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

Summary 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.