Research in context
Evidence before this study
For the past 25 years, most asthma guidelines have consistently recommended treatment according to level of baseline symptom frequency; patients with intermittent symptoms, mostly classified as 2 days or fewer per week, are generally prescribed short-acting β2 agonist (SABA) reliever, while only patients with so-called persistent asthma are eligible for inhaled corticosteroids (ICS) therapy. We did a systematic review to identify studies comparing ICS and placebo in patients with mild intermittent asthma, identified by baseline symptoms or SABA use ≤2 days per week. We searched PubMed using the following string: “((Asthma[MeSH Terms]) AND (mild[Title/Abstract] OR intermittent[Title/Abstract]) AND placebo[Title/Abstract]) AND (randomized controlled trial[Publication Type] OR meta-analysis[Publication Type]) AND (*corticosteroid OR corticosteroid* OR budesonide OR fluticasone OR beclometasone OR beclomethasone OR mometasone OR ciclesonide) AND ((‘1990/01/01’[EDAT] : ‘2015/04/20’[EDAT]) OR (‘1990/01/01’[PDAT]: ‘2015/04/20’[PDAT])) AND (‘humans’[MeSH Terms])”. We also searched the most recent Cochrane reviews of each of the above ICS.
A total of six studies comparing ICS and placebo in people with mild asthma remained for evaluation. Only two very small studies restricted enrolment to people with symptoms less than or equal to 2 days per week. None of the other studies included in this literature review assessed treatment efficacy according to the level of baseline symptoms, so it is unclear whether patients with less frequent asthma symptoms at baseline benefit from ICS treatment, or whether there is evidence to support the present symptom-based criteria for initiating ICS. In the present study, we seek to assess these issues.
Added value of this study
To our knowledge, this study is the first to assess the appropriateness of long-standing criteria for initiation of ICS treatment in mild asthma. In this post-hoc investigation of a large pragmatic study of patients with recently diagnosed asthma (within the previous 2 years), we compared the efficacy of low-dose budesonide versus placebo on asthma outcomes, dividing participants by baseline asthma symptom frequency (0–1 symptom days per week, >1 to ≤2 symptom days per week, and >2 symptom days per week). We found that the use of once-daily, low-dose budesonide increases time to first severe asthma-related events (emergency visits, hospital admission, or death), halves the risk of severe exacerbations, reduces lung function decline, and improves asthma symptoms compared with placebo, irrespective of baseline symptom frequency (or any other criterion for so-called persistent asthma). We thus found no evidence to support the past recommendation that patients with asthma should be treated with SABA alone unless their symptoms exceed 2 days per week at presentation.
Implications of all the available evidence
Low-dose ICS leads to substantial risk reduction in mild asthma, both for exacerbations and for decline in lung function, in patients with infrequent baseline symptoms who would not previously have been considered for ICS treatment. The findings challenge long-standing assumptions about the risks of so-called mild asthma, and suggest that decisions about ICS treatment in such patients should be made on the basis of population risk reduction, rather than only on symptom frequency. However, regular daily ICS treatment might not necessarily be appealing to clinicians and patients, because of concerns about adherence and side-effects. Alternative treatment options with an as-needed combination of ICS and β2 agonist might be more acceptable to clinicians and patients, and are being investigated.