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Canadian Family Physician Medecin de... Jun 2022
Topics: Bronchiolitis, Viral; Bronchodilator Agents; Humans
PubMed: 35701205
DOI: 10.46747/cfp.6806429 -
MMW Fortschritte Der Medizin Apr 2021
Review
Topics: Bronchodilator Agents; Budesonide; COVID-19; Formoterol Fumarate; Humans; SARS-CoV-2
PubMed: 33904080
DOI: 10.1007/s15006-021-9864-0 -
Respiratory Research Oct 2019Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease... (Comparative Study)
Comparative Study Randomized Controlled Trial
Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial.
BACKGROUND
Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids.
METHODS
The 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to umeclidinium/vilanterol 62.5/25 μg once-daily, umeclidinium 62.5 μg once-daily or salmeterol 50 μg twice-daily. The primary endpoint was trough forced expiratory volume in 1 s (FEV) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions.
RESULTS
Change from baseline in trough FEV at Week 24 was 66 mL (95% confidence interval [CI]: 43, 89) and 141 mL (95% CI: 118, 164) greater with umeclidinium/vilanterol versus umeclidinium and salmeterol, respectively (both p < 0.001). Umeclidinium/vilanterol demonstrated consistent improvements in Transition Dyspnoea Index versus both monotherapies at Week 24 (vs umeclidinium: 0.37 [95% CI: 0.06, 0.68], p = 0.018; vs salmeterol: 0.45 [95% CI: 0.15, 0.76], p = 0.004) and all other symptom measures at all time points. Regardless of the clinically important deterioration definition considered, umeclidinium/vilanterol significantly reduced the risk of a first clinically important deterioration compared with umeclidinium (by 16-25% [p < 0.01]) and salmeterol (by 26-41% [p < 0.001]). Safety profiles were similar between treatments.
CONCLUSIONS
Umeclidinium/vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimise therapy in this patient group.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Salmeterol Xinafoate; Treatment Outcome
PubMed: 31666084
DOI: 10.1186/s12931-019-1193-9 -
Canadian Family Physician Medecin de... May 2022
Topics: Bronchodilator Agents; Budesonide; COVID-19; Humans; SARS-CoV-2
PubMed: 35552214
DOI: 10.46747/cfp.6805355 -
La Tunisie Medicale Mar 2023The diagnosis and management of the most prevalent chronic respiratory diseases partially rely on parameters obtained from pulmonary functional tests (PFTs), including...
The diagnosis and management of the most prevalent chronic respiratory diseases partially rely on parameters obtained from pulmonary functional tests (PFTs), including spirometry, plethysmography, and carbon monoxide diffusion capacity (DLCO) measurement. In practice, the interpretation of PFTs' parameters is based on international recommendations issued by renowned scientific societies such as the American Thoracic Society (ATS) and the European Respiratory Society (ERS). The interpretation standards for PFTs established by ATS/ERS in 2005 were updated in 2022. According to the ATS/ERS-2022 standards, the interpretation of PFTs can be summarized in five steps. The first step involves comparing the determined parameters with those observed in a reference population of healthy individuals. This step helps determine whether the determined parameters are low, normal, or elevated. The second step aims to identify potential ventilatory impairments, such as obstructive and/or restrictive ventilatory impairments, which can be observed in certain chronic respiratory or extrarespiratory diseases. The third step involves assessing the severity of the identified ventilatory impairment or the decrease in DLCO. The fourth step entails evaluating the response to bronchodilator testing, if performed. Finally, if previous PFTs results are available, it is important to identify significant changes in certain PFTs parameters over time by comparing current and previous results. This clinical practice guide provides a comprehensive synthesis of the different steps in PFTs interpretation, taking into account the recommendations from ATS/ERS-2022.
Topics: Humans; Respiratory Function Tests; Spirometry; Bronchodilator Agents; Plethysmography
PubMed: 38263920
DOI: No ID Found -
Respiratory Care Apr 2022Bronchodilation testing is an important component of spirometry testing, and omitting this procedure has potential clinical implications toward diagnosing respiratory...
BACKGROUND
Bronchodilation testing is an important component of spirometry testing, and omitting this procedure has potential clinical implications toward diagnosing respiratory diseases. We aimed to estimate the impact of bronchodilator testing in accurately diagnosing COPD and differentiating COPD from asthma-COPD overlap (ACO).
METHODS
The National Health and Nutrition Examination Survey data were analyzed from 2007-2012. Airflow limitation was defined by FEV/FVC < 0.7. Subjects with pre-bronchodilator airflow limitation were classified into pre-but-not-post-bronchodilator airflow limitation and post-bronchodilator airflow limitation groups. Spirometry-confirmed COPD was defined by persistent airflow limitation on post-bronchodilator spirometry. The American Thoracic Society (ATS) and the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) definitions were used to identify possible ACO subjects.
RESULTS
We identified 11,763 subjects ≥ 40 y of age eligible for spirometry; 625 of them had a pre-bronchodilator FEV/FVC < 0.7 and completed post-bronchodilator spirometry that met ATS spirometry quality standards. A total of 244 (39%) of these subjects had only pre-not-post-bronchodilator airflow limitation, thereby not meeting the definition of spirometrically confirmed COPD. The prevalence of ACO was 7.6% using the modified ATS definition and 19.8% using the modified SEPAR criteria. When bronchodilator testing-based criteria were excluded from ATS and SEPAR definitions, the number of ACO subjects decreased by 39.3% and 12.3%, respectively.
CONCLUSIONS
Spirometry with bronchodilation is an important element in the accurate diagnosis of ACO and COPD. Spirometry performed without bronchodilator testing may lead to an estimated misclassification of ACO by 7.6% to 19.8% and overdiagnosis of COPD by 39%.
Topics: Asthma; Bronchodilator Agents; Forced Expiratory Volume; Humans; Nutrition Surveys; Pulmonary Disease, Chronic Obstructive; Spirometry; Vital Capacity
PubMed: 35338095
DOI: 10.4187/respcare.09215 -
The Cochrane Database of Systematic... Jun 2022Respiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of... (Review)
Review
BACKGROUND
Respiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of respiratory problems. Bronchodilator therapy is used to relieve symptoms of shortness of breath and to open the airways to allow clearance of mucus. Despite the widespread use of inhaled bronchodilators in CF, there is little objective evidence of their efficacy. A Cochrane Review looking at both short- and long-acting inhaled bronchodilators for CF was withdrawn from the Cochrane Library in 2016. That review has been replaced by two separate Cochrane Reviews: one on long-acting inhaled bronchodilators for CF, and this review on short-acting inhaled bronchodilators for CF. For this review 'inhaled' includes the use of pressurised metered dose inhalers (MDIs), with or without a spacer, dry powder devices and nebulisers.
OBJECTIVES
To evaluate short-acting inhaled bronchodilators in children and adults with CF in terms of clinical outcomes and safety.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books on 28 March 2022 and searched trial registries for any new or ongoing trials on 12 April 2022. We also searched the reference lists of relevant articles and reviews.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) or quasi-RCTs that looked at the effect of any short-acting inhaled bronchodilator delivered by any device, at any dose, at any frequency and for any duration compared to either placebo or another short-acting inhaled bronchodilator in people with CF. We screened references as per standard Cochrane methodology.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and assessed risk of bias using the Cochrane RoB 1 tool. Where we were not able to enter data into our analyses we reported results directly from the papers. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 11 trials from our systematic search, with 191 participants meeting our inclusion criteria; three of these trials had three treatment arms. Eight trials compared short-acting inhaled beta-2 agonists to placebo and four trials compared short-acting inhaled muscarinic antagonists to placebo. Three trials compared short-acting inhaled beta-2 agonists to short-acting inhaled muscarinic antagonists. All were cross-over trials with only small numbers of participants. We were only able to enter data into the analysis from three trials comparing short-acting inhaled beta-2 agonists to placebo. Short-acting inhaled beta-2 agonists versus placebo All eight trials (six single-dose trials and two longer-term trials) reporting on this comparison reported on forced expiratory volume in 1 second (FEV), either as per cent predicted (% predicted) or L. We were able to combine the data from two trials in a meta-analysis which showed a greater per cent change from baseline in FEV L after beta-2 agonists compared to placebo (mean difference (MD) 6.95%, 95% confidence interval (CI) 1.88 to 12.02; 2 trials, 82 participants). Only one of the longer-term trials reported on exacerbations, as measured by hospitalisations and courses of antibiotics. Only the second longer-term trial presented results for participant-reported outcomes. Three trials narratively reported adverse events, and these were all mild. Three single-dose trials and the two longer trials reported on forced vital capacity (FVC), and five trials reported on peak expiratory flow, i.e. forced expiratory flow between 25% and 75% (FEF). One trial reported on airway clearance in terms of sputum weight. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists on any of the outcomes we assessed. Short-acting inhaled muscarinic antagonists versus placebo All four trials reporting on this comparison looked at the effects of ipratropium bromide, but in different doses and via different delivery methods. One trial reported FEV % predicted; three trials measured this in L. Two trials reported adverse events, but these were few and mild. One trial reported FVC and three trials reported FEF. None of the trials reported on quality of life, exacerbations or airway clearance. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled muscarinic antagonists on any of the outcomes we assessed. Short-acting inhaled beta-2 agonists versus short-acting inhaled muscarinic antagonists None of the three single-dose trials reporting on this comparison provided data we could analyse. The original papers from three trials report that both treatments lead to an improvement in FEV L. Only one trial reported on adverse events; but none were experienced by any participant. No trial reported on any of our other outcomes. We judged the certainty of evidence to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists compared to short-acting inhaled muscarinic antagonists on any of the outcomes we assessed.
