Abstract
BACKGROUND: The heterogeneity of childhood wheezing illnesses is associated with viral and host factors. Human rhinoviruses (HRV) are the major pathogens in severe wheezing in young children. The single nucleotide polymorphism (SNP) rs6967330 G > A proved to heighten the risk of wheezing. However, the relation between rs6967330 variants of cadherin-related family member 3 (CDHR3) and wheezing induced by human rhinovirus (HRV)-C has not been determined. METHODS: A total of 11,756 respiratory specimens collected from hospitalized children with acute respiratory infections (ARIs) between September 2017 and March 2023 were screened for enterovirus (EV)/HRVs by the capillary electrophoresis-based multiplex PCR (CEMP) assay, and those positive only for HRVs were amplified and sequenced for HRV and CDHR3 genotyping. The clinical data of the enrolled patients were obtained and analyzed. RESULTS: EV/HRVs (15.2%; 1,616/10,608) were the more common viruses detected in inpatients with ARIs. Among the enrolled samples, 148 were positive for HRV-A (49.83%; 148/297), 129 for HRV-C (43.4%; 129/297), and 20 for HRV-B (6.7%; 20/297). More patients infected with HRV-C had history of allergy (P = 0.004), family history of asthma (P = 0.001), wheezing (P = 0.005) and asthma (P = 0.001) than those infected with HRV-A or HRV-B, while patients infected with HRV-C were less likely to have older siblings compared to those infected with HRV-A (P = 0.014). The rs6967330-A variant was related to a high incidence of the three concave signs (P = 0.047), asthma exacerbation (P = 0.025), a higher risk of HRV-C infection determined by the dominant model (OR 1.91, 95% confidence interval 1.05-3.48; P = 0.033), and a high proportion of wheezing (56.67%) in patients infected with HRV-C. CONCLUSIONS: HRV-C is the dominant species responsible for HRV-induced wheezing. The rs6967330-A variant is a risk factor for HRV-C infection, and was associated with the high rate of wheezing induced by HRV-C.