Over the years, the scope of outcomes assessment in chronic obstructive pulmonary disease (COPD) has broadened, allowing for the evaluation of various patient-reported outcomes (PROs).,As it still remains unclear whether and to what extent PROs mirror the exercise performance of patients with COPD, the current study aimed to assess the association between different exercise test outcomes and PROs, before and after pulmonary rehabilitation (PR).,Correlations between PROs used to describe health-related quality of life (HRQoL), mood status, level of care dependency and dyspnea in patients with COPD and commonly used laboratory- and field-based exercise test outcomes were evaluated in 518 individuals with COPD attending PR.,Overall, correlations between PROs and exercise test outcomes at baseline were statistically significant.,The correlation between modified Medical Research Council (mMRC) dyspnea score and 6-min walking distance (6MWD) was strongest (ρ:-0.65; p<0.001).,HRQoL related PROs showed weak correlations with exercise outcomes at baseline.,Moderate correlations were found between St George’s Respiratory Questionnaire total score and 6MWD (r:-0.53; p<0.001) and maximal workload achieved during cardiopulmonary exercise testing (ρ:-0.48; p<0.001); and between Clinical COPD Questionnaire (CCQ) total score and 6MWD (r:-0.48; p<0.001) and maximal workload (ρ:-0.43; p<0.001).,When significant, correlations between changes in exercise test outcomes and changes in PROs after PR were generally very weak or weak.,The highest correlation was found between changes in CCQ total score and changes in 6MWD (ρ: − 0.36; p<0.001).,PROs and exercise test outcomes, although significantly correlated with each other, assess different disease features in patients with COPD.,Individual PROs need to be supported by additional functional measurements whenever possible, in order to get a more detailed insight in the effectiveness of a PR program.,Netherlands Trial Register (NL3263/NTR3416).,Registered 2 May 2012. | Chronic obstructive pulmonary disease (COPD) has been considered a significant health challenge globally in recent years, which affects different aspects of the quality-of-life (QoL).,A review was conducted of research output, research topics, and landscape to have a global view of the papers mentioning the interventions to increase QoL of patients with COPD.,A total of 3242 research items from Web of Science during the period 1990-2018 were downloaded and analyzed.,Analyses based on the different levels of data and methods using using VOSviewer software tool (version 1.16.15, Centre for Science and Technology Studies (CWTS), Leiden University, Leiden, The Netherlands) and Latent Dirichlet allocation.,By exploring the trends in research productivity and topics, an increase was found in the number of papers mentioning non-pharmacological interventions as well as mental health illness and QoL among patients with COPD.,In conclusion, the research on the interventions to increase the QoL of patients with COPD has attracted scientists globally.,It is suggested that more research should be conducted on the effectiveness of non-pharmacological therapies to increase QoL of patients with COPD that can be applied broadly in the community.,The collaboration and support from developed countries to developing countries are needed to increase the QoL of people living with COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | COPD exacerbations are responsible for the morbidity and mortality of this disease.,The relationship between exacerbations and patient-related clinical outcomes is not clearly understood.,A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 μg daily was conducted to examine relationships between exacerbations and other clinical outcomes.,The relationship between FEV1, St.,George’s Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2).,921 patients participated in the trials (mean age 65 years, mean FEV1 = 1.02 L (39% predicted).,The percent change from baseline in FEV1 in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was −3.4%, −3.4%, −5.7% and −6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively.,Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations.,In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores.,A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments.,In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV1, TDI, and SGRQ.,A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes. | 1 |
Patients with COPD often experience severe exacerbations involving hospitalization, which accelerate lung function decline and reduce quality of life.,This study aimed to develop and validate a predictive model to identify patients at risk of developing severe COPD exacerbations using administrative claims data, to facilitate appropriate disease management programs.,A predictive model was developed using a retrospective cohort of COPD patients aged 55-89 years identified between July 1, 2010 and June 30, 2013 using Humana’s claims data.,The baseline period was 12 months postdiagnosis, and the prediction period covered months 12-24.,Patients with and without severe exacerbations in the prediction period were compared to identify characteristics associated with severe COPD exacerbations.,Models were developed using stepwise logistic regression, and a final model was chosen to optimize sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV).,Of 45,722 patients, 5,317 had severe exacerbations in the prediction period.,Patients with severe exacerbations had significantly higher comorbidity burden, use of respiratory medications, and tobacco-cessation counseling compared to those without severe exacerbations in the baseline period.,The predictive model included 29 variables that were significantly associated with severe exacerbations.,The strongest predictors were prior severe exacerbations and higher Deyo-Charlson comorbidity score (OR 1.50 and 1.47, respectively).,The best-performing predictive model had an area under the curve of 0.77.,A receiver operating characteristic cutoff of 0.4 was chosen to optimize PPV, and the model had sensitivity of 17%, specificity of 98%, PPV of 48%, and NPV of 90%.,This study found that of every two patients identified by the predictive model to be at risk of severe exacerbation, one patient may have a severe exacerbation.,Once at-risk patients are identified, appropriate maintenance medication, implementation of disease-management programs, and education may prevent future exacerbations. | Forecasting hospitalization in patients with COPD has gained significant interest in the field of COPD care.,There is a need to find simple tools that can help clinicians to stratify the risk of hospitalization in these patients at the time of care.,The perception of quality of life has been reported to be independently associated with hospitalizations, but questionnaires are impractical for daily clinical use.,Individual questions from valid questionnaires can have robust predictive abilities, as has been suggested in previous reports, as a way to use patient-reported outcomes to forecast important events like hospitalizations in COPD.,Our primary aim was to assess the predictive value of individual questions from the Chronic Respiratory Questionnaire Self-Assessment Survey (CRQ-SAS) on the risk of hospitalization and to develop a clinically relevant and simple algorithm that clinicians can use in routine practice to identify patients with an increased risk of hospitalization.,A total of 493 patients with COPD prospectively recruited from an outpatient pulmonary clinic completed the CRQ-SAS, demographic information, pulmonary function testing, and clinical outcomes.,The cohort had a mean age of 70 years, was 54% male, with forced expiratory volume in 1 second percentage predicted 42.8±16.7, and modified Medical Research Council dyspnea scale score of 2±1.13.,Our analysis validated the original CRQ-SAS domains.,Importantly, recursive partitioning analysis identified three CRQ-SAS items regarding fear or panic of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms that were highly predictive of hospitalization.,We propose a robust (area under the curve =0.70) but short and easy algorithm for daily clinical care to forecast hospitalizations in patients with COPD.,We identified three themes - fear of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms - as important patient-reported outcomes to predict hospitalizations, and propose a short and easy algorithm to forecast hospitalizations in patients with COPD. | 1 |
Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. | 1 |
In COPD patients, fatal and non-fatal respiratory-related events are influenced by age, severity of respiratory disease, and comorbidities.,Analyze the effects of edentulism, periodontal disease and systemic biomarkers of inflammation on the occurrence of serious fatal and non-fatal respiratory-related events among subjects with COPD.,Cases were identified from Dental Atherosclerosis Risk in Communities study.,Edentulism was defined as study participants without any natural teeth or implants.,Participants with one or more natural teeth (comprising 11,378 subjects) were studied as dentate subjects.,Periodontal disease status among dentate individuals was determined using the consensus definitions published by the joint Center for Disease Control/American Association of Periodontology working group).,Adjusted Hazard Models are developed to evaluate the relationship between edentulism/periodontal disease and COPD Related Events.,Models were then stratified by GOLD Stage I, II and III/IV.,Serum biomarkers were also evaluated to explore the effect of systemic inflammation.,A statistically significant association was found between oral health status and COPD-related events, even adjusting for conditions such as hypertension, smoking and diabetes.,Edentulous individuals who had been diagnosed with COPD had a higher incidence and were at greater risk of having a COPD related event (hospitalization and death) than individuals who had teeth and whose mouths had healthy periodontal status.,However, being edentulous did not convey excess risk for COPD-related events for those study participants who were classified as GOLD III/IV at baseline.,Finally, we showed that individuals who had levels of serum IL-6 in the highest two quartiles were at even higher risk for COPD-related events.,These findings suggest that the risk for COPD-related events after adjusting for potential confounders may be attributable to both edentulism and elevated serum IL-6 levels. | Many epidemiological studies have found a positive association between periodontal disease (PD) and risk of chronic obstructive pulmonary disease (COPD), but this association is varied and even contradictory among studies.,We performed a meta-analysis to ascertain the relationship between PD and COPD.,PubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD.,Data from the studies selected were extracted and analyzed independently by two authors.,The meta-analysis was performed using the Comprehensive Meta-Analysis software.,Fourteen observational studies (one nested case-control, eight case-control, and five cross-sectional) involving 3,988 COPD patients were yielded.,Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; P<0.001), with sensitivity analysis showing that the result was robust.,Subgroups analyses according to study design, ethnicity, assessment of PD/COPD, and adjusted/unadjusted odds ratios also revealed a significant association.,Publication bias was detected.,Based on current evidence, PD is a significant and independent risk factor of COPD.,However, whether a causal relationships exists remains unclear.,Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third commonest cause of death globally, and manifests as a progressive inflammatory lung disease with no curative treatment.,The lung microbiome contributes to COPD progression, but the function of the gut microbiome remains unclear.,Here we examine the faecal microbiome and metabolome of COPD patients and healthy controls, finding 146 bacterial species differing between the two groups.,Several species, including Streptococcus sp000187445, Streptococcus vestibularis and multiple members of the family Lachnospiraceae, also correlate with reduced lung function.,Untargeted metabolomics identifies a COPD signature comprising 46% lipid, 20% xenobiotic and 20% amino acid related metabolites.,Furthermore, we describe a disease-associated network connecting Streptococcus parasanguinis_B with COPD-associated metabolites, including N-acetylglutamate and its analogue N-carbamoylglutamate.,While correlative, our results suggest that the faecal microbiome and metabolome of COPD patients are distinct from those of healthy individuals, and may thus aid in the search for biomarkers for COPD.,Chronic obstructive pulmonary disease (COPD) is a progressing disease, with lung but not gut microbiota implicated in its etiology.,Here the authors compare the stool from patients with COPD and healthy controls to find specific gut bacteria and metabolites associated with active disease, thereby hinting at a potential role for the gut microbiome in COPD. | Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).,We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.,Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.,Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD.,While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella.,Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.,Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations.,These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.,The online version of this article (10.1186/s12931-019-1085-z) contains supplementary material, which is available to authorized users. | 1 |
