Asthma and lower airway disease
Exhaled nitric oxide, lung function, and exacerbations in wheezy infants and toddlers

https://doi.org/10.1016/j.jaci.2010.03.023Get rights and content

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.

Section snippets

Subjects

Children 6 to 24 months of age with 3 or more episodes of physician-diagnosed wheezing treated with bronchodilators or corticosteroids were recruited for a single-center longitudinal study. Subjects with birth at less than 36 weeks' gestation, congenital heart disease, dysphagia, severe gastroesophageal reflux, or upper airway obstruction were excluded. Systemic or inhaled corticosteroid treatment was not permitted for 3 weeks before baseline lung function and FENO measurement. Thereafter,

Results

Forty-seven infants and toddlers were recruited with a mean age of 15.6 months (SD, ±5.2 months) at enrollment. Technically acceptable RVRTC flow-volume curves were obtained from 44 subjects at enrollment. Baseline characteristics of the cohort are presented in Table I. The mean FEV0.5, FEF25-75, and FEF75z scores for the cohort at enrollment were significantly less than zero (a z score equal to zero represents the mean value of published normative data). Four subjects were lost to follow-up,

Discussion

In a cohort of infants and toddlers with a history of recurrent episodes of wheezing, we found that enrollment SB-eNO levels were not associated with baseline forced expiratory volumes or flows. However, enrollment SB-eNO levels were significantly higher in subjects with a subsequent decrease in lung function than in subjects with an increase in lung function over 6 months of follow-up. SB-eNO levels were significantly higher in subjects with bronchodilator responsiveness. A higher enrollment

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    Supported by National Heart, Lung, and Blood InstituteK23HL077626; CTSA grant no. I ULI RR025014-01; and Seattle Children's Hospital.

    Disclosure of potential conflict of interest: J. S. Debley has received research support from the National Institutes of Health/National Heart, Lung, and Blood Institute, American Lung Association, and Merck & Co. The rest of the authors have declared they have no conflict of interest.

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