Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme

Abstract

Background: Overuse of short-acting β₂-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA (over)use on asthma exacerbations and mortality are scarce, prompting initiation of the global SABINA (SABA use IN Asthma) programme.

Methods: By linking data from Swedish national registries, asthma patients aged 12-45 years with two or more collections of drugs for obstructive lung disease during 2006-2014 were included. SABA overuse was defined as collection of more than two SABA canisters in a 1-year baseline period following inclusion. SABA use was grouped into 3-5, 6-10 and ≥11 canisters per baseline-year. Cox regression was used to examine associations between SABA use and exacerbation (hospitalisations and/or oral corticosteroid claims) and mortality.

Results: The analysis included 365 324 asthma patients (mean age 27.6 years; 55% female); average follow-up was 85.4 months. 30% overused SABA, with 21% collecting 3-5 canisters per year, 7% collecting 6-10 canisters per year and 2% collecting ≥11 canisters per year. Increasing number of collected SABA canisters was associated with increased risk of exacerbation, as follows. 3-5 canisters: hazard ratio (HR) 1.26 (95% CI 1.24-1.28); 6-10 canisters: 1.44 (1.41-1.46); and ≥11 canisters: 1.77 (1.72-1.83), compared to two or fewer canisters per year. Higher SABA use was associated with incrementally increased mortality risk (2564 deaths observed), as follows. 3-5 canisters: HR 1.26 (95% CI 1.14-1.39); 6-10 canisters 1.67 (1.49-1.87); and ≥11 canisters: 2.35 (2.02-2.72) compared to two or fewer canisters per year.

Conclusion: One-third of asthma patients in Sweden collected three or more SABA canisters annually. SABA overuse was associated with increased risks of exacerbation and mortality. These findings emphasise that monitoring of SABA usage should be key in improving asthma management.

FIGURE 1

Flow chart of study population. SABA: short-acting β₂-agonist.

FIGURE 2

Associations between baseline short-acting β₂-agonist (SABA) use and treatment step and subsequent risk of asthma exacerbation. Adjusted for age at asthma diagnosis, sex, treatment step and comorbidity. ≤2 canisters: patients collecting two or fewer SABA canisters during the baseline year; ≥3 canisters: patients collecting three or more SABA canisters during the baseline year; HR: hazard ratio.

FIGURE 3

Exacerbation-free survival in different baseline period short-acting β₂-agonist (SABA) use groups. a) Patients not treated with inhaled corticosteroids (ICS) during the baseline year, n=100 588; b) patients treated with ICS during the baseline year, n=264 736.

FIGURE 4

Kaplan–Meier plot of overall survival by baseline short-acting β₂-agonist (SABA) use.

FIGURE 5

Association between baseline short-acting β₂-agonist (SABA) use and risk of mortality. a) Overall mortality; b) asthma-related mortality; c) respiratory-related mortality. Adjusted for treatment step, Charlson Comorbidity Index, sex and age. ≤2 canisters: patients collecting two or fewer SABA canisters during the baseline year; ≥3 canisters: patients collecting three or more SABA canisters during the baseline year; HR: hazard ratio.