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

NCT07867184 | Enrolling By Invitation

• 2 other identifiers: 10002586002586-I
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

Study Description: This observational natural history study (FLARES) will define the acute and longterm airway, respiratory and immune consequences of anthropogenic smoke exposures that arise from urban and wildland urban interface (WUI) fires. Given their disproportionate exposure, firefighters will be used as a model. The protocol integrates (1) standardized clinical phenotyping, (2) detailed exposure assessment, and (3) multi-omic profiling to enable evidence-based management of smoke- and pollutant-related respiratory impairment. FLARES will enroll firefighter recruits and active-duty firefighters. Firefighters will be followed longitudinally with twice annual visits to the NIH Clinical Center (NIH CC) and will undergo event-driven evaluations including paired pre- and postexposure assessments around planned fire exposures (eg, live fire simulations) and assessments following unplanned exposures. Systematic evaluation of the upper and lower airways will be coupled with an exposure-informed biorepository of biospecimens - blood, nasal lining fluid, particulates exhaled from deep airways and urine- for multi-omic and exposome analyses to elucidate molecular pathways of smoke- and chemical -related injury. Assessments will include sinus and chest imaging (baseline and 3-year CT with interval magnetic resonance imaging \[MRI\]), pulmonary function testing (PFT), and detailed exposure questionnaires. Pre/post exposure comparisons and longitudinal trajectories of firefighters will be used to identify early biomarkers, multi-omic trajectories, and clinical indices of perturbed respiratory immunity and sinopulmonary disease in relation to exposure characteristics (eg, frequency, duration, intensity, and fire type), including the growing burden of anthropogenic smoke exposures in the context of climate change. Objectives: Primary Objective: Assess changes in multi-omic signatures within airway epithelium/fluids, peripheral blood, and/or urine following anthropogenic smoke exposure. Secondary Objective: Determine development or progression of upper and/or lower airway disease following anthropogenic smoke exposure at a 3-year interval. Tertiary Objective: Assess multi-site exposome shifts following anthropogenic smoke exposure. Exploratory Objectives:

• Perform power calculations for untargeted metabolomic signatures using data from pilot of metabolomic pathway assessment of sigmaOH-fluorenes and sigmaOHphenanthrenes pre and post live fire simulator.
• Assess multi-omic shifts following anthropogenic smoke exposure with standard fire department exposure collection data (eg, nature of biofuel, ambient conditions, personal protective equipment use and condition, decontamination practices).
• Assess organ-specific blood biomarkers on basis of omics level analysis (eg, assess markers of end-neurologic damage in the event of metabolomics pathways suggestive of neurotoxic exposures such as lead or mercury). Endpoints: Primary Endpoints: Fold differences in methylation, transcription, proteomic and/or metabolic pathways:
• Initial pilot of metabolomic data will include pathway assessment of sigmaOHfluorenes and sigmaOH-phenanthrenes pre and post live fire simulator.
• Comparing baseline to acute and subacute phases of anthropogenic smoke exposures (eg, firefighter specific monitoring of either planned or unplanned smoke exposure) relative to preceding baseline.
• Comparing longitudinal changes within individual firefighters relative to time in service. Primary endpoints may be assessed in context of acute exposures: 0-14 days after defined smoke exposure episode, subacute (15-90 days) post exposure, and chronic (repeated and/or \> 90 days post exposure). Secondary Endpoints: 3-year incidence of participant-reported symptoms corroborated by objective physiologic or inflammatory changes. 1 or more domains identified as meeting at least 1 subjective measure AND at least 1 corresponding objective measure (eg, Chronic Airway Assessment Test \[CAAT\] \>= 8 AND fractional exhaled nitric oxide \[FeNO\] \> 50 ppb). Tertiary Endpoint: Direct or estimated smoke chemical levels on wearable, under uniform monitors relative to neutral-location controls (eg, fire station or home) and post-exposure urine versus pre-exposure urine. Exploratory Endpoints:
• Power calculation for untargeted metabolomics experiments using pilot of metabolomic pathway assessment of sigmaOH-fluorenes and sigmaOHphenanthrenes pre and post live fire simulator.
• Fold differences in methylation, transcription, proteomic and/or metabolic pathways in linear mixed-effects models adjusted for individual aspects of standard International Public Safety Data Institute (IPSDI) Exposure Tracker firefighter reporting systems.
• Direct or estimated smoke chemical levels on w...

Conditions

Anosmia; Chronic Obstructive Pulmonary Disease; Hyposmia; Chronic Rhinosinusitis; Asthma

Keywords

Firefighter; Respiratory; Smoke; Urban; Fire; Natural History

Outcome Measures

Primary Outcomes (1)

• Fold differences in methylation, transcription, proteomic and/or metabolic pathways:1. After defined smoke exposure episode 2. Subacute post exposure 3. Chronic (repeated and/or > 90 days post exposure

  Assess changes in multi-omic signatures within airway epithelium/fluids, peripheral blood, and/or urine following anthropogenic smoke exposure

  1. 0-14 days 2. 15-90 days 3. > 90 days

Secondary Outcomes (1)

• Incidence of participant-reported symptoms corroborated by objective physiologic or inflammatory changes. 1 or more domains identified as meeting at least 1 subjective measure and at least 1 corresponding objective measure, eg, CAAT > 8 AND F...

  3 year interval

Study Arms (1)

Firefighters

Healthy firefighter cadets, recruits and active-duty firefighters aged 18 to 65 without history of recreational smoke exposure who are employed within the Maryland, Virginia, and the District of Columbia area.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy firefighter cadets, recruits and active-duty firefighters aged 18 to 65 without history of recreational smoke exposure who are employed within the Maryland, Virginia, and the District of Columbia area.

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Aged 18 to 65 at time of enrollment. Firefighters over the age of 65 may be enrolled per investigator discretion.
• In good general health as evidenced by medical history.
• 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.
• Able to provide informed consent.
• Willing to allow biological samples and data to be stored for future research.
• Have permission of active-duty command to participate in study.
• Are an active-duty veteran or recruit firefighter eligible to participate in planned or unplanned firefighting scenarios.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Current use of tobacco, marijuana, vaping/e-cigarette or any illicit inhaled, ingested, or injected drugs within 1 year of enrollment.
• Pregnancy or lactation.
• Treatment with an investigational drug/intervention or immunosuppressive/immunomodulatory medications within 2 years of enrollment.
• Current smoker, or tobacco use within 1 year of enrollment or greater than 5 pack-years cumulatively.
• 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.
• Known inborn error of immunity as cited by the most recent classification of the International Union of Immunological Societies.
• Malignancy within 5 years.
• 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.
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anosmia; Pulmonary Disease, Chronic Obstructive; Asthma

Condition Hierarchy (Ancestors)

Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Danielle C Flood, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2026
• First Posted: October 9, 2026
• Study Start (Estimated): October 14, 2026
• Primary Completion (Estimated): October 31, 2031
• Study Completion (Estimated): October 31, 2036
• Last Updated: October 9, 2026

Record last verified: 2026-10-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Exact time frame is unknown. Will be completed per NIH Data Sharing Policy and publication requirements.@@@@@@
• Access Criteria: Per PI discretion and repository requirements.

Locations

US (1)