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Purpose: The complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studieshave yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis duringearly life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphismon the development of childhood asthma. Methods: This cross-sectional study involved 7,389 middle school students who were from 8 areas ofSeoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 wasgenotyped in 1,395 middle school students from two areas using the TaqMan assay. Results: Bronchiolitis in the first 2 years of life, antibiotic exposureduring the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibioticuse and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P valuefor interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma wasincreased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87). Conclusions: Early-life antibiotic exposures and a historyof bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptiblesubjects.

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