Effect of elevated exhaled nitric oxide levels on the risk of respiratory tract illness in preschool-aged children with moderate-to-severe intermittent wheezing

Abstract

Background The fractional concentration of exhaled nitric oxide (FeNO) is a noninvasive marker for airway inflammation but requires further study in pre-school children to determine its clinical relevance. Objective To determine whether the risk of respiratory tract illnesses (RTI), disease burden and atopic features are related to FeNO in preschool children with moderate-to-severe intermittent wheezing. Methods We determined FeNO using the off-line tidal breathing technique in 89 children, 12–59 months old, with moderate-severe intermittent wheezing. Risk of RTI was determined by comparing participants with baseline FeNO >75th percentile (24.4ppb) to those with FeNO ≤75th percentile using Cox regression analysis. Results The risk of RTI was significantly higher in children with FeNO >24.4ppb relative to those with lower FeNO values (adjusted RR= 3.8, 95% CI: 1.74–8.22; p=0.0008). FeNO levels >24ppb were associated with a greater number of positive skin tests to aeroallergens (p=0.03), but not with other atopic characteristics or historic parameters of illness burden. Conclusion Elevated FeNO in preschool children with moderate-to-severe intermittent wheezing was associated with an increased risk of RTI during a one-year follow-up. In addition, higher FeNO was associated with aeroallergen sensitization.

The Asthma Predictive Index: A very useful tool for predicting asthma in young children

“…However, the API, rather than the mAPI, is used to predict asthma in longitudinal studies. 25,26 In most health care settings, it is easier, cheaper, and probably more reliable (allergens vary with region) to determine eosinophilia counts in blood samples than to determine allergic sensitization with a skin prick test or by measuring specific IgEs. The members of the Multicentre Allergy Study performed multiple skin and IgE tests on subjects throughout childhood and used mathematic modeling to show that specific IgE responses did not reflect a single phenotype of atopy; only atopy to multiple factors at early ages predicted asthma at the age of 8 years.…”

“…32,33 The API is also the only index used in studies to determine relationships between biomarkers, such as comparing fraction of exhaled nitric oxide (FeNO) 25,34 or early lung function (Garcia-Marcos, personal communication). Recently, a prospective cohort study of 391 young children (age, 3-47 months) showed that wheezy young children with a stringent API have increased levels of FeNO compared with those seen in children with recurrent wheeze and a loose API or children with recurrent cough.…”

Guideline-Recommended Fractional Exhaled Nitric Oxide Is a Poor Predictor of Health-care Use Among Inner-city Children and Adolescents Receiving Usual Asthma Care

“…Studies in preschool children have suggested that F eno testing may be a benefi cial tool predicting future asthma. [25][26][27][28][29] Debley et al 26 found F eno level to be predictive of changes in lung function and risk of future wheezing, suggesting a role for prediction of future asthma in infants and toddlers. A large cohort study in The Netherlands also suggested that F eno measured before the age of 4 years was predictive of wheeze up to age 8.…”

Exhaled Nitric Oxide Predicts Persistence Of Wheezing, Exacerbations, And Decline In Lung Function In Wheezy Infants And Toddlers

“…[26] However, the mean enrollment age was >3 years, and most children < 3yrs. could not perform acceptable tidal breathing FE NO measurements, indicating that unsedated tidalbreathing FE NO may be technically challenging to measure in infants/toddlers.…”

“…could not perform acceptable tidal breathing FE NO measurements, indicating that unsedated tidalbreathing FE NO may be technically challenging to measure in infants/toddlers. [26] Additional limitations of tidal breathing-FE NO in infants include: potential nasal NO contamination as nasal NO production far exceeds lower airway production, and variable expiratory flow which is problematic due the highly flow dependent nature of FE NO [27,28].…”