Association of annual polycyclic aromatic hydrocarbons (PAHs) exposure with cellular immune responses and yearly decline of lung function in asthma

Polycyclic aromatic hydrocarbons (PAHs), the major traffic-related air pollutants, may worsen asthma severity by increasing Th2 and Th17 cytokines, and inducing release of epithelial cytokines to affect differentiation of innate lymphocytes (ILCs). We investigated whether these immune responses are associated with exposure to PAHs and with decline of lung function in asthmatics. 83 asthmatics were living in either high air pollution area (n=40, HAP exposure: >0.86 ng/m³/yr) or moderate to low air pollution area (n=43, LAP exposure: 0.54-0.86 ng/m³/yr), levels estimated from established grid-scale PM2.5-PAH concentration monitoring network. We collected peripheral monocytes (PMBC) to assess the activity of Th2, Th17 and Treg cells and immunostaining with multiple colors was used to analyze the presence of ILC1, ILC2 and ILC3 cells. Annual decline of lung function (FVC, r=-0.633; FEV₁, r=-0.434) was inversely correlated with annual exposure to PAHs in HAP asthmatics (n=40, p<0.01), but this was not found in LAP asthmatics. HAP asthmatics had higher expression of IL33, IL25, TSLP and IL17A mRNA in airway tissue. Circulating ILC2 (52.6±3.9%, p<0.001) and ILC3 cells (31.9±4.2%, p<0.001) in PBMC derived from HAP asthmatics were higher than ILC2 (19.7±2.7%) and ILC3 (4.0±1.1%) cells of LAP asthmatics. The ILC2 and ILC3 cells were inversely correlated to annual decline of lung function in asthmatics. IL4, IL5, RORrt and GATA3 mRNA in PBMC of HAP asthmatics were significantly higher than those in LAP asthmatics. We propose that this immune dysfunction may accelerate the decline of lung function in asthmatics exposed to high concentrations of PAHs.