Evidence is scarce on the relative risk-benefit of inhaled triple therapy, consisting of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist, versus dual ...bronchodilation for chronic obstructive pulmonary disease (COPD). We aimed to compare a single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium (IND/GLY) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment.
This randomised, parallel-group, double-blind, double-dummy study was done at 187 sites across 17 countries. Eligible patients had symptomatic COPD, severe or very severe airflow limitation, at least one moderate or severe exacerbation in the previous year, and were receiving inhaled maintenance medication. After a 2 week run-in period with one inhalation per day of IND/GLY (85 μg/43 μg), patients were randomly assigned (1:1), via an interactive response technology system, to receive 52 weeks of treatment with two inhalations of extrafine BDP/FF/G (87 μg/5 μg/9 μg) twice per day or one inhalation of IND/GLY (85 μg/43 μg) per day. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was the rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment in all randomised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02579850.
Between May, 29 2015, and July 10, 2017, 1532 patients received BDP/FF/G (n=764) or IND/GLY (n=768). Moderate-to-severe exacerbation rates were 0·50 per patient per year (95% CI 0·45–0·57) for BDP/FF/G and 0·59 per patient per year (0·53–0·67) for IND/GLY, giving a rate ratio of 0·848 (0·723–0·995, p=0·043) in favour of BDP/FF/G. Adverse events were reported by 490 (64%) of 764 patients receiving BDP/FF/G and 516 (67%) of 768 patients receiving IND/GLY. Pneumonia occurred in 28 (4%) patients receiving BDP/FF/G versus 27 (4%) patients receiving IND/GLY. One treatment-related serious adverse event occurred in each group: dysuria in a patient receiving BDP/FF/G and atrial fibrillation in a patient receiving IND/GLY.
In patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation history despite maintenance therapy, extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY, without increasing the risk of pneumonia.
Chiesi Farmaceutici.
World No Tobacco Day: what's in it for us? Vestbo, Jørgen; Pisinger, Charlotta
American journal of physiology. Lung cellular and molecular physiology,
05/2020, Letnik:
318, Številka:
5
Journal Article
COPD can be diagnosed early using spirometry, but spirometry use is only recommended in symptomatic smokers, even though early stages of COPD can be asymptomatic. We investigated the prognosis of ...individuals with asymptomatic and symptomatic, undiagnosed COPD in the general population in Denmark.
In this prospective cohort study, we analysed data from 95 288 individuals aged 20-100 years from the Copenhagen General Population Study. 32 518 (34%) of these individuals were regarded as being at high risk for COPD (defined as individuals aged 40 years or older, with cumulative tobacco consumption of ten pack-years or higher, and without self-reported or a previous hospital contact for asthma). COPD was defined as FEV
/forced vital capacity (FVC) of less than 70% and less than the lower limit of normal, and FEV
of less than 80% of the predicted normal value. Individuals were considered undiagnosed if neither a previous COPD hospital contact, nor medical treatment for COPD, was registered. We obtained information on exacerbations and pneumonia from the National Danish Patient Registry and vital status from the National Danish Civil Registration System, and cause of death from the National Danish Causes of Death Registry. We used Cox proportional hazard models to assess risk of exacerbations, pneumonia, deaths due to respiratory causes, and deaths from all causes from 2003 to 2014.
Between Nov 26, 2003, and July 10, 2013, 95 288 individuals were screened and 32 518 (34%) were at high risk of having COPD. 3699 (11%) of these participants met the COPD criteria and 2903 (78%) were undiagnosed, of whom 2052 (71%) were symptomatic. During a median follow-up of 6·1 years (IQR 4·9), we recorded 800 exacerbations, 2038 cases of pneumonia, and 2789 deaths in the 32 518 individuals at high risk of having COPD, including 152 deaths due to respiratory disease. Compared with individuals without COPD, the age and sex adjusted hazard ratio (HR) was 5·0 (95% CI 2·8-8·9) for exacerbations, 1·7 (1·3-2·2) for pneumonia, 0·7 (0·2-3·0) for death from respiratory causes, and 1·3 (1·1-1·6) for death from all causes in individuals with undiagnosed, asymptomatic COPD. Corresponding HRs were 15·5 (11·0-21·8) for exacerbations, 2·8 (2·4-3·3) for pneumonia, 4·3 (2·8-6·7) for death from respiratory causes, and 2·0 (1·8-2·3) for death from all causes in individuals with undiagnosed, symptomatic COPD.
Individuals with undiagnosed, symptomatic COPD had an increased risk of exacerbations, pneumonia, and death. Individuals with undiagnosed, asymptomatic COPD had an increased risk of exacerbations and pneumonia. These findings suggest that better initiatives for early diagnosis and treatment of COPD are needed.
The Danish Lung Association, the Danish Cancer Society, Herlev and Gentofte Hospital, Copenhagen University Hospital, and University of Copenhagen.
Long-term prognosis of patients with characteristics of both chronic obstructive pulmonary disease (COPD) and asthma, named asthma-COPD overlap, is poorly described. We investigated the long-term ...prognosis of individuals with different types of chronic airway disease, with a special focus on individuals with asthma-COPD overlap.
