Determinants of Exhaled Nitric Oxide Levels (FeNO) in Childhood Atopic Asthma: Evidence for Neonatal Respiratory Distress as a Factor Associated With Low FeNO Levels

Abstract

Background. In allergic asthmatic children exhaled nitric oxide (FeNO) levels are related to eosinophilic inflammation by correlation analysis. Whether FeNO can be modified by factors potentially influencing the natural history of asthma in early life is not known. Objective. To evaluate the frequency of anamnestic factors influencing the natural history of asthma and to identify potential determinants for elevated or low FeNO levels by multivariate analysis. Methods. One hundred seventy-one children with mild-moderate asthma were stratified according to their FeNO levels into three groups: low (<20 ppb), mid (20–40 ppb), and high (>40 ppb). The frequency of nine anamnestic factors together with indices of allergic sensitization (total and allergen-specific immunoglobulin E [IgE], blood eosinophil counts) and of airflow limitation (forced expiratory volume in one second [FEV1]% predicted) were evaluated. Results. Among factors related to the patient history, neonatal respiratory distress was reported only in children with low FeNO levels, whereas this factor was never reported in children with mid-to-high FeNO levels (p = .008). As compared with low FeNO group, mid and high FeNO groups showed higher eosinophil counts and a tendency to have lower FEV1 values. By multivariate analysis, four factors (eosinophils >300 cells/mm3, cat-specific IgE, house dust mites [HDM]-specific IgE, FEV1 ≤86% predicted) turned out to be significantly associated with mid-high FeNO levels and two factors (eosinophils >600 cells/mm3, total IgE >355 kU/L) with high FeNO levels. Conclusions. Besides confirming the well-known tight association between blood eosinophilia and/or allergic sensitization and FeNO, these data provide new evidence for neonatal respiratory distress as potential factor associated with low FeNO levels in childhood atopic asthma.