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

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

Study Overview

• Status: Completed
• Conditions: Response of Viral Infection to Woodsmoke
• Intervention / Treatment: Other: wood smoke; Other: clean air

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • center for envionmental medicine asthma an lung biology at the EPA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Wood smoke; The dose of WSP to be used (500 µg/m3 for 2 hours) is based on prior studies which indicate the exposure is well tolerated, and is similar to that found in some indoor exposures in homes heated by wood burning (24-26). The route of administration (breathing air containing WSP at rest, nasally) is intended to mimic natural exposures.	Other: wood smoke
Placebo Comparator: clean air; Chapel Hill air which has been filtered to remove ambient air pollutants.	Other: clean air

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-13	Change in IL-13 and ECP in nasal lavage fluids (NLF) compared to pre-virus baseline	1-21 days

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Environmental Health Sciences (NIEHS); Environmental Protection Agency (EPA)

Publications and helpful links

General Publications

• Rebuli ME, Speen AM, Martin EM, Addo KA, Pawlak EA, Glista-Baker E, Robinette C, Zhou H, Noah TL, Jaspers I. Wood Smoke Exposure Alters Human Inflammatory Responses to Viral Infection in a Sex-Specific Manner. A Randomized, Placebo-controlled Study. Am J Respir Crit Care Med. 2019 Apr 15;199(8):996-1007. doi: 10.1164/rccm.201807-1287OC.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 3, 2014
• First Submitted That Met QC Criteria: July 2, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): June 11, 2015
• Last Update Submitted That Met QC Criteria: June 9, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: LAIV; Flumist; wood smoke
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Virus Diseases
• Other Study ID Numbers: 13-3076; 5R01ES013611-09 (U.S. NIH Grant/Contract)