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 (PM2.5) 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 PM2.5 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 PM2.5, 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.