In this study, the following subjects will be exposed to human rhinovirus (HRV): * those with classification of mild-moderate asthma * healthy control subjects. The investigators will study the kinetics of HRV-induced inflammatory and remodeling responses in a well characterized group of asthmatic subjects and compare these outcomes to those in a healthy, non-asthmatic control group.
Although changes in the lungs, known as remodeling, are a feature of asthma, the causes and mechanisms involved in the process have not yet been found. Recently, it has been established that remodeling can be observed in children prior to a formal diagnosis of asthma. Clinical studies indicate that HRV, "common cold" infections, are a common cause of recurrent respiratory illnesses in childhood, and children with HRV-associated wheezing episodes have an increased risk of developing asthma. This led to the hypothesis that HRV infections may play a central role in the start of the airway remodeling leading to asthma. The goal of this study is to determine if alterations in relevant airway remodeling growth factors differ between healthy controls and asthmatic subjects, pre- and post-HRV infection. These growth factors will be assessed in bronchoalveolar lavage (BAL) fluid and endobronchial biopsy tissues and correlated with viral levels in both nasal lavage and BAL fluid.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
2
Experimental rhinovirus infection: an FDA approved, GMP-grade HRV-39 stock (gift from Dr. Ronald B. Turner, University of Virginia), which has now been approved by Health Canada for human experimental use, will be used in this study.
The purpose of this test is to determine if lung airways narrow by more than 20%, which confirms an asthma diagnosis.
University of Calgary
Calgary, Alberta, Canada
Bronchial Alveolar Lavage (BAL) Fluid Protein Levels
The primary endpoint will be the protein levels in BAL fluid at Day 4 (post-infection) minus the value at Day -7 (pre-infection) for each of MMP-9, VEGF amphiregulin and activin A.
Time frame: Day -7 and Day 4
Quantitative Changes in Gene Expression Between Groups
Quantitative changes in gene expression between groups in BAL fluid, bronchial brushings, nasal scrapings and mucosal biopsies, for selected airway remodeling mediator genes, including MMP-9, amphiregulin, VEGF and activin A.
Time frame: Day -7 and Day 4
Changes in symptom scores, viral titers, spirometry, airway responsiveness (PC20 methacholine) and FeNO levels.
Time frame: Day -7 and Day 4
Quantification of inflammatory cells in the lower airways, assessed in BAL fluid and bronchial biopsies.
Time frame: Day -7 and Day 4
Correlation of gene expression and protein levels of selected mediators with viral titer, symptom scores and numbers of inflammatory cells in the upper and lower airways.
Time frame: Day -7 and Day 4
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This process uses a rhinoprobe to gently scrape the mucosal lining of the nose
For the purposes of this study, allergy skin testing will be done with the following aero-allergens: cat epidermis, dog epidermis, horse, grass mix, tree mix, weed mix, ragweed and house dust mite, along with a histamine positive control and a buffer \& glycerol negative control.
Peripheral blood for assessment of neutralizing antibodies to HRV-39
A small flexible tube the size of a pencil, with a video-camera built into the tip (called a bronchoscope), will be inserted through the nose or mouth and down into the lungs.