Metrics of salbutamol use as predictors of future adverse outcomes in asthma

BACKGROUND: Beta-agonist overuse is associated with adverse outcomes in asthma, however, the relationships between different metrics of salbutamol use and future risk are uncertain. OBJECTIVE: To investigate the relationship between metrics of salbutamol use and adverse outcome. METHODS: In a 24-week randomized controlled trial of 303 asthma patients at risk of severe exacerbations which compared the efficacy and safety of combination budesonide/formoterol inhaler according to a single inhaler regimen (SMART) with a fixed-dose regimen with salbutamol as reliever ('Standard'), actual medication use was measured by electronic monitoring (Australian New Zealand Clinical Trials Registry Number ACTRN12610000515099). A nested cohort study explored the relationship between metrics of baseline salbutamol use over 2 weeks and future severe asthma exacerbations, poor asthma control (ACQ-5 ≥ 1.5) or 'extreme' salbutamol overuse (> 32 salbutamol actuations/24-h period). RESULTS: Higher mean daily salbutamol use (per two actuations/day) Odds ratio (OR) (95% CI) 1.24 (1.06-1.46), higher days of salbutamol use (per 2 days in 2 weeks) OR 1.15 (1.00-1.31) and higher maximal 24-h use (per two actuations/day) OR 1.09 (1.02-1.16) were associated with future severe exacerbations. Higher mean daily salbutamol use was associated with future poor asthma control OR 1.13 (1.02-1.26). Higher mean daily salbutamol use OR 2.73 (1.84-4.07), number of days of use OR 1.46 (1.24-1.71), and maximal daily use OR 1.57 (1.31-1.89) were associated with an increased risk of future extreme salbutamol overuse. CONCLUSION AND CLINICAL RELEVANCE: Electronically recorded frequency of current salbutamol use is a strong predictor of risk of future adverse outcomes in asthma, with average daily use performing the best. These findings provide new information for clinicians considering metrics of salbutamol as predictors of future adverse outcomes in asthma.