Exhaled nitric oxide, lung function, and exacerbations in wheezy infants and toddlers

Background: There are limited data assessing the relationship between fraction of exhaled nitric oxide and lung function or exacerbations in infants with recurrent wheezing. Objectives: In a longitudinal pilot study of children less than 2 years old, we assessed whether baseline fraction of exhaled nitric oxide was associated with lung function, bronchodilator responsiveness, changes in lung function, or subsequent exacerbations of wheezing. Methods: Forced expiratory flows and volumes using the raised-volume rapid thoracic compression method were measured in 44 infants and toddlers (mean age, 15.7 months) with recurrent wheezing. Single-breath exhaled nitric oxide (SB-eNO) was measured at 50 mL/s. Lung function was again measured 6 months after enrollment. Results: At enrollment, forced expiratory volume in 0.5 seconds (FEV0.5), forced expiratory flow at 25% to 75% of expiration (FEF25-75), and forced expiratory flow at 75% of expiration (FEF75) z scores for the cohort were significantly less than zero. There was no correlation between enrollment SB-eNO levels and enrollment lung function measures. SB-eNO levels were higher in infants with bronchodilator responsiveness (46.1 vs 23.6 ppb, P < .001) and was associated with a decrease in FEV0.5 (r = 0.54, P = .001), FEF25-75 (r = 0.6, P < .001), and FEF75 (r = 0.55, P = .001) over 6 months. A 10-ppb increase in SB-eNO level was associated with a 0.4-point z score decrease in FEV0.5, a 0.4-point z score decrease in FEF25-75, and a 0.42-point z score decrease in FEF75. SB-eNO level was superior to lung function and bronchodilator responsiveness in predicting subsequent wheezing treated with systemic steroids. Conclusions: SB-eNO level might predict changes in lung function and risk of future wheezing and holds promise as a biomarker to predict asthma in wheezy infants and toddlers. (J Allergy Clin Immunol 2010;125:1228-34.)