Extreme Cold Events and Pediatric Asthma Outpatient Visits: The Modifying Role of Ambient Carbon Monoxide and Sulfur Dioxide

Xing Gong,1,* Li Wei,1,* Yunshu Xu,2 Changdi Xu,3 Yi Zhang,1 Fengxia Sun,1 Man Tian,3 Liya Wang,4 Hengxue Wang,5 Ming Ge,1 Feng Liu,3 Lilin Xiong,1 Wei Pan61Department of Environment Health Promotion, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 2Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3Department of Respiratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Physical and Chemical Inspection, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 5Department of Acute Infectious Diseases Control and Prevention, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 6Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lilin Xiong, Department of Environment Health Promotion, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, People’s Republic of China, Email hzxionglilin@163.com Wei Pan, Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China, Email panwei303303@sina.comPurpose: Extreme cold exposure may trigger respiratory morbidity in children, but whether concurrent ambient air pollution modifies cold-related risks of pediatric asthma remains unclear. This study evaluated associations between extreme cold events and pediatric asthma outpatient visits and assessed whether these associations differed according to ambient pollutant concentrations.Patients and methods: We conducted a time-series study of 62,167 pediatric asthma outpatient visits among children diagnosed with asthma at a tertiary children’s hospital in Nanjing, China, from 2019 to 2024. Daily asthma visits were linked with meteorological variables and ambient concentrations of PM10, PM2.5, NO2, SO2, CO, and O3. Extreme cold events were defined as ≥ 2, ≥ 3, or ≥ 4 consecutive days with daily mean temperature ≤ 4.5°C (the 10th percentile of the study-period distribution). Quasi-Poisson distributed-lag non-linear models were used to estimate cumulative relative risks over lag 0– 14 days. Pollutant-related effect modification was evaluated using stratified analyses and interaction measures.Results: Overall, extreme cold events were not significantly associated with pediatric asthma outpatient visits. However, stronger associations were observed during periods with higher CO and SO2 concentrations. For lag 0– 14 days, cumulative relative risks for ≥ 2-day cold events were 2.60 (95% CI: 1.13– 5.95) in the higher-CO stratum and 3.41 (95% CI: 1.15– 10.11) in the higher-SO2 stratum. Similar patterns were observed for longer cold-event definitions. Multiplicative interactions were identified for both CO and SO2, whereas additive interaction evidence was clearer for CO. Other pollutants showed less consistent modification patterns.Conclusion: The association between extreme cold events and pediatric asthma outpatient visits may depend on concurrent gaseous pollutant conditions. Relatively elevated CO and SO2 may help identify cold-event periods with greater pediatric asthma outpatient burden.Keywords: pediatric asthma outpatient visits, extreme cold events, ambient air pollutants, distributed-lag non-linear models, effect modification