NCT01159782

Mechanisms of Rhinovirus Induced Asthma Exacerbations

Completed NA Last updated 6 March 2025

What this trial tests

NA trial testing Rhinovirus infection in Rhinovirus Infection in Asthma in 46 participants. Completed in 30 April 2014.

Timeline

12 October 2011

Primary endpoint
30 April 2014

30 April 2014

Quick facts

Lead sponsor	Imperial College London
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	46
Start date	12 October 2011
Primary completion	30 April 2014
Estimated completion	30 April 2014
Sites	1 location across United Kingdom

Drugs / interventions tested

• Rhinovirus infection

Conditions studied

• Rhinovirus Infection in Asthma — all drugs for Rhinovirus Infection in Asthma →

Sponsor

Imperial College London

Who can join

Adults 18 to 55, any sex, with Rhinovirus Infection in Asthma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.
   Radzikowska U, Eljaszewicz A, Tan G, Stocker N, et al · · 2023 · cited 45× · PMID 37087523 · DOI 10.1038/s41467-023-37470-4