Exhaled Nitric Oxide in Wheezy Infants Predicts Persistent Atopic Asthma and Exacerbations at School Age.

BACKGROUND: There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO) in infants/toddlers with recurrent wheezing for asthma at school age. OBJECTIVES: In a cohort of infants/toddlers with recurrent wheezing determine the predictive values of sedated single-breath FENO (SB-FENO) and awake tidal-breathing mixed-expired FENO (tidal-FENO) for active asthma, severe exacerbations, and lung function at age 6 years. METHODS: In 44 infants/toddlers, SB-FENO was measured under sedation at 50 mL/sec in conjunction with forced expiratory flow and volume measurements, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes and lung function were assessed at age 6 years in 36 subjects. RESULTS: Enrollment SB-FENO was significantly higher among subjects with active asthma at age 6 years than among subjects without asthma (36.4 vs. 16.9 ppb, p < 0.0001), and the odds of asthma was 7.6 times greater (OR 7.6; 95% CI 1.8-31.6) for every 10 ppb increase in enrollment SB-FENO. A ROC analysis demonstrated that an enrollment SB-FENO > 31.5 ppb predicted active asthma at age 6 years with an area under the curve (AUC) of 0.92 (95% CI: 0.82-1). SB-FENO was also higher among subjects who experienced severe asthma exacerbations during the year preceding age of 6 years. SB-FENO at enrollment and lung function measures at age 6 years were modestly correlated (FEV1: r = -0.4; FEF25-75: r = -0.41; FEV1/FVC ratio: r=-0.46), and SB-FENO was significantly higher among subjects with bronchodilator responsiveness (BDR) at age 6 years. Tidal-FENO was not predictive of active asthma, exacerbations, or lung function at age 6 years. CONCLUSION: In wheezy infants/toddlers, SB-FENO was predictive of school-age asthma and associated with lung function measures at age 6 years.

Lung function and biomarkers of airway inflammation during and after hospitalization for acute exacerbations of childhood asthma associated with viral respiratory symptoms.

BACKGROUND: There are limited data assessing relationships between biomarkers of inflammation and lung function after hospitalization for asthma exacerbations in children. OBJECTIVE: To assess the associations in asthmatic children among changes in lung function, fraction of exhaled nitric oxide (FENO), and cysteinyl leukotrienes (CysLTs) in exhaled breath condensate (EBC) after hospitalization for acute asthma. METHODS: Spirometry and FENO were measured and EBC collected for CysLT measurement from 40 children during and 1, 2, and 4 weeks after hospitalization for an asthma exacerbation and during a single-study visit for 40 healthy children. RESULTS: Enrollment FENO and EBC CysLT concentrations were higher in the children with asthma than in healthy individuals (mean FENO, 31.6 vs 7 ppb; P < .0001; mean EBC CysLT, 7.9 vs 4.9 ppb; P = .03). Among children with asthma, improvement in lung function reached a plateau within 2 weeks after hospital discharge. The EBC CysLT concentrations were not associated with changes in lung function, use of albuterol, or use of inhaled corticosteroids (ICSs). Among asthmatic children enrollment FENO was not associated with changes in lung function during follow-up. However, among children who had an elevated enrollment FENO (≥25 ppb), patients who did not use ICSs after hospital discharge had lower end-of-study lung function than those who used ICSs. At 2 and 4 weeks after hospital discharge, FENO was higher among patients who reported albuterol use more than twice weekly and among patients who reported no ICS use. CONCLUSION: FENO measured at hospital discharge among children hospitalized with acute asthma may be useful in identifying patients who will respond to ICS therapy.

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 (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. 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.