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The Cochrane Database of Systematic... Dec 2017Cystic fibrosis is a life-limiting inherited condition which affects one in 2500 newborns in the UK and 70,000 children and adults worldwide. The condition is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cystic fibrosis is a life-limiting inherited condition which affects one in 2500 newborns in the UK and 70,000 children and adults worldwide. The condition is multifaceted and affects many systems in the body. The respiratory system is particularly affected due to a build up of thickened secretions and a predisposition to infection. Inhaled bronchodilators are prescribed for 80% of people with cystic fibrosis in order to widen the airways and alleviate symptoms. Both short- and long-acting inhaled bronchodilators are used to improve respiratory symptoms. Short-acting inhaled bronchodilators take effect in minutes and typically last for four to eight hours (muscarinic antagonists). Long-acting inhaled bronchodilators also take effect within minutes but typically last for around 12 hours and sometimes longer. This review is one of two which are replacing a previously published review of both long- and short-acting inhaled bronchodilators.
OBJECTIVES
This review aims to evaluate long-acting inhaled bronchodilators in children and adults with cystic fibrosis in terms of clinical outcomes and safety. If possible, we aimed to assess the optimal drug and dosage regimen.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 10 October 2017.We also carried out a separate search of Embase and the reference lists of included trials. We searched clinical trials registries for any ongoing trials and made contact with pharmaceutical companies for any further trials.Date of Embase search: 11 October 2017.
SELECTION CRITERIA
Randomised or quasi-randomised parallel trials comparing long-acting inhaled bronchodilators (beta-2 agonists and muscarinic antagonists) with placebo, no treatment or a different long-acting inhaled bronchodilator in adults and children with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Both authors independently assessed trials for inclusion (based on title, abstract and full text). The authors independently assessed the included trials for quality and risk of bias and extracted data. Discrepancies were resolved by a third party.
MAIN RESULTS
The searches identified 195 unique references, of which 155 were excluded on title and abstract. We assessed the full texts of the remaining references, excluded 16 trials (28 references) and included four trials (12 references) in the review with 1082 participants.One trial (n = 16) measuring the effect of beta-2 agonists reported an improvement in forced expiratory volume at one second (FEV) after treatment (at one month), but the trial was small with an unclear risk of bias so we judged the evidence to be very low quality. The trial did not report on participant-reported outcomes, quality of life or adverse events.Three trials (n = 1066) looked at the effects of the muscarinic antagonist tiotropium at doses of 2.5 µg and 5.0 µg in both the short term (up to 28 days) and the longer term (up to three months). Only one of the trials reported the change in FEV (L) after 28 days treatment and showed no significant difference between groups; with 2.5 µg tiotropium, mean difference (MD) -0.02 (95% confidence interval (CI) -0.13 to 0.09), or 5.0 µg tiotropium, MD 0.00 (95% CI -0.10 to 0.10) (moderate-quality evidence). All three trials of muscarinic antagonists provided data on adverse events which were found to differ little from placebo at doses of 2.5 µg, risk ratio (RR) 1.01 (95% CI 0.92 to 1.11) or 5.0 µg, RR 0.98 (95% CI 0.90 to 1.06). Very little participant-reported outcome data or quality of life data were available for analysis. Two of the trials were at low risk of bias overall whilst the remaining trial was at an unclear risk overall.
AUTHORS' CONCLUSIONS
Neither long-acting beta-2 agonists nor long-acting muscarinic antagonist bronchodilators demonstrate improvement in our primary outcome of FEV. No difference was observed between intervention and placebo in terms of quality of life or adverse events. The quality of evidence for the use of beta-2 agonists was very low. The use of a long-acting inhaled bronchodilator may help to reduce the burden of treatment for people with cystic fibrosis as it is taken less often than a short-acting inhaled bronchodilator, but future trials would benefit from looking at the effects on our primary outcomes (spirometric changes from baseline, quality of life and adverse effects) in the longer term.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Cystic Fibrosis; Disease Progression; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Tiotropium Bromide
PubMed: 29253920
DOI: 10.1002/14651858.CD012102.pub2 -
Respiratory Care Sep 2009Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease that results from complications related to the lung injury during the treatment of...
Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease that results from complications related to the lung injury during the treatment of respiratory distress syndrome, or develops in older infants when abnormal lung growth occurs. The definition and classification of BPD have changed since the original diagnosis was established many years ago. The incidence of BPD continues to grow as lower-birth-weight infants continue to survive. The primary focus of all treatment associated with premature infants is on prevention of BPD. Surfactant replacement, invasive and noninvasive ventilation techniques, management of the patent ductus arteriosus, cautious management of oxygen therapy, caffeine, inhaled nitric oxide, and changes in delivery room practices have been studied to assess their effects on the development of the disease. Other strategies used to reduce the long-term effects of this chronic lung disease include bronchodilators, inhaled and systemic steroids, nutrition management, and selected ventilator strategies. The prevention of BPD is targeted at minimizing effects of this pulmonary disease and preventing the long-term sequelae associated with its treatment.
Topics: Bronchodilator Agents; Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Oxygen Inhalation Therapy; Positive-Pressure Respiration; Pulmonary Surfactants; Steroids
PubMed: 19712501
DOI: No ID Found -
The Journal of Allergy and Clinical... Mar 2020Bronchodilator reversibility measures are often associated with poor asthma outcomes in children. Whether bronchodilator dose responsiveness is similarly useful in...
BACKGROUND
Bronchodilator reversibility measures are often associated with poor asthma outcomes in children. Whether bronchodilator dose responsiveness is similarly useful in children is unclear.
OBJECTIVE
We hypothesized that children and adolescents requiring higher doses of bronchodilator to achieve maximal bronchodilation would have unique risk factors and increased risk of future exacerbation.
METHODS
Children (6-11 years, N = 299) and adolescents (12-21 years, N = 331) with confirmed asthma underwent clinical phenotyping procedures and a test of maximal bronchodilation with escalating doses of albuterol sulfate up to 720 mcg. Outcome measures were assessed at 12 months and included exacerbations treated with systemic corticosteroids, emergency department (ED) visits, and hospitalizations for asthma.
RESULTS
A total of 6.7% of children and 9.3% of adolescents had poor bronchodilator dose responsiveness, defined as attainment of maximal forced expiratory volume in 1 second with 720 mcg albuterol. Risk factors included type 2 inflammation, prior exacerbations, and greater asthma severity; historical pneumonia and tobacco exposure were also risk factors in children. Children and adolescents with poor bronchodilator dose responsiveness did not have increased current symptoms or impaired quality of life, but had approximately 2-fold increased odds of exacerbation or ED visit and approximately 3-fold increased odds of hospitalization by 12 months, independent of airflow obstruction.
CONCLUSIONS
Bronchodilator dose responsiveness may be useful for phenotyping and may be of utility in practice and future studies focused on asthma outcomes or quantification of treatment responses. In children and adolescents, this phenotype of poor bronchodilator responsiveness may be associated with periods of relatively stable disease yet marked airway constriction in response to triggers, including tobacco smoke, respiratory infections/pneumonia, and aeroallergens.
Topics: Adolescent; Albuterol; Asthma; Bronchodilator Agents; Child; Forced Expiratory Volume; Humans; Quality of Life
PubMed: 31614217
DOI: 10.1016/j.jaip.2019.09.033 -
The American Journal of Medicine Jun 2018The incidence of chronic obstructive pulmonary disease (COPD) is rising in the United States, and the disease represents a significant source of morbidity and mortality.... (Review)
Review
The incidence of chronic obstructive pulmonary disease (COPD) is rising in the United States, and the disease represents a significant source of morbidity and mortality. Primary care providers face many challenges in COPD diagnosis and treatment, as different clinical phenotypes require personalized treatment approaches. Patient adherence and inhaler technique also contribute to treatment outcomes. Around 48% of primary care providers are unaware of guidelines and recommendations for COPD diagnosis and treatment, which may lead to misdiagnosis or undertreatment of COPD symptoms. Inadequately treated COPD can impair patients' quality of life and ability to perform everyday activities. Long-acting bronchodilator therapy is the cornerstone treatment for patients with COPD; combinations of bronchodilators of different pharmacological classes have shown improved efficacy vs monotherapy. We review the rationale behind fixed-dose dual bronchodilator therapy, evidence for the 4 currently Food and Drug Administration-approved long-acting anticholinergic bronchodilators/long-acting β-agonists fixed combinations, patient suitability for the available inhaler devices, and practical guidance to optimize personalized care for patients with COPD.
Topics: Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Cholinergic Antagonists; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 29305841
DOI: 10.1016/j.amjmed.2017.12.018 -
Respirology (Carlton, Vic.) Jul 2021Pharmacological treatment for chronic obstructive pulmonary disease (COPD) aims to alleviate symptoms and reduce the future risk of events such as exacerbations, disease... (Meta-Analysis)
Meta-Analysis Review
Pharmacological treatment for chronic obstructive pulmonary disease (COPD) aims to alleviate symptoms and reduce the future risk of events such as exacerbations, disease progression and death. The heterogeneity of COPD results in variable responses to pharmacological interventions. COPD treatment has evolved towards a precision medicine approach, integrating clinical and biomarker information in order to optimize treatment decisions for each individual. The evidence supporting the use of blood eosinophil counts to predict responses to inhaled corticosteroids (ICS) in COPD patients has led to the adoption of this biomarker for use in clinical practice. The development of novel double and triple inhaled combination treatments containing long-acting bronchodilators with or without ICS has involved some landmark randomized controlled trials in COPD patients. These studies have provided valuable evidence to direct the use of different classes of combination treatments. However, there are still some unresolved questions and debates. This review article describes the advances in the pharmacological treatment of COPD, particularly the personalization of treatment. The evidence base for current recommendations is discussed, and controversial issues are dissected.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Disease Progression; Drug Therapy, Combination; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 33829619
DOI: 10.1111/resp.14046 -
Respiratory Medicine May 2019Asthma is often associated with different comorbidities such as cardiovascular diseases, depression, diabetes mellitus, dyslipidaemia, osteoporosis, rhinosinusitis and... (Review)
Review
Asthma is often associated with different comorbidities such as cardiovascular diseases, depression, diabetes mellitus, dyslipidaemia, osteoporosis, rhinosinusitis and mainly gastro-oesophageal reflux disease and allergic rhinitis. Although bronchodilators play an important role in the treatment of asthma, there is no overall description of their impact on comorbid asthma, regardless of whether favourable or negative. This narrative review examines the potential effects of bronchodilators on comorbidities of asthma.
Topics: Anxiety; Asthma; Bronchodilator Agents; Cardiovascular Diseases; Death, Sudden; Depression; Diabetes Mellitus; Gastroesophageal Reflux; Humans; Obesity; Rhinitis, Allergic
PubMed: 31047116
DOI: 10.1016/j.rmed.2019.04.001 -
Journal of Applied Physiology... Apr 2021We previously documented, in patients with asthma, three different profiles of bronchodilation induced by short-acting β-2 mimetics (SABA), characterized by dilation up... (Clinical Trial)
Clinical Trial
We previously documented, in patients with asthma, three different profiles of bronchodilation induced by short-acting β-2 mimetics (SABA), characterized by dilation up to central, preacinar, and intra-acinar airways assessed by ventilation distribution tests and associated with no change, increase, and decrease of fractional exhaled nitric oxide concentration (FENO), respectively. To investigate the dynamics of these profiles over the entire SABA action period, assuming that bronchodilation of proximal and peripheral airways could exhibit varying kinetics due to differences in the distribution of β-2 receptors in both the central and peripheral human airways. FENO, forced expired volume in one second (FEV), and the slope () of He and SF phase III (single-breath test) were measured in asthma patients before, and up to 6 h after SABA inhalation (salbutamol 400 µg). and decrease reflects pre- and intra-acinar obstruction relief, respectively. Thirty patients with asthma (12F/18M, aged 45 ± 18 yr) were divided into groups with positive (NO+, = 9), negative (NO-, = 11), and no (NO=, = 10) FENO acute change. In the NO- group, FEV increased for up to 4 h, whereas FENO, , and decreased in the early phase only. In stark contrast, in the NO+ group, FEV increased in the early phase only whereas the FENO increase and the decrease lasted for up to 4 h. This study documents various profiles of SABA-induced bronchodilation in patients with asthma, differing both by sites and dynamics of the bronchodilator process. So, detailed understanding of the bronchodilator effect of β2-agonists in asthma should not solely be limited to studying their impact on FEV. FEV increase usually observed after the inhalation of short-acting β2-agonists in asthma patients tends to involve peripheral airways. This study shows that the heterogeneity of responses to short-acting β2-agonists in asthma not only involves distinct sites of bronchodilation, but also distinct sequences between these sites. This indicates that a detailed understanding of the bronchodilator effect of β2-agonists in asthma should not be limited to studying its early impact on FEV.
