Personal Exposure to PM2.5 and O3 Induced Heterogeneous Inflammatory Responses and Modifying Effects of Smoking: A Prospective Panel Study in COPD Patients

Air pollution and smoking are major contributors to chronic obstructive pulmonary disease (COPD), primarily through inflammatory responses. We performed this prospective panel study among 107 COPD patients (372 repeated measurements) with personal monitoring of fine particulate matter (PM_2.5) and ozone (O₃), two primary pollutants contributing to the COPD disease burden, to investigate the interactive effects of air pollutants and smoking on inflammatory profiles. Exhaled nitric oxide and hydrogen sulfide were detected to assess airway eosinophilic and neutrophilic inflammation, respectively. Fasting blood was collected to count inflammatory cells and detect type-1, type-2, type-17, and regulatory T (Treg) cytokines. We found PM_2.5 mainly induced neutrophilic inflammation, manifesting as stronger airway inflammation in non-smokers and greater increases in blood neutrophils in current smokers (P-interaction<0.05), particularly those with neutrophilic phenotype. Conversely, O₃ primarily induced nasal and circulating eosinophilic inflammation, with non-smokers showing heightened susceptibility. These effects were modified by type-1/type-2 and type-17/Treg immune imbalances in both non-smokers and current smokers. Specifically, type-1 and type-17-skewed immunity exacerbated the neutrophilic effects of PM_2.5, while type-2 and Treg-skewed immunity aggravated the eosinophilic responses to O₃. This study emphasizes the need for personalized prevention strategies to protect COPD patients from the detrimental impacts of air pollution and smoking.

Environmental Implication

Air pollution and cigarette smoke are two major environmental hazardous materials that contribute to approximately 22.6% of total global deaths. They play particularly significant roles in the pathological development of chronic obstructive pulmonary disease (COPD), primarily through inflammatory responses. This prospective panel study is the first to elucidate the interactive role of air pollution and smoking in driving inflammatory heterogeneity of COPD, through precise personal exposure monitoring and prospective repeated measurements of inflammatory profiles. These findings provide novel insights for developing personalized environmental prevention strategies to protect susceptible populations from the hazardous impacts of air pollution and smoking.