We assigned participants from the Copenhagen City Heart Study into six subgroups: healthy never-smokers, ever-smokers without asthma and COPD, those with asthma with low cumulated smoking exposure and no airflow limitation, those with COPD, those with asthma-COPD overlap with asthma onset before the age of 40 years, and those with asthma-COPD overlap with asthma onset after the age of 40 years. We defined asthma-COPD overlap as current self-reported asthma and a postbronchodilatatory forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio of less than 0·7, without any restrictions regarding smoking. We investigated the course of FEV1 decline for 18 years and risk of admission to hospital due to exacerbations or pneumonias and respiratory and all-cause mortality for 22 years. We analysed FEV1 decline in the six groups using a linear mixed-effects model.
We included 8382 participants from the Copenhagen City Heart Study in our study: 2199 never-smokers, 5435 ever-smokers, 158 with asthma, 320 with COPD, 68 with asthma-COPD overlap with early-onset asthma, and 202 with asthma-COPD overlap with late-onset asthma. The multivariable-adjusted decline in FEV1 in asthma-COPD overlap with early-onset asthma was 27·3 mL (standard error 5·0) per year, which did not differ significantly from the decline of 20·9 mL (1·2) per year in healthy never-smokers (p=0·19). FEV1 decline in individuals with asthma-COPD overlap with late-onset asthma was 49·6 mL (3·0) per year, higher than the decline in asthma-COPD overlap with early-onset asthma (p=0·0001), the decline of 39·5 mL (2·5) per year in COPD (p=0·003), and the decline in healthy never-smokers (p<0·0001). Hazard ratios for hospital admissions due to exacerbations of asthma or COPD were 39·48 (95% CI 25·93-60·11) in asthma-COPD overlap with early-onset asthma, 83·47 (61·67-112·98) in asthma-COPD overlap with late-onset asthma, 23·80 (17·43-33·50) in COPD, and 14·74 (10·06-21·59) in asthma compared with never-smokers without lung disease (all p<0·0001). Life expectancy was 9·3 years (5·4-13·1) shorter in participants with asthma-COPD overlap with early-onset asthma, 12·8 years (11·1-14·6) shorter in those with asthma-COPD overlap with late-onset asthma, 10·1 years (8·6-11·5) shorter in those with COPD (all p<0·0001), and 3·3 years (1·0-5·5) shorter in those with asthma (p=0·004) than in healthy never-smokers.
Prognosis of individuals with asthma-COPD overlap is poor and seems to be affected by the age of recognition of asthma, being worst in those with late asthma onset (after 40 years of age). Such patients should be followed up closely to prevent fast lung function decline and exacerbations.
Capital Region of Copenhagen, Danish Heart Foundation, Danish Lung Foundation, Velux Foundation, AstraZeneca.
The article discusses the use of simple diagnostic technique like spirometry for the early detection of COPD. The ratio of FEV1: FVC, postbronchodilator is considered to be a better diagnostic ...technique as it measures the rate of airflow obstruction.
We tested whether emphysema progression accompanies enhanced tissue loss in other body compartments in 1817 patients from the ECLIPSE chronic obstructive pulmonary disease (COPD) cohort.Clinical and ...selected systemic biomarker measurements were compared in subjects grouped by quantitative tomography scan emphysema quartiles using the percentage of low attenuation area (LAA%). Lowest and highest quartile patients had amino-acid metabolomic profiles. We related LAA% to 3 years decline in lung function (forced expiratory volume in 1 s (FEV
)), body mass index (BMI), fat-free mass index (FFMI) and exacerbations, hospitalisations and mortality rates.Participants with more baseline emphysema had lower FEV
, BMI and FFMI, worse functional capacity, and less cardiovascular disease but more osteoporosis. Systemic C-reactive protein and interleukin-6 levels were similar among groups, but club cell protein 16 was higher and interleukin-8, surfactant protein D and soluble receptor for advanced glycation end product were lower with more emphysema. Metabolomics differed between extreme emphysema quartiles. Patients with more emphysema had accelerated FEV
, BMI and FFMI decline and more exacerbations, hospitalisations and mortality.COPD patients with more emphysema undergo excessive loss of pulmonary and extrapulmonary tissue, which is probably related to abnormal tissue maintenance. Because of worse clinical outcomes, we propose this subgroup be named the multi-organ loss of tissue (MOLT) COPD phenotype.
Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities.
To test the hypothesis that elevated ...levels of three inflammatory biomarkers are associated with increased risk of comorbidities in COPD.
We examined 8,656 patients with COPD from two large Danish population studies and during a median 5 years' follow-up recorded hospital admissions due to major comorbidities as endpoints.
