Do early-life allergic sensitisation and respiratory infection interact to increase asthma risk?

Objective The 'two-hit' hypothesis theorizes that early life allergic sensitisation and respiratory infection interact to increase asthma risk. Methods We sought to determine in a high allergy risk birth cohort whether interactions between early life allergic sensitisation and respiratory infection were associated with increased risk for asthma at ages 6-7 years and 18 years. Allergic sensitisation was assessed at 6, 12, and 24 months by skin prick testing to 3 food and 3 aeroallergens. Respiratory infection was defined as reported "cough, rattle, or wheeze" and assessed 4-weekly for 15 months, at 18 months, and age 2 years. Regression analysis was undertaken with parent-reported asthma at age 6-7 years and doctor diagnosed asthma at 18 years as distinct outcomes. Interactions between allergic sensitisation and respiratory infection were explored with adjustment made for potential confounders. Results Odds of asthma were higher in sensitised compared to non-sensitised children at age 6-7 years (OR = 14.46; 95%CI 3.99-52.4), There was no evidence for interactions between allergic sensitisation and early life respiratory infection, with a greater frequency of respiratory infection up to 2 years of age associated with increased odds for asthma at age 6-7 years in both sensitised (OR = 1.13; 95%CI:1.02-1.25, n = 199) and non-sensitised children(OR = 1.31; 1.11-1.53, n = 211) (p interaction = 0.089). At age 18 years, these associations were weaker. Conclusions Our findings do not support 'two-hit' interactions between early life allergic sensitisation and respiratory infection on asthma risk. Both early life respiratory infections and allergic sensitisation were risk factors and children with either should be monitored closely for development of asthma.