SABA Overuse Linked to Increased Mortality, Acute Exacerbations in Asthma

Short-acting beta-agonist (SABA) overuse is associated with increased rates of mortality and acute exacerbations in patients with asthma, according to findings from a recent study.1

Results of the systematic review and meta-analysis provide high-level evidence supporting current asthma treatment guidelines from the Global Initiative for Asthma, which advise against SABA monotherapy for the management of asthma.1

In a 2019 update to its global strategy for asthma management and prevention, the Global Initiative for Asthma indicated it no longer recommends SABA-only treatment for adults and adolescents with asthma, citing strong evidence that SABA monotherapy increases the risk of severe exacerbations and asthma-related death. Instead, it supports the use of symptom-driven or daily inhaled corticosteroid-containing controller treatment.2

“While numerous observational studies highlight the association between SABA overuse and increased asthma complications, high-quality evidence remains limited,” Kevin Sheng-Kai Ma, of the Center for Global Health at Perelman School of Medicine at the University of Pennsylvania, and colleagues wrote.1

To substantiate the association between SABA overuse and adverse outcomes in patients with asthma, investigators conducted a comprehensive literature search of PubMed, Embase, Web of Science, and Cochrane Database of Systematic Reviews databases for peer-reviewed original articles published from 1981 to November 2023 that provided primary data comparing outcomes among patients with asthma who excessively used or were prescribed SABA with those who did not. For inclusion, studies were required to bel randomized controlled trials (RCTs), prospective or retrospective cohort studies, and cross-sectional studies published in English.1

Their search primarily focused on single-use SABA inhalers, such as albuterol or levalbuterol, and excluded combination inhalers or nebulized formulations of ICS, such as budesonide. The primary outcomes were acute exacerbations and all-cause mortality.1

Out of 626 identified records, 27 studies were included in the analysis, including 2 RCTs, 1 prospective cohort study, 12 retrospective cohort studies, and 12 cross-sectional studies.1

Investigators pooled 9 studies, including 4 retrospective cohort studies, 1 RCT, and 4 cross-sectional studies, to assess the association between SABA overuse, defined as ≥ 3 SABA canisters per year, and acute exacerbations. Random-effects meta-analysis revealed a statistically significant increase in the risk of acute exacerbations among patients in the SABA overuse group compared to the control group (risk ratio [RR], 1.93; 95% CI, 1.24–3.03; I2 = 99.9%).1

Further analysis stratified by study design revealed SABA overuse was associated with a significantly increased risk of acute exacerbations compared to controls within retrospective cohort studies (RR, 1.88; 95% CI, 1.43–2.47; I2 = 99.2%) and cross-sectional studies (RR, 2.23; 95% CI, 1.04–4.77; I2 = 99.7%).1

Investigators additionally pooled data from 2 retrospective cohort studies and 1 cross-sectional study to evaluate the effect of SABA overuse on all-cause mortality. The random-effects model meta-analysis comprising 130,629 participants in the SABA overuse group and 300,451 in the control group suggested SABA overuse was associated with a significantly increased all-cause mortality rate (RR, 2.04; 95% CI, 1.37–3.04; I2 = 98.3%).1

“These findings align with previous literature and offer stronger evidence supporting current asthma treatment guidelines, which recommend SABA in combination with ICS or as needed in select populations. Importantly, the confounding factor of low concomitant ICS use may lead to adverse effects of SABA overuse,” investigators concluded.1 “Research is needed to elucidate the mechanisms underlying SABA overuse-related adverse effects, and to support healthcare providers and policymakers in implementing regulations to reduce the asthma-related disease burden associated with SABA overuse.”

References

1. Tsao CL, Chan SY, Lee MH, et al. Adverse Outcomes Associated With Short-Acting Beta-Agonist Overuse in Asthma: A Systematic Review and Meta-Analysis. Allergy. doi:10.1111/all.16538

2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. June 2019. Accessed June 18, 2025. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf