Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age

BackgroundNitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX).MethodsWe followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88; EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine samples (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models.ResultseNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: –0.49, 95% CI –0.95 to –0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: –0.004, 95% CI –0.008 to –0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%–24% for every unit increase in eNO ppb.ConclusionHigher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.