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

Abstract

Maria P White,1 Tessa K Kolstad,1 Molly Elliott,2 Elizabeth S Cochrane,2 David C Stamey,2 Jason S Debley1,2 1Center for Immunity and Immunotherapies, Seattle Children’s Research Institute, Seattle, WA, USA; 2Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, University of Washington, Seattle, WA, USACorrespondence: Jason S DebleyDepartment of Pediatrics, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, University of Washington, 4800 Sand Point Way NE, Seattle, WA 98105, USATel [phone]Fax [phone]Email [email protected]: 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.Keywords: exhaled nitric oxide, FENO, recurrent wheezing, infants, asthma, pulmonary function, exacerbations

Keywords

• exhaled nitric oxide
• feno
• recurrent wheezing
• infants
• asthma
• pulmonary function
• exacerbations.