Topics: Adult; Albuterol; Asthma; Bronchodilator Agents; Exhalation; Female; Forced Expiratory Volume; Humans; Kinetics; Male; Middle Aged; Nitric Oxide
PubMed: 33444118
DOI: 10.1152/japplphysiol.00643.2020 -
NPJ Primary Care Respiratory Medicine Oct 2021Inhaled bronchodilators are central for the treatment of chronic obstructive pulmonary disease (COPD), as they can provide symptom relief and reduce the frequency and... (Review)
Review
Inhaled bronchodilators are central for the treatment of chronic obstructive pulmonary disease (COPD), as they can provide symptom relief and reduce the frequency and severity of exacerbations while improving health status and exercise tolerance. In 2017, glycopyrrolate (GLY) delivered via the eFlow® closed system (CS) nebulizer (nebulized GLY; 25 µg twice daily), was approved by the US Food and Drug Administration for maintenance treatment of moderate-to-very-severe COPD. This approval was based largely on results from the replicate, placebo-controlled, Phase III clinical trials- GOLDEN 3 and 4. In this review, we summarize key findings from secondary analyses of the GOLDEN 3 and 4 studies, and provide a comprehensive overview that may assist both pulmonologists and primary-care providers in their treatment decisions. Comorbidities are common among patients with COPD in clinical practice and may impact bronchodilator efficacy. This review highlights outcomes among subpopulations of patients with comorbidities (e.g., anxiety/depression, cardiovascular disease), and their impact on the efficacy of nebulized GLY. In addition, the efficacy and safety of nebulized GLY across various demographics (e.g., age, gender) and baseline disease characteristics (e.g., disease severity, rescue medication use) are discussed. Real-world outcomes with nebulized GLY, including device satisfaction, healthcare resource utilization, and exacerbations, are also presented. These secondary analyses and real-world data complement the primary results with nebulized GLY from Phase III studies and support the need for the inclusion of patients representative of real-world clinical practice in RCTs. In addition, these data suggest that RCTs for COPD therapies should be complemented with real-world observational studies.
Topics: Administration, Inhalation; Bronchodilator Agents; Glycopyrrolate; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 34620878
DOI: 10.1038/s41533-021-00255-7 -
American Journal of Respiratory Cell... Oct 2022
Topics: Animals; Anti-Anxiety Agents; Asthma; Bronchodilator Agents; Calcium; GABA-A Receptor Agonists; Mice; gamma-Aminobutyric Acid
PubMed: 35901197
DOI: 10.1165/rcmb.2022-0287ED -
European Respiratory Review : An... Jun 2021Most patients with COPD are recommended to initiate maintenance therapy with a single long-acting bronchodilator, such as a long-acting muscarinic antagonist or... (Review)
Review
Most patients with COPD are recommended to initiate maintenance therapy with a single long-acting bronchodilator, such as a long-acting muscarinic antagonist or long-acting β-agonist. However, many patients receiving mono-bronchodilation continue to experience high symptom burden, suggesting that patients are frequently not receiving optimal treatment. Treatment goals for COPD are often broad and not individually tailored, making initial treatment response assessments difficult. A personalised approach to initial maintenance therapy, based upon an individual's symptom burden and exacerbation risk, may be more appropriate.An alternative approach would be to maximise bronchodilation early in the disease course of all patients with COPD. Evidence suggests that dual bronchodilation has greater and consistent efficacy for lung function and symptoms than mono-bronchodilation, whilst potentially reducing the risk of exacerbations and disease deterioration, with a similar safety profile to mono-bronchodilators. Improvements in lung function and symptoms between dual- and mono-bronchodilation have also been demonstrated in maintenance-naïve patients, who are most likely to resemble those at first presentation in a clinical setting. Despite promising results, there are several evidence gaps that need to be addressed to allow decision makers to evaluate the merits of a widespread earlier introduction of dual bronchodilation.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 34415847
DOI: 10.1183/16000617.0023-2021