Variations in exhaled nitric oxide in children with asthma during a 1-week stay in a mountain village sanatorium

Knowing about spontaneous variations in the fractional concentration of exhaled nitric oxide (FE(NO)) could improve monitoring of airway inflammation in asthmatic children. We aimed to assess FE(NO) variations (expiratory flow 50 mL/sec) in subjects maintained in similar environmental conditions. We tested spirometry and FE(NO) in symptom-free asthmatic children (9 corticosteroid-naive, 8 corticosteroid-treated) during a 1-week stay in a countryside sanatorium and in their healthy relatives (n = 12) staying in the immediate neighborhood on summer holiday (total 29 children, M/F: 14/15, 5.8-16.8 yrs). Testing sessions were repeated every 12 hours (8: 00 AM, 8: 00 PM) for 2 days and again on day 7. Measurements were defined as reproducible when they agreed with an intraclass correlation coefficient (ICC) above 0.60; deviation from mean differences was assessed by the coefficient of repeatability (CR = 2 SD). Lung function remained constant throughout the week in all groups. Baseline FE(NO) levels in corticosteroid-naive asthmatic children tended to decrease at the end of the week (from 13.9 ppb, 95% CI 12.2-19.1 to 9.2 ppb, 95% CI 5.8-15.9, p = 0.057). No differences were found between nocturnal and diurnal FE(NO). Within-session reproducibility for two FE(NO) measurements was high (ICC 0.99 in all groups and CR, 0.9 to 1.3 ppb). Between-session FE(NO) reproducibility at 12 hours and 24 hours was still high for each group but decreased markedly after 6 days in corticosteroid-naive asthmatic children (ICC 0.79 and CR 9.6 ppb at 24 hours vs. ICC 0.13 and CR 20.8 ppb after 6 days), whereas it decreased slightly in corticosteroid-treated asthmatics (from ICC 0.89 and CR 3.1 ppb to ICC 0.88 and CR 3.0 ppb) and healthy children (from ICC 0.79 and CR 4.8 ppb to ICC 0.65 and CR 5.7 ppb). In conclusion, in healthy subjects and in asthmatic children receiving therapy with inhaled corticosteroids (but not in corticosteroid-naive subjects), FE(NO) measurements are reproducible across a week.