SABA overuse associated with increased risk for exacerbations among children with asthma

Defined as three or more canisters a year, overuse of short-acting beta 2 agonists was associated with increased risk for exacerbations among children with asthma, according to a study published in Pediatric Allergy and Immunology.

These risks were particularly high among children who did not have comorbid atopic diseases, Erik Melén, MD, PhD, professor of pediatrics in the department of clinical sciences and education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden, and colleagues wrote.

The researchers analyzed data from 219,561 patients (40.2% girls), including 52.1% who were aged 0 to 5 years, 26.5% who were aged 6 to 11 years and 21.4% who were aged 12 to 17 years. Specifically, 21.9% of those aged 0 to 5 years, 49.1% of those aged 6 to 11 and 58.5% of those aged 12 to 17 years had comorbid atopic disease.

At baseline, 65.7% of those aged 0 to 5 years, 72.8% of those aged 6 to 11 years and 73.5% of those aged 12 to 17 years collected no canisters with inhaled corticosteroids (ICS) or one or two ICS canisters.

Baseline exacerbation rates (per 100 person-years) included 16.52 (95% CI, 16.29-16.76) for those aged 0 to 5 years, 12.19 (95% CI, 11.91-12.48) for those aged 6 to 11 years and 16.09 (95% CI, 15.73-16.45) for those aged 12 to 17 years.

Also during the baseline year, 45.4% of those aged 0 to 5 years, 31.7% of those aged 6 to 11 years and 26.5% of those aged 12 to 17 years claimed three or more short-acting beta 2 agonist (SABA) canisters. Across age groups, SABA collections increased with numbers of ICS canisters and treatment steps at baseline.

Follow-ups at 1 year revealed increases in unadjusted exacerbation rates with baseline SABA collection for all age groups, with the lowest rates among the youngest group and the highest rates among the oldest group.

When collections of three or more SABA canisters were compared with collections of zero to two canisters, the 1-year follow-up revealed increased exacerbation rates including incident rate ratios of 1.35 (95% CI, 1.29-1.42) for the group aged 0 to 5 years, 1.22 (95% CI, 1.15-1.29) for the group aged 6 to 11 years and 1.26 (95% CI, 1.19-1.34) for the group aged 12 to 17 years.

The researchers further said they found a dose-response relation when they examined SABA as an ordinal and continuous variable, with similar results seen during 3 years of follow-up.

Children with and without overuse both experienced a significant association between baseline SABA collection and risk for asthma exacerbations when stratified by presence of atopic disease, with the association stronger among those who did not have comorbid atopic disease (P < .001).

The researchers also found an association between the collection of three or more SABA canisters at baseline compared with the use of zero to two canisters and a greater risk for any asthma exacerbation during a 1 year follow-up among patients with nonatopic disease vs. those with atopic disease.

Incident rate ratios for this association included 1.44 (95% CI, 1.35-1.54) vs. 1.21 (95% CI, 1.12-1.31) for the group aged 0 to 5 years, 1.32 (95% CI, 1.17-1.49) vs. 1.14 (95% CI, 1.07-1.22) for the group aged 6 to 12 years and 1.44 (95% CI, 1.27-1.64) vs. 1.2 (95% CI, 1.12-1.28) for the group aged 12 to 17 years.

This relationship persisted through 3 years of follow-up, the researchers continued, adding that they observed similar results for the risk for the first exacerbation in the overall analysis and when they stratified for atopic disease regardless of the follow-up period.

The predicted rate for any type of exacerbation during the 1 year follow-up increased with higher SABA canister collection at baseline with stratification by presence of atopic disease as well.

There also was a steeper increase in exacerbation rate with high SABA canister collection among patients with nonatopic disease even though there was a lower exacerbation rate with collection of zero SABA canisters among these patients, compared with those with atopic disease.

Overall, the researchers said that SABA overuse was associated with a 35% increased risk for exacerbations among the group aged 0 to 5 years, 22% among the group aged 6 to 11 years and 26% for the group aged 12 to 17 years, regardless of atopic status at baseline.

When atopic status was considered, risks increased by 32% to 44% across the age groups for the patients who did not have comorbid atopic disease compared with 14% to 21% across the age groups for those with comorbid atopic disease.

Considering these findings, the researchers called for educational initiatives that target pediatric patients, their caregivers and clinicians designed to align asthma treatment with updated global evidence-based recommendations.