Mechanisms of Rhinovirus Induced Asthma Exacerbations

March 3, 2025 updated by: Imperial College London

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • London, England, United Kingdom, W2 1PG
        • National Heart and Lung Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion criteria for asthmatics:

Age 18-55 years Doctor diagnosis of asthma Histamine PC20 < 8 mg/mL Mild-to-moderate disease based on 2004 GINA criteria Treatment with either short-acting β-agonists (SABA) alone or with maintenance inhaled corticosteroids (daily dose between 200 μg and 1000 μg BDP equivalent) Worsening asthma symptoms with infection since last change in asthma therapy Atopic on skin testing (≥ 1 positive skin prick test on a panel of 10 aeroallergens)

Inclusion criteria for healthy subjects:

Age 18-55 years No history or clinical diagnosis of asthma or any other significant respiratory disease No history of allergic rhinitis or eczema Negative responses on skin prick testing (PC)20 > 8 µg/mL Absence of significant systemic disease

Exclusion criteria for asthmatics:

History of severe asthma defined by GINA Smoking history over past 6 months or > 5 pack year history Current symptoms of allergic rhinitis Current or previous history of significant respiratory disease (other than asthma) Any clinically relevant abnormality on screening or detected significant systemic disease Asthma exacerbation or viral illness within the previous 6 weeks Treatment with oral corticