Clinical phenotypes of bronchial hyperresponsiveness in school-aged children

Abstract Background Bronchial hyperresponsiveness (BHR), one of the key features of asthma, shows a diverse natural course in school-aged children, but, studies on BHR phenotypes are lacking. Objective We classified BHR phenotypes according to onset age and persistence in children and investigated the characteristics and factors associated with each phenotype in a longitudinal study. Methods We analyzed 1,305 elementary school children from the Children's HEalth and Environmental Research (CHEER) study, a 4-year prospective follow-up study with 2-year intervals starting at a mean age of 7 years. Total serum IgE levels and blood eosinophils (%) were measured, and allergy work-up including methacholine challenge tests with ISSAC questionnaire were performed at each survey. Results We classified the four BHR phenotypes as non-BHR (n=942, 72.2%), early-onset transient BHR (n=201, 15.4%), late-onset BHR (n=87, 6.7%), and early-onset persistent BHR (n=75, 5.7%). Early-onset persistent BHR is characterized by an increased eosinophils (%), total serum IgE level, sensitization rate, a decreased lung function and an increased risk of newly diagnosed asthma during follow-up (aOR, 3.89; 95% CI, 1.70-8.88). The two early-onset phenotypes were associated with peripheral airway dysfunction. The late-onset BHR phenotype related with increased risks of AR symptoms at baseline and later sensitization against inhalant allergens. Conclusion The early-onset persistent BHR phenotype in school-aged children is associated with high atopic burden and increased risk of newly diagnosed asthma, whereas the late-onset BHR phenotype related with later sensitization and AR symptoms. Diverse BHR phenotypes in children have specific characteristics that require targeted follow-ups.