Are known biomarkers for asthma present in early infancy?

Background

Exhaled nitric oxide (FE_NO) is a biomarker for eosinophilic airway inflammation [1]. Elevated FE_NO has been proposed as a marker for diagnosing asthma and predicting asthma exacerbations [2]. We wished to examine the association between known asthma risk factors and FE_NO. A sub cohort of children (n=222) participating in the Canadian Healthy Infant Longitudinal Development (CHILD) study underwent infant pulmonary function tests (IPFTs) during the first year of life.

Methods

Risk factors were obtained from a subset of available CHILD questionnaires administered prenatally and 3 times during the first year of life. FE_NO was collected using a multiple-breath sampling technique during quiet tidal breathing at the 3 month visit, 1 year visit, or both visits. Prenatal smoke exposure was defined as any maternal smoking, including mothers who stopped or cut down on smoking during pregnancy. Postnatal smoke exposure was defined as any exposure in or away from the home up to 1 year of age. Parental asthma was defined as self-reported or doctor diagnosed asthma. Parental atopic status was confirmed by allergy skin tests. T-tests with Bonferroni correction for multiple comparisons were used to compare FE_NO in the exposed and unexposed groups (α=0.004).

Results

At the 3 month visit, 134 infants attended the IPFT lab, and 84 of 117 attempted eNO tests were successfully analyzed; mean FE_NO was 16.8±8.1ppb. At the 1 year visit, 181 infants attended the IPFT lab and 138 of 158 attempted eNO tests were successfully analyzed; mean FE_NO was 15.3±9.7ppb. Prenatal smoking rates were low (3% and 6%) and showed no association with FE_NO (Table 1). Postnatal smoke exposure was also not associated with FE_NO. FE_NO was not statistically different in infants whose mothers or fathers had a history of asthma or atopic status, compared to those without. Having siblings was not significantly associated with FE_NO after applying the Bonferroni correction.

Table 1

Conclusions

Smoke exposure was not related to FE_NO, however no nicotine biomarker was assessed and smoking rates were low. Maternal and paternal histories were not associated with FE_NO levels in healthy children up to 1 year of age. None of the risk factors were statistically significantly associated with FE_NO, however infants with siblings were observed to have a lower FE_NO than infants without siblings at the 1 year visit. A larger sample size is required to increase the power of these tests. Further factors must be studied to explain the variation in FE_NO measures seen.