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

Authors White MP, Kolstad TK, Elliott M, Cochrane ES, Stamey DC, Debley JS

Received 18 August 2019

Accepted for publication 21 November 2019

Published 7 January 2020 Volume 2020:13 Pages 11—22

DOI https://doi.org/10.2147/JAA.S227732

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Amrita Dosanjh


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, USA

Correspondence: Jason S Debley
Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, University of Washington, 4800 Sand Point Way NE, Seattle, WA 98105, USA
Tel +1 206-987-2174
Fax +1 206-987-2639
Email jason.debley@seattlechildrens.org

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.

Keywords: exhaled nitric oxide, FENO, recurrent wheezing, infants, asthma, pulmonary function, exacerbations


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