Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years

Background: Fractional exhaled nitric oxide (FENO) is used in monitoring of asthma. Objectives: The aim of this multicenter study was to establish normal values of FENO and assess feasibility in children with a standardized method and equipment approved for clinical use. Methods: FENO was measured in healthy subjects of 4 to 17 years according to American Thoracic Society guidelines (single breath online, exhalation flow 50 mL/s) with a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden) in 3 European and 2 US centers. Each child performed 3 acceptable nitric oxide measurements within 6 attempts and completed an extended International Study of Asthma and Allergy in Children questionnaire. Results: Measurement of FENO was attempted in 522 children. Four hundred five children completed the study according to the protocol. Geometric mean FENO in 405 children was 9.7 ppb, and the upper 95% confidence limit was 25.2 ppb. FENO increased significantly with age, and higher FENO was seen in children with self-reported rhinitis/conjunctivitis or hay fever. The success rate was age-dependent and improved from 40% in the children 4 years old to almost 100% from the age of 10 years. The repeatability of 3 approved measurements was 1.6 ppb (95% CI, 1.49-1.64 ppb). Conclusion: FENO in healthy children is below 15 to 25 ppb depending on age and self-reported atopy. Measurement of FENO by NIOX® is simple and safe and has a good repeatability. Feasibility depends on age and may be difficult in the preschool child.

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