Rhinovirus Infection in Asthma Clinical Trial
Official title:
Human Model of Rhinovirus Induced Acute Asthma Exacerbations
We, the investigators, hypothesise that there are distinct gene profiles in
rhinovirus-induced acute exacerbations of asthma. We further hypothesise that these changes
in gene expression involve both known mediators of the asthma phenotype as well as other
molecules not previously associated with asthma.
The primary objective of this study is to use gene array analysis to determine
differentially expressed genes in bronchial epithelial cells and alveolar macrophages from
normal and asthmatic subjects before and during rhinovirus infection in vivo. A secondary
objective is to determine whether any altered expressions are related to symptom severity,
virus load, lung function or airway inflammation in vivo.
We plan to recruit 45 subjects: 15 healthy volunteers, 15 asthmatics naïve to inhaled
corticosteroid therapy, and 15 asthmatics on inhaled corticosteroids who will undergo two
bronchoscopies, one prior to infection with rhinovirus and the second 4 days post
inoculation. Bronchial brushings, biopsies and bronchoalveolar lavage (BAL) will be
performed. RNA will be extracted with TRIzol reagent (Invitrogen, Carlsbad, CA) and purified
by passage through RNeasy columns (Qiagen, Valencia, CA). Exon 1.0ST array chips
(Affymetrix, Santa Clara, CA) will be used to analyse changes in gene expression. These are
the most powerful genome expression tools available with 1.4 million probe sets and over 5.5
million features per array. Genes found to be significantly upregulated will be confirmed by
quantitative RT-PCR.
Using a novel method of collecting undiluted bronchial epithelial lining fluid
(bronchosorption) large numbers of proteins will be measured with a MesoScale Discovery
multiplexed array system (MesoScale Discovery, Gaithersburg, Md) allowing further
confirmation of the gene array results as well as providing in vivo evidence of dysregulated
protein production in asthmatics. Gene expression and protein levels will be correlated with
viral load, symptom scores, lung function and airway inflammation in vivo.
This study represents the first comprehensive evaluation of changes in bronchial epithelial
gene expression during rhinovirus infection in vivo and therefore has the potential to
provide significant insights into the host response in asthma and identify potential novel
targets for further evaluation.
n/a
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01773590 -
Mechanisms of Interplay Between Allergy and Viruses in Asthma
|
N/A |