Modification of asthma treatment efficacy by healthcare access: A reanalysis of AsthmaNet Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) clinical trial

Abstract

Background: While randomized controlled trials (RCTs) in asthma management are designed to balance known and unknown variables across treatment groups, including social and environmental co-exposures, it remains important to consider how these co-exposures influence disease progression and treatment outcomes. The importance of considering socio-environmental co-exposures in the context of asthma is twofold: 1) asthma disproportionately affects low-income urban communities, where air pollution and chronic stress are pervasive; and 2) despite the wide range of asthma treatments, inadequate disease control persists.

Methods: In the present ancillary study of the Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) RCT, we investigated how socio-environmental factors, such as air pollution exposure and healthcare access, modify the effect of inhaled corticosteroid (ICS) therapy in children with asthma. The original STICS RCT evaluated the efficacy and safety of increasing the dose of inhaled glucocorticoids from a baseline daily low dose to five times the daily dose for 7 days in school-age children with mild -to-moderate persistent asthma who began to have short-term loss of asthma control (Jackson et al., 2018 Mar 8) [1]. Our study adds onto those findings by incorporating residential level particulate matter 2.5 μg/m3 (PM2.5) and geographic health provider shortage areas (HPSA) as potential modifiers.

Results: Consistent with the main trial results, we did not find a difference in the number of exacerbations between treatment arms. However, we found the effect of receiving 5xICS, as compared with 1xICS on the time to prednisone was significantly different for children living in areas a shortage of health professionals (HR: 2.09; 95 % CI: 0.74, 5.95) than for children living in no shortage areas (HR: 0.40; 95 % CI: 0.21, 0.77).

Conclusion: This finding underscores the importance of considering environmental and social factors in asthma treatment.

Trial registration: ClinicalTrials.gov ID NCT02066129 https://clinicaltrials.gov/study/NCT02066129.

Keywords: ICS; Pediatric asthma; RCT; SDOH.

Fig. 1.

Associations between treatment with 5xICS (versus 1xICS) and severe asthma exacerbations treated with systemic glucocorticoids by A) Median dichotomized NO₂ exposure among children in STICS trial, B) Median dichotomized O₃ exposure among children in STICS trial C) Median dichotomized PM_2.5 exposure among children in STICS trial. Incidence Rate Ratios (IRR) and 95 % confidence intervals are presented, and P-values shown are for the interaction term between treatment and each modifier.

Fig. 2.

Associations between treatment with 5xICS (versus 1xICS) and severe asthma exacerbations treated with systemic glucocorticoids by 1) Health provider shortage areas (left) 2) Medically Underserved Areas (right). Incidence Rate Ratios (IRR) and 95 % confidence intervals are presented, and P-values shown are for the interaction term between treatment and each modifier.

Fig. 3.

Time to prednisone use in non-HPSA and HPSA (left) areas (p for interaction = 0.01). Time to treatment failure in non-HPSA and HPSA (right) areas (p for interaction 0.03). Blue line = low dose group (1xICS); red line = high dose group (5xICS).