Factors associated with elevated exhaled nitric oxide fraction in infants with recurrent respiratory symptoms

Exhaled nitric oxide fraction (F-eNO) has been proposed as a noninvasive marker of eosinophilic bronchial inflammation in active asthma, and supposed to reflect responsiveness to corticosteroid therapy. There are several factors influencing F-eNO, and its role in early childhood respiratory disorders needs to be established. Between 2004 and 2008, 444 children aged <3 yrs with recurrent lower respiratory tract symptoms were referred to a tertiary centre for further investigation. 136 full-term, steroid-free, infection-free infants, median age of 16.4 months (range 4.0-26.7 months), successfully underwent measurement of F-eNO, lung function tests, and a dosimetric methacholine challenge test. The median level of F-eNO was 19.3 ppb (interquartile range 12.3-26.9 ppb). Elevated F-eNO (>= 27 ppb, the highest quartile) was associated with maternal history of asthma (adjusted OR 3.2, 95% CI 1.3-8.1; p=0.012), and increased airway responsiveness (the provocative dose of methacholine causing a 40% fall in maximal expiratory flow at functional residual capacity <= 0.30 mg) (adjusted OR 4.1, 95% CI 1.4-12.7; p=0.012). Atopy, blood eosinophilia and lung function were not associated with elevated F-eNO. In conclusion, maternal history of asthma, and increased airway responsiveness are associated with elevated F-eNO in infants with recurrent lower respiratory tract symptoms.