BACKGROUND: -agonist (ICS + LABA) therapy in preschool children with asthma remains limited, and guideline recommendations remain cautious. However, real-world effectiveness in high-risk young children has not been adequately characterized. OBJECTIVE: To evaluate short- and long-term effectiveness of ICS + LABA initiation on severe asthma exacerbations (SAEs) and determine whether early-life asthma risk burden modifies treatment response. METHODS: We conducted a retrospective longitudinal cohort study using electronic health record data from the Indiana Network for Patient Care (2010-2024). Children aged ≤11 years with asthma who initiated ICS + LABA between 2010 and 2023 and had ≥12 months of pre- and post-initiation follow-up were included. The primary outcome was ≥1 SAE per year, defined per ATS/ERS criteria as asthma-related hospitalization or emergency department admission. Piecewise generalized linear mixed-effects models estimated annualized changes in SAE odds before versus after ICS + LABA initiation. Recurrent events were analyzed using Andersen-Gill models. Effect modification by age at diagnosis, age at prior ICS initiation, and early-life asthma risk burden (passive digital marker PDM score) was assessed. RESULTS: Among 249 children (mean age at asthma diagnosis 2 years; at ICS + LABA initiation 5 years), annualized SAE incidence increased before initiation and declined thereafter. Adjusted SAE odds decreased by 15% per year following ICS + LABA initiation (aOR 0.85; 95% CI 0.58-0.98). Recurrent-event modeling demonstrated a 68% reduction in SAE hazard after ICS + LABA initiation (aHR 0.32; 95% CI 0.26-0.38), exceeding reductions observed with ICS alone (aHR 0.49). Treatment benefit was greatest among children initiating ICS before age 5 years (aOR 0.77; 95% CI 0.65-0.92) and those with high early-life asthma risk burden (aOR 0.80; 95% CI 0.67-0.97). No significant heterogeneity was observed by sex, race, or formulation. CONCLUSIONS: ICS + LABA initiation was associated with sustained reductions in severe exacerbations, including among preschool children, in real-world clinical practice. These findings suggest that strict age-based treatment restrictions may not fully capture heterogeneity in exacerbation risk and support further prospective evaluation of risk-stratified escalation strategies.
Owora et al. (Mon,) studied this question.