Early-life allergic sensitization and respiratory infection-Two hits on lung function?

Background: Allergic sensitization and respiratory infections commonly occur in childhood. Interplay between them in asthma development is known as the 'two-hit' hypothesis. There has been no previous investigation of this hypothesis on adult lung function.

Objective: In a birth cohort at high risk for allergic diseases, we investigated interactions between these two factors and lung function outcomes into adulthood.

Methods: Allergic sensitization was assessed at age 24 months by skin prick testing to aero and food allergens. Respiratory infection was defined as cough, rattle or wheeze measured by frequent questionnaires up to age 24 months. Regression models were utilized to identify interactions between these exposures and associations with lung function at ages 12, 18 and 25 years.

Results: At age 25 years, those sensitized at age 2 years(n = 118) demonstrated reductions in pre-bronchodilator FEV₁ of 0.06(95% CI: -0.12, 0.00, z-score units, p = .055) for each additional month of respiratory infections. Those not sensitized (n = 120) had increases in pre-bronchodilator FEV₁ of 0.07 (95% CI: 0.02, 0.13, z-score units, p = .012) for each additional month of respiratory infection(p_interaction = .012). Similar findings were noted for FEV₁/FVC ratio(p_interaction = .011), FEF_25-75(p_interaction = .007) and absolute change in pre and post bronchodilator lung function. At 18 years, findings were similar; however, there was less evidence for interactions at 12 years.

Conclusion: Our study findings support the 'two-hit' hypothesis of interactions between early-life allergic sensitization and increasing respiratory infections, and impairment in lung function up to age 25 years. Early childhood respiratory infections however had different impacts on lung function depending upon the presence or absence of allergic sensitization.