Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)

Background: Exposure to smoke increases the risk of many diseases. People can be exposed to dangerous levels of smoke during wildfires. Also, smoke from fires that burn manmade materials may contain toxic chemicals. Researchers want to know more about how breathing smoke affects a person s airways (nose, sinuses, lungs) and immune system. Objective: To learn how exposure to smoke over time affects the health of people who work as firefighters. Eligibility: Healthy, nonsmoking people aged 18 to 65 years who work as firefighters. Some people older than 65 may also be included. Design: Participants will have study visits about every 6 months for up to 10 years. They will also have visits after a smoke exposure event. Some visits may be by telehealth. Each visit will include some or all of the following: Imaging scans of the sinuses or chest. Sample collection. These will include blood, nasal fluids, a skin swab, urine, and fluid coughed up from the lungs. Lung function test. Participants will blow air into a machine that measures the volume moving in and out of their lungs. Particles in exhaled air (PExA). Participants will breathe into a device that collects particles. Heart function test. Smell test. Participants will identify odors on scratch-and-sniff cards. Wearable air monitors. Participants may be asked to wear a device that measures particles and chemicals in the air around them for 1 to 20 days. International Public Safety Data Institute (IPSDI) reports. Participants will provide copies of these fire suppression event reports, if they are available. Participants who have exams of the airways as part of their routine health care may have extra tissue samples collected for research.

* INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all of the following criteria: 1. Stated willingness to comply with all study procedures and availability for the duration of the study. 2. Aged 18 to 65 at time of enrollment. Firefighters over the age of 65 may be enrolled per investigator discretion. 3. In good general health as evidenced by medical history. 4. Have or are willing to obtain a non-NIH primary physician who will manage all health conditions and be responsive for emergency medical treatment, if required. 5. Able to provide informed consent. 6. Willing to allow biological samples and data to be stored for future research. 7. Have permission of active-duty command to participate in study. 8. Are an active-duty veteran or recruit firefighter eligible to participate in planned or unplanned firefighting scenarios. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: 1. Current use of tobacco, marijuana, vaping/e-cigarette or any illicit inhaled, ingested, or injected drugs within 1 year of enrollment. 2. Pregnancy or lactation. 3. Treatment with an investigational drug/intervention or immunosuppressive/immunomodulatory medications within 2 years of enrollment. 4. Current smoker, or tobacco use within 1 year of enrollment or greater than 5 pack-years cumulatively. 5. Conditions detailed as disqualifying under NFPA Form 1582 pertaining to 1) nose, oropharynx, trachea, and larynx and 2) lung and chest wall pathologies at time of enrollment. 6. Known inborn error of immunity as cited by the most recent classification of the International Union of Immunological Societies. 7. Malignancy within 5 years. 8. Presence of condition(s) that, in the judgment of the investigator or the referring physician, may put the participant at undue risk or make them unsuitable for participation in the study. Participants will be selected in an equitable manner from the available pool of potentially eligible individuals, without regard to factors such as sex, race, ethnicity, socioeconomic status, etc, except for age, as described below. We note that, given their non-volunteer (ie salaried) status, active-duty firefighters and recruits are screened by NFPA Form 1582 for medical conditions precluding active firefighting duties, which is inclusive of above conditions with the exception of known inborn error of immunity. Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the principal investigator. Study staff should be notified of co-enrollment on any other protocol. Exclusion of Special Populations: -Adults Over the Age of 65 Federal firefighters have a maximum retirement age of 57 years; although there are local departments with individuals over this age. Firefighters over the age of 65 at enrollment who meet all other eligibility criteria will require special permission from investigators to participate in this study. Exceptions will be made on a case-by-case basis to ensure that age-matched cases do not skew disproportionately to an older population. -Adults Who Lack, or Lose, Decision-Making Capacity to Consent to Research Participation Given the known dangers associated with firefighting, it would be unethical to include individuals who lack decision-making capacity to consent. -Exclusion During Pregnancy Women who are/become pregnant will be excluded from the study while pregnant and/or lactating given condition specific physiology that may confound the objectives of the study. In the event of pregnancy in a study participant, the participant will temporarily pause all study related activities. Participants may resume study activities 4 weeks after the conclusion of the pregnancy or cessation of lactation. -Children Children will be excluded from this study given the age minimums to attend firefighting academies.