Distinct Clinical and Cytokine Features of Moderate-Severe Persistent AR Phenotype by ARIA Classification: COCOA

The prevalence of allergic rhinitis (AR) has increased rapidly. However, the AR phenotype in the general population remains poorly explored. In this study, we aimed to determine the distinct features of AR phenotypes according to Allergic Rhinitis and its Impact on Asthma (ARIA) classification in Korean children.

We enrolled 1,113 children aged 7 years from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study. AR was diagnosed by a physician at each scheduled visit, and the AR phenotype was defined according to the ARIA classification. We analyzed the results of skin prick tests and performed cytokine assays using blood samples collected at ages 3 and 7.

The prevalence of AR at age 7 was 48.9%, while that of moderate-to-severe persistent AR phenotype was 4.4%. Cesarean delivery was associated with the mild-intermittent AR phenotype, while prenatal antibiotic use was linked to the moderate-to-severe persistent phenotype. Sensitization to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), birch, and Japanese hop at age 3 and sensitization to Der p, Der f, birch, oak, and cat at age 7 increased the risk of moderate-to-severe persistent AR phenotype. Upon cytokine analysis, interleukin (IL)-4 tended to be elevated at age 3 in children with moderate-to-severe persistent AR. By age 7, concentrations of IL-5 and IL-17A were significantly higher in children with moderate-to-severe persistent AR phenotype.

These findings suggest that 4.4% of Korean children had a moderate-to-severe persistent AR phenotype, as defined by ARIA. Early sensitization to Der p, Der f, birch, and Japanese hop at age 3 and prenatal antibiotic use are risk factors. Furthermore, this phenotype may involve both T helper 2 and T helper 17-related immune responses, reflecting a potential shift toward more complex or mixed patterns of inflammation.