A pair of review articles examines our current understanding of the biology, diagnosis, and treatment of chronic obstructive pulmonary disease. This article focuses on the clinical aspects of COPD.
This randomized trial compared a long-acting beta-agonist (LABA) plus a glucocorticoid with a LABA plus a long-acting muscarinic antagonist for preventing exacerbations of chronic obstructive ...pulmonary disease. The exacerbation rate was lower with the latter treatment.
Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with an accelerated decline in lung function,
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impaired quality of life,
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hospitalization,
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and increased mortality.
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COPD exacerbations are costly to health care systems.
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Thus, prevention of exacerbations is a key goal in the management of COPD.
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Inhaled long-acting bronchodilators not only control symptoms but also prevent COPD exacerbations.
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Inhaled glucocorticoids are also known to reduce the frequency of exacerbations and have been studied in combination with inhaled long-acting beta-agonists (LABAs).
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In one trial, the combination of a LABA plus an inhaled glucocorticoid (salmeterol–fluticasone) in fixed doses and . . .
Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of ...side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.
Wedzicha discusses the study by Labaki and coauthors on causes of death related to lung function impairment in former or current smokers from the COPDgene (Genetic Epidemiology of COPD) study. The ...study has recruited subjects with COPD of all severities. A total of 10,132 subjects were included, among whom 2,200 deaths occurred; they were followed for 10.1 years and divided into those with normal spirometry, a group with preserved ratio impaired spirometry (PRISm), and then Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and 2 and GOLD 3 and 4 groups. Data on causes of death were available on just over 75% of the deaths, and these were adjudicated after review of death certificates, medical records, and next-of-kin interviews. Analysis of the missing mortality data suggested that those subjects had clinical features similar to those of subjects with mortality causes documented.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are episodes of symptom worsening which have significant adverse consequences for patients. Exacerbations are highly ...heterogeneous events associated with increased airway and systemic inflammation and physiological changes. The frequency of exacerbations is associated with accelerated lung function decline, quality of life impairment and increased mortality. They are triggered predominantly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. A proportion of patients appear to be more susceptible to exacerbations, with poorer quality of life and more aggressive disease progression than those who have infrequent exacerbations. Exacerbations also contribute significantly to healthcare expenditure. Prevention and mitigation of exacerbations are therefore key goals of COPD management.
This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations.Comprehensive evidence syntheses, including meta-analyses, 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 and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation.The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.
Patients with COPD were randomly assigned to triple inhaled therapy with either a 160-μg or 320-μg dose of budesonide or to one of two dual therapies. Both triple regimens were superior to the dual ...regimens with respect to the rate of moderate or severe exacerbations; no difference was observed between the triple regimens.
Studies have suggested some patients with asthma are at risk of severe coronavirus disease (COVID-19), but they have had limited data on asthma phenotype and have not considered if risks are specific ...to COVID-19.
To determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalization rates with influenza and pneumonia.
Electronic medical records were used to identify patients with asthma and match them to the general population. Patient-level data were linked to Public Health England severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type 2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression.
A total of 434,348 patients with asthma and 748,327 matched patients were included. All patients with asthma had a significantly increased risk of a General Practice diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (hazard ratio HR, 1.27; 95% confidence interval CI, 1.01-1.61), intermittent ICS plus add-on asthma medication use (HR, 2.00; 95% CI, 1.43-2.79), regular ICS plus add-on use (HR, 1.63; 95% CI, 1.37-1.94), or with frequent exacerbations (HR, 1.82; 95% CI, 1.34-2.47) was significantly associated with hospitalization. These phenotypes were significantly associated with influenza and pneumonia hospitalizations. Only patients with regular ICS plus add-on asthma therapy (HR, 1.70; 95% CI, 1.27-2.26) or frequent exacerbations (HR, 1.66; 95% CI, 1.03-2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes.
More severe asthma was associated with more severe COVID-19 outcomes, but type 2 inflammation was not. The risk of COVID-19 hospitalization appeared to be similar to the risk with influenza or pneumonia.
Background
Non‐invasive ventilation (NIV) with bi‐level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory failure (AHRF) ...secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
Objectives
To compare the efficacy of NIV applied in conjunction with usual care versus usual care involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The aim of this review is to update the evidence base with the goals of supporting clinical practice and providing recommendations for future evaluation and research.
Search methods
We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and PsycINFO, and through handsearching of respiratory journals and meeting s. This update to the original review incorporates the results of database searches up to January 2017.
Selection criteria
All randomised controlled trials that compared usual care plus NIV (BiPAP) versus usual care alone in an acute hospital setting for patients with AECOPD due to AHRF were eligible for inclusion. AHRF was defined by a mean admission pH < 7.35 and mean partial pressure of carbon dioxide (PaCO2) > 45 mmHg (6 kPa). Primary review outcomes were mortality during hospital admission and need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in arterial blood gases.
Data collection and analysis
Two review authors independently applied the selection criteria to determine study eligibility, performed data extraction, and determined risk of bias in accordance with Cochrane guidelines. Review authors undertook meta‐analysis for data that were both clinically and statistically homogenous, and analysed data as both one overall pooled sample and according to two predefined subgroups related to exacerbation severity (admission pH between 7.35 and 7.30 vs below 7.30) and NIV treatment setting (intensive care unit‐based vs ward‐based). We reported results for mortality, need for endotracheal intubation, and hospital length of stay in a 'Summary of findings' table and rated their quality in accordance with GRADE criteria.
Main results
We included in the review 17 randomised controlled trials involving 1264 participants. Available data indicate that mean age at recruitment was 66.8 years (range 57.7 to 70.5 years) and that most participants (65%) were male. Most studies (12/17) were at risk of performance bias, and for most (14/17), the risk of detection bias was uncertain. These risks may have affected subjective patient‐reported outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.
Use of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N = 17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality owing to uncertainty regarding risk of bias for several studies. Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome. NIV use was also associated with reduced length of hospital stay (mean difference (MD) ‐3.39 days, 95% CI ‐5.93 to ‐0.85; N = 10 studies), reduced incidence of complications (unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of oxygen (PaO2) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one hour. A trend towards improvement in PaCO2 was observed, but this finding was not statistically significant (MD ‐4.62 mmHg, 95% CI ‐11.05 to 1.80 mmHg; N = 8 studies). Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the NIV group than in the usual care group). Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of NIV on PaCO2. Treatment intolerance was significantly greater in the NIV group than in the usual care group (risk difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis showed a non‐significant trend towards reduction in dyspnoea with NIV compared with usual care (standardised mean difference (SMD) ‐0.16, 95% CI ‐0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between‐group differences.
Authors' conclusions
Data from good quality randomised controlled trials show that NIV is beneficial as a first‐line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD). The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH < 7.30), and when NIV is applied within the intensive care unit (ICU) or ward setting.
Professor Gavin Donaldson. 1961-2023 Wedzicha, Jadwiga A; Emeritus, Editor
American journal of respiratory and critical care medicine,
08/2023, Volume:
208, Issue:
4
Journal Article
Peer reviewed
Open access
An obituary for Gavin Donaldson, the scientist who died on February 20, 2023, is presented. Donaldson was born in Lancashire, England, on April 25, 1961, but the family soon moved to Cheltenham, ...Gloucestershire, where Donaldson spent his childhood and went to school. After obtaining his first degree, he studied for a Ph.D. on the physiology of temperature regulation at Queen Mary University of London under the supervision of Professor Bill Keatinge. During this time, he coordinated the prestigious Eurowinter study with Bill and traveled to Siberia to study cold exposures. Donaldson was immensely proud of this work; he wrote reports for the English Department of Health on the effects of low temperatures on health and had a lifelong interest in the field.
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