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Published on: August 7, 2017
Hemoglobin-to-Red cell distribution width ratio and asthma risk: cross-population validation and vitamin D mediation
Yanbiao Xiao1, Jun Lai2, Yanglin Zhang1
1Department of Plastic Surgery, Ganzhou Dermatosis Hospital, Ganzhou, Jiangxi Province, China.
Purpose:
This study aimed to explore the association between hemoglobin-to-red blood cell distribution width ratio (HRR) and asthma risk using a large U.S. population-based cohort (NHANES), and to validate the core association in an independent Chinese clinical cohort (Ganzhou People's Hospital) to improve cross-population generalizability. The mediating role of vitamin D in the HRR-asthma association was further explored only in the NHANES discovery cohort.
Patients And Methods:
Data from NHANES 2011-2018 and 2021-2023 (n = 19,140) were used as the discovery cohort. An independent clinical cohort from Ganzhou People's Hospital (n = 519) was used for external validation. Logistic regression models were constructed to assess the HRR-asthma association with stepwise adjustment for confounders. Variance inflation factor (VIF) was used to examine multicollinearity. Discrimination (AUC), calibration (Hosmer-Lemeshow test), and clinical utility (DCA) were evaluated. Mediation analysis was only performed in the NHANES cohort due to unavailability of vitamin D data in the clinical cohort.
Results:
In the NHANES cohort, fully adjusted logistic regression showed a significant inverse association between HRR and asthma (OR = 0.60, 95%CI: 0.45-0.80, P < 0.001), and vitamin D completely mediated this association (indirect effect β=0.011, P = 0.001). In the Ganzhou cohort, the inverse association was consistently validated (fully adjusted OR = 0.21, 95%CI: 0.06-0.75, P = 0.017). The HRR-integrated multivariable model showed moderate discrimination in the NHANES cohort (AUC=0.539, 95%CI: 0.528-0.551) with good calibration (P = 0.32). In the Ganzhou cohort, the multivariable prediction model exhibited moderate discriminatory ability (AUC=0.718, 95%CI: 0.667-0.770), whereas HRR alone showed low-to-moderate discrimination (AUC=0.375, equivalent to 0.625 for the inverse association).
Conclusion:
HRR is inversely associated with asthma risk across U.S. general and Chinese clinical populations. Vitamin D fully mediates the association in NHANES but could not be validated in the clinical cohort. HRR is a simple, low-cost, cross-population risk-associated component within a comprehensive clinical prediction model, rather than a standalone diagnostic marker.
