Smoke Exposure, Influenza
Conditions
Keywords
LAIV, Flumist, Influenza, Wood Smoke, Smoke, Fire
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.
Interventions
BIOLOGICALLAIV nasal vaccine is chosen as a model viral infection
Inoculation with LAIV
OTHERWood smoke
Wood smoke exposure concentrations at 500 ug/m3 for two hours.
BIOLOGICALPlacebo for LAIV nasal vaccine is chosen as a model viral infection
Placebo for LAIV inoculation. Nasal administration of normal saline.
OTHERPlacebo for Wood Smoke (clean Air Exposure)
Clean Air Exposure for 2 hours
Sponsors
National Institutes of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
This is a randomized, double-blinded study so packaging and labeling by IDS is such that both study participants and study personnel (lab techs) will be blinded to the treatment (either LAIV or placebo) given. Due to the smell of the WS it will not be possible to completely blind subjects or coordinators as to exposure. The contractor maintaining the woodsmoke exposure chamber add a small amount of woodsmoke into the chamber to minimize bias. The risk for bias is felt to be minimal because all of the study's primary and most of the secondary outcomes are laboratory assays for which the technicians performing the assays will be blinded as to subject group. Unblinding will occur at the conclusion of the study or earlier if needed for safety purposes and as dictated by the UNC IRB, study sponsor, and DSMB.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| Peak Day of Nasal virus anti-bodies | Day 0 to Day 21 | Peak day of virus-specific antibody levels in nasal secretions |
| 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 |
Countries
United States
Outcome results
None listed