Woodsmoke Exposure, Influenza Infection, and Nasal Immunity

Phase 4SuspendedNCT06841913

University of North Carolina, Chapel Hill112 enrolled

Overview

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

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

112

Conditions

Smoke Exposure Influenza

Interventions

LAIV nasal vaccine is chosen as a model viral infectionBIOLOGICAL

Inoculation with LAIV

Wood smokeOTHER

Wood smoke exposure concentrations at 500 ug/m3 for two hours.

Placebo for LAIV nasal vaccine is chosen as a model viral infectionBIOLOGICAL

Placebo for LAIV inoculation. Nasal administration of normal saline.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 49 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Human Studies Facility

Chapel Hill, North Carolina, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Day 0 to Day 7

Virus Quantity (AUC)

Virus quantity in nasal secretions

Time frame: Day 0 to Day 7

Nasal Neutrophils (AUC)

nasal secretion

Time frame: Day 0 to Day 7

Nasal Viral Antibodies (AUC)

virus-specific antibody levels in nasal secretions

Time frame: Day 0 to Day 7

Blood Viral Antibodies (AUC)

virus-specific antibody levels in blood

Time frame: Day 0 to Day 7

Secondary Outcomes

Peak Tissue gene expression

Peak value of Tissue-level gene expression (genes identified as responsive to WS and/or LAIV)

Data from ClinicalTrials.gov

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