The burden of exacerbations in mild asthma: a systematic review

BACKGROUND: Although most patients with asthma have mild disease, data on how mild asthma is defined, and how frequently exacerbations occur in this patient population are scarce, so we aimed to redress this. METHODS: We searched Medline and Medline In-Process (PubMed), and Embase in OVID for English-language publications containing "mild asthma" plus at least one relevant therapy and outcome/keyword, limited to randomised controlled trials (RCTs) and observational studies published between January 1990 and February 2019. Publications were filtered to ensure appropriate data extraction. The main outcomes were the definitions of mild asthma and exacerbations, baseline exacerbation rates and exacerbation data for placebo recipients in prospective studies. Meta-analysis of exacerbation rates was planned. FINDINGS: Of 4064 articles identified, 64 were included in our review (49 743 subjects); 54 RCTs and 10 observational/other studies. Six main types of definitions of mild asthma were identified. While care was taken to ensure inclusion only of patients with mild asthma, marked heterogeneity was revealed in the definitions of mild asthma and hence the study populations. Reporting of exacerbations also varied widely between studies, precluding meta-analysis. Between 0-22% of patients were hospitalised for asthma or had a severe exacerbation in the previous year, according to baseline data from prospective studies. In RCTs, severe exacerbation rates in placebo recipients taking only short-acting β₂-agonist therapy ranged from 0.20-2.88 per year. CONCLUSIONS: These data provide new evidence of the burden of exacerbations in mild asthma and highlight the need for standardised definitions of mild asthma and of exacerbations to progress further research.