• Andrew J Collaro, Anne B Chang, Julie M Marchant, Don Vicendese, Mark D Chatfield, Johanna F Cole, Tamara L Blake, and Margaret S McElrea.
• Department of Respiratory and Sleep Medicine, Queensland Children's Hospital, South Brisbane, QLD, Australia; Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, QLD, Australia. Electronic address: andrew.collaro@health.qld.gov.au.
• Chest. 2023 Mar 1; 163 (3): 624633624-633.

BackgroundFractional exhaled nitric oxide (Feno), used as a biomarker, is influenced by several factors including ethnicity. Normative data are essential for interpretation, and currently single cutoff values are used in children and adults.Research QuestionAccounting for factors that influence Feno, (1) what are appropriate predicted and upper limit of normal (ULN) Feno values in an underserved population (First Nations Australians), (2) how do these values compare with age-based interpretive guidelines, and (3) what factors influence Feno and what is the size of the effect?Study Design And MethodsFeno data of First Nations Australians (age < 16 years, n = 862; age ≥ 16 years, n = 348) were obtained. Medical history using participant questionnaires and medical records were used to define healthy participants. Flexible regression using spline functions, as used by the Global Lung Function Initiative, were used to generate predicted and ULN values.ResultsLook-up tables for predicted and ULN values using age (4-76 years) and height (100-200 cm) were generated and are supplied with a calculator for clinician use. In healthy First Nations children (age < 18 years), ULN values ranged between 25 and 60 parts per billion (ppb) when considering only biologically plausible age and height combinations. For healthy adults, ULN values ranged between 39 and 88 ppb. Neither the current Feno interpretation guidelines, nor the currently recommended cutoff of 50 ppb for First Nations children 16 years of age or younger were appropriate for use in this cohort. Our modelling revealed that predicted and ULN values of healthy participants varied nonlinearly with age and height.InterpretationBecause single pediatric, adult, or all-age Feno cutoff values used by current interpretive guidelines to define abnormality fail to account for factors that modify Feno values, we propose predicted and ULN values for First Nations Australians 4 to 76 years of age. Creating age- and height-adjusted predicted and ULN values could be considered for other ethnicities.Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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