Effects of Wood Smoke Particles on Influenza-induced Nasal Inflammation in Normal Volunteers

Effects of Wood Smoke Particles on Influenza-induced Nasal Inflammation in Normal Volunteers

This study is focused on the pathophysiology underlying the association between exposure to particulate pollutants and risk for/response to viral infection. The investigators hypothesize that exposure to wood smoke particles (WSP) enhances influenza virus-induced granulocyte and NK cell activation, via hyaluronic acid-mediated effects on IFNg production. Oxidant stress and viral replication may also be affected. As an NIH funded ViCTER project, the purpose of the study is also to test novel assays of granulocyte activation (Doershuk lab) and lipid mediator activation (Albritton lab) which have not previously been used in this type of research.

Healthy, nonsmoking adults age 18-40 years will be recruited. This is a randomized, placebo controlled study comparing NLF granulocyte responses to LAIV administered after either WSP or clean air, in normal healthy volunteers. Subjects receive either WSP or placebo (clean air), followed by a standardized dose of LAIV and serial post-infection sampling of nasal lavage fluids, nasal biopsy and blood

Inclusion Criteria:

1. Normal lung function, defined as (Knudson 1976/1984 predicted set): FVC > 75 % predicted for gender, ethnicity, age and height; FEV1 >75 % predicted ; FEV1/FVC ratio >0.70 and < 0.90.
2. Oxygen saturation of > 94%
3. Normal blood pressure (Systolic between 140 - 90, Diastolic between 90-60 mm Hg)
4. Symptom Score no greater than 6 (out of a possible 39) for total symptom score
5. On the day of a challenge, body temperature must be no greater than 37.8 degrees, measured orally

Exclusion Criteria:

1. 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)
2. Positive pregnancy test within 48 hours of the time of challenge
3. 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 and does not smoke at all 1 week prior to entrance in the study.
4. Receipt of LAIV in the current season
5. History of allergy to eggs
6. 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
7. Unspecified illnesses, which in the judgment of the investigator increase the risk associated with the experimental LAIV infection, will be a basis for exclusion.
8. Expected exposure of subject to immunocompromised individuals (who can be infected by LAIV) for the 3 weeks following LAIV inoculation