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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 -
The Cochrane Database of Systematic... Feb 2016This review has been withdrawn because it has been split into the following reviews: 'Long‐acting inhaled bronchodilators for cystic fibrosis' and 'Short‐acting... (Review)
Review
This review has been withdrawn because it has been split into the following reviews: 'Long‐acting inhaled bronchodilators for cystic fibrosis' and 'Short‐acting inhaled bronchodilators for cystic fibrosis'. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Adrenergic beta-Agonists; Adult; Albuterol; Bronchial Hyperreactivity; Bronchodilator Agents; Child; Cystic Fibrosis; Humans; Ipratropium; Randomized Controlled Trials as Topic; Salmeterol Xinafoate
PubMed: 26866910
DOI: 10.1002/14651858.CD003428.pub3 -
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 -
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 -
Pulmonary Pharmacology & Therapeutics Aug 2018Doxofylline is an effective bronchodilator for relieving airway obstruction in patients with asthma or chronic obstructive pulmonary disease (COPD), and displays a... (Meta-Analysis)
Meta-Analysis Review
Doxofylline is an effective bronchodilator for relieving airway obstruction in patients with asthma or chronic obstructive pulmonary disease (COPD), and displays a better safety profile with respect to theophylline. Herein, we performed a pairwise meta-analysis of the currently available data to provide consistent and homogeneous findings on the impact of this xanthine in COPD patients. Results obtained from 820 patients were selected from 20 clinical trials. Meta-regression was performed to examine the source of heterogeneity between-studies and identify potential confounder covariates. The quality of the evidence was assessed by the GRADE system. Doxofylline induced a significant (P < 0.001) increase in forced expiratory volume in 1 s (FEV) of 8.20% (95%CI 4.00-12.41; I 93%) and 317 ml (95%CI 19-439; I 87%) compared with baseline. The total administered dose of doxofylline significantly (P < 0.001) interacted with the size of the effect estimates detected for FEV. Doxofylline induced a significant (P < 0.001), although moderate, increase in adverse events (AEs) frequency (proportion 0.03, 95%CI 0.02-0.04; I 88%), but only epigastralgia, nausea, dyspepsia and headache were statistically significant (P < 0.05). The GRADE analysis indicated high quality of evidence (++++) for the impact of doxofylline on FEV, and moderate quality of evidence (+++) for the safety profile in COPD patients. Doxofylline is an effective and safe medicine when administered to patients with COPD and can be considered as an alternative to theophylline.
Topics: Bronchodilator Agents; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Theophylline; Treatment Outcome
PubMed: 29705620
DOI: 10.1016/j.pupt.2018.04.010 -
The Cochrane Database of Systematic... Dec 2016Chronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume and decreased pulmonary resistance have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators might have a role in the prevention and treatment of CLD.
OBJECTIVES
To determine the effect of bronchodilators given as prophylaxis or as treatment for CLD on mortality and other complications of preterm birth in infants at risk for or identified as having CLD.
SEARCH METHODS
On 2016 March 7, we used the standard strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (from 1966), Embase (from 1980) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982). We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We applied no language restrictions.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials involving preterm infants were eligible for inclusion. Initiation of bronchodilator therapy for prevention of CLD had to occur within two weeks of birth. Treatment of patients with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation, by metered dose inhaler (with or without a spacer device) or by intravenous or oral administration versus placebo or no intervention. Eligible studies had to include at least one of the following predefined clinical outcomes: mortality, CLD, number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, intraventricular haemorrhage (IVH) of any grade, necrotising enterocolitis (NEC), sepsis and adverse effects of bronchodilators.
DATA COLLECTION AND ANALYSIS
We used the standard method described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors extracted and assessed all data provided by each study. We reported risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence interval (CI) for dichotomous outcomes and mean difference (MD) for continuous data. We assessed the quality of the evidence by using the GRADE approach.
MAIN RESULTS
For this update, we identified one new randomised controlled trial investigating effects of bronchodilators in preterm infants. This study, which enrolled 73 infants but reported on 52 infants, examined prevention of CLD with the use of aminophylline. According to GRADE, the quality of the evidence was very low. One previously included study enrolled 173 infants to look at prevention of CLD with the use of salbutamol. According to GRADE, the quality of the evidence was moderate. We found no eligible trial that studied the use of bronchodilator therapy for treatment of individuals with CLD. Prophylaxis with salbutamol led to no statistically significant differences in mortality (RR 1.08, 95% CI 0.50 to 2.31; RD 0.01, 95% CI -0.09 to 0.11) nor in CLD (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17). Results showed no statistically significant differences in other complications associated with CLD nor in preterm birth. Investigators in this study did not comment on side effects due to salbutamol. Prophylaxis with aminophylline led to a significant reduction in CLD at 28 days of life (RR 0.18, 95% CI 0.04 to 0.74; RD -0.35, 95% CI -0.56 to -0.13; NNTB 3, 95% CI 2 to 8) and no significant difference in mortality (RR 3.0, 95% CI 0.33 to 26.99; RD 0.08, 95% CI -0.07 to 0.22), along with a significantly shorter dependency on supplementary oxygen in the aminophylline group compared with the no treatment group (MD -17.75 days, 95% CI -27.56 to -7.94). Tests for heterogeneity were not applicable for any of the analyses, as each meta-analysis included only one study.
AUTHORS' CONCLUSIONS
Data are insufficient for reliable assessment of the use of salbutamol for prevention of CLD. One trial of poor quality reported a reduction in the incidence of CLD and shorter duration of supplementary oxygen with prophylactic aminophylline, but these results must be interpreted with caution. Additional clinical trials are necessary to assess the role of bronchodilator agents in prophylaxis or treatment of CLD. Researchers studying the effects of bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes. We identified no trials that studied the use of bronchodilator therapy for treatment of CLD.
Topics: Albuterol; Aminophylline; Beclomethasone; Bronchodilator Agents; Chronic Disease; Drug Therapy, Combination; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Randomized Controlled Trials as Topic
PubMed: 27960245
DOI: 10.1002/14651858.CD003214.pub3 -
American Journal of Respiratory and... Jul 2022Exacerbations of chronic obstructive pulmonary disease (COPD) are an important endpoint in multinational clinical treatment trials, but the observed event rate is often... (Review)
Review
Exacerbations of chronic obstructive pulmonary disease (COPD) are an important endpoint in multinational clinical treatment trials, but the observed event rate is often lower than anticipated and appears to vary between countries. We investigated whether systematic differences in national exacerbation rates might explain this observed variation. We reviewed data from three large multicenter international randomized trials conducted over an 18-year period with different designs and clinical severities of COPD, comparing bronchodilator and/or inhaled corticosteroids with bronchodilators alone and/or placebo. Exacerbations were defined by antibiotic and/or oral corticosteroid use (moderate) or need for hospitalization (severe). We calculated crude exacerbation rates in the 30 countries contributing 30 or more patients to at least two trials. We grouped data by exacerbation rate based on their first study contribution. For the 29,756 patients in 41 countries analyzed, the mean exacerbation rate was two- to threefold different between the highest and lowest tertiles of the recruiting nations. These differences were not explained by demographic features, study protocol, or reported exacerbation history at enrollment. Of the 18 countries contributing to all trials, half of those in the highest and half in the lowest tertiles of exacerbation history remained in these groups across trials. Severe exacerbations showed a different rank order internationally. Countries contributing to COPD trials differ consistently in their reporting of healthcare-defined exacerbations. These differences help explain why large studies have been needed to show differences between treatments that decrease exacerbation risk.
Topics: Adrenal Cortex Hormones; Bronchodilator Agents; Disease Progression; Hospitalization; Humans; Multicenter Studies as Topic; Pulmonary Disease, Chronic Obstructive
PubMed: 35363593
DOI: 10.1164/rccm.202111-2630OC -
Thorax Sep 2023Although obstructive airway disease has been shown to be associated with prematurity, other spirometry phenotypes are less well described.
INTRODUCTION
Although obstructive airway disease has been shown to be associated with prematurity, other spirometry phenotypes are less well described.
OBJECTIVES
We characterised abnormal spirometry phenotypes in preterm-born children, including prematurity-associated obstructive lung disease (POLD, forced expiratory volume in 1 s (FEV)
bronchodilator responsiveness and fractional exhaled nitric oxide (FE). METHODS
768 children, aged 7-12 years, underwent FE measurements and spirometry before and after salbutamol. Groups were compared using parametric tests; multinomial regression was used.
RESULTS
22.6% of 544 preterm-born (mean gestation: 31 weeks) and 9.2% of 195 term-born children, with satisfactory data available, were classified into one of four abnormal spirometry groups. Each phenotype was generally more prevalent in preterm-born children than in the term-born children. For the preterm group, POLD-reversible (4.4%) was associated with increased FE, bronchopulmonary dysplasia (BPD) and intrauterine growth restriction. POLD-fixed group (3.3%) did not have increased FE but was associated with BPD. 41% of the pDysanapsis group (5.9%) had bronchodilator response, 31% had increased FE and was associated with postnatal weight gain. In the pPRISm group (9%), 13% responded to bronchodilators, FE was not increased and was non-significantly associated with body mass index (p=0.064).
CONCLUSIONS
Further to airway obstruction, we describe airway dysanapsis and pPRISm spirometry phenotypes in survivors of prematurity, both of which have poor outlook in other disease groups. By identifying specific phenotypes, targeted therapy can be developed to improve long-term outcomes.
Topics: Humans; Infant, Newborn; Bronchodilator Agents; Bronchopulmonary Dysplasia; Forced Expiratory Volume; Lung; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Spirometry; Vital Capacity; Premature Birth; Infant, Premature
PubMed: 36725332
DOI: 10.1136/thorax-2022-219301 -
The European Respiratory Journal Jun 2022
Topics: Bronchiectasis; Bronchodilator Agents; Cross-Over Studies; Humans; Tiotropium Bromide
PubMed: 35680152
DOI: 10.1183/13993003.03127-2021 -
Molecules (Basel, Switzerland) Oct 2021is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for...
is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of in diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of (Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K (80 mM)-induced, and carbachol (1 µM)-induced jejunum contractions in a concentration-dependent manner similar to dicyclomine and dantrolene. Pp.Cr showed a rightward parallel shift of concentration-response curves (CRCs) of Cch after a non-parallel shift similarto dicyclomine and shifted CRCs of Ca to rightward much likeverapamil and dantrolene, demonstrating the coexistence of antimuscarinic and Ca antagonistic mechanism. Furthermore, Pp.Cr, dicyclomine, and dantrolene relaxed K (80 mM)-induced and Cch (1 µM)-induced tracheal contractions and shifted rightward CRCs of Cch similar to dicyclomine, signifying the dual blockade. Additionally, Pp.Cr also relaxed the K (80 mM)-induced and phenylephrine (1 µM)-induced aortic contraction, similarly to verapamil and dantrolene, suggesting Ca channel antagonism. Here, we explored for the first time thespasmolytic and bronchodilator effects of Pp.Crand whether they maybe due to the dual blockade of Ca channels and muscarinic receptors, while the vasodilator effect might be owing to Ca antagonism. Our results provide the pharmacological evidence that could be a new potential therapeutic option to treat gastrointestinal, respiratory, and vascular diseases. Hence, there is a need for further research to explore bioactive constituent of as well as further investigation by suitable experimental models are required to further confirm the importance and usefulness of in diarrhea, asthma, and hypertension treatment.
Topics: Animals; Biological Products; Bronchodilator Agents; Calcium Channel Blockers; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Mice; Molecular Structure; Muscarinic Antagonists; Parasympatholytics; Parmeliaceae; Spectrum Analysis; Toxicity Tests, Acute; Vasodilator Agents
PubMed: 34770756
DOI: 10.3390/molecules26216348