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Exhaled Nitric Oxide in Wheezy Infants Predicts Persistent Atopic Asthma and Exacerbations at School Age
Maria P White1, Tessa K Kolstad1, Molly Elliott2
1Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Insights
Fraction of exhaled nitric oxide (FeNO) measured during sedated single-breath tests in infants with recurrent wheezing predicts school-age asthma. This FeNO measurement also correlates with lung function at age 6 years.
Area of Science:
- Pediatric Respiratory Medicine
- Allergy and Immunology
- Pulmonary Diagnostics
Background:
- Limited data exists on the predictive value of fraction of exhaled nitric oxide (FeNO) in infants/toddlers with recurrent wheezing for asthma development at school age.
- Recurrent wheezing in early childhood is a common condition with variable progression to persistent asthma.
- Early identification of children at risk for persistent asthma is crucial for timely intervention.
Purpose of the Study:
- To determine the predictive value of sedated single-breath FeNO (SB-FeNO) and awake tidal-breathing FeNO (tidal-FeNO) for active asthma at age 6 years.
- To assess the association of these FeNO measurements with severe asthma exacerbations and lung function at school age.
Main Methods:
- A cohort of 44 infants/toddlers with recurrent wheezing underwent SB-FeNO measurements under sedation and tidal-FeNO measurements while awake.
- Forced expiratory flow and volume measurements were performed concurrently with SB-FeNO.
- Clinical outcomes, including active asthma and severe exacerbations, and lung function were assessed at age 6 years in 36 subjects.
Main Results:
- Enrollment SB-FeNO was significantly higher in children with active asthma at age 6 (36.4 ppb) compared to those without asthma (16.9 ppb).
- Each 10 ppb increase in enrollment SB-FeNO was associated with a 7.6-fold greater odds of asthma at age 6 (OR 7.6).
- An SB-FeNO level > 31.5 ppb predicted active asthma at age 6 with high accuracy (AUC 0.92). SB-FeNO also correlated with poorer lung function (FEV1, FEF25-75, FEV1/FVC) and was higher in those with bronchodilator responsiveness. Tidal-FeNO showed no predictive value.
Conclusions:
- Sedated single-breath FeNO is a valuable predictor of school-age asthma in infants and toddlers with recurrent wheezing.
- SB-FeNO measurements in early childhood are associated with lung function parameters and bronchodilator responsiveness at age 6 years.
- Awake tidal-breathing FeNO measurements are not predictive of asthma outcomes in this age group.
Background:
There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO) in infants/toddlers with recurrent wheezing for asthma at school age.
Objectives:
In a cohort of infants/toddlers with recurrent wheezing determine the predictive values of sedated single-breath FENO (SB-FENO) and awake tidal-breathing mixed-expired FENO (tidal-FENO) for active asthma, severe exacerbations, and lung function at age 6 years.
Methods:
In 44 infants/toddlers, SB-FENO was measured under sedation at 50 mL/sec in conjunction with forced expiratory flow and volume measurements, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes and lung function were assessed at age 6 years in 36 subjects.
Results:
Enrollment SB-FENO was significantly higher among subjects with active asthma at age 6 years than among subjects without asthma (36.4 vs. 16.9 ppb, p < 0.0001), and the odds of asthma was 7.6 times greater (OR 7.6; 95% CI 1.8-31.6) for every 10 ppb increase in enrollment SB-FENO. A ROC analysis demonstrated that an enrollment SB-FENO > 31.5 ppb predicted active asthma at age 6 years with an area under the curve (AUC) of 0.92 (95% CI: 0.82-1). SB-FENO was also higher among subjects who experienced severe asthma exacerbations during the year preceding age of 6 years. SB-FENO at enrollment and lung function measures at age 6 years were modestly correlated (FEV1: r = -0.4; FEF25-75: r = -0.41; FEV1/FVC ratio: r=-0.46), and SB-FENO was significantly higher among subjects with bronchodilator responsiveness (BDR) at age 6 years. Tidal-FENO was not predictive of active asthma, exacerbations, or lung function at age 6 years.
Conclusion:
In wheezy infants/toddlers, SB-FENO was predictive of school-age asthma and associated with lung function measures at age 6 years.
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