Abstract Rationale Respiratory infections in infancy occur during a critical period of lung growth and immune maturation. Most viral infections in the first year of life are caused by Respiratory Syncytial Virus (RSV). While severe bronchiolitis has been consistently linked to an increased risk of developing asthma, the long-term consequences of milder, community-managed infections remain poorly understood. Methods A nationwide retrospective case-control study was conducted using the Clalit Health Services (CHS) database. The cohort included 110,927 infants born between 2015 and 2023 who were younger than 12 months and had at least one visit to a pediatric community clinic during the RSV seasons (November 1 to March 31). Infants diagnosed with respiratory conditions comprised the Community-Attended Respiratory Symptoms (CARS) group, while those with non-respiratory visits served as Medically Attended Non-Respiratory Controls (MANRC). Asthma incidence up to age six was determined using the validated Asthma Integrated Diagnosis Index (AIDI). Multivariate models were adjusted for sex, ethnicity, season of birth, prematurity, cesarean delivery, and underlying comorbidities. Results The study included 58,576 CARS and 52,351 MANRC infants. Adjusted analyses showed markedly higher acute healthcare utilization during the first RSV season of life in CARS infants, including systemic corticosteroids (adjusted-IRR 9.7; 95% CI 9.1-10.4), inhaled corticosteroids (adjusted-IRR 10.7; 9.9-11.5), β-agonists (adjusted-IRR 14.6; 13.8-15.5), and hospitalization duration (adjusted-IRR 2.0; 2.0-2.1; all p 0.001). Long-term models showed sustained excess utilization through age six: pediatric pulmonologist visits (adjusted-IRR 1.81), respiratory-related ED visits (adjusted-IRR 1.37), and hospitalizations (adjusted-IRR 1.30). AIDI was 26% vs. 16% (adjusted-OR 1.71; 95% CI 1.66-1.76; p 0.001). Conclusions Mild, medically attended respiratory infections during infancy were independently associated with increased asthma risk and greater long-term respiratory-related healthcare utilization. These findings suggest that early viral exposures, largely dominated by RSV during the study season, may contribute to, or serve as a marker of, subsequent lung maldevelopment and immune dysregulation. This abstract is funded by: Sanofi and AstraZeneca funded this study. Lital Hertz and Oliver Martyn are employees of and may own stock/share options in Sanofi.
Hazan et al. (Fri,) studied this question.