We measured baseline C-reactive protein (CRP), fibrinogen, and leukocyte count, and recorded admissions due to ischemic heart disease, myocardial infarction, heart failure, type II diabetes, lung cancer, pneumonia, pulmonary embolism, hip fracture, and depression for all participants. Multifactorially adjusted risk of ischemic heart disease was increased by a factor of 2.19 (95% confidence interval, 1.48-3.23) in individuals with three biomarkers elevated (CRP > 3 mg/L, fibrinogen > 14 μmol/L, and leukocyte count > 9 × 10(9)/L) versus individuals with all three biomarkers at or below these limits. Corresponding hazard ratios were 2.32 (1.34-4.04) for myocardial infarction, 2.63 (1.71-4.04) for heart failure, 3.54 (2.03-6.19) for diabetes, 4.00 (2.12-7.54) for lung cancer, and 2.71 (2.03-3.63) for pneumonia. There were no consistent differences in risk of pulmonary embolism, hip fracture, or depression as a function of these three biomarkers.
Simultaneously elevated levels of CRP, fibrinogen, and leukocyte count are associated with a two- to fourfold increased risk of major comorbidities in COPD. These biomarkers may be an additional tool for clinicians to conduct stratified management of comorbidities in COPD.
Summary Study objectives The aim of this analysis was to understand the implications of the GOLD 2011 multidimensional system for the assessment and management of COPD, using data from a real-world ...observational study. Methods Data were drawn from the Adelphi Respiratory Disease Specific Programme, a cross-sectional survey of consulting patients in five European countries and in the US undertaken between June and September 2011. Patients were classified using both the GOLD 2010 and revised GOLD 2011 criteria, and profiled with regards to demographics, disease characteristics and treatment patterns. Results Information on 3813 COPD patients was collected. Disease characteristics showed a general tendency to worsen in parallel with worsening of symptoms. When comparing dual versus single risk criteria, the inclusion of exacerbation history resulted in an increase in the number of patients in high risk groups. The highest proportions of patients receiving inhaled corticosteroids (ICS) were in group D. However, a considerable proportion of patients in low risk groups were receiving ICS/long-acting β2 agonists. Conclusions Our analysis confirmed the relationship between higher symptomatic burden, increased airflow limitation and exacerbation, and further illustrated the importance of including exacerbation history in the assessment of COPD to identify patients at high risk. As based on data from current clinical practice, this study also highlighted the frequent and potentially inappropriate use of ICS and bronchodilators in patients at low risk of experiencing exacerbations.
Beta-blockers in COPD: time for reappraisal Lipworth, Brian; Wedzicha, Jadwiga; Devereux, Graham ...
The European respiratory journal,
09/2016, Letnik:
48, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The combined effects on the heart of smoking and hypoxaemia may contribute to an increased cardiovascular burden in chronic obstructive pulmonary disease (COPD). The use of beta-blockers in COPD has ...been proposed because of their known cardioprotective effects as well as reducing heart rate and improving systolic function. Despite the proven cardiac benefits of beta-blockers post-myocardial infarction and in heart failure they remain underused due to concerns regarding potential bronchoconstriction, even with cardioselective drugs. Initiating treatment with beta-blockers requires dose titration and monitoring over a period of weeks, and beta-blockers may be less well tolerated in older patients with COPD who have other comorbidities. Medium-term prospective placebo-controlled safety studies in COPD are warranted to reassure prescribers regarding the pulmonary and cardiac tolerability of beta-blockers as well as evaluating their potential interaction with concomitant inhaled long-acting bronchodilator therapy. Several retrospective observational studies have shown impressive reductions in mortality and exacerbations conferred by beta-blockers in COPD. However, this requires confirmation from long-term prospective placebo-controlled randomised controlled trials. The real challenge is to establish whether beta-blockers confer benefits on mortality and exacerbations in all patients with COPD, including those with silent cardiovascular disease where the situation is less clear.
Abstract
Background
Advanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication.
Aspergillus
sensitisation may ...worsen symptoms in COPD.
Methods
We identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC < 70% and FEV1 < 80%) using standardised criteria in multiple countries, to re-estimate the prevalence of COPD. Hospitalised COPD patients develop IA in 1.3–3.9%, based on positive cultures of
Aspergillus
spp. and radiological findings. Given limited data on per-patient annual hospitalisation rates, we assumed a conservative 10.5% estimate. Annual IA mortality in COPD was estimated using the literature rates of 43–72%. A separate literature search assessed the impact of
Aspergillus
sensitisation on severity of COPD (by FEV1).
Results
We re-estimated the global prevalence of COPD GOLD stages II-IV at 552,300,599 people (7.39% of the population) with 339,206,893 (8.58%) in Asia, 85,278,783 (8.52%) in the Americas, 64,298,051 (5.37%) in Africa, 59,484,329 (7.77%) in Europe and 4,032,543 (10.86%) in Oceania. An estimated 57,991,563 (10.5%) people with COPD are admitted to hospital annually and of these 753,073 (1.3%) – 2,272,322 (3.9%) develop IA and 540,451–977,082 deaths are predicted annually.
Aspergillus
sensitisation prevalence in COPD was 13.6% (7.0–18.3%) and not related to lower predicted FEV1% (
P
> 0.05).
Conclusions
The prevalence of COPD is much higher than previously estimated. Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths. Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality.
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