Pediatric Pulmonology 22396401 (1996) z Diagnostic and Therapeutic Methods - Measurement of Expired Nitric Oxide Levels in Children S. Dinarevic, MD, MedSci, C.A. Byrnes, MBchB, A. Bush, MD, MRCP, and E.A. Shinebourne, MD, FRCP Summary. Nitric oxide (NO) can be measured directly in expired air in adults. The purpose of our study was to measure NO levels in children and to compare these values with adults. Exhaled NO was measured in 39 normal prepubertalchildren (23 girls), aged 9-11 years (mean, 9.9 years). Exhaled NO was measured by the chemiluminescencemethod that zyxw is sensitive in a range of 2 to 4,000 ppb of NO on an adapted analyzer (Dasibi Environmental). Wearing a nose clip, zyxwvutsrqp 5 measurements were recorded in each child with exhalation 1) directly into the NO analyzer (flow rate 240 mUmin) with measurements of NO, carbon dioxide, and mouth pressure; and 2) using a T-piece to allow measurements at a different flow rate. For all measurements, background NO levels were less than 10 ppb. The mean direct level was 49.6 ppb, SD 37.8 (range, 11.5-197.2 ppb) compared with T-piece levels of 29.2 ppb, SD 27.1 (range, 5.1-141.2 ppb). There was no significant difference between boys and girls for direct or T-piece recordings. Mean direct NO in boys was 43.1 ppb, SD 40.5 and in girls 55.2 ppb, SD 35.4; mean T-piece in boys was 25.6 ppb, SD 29.2, and in girls 33.8 ppb, SD 25.1. Mean NO levels in prepubertal children are lower than in adults and show no difference between males and females. Pediatr Pulmonol. 1996; 22:396-401. zyxwvutsr D 1996 Wiley-Liss, Inc Key words: Nitric oxide, expired gas, normal values INTRODUCTION The highly reactive molecule nitric oxide (NO) is syn- thezised from the semi-essential amino acid L-arginine by the enzyme nitric oxide synthase.1.2 NO is involved in many biological p r o c e ~ s e s s . ~ ~ ~ In the respiratory system NO is an inflammatory mediator as well as a bronchodila- tor and non-adrenergic and non-cholinergic neurotrans- Under physiological conditions NO is released by the action of a constitutive calcium-dependent enzyme (nitric oxide synthase), while in response to immunologi- cal stimulation or inflammation nitric oxide is also synthe- sised by an inducible calcium-independent NO synthase.’ Levels of NO can be measured directly in expired air. Previous studies have shown different levels of peak expiratory NO measured in animals and human with differences between men and women.’ Measure- ments of exhaled NO may reflect airway inflammation.* We also now know that peak NO levels are dependent on measurement conditions.’ The aim of this study was to determine NO levels in healthy children and compare these values with adults. MATERIALS AND METHODS Following approval from the Hospital Research Ethics Committee we recruited 39 children of varying ethnic 0 1996 Wiley-Liss, Inc. background (23 girls and 16 boys) from a local primary school. Their age range was 9-11 years (mean, 9.9 years). All children completed a health questionnaire. Each child was examined and measures of height (Harpenden stadi- ometer) and weight (minimal underwear, digital Seca scale) were taken. The best of three reproducible flow volume loops was recorded (Compact Vitallograph). Equipment Exhaled NO was measured by the chemiluminescence method, which is sensitive to 24,000 ppb (per volume) of NO on an adapted analyzer (Dasibi Environmental) with a 95% response time of 6.4 seconds. The carbon dioxide levels were measured with a Morgan capnograph in volume percent of expired gas with a 95% response of 141.5 ms. Flow was measured in mumin with a low- From the Paediatric Cardiology and Paediatric Respiratory Depart- ments, Royal Brompton Hospital, London, United Kingdom. Received September 11, 1995; (revision) accepted for publication June 11, 1996. Address correspondence and reprint requests to Dr. Elliot Shinebourne, Paediatric Cardiology Department, Royal Bromptom Hospital, Sydney Street, London SW3 6NP, U.K.