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

Abstract

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.

The association of exhaled nitric oxide with air pollutants in young infants of asthmatic mothers

“…In addition to asthma, elevated eNO has been reported in other inflammatory disorders in infants: established bronchopulmonary dysplasia [7], eczema [8] and airway hyperresponsiveness in infants with recurrent lower respiratory tract symptoms [9]. Contrasting this, we have recently shown that lower eNO at six weeks of age is associated with higher rates of bronchiolitis and wheeze in the first year of life [10], and decreased eNO has been described in infants with cystic fibrosis [11], respiratory syncytial virus bronchiolitis [12], wheezy bronchitis [13], and rhinorrhoea [14] making the role of eNO in respiratory disorders manifesting in early life more cryptic.…”

Newcastle 1000 (NEW1000) Study: an Australian population-based prospective pregnancy cohort study design and protocol

“…Infant assessments and measurements including abdominal and head circumference, middle upper arm circumference, length, weight and body composition (measured by the CosMed Peapod unit)34 will be undertaken on the postnatal ward of the hospital and at HMRI during the 6-week and 6-month postpartum appointments. A subgroup of infants will receive infant lung function testing at 6 weeks postpartum, using previously published protocols 35–37…”

“…A subgroup of infants will receive infant lung function testing at 6 weeks postpartum, using previously published protocols. [35][36][37] Questionnaires A link to online questionnaires will be emailed to participants at 14, 20, 28 and 36 weeks antenatally and 6 weeks and 6 months postnatally. Questionnaires will be 'open' for 2 weeks at each timepoint and participants will be able to save and return to the questionnaires if they cannot complete them in one sitting.…”