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 (FE_NO) 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 FE_NO (SB-FE_NO) and awake tidal-breathing mixed-expired FE_NO (tidal-FE_NO) for active asthma, severe exacerbations, and lung function at age 6 years. Methods: In 44 infants/toddlers, SB-FE_NO was measured under sedation at 50 mL/sec in conjunction with forced expiratory flow and volume measurements, and tidal-FE_NO was measured during awake tidal breathing. Clinical outcomes and lung function were assessed at age 6 years in 36 subjects. Results: Enrollment SB-FE_NO 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-FE_NO. A ROC analysis demonstrated that an enrollment SB-FE_NO > 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-FE_NO was also higher among subjects who experienced severe asthma exacerbations during the year preceding age of 6 years. SB-FE_NO 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-FE_NO was significantly higher among subjects with bronchodilator responsiveness (BDR) at age 6 years. Tidal-FE_NO was not predictive of active asthma, exacerbations, or lung function at age 6 years. Conclusion: In wheezy infants/toddlers, SB-FE_NO was predictive of school-age asthma and associated with lung function measures at age 6 years.