Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers

Background: There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO ) for persistence of wheezing, exacerbations, or lung function change over time in infants/toddlers with recurrent wheezing.

Objectives: In an ongoing longitudinal cohort of infants and toddlers with recurrent wheezing, we compared predictive values of single-breath FENO (SB-FENO ), tidal-breathing mixed expired FENO (tidal-FENO ), bronchodilator responsiveness (BDR) and the Castro-Rodriquez Asthma Predictive Index (API) for persistence of wheezing, exacerbations and lung function change through age 3 years.

Methods: Enrolment forced expiratory flows and volumes infant pulmonary function tests (iPFTs) were measured in 44 infants/toddlers using the raised volume rapid thoracoabdominal compression method. SB-FENO was measured at 50 mL/s, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes were assessed at age 3 years in 42 infants. Follow-up iPFTs were completed between ages 2.5-3 years in 32 subjects.

Results: An enrolment SB-FENO concentration ≥ 30 p.p.b. predicted persistence of wheezing at age 3 years with a sensitivity of 77%, a specificity of 94%, and an area under the curve (AUC) of 0.86 (95% CI: 0.74-0.98). The sensitivity, specificity, positive predictive, and negative predictive values of SB-FENO for persistence of wheezing and exacerbations were superior to tidal-FENO , BDR, and the API. SB-FENO ≥ 30 p.p.b. and tidal-FENO ≥ 7 p.p.b. measured at enrolment was associated with a decline in both FEV0.5 and FEF25-75 between enrolment and age 3 years.

Conclusions: In wheezy infants/toddlers, SB-FENO was superior to tidal-FENO , BDR, and the API in predicting future exacerbations and persistence of wheezing at age 3 years. Both SB-FENO and tidal-FENO were associated with lung function decline over time.