In patients with chronic obstructive pulmonary disease (COPD), lung function decreases rapidly. Analysis of data from a large observational study of COPD showed that the rate of such loss is highly ...variable, and current smoking was associated with a rapid loss.
Since the seminal studY by Fletcher et al. in the 1970s,
1
,
2
it has been widely accepted that chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in forced expiratory volume in 1 second (FEV
1
). However, surprisingly few longitudinal studies of patient cohorts have provided detailed data regarding the rate of decline in FEV
1
,
3
–
8
and none of these studies have related changes in FEV
1
to specific subgroups of patients with COPD or to levels of systemic biomarkers. We used data from a large, observational, 3-year study that included detailed assessments of patients . . .
Chronic obstructive pulmonary disease (COPD) can develop not only through a lung function trajectory dominated by an accelerated decline of FEV
from normal maximally attained FEV
in early adulthood ...(normal maximally attained FEV
trajectory) but also through a trajectory with FEV
below normal in early adulthood (low maximally attained FEV
trajectory).
To test whether the long-term risk of exacerbations and mortality differs between these two subtypes of COPD.
The cohort included 1,170 young adults enrolled in the Copenhagen City Heart Study during the 1970s and 1980s. In 2001-2003, which served as the baseline for the present analyses, 79 participants had developed COPD through normal maximally attained FEV
trajectory, 65 had developed COPD through low maximally attained FEV
trajectory, and 1,026 did not have COPD.
From 2001 until 2018, we observed 139 severe exacerbations of COPD and 215 deaths, of which 55 were due to nonmalignant respiratory disease. In Cox models, there was no difference with regard to risk of severe exacerbations between the two trajectories, but individuals with normal maximally attained FEV
had an increased risk of nonmalignant respiratory disease mortality (using inverse probability of censoring weighting with adjusted hazard ratio HR, 6.20; 95% confidence interval CI, 2.09-18.37;
= 0.001) and all-cause mortality (adjusted HR, 1.93; 95% CI, 1.14-3.26;
= 0.01) compared with individuals with low maximally attained FEV
.
COPD developed through normal maximally attained FEV
trajectory is associated with an increased risk of respiratory and all-cause mortality compared with COPD developed through low maximally attained FEV
trajectory.
IMPORTANCE Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients. OBJECTIVE To test the hypothesis that ...elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study examining 61 650 participants with spirometry measurements from the Copenhagen City Heart Study (2001-2003) and the Copenhagen General Population Study (2003-2008). Of these, 6574 had COPD, defined as a ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity below 0.7. MAIN OUTCOMES AND MEASURES Baseline levels of C-reactive protein (CRP) and fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations. Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD. Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L, 14 μmol/L, and 9 ×109/L, respectively. RESULTS During follow-up, 3083 exacerbations were recorded (mean, 0.5/participant). In the first year of follow-up, multivariable-adjusted odds ratios for having frequent exacerbations were 1.2 (95% CI, 0.7-2.2; 17 events/1000 person-years) for individuals with 1 high biomarker, 1.7 (95% CI, 0.9-3.2; 32 events/1000 person-years) for individuals with 2 high biomarkers, and 3.7 (95% CI, 1.9-7.4; 81 events/1000 person-years) for individuals with 3 high biomarkers compared with individuals who had no elevated biomarkers (9 events/1000 person-years; trend: P = 2 × 10−5). Corresponding hazard ratios using maximum follow-up time were 1.4 (95% CI, 1.1-1.8), 1.6 (95% CI, 1.3-2.2), and 2.5 (95% CI, 1.8-3.4), respectively (trend: P = 1 × 10−8). The addition of inflammatory biomarkers to a basic model including age, sex, FEV1 percent predicted, smoking, use of any inhaled medication, body mass index, history of previous exacerbations, and time since most recent prior exacerbation improved the C statistics from 0.71 to 0.73 (comparison: P = 9 × 10−5). Relative risks were consistent in those with milder COPD, in those with no history of frequent exacerbations, and in the 2 studies separately. The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers (vs no high biomarkers) were 62% (vs 24%) for those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades C-D (n = 558), 98% (vs 64%) in those with a history of frequent exacerbations (n = 127), and 52% (vs 15%) for those with GOLD grades 3-4 (n = 465). CONCLUSIONS AND RELEVANCE Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations, even in those with milder COPD and in those without previous exacerbations. Further investigation is needed to determine the clinical value of these biomarkers for risk stratification.
It had been thought that most people with chronic obstructive pulmonary disease had normal lung function in mid-adult life and then lost it rapidly. In this study, many people with COPD already had ...low lung function in mid-adult life, before COPD developed.
Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death worldwide.
1
Since the research by Fletcher and colleagues in the 1970s,
2
,
3
the prevailing paradigm of COPD pathogenesis has been that, in susceptible persons, exposure to particulate matter — especially tobacco smoke — leads to clinical disease through acceleration of the age-related decline in lung function, as assessed by the forced expiratory volume in 1 second (FEV
1
). Subsequent population studies supported this paradigm and led to therapeutic trials aimed at reducing the rapid decline in FEV
1
.
4
–
11
Surprisingly, the observed declines in FEV . . .
This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory ...Society and the American Thoracic Society.Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable (benefits) and undesirable consequences (burden in the form of adverse effects and cost), quality of evidence, feasibility, and acceptability of various interventions, the Task Force made recommendations for mucolytic, long-acting muscarinic antagonist, phosphodiesterase-4 inhibitor (roflumilast) and macrolide therapy, as well as a conditional recommendation against fluoroquinolone therapy. All of the recommendations were conditional, except for a strong recommendation for the use of a long-acting antimuscarinic agent
a long-acting β
-adrenergic, indicating that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.The guideline summarises the evidence and provides recommendations for pharmacological therapy for the prevention of COPD exacerbations.
With increasing climate change, all sources of greenhouse gases must be considered. Hydrofluorocarbon (HFC) propellants are used in all pressurised metered dose inhalers (pMDIs) and, although they ...are not as ozone-depleting as the earlier chlorofluorocarbons (CFCs), they are potent greenhouse gases and there is a general ask for reduction in their use 1. In this respect, respiratory doctors indirectly affect climate change through their prescription patterns 2, something only few are aware of, and which may be difficult to translate and explain to patients. To illustrate the impact of switching from pMDIs to dry powder inhalers (dMDIs) we wanted to compare climate impact of inhaler switching to climate costs of well-known items and activities in Denmark, a country with a population of 6 million inhabitants.
Carbon footprint of MDIs can be translated into measures that are intuitive to both patients and health professionals
https://bit.ly/45iVbHC
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.
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