NTR 1756.

The preservation of 3 predictors in models derived from variable populations and the fairly consistent predictive properties of most models in 2 distinct validation populations suggest the feasibility of a generalizable model predicting severe exacerbations. Nevertheless, improvement of the models is warranted because predictive performances are below the desired level.

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma.Design Systematic review and network meta-analysis using Bayesian statistics.Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate.Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome.Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy.Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports. IntroductionAsthma is a widespread chronic airway disease characterised by an unpredictable course.1 Preventing exacerbations is considered a major long term treatment goal in international guidelines.1 These episodes of sudden deterioration of symptoms and airways obstruction result in a burden to the patient and use of expensive medical resources. Asthma related healthcare expenses in patients with exacerbations are double ($1740 (£1035; €1257) v $847) those of patients without exacerbations. Although inhaled corticosteroids-anti-inflammatory controller drugs-are currently the cornerstone of preventing asthma exacerbations, 4-6 several other agents or combination strategiesCorrespondence to: R J B Loymans r.j.loijmans@amc.nl Extra material supplied by the author (see http://www.bmj.com/content/348/bmj.g3009?tab=related#webextra) Table S1: data from included studies Table S2: risk of bias assessment of included studies Table S3: reported harms in included studies Figure S1: analysis with non-imputed data Figure S2: sensitivity analyses for severe exacerbations Figure S3: funnel plots of direct comparisons with five or more studies, for severe exacerbationsNo commercial reuse: See rights and repr...

Currently there is no commonly accepted definition for asthma exacerbations. A prospective definition is desirable. This could be obtained by phenotyping asthma exacerbations based on clinical signs, lung function parameters and possibly other biomarkers.