Woodsmoke Exposure, Influenza Infection, and Nasal Immunity (SmokeyFlu)

The Effects of Woodsmoke Exposure on Nasal Immune Responses to Influenza Infection in Normal Human Volunteers

This study will investigate the effects of woodsmoke (WS) exposure on human nasal mucosal immune responses to viral infection. The study tests the hypotheses that WS exposure modifies biomarkers of nasal mucosal immune function, increases in Live Attenuated Influenza Virus (LAIV) -induced nasal symptoms, and reduces mucosal antibody production.

Study Overview

• Status: Recruiting
• Conditions: Influenza; Smoke Exposure
• Intervention / Treatment: Biological: LAIV nasal vaccine is chosen as a model viral infection; Other: Wood smoke; Biological: Placebo for LAIV nasal vaccine is chosen as a model viral infection; Other: Placebo for Wood Smoke (clean Air Exposure)

Detailed Description

This study will investigate the effects of woodsmoke (WS) exposure on human nasal mucosal immune responses to viral infection. The study tests the hypotheses that WS exposure modifies biomarkers of nasal mucosal immune function, increases LAIV-induced nasal symptoms, and reduces mucosal antibody production. Healthy volunteers will be randomized for a 2-hr exposure to WS or placebo (filtered air) and then inoculated with either live attenuated influenza virus (LAIV) or placebo. Nasal mucosal samples, symptoms, and peripheral blood will be collected on days 1,2,3,7, and 21 post-exposure/LAIV and assessed for a) mucosal antiviral responses using targeted and non-targeted analysis of the secretome and tissue-level gene expression; b) symptoms, virus quantity, differential cell count, and virus-specific antibody levels; and c) biomarker signatures associated with infection outcomes using computational modeling tools.

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Carole Robinette, MS; Phone Number: 919 966-5638; Email: carole_robinette@med.unc.edu
• Study Contact Backup: Name: Chris Brooks; Email: chris_brooks@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • Mary Ellen Jones

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Normal lung function,
• oxygen saturation of >94%,
• normal blood pressure,
• no respiratory symptoms on history, no abnormalities on exam, normal pulmonary function testing,
• 18-49 Years of age.

Exclusion Criteria:

• A history of significant chronic illnesses (to include diabetes, autoimmune diseases, immunodeficiency state, known ischemic heart disease, chronic respiratory diseases such as chronic obstructive pulmonary disease or asthma, hypertension)
• Positive pregnancy test within 48 hours of the time of challenge
• Use of any inhaled substance (for medical or recreational purposes).
• Nonsmokers must have been abstinent from smoking for the prior 12 months, having not smoked more than 1 pack over the course of the previous year.
• History of allergy to eggs
• Acute, non-chronic, medical conditions, including (but not limited to) pneumonia or bronchitis requiring antibiotics, febrile illnesses, flu-like symptoms must be totally resolved symptomatically for 3 weeks
• Unspecified illnesses, which in the judgment of the investigator increase the risk associated with the experimental LAIV infection, will be a basis for exclusion.
• Expected exposure of subject to immunocompromised individuals (who can be infected by LAIV) for the 3 weeks following LAIV inoculation.
• Use of immunosuppressive drugs within the past 6 months.
• Previous Woodsmoke exposure <3 weeks, which is considered to an appropriate washout period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Wood smoke followed by LAIV; Participants will receive LAIV after a 2 hour wood smoke exposure.	Biological: LAIV nasal vaccine is chosen as a model viral infection; Inoculation with LAIV; Other Names: Flumist; Live Attenuated Influenza Vaccine; Other: Wood smoke; Wood smoke exposure concentrations at 500 ug/m3 for two hours.
Active Comparator: Wood smoke followed by Placebo; Participants will receive a LAIV placebo after a 2 hour wood smoke exposure.	Other: Wood smoke; Wood smoke exposure concentrations at 500 ug/m3 for two hours.; Biological: Placebo for LAIV nasal vaccine is chosen as a model viral infection; Placebo for LAIV inoculation. Nasal administration of normal saline.
Active Comparator: Clean Air followed by LAIV; Participants will receive LAIV after a 2 hour clean air exposure.	Biological: LAIV nasal vaccine is chosen as a model viral infection; Inoculation with LAIV; Other Names: Flumist; Live Attenuated Influenza Vaccine; Other: Placebo for Wood Smoke (clean Air Exposure); Clean Air Exposure for 2 hours
Placebo Comparator: Clean Air followed by Placebo; Participants will receive a LAIV placebo after a 2 hour clean air exposure.	Biological: Placebo for LAIV nasal vaccine is chosen as a model viral infection; Placebo for LAIV inoculation. Nasal administration of normal saline.; Other: Placebo for Wood Smoke (clean Air Exposure); Clean Air Exposure for 2 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal Mucosal secretome (AUC)	Analysis of the nasal mucosal secretome (secreted factors identified as responsive to WS and/or LAIV). Area under the curve (AUC) will be calculated for each proteomic profile. Descriptive statistics (means and standard deviations) will be computed for outcomes of interest (AUCs), assuming normal distribution as in previous studies.	Day 0 to Day 7
Gene Expression (AUC)	Tissue-level gene expression (genes identified as responsive to WS and/or LAIV) and assessed for: tissue-level gene expression and untargeted metabolomic and proteomic profiles. Area under the curve (AUC) will be calculated for each gene profile. Descriptive statistics (means and standard deviations) will be computed for outcomes of interest (AUCs), assuming normal distribution as in previous studies.	Day 0 to Day 7
Virus Quantity (AUC)	Virus quantity in nasal secretions	Day 0 to Day 7
Nasal Neutrophils (AUC)	nasal secretion	Day 0 to Day 7
Nasal Viral Antibodies (AUC)	virus-specific antibody levels in nasal secretions	Day 0 to Day 7
Blood Viral Antibodies (AUC)	virus-specific antibody levels in blood	Day 0 to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Tissue gene expression	Peak value of Tissue-level gene expression (genes identified as responsive to WS and/or LAIV)	Day 0 to Day 21
Peak nasal secretome	Peak Analysis value of the nasal mucosal secretome (secreted factors identified as responsive to WS and/or LAIV)	Day 0 to Day 21
Peak Nasal Virus quantity	Peak value of Virus quantity in nasal secretions	Day 0 to day 21
Peak nasal neutrophils	Peak value of nasal neutrophils	Day 0 to Day 21
Peak Nasal virus anti-bodies	Peak value of virus-specific antibody levels in nasal secretions	Day 0 to Day 21
Peak blood virus anti-bodies	Peak value of virus-specific antibody levels in blood	Day 0 to Day 21
Peak Day of Tissue Gene Expression	Peak Day of Tissue-level gene expression (genes identified as responsive to WS and/or LAIV)	Day 0 to Day 21
Peak Day of nasal secretome	Peak Analysis Day of the nasal mucosal secretome (secreted factors identified as responsive to WS and/or LAIV)	Day 0 to Day 21
Peak Day of Nasal Virus quantity	Peak Day of Virus quantity in nasal secretions	Day 0 to day 21
Peak Day of nasal neutrophils	Peak Day of nasal secretion	Day 0 to Day 21
Peak Day of Nasal virus anti-bodies	Peak day of virus-specific antibody levels in nasal secretions	Day 0 to Day 21
Peak Day of blood virus anti-bodies	Peak Day of virus-specific antibody levels in blood	Day 0 to Day 21
Peak Symptom score	Flu symptom questionnaire. A score from 0-18 will be recorded. Zero being symptom free and 18 the most symptomatic.	Day 0-21
Peak day of symptom score	Flu symptom questionnaire. A score from 0-18 will be recorded. Zero being symptom free and 18 the most symptomatic. The day in which there is the highest score will be recorded.	Day 0-21

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institutes of Health (NIH); National Institute of Environmental Health Sciences (NIEHS)
• Investigators: Principal Investigator: Meghan Rebuli, PhD, UNC; Principal Investigator: Terry Noah, MD, UNC

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: February 17, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Influenza; Smoke; LAIV; Fire; Flumist; Wood Smoke
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Influenza Vaccines; FluMist
• Other Study ID Numbers: 24-1802; 1R01ES036209-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Primary and Secondary Outcomes data.
• IPD Sharing Time Frame: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication.
• IPD Sharing Access Criteria: The investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes