Association Between Long‐Term Exposure to Ambient Air Pollution and the Risk of Recurrent Asthma Hospitalizations

Asthma is a chronic inflammatory airway disease characterized by variable respiratory symptoms and airflow limitation. Air pollution can cause oxidative damage to airways and human immune system, leading to inflammation, remodeling, and allergy [1, 2]. These biological responses may trigger exacerbation of asthma, which would lead to hospitalization. Previous research has primarily concentrated on the impact of air pollution on single instances of asthma hospital admission [3]. This approach has neglected subsequent readmissions, which may fail to take into account the dynamic nature of asthma and the potential for varying long-term effects of air pollution over asthma progression. Herein, we aimed to assess the effects of long-term ambient air pollution exposure on recurrent asthma hospitalizations. Recently, based on the prospective UK biobank cohort, we developed a Prentice, Williams, and Peterson's Calendar Time model to investigate the potential effects of nitrogen dioxide (NO2), nitrogen oxides (NOX), and particulate matter (PM2.5 and PM10) on both initial and recurrent hospital readmissions for asthma, after adjusting for various potential covariates including sociodemographic characteristics and lifestyle factors (Appendix S1). Asthma was defined by the International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes J45 and J46, and asthma hospitalizations were obtained from hospital inpatient records. Individual exposure was determined by matching residential addresses to the annual average ambient air pollution level from the year prior to recruitment information. Due to authorization constraints, we were granted access only to participants' information of location coordinates at a resolution of 1 km, rather than the highest available resolution of 100 m in the UK biobank, which represented a limitation of our study. These exposures were then weighted based on the duration of residence at each address during that year. During a median follow-up time of 13.4 years, out of 439,938 participants without a history of asthma at baseline, 13,697 (3.11%) experienced asthma hospitalization, among which 6882 (50.25%) had subsequent readmissions with a median of two rehospitalizations for asthma (Figure S1). The asthma hospitalization rate tended to increase with the number of prior asthma admission events. Compared to individuals without asthma hospitalization, individuals who experienced an asthma hospitalization, especially those with recurrent hospitalizations, were more likely to be female, be current smokers, and have been exposed to higher levels of air pollution (Table S1). Our study found that long-term exposure to four air pollutants was associated with an increased risk of asthma hospitalization, and the exposure-response relationships were generally linear (Figure S2). Hazard ratios of asthma hospital admission associated with per interquartile range increase in NO2, NOX, PM2.5, and PM10 were 1.051 (95% CI: 1.032, 1.069), 1.044 (95% CI: 1.027, 1.062), 1.068 (95% CI: 1.043, 1.094), and 1.066 (95% CI: 1.038, 1.094), respectively (Table 1). PM2.5 showed a stronger effect on asthma hospitalization than oxynitride. This may be due to its direct deposition in the airways, which damages epithelial cells and triggers oxidative stress and inflammation [4], while oxynitride, being a relatively weak oxidant [2], has less impact on these processes. Significant effects of pollutants were also observed on readmission, and the effects, except for PM2.5, were slightly greater than those on first admission (Figure 1). The findings indicated that air pollution exposure played a crucial role in asthma exacerbation. This aligns with the findings of Andersen et al. [5], who reported that individuals with a prior history of asthma hospitalizations had a markedly higher risk of first asthma hospital admission after baseline due to NO₂ exposure. Subgroup analysis showed that males exhibited greater vulnerability to asthma admissions associated with NO2, NOX, and PM10 (Table S2). The possible explanation is that males typically have larger airway dimensions or spend more time outdoors than females. Compared to non-smokers, smokers exhibited significantly greater sensitivity to initial asthma hospitalization triggered by PM2.5. This may be attributed to (1) the more rapid decline in lung function in smokers with asthma than in non-smokers [5, 6] and (2) a higher average level of ambient PM2.5 in areas where smokers resided (Table S3). The higher prevalence of smoking among men than among women (14.6% vs. 9.8%) cannot explain the greater effect of air pollutants in men, since smoking status was controlled for in the subgroup analyses by sex. In conclusion, our findings indicate that long-term exposure to air pollutants is associated with an increased risk of both initial and recurrent asthma hospitalizations. These findings highlight the importance of air quality management and targeted interventions especially for individuals with asthma to reduce exacerbation. Chun-Quan Ou initiated the study. Xiao-Han Xu, Hao-Neng Huang, and Yi-Ming Tao helped in data collection. Jin-Lun Zhang and Chong-Ye Zhao analyzed the data and wrote the original draft. Xiao-Han Xu, Chen Shi, Li Li, and Chun-Quan Ou contributed to the manuscript revising. All authors helped in final approval of the manuscript. The authors declare no conflicts of interest. Data from the UK Biobank (http://www.ukbiobank.ac.uk/) are available to all researchers upon making an application. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.