To describe the temporal and spatial trends of mortality and disability adjusted life years (DALYs) due to chronic respiratory diseases, by age and sex, across the world during 1990-2017 using data from the Global Burden of Disease Study 2017.,Systematic analysis.,The Global Burden of Diseases, Injuries, and Risk Factors Study 2017.,Mortality and DALYs from chronic respiratory diseases were estimated from the Global Burden of Disease Study 2017 using DisMod-MR 2.1, a Bayesian meta-regression tool.,The estimated annual percentage change of the age standardised mortality rate was calculated using a generalised linear model with a Gaussian distribution.,Mortality and DALYs were stratified according to the Socio-demographic index.,The strength and direction of the association between the Socio-demographic index and mortality rate were measured using the Spearman rank order correlation.,Risk factors for chronic respiratory diseases were analysed from exposure data.,Between 1990 and 2017, the total number of deaths due to chronic respiratorydiseases increased by 18.0%, from 3.32 (95% uncertainty interval 3.01 to 3.43) million in 1990 to 3.91 (3.79 to 4.04) million in 2017.,The age standardised mortality rate of chronic respiratory diseases decreased by an average of 2.41% (2.28% to 2.55%) annually.,During the 27 years, the annual decline in mortality rates of chronic obstructive pulmonary disease (COPD; 2.36%, uncertainty interval 2.21% to 2.50%) and pneumoconiosis (2.56%, 2.44% to 2.68%) has been slow, whereas the mortality rate for interstitial lung disease and pulmonary sarcoidosis (0.97%, 0.92% to 1.03%) has increased.,Reductions in DALYs for asthma and pneumoconiosis have been seen, but DALYs due to COPD, and interstitial lung disease and pulmonary sarcoidosis have increased.,Mortality and the annual change in mortality rate due to chronic respiratory diseases varied considerably across 195 countries.,Assessment of the factors responsible for regional variations in mortality and DALYs and the unequal distribution of improvements during the 27 years showed negative correlations between the Socio-demographic index and the mortality rates of COPD, pneumoconiosis, and asthma.,Regions with a low Socio-demographic index had the highest mortality and DALYs.,Smoking remained the major risk factor for mortality due to COPD and asthma.,Pollution from particulate matter was the major contributor to deaths from COPD in regions with a low Socio-demographic index.,Since 2013, a high body mass index has become the principal risk factor for asthma.,Regions with a low Socio-demographic index had the greatest burden of disease.,The estimated contribution of risk factors (such as smoking, environmental pollution, and a high body mass index) to mortality and DALYs supports the need for urgent efforts to reduce exposure to them. | Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation associated with an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking.,Increased oxidative burden plays an important role in the pathogenesis of COPD.,There is a delicate balance between the toxicity of oxidants and the protective function of the intracellular and extracellular antioxidant defense systems, which is critically important for the maintenance of normal pulmonary functions.,Several biomarkers of oxidative stress are available and have been evaluated in COPD.,In this review, we summarize the main literature findings about circulating oxidative stress biomarkers, grouped according to their method of detection, measured in COPD subjects. | 1 |
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. | Patients with COPD experience respiratory symptoms, impairments of daily living and recurrent exacerbations.,The aim of integrated disease management (IDM) is to establish a programme of different components of care (ie, self-management, exercise, nutrition) in which several healthcare providers (ie, nurses, general practitioners, physiotherapists, pulmonologists) collaborate to provide efficient and good quality of care.,The aim of this Cochrane systematic review was to evaluate the effectiveness of IDM on quality of life, exercise tolerance and exacerbation related outcomes.,Searches for all available evidence were carried out in various databases.,Included randomised controlled trials (RCTs) consisted of interventions with multidisciplinary (≥2 healthcare providers) and multitreatment (≥2 components) IDM interventions with duration of at least 3 months.,Two reviewers independently searched, assessed and extracted data of all RCTs.,A total of 26 RCTs were included, involving 2997 patients from 11 different countries with a follow-up varying from 3 to 24 months.,In all 68% of the patients were men, with a mean age of 68 years and a mean forced expiratory volume in 1 s (FEV1) predicted value of 44.3%.,Patients treated with an IDM programme improved significantly on quality of life scores and reported a clinically relevant improvement of 44 m on 6 min walking distance, compared to controls.,Furthermore, the number of patients with ≥1 respiratory related hospital admission reduced from 27 to 20 per 100 patients.,Duration of hospitalisation decreased significantly by nearly 4 days. | 1 |
Nighttime symptoms can negatively impact the quality of life of patients with chronic obstructive pulmonary disease (COPD).,The Nighttime Symptoms of COPD Instrument (NiSCI) was designed to measure the occurrence and severity of nighttime symptoms in patients with COPD, the impact of symptoms on nighttime awakenings, and rescue medication use.,The objective of this study was to explore item reduction, inform scoring recommendations, and evaluate the psychometric properties of the NiSCI.,COPD patients participating in a Phase III clinical trial completed the NiSCI daily.,Item analyses were conducted using weekly mean and single day scores.,Descriptive statistics (including percentage of respondents at floor/ceiling and inter-item correlations), factor analyses, and Rasch model analyses were conducted to examine item performance and scoring.,Test-retest reliability was assessed for the final instrument using the intraclass correlation coefficient (ICC).,Correlations with assessments conducted during study visits were used to evaluate convergent and known-groups validity.,Data from 1,663 COPD patients aged 40-93 years were analyzed.,Item analyses supported the generation of four scores.,A one-factor structure was confirmed with factor analysis and Rasch analysis for the symptom severity score.,Test-retest reliability was confirmed for the six-item symptom severity (ICC, 0.85), number of nighttime awakenings (ICC, 0.82), and rescue medication (ICC, 0.68) scores.,Convergent validity was supported by significant correlations between the NiSCI, St George’s Respiratory Questionnaire, and Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Respiratory Symptoms scores.,The results suggest that the NiSCI can be used to determine the severity of nighttime COPD symptoms, the number of nighttime awakenings due to COPD symptoms, and the nighttime use of rescue medication.,The NiSCI is a reliable and valid instrument to evaluate these concepts in COPD patients in clinical trials and clinical practice.,Scoring recommendations and steps for further research are discussed. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
The incidence and prevalence of chronic obstructive pulmonary disease (COPD) is associated with increasing age.,Osteoarthritis is also a growing problem in the aging population, and total knee replacement (TKR) is a common surgical procedure for this population.,An increasing number of COPD patients are receiving TKR, but few studies have examined the complications and outcomes after TKR in COPD patients.,The purpose of this study was to investigate the complications, including mortality, wound infections, hospitalization readmission, pneumonia (PN), and cerebrovascular accidents (CVAs) in patients with COPD after receiving TKR.,The National Health Insurance operated by the government is a nationwide health care program with universal coverage in Taiwan.,It covers approximately 99% of the total Taiwanese population of 23 million people.,In this case-control study, we analyzed the longitudinally linked National Health Insurance Research Database, which consists of a cohort of 1,000,000 randomly selected enrollees retrospectively followed from 1996 to 2010.,This study analyzed patients who underwent TKR surgery between January 1, 2004 and December 31, 2009 by identifying the International Classification of Diseases, Ninth Revision, Clinical Modification code.,We separated patients into COPD and non-COPD groups.,Five study outcomes and complications were measured after TKR, including mortality for 1 and 3 years, wound infections for 1 and 2 years, hospitalization readmission for 30 and 90 days, PN for 30 and 90 days, and CVAs.,A total of 3431 patients who underwent TKR surgery were identified, including 358 patients with COPD and 3073 patients without COPD.,The COPD group had a higher percentage of 90-day PN (3.7% vs.,1.1%), 30-day readmission (7.0% vs.,4.0%), 30-day CVA (1.7% vs.,0.6%), 90-day CVA (3.9% vs.,2.1%), and 3-year mortality (3.9% vs.,2.1%) than the non-COPD group.,COPD was associated with 90-day PN (adjusted hazard ratio[HR)] = 2.12, P = 0.030) after adjusting for sex, cardiovascular disease, and CVA occurrence.,Patients with COPD had a higher risk of PN after TKR than patients without COPD, but no significant differences were found for CVAs and mortality. | Patients with chronic obstructive pulmonary disease (COPD) have a high risk of osteoporosis and fractures.,The incidence rate of hip fracture has steadily increased over time and is a major common event in patients with osteoporosis and COPD.,Total hip replacement (THR) is commonly performed in patients with hip fracture.,Our aim was to compare the complications of THR between patients with and without COPD.,Longitudinally linked data from the National Health Insurance Research Database, which consists of registration, claims, and reimbursement records, for a cohort of 1,000,000 randomly selected enrollees traced retrospectively from 1996 to 2000 in Taiwan.,Patients who had undergone THR surgery between January 1, 2004, and December 31, 2008, were identified and divided into COPD and non-COPD cohorts.,Outcomes and complications, including 90-day mortality, 1-year mortality, 1-year wound infection, 30-day readmission for hospitalization, 30-day pneumonia, 30-day acute respiratory failure, 30-day cerebrovascular accident, and length of stay during hospitalization, were measured after THR.,The COPD group had a significantly higher ratio of complications, including 30-day readmission (14.0% vs 8.4%), 30-day pneumonia (10.4% vs 4.4%), 30-day acute respiratory failure (1.5% vs 0.5%), 1-year mortality (6.9% vs 2.7%), and length of stay in the hospital (10.6% vs 0.8%) than the non-COPD group.,In addition to airway diseases, patients in the COPD group had higher mortality than those in non-COPD group after THR.,Surgeons should give more attention to airway evaluation and selection of patients with COPD for THR. | 1 |
Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan.,We evaluated the effects of long-term lysozyme administration on COPD exacerbation.,In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected.,Lysozyme (270 mg) or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators.,COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed.,An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication.,The primary endpoint was exacerbation rate.,A total of 408 patients were randomly assigned to the lysozyme and placebo groups.,The baseline characteristics were similar between the two groups.,The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression).,However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6).,Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group.,The levels of improvement in forced expiratory volume in 1 second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52 weeks of the study.,The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation. | The aim of this study was to evaluate the relationship between computed tomography assessed lobe-based lung parameters and the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD), including the frequency of exacerbation and annual change in forced expiratory volume in 1 second (FEV1).,We studied 65 patients with COPD.,We reconstructed computed tomography images to trace the bronchial tree from right B1 to B10 and created 3 cm circle images around the airways exactly perpendicular to the airway axis in the central, middle, and peripheral zones of the bronchi.,The number of airways and vessels, airway inner diameter and area of emphysema in the circles were calculated for each segment.,Then, we analyzed the relationships between the lobe-based image parameters and the frequency of exacerbation and annual decline in the FEV1.,In addition, we assessed the effects of proximal airway lumen-obliterated emphysema (ALOE) on these clinical features.,The airway diameter was not associated with the frequency of exacerbation or annual decline in FEV1.,Among the structural parameters, lower lobe emphysema was most associated with the frequency of exacerbation.,The reductions in the number of airways and vessels in total lobe were associated with the annual decline in FEV1.,The subgroup of patients with ALOE demonstrated lower FEV1 and more frequent exacerbation than those without ALOE.,Lower lobe emphysema predicts frequent COPD exacerbation, whereas the annual decline in FEV1 is associated with the number of airways and vessels in total lobe. | 1 |
Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. | Glucocorticoids are the most effective antiinflammatory agents for the treatment of chronic inflammatory diseases even though some diseases, such as chronic obstructive pulmonary disease (COPD), are relatively glucocorticoid insensitive.,However, the molecular mechanism of this glucocorticoid insensitivity remains uncertain.,We show that a defect of glucocorticoid receptor (GR) deacetylation caused by impaired histone deacetylase (HDAC) 2 induces glucocorticoid insensitivity toward nuclear factor (NF)-κB-mediated gene expression.,Specific knockdown of HDAC2 by RNA interference resulted in reduced sensitivity to dexamethasone suppression of interleukin 1β-induced granulocyte/macrophage colony-stimulating factor production.,Loss of HDAC2 did not reduce GR nuclear translocation, GR binding to glucocorticoid response element (GRE) on DNA, or GR-induced DNA or gene induction but inhibited the association between GR and NF-κB.,GR becomes acetylated after ligand binding, and HDAC2-mediated GR deacetylation enables GR binding to the NF-κB complex.,Site-directed mutagenesis of K494 and K495 reduced GR acetylation, and the ability to repress NF-κB-dependent gene expression becomes insensitive to histone deacetylase inhibition.,In conclusion, we show that overexpression of HDAC2 in glucocorticoid-insensitive alveolar macrophages from patients with COPD is able to restore glucocorticoid sensitivity.,Thus, reduction of HDAC2 plays a critical role in glucocorticoid insensitivity in repressing NF-κB-mediated, but not GRE-mediated, gene expression. | 1 |
Underdiagnosis of chronic obstructive pulmonary disease (COPD) is widespread.,Early detection of COPD may improve the outcome by timely smoking cessation, a change in lifestyle, and treatment with an inhaled bronchodilator (BD).,The objective of this study was to evaluate the diagnostic role of BD reversibility testing in early COPD case finding.,General practitioners (n=241) consecutively recruited subjects aged ≥35 years with relevant exposure (history of smoking, and/or occupational exposure) and at least one respiratory symptom.,Information on age, smoking status, body mass index, dyspnea score (Medical Research Council scale), and spirometry was obtained.,Individuals with airway obstruction (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] <0.70) underwent a BD test with an inhaled β2 agonist, which was considered positive if ΔFEV1 was >0.20 L and >12%.,Asthma and COPD were, respectively, defined as an FEV1 increase >0.50 L and a post-BD FEV1/FVC <0.70.,In total, 4,049 subjects (51% male) were included (mean age 58 years, body mass index 27, 32 pack-years of smoking).,A significant BD response was found in 143 (15%) of the 937 subjects (23%) with airway obstruction at screening spirometry.,In 59% of these subjects, the post-BD FEV1/FVC remained <0.70.,In 24% of the subjects with pre-BD airway obstruction, the post-BD FEV1/FVC ratio was within the reference range.,In subjects with confirmed COPD, the mean increase in FEV1 following BD was 0.11 L±0.10 L.,The subjects with COPD and a significant BD response were characterized by a higher prevalence of dyspnea (72% versus 57%, P=0.02) but less cough (55% versus 75%, P=0.001) when compared with COPD subjects without BD reversibility.,Administration of a BD in COPD case finding is important in order to determine the post-BD FEV1/FVC ratio.,Exclusion of subjects with a significant BD response may result in underdiagnosis of COPD, and we question the need for the BD reversibility test in the diagnostic screening algorithm in early COPD case finding. | This report updates surveillance results for COPD in the United States.,For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed.,In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD.,From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019).,In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD.,From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001).,In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD.,Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033).,There were 133,575 deaths (63.1 per 100,000) from COPD in 2010.,The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163).,Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001).,Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed.,Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States. | 1 |
This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT).,Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database.,MITT was defined as subjects with ≥1 overlapping days’ supply of three COPD medications (ICS, LABA, and LAMA).,Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up.,In addition, analyses were stratified by number of inhalers.,In total, 14,635 MITT users were identified (mean age, 62 years).,Mean PDC for MITT at 12 months was 0.37%.,Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively.,The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT.,Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up.,Patients with COPD had low adherence to and persistence with MITT in a real-world setting.,Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT.,Reducing the number of inhalers may improve overall adherence to intended triple therapy. | The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460. | 1 |
While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population.,This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials.,In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol.,We assessed the forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response and trough FEV1 response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg.,Treatment-emergent adverse events were recorded throughout treatment and ≤21 days after study medication.,In the East Asian population, 1,152 patients were randomized (5,163 overall).,After 24 weeks, FEV1 AUC0-3 and trough FEV1 responses were greater (P<0.0001) with tiotropium/olodaterol 5/5 μg in both populations versus tiotropium or olodaterol.,The East Asian population showed slightly greater trough FEV1 treatment differences between tiotropium/olodaterol 5/5 μg and tiotropium compared to the overall population.,Generally, no increase in adverse events was seen with tiotropium/olodaterol 5/5 μg compared to tiotropium and olodaterol in either population.,The efficacy and safety profile of tiotropium/olodaterol 5/5 μg has been demonstrated for both East Asian and global populations. | The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado® 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD.,However, there may be racial differences in the effects of T+O on lung function in patients with COPD.,In this Tonado® subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants.,Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George’s Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history.,A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher.,At Week 24, mean improvements with T+O 5/5 μg in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 μg.,Mean improvements with T+O 5/5 μg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 μg.,SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies.,Responses were similar in the overall population.,Adverse-event incidence was generally balanced across treatment groups.,Consistent with results from the overall population, T+O 5/5 μg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado®. | 1 |
Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF).,HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD).,However, the prognostic role of NP in COPD patients remains unclear.,The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients.,We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients.,Nine studies were considered for qualitative analysis for a total of 2788 patients.,Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis.,Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively).,The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age).,NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD. | Cardiovascular diseases are an important cause of morbidity and mortality in chronic obstructive pulmonary disease patients.,The increased inflammatory biomarker levels predict exacerbations and are associated with cardiovascular diseases in stable chronic obstructive pulmonary disease patients but their role in the settings of acute chronic obstructive pulmonary disease exacerbations has not been determined.,To analyse the association between inflammatory biomarkers and heart failure and also to determine the predictors of mortality in patients with exacerbations of chronic obstructive pulmonary disease.,Prospective observational study.,We analysed 194 patients admitted for acute exacerbation of chronic obstructive pulmonary disease at The Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia.,In all patients, C-reactive protein, fibrinogen, N-terminal of the pro-hormone brain natriuretic peptide and white blood count were measured and transthoracic echocardiography was performed.,There were 119 men (61.3%) and the median age was 69 years (interquartile range 62-74).,Left ventricular systolic dysfunction (ejection fraction <50%) was present in 47 (24.2%) subjects.,Patients with left ventricular systolic dysfunction had higher C-reactive protein levels (median 100 vs. 31 mg/L, p=0.001) and fibrinogen (median 5 vs. 4 g/L, p=<0.001) compared to those with preserved ejection fraction.,The overall hospital mortality was 8.2% (16/178).,The levels of C-reactive protein, fibrinogen, N-terminal pro-brain natriuretic peptide and ejection fraction predicted hospital mortality in univariate analysis.,After adjusting for age, hypoxemia and C-reactive protein, ejection fraction remained significant predictors of hospital mortality (OR 3.89, 95% CI 1.05-15.8).,Nearly a quarter of patients with the exacerbation of chronic obstructive pulmonary disease present with left ventricular systolic dysfunction which may be associated with mortality. | 1 |
Dysfunctional innate responses of alveolar macrophages to nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae contribute to morbidity in chronic obstructive pulmonary disease (COPD).,Our earlier studies discovered impaired COPD alveolar macrophage responses to Toll-like receptor (TLR) ligands of nontypeable H. influenzae and provide rationale for further evaluation of TLR signaling.,While the role of TLR single nucleotide polymorphisms is increasingly recognized in inflammatory diseases, TLR single nucleotide polymorphisms in COPD have only recently been explored.,We hypothesized that specific TLR polymorphisms are associated with dysfunctional innate immune COPD alveolar macrophage responses and investigated polymorphisms of TLR2(Arg753Gln), TLR4(Thr399Ile; Asp299Gly), and TLR9(T1486C; T1237C).,DNA was purified from cells of 1) healthy nonsmokers (n = 20); 2) COPD ex-smokers (n = 83); 3) COPD active smokers (n = 93).,DNA amplifications (polymerase chain reaction) were performed for each SNP.,Alveolar macrophages from each group were incubated with nontypeable H. influenzae, M. catarrhalis and S. pneumoniae.,Cytokine induction of macrophage supernatants was measured and the association with TLR single nucleotide polymorphism expression was determined.,No significant inter-group differences in frequency of any TLR SNP existed.,However both TLR9 single nucleotide polymorphisms were expressed in high frequency.,Among COPD ex-smokers, diminished IL-8 responsiveness to nontypeable H. influenzae, M. catarrhalis and S. pneumoniae was strongly associated with carriage of TLR9(T1237C) (p = 0.02; p = 0.008; p = 0.02), but not TLR9(T1486C).,Carriage of TLR9(T1237C), but not TLR9(T1486C), correlated with diminished FEV1%predicted (p = 0.037).,Our results demonstrate a notable association of TLR9(T1237C) expression with dysfunctional innate alveolar macrophage responses to respiratory pathogens and with severity of COPD. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
Reports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations.,However, the magnitude of this reduction varies between studies.,Electronic databases were searched from January 2020 to May 2021.,Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria.,A modified version of the Newcastle-Ottawa Scale was used to assess study quality.,A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions.,Exacerbation reduction was compared against the COVID-19 Containment and Health Index.,A total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries.,Nine studies could be included in the meta-analysis.,The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44-0.57).,Findings on the rate of community-treated exacerbations were inconclusive.,Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period.,There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53).,There was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations.,Future guidelines should consider including recommendations on respiratory virus infection control measures to reduce the burden of COPD exacerbations beyond the pandemic period. | Despite optimal pharmacological therapy and pulmonary rehabilitation, patients with COPD continue to be breathless.,There is a need to develop additional strategies to alleviate symptoms.,Learning to sing requires control of breathing and posture and might have benefits that translate into daily life.,To test this hypothesis we performed a randomised controlled trial, comparing a six week course of twice weekly singing classes to usual care, in 28 COPD patients.,The experience of singing was assessed in a qualitative fashion, through interviews with a psychologist.,In addition, we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops.,In the RCT, the physical component score of the SF36 improved in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. -3.8(8.4) p = 0.02.,Singers also had a significant fall in HAD anxiety score; -1.1(2.7) vs.,+0.8(1.7) p = 0.03.,Singing did not improve single breath counting, breath hold time or shuttle walk distance.,In the qualitative element, 8 patients from the singing group were interviewed.,Positive effects on physical sensation, general well-being, community/social support and achievement/efficacy emerged as common themes. 150 participants in open workshops completed a questionnaire. 96% rated the workshops as "very enjoyable" and 98% thought the workshop had taught them something about breathing in a different way. 81% of attendees felt a "marked physical difference" after the workshop.,Singing classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease; no adverse consequences of participation were observed.,Current Controlled Trials - ISRCTN17544114. | 1 |
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. | COPD exerts a substantial burden on health and health care systems globally and will continue to do so for the foreseeable future.,Treatment however can be costly and health care providers are interested in both whether treatments can offer improvements in disease burden and whether they represent value for money.,Economic evaluations seek to resolve this issue by producing results that can be used to inform and assist the decision maker in allocating scarce health care resources.,In this paper we introduce economic evaluation and then use these themes to review and critically appraise the existing COPD economic evaluations, in order to assess quality in light of today’s standards.,The use of existing economic evaluations in informing the decision maker is then discussed.,Ten out of the fifteen studies were clinical trial or observational study based, and the remaining five on a decision analytic model.,Study design, interventions, outcome measures and the use of uncertainty varied considerably; consequentially the results are difficult to compare in any consistent manner.,Efforts for future studies to harmonize study design and methodology, particularly towards adopting a modeling framework, using current treatment as comparator and adopting a common effectiveness measure, such as the QALY, should be made in order to produce results that are comparable and useful to a decision maker. | 1 |
Telehealth services can improve the quality of health services for chronic obstructive pulmonary disease (COPD) management, but the clinical benefits for patients yet not clear.,It is crucial to develop a strategy that supports the engagement of healthcare professionals to promote the sustainable adoption of telehealth services further.,The aim of the study was to show how variables related to the perception of telehealth services for COPD by different healthcare professionals interact to influence its adoption and to generate advice for future telehealth service implementation.,Data was thematically synthesized from published qualitative studies to create causal loop diagrams, further validated by expert interviews.,These diagrams visualize dependencies and their polarity between different variables.,Adoption of telehealth services from the nurse’s perspective is directly affected by change management and autonomous decision making.,From the physician’s perspective, perceived value is the most important variable.,Physical activity management and positive user experience are considered affecting perceived value for physiotherapists.,There is no consensus where self-management services should be positioned in the COPD care pathway.,Our results indicate how complex interactions between multiple variables influence the adoption of telehealth services.,Consequently, there is a need for multidimensional interventions to achieve adoption.,Moreover, key variables were identified that require attention to ensure success of telehealth services.,Furthermore, it is necessary to explore where self-management services are best positioned in the care pathway of COPD patients. | 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 |
Smoking activates and recruits inflammatory cells and proteases to the airways.,Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema.,However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown.,We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago.,39 COPD outpatients - smokers (n = 22) and ex-smokers (n = 17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups.,IS and BAL samples were obtained for differential and MMP-12+-macrophages count analysis.,The number of IS neutrophils was higher in both COPD groups compared to both controls.,The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers.,The number of BAL MMP-12+-macrophages was higher in COPD smokers (1.6 ± 0.3 × 106/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9 ± 0.4, 0.4 ± 0.2, 0.2 ± 0.1 × 106/ml respectively, p < 0.05).,The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation.,Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by the interaction of genetic susceptibility and environmental influences.,There is increasing evidence that genes link to disease pathogenesis and heterogeneity by causing variation in protease anti-protease systems, defence against oxidative stress and inflammation.,The main methods of genomic research for complex disease traits are described, together with the genes implicated in COPD thus far, their roles in disease causation and the future for this area of investigation. | 1 |
Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD) exacerbation and influence their outcomes.,We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006-2012.,We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%).,Pneumonia was frequent in first-time exacerbations (36.1%), but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation.,Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012.,Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period.,A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission (7.7% vs 12.5%), and several acute procedures.,Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17-1.24).,Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11-1.18), and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07-1.13).,In contrast, the aHR of a subsequent exacerbation was 8%-13% lower for patients with pneumonic exacerbations.,Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care utilization and higher mortality.,Nonpneumonic COPD exacerbations predict increased risk of subsequent exacerbations. | Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines. | 1 |
The relationship between surfactant-associated protein D polymorphisms and chronic obstructive pulmonary disease risk remains controversial.,This article is the first to systematically evaluate this relationship.,A comprehensive worldwide search was conducted for relevant literature on surfactant-associated protein D gene mutations and chronic obstructive pulmonary disease risk prediction.,Study quality was evaluated using the Newcastle-Ottawa scale.,After four genetic models (the allele, additive, recessive, and dominant models) were identified, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were applied in this meta-analysis.,The meta-analysis included 659 individuals in the case group and 597 in the control group.,In the Asian population, none of the four genetic models revealed any significant association between rs2243639 genotype and the risk of chronic obstructive pulmonary disease.,In Caucasians, however, the recessive model exhibited significant risk associated with rs2243639.,Furthermore, there was a significant association between rs721917 genotype and the risk of chronic obstructive pulmonary disease in the Asian population.,In contrast, none of the four gene models revealed any significant risk associated with this gene in the Caucasian population.,This meta-analysis suggests that rs2243639 is not related to the risk of chronic obstructive pulmonary disease in the Asian population but is related to this risk in the Caucasian population.,Regarding rs721917, the T allele may increase the risk of chronic obstructive pulmonary disease in the Asian population. | The association between TNF-α −308 G/A polymorphism and COPD remains controversial due to insufficiently strict study designs and small group sizes among different studies.,In the present study, a meta-analysis update which followed a stricter procedure was performed to obtain a clearer understanding of this association.,A comprehensive database search was conducted to identify the case-control studies published up to July 2015 which reported an association between the TNF-α −308 G/A polymorphism and COPD risk.,Data were extracted to calculate pooled odds ratios with 95% confidence intervals under the most appropriate genetic and allelic models.,Sensitivity was analyzed, and heterogeneity as well as publication bias was assessed.,Thirty-eight eligible studies, comprising 3,951 COPD cases and 5,110 controls, were included in this study, among which 22 studies comprising 2,067 COPD cases and 2,167 controls were performed in Asians, and 16 studies comprising 1,884 COPD cases and 2,943 controls were in non-Asians.,The overall result showed that TNF-α −308 G/A polymorphisms were significantly associated with increased COPD risk in both the codominant genetic and allelic models.,Individuals with the GA or AA genotype were more susceptible to COPD development than those with the GG genotype.,In addition, individuals with the AA genotype were more susceptible to developing COPD than those with the GA genotype.,The subgroup analysis stratified by ethnicity supported the results in Asians but not in non-Asians.,However, no association was found between TNF-α −308 G/A polymorphisms and COPD susceptibility either in Asians or in non-Asians in the meta-analysis conducted with restriction to former/current smokers.,The present meta-analysis suggested that the TNF-α −308 G/A polymorphism was associated with an increased risk of COPD among Asians but not in non-Asians.,Furthermore, individuals with the AA genotype of TNF-α −308 were more susceptible to developing COPD. | 1 |
Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD).,To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD.,The aim of this study was to examine the association between haplotypes of CRP, IL6 and FGB genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition).,Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers.,Plasma levels of CRP, IL-6 and FG were measured in the total study group.,Differences in haplotype distributions were tested using the global and haplotype-specific statistics.,Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients.,However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile).,Global test for haplotype effect indicated association of CRP gene and CRP plasma levels (P = 0.0004) and IL6 gene and COPD (P = 0.003).,Subsequent analysis has shown that IL6 haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005).,None of the genes were associated with COPD-related phenotypes.,Our findings suggest that common genetic variation in CRP and IL6 genes may contribute to heterogeneity of COPD population associated with systemic inflammation. | 1 |
Chronic obstructive pulmonary disease (COPD) has significant systemic effects that substantially impact quality of life and survival.,The purpose of this study was to assess and compare peripheral muscle strength and endurance, exercise capacity, fatigue perception and quality of life between patients with COPD and healthy subjects.,Twenty COPD patients (mean FEV1 49.3 ± 19.2%) and 20 healthy subjects were included in the study.,Pulmonary function testing and six-minute walk test (6MWT) were performed.,Peripheral muscle strength was measured with a hand-held dynamometer, peripheral muscle endurance was evaluated with sit-ups, squats and modified push-ups tests.,Fatigue perception was assessed using the Fatigue Impact Scale (FIS) and Fatigue Severity Scale (FSS).,General quality of life was determined with the Nottingham Health Profile (NHP), and cough-specific quality of life was evaluated with the Leicester Cough Questionnaire (LCQ).,Pulmonary functions, strength of shoulder abductor and flexor muscles, numbers of sit-ups and squats, 6MWT distance and 6MWT% were significantly lower in COPD patients than in healthy subjects (p < 0.05).,FIS psychosocial sub-dimension and total scores, NHP scores for all sub-dimensions except pain sub-dimension of the COPD group were significantly higher than those of healthy subjects (p < 0.05).,The LCQ physical, psychological and social sub-dimensions and total scores were significantly lower in COPD patients than in healthy subjects (p < 0.05).,Pulmonary functions, peripheral muscle strength and endurance, exercise capacity and quality of life were adversely affected in patients with COPD.,There are greater effect of fatigue on psychosocial functioning and general daily life activities and effect of cough on the quality of life in patients with COPD.,This study supports the idea that COPD patients must be evaluated in a comprehensive manner for planning pulmonary rehabilitation programs. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | 1 |
To evaluate the effectiveness of a pilot community pharmacy care model for patients with chronic obstructive pulmonary disease (COPD) to improve: 1) inhaler technique; 2) medication adherence; and 3) uptake of non-pharmacological treatment and prevention activities.,Forty “host” pharmacies in Sydney were invited to recruit eligible patients and to provide a counselling room/area in their pharmacy for service provision.,Eligible patients were referred to two “consultant” pharmacists, specifically trained to deliver a specialized pharmacy COPD service which involved 3 in-pharmacy visits and 2 follow-up phone calls over a 6-month period.,The service consisted of 1) inhaler technique assessment; 2) medication adherence assessment; and 3) referrals to the patient’s general practitioner (GP) to facilitate the uptake of non-pharmacological resources as well as to review COPD medications/devices, as required.,Pre-post analyses were conducted using paired Student’s t-test and Wilcoxon Signed Rank Test for independent variables and chi-squared tests for proportional data.,Nine “host” pharmacies recruited 40 patients, of whom 37 completed the baseline Visit and 27 completed all Visits.,A total of 270 interventions were provided by the “consultant” pharmacists with most provided at Visit 1 (176).,The most common interventions were addressing patient gaps in COPD knowledge and inhaler technique.,A total of 119 referrals were made to GPs for various reasons, the most common being for a COPD action plan, pulmonary rehabilitation, or pneumonia vaccination.,There were significant improvements pre-post intervention in inhaler use competence, COPD knowledge, immunization rate for pneumonia, exacerbation rate and COPD plan ownership.,In this pilot study, the specialized pharmacy-based COPD care model delivered by “consultant” pharmacists in community pharmacies provided significant health benefits for patients.,Further research is needed to assess the model’s effectiveness in a larger population as well as when measured against standard care. | In light of the growing burden of COPD, there is increasing focus on the role of self-management for this population.,Currently, self-management varies widely.,Little is known either about nurses’ and allied health professionals’ (AHPs’) understanding and provision of self-management in clinical practice.,This study explores nurses’ and AHPs’ understanding and implementation of supported COPD self-management within routine clinical practice.,Nurses and AHPs participated in face-to-face semistructured interviews to explore their understanding and provision of COPD self-management, as well as their perceptions of the challenges to providing such care.,Purposive sampling was used to select participants from a range of professions working within primary, community, and secondary care settings.,Three researchers independently analyzed each transcript using a thematic approach.,A total of 14 participants were interviewed.,Nurses and AHPs viewed self-management as an important aspect of COPD care, but often misunderstood what it involved, leading to variation in practice.,A number of challenges to supporting self-management were identified, which related to lack of time, lack of insight regarding training needs, and assumptions regarding patients’ perceived self-management abilities.,Nurses and AHPs delivering self-management require clear guidance, training in the use of effective self-management skills, and education that challenges their preconceptions regarding patients.,The design of health care services also needs to consider the practical barriers to COPD self-management support for the implementation of such interventions to be successful. | 1 |
The increasing prevalence of chronic diseases requires changes in health care delivery.,In COPD, telemedicine appears to be a useful tool.,Our objective was to evaluate the efficacy (in improving health care-resource use and clinical outcomes) of a telemonitoring-based program (telEPOC) in COPD patients with frequent hospitalizations.,We conducted a nonrandomized observational study in an intervention cohort of 119 patients (Galdakao-Usansolo Hospital) and a control cohort of 78 patients (Cruces Hospital), followed up for 2 years (ClinicalTrials.gov identifier: NCT02528370).,The inclusion criteria were two or more hospital admissions in the previous year or three or more admissions in the previous 2 years.,The intervention group received telemonitoring plus education and controls usual care.,Most participants were men (13% women), and the sample had a mean age of 70 years, forced expiratory volume in 1 second of 45%, Charlson comorbidity index score of 3.5, and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index score of 4.1.,In multivariate analysis, the intervention was independently related to lower rates of hospital admission (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.27-0.54; P<0.0001), emergency department attendance (OR 0.56, 95% CI 0.35-0.92; P<0.02), and 30-day readmission (OR 0.46, 95% CI 0.29-0.74; P<0.001), as well as cumulative length of stay (OR 0.58, 95% CI 0.46-0.73; P<0.0001).,The intervention was independently related to changes in several clinical variables during the 2-year follow-up.,An intervention including telemonitoring and education was able to reduce the health care-resource use and stabilize the clinical condition of frequently admitted COPD patients. | Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy.,GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.,In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices).,The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12.,Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.,A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study.,On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001).,IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01).,TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05).,The incidence of adverse events was similar for the two treatment groups.,In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes. | 1 |
Early identification of preventable risk factors of COPD progression is important.,Whether exacerbations have a negative impact on disease progression is largely unknown.,We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD.,Patients diagnosed with mild/moderate COPD (obstruction and FEV1% predicted 50-90%), aged ≥35 years, and a smoking history, who had ≥6 years of UK electronic medical records after initiation of maintenance therapy were studied.,Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥1 exacerbation over a 6-year period and FEV1 decline, adjusted for sex, age, anthropometrics and smoking habits.,Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization.,Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥1 exacerbation.,The mean annual FEV1 decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥1 exacerbation every year.,Patients with more years with ≥1 exacerbation had a lower mean FEV1 at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations.,When counting years with ≥2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV1 at diagnosis).,Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies. | Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories.,The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients.,This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland.,The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices.,DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46-1.57) for DOSE, 1.16 (1.12-1.20) for ADO index and 1.50 (1.33-1.68) and 1.23 (1.10-1.39), respectively, for hospitalisations.,Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items.,The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups.,The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them.,None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality.,The GOLD categories predict future risk inconsistently.,The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions. | 1 |
The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y | Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality.,Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care.,A web-based pilot survey was conducted to evaluate the primary care physician’s, or general practitioner’s (GP’s), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory.,The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant.,This survey demonstrated that the GPs’ understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management.,A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa.,Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%).,Management of COPD was well below guideline-recommended levels in most of the regions investigated.,The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied. | 1 |
High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids.,However, the prognostic role of blood eosinophil count remains underexplored.,Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.,Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital.,The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%-5%), and low (<2%).,The high group had longer six-minute walk distance (high =445.8±81.4, middle =428.5±88.0, and low =414.7±86.3 m), higher body mass index (23.3±3.1, 23.1±3.1, and 22.5±3.2 kg/m2), lower emphysema index (18.5±14.1, 22.2±15.3, and 23.7±16.3), and higher inspiratory capacity/total lung capacity ratio (32.6±7.4, 32.4±9.2, and 29.9% ± 8.9%) (P<0.05).,The survival period increased with increasing blood eosinophil count (high =9.52±0.23, middle =8.47±1.94, and low =7.42±0.27 years, P<0.05).,Multivariate linear regression analysis revealed that the emphysema index was independently and negatively correlated with blood eosinophil count (P<0.05).,In COPD, the severity of emphysema was independently linked with low blood eosinophil count and the longer survival period was associated with increased blood eosinophil count, though it was not proven in the multivariate analysis. | Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD).,Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results.,Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium).,To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample.,We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/−10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations.,The analysis included 16,936 genotyped and imputed SNPs.,No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3×10−5.,The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81×10−5), CNTN5 (P = 4.37×10−4), and TRPV4 (P = 1.58×10−3).,Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41×10−5), followed by PDE4D (P = 1.22×10−4).,The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38×10−4), and ESR1 (P = 5.42×10−4) among ever-smokers.,Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population.,Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population. | 1 |
The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD).,Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents.,This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.,5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat® inhaler).,Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline).,Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.,Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05).,FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.,Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment.,Improvements from baseline in lung function were generally greater in patients with less severe disease.,Boehringer Ingelheim.,Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.,The online version of this article (doi:10.1007/s12325-015-0218-0) contains supplementary material, which is available to authorized users. | Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease.,To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT).,Qualitative: patient focus group and interviews to address content validity.,Quantitative: secondary data analyses to test reliability and validity.,Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male.,Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure.,Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male.,Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score.,Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively.,Validity: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms).,RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05).,E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001).,Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD.,Further study of sensitivity to change is warranted. | 1 |
Pain, a symptom often present in patients with Chronic Obstructive Pulmonary Disease (COPD), alters quality of life.,COPD exacerbation augments several mechanisms that may cause pain (dyspnea, hyperinflation and inflammation) and therefore we hypothesized that pain might be increased during exacerbation.,A prospective cohort study was conducted in patients admitted for acute exacerbations of COPD (AECOPD) in two emergency departments in France and Canada.,Patients with cancer-related pain or recent trauma were not included.,The Short Form McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory (BPI) scale were used to evaluate pain intensity and location.,Patients also completed the Borg Dyspnea Scale and Hospital Anxiety and Depression Scale.,The questionnaires were completed again during an outpatient assessment in the stable phase.,The primary outcome was difference in pain intensity (SF-MPQ) between the exacerbation and stable phases.,Fifty patients were included.,During exacerbation, 46 patients (92%) reported pain compared to 29 (58%) in the stable phase (p<0.001).,Pain intensity was higher during exacerbation (SF-MPQ 29.7 [13.6-38.2] vs.,1.4 [0.0-11.2]; p<0.001).,Pain was predominantly located in the chest during exacerbation and in the limbs during the stable phase.,Pain intensity during exacerbation correlated with anxiety score.,The frequency and intensity of pain were higher during AECOPD, with a specific distribution.,Pain should therefore be routinely assessed and treated in patients with AECOPD. | Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease.,A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS).,Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants.,The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice.,Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h.,GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues.,GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL) activity in lung and liver tissue.,GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged.,Next, the time course of rebound in GSH levels after the CS exposure was examined.,CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months.,Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis.,Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels.,CS exposures evoke a powerful GSH adaptive response in the lung and systemically.,These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels.,Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD. | 1 |
Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis.,However, studies in human subjects are limited.,p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control.,Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals.,Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups.,Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups.,On the other hand, bcl2 expression did not differ between the two groups in all three cell types.,The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients.,Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD. | Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease.,We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease.,Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control).,Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration.,Mean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm).,Emphysema mice lost body weight, controls gained weight.,Running distance was shorter in emphysema than in controls.,Diaphragm muscle length was shorter in controls compared to emphysema.,Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms.,Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls.,Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length.,The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation.,The model may deepen our understanding of systemic aspects of COPD. | 1 |
COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | 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 |
The extent of the survival benefit of augmentation therapy for alpha-1 antitrypsin deficiency (AATD) in individuals with advanced COPD is difficult to define.,We performed a retrospective analysis using all available data from the observational registry of individuals with severe deficiency of alpha-1 antitrypsin (AAT) conducted by the NHLBI investigators.,Individuals (N=1129) with severe deficiency of AAT were evaluated for mortality using all data sources and stratified by 10% increments of baseline forced expiratory volume in 1 second (FEV1) percent predicted and by augmentation therapy status (ever receiving versus never receiving).,Kaplan-Meier survival curves were constructed for each of the deciles comparing survival in treated vs non-treated groups.,A multivariable model was performed to define the correlates of survival in individuals with FEV1 <30% predicted.,Amongst all subjects, augmentation was associated with improved survival (p<0.0001).,Among the individuals ever receiving augmentation therapy, survival was better than for those not receiving augmentation at all 10% increments of FEV1% predicted from 10% to 60% (P values <0.05 in all deciles).,In subgroups of participants with hyperinflation defined as residual volume (RV)>120% predicted and in subgroups of participants with reduced diffusing capacity for carbon monoxide (DLCO) <70% predicted, there was significantly better survival for those ever receiving augmentation therapy than for those who never received augmentation (p<0.001).,A multivariable analysis showed that mortality benefit is influenced by age, DLCO % predicted, and augmentation therapy.,There is a survival benefit from augmentation therapy in AATD between FEV1 values in the 10-60% predicted range.,Screening and treatment of AATD patients should therefore not be limited by the severity of illness as defined by FEV1. | Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | 1 |
Chronic respiratory diseases (CRDs) are leading causes of morbidity worldwide.,However, the spatial and temporal trends in prevalence and incidence of CRDs have not been estimated.,Based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, we analyzed the prevalence and incidence trends of CRDs from 1990 to 2017 according to age, sex, region and disease pattern.,Furthermore, the correlations between the incidence and the World Bank income levels, sociodemographic index (SDI), and human development index (HDI) levels were analyzed to assess the factors affecting incidence.,The total number of CRD cases increased by 39.5% from 1990 to 2017, nevertheless, the age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) showed decreasing trends.,The ASIRs of CRD, chronic obstructive pulmonary disease (COPD), pneumoconiosis, and asthma decreased, whereas the ASIR of interstitial lung disease and pulmonary sarcoidosis increased during the past 27 years.,Significant differences between males and females in the incidence rates of pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis were observed.,Elderly people especially suffered from CRDs, except for asthma.,For COPD, the ASIR decreased from low-SDI regions to high-SDI regions.,The ASIR of interstitial lung disease and pulmonary sarcoidosis in the high-SDI region was highest and have increased mostly.,The ASIRs for pneumoconiosis and asthma were inversely related to the HDI.,In 2017, CRDs were still the leading causes of morbidity worldwide.,A large proportion of the disease burden was attributed to asthma and COPD.,The incidence rates of all four types of CRDs varied greatly across the world.,Statistically significant correlation was found between the ASIR and SDI/HDI. | 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. | 1 |
Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD).,Thus, health care professionals (HCPs) play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence.,However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.,The Real-life Experience and Accuracy of inhaLer use (REAL) survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy.,All results are based on patient-reported data.,The survey was conducted between January 4, 2016 and February 2, 2016.,A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201) with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey.,Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020).,Eighty-three percent of patients indicated that a demonstration (in-person) was “very helpful” versus 58% for video.,Patient preferences for training methods were as follows: demonstration of inhaler use (83%), video (58%), instructions for use (51%), and leaflet (34%).,Twenty-nine percent of patients had not been checked to see if they were using their device correctly by a HCP within the last two years.,Patients who were checked were significantly more adherent than unchecked patients (p=0.020).,The majority of the patients using Breezhaler reported either being very confident or confident of having taken a full dose, which was higher than those using Genuair, Ellipta (α=0.05), and Respimat (α=0.05).,Treatment adherence in the last 30 days was highest with Breezhaler followed by Respimat, Ellipta, and Genuair.,The REAL survey identified attributes that influenced patient adherence and optimal inhaler use.,Predictive attributes that influence patient adherence which HCPs should be aware of include age and disease severity.,Modifiable attributes which the HCP can influence include correct inhaler use training, choice of training methods, checking patient inhaler technique at subsequent visits, and device selection.,Inhalers are integral in the effective management of patients with COPD; it is therefore important that patients use the inhaler correctly and have full confidence in the dosage. | In addition to clinical comorbidities, psychological and neuropsychological problems are frequent in COPD and may affect pulmonary rehabilitation delivery and outcome.,The aims of the study were to describe a COPD population in a rehabilitative setting as regards the patients depressive symptoms, anxiety, mild cognitive impairment (MCI) and self-reported adherence and to analyze their relationships; to compare the COPD sample MCI scores with normative data; and to investigate which factors might predict adherence to prescribed physical exercise.,This was a multicenter observational cross-sectional study.,Of the 117 eligible stable COPD inpatients, 84 were enrolled according to Global initiative for chronic Obstructive Lung Disease (GOLD) criteria (mainly in Stage III-IV).,The assessment included Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), anxiety, depression and self-reported pharmacological and nonpharmacological adherence.,From the MMSE, 3.6% of patients were found to be impaired, whereas from the MoCA 9.5% had a likely MCI.,Patients referred had mild-severe depression (46.7%), anxiety (40.5%), good pharmacological adherence (80.3%) and difficulties in following prescribed diet (24.1%) and exercise (51.8%); they struggled with disease acceptance (30.9%) and disease limitations acceptance (28.6%).,Most of them received good family (89%) or social (53%) support.,Nonpharmacological adherence, depression, anxiety and MCI showed significant relations with 6-minute walking test, body mass index (BMI) and GOLD.,Depression was related to autonomous long-term oxygen therapy modifications, disease perception, family support and MCI.,In the multivariate logistic regression analysis, higher BMI, higher depression and lower anxiety predicted lower adherence to exercise prescriptions (P=0.0004, odds ratio =0.796, 95% CI =0.701, 0.903; P=0.009, odds ratio =0.356, 95% CI =0.165, 0.770; and P=0.05, odds ratio =2.361, 95% CI =0.995, 5.627 respectively).,In COPD patients, focusing on pharmacological and nonpharmacological adherence enhance the possibility of tailored pulmonary rehabilitation programs. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally.,Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97.,A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank.,The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways.,We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications. | CD8 cells may contribute towards an autoimmune process in COPD.,Down regulation of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with consequent T cell dysfunction.,We hypothesise that TCR signalling is abnormal in COPD pulmonary CD8 cells.,Micro-array gene expression analysis of blood and pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from smoker controls (S).,We focused on the TCR signalling pathway, with validation of key findings using polymerase chain reaction and immunofluorescence.,TCR signalling molecules in COPD pulmonary CD8 cells were down regulated compared to blood CD8 cells (CD247: fold change (FC) −2.43, Q = 0.001; LCK: FC −2.25, Q = 0.01).,Micro-array analysis revealed no significant differences between COPD and S pulmonary CD8 cells.,However, PCR revealed significantly lower gene expression levels of CD247 (FC −1.79, p = 0.04) and LCK (FC −1.77, p = 0.01) in COPD compared to S pulmonary CD8 cells.,CD247 down regulation in COPD CD8 cells was confirmed by immunofluorescent staining of bronchoalveolar lavage cells: Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non-smoker CD8 cells (mean 88.9 vs 75.2%, p<0.05) There is down regulation of TCR signalling molecules in COPD pulmonary CD8 cells.,This may cause T cell dysfunction. | 1 |
Exposure to cigarette smoking can increase the risk of cancers and cardiovascular and pulmonary diseases.,However, the underlying mechanisms of how smoking contributes to disease risks are not completely understood.,Epigenome-wide association studies (EWASs), mostly in non-Asian populations, have been conducted to identify smoking-associated methylation alterations at individual probes.,There are few data on regional methylation changes in relation to smoking.,Few data link differential methylation in blood to differential gene expression in lung tissue.,We identified 108 significant (false discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87 significant differentially methylated regions (DMRs) (multiple-testing corrected p < 0.01) in current compared to never smokers from our EWAS of cotinine-validated smoking in blood DNA from a Korean chronic obstructive pulmonary disease cohort (n = 100 including 31 current, 30 former, and 39 never smokers) using Illumina HumanMethylation450 BeadChip.,Of the 108 DMPs (FDR < 0.05), nine CpGs were statistically significant based on Bonferroni correction and 93 were novel including five that mapped to loci previously associated with smoking.,Of the 87 DMRs, 66 were mapped to novel loci.,Methylation correlated with urine cotinine levels in current smokers at six DMPs, with pack-years in current smokers at six DMPs, and with duration of smoking cessation in former smokers at eight DMPs.,Of the 143 genes to which our significant DMPs or DMRs annotated, gene expression levels at 20 genes were associated with pack-years in lung tissue transcriptome data of smokers (Asan Biobank, n = 188).,Our study of differential methylation in Koreans confirmed previous findings from non-Asian populations and revealed novel loci in relation to smoking.,Smoking-related differential methylation in blood is associated with gene expression in lung tissue, an important target of adverse health effects of smoking, supporting the potential functional importance of methylation in smoking-related disease.,The online version of this article (doi:10.1186/s13148-016-0266-6) contains supplementary material, which is available to authorized users. | Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood.,As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression.,Here we show that polymeric immunoglobulin receptor-deficient (pIgR−/−) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age.,Progressive airway wall remodelling and emphysema in pIgR−/− mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase.,Re-derivation of pIgR−/− mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling.,These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema.,The mechanisms driving lung inflammation and remodelling in chronic obstructive pulmonary disease (COPD) are incompletely understood.,Here the authors show that lack of secretory IgA promotes bacterial invasion in small airways, resulting in leukocyte recruitment and a COPD-like phenotype. | 1 |
In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.,Relevant studies were identified through MEDLINE searches.,Using random effects models, summary effects of specific previous conditions were evaluated separately and combined.,Stratified analyses were conducted based on smoking status, gender, control sources and continent.,A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies).,The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22-1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies).,Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97-1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).,Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer. | Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia.,These features are partially attributed to activation of the epidermal growth factor receptor (EGFR).,Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists.,We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.,114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted.,Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.,Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression.,Epithelial features were not different between short-term quitters (<3.5 years) and current smokers.,Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs.,14.4%, p = 0.005; 7.9% vs.,13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs.,18.6%, p < 0.001).,Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).,NCT00158847 | 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. | Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common, preventable disease of airflow limitation that accounts for the third leading deaths of any disease process in the worldwide.,Health benefits of liuzijue qigong (LQG) on patients with stable COPD has been assessed.,This study was designed to perform a systemic review and meta-analysis of the effect of Liuzijue breathing exercise on patients with stable COPD.,Published articles from 1970 to December 2020 were conducted using electronic searches.,Two independents reviewers conducted data extraction.,The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies.,A total of 16 eligible trials with 1039 patients with stable COPD were identified.,Compared with control group, the pool meta-analysis of LQG showed a significant improvement in forced expiratory volume in one second (FEV1) (MD = −0.16, 95% CI [0.09, 0.23], P < .00001), FEV1% (MD = 9.71, 95% CI [8.44, 10.98], P < .00001), the ratio of forced expiratory volume to forced vital capacity in the first second (FEV1/FVC [%]) (MD = 4.81, 95% CI [2.12, 7.51], P = .0005), 6 minutes walking distance (6MWD) (MD = 21.89, 95% CI [14.67, 29.11], P < .00001), health-related quality of life (SMD = −0.84, 95% CI [−1.12,-0.55], P < .00001) and modified medical research council dyspnea scale (mMRC) (MD = −0.73, 95% CI [−0.96, −0.50], P < .00001).,The observed effect was more pronounced for short term and medium-term duration interventions of study.,It also showed improvements in the secondary outcome measures by LQG.,In this systematic review and meta-analysis, LQG can improve lung ventilation function, exercise endurance and health-related quality of life of patients with stable COPD.,This study is a systematic review and it does not involve harming to the rights of participants.,Ethical approval will not be require for this study.,The research results may be published in a peer-reviewed journals. | Patients with chronic obstructive pulmonary disease (COPD) fall frequently, although the risk of falls may seem less important than the respiratory consequences of the disease.,Nevertheless, falls are associated to increased mortality, decreased independence and physical activity levels, and worsening of quality of life.,The aims of this systematic review was to evaluate information in the literature with regard to whether impaired postural control is more prevalent in COPD patients than in healthy age-matched subjects, and to assess the main characteristics these patients present that contribute to impaired postural control.,Five databases were searched with no dates or language limits.,The MEDLINE, PubMed, EMBASE, Web of Science, and PEDro databases were searched using “balance”, “postural control”, and “COPD” as keywords.,The search strategies were oriented and guided by a health science librarian and were performed on March 27, 2014.,The studies included were those that evaluated postural control in COPD patients as their main outcome and scored more than five points on the PEDro scale.,Studies supplied by the database search strategy were assessed independently by two blinded researchers.,A total of 484 manuscripts were found using the “balance in COPD or postural control in COPD” keywords.,Forty-three manuscripts appeared more than once, and 397 did not evaluate postural control in COPD patients as the primary outcome.,Thus, only 14 studies had postural control as their primary outcome.,Our study examiners found only seven studies that had a PEDro score higher than five points.,The examiners’ interrater agreement was 76.4%.,Six of those studies were accomplished with a control group and one study used their patients as their own controls.,The studies were published between 2004 and 2013.,Patients with COPD present postural control impairment when compared with age-matched healthy controls.,Associated factors contributing to impaired postural control were muscle weakness, physical inactivity, elderly age, need for supplemental oxygen, and limited mobility. | 1 |
The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades.,However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up.,We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies.,Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD.,In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association.,22 studies comprising 21,150 participants were included in this analysis.,Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR = 1.34, 95% CI = 1.01-1.78), whereas overweight (RR = 0.47, 95% CI = 0.33-0.68) and obese (RR = 0.59, 95% CI = 0.38-0.91) patients were associated with lower mortality.,We further performed a baseline risk-adjusted analysis and obtained statistically similar results.,Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality.,However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies. | Cardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge.,The factors associated with cTnT elevation in COPD are not known.,From our hospital's database, all patients admitted with COPD exacerbation in 2000-03 were identified. 441 had measurement of cTnT performed.,Levels of cTnT ≥ 0.04 μg/l were considered elevated.,Clinical and historical data were retrieved from patient records, hospital and laboratory databases.,Odds ratios for cTnT elevation were calculated using logistic regression.,120 patients (27%) had elevated cTnT levels.,The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration.,The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20-1.94) for a 5 × 106/ml increase in neutrophils, 1.21 (1.12-1.32) for a 10 μmol/l increase in creatinine, 0.80 (0.69-0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09-1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15-1.82) for a 10 point increase in CIIS.,Multiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD.,The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury. | 1 |
Increased stroke risk among chronic obstructive pulmonary disease patients has not yet been established.,In this study, we conducted a systematic review and meta-analysis to assess stroke risk among chronic obstructive pulmonary disease patients.,PubMed, EMBASE, and the Cochrane Library were systematically searched from database inception until December 31, 2016 to identify longitudinal observational studies that investigated the association between chronic obstructive pulmonary disease and stroke.,Stroke risk was quantified by overall and subgroup analyses, and a pooled hazard ratio was calculated.,Study quality was evaluated using the Newcastle-Ottawa Scale.,Publication bias was assessed using Begg’s rank correlation test.,Eight studies met the inclusion criteria.,In a random-effects model, significantly increased stroke risk was observed among chronic obstructive pulmonary disease patients (hazard ratio, 1.30; 95% confidence interval, 1.18-1.43).,In subgroup analyses stratified by stroke subtype, study quality, and adjustment by socioeconomic status, the association between increased stroke risk and chronic obstructive pulmonary disease patients was robust.,Statistically significant publication bias was not detected.,In summary, chronic obstructive pulmonary disease was found to be associated with increased stroke risk.,Additional prospective studies are required to elucidate the mechanisms underlying the increase in stroke risk and identify effective preventive interventions. | Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD) is complicated by the presence of comorbidities.,The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data.,This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES), 1999-2008.,COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded.,Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment.,Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs.,36.9%), depression (20.6% vs.,12.5%), osteoporosis (16.9% vs.,8.5%), cancer (16.5% vs.,9.9%), coronary heart disease (12.7% vs.,6.1%), congestive heart failure (12.1% vs.,3.9%), and stroke (8.9% vs.,4.6%).,Subjects with COPD were also more likely to report mobility difficulty (55.6% vs.,32.5%), use of >4 prescription medications (51.8% vs.,32.1), dizziness/balance problems (41.1% vs.,23.8%), urinary incontinence (34.9% vs.,27.3%), memory problems (18.5% vs.,8.8%), low glomerular filtration rate (16.2% vs.,10.5%), and visual impairment (14.0% vs.,9.6%).,All reported comparisons have p < 0.05.,Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities.,This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed), a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity. | 1 |
To assess the distribution of high-sensitivity cardiac troponin T (hs-cTnT) concentrations in stable chronic obstructive pulmonary disease (COPD), and whether hs-cTnT is associated with pulmonary function.,Prospectively designed, cross-sectional study.,Outpatient clinic of Norwegian teaching hospital and community-based setting.,Sample of 101 stable COPD patients from the hospital's outpatient clinic and 120 individuals derived from a random general population sample.,Ratio of hs-cTnT in stable COPD patients compared with references from the general population.,Change in ratio of hs-cTnT per unit increase of relevant covariables.,The crude geometric means of circulating hs-cTnT in the cases and the references were 7.75 and 3.01 ng/l, respectively (p <0.001); that is, a relative ratio of 2.57 (95% CI 2.05 to 3.23).,After adjustment for relevant confounders, this ratio was moderately attenuated to 1.65 (1.31-2.08).,In the total study cohort, as well as among stable COPD patients, we found a significant positive association between hs-cTnT and interleukin-6 concentrations (p <0.001) and the presence of pathologic Q waves (p=0.023).,Among stable COPD patients, one quartile increase in forced expiratory volume 1 was associated with a 39% decrease in hs-cTnT and patient category (Global Initiative of Obstructive Lung Disease classification 2011) was positively associated with hs-cTnT (p trend <0.001) after multivariate adjustment.,Stable COPD is independently associated with higher hs-cTnT compared with randomly drawn subjects from the general population.,In patients with stable COPD, higher hs-cTnT seems to be associated with immune activation and the severity of the disease. | 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 |
Little is known about the role of guidelines for the practical management of chronic obstructive pulmonary disease (COPD) by office-based pulmonary specialists.,The aim of this study was to assess their outpatient management in relation to current guideline recommendations for COPD.,A nationwide prospective cross-sectional COPD questionnaire survey in the form of a multiple-choice questionnaire was sent to 1000 office-based respiratory specialists in Germany.,The product-neutral questions focused on routine COPD management and were based on current national and international COPD guideline recommendations being consistent in severity classification and treatment recommendations.,A total of 590 pulmonary specialists (59%) participated in the survey.,Body plethysmography was considered the standard for diagnosis (65.9%), followed by spirometry (32%).,Most respondents were able to cite the correct spirometric criteria for classifying moderate (87%) to very severe COPD (77%).,A quarter of the respondents equated the World Health Organization (WHO) definition of chronic bronchitis with COPD.,Notably, most participants preferred the updated national COPD guidelines (51.4%) to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (40.2%).,Improvement of functional exercise capacity and quality of life were considered the two most relevant treatment goals; whereas impact on mortality was secondary.,Treatment of COPD largely complied with the guidelines.,However, a significant percentage of the pulmonary specialists differed in their assessment of the benefits of various therapeutic measures from evidence-based results.,Referral for pulmonary rehabilitation was uncommon, regardless of the severity of COPD.,The findings of this large national survey suggest that most pulmonary specialists adhere to the current COPD guideline recommendations in daily practice.,However, physicians’ knowledge of guidelines is not sufficient as the sole benchmark when assessing their implementation in day-to-day practice.,Necessary changes in the health care system must include more effective ways to transfer knowledge to clinical practice and to give access to interventions of proven clinical benefit. | Guidelines on COPD diagnosis and management encourage primary care physicians to detect the disease at an early stage and to treat patients according to their condition and needs.,Problems in guideline implementation include difficulties in diagnosis, using spirometry and the disputed role of reversibility testing.,These lead to inaccurate diagnostic registers and inadequacy of administered treatments.,This study represents an audit of COPD diagnosis and management in primary care practices in Devon.,Six hundred and thirty two patients on COPD registers in primary care practices were seen by a visiting Respiratory Specialist Nurse.,Diagnoses were made according to the NICE guidelines.,Reversibility testing was carried out either routinely or based on clinical indication in two sub-samples.,Dyspnoea was assessed.,Data were entered into a novel IT-based software which computed guideline-based treatment recommendations.,Current and recommended treatments were compared.,Five hundred and eighty patients had spirometry.,Diagnoses of COPD were confirmed in 422 patients (73%).,Thirty nine patients were identified as asthma only, 94 had normal spirometry, 23 were restrictive and 2 had a cardiac disorder.,Reversibility testing changed diagnosis of 11% of patients with airflow obstruction, and severity grading in 18%.,Three quarters of patients with COPD had been offered practical help with smoking cessation.,Short and long-acting anticholinergics and long acting beta-2 agonists had been under-prescribed; in 15-18% of patients they were indicated but not received.,Inhaled steroids had been over-prescribed (recommended in 17%; taken by 60%), whereas only 4% of patients with a chronic productive cough were receiving mucolytics.,Pulmonary rehabilitation was not available in some areas and was under-used in other areas.,Diagnostic registers of COPD in primary care contain mistakes leading to inaccurate prevalence estimates and inappropriate treatment decisions.,Use of pre-bronchodilator readings for diagnosis overestimates the prevalence and severity in a significant minority, thus post bronchodilator readings should be used.,Management of stable COPD does often not correspond to guidelines.,The IT system used in this study has the potential to improve diagnosis and management of COPD in primary care. | 1 |
Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary disease (COPD) which carries substantial morbidity and mortality.,We explored the association between emphysema and body height in 726 patients with COPD using computed tomography as the reference diagnostic standard for emphysema.,We applied univariate analysis to look for differences between patients with emphysema and those without, and multivariate logistic regression to identify significant predictors of the risk of emphysema.,As covariates we included age, sex, body height, body mass index, pack-years of smoking, and forced expiratory volume in one second (FEV1) as percent predicted.,The overall prevalence of emphysema was 52%.,Emphysemic patients were significantly taller and thinner than non-emphysemic ones, and featured significantly higher pack-years of smoking and lower FEV1 (P < 0.001).,The prevalence of emphysema rose linearly by 10-cm increase in body height (r2 = 0.96).,In multivariate analysis, the odds of emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one-centimeter increase in body height, and remained unchanged after adjusting for all the potential confounders considered (P < 0.001).,The odds of emphysema were not statistically different between males and females.,In conclusion, body height is a strong, independent risk factor for emphysema in COPD. | Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality.,Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone.,To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach.,Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database.,Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used.,169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2).,20.1% died; mean survival was 115.4 months.,Age (HR = 1.098, 95% Cl = 1.04-1.252) and emphysema score (HR = 1.034, 95% CI = 1.007-1.07) were the only independent predictors of mortality.,Pulmonary artery dimensions were not associated with survival.,An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals.,Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied.,This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted).,This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094-10.412) than either individual component alone.,Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone. | 1 |
The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components.,Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown.,The aim of this study was to assess the cost-utility and budget impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.,A cost-utility study was performed, using an individual-level Markov model.,To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium-olodaterol TOnado trial.,In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium-olodaterol FDC was compared with tiotropium.,Cost-utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis.,The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%).,Both univariate and probabilistic sensitivity analyses were performed.,Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.,As a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY.,Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY.,Results were robust in univariate and probabilistic sensitivity analyses.,Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence.,Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.,Tiotropium-olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds. | Several new fixed-dose combination bronchodilators have been recently launched, and assessing their efficacy relative to each other, and with open dual combinations is desirable.,This network meta-analysis (NMA) assessed the efficacy of umeclidinium and vilanterol (UMEC/VI) with that of available dual bronchodilators in single/separate inhalers.,A systematic literature review identified randomized controlled trials of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years), assessing the efficacy of combination bronchodilators in single or separate inhalers.,Comparative assessment was conducted on change from baseline in trough forced expiratory volume in 1 second (FEV1), St George’s Respiratory Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores, and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian framework.,A systematic literature review identified 77 articles of 26 trials comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus tiotropium (TIO) 18 μg, salmeterol plus TIO, or indacaterol plus TIO, with TIO and placebo as common comparators at 12 weeks and approximately 24 weeks.,The NMA showed that at 24 weeks, efficacy of UMEC/VI was not significantly different compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: −14.2, 42.3]), SGRQ total score (0.18 [−1.28, 1.63]), TDI focal score (−0.30 [−0.73, 0.13]), and rescue medication use (0.02 [−0.27, 0.32]); compared with salmeterol plus TIO on trough FEV1 (67.4 mL [−25.3, 159.4]), SGRQ total score (−0.11 [−1.84, 1.61]), and TDI focal score (0.58 [−0.33, 1.50]); and compared with formoterol plus TIO 18 μg on SGRQ total score (−0.68 [−1.77, 0.39]).,Results at week 12 were consistent with week 24 outcomes.,Due to lack of availability of evidence, no comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks.,UMEC/VI has comparable efficacy to other dual-bronchodilator combinations on available efficacy endpoints. | 1 |
There is a need to increase and maintain physical activity in patients with chronic obstructive pulmonary disease (COPD).,We assessed 12-month efficacy and effectiveness of the Urban Training intervention on physical activity in COPD patients.,This randomised controlled trial (NCT01897298) allocated 407 COPD patients from primary and hospital settings 1:1 to usual care (n=205) or Urban Training (n=202).,Urban Training consisted of a baseline motivational interview, advice to walk on urban trails designed for COPD patients in outdoor public spaces and other optional components for feedback, motivation, information and support (pedometer, calendar, physical activity brochure, website, phone text messages, walking groups and a phone number).,The primary outcome was 12-month change in steps·day−1 measured by accelerometer.,Efficacy analysis (with per-protocol analysis set, n=233 classified as adherent to the assigned intervention) showed adjusted (95% CI) 12-month difference +957 (184-1731) steps·day−1 between Urban Training and usual care.,Effectiveness analysis (with intention-to-treat analysis set, n=280 patients completing the study at 12 months including unwilling and self-reported non-adherent patients) showed no differences between groups.,Leg muscle pain during walks was more frequently reported in Urban Training than usual care, without differences in any of the other adverse events.,Urban Training, combining behavioural strategies with unsupervised outdoor walking, was efficacious in increasing physical activity after 12 months in COPD patients, with few safety concerns.,However, it was ineffective in the full population including unwilling and self-reported non-adherent patients.,Urban Training in COPD increased physical activity after 12 months but not in self-reported non-adherent patientshttp://ow.ly/dc2C30lnAEs | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | Cigarette smoke exposure including biologically active lipopolysaccharide (LPS) in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM) and alveolar epithelial cells leading to production of inflammatory mediators.,This represents a crucial mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Respiratory pathogens are a major cause of exacerbations leading to recurrent cycles of injury and repair.,The interaction between pathogen-associated molecular patterns and the host is mediated by pattern recognition receptors (PRR's).,In the present study we characterized the expression of Toll-like receptor (TLR)- 2, TLR4 and CD14 on human AM compared to autologous monocytes obtained from patients with COPD, healthy smokers and non-smokers.,The study population consisted of 14 COPD patients without evidence for acute exacerbation, 10 healthy smokers and 17 healthy non-smokers stratified according to age.,The expression of TLR2, TLR4 and CD14 surface molecules on human AM compared to autologous monocytes was assessed ex vivo using FACS analysis.,In situ hybridization was performed on bronchoalveolar lavage (BAL) cells by application of the new developed HOPE-fixative.,The expression of TLR2, TLR4 and CD14 on AM from COPD patients, smokers and non-smokers was reduced as compared to autologous monocytes.,Comparing AM we detected a reduced expression of TLR2 in COPD patients and smokers.,In addition TLR2 mRNA and protein expression was increased after LPS stimulation on non-smokers AM in contrast to smokers and COPD patients.,Our data suggest a smoke related change in the phenotype of AM's and the cellular response to microbial stimulation which may be associated with impairment of host defenses in the lower respiratory tract. | 1 |
Exposure to cigarette smoking can increase the risk of cancers and cardiovascular and pulmonary diseases.,However, the underlying mechanisms of how smoking contributes to disease risks are not completely understood.,Epigenome-wide association studies (EWASs), mostly in non-Asian populations, have been conducted to identify smoking-associated methylation alterations at individual probes.,There are few data on regional methylation changes in relation to smoking.,Few data link differential methylation in blood to differential gene expression in lung tissue.,We identified 108 significant (false discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87 significant differentially methylated regions (DMRs) (multiple-testing corrected p < 0.01) in current compared to never smokers from our EWAS of cotinine-validated smoking in blood DNA from a Korean chronic obstructive pulmonary disease cohort (n = 100 including 31 current, 30 former, and 39 never smokers) using Illumina HumanMethylation450 BeadChip.,Of the 108 DMPs (FDR < 0.05), nine CpGs were statistically significant based on Bonferroni correction and 93 were novel including five that mapped to loci previously associated with smoking.,Of the 87 DMRs, 66 were mapped to novel loci.,Methylation correlated with urine cotinine levels in current smokers at six DMPs, with pack-years in current smokers at six DMPs, and with duration of smoking cessation in former smokers at eight DMPs.,Of the 143 genes to which our significant DMPs or DMRs annotated, gene expression levels at 20 genes were associated with pack-years in lung tissue transcriptome data of smokers (Asan Biobank, n = 188).,Our study of differential methylation in Koreans confirmed previous findings from non-Asian populations and revealed novel loci in relation to smoking.,Smoking-related differential methylation in blood is associated with gene expression in lung tissue, an important target of adverse health effects of smoking, supporting the potential functional importance of methylation in smoking-related disease.,The online version of this article (doi:10.1186/s13148-016-0266-6) contains supplementary material, which is available to authorized users. | Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations.,The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract.,The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations.,In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD.,In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes.,This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. | 1 |
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