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Deutsches Arzteblatt International Jun 2023Chronic obstructive pulmonary disease (COPD) is the third most common cause of death around the world. The affected patients suffer not only from impaired lung function,... (Review)
Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is the third most common cause of death around the world. The affected patients suffer not only from impaired lung function, but also from a wide variety of comorbidities. Their cardiac comorbidities, in particular, lead to increased mortality.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad.
RESULTS
The usual diagnostic criteria for COPD are a post-bronchodilator FEV1/FVC quotient below the fixed threshold of 0.7, or, preferably, below the lower limit of normal (LLN) according to the GLI reference values for the avoidance of over- and underdiagnosis. The overall prognosis is markedly affected by comorbidities of the lung itself and those that involve other organs; in particular, many persons with COPD die of heart disease. The potential presence of heart disease must be borne in mind in the evaluation of patients with COPD, as lung disease can impair the detection of heart disease.
CONCLUSION
As patients with COPD are often multimorbid, the early diagnosis and adequate treatment not only of their lung disease, but also of their extrapulmonary comorbidities are very important. Well-established diagnostic instruments and well-tested treatments are available and are described in detail in the guidelines concerning the comorbidities. Preliminary observations suggest that more attention should be paid to the potential positive effects of treating comorbidities on the lung disease itself, and vice versa.
Topics: Humans; Vital Capacity; Forced Expiratory Volume; Pulmonary Disease, Chronic Obstructive; Lung; Heart Diseases
PubMed: 36794439
DOI: 10.3238/arztebl.m2023.027 -
American Journal of Respiratory and... Aug 2023Ensifentrine is a novel, selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and antiinflammatory effects. Replicate phase III trials of... (Randomized Controlled Trial)
Randomized Controlled Trial
Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials).
UNLABELLED
Ensifentrine is a novel, selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and antiinflammatory effects. Replicate phase III trials of nebulized ensifentrine were conducted (ENHANCE-1 and ENHANCE-2) to assess these effects in patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of ensifentrine compared with placebo for lung function, symptoms, quality of life, and exacerbations in patients with COPD. These phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled trials were conducted between September 2020 and December 2022 at 250 research centers and pulmonology practices in 17 countries. Patients aged 40-80 years with moderate to severe symptomatic COPD were enrolled. Totals of 760 (ENHANCE-1) and 789 (ENHANCE-2) patients were randomized and treated, with 69% and 55% receiving concomitant long-acting muscarinic antagonists or long-acting β-agonists, respectively. Post-bronchodilator FEV percentage predicted values were 52% and 51% of predicted normal. Ensifentrine treatment significantly improved average FEV area under the curve at 0-12 hours versus placebo (ENHANCE-1, 87 ml [95% confidence interval, 55, 119]; ENHANCE-2, 94 ml [65, 124]; both < 0.001). Ensifentrine treatment significantly improved symptoms (Evaluating Respiratory Symptoms) and quality of life (St. George's Respiratory Questionnaire) versus placebo at Week 24 in ENHANCE-1 but not in ENHANCE-2. Ensifentrine treatment reduced the rate of moderate or severe exacerbations versus placebo over 24 weeks (ENHANCE-1, rate ratio, 0.64 [0.40, 1.00]; = 0.050; ENHANCE-2, rate ratio, 0.57 [0.38, 0.87]; = 0.009) and increased time to first exacerbation (ENHANCE-1, hazard ratio, 0.62 [0.39, 0.97]; = 0.038; ENHANCE-2, hazard ratio, 0.58 [0.38, 0.87]; = 0.009). Adverse event rates were similar to those for placebo. Ensifentrine significantly improved lung function in both trials, with results supporting exacerbation rate and risk reduction in a broad COPD population and in addition to other classes of maintenance therapies. Clinical trial registered with www.
CLINICALTRIALS
gov and EudraCT (ENHANCE-1, www.
CLINICALTRIALS
gov identifier NCT04535986, EudraCT identifier 2020-002086-34; ENHANCE-2, www.
CLINICALTRIALS
gov identifier NCT04542057, EudraCT identifier 2020-002069-32).
Topics: Humans; Bronchodilator Agents; Double-Blind Method; Forced Expiratory Volume; Phosphoric Diester Hydrolases; Pulmonary Disease, Chronic Obstructive; Quality of Life; Adult; Middle Aged; Aged; Aged, 80 and over
PubMed: 37364283
DOI: 10.1164/rccm.202306-0944OC -
JAMA Jun 2023Airway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients... (Observational Study)
Observational Study
IMPORTANCE
Airway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients with COPD is unknown.
OBJECTIVE
To determine whether airway mucus plugs identified on chest computed tomography (CT) were associated with increased all-cause mortality.
DESIGN, SETTING, AND PARTICIPANTS
Observational retrospective analysis of prospectively collected data of patients with a diagnosis of COPD in the Genetic Epidemiology of COPD cohort. Participants were non-Hispanic Black or White individuals, aged 45 to 80 years, who smoked at least 10 pack-years. Participants were enrolled at 21 centers across the US between November 2007 and April 2011 and were followed up through August 31, 2022.
EXPOSURES
Mucus plugs that completely occluded airways on chest CT scans, identified in medium- to large-sized airways (ie, approximately 2- to 10-mm lumen diameter) and categorized as affecting 0, 1 to 2, or 3 or more lung segments.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality, assessed with proportional hazard regression analysis. Models were adjusted for age, sex, race and ethnicity, body mass index, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease.
RESULTS
Among the 4483 participants with COPD, 4363 were included in the primary analysis (median age, 63 years [IQR, 57-70 years]; 44% were women). A total of 2585 (59.3%), 953 (21.8%), and 825 (18.9%) participants had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. During a median 9.5-year follow-up, 1769 participants (40.6%) died. The mortality rates were 34.0% (95% CI, 32.2%-35.8%), 46.7% (95% CI, 43.5%-49.9%), and 54.1% (95% CI, 50.7%-57.4%) in participants who had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. The presence of mucus plugs in 1 to 2 vs 0 and 3 or more vs 0 lung segments was associated with an adjusted hazard ratio of death of 1.15 (95% CI, 1.02-1.29) and 1.24 (95% CI, 1.10-1.41), respectively.
CONCLUSIONS AND RELEVANCE
In participants with COPD, the presence of mucus plugs that obstructed medium- to large-sized airways was associated with higher all-cause mortality compared with patients without mucus plugging on chest CT scans.
Topics: Female; Humans; Male; Middle Aged; Airway Obstruction; Forced Expiratory Volume; Lung; Mucus; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Retrospective Studies; Tomography, X-Ray Computed; Aged; Aged, 80 and over; Cigarette Smoking
PubMed: 37210745
DOI: 10.1001/jama.2023.2065