Background Biomarkers, preferably non-invasive, that predict asthma inception children are lacking. Objective Little is known about biomarkers of type 2 inflammation in early life in relation to asthma inception. We evaluated aeroallergen sensitization, peripheral blood eosinophils and serum periostin as potential biomarkers of asthma in children. Methods Children enrolled in the Childhood Origins of ASThma (COAST) study were followed prospectively from birth. Blood samples were collected at ages 2, 4, 6, and 11 years, and serum-specific IgE, blood eosionophils and periostin were measured in 244 children. Relationships among these biomarkers, age and asthma were assessed. Results Serum periostin levels were approximately 2–3 fold higher in children than previously-observed adult levels. Levels were highest at 2 years (145 ng/mL), and did not change significantly between 4 and 11 years (128 and 130 ng/mL). Age 2 periostin≥150 ng/mL predicted asthma at age 6 [Odds Ratio (OR) 2.3 95%CI (1.3–4.4)]. Eosinophil count ≥300 cells/ul and aeroallergen sensitization at age 2 were each associated with increased risk of asthma at age 6 [OR 3.1(1.7–6.0) and 3.3(1.7–6.3)]. Children with any two of the biomarkers had significantly increased risk of developing asthma by school age [≥2 biomarkers vs. none OR= 6.6 (95%CI 2.7–16.0). Conclusion Serum periostin levels are significantly higher in children than adults, likely due to bone turnover, which impairs clinical utility in children. Early life aeroallergen sensitization and elevated blood eosinophils are robust predictors of asthma development. Children with evidence of activation of multiple pathways of type 2 inflammation in early life are at greatest risk for asthma development.

Purpose of review Understanding factors that lead to asthma development in early life is essential to developing strategies aimed at primary or secondary prevention. Recent findings This article will review current evidence addressing the development of early life allergic sensitization in relation to microbes and the gut and airway microbiome. Wheezing illnesses, particularly viral, remain a significant risk factor for asthma inception; however, bacterial pathogens have recently emerged as an additional important contributor to asthma risk, either alone or as cofactors with viral infections. The combined influence and interaction of early life viral wheezing and aeroallergen sensitization is important, with allergic sensitization preceeding the onset of viral wheeze. Lastly, we review recent data from longitudinal studies regarding the development of irreversible airway obstruction and its impact on the natural history of asthma. Summary The development of asthma remains complex and incompletely understood. There is interplay between genetic predisposition and environmental exposures, including allergens and microbes. Interventions aimed at these risk factors during the preschool years may prevent the longitudinal course of asthma progression to irreversible airway obstruction.

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Viral respiratory wheezing illnesses are common in early childhood, and many children who wheeze subsequently develop asthma. In the Childhood Origins of ASThma (COAST) cohort, we have previously reported that rhinovirus (RV) wheezing illnesses in infancy and early childhood are the most robust predictor of subsequent asthma development in high-risk children at age 6 years, regardless of aeroallergen sensitization or other risk factors.(1) However, a similar high-risk birth cohort has recently reported that the number of lower respiratory episodes in the first three years of life, as opposed to a specific viral or bacterial etiology, is associated with asthma risk, and suggested that the specific microbiologic trigger is not important for the risk of later asthma development.(2) This discrepancy in the literature is important to address as it may impact how risk of childhood asthma is ascertained; accurate identification of high-risk children may be key to asthma prevention. Therefore, we assessed the contribution of etiology and frequency of wheezing illnesses on asthma risk from ages 6 to 13 years in the COAST birth cohort study, which included children born to parents with either allergy or asthma. We hypothesized that the number of RV wheezing illnesses would be a more robust predictor of asthma development and persistence when compared to the number of non-RV wheezing illnesses.

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