Clinical trial NCT06841913: Woodsmoke Exposure, Influenza Infection, and Nasal Immunity
Official title: The Effects of Woodsmoke Exposure on Nasal Immune Responses to Influenza Infection in Normal Human Volunteers
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Smoke Exposure
Influenza
Keywords: LAIV
Flumist
Influenza
Wood Smoke
Smoke
Fire
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Environmental Health Sciences (NIEHS)
First posted: 2025-02-24
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 25% of participants (N=100 total for the study) will undergo each of the following.

Wood smoke followed by LAIV (N=25) Wood smoke followed by Placebo (N=25) Clean Air followed by LAIV (N=25) Clean Air followed by Placebo (N=25)

Males and females will be equally enrolled into each of the above cohorts.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Nasal Mucosal secretome (AUC)
timeFrame: Day 0 to Day 7
measure: Gene Expression (AUC)
timeFrame: Day 0 to Day 7
measure: Virus Quantity (AUC)
timeFrame: Day 0 to Day 7
measure: Nasal Neutrophils (AUC)
timeFrame: Day 0 to Day 7
measure: Nasal Viral Antibodies (AUC)
timeFrame: Day 0 to Day 7
measure: Blood Viral Antibodies (AUC)
timeFrame: Day 0 to Day 7
Secondary outcomes:
measure: Peak Tissue gene expression
timeFrame: Day 0 to Day 21
measure: Peak nasal secretome
timeFrame: Day 0 to Day 21
measure: Peak Nasal Virus quantity
timeFrame: Day 0 to day 21
measure: Peak nasal neutrophils
timeFrame: Day 0 to Day 21
measure: Peak Nasal virus anti-bodies
timeFrame: Day 0 to Day 21
measure: Peak blood virus anti-bodies
timeFrame: Day 0 to Day 21
measure: Peak Day of Tissue Gene Expression
timeFrame: Day 0 to Day 21
measure: Peak Day of nasal secretome
timeFrame: Day 0 to Day 21
measure: Peak Day of Nasal Virus quantity
timeFrame: Day 0 to day 21
measure: Peak Day of nasal neutrophils
timeFrame: Day 0 to Day 21
measure: Peak Day of Nasal virus anti-bodies
timeFrame: Day 0 to Day 21
measure: Peak Day of blood virus anti-bodies
timeFrame: Day 0 to Day 21
measure: Peak Symptom score
timeFrame: Day 0-21
measure: Peak day of symptom score
timeFrame: Day 0-21
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Human Studies Facility
state: North Carolina
Study officials:
affiliation: UNC
name: Meghan Rebuli, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNC
name: Terry Noah, MD
role: PRINCIPAL_INVESTIGATOR
References: