Ambient Air Pollution and Kawasaki Disease in Korean Children: A Study of the National Health Insurance Claim Data

Abstract

Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects children under 5 years of age. Some researchers suggested a potential triggering effect of air pollution on KD, but the findings are inconsistent and limited by small sample size. We investigated the association between ambient air pollution and KD among the population of South Korea younger than 5 years using the National Health Insurance claim data between 2007 and 2019. Methods and Results We obtained the data regarding particulate matter ≤10 or 2.5 µm in diameter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone from 235 regulatory monitoring stations. Using a time‐stratified case‐crossover design, we performed conditional logistic regression to estimate odds ratios (OR) of KD according to interquartile range increases in each air pollutant concentration on the day of fever onset after adjusting for temperature and relative humidity. We identified 51 486 children treated for KD during the study period. An interquartile range increase (14.67 μg/m 3 ) of particulate matter ≤2.5 µm was positively associated with KD at lag 1 (OR, 1.016; 95% CI, 1.004–1.029). An interquartile range increase (2.79 ppb) of sulfur dioxide concentration was associated with KD at all lag days (OR, 1.018; 95% CI, 1.002–1.034 at lag 0; OR, 1.022; 95% CI, 1.005–1.038 at lag 1; OR, 1.017; 95% CI, 1.001–1.033 at lag 2). Results were qualitatively similar in the second scenario of different fever onset, 2‐pollutant model and sensitivity analyses. Conclusions In a KD‐focused national cohort of children, exposure to particulate matter ≤2.5 µm and sulfur dioxide was positively associated with the risk of KD. This finding supports the triggering role of ambient air pollution in the development of KD.

Spatiotemporal clusters of Kawasaki disease in South Korea from 2008 to 2017: A municipal-level ecological study

“…A longitudinal study in Japan that presents an insignificant decrease in KD admission during the COVID-19 pandemic quarantine indicates the possibility of other factors besides infectious triggers, while the lack of data also precluded the stratification of study subjects ( 37 ). Adding a spatial perspective and proper stratification to temporal associations that have been explored in previous studies between KD and infectious diseases [e.g., varicella and respiratory infections caused by rhinoviruses ( 9 , 38 ) and respiratory syncytial virus ( 9 ), human bocaviruses ( 10 ) and enteroviruses ( 10 , 38 ), pertussis ( 39 , 40 ), and human coronaviruses ( 38 , 41 )] or environmental factors [e.g., air pollutants ( 13 , 42 ) and temperature ( 42 )] might help understand the etiology of KD.…”

“…In particular, spatiotemporal analysis is required for an accurate description of disease distribution and transmission patterns (8), as the results could lead to valuable insights into disease causality. However, most previous studies have limitations in settling on a temporal perspective without considering a spatial perspective (9)(10)(11)(12)(13) and some studies with spatiotemporal axes have limitations in exploring national representative data (14-17). Furthermore, studies with sex stratification could provide evidence for the etiology.…”

Environmental Exposures and Pediatric Cardiology: A Scientific Statement From the American Heart Association

“…29 In children <5 years of age, short-term exposure to PM and sulfur dioxide was positively associated with the risk of KD. 30 In Japan, researchers observed that increased temperature combined with high nitric oxide and sulfur dioxide concentrations was associated with KD incidence. 31 Another study from Japan found an association between PM and KD concurrently with observed association between PM and asthma admissions, mechanistically supporting the plausibility of the association.…”

CD14 down‐modulation as a real‐time biomarker in Kawasaki disease

“…9 Oxidative stress plays a critical role in the development of KD in conjunction with inflammation. [10][11][12] Environmental pollutants induce oxidative stress by upregulating reactive oxygen species (ROS) levels. Elevated ROS result in the oxidation of low-density lipoprotein (LDL), generating DAMPs.…”

“…Oxidative stress plays a critical role in the development of KD in conjunction with inflammation 10–12 . Environmental pollutants induce oxidative stress by upregulating reactive oxygen species (ROS) levels.…”