AUTHORS' CONCLUSIONS
All included trials in this review are small and of a cross-over design. Most trials looked at very short-term effects of inhaled bronchodilators, and therefore did not measure longer-term outcomes. The certainty of evidence across all outcomes was very low, and therefore we have been unable to describe any effects with certainty.
Topics: Administration, Inhalation; Adult; Bronchodilator Agents; Child; Cystic Fibrosis; Forced Expiratory Volume; Humans; Muscarinic Antagonists
PubMed: 35749226
DOI: 10.1002/14651858.CD013666.pub2 -
The European Respiratory Journal Dec 2019
Topics: Asthma; Bronchodilator Agents; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 31801818
DOI: 10.1183/13993003.02036-2019 -
Current Allergy and Asthma Reports Dec 2021Several genome-wide association studies (GWASs) of bronchodilator response (BDR) to albuterol have been published over the past decade. This review describes current... (Review)
Review
PURPOSE OF REVIEW
Several genome-wide association studies (GWASs) of bronchodilator response (BDR) to albuterol have been published over the past decade. This review describes current knowledge gaps, including pharmacogenetic studies of albuterol response in minority populations, effect modification of pharmacogenetic associations by age, and relevance of BDR phenotype characterization to pharmacogenetic findings. New approaches, such as leveraging additional "omics" data to focus pharmacogenetic interrogation, as well as developing polygenic risk scores in asthma treatment responses, are also discussed.
RECENT FINDINGS
Recent pharmacogenetic studies of albuterol response in minority populations have identified genetic polymorphisms in loci (DNAH5, NFKB1, PLCB1, ADAMTS3, COX18, and PRKG1), that are associated with BDR. Additional studies are needed to replicate these findings. Modification of the pharmacogenetic associations for SPATS2L and ASB3 polymorphisms by age has also been published. Evidence from metabolomic and epigenomic studies of BDR may point to new pharmacogenetic targets. Lastly, a polygenic risk score for response to albuterol has been developed but requires validation in additional cohorts. In order to expand our knowledge of pharmacogenetics of BDR, additional studies in minority populations are needed. Consideration of effect modification by age and leverage of other "omics" data beyond genomics may also help uncover novel pharmacogenetic loci for use in precision medicine for asthma treatment.
Topics: Albuterol; Bronchodilator Agents; Genome-Wide Association Study; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide
PubMed: 34958416
DOI: 10.1007/s11882-021-01023-w -
International Journal of Chronic... 2023Ensifentrine is a novel, potent, and selective dual inhibitor of phosphodiesterase (PDE)3 and PDE4 designed for delivery by inhalation that combines effects on airway... (Review)
Review
Ensifentrine is a novel, potent, and selective dual inhibitor of phosphodiesterase (PDE)3 and PDE4 designed for delivery by inhalation that combines effects on airway inflammation, bronchodilation and ciliary function in bronchial epithelia. In Phase 2 studies in subjects with COPD, ensifentrine demonstrated clinically meaningful bronchodilation and improvements in symptoms and health-related quality of life when administered alone or in combination with current standard of care therapies. Ensifentrine is currently in late-stage clinical development for the maintenance treatment of patients with COPD. This review summarizes non-clinical data as well as Phase 1 and Phase 2 efficacy and safety results of nebulized ensifentrine relevant to the maintenance treatment of patients with COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Phosphodiesterase 4 Inhibitors; Isoquinolines; Administration, Inhalation; Bronchodilator Agents
PubMed: 37533771
DOI: 10.2147/COPD.S413436