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

Abstract

There are limited data assessing the relationship between fraction of exhaled nitric oxide and lung function or exacerbations in infants with recurrent wheezing. 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. 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. At enrollment, forced expiratory volume in 0.5 seconds (FEV(0.5)), forced expiratory flow at 25% to 75% of expiration (FEF(25-75)), and forced expiratory flow at 75% of expiration (FEF(75)) 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 FEV(0.5) (r = -0.54, P = .001), FEF(25-75) (r = -0.6, P < .001), and FEF(75) (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 FEV(0.5), a 0.4-point z score decrease in FEF(25-75), and a 0.42-point z score decrease in FEF(75). SB-eNO level was superior to lung function and bronchodilator responsiveness in predicting subsequent wheezing treated with systemic steroids. 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.