Woodsmoke Exposure, Influenza Infection, and Nasal Immunity

Phase 4

Not yet recruiting

• Conditions: Smoke Exposure; Influenza
• Interventions: 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)

• Registration Number: NCT06841913
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

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.

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 Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-17
• Study First Submitted QC: 2025-02-17
• Last Update Submitted: 2025-02-21
• Study First Posted: 2025-02-24
• Last Update Posted: 2025-02-25
• Study Start: 2025-03-01
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 112

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Wood smoke followed by LAIV	LAIV nasal vaccine is chosen as a model viral infection	Participants will receive LAIV after a 2 hour wood smoke exposure.
Wood smoke followed by LAIV	Wood smoke	Participants will receive LAIV after a 2 hour wood smoke exposure.
Wood smoke followed by Placebo	Wood smoke	Participants will receive a LAIV placebo after a 2 hour wood smoke exposure.
Wood smoke followed by Placebo	Placebo for LAIV nasal vaccine is chosen as a model viral infection	Participants will receive a LAIV placebo after a 2 hour wood smoke exposure.
Clean Air followed by LAIV	LAIV nasal vaccine is chosen as a model viral infection	Participants will receive LAIV after a 2 hour clean air exposure.
Clean Air followed by LAIV	Placebo for Wood Smoke (clean Air Exposure)	Participants will receive LAIV after a 2 hour clean air exposure.
Clean Air followed by Placebo	Placebo for LAIV nasal vaccine is chosen as a model viral infection	Participants will receive a LAIV placebo after a 2 hour clean air exposure.
Clean Air followed by Placebo	Placebo for Wood Smoke (clean Air Exposure)	Participants will receive a LAIV placebo after a 2 hour clean air exposure.

Primary Outcome Measures

Name	Time	Method
Nasal Mucosal secretome (AUC)	Day 0 to Day 7	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.
Gene Expression (AUC)	Day 0 to Day 7	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.
Virus Quantity (AUC)	Day 0 to Day 7	Virus quantity in nasal secretions
Nasal Neutrophils (AUC)	Day 0 to Day 7	nasal secretion
Nasal Viral Antibodies (AUC)	Day 0 to Day 7	virus-specific antibody levels in nasal secretions
Blood Viral Antibodies (AUC)	Day 0 to Day 7	virus-specific antibody levels in blood

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Human Studies Facility; 🇺🇸 Chapel Hill, North Carolina, United States