Exhaled Nitric Oxide in Wheezy Infants Predicts Persistent Atopic Asthma and Exacerbations at School Age

Background: There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO) in infants/toddlers with recurrent wheezing for asthma at school age. Objectives: In a cohort of infants/toddlers with recurrent wheezing determine the predictive values of sedated single-breath FENO (SB-FENO) and awake tidal-breathing mixed-expired FENO (tidal-FENO) for active asthma, severe exacerbations, and lung function at age 6 years. Methods: In 44 infants/toddlers, SB-FENO was measured under sedation at 50 mL/sec in conjunction with forced expiratory flow and volume measurements, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes and lung function were assessed at age 6 years in 36 subjects. Results: Enrollment SB-FENO was significantly higher among subjects with active asthma at age 6 years than among subjects without asthma (36.4 vs. 16.9 ppb, p < 0.0001), and the odds of asthma was 7.6 times greater (OR 7.6; 95% CI 1.8-31.6) for every 10 ppb increase in enrollment SB-FENO. A ROC analysis demonstrated that an enrollment SB-FENO > 31.5 ppb predicted active asthma at age 6 years with an area under the curve (AUC) of 0.92 (95% CI: 0.82-1). SB-FENO was also higher among subjects who experienced severe asthma exacerbations during the year preceding age of 6 years. SB-FENO at enrollment and lung function measures at age 6 years were modestly correlated (FEV1: r = -0.4; FEF25-75: r = -0.41; FEV1/FVC ratio: r=-0.46), and SB-FENO was significantly higher among subjects with bronchodilator responsiveness (BDR) at age 6 years. Tidal-FENO was not predictive of active asthma, exacerbations, or lung function at age 6 years. Conclusion: In wheezy infants/toddlers, SB-FENO was predictive of school-age asthma and associated with lung function measures at age 6 years.