The short-term benefits of inhaled corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are greater in patients with evidence of eosinophilic airway inflammation. We ...investigated whether blood eosinophil count is a useful biomarker of the long-term effect of the inhaled corticosteroid fluticasone furoate on exacerbation frequency.
We did a post-hoc analysis of data from two replicate, randomised, double-blind trials of 12 months' duration (Sept 25, 2009 to Oct 21, 2011 and Oct 17, 2011) in which once a day vilanterol 25 μg was compared with 25 μg vilanterol plus 50 μg, 100 μg, or 200 μg fluticasone furoate in patients with moderate-to-severe COPD and a history of one or more exacerbation in the previous year. We compared exacerbation rates according to two baseline eosinophil cell count strata (<2% and ≥2%), and according to four baseline percentage groupings. We also assessed lung function and incidence of pneumonia per strata in treatment groups.
We included 3177 patients in the analyses, with 2083 patients (66%) having an eosinophil count of 2% or higher at study entry. Across all doses of inhaled corticosteroids, fluticasone furoate and vilanterol reduced exacerbations by 29% compared with vilanterol alone (mean 0·91 vs 1·28 exacerbations per patient per year; p<0·0001) in patients with eosinophil counts of 2% or higher, and by 10% (0·79 vs 0·89; p=0·2827) in patients with eosinophil counts lower than 2%. Reductions in exacerbations with fluticasone furoate and vilanterol, compared with vilanterol alone, were 24% in patients with baseline eosinophil counts of ≥2-<4%, 32% for those with counts of 4-<6%, and 42% for those with eosinophil counts of ≥6%. In patients treated with vilanterol alone, exacerbation rates increased progressively with increasing eosinophil count percentage category. Improvement in trough forced expiratory volume in 1 s (FEV1) and the increased risk of pneumonia with fluticasone furoate and vilanterol compared with vilanterol alone were not associated with eosinophil count.
Blood eosinophil count is a promising biomarker of response to inhaled corticosteroids in patients with COPD. Blood eosinophil count could potentially be used to stratify patients for different exacerbation rate reduction strategies.
GlaxoSmithKline (study ID 201595).
Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung associated with progressive airflow limitation and punctuated by episodes of acute exacerbation. There is growing ...recognition that the inflammatory state associated with COPD is not confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs. Epidemiologic and mechanistic studies indicate that COPD is associated with a high frequency of coronary artery disease, congestive heart failure and cardiac arrhythmias, independent of shared risk factors. Possible pathways include complex interrelationships between chronic low-grade systemic inflammation and oxidative stress as well as shared risk factors such as age, cigarette smoking, and environmental pollutants. In this review, we provide an overview of the epidemiologic data linking COPD with cardiovascular disease, comment on the interrelationships among COPD, inflammation, and cardiovascular disease, and highlight diagnostic and therapeutic challenges.
...analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study shows that in 2019, pollution from ambient particulate matter and occupational exposure to particulate matter, gases, ...and fumes accounted for 36·3% of the attributable risk for COPD compared with 46% of cases attributable to smoking.2–4 In addition, since 1990, the risk for COPD attributable to smoking has declined globally while that related to ambient and occupational exposures has continued to increase, particularly in low-income and lower-middle-income countries.3,4 Although never-smokers with COPD tend to have milder respiratory symptoms, less emphysema, and less lung function impairment, exacerbations can still be frequent.2 One objective of the Commission was to highlight the changing epidemiology of COPD risk factors, not to detract from efforts to control tobacco and support smoking cessation, but to raise awareness of what might be the next drivers of the COPD epidemic. MTD reports grants or contracts from the American Lung Association, the US Department of Defense, and the US National Institutes of Health; consulting fees from AstraZeneca, GlaxoSmithKline, Novartis, Pulmonx, and Teva; and support for attending meetings from Pulmonx. DS reports a grant from the Swiss National Foundation (SNF 320030_189280); unrestricted grants from Curetis, AstraZeneca, and Boston Scientifics (paid to their institution); honoraria for participation in data safety monitoring or advisory boards or talks for CSL Behring, Berlin-Chemie Menarini, Novartis, GlaxoSmithKline, AstraZeneca, Vifor, Merck, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, and Chiesi; and is the current Global Initiative for Chronic Obstructive Lung Disease representative for Switzerland, the immediate past Education Council Chair of the European Respiratory Society, and current President of the Education Committee of the Swiss Respiratory Society.
Mucus stasis in chronic obstructive pulmonary disease (COPD) is a significant contributor to morbidity and mortality. Potentiators of cystic fibrosis transmembrane conductance regulator (CFTR) ...activity pharmacologically enhance CFTR function; ivacaftor is one such agent approved to treat CF patients with the G551D-CFTR gating mutation. CFTR potentiators may also be useful for other diseases of mucus stasis, including COPD.
In primary human bronchial epithelial cells, exposure to cigarette smoke extract diminished CFTR-mediated anion transport (65.8±0.2% of control, P<0.005) and mucociliary transport (0.17±0.05 µm/sec vs. 2.4±0.47 µm/sec control, P<0.05) by reducing airway surface liquid depth (7.3±0.6 µm vs. 13.0±0.6 µm control, P<0.005) and augmenting mucus expression (by 64%, P<0.05) without altering transepithelial resistance. Smokers with or without COPD had reduced CFTR activity measured by nasal potential difference compared to age-matched non-smokers (-6.3±1.4 and -8.0±2.0 mV, respectively vs. -15.2±2.7 mV control, each P<0.005, n = 12-14/group); this CFTR decrement was associated with symptoms of chronic bronchitis as measured by the Breathlessness Cough and Sputum Score (r = 0.30, P<0.05) despite controlling for smoking (r = 0.31, P<0.05). Ivacaftor activated CFTR-dependent chloride transport in non-CF epithelia and ameliorated the functional CFTR defect induced by smoke to 185±36% of non-CF control (P<0.05), thereby increasing airway surface liquid (from 7.3±0.6 µm to 10.1±0.4 µm, P<0.005) and mucociliary transport (from 0.27±0.11 µm/s to 2.7±0.28 µm/s, P<0.005).
Cigarette smoking reduces CFTR activity and is causally related to reduced mucus transport in smokers due to inhibition of CFTR dependent fluid transport. These effects are reversible by the CFTR potentiator ivacaftor, representing a potential therapeutic strategy to augment mucociliary clearance in patients with smoking related lung disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) are both significant burdens on the healthcare system and often coexist. Mechanistic links between the two conditions and ...their clinical impact are increasingly understood.
Recent studies demonstrate multiple mechanisms by which the pathobiology of COPD may have negative effects on the cardiovascular system. These include extrapulmonary consequences of the COPD inflammatory state, cardiac autonomic dysfunction, which has been recently implicated in worsening respiratory symptoms and exacerbation risk, and mechanical effects of lung hyperinflation on left ventricular diastolic function.Clinical studies have consistently shown a high prevalence of CVD in COPD patients and worsened outcomes (and vice versa ). Exacerbations of COPD have also been demonstrated to dramatically increase the risk of cardiovascular events. While some safety concerns exist, medications for COPD and cardiovascular disease should be used in accordance with respective guidelines. However, real-world data show suboptimal management for patients with COPD and CVD.
COPD and cardiovascular disease have complicated interrelationships. Further mechanistic studies may lead to defining better targets for interventions. Education for medical professionals and implementation of novel screening protocols should be encouraged to fill in the gaps in clinical care for these patients.
Background COPD is associated with significant morbidity primarily driven by acute exacerbations. Relative pulmonary artery (PA) enlargement, defined as a PA to ascending aorta (A) diameter ratio ...greater than one (PA:A > 1) identifies patients at increased risk for exacerbations. However, little is known about the correlation between PA:A, echocardiography, and invasive hemodynamics in COPD. Methods A retrospective observational study of patients with severe COPD being evaluated for lung transplantation at a single center between 2007 and 2011 was conducted. Clinical characteristics, CT scans, echocardiograms, and right-sided heart catheterizations were reviewed. The PA diameter at the bifurcation and A diameter from the same CT image were measured. Linear and logistic regression were used to examine the relationships between PA:A ratio by CT scan and PA systolic pressure (PASP) by echocardiogram with invasive hemodynamics. Receiver operating characteristic analysis assessed the usefulness of the PA:A ratio and PASP in predicting resting pulmonary hypertension (PH) (mean pulmonary artery pressure mPAP > 25 mm Hg). Results Sixty patients with a mean predicted FEV1 of 27% ± 12% were evaluated. CT scan-measured PA:A correlated linearly with mPAP after adjustment for multiple covariates ( r = 0.30, P = .03), a finding not observed with PASP. In a multivariate logistic model, mPAP was independently associated with PA:A > 1 (OR, 1.44; 95% CI, 1.02-2.04; P = .04). PA:A > 1 was 73% sensitive and 84% specific for identifying patients with resting PH (area under the curve, 0.83; 95% CI, 0.72-0.93; P < .001), whereas PASP was not useful. Conclusions A PA:A ratio > 1 on CT scan outperforms echocardiography for diagnosing resting PH in patients with severe COPD.
Dransfield and Singh discuss their study on the relationships between pneumonia risk and inhaled corticosteroids (ICS) use, blood eosinophil counts, and chronic bacterial infection (CBI) of the ...airways (assessed using sputum samples) from a cohort of 201 patients with chronic obstructive pulmonary disease (COPD). An important novel aspect of this study is that bacterial infection data is included in the analysis of pneumonia risk. Bacterial isolates were detected in 42.3% of patients on at least one occasion, whereas CBI was present in 22.4%. The results demonstrate complex interactions between pneumonia risk factors, further highlighted in the network analysis model.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk.
Determine whether ...AECOPD events are associated with increased risk of subsequent CVD.
We performed a secondary cohort analysis of the SUMMIT (Study to Understand Mortality and Morbidity) trial, a convenience sample of current/former smokers with moderate COPD from 1,368 centers in 43 countries. All had CVD or increased CVD risk. AECOPD was defined as an increase in respiratory symptoms requiring treatment with antibiotics, systemic corticosteroids, and/or hospitalization. CVD events were a composite outcome of cardiovascular death, myocardial infarction, stroke, unstable angina, and transient ischemic attack. All CVD events were adjudicated. Cox proportional hazards models compared the hazard for a CVD event before AECOPD versus after AECOPD.
Among 16,485 participants in SUMMIT, 4,704 participants had at least one AECOPD and 688 had at least one CVD event. The hazard ratio (HR) for CVD events after AECOPD was increased, particularly in the first 30 days after AECOPD (HR, 3.8; 95% confidence interval, 2.7-5.5) and was elevated up to 1 year after AECOPD. The 30-day HR after hospitalized AECOPD was more than twofold greater (HR, 9.9; 95% confidence interval, 6.6-14.9).
In patients with COPD with CVD or risk factors for CVD, exacerbations confer an increased risk of subsequent CVD events, especially in hospitalized patients and within the first 30 days after exacerbation. Patients and clinicians should have heightened vigilance for early CVD events after AECOPD. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676).
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