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

Wadhwa V, Dharmage SC, Wurzel D, et al. Pediatr Allergy Immunol. 2025; 36:e70115. doi:10.1111/pai.70115

Abstract

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

Association between respiratory infection (increasing number of
months) and allergic sensitization with change in lung function
z-scores (post-bronchodilator)—sensitization status at 2 years.

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(pinteraction = .012). Similar findings were noted for FEV1/FVC ratio(pinteraction = .011), FEF25–75(pinteraction = .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.

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