Severe asthma exacerbations associated with short-acting beta 2 agonist use

Increasing exposure to short-acting beta 2 agonist rescue or reliever medication appeared associated with greater risk for severe asthma exacerbations regardless of inhaled corticosteroid use, according to study results.

Published in The Journal of Allergy and Clinical Immunology: In Practice, the study results suggest that rescue/reliever management using short-acting beta 2 agonist (SABA) monotherapy should be avoided, according to the researchers.

Jennifer K. Quint, MD, PhD, FRCP, professor of respiratory epidemiology at Imperial College London National Heart and Lung Institute, and colleagues examined data from 1,033,564 patients in the SABa use IN Asthma (SABINA) series of observational studies including 10 North American and European datasets.

Patients were aged 12 years and older with asthma and had been prescribed or possessed at least one SABA canister per year. Mean ages ranged across the datasets from 23.2 years (U.S. Medicaid cohort) to 72.2 years (U.S. Medicare cohort), and most patients were women (range across datasets, 55.8%-68.2%).

With a Global Initiative for Asthma (GINA) score of one or two, 56.5% of patients had mild asthma. Also, 40.2% of patients were prescribed or possessed three or more SABA canisters a year, and only 39.2% of patients with GINA scores between 2 and 5 received maintenance therapy 50% or more of the time.

Patients who were prescribed or who possessed one or two SABA canisters per year had a numerically lower mean number of severe exacerbations than patients who were prescribed or who possessed three or more canisters per year in every dataset but one, with the greatest association observed in Poland (incidence rate ratio [IRR] = 2.15; 95% CI, 2.01-2.3).

The exception was the dataset based on Medicare findings, in which patients who were prescribed or who possessed one or two canisters per year saw higher incidence of severe exacerbations than patients with three or more canisters per year (IRR = 0.89; 95% CI, 0.86-0.91).

Patients who had GINA scores of three to five and three or more prescriptions or possessions of SABA canisters per year experienced more severe exacerbations than patients with fewer canisters per year across all countries and datasets.

Within the U.S. datasets, patients with GINA scores between two and five had higher incidences of severe exacerbations with three or more vs. one to two SABA canisters per year (IRR = 1.23; 95% CI, 1.22-1.24) than those with GINA scores between 1 and 5 (IRR = 1.03; 95% CI, 1.02-1.04).

In fact, the researchers wrote, there was an association between use of three or more SABA canisters per year and increased incidence of exacerbations that required emergency, face-to-face evaluations with health care providers or hospitalizations among patients treated via SABA monotherapy in the U.S. (IRR = 1.31; 95% CI, 1.29-1.34).

“These data are concordant with observations that U.S. patients and health care providers tend to underestimate the consequences of asthma symptoms, relying predominantly on

SABA for rapid relief,” the researchers wrote. “These findings suggest the need for inhaled corticosteroid administration, either as regular maintenance treatment or intermittently, to address variability in airway inflammation in SABA monotherapy-treated patients and lend support to the GINA recommendation of not distinguishing intermittent from mild persistent asthma.”

Overall, the researchers found a 32.2% (adjusted IRR = 1.32; 95% CI, 1.18-1.49) greater risk for severe exacerbations among patients who were prescribed or who possessed three or more canisters per year than those with one or two canisters, independent of inhaled corticosteroid use or other exacerbation risk factors.

These findings indicate that asthma may remain uncontrolled even though these patients have potentially reasonable exposure to their prescribed maintenance therapy, showing that their asthma severity may be underestimated, the researchers wrote.

Providers may use yearly SABA canister prescription and possession totals of three or more as a practical and quantitative measure of reliance on SABA and as an aid in tracking rescue and reliever use, the researchers continued, adding that careful monitoring of SABA use at any level could help identify at-risk patients.