Project Abstract Unlike the sporadic exposure of the general population in wildfire prone areas, exposure of wildland firefighters (WFFs) to WF smoke is recurrent, and has recently become more so due to the increase in the acreage of land burned by wildfires and prescribed (managed) fires. WFFs are exposed to elevated levels of WF smoke while working at wildland fires. The airborne concentrations of the reactive particles in WF smoke at the fireline are at least an order of magnitude higher than the health-based air quality standards in the U.S. The inhalation exposure of WFFs at the fireline is exacerbated because they work extended hours on multiple days per year at the fireline. Additionally, wildland firefighting is conducted mostly without any respiratory protection, as no respirator is currently approved for the profession. Nevertheless, knowledge about the chronic respiratory effects of such exposure is lacking. The proposed study is designed to address NIOSH’s “Public Safety” sector, and its “Respiratory Health” and “Cancer, Reproductive, and Cardiovascular Diseases” cross-sectors by assessing the association between occupational WF smoke exposure and subclinical indicator of pulmonary health impairment and cancer-related molecular changes in the respiratory airways. Therefore, the hypotheses of the proposed study are: 1) that cumulative recurrent WF smoke exposure induces adverse long-term respiratory effects among WFFs, and 2) that a situational use of an air purifying respirator (APR) during periods of peak particulate exposure concentrations will reduce exposure and adverse acute physiological responses. The first hypothesis will be tested by comparing changes in DNA methylation and gene expression in the nasal epithelium and lung function across a three-year period between WFFs and a control group of emergency medical technicians (EMTs) matched by age, sex and ethnicity (N = 50/group). The proposed outcomes are disease precursors and are relevant for characterizing risk of disease that may evolve long after exposure or retirement. The second hypothesis will be tested by comparisons of cross-shift changes in urinary biomarkers of exposure, gene expression in the nasal epithelium, and serum pro-inflammatory cytokines among WFFs (N = 35) between occasions when they wear the APR and when they do not, while working at prescribed burns. The objective of the proposed study is well aligned with NIOSH’s priority extramural research goals to reduce occupational cancer and respiratory disease and exposures causing them. Following the completion of the study, we would have determined the adverse respiratory effects of cumulative occupational exposure to WF smoke and a practical approach to mitigate them. The envisaged outputs from the proposed research, which would include publicly accessible results and publications, would directly inform NIOSH’s priority goal to reduce incidence of exposure and illnesses among wildland firefighters. These ou...