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Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents: a systematic review and meta-analysis.

ABSTRACT: Leukotriene-receptor antagonists (LTRAs) are recommended as an alternative treatment in patients with mild asthma, but their effect compared with placebo is unclear.To determine the benefits and harms of LTRAs as monotherapy or in combination with inhaled corticosteroids compared with placebo in adults and adolescents with asthma.MEDLINE and the Cochrane Central Register of Controlled Trials from inception through June 2015.Peer-reviewed, English-language, randomized, controlled trials in patients with asthma that reported the effect of LTRAs versus placebo on measures of asthma control.Three researchers extracted data on study population, interventions, outcome measures, and adverse events. One researcher assessed risk of bias.Of the 2008 abstracts that were screened, 50 trials met eligibility criteria. Random-effects meta-analyses of 6 trials of LTRA monotherapy showed that LTRAs reduced the risk for an exacerbation (summary risk ratio [RR], 0.60 [95% CI, 0.44 to 0.81]). In 4 trials of LTRAs as add-on therapy to inhaled corticosteroids, the summary RR for exacerbation was 0.80 (CI, 0.60 to 1.07). Leukotriene-receptor antagonists either as monotherapy or as add-on therapy to inhaled corticosteroids increased FEV1, whereas FEV1 percentage of predicted values was improved only in trials of LTRA monotherapy. Adverse event rates were similar in the intervention and comparator groups.Variation in definitions and reporting of outcomes, high risk of bias in some studies, heterogeneity of findings, possible selective outcome reporting bias, and inability to assess the effect of asthma severity on summary estimates.Leukotriene-receptor antagonists as monotherapy improved asthma control compared with placebo, but which patients are most likely to respond to treatment with LTRAs remains unclear.National Institutes of Health.

SUBMITTER: Miligkos M

PROVIDER: S-EPMC4648683 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents: a systematic review and meta-analysis.

Miligkos Michael M Bannuru Raveendhara R RR Alkofide Hadeel H Kher Sucharita R SR Schmid Christopher H CH Balk Ethan M EM

Annals of internal medicine 20150922 10

<h4>Background</h4>Leukotriene-receptor antagonists (LTRAs) are recommended as an alternative treatment in patients with mild asthma, but their effect compared with placebo is unclear.<h4>Purpose</h4>To determine the benefits and harms of LTRAs as monotherapy or in combination with inhaled corticosteroids compared with placebo in adults and adolescents with asthma.<h4>Data sources</h4>MEDLINE and the Cochrane Central Register of Controlled Trials from inception through June 2015.<h4>Study select ...[more]

PMID: 26390230

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Project description:BackgroundAsthma is the most common chronic condition of childhood. Leukotriene receptor antagonists (LTRAs) are included in international guidelines for children and young people (CYP), but there have been highly publicised concerns about potential adverse effects. The aim was to identify and understand the reported frequency of adverse drug reactions (ADRs) attributed to LTRAs in CYP with asthma.MethodsEmbase, MEDLINE, PubMed and CINAHL were searched up to October 2020. Reference lists of eligible papers were manually screened. Eligible studies identified adverse events attributed to an LTRA in individuals aged between 0 and 18 years diagnosed with asthma. Four different tools were used to assess risk of bias or quality of data to accommodate the papers assessed.ResultsThe search identified 427 papers after deduplication; 15 were included (7 case reports, 7 case-controlled or cohort studies and 1 randomised control trial (RCT)). 7012 patients were recorded, of which 6853 received an LTRA. 13 papers examined the ADRs attributed to montelukast, one to pranlukast and one to unspecified LTRAs. After language standardisation, 48 ADRs were found, 20 of which were psychiatric disorders. Across all studies, the most commonly reported ADRs were 'anxiety', 'sleep disorders' and 'mood disorders'. The frequency of ADRs could be calculated in seven of the eight studies. Applying standardised frequency terms to the prospective studies and RCT, there were 14 'common' and 'uncommon' ADRs. 'Common' ADRs included 'agitation/hyperactivity/irritability/nervousness', 'aggression' and 'headache'. The case reports showed a similar pattern, describing 46 different ADRs experienced by a total of eight patients.ConclusionsLTRAs have a wide range of suspected ADRs in CYP, predominantly gastrointestinal and neuropsychiatric disorders. Careful monitoring of CYP with asthma is required, both to assess and manage ADRs and to step treatment down when clinically stable.Prospero registration numberCRD42020209627.

Project description:Rationale: Acute exposure to ambient particle matter is associated with increased levels of the cysteinyl leukotriene (CysLT) biomarker, urinary leukotriene E4 (uLTE4), in subjects with asthma. Objectives: The role of CysLTs in mediating asthma worsening after particulate matter exposures was explored. Methods: Daily concentrations of particulate matter of 2.5 ?m and smaller diameter (PM2.5) and repeated measurements of albuterol use over a 5-month period were collected in 44 urban school children with persistent asthma. DNA was analyzed for gene polymorphisms on genes involved in the CysLT pathway to identify gene–environment interactions. An experimental challenge study in 16 adults with mild, nonpersistent asthma was performed to define biological pathways explaining these gene–environment interactions. Subjects in the challenge study were exposed on two different days to filtered air or diesel exhaust (300 ?g PM2.5/m3). FEV1 and CysLT-related gene DNA methylation and messenger RNA expression changes were measured before and 6 hours after exposure challenges. Results: In school children with asthma, associations between PM2.5 and school-time albuterol usage were significantly greater in those with the variant C allele in the CysLT receptor 1 (CysLTR1) rs320995 locus (5.4% increase per interquartile range PM2.5 increase) compared with those homozygous for the wild-type T allele (1.6% decrease; P?=?0.005 for allele?×?PM2.5 interaction). In the challenge study, declines in forced expiratory volume in 1 second after diesel exhaust exposure were associated with lower CysLTR1 expression (r2?=?0.52; P?=?0.01), which, in turn, was associated with decreased leukotriene C4 synthase cg1631890 (P?=?0.02) and increased CysLTR1 cg26848126 (P?=?0.01) methylation, as assessed in a multivariable model (r2?=?0.69). Conclusions: Health effects of acute particulate exposure on asthma are associated with changes in CysLTR1 expression and methylation of CpG sites on CysLTR1 and leukotriene C4 synthase genes.

Dataset Information

Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents: a systematic review and meta-analysis.

Publications

Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents: a systematic review and meta-analysis.

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