Abstract
Previous research has primarily focused on the impact of climatic variables and air pollution on Hand, Foot, and Mouth Disease (HFMD). However, there remains limited understanding of how air pollution levels modify these relationships across different regions and populations. This study employed a two-stage, multi-city time-series analysis using data from 13 cities in Jiangsu Province (2015-2023) to explore these effects. A multistage analytical approach, including the distributed lag non-linear model, multivariate meta-regression, and attributable risk calculation, was used to quantify the association between climatic variables, air pollutants, and HFMD. Findings indicated that HFMD incidence is closely associated with meteorological conditions, with peak risk at 24.8°C for average temperature and 89.2% for average relative humidity. Low average wind speed and short sunshine hours (SH) also contributed to increased risk. Air pollutants, such as PM(2.5), SO(2), and O(3), significantly modified these associations. For example, PM(2.5) and SO(2) increased HFMD risk at higher temperatures, while O(3) reduced risk. Under low humidity, some pollutants exhibited protective effects, though risk increased with high humidity. NO(2) had the strongest influence in reducing variability, while high PM(2.5) and SO(2) concentrations weakened the protective effects of SH. These findings emphasize the non-linear influence of climatic variables on HFMD risk and suggest that air pollution's modification of these relationships varies by gender, age, and location. This provides important insights for developing targeted, timely public health warnings.