Background Children born preterm with chronic lung disease of Immaturity (CLDI) frequently present with obstructive lung function, yet optimal bronchodilator therapy remains uncertain. Previous studies focused on β2-agonists, while evidence for muscarinic antagonist therapy is limited. Methods We conducted a prospectively planned cross-sectional study of preterm-born children (<35 weeks) with CLDI and obstructive spirometry (FEV1 z-score < –1.64). Of 73 screened, 64 were enrolled and 55 completed the protocol. Each attended three randomized crossover visits with salbutamol, ipratropium bromide, or fenoterol/ipratropium combination. Spirometry was performed before and after administration. Results Overall, 48 children demonstrated bronchodilator responsiveness to at least one agent. Response rates were 56.4% for salbutamol (95% CI 43–70), 58.2% for ipratropium (95% CI 45–71), and 65.5% for the combination (95% CI 53–78), with no significant differences (McNemar’s test, p = 0.45). Exclusive responses were observed in 9.1% to salbutamol (95% CI 3.0 - 20.0), 5.5% to ipratropium (95% CI 1.1 – 15.1), and 9.1% to the combination (95% CI 3.0 - 20.0). Among children with reversibility, repeated-measures ANOVA showed no significant effect of drug (F = 0.1, p = 0.9), phenotype (F = 2.46, p = 0.12), or their interaction (F = 1.1, p = 0.34). Conclusions In our cohort, 87% of preterm-born children with CLDI exhibit reversible bronchial obstruction, with a substantial subset responding exclusively to a single bronchodilator. Due to the fact that single-drug testing may underestimate reversibility, individualized bronchodilator testing should be incorporated into care, and its long-term implications merit further study.
