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

University of North Carolina (UNC)

Status and phase: Suspended; Phase 4

Conditions: Smoke Exposure; Influenza

Treatments: 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)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06841913

24-1802

1R01ES036209-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 112 estimated patients

Sex: All

Ages: 18 to 49 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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112 participants in 4 patient groups, including a placebo group

Wood smoke followed by LAIV

Experimental group

Description:

Participants will receive LAIV after a 2 hour wood smoke exposure.

Treatment:

Other: Wood smoke

Biological: LAIV nasal vaccine is chosen as a model viral infection

Wood smoke followed by Placebo

Active Comparator group

Description:

Participants will receive a LAIV placebo after a 2 hour wood smoke exposure.

Treatment:

Biological: Placebo for LAIV nasal vaccine is chosen as a model viral infection

Other: Wood smoke

Clean Air followed by LAIV

Active Comparator group

Description:

Participants will receive LAIV after a 2 hour clean air exposure.

Treatment:

Other: Placebo for Wood Smoke (clean Air Exposure)

Biological: LAIV nasal vaccine is chosen as a model viral infection

Clean Air followed by Placebo

Placebo Comparator group

Description:

Participants will receive a LAIV placebo after a 2 hour clean air exposure.

Treatment:

Other: Placebo for Wood Smoke (clean Air Exposure)

Biological: Placebo for LAIV nasal vaccine is chosen as a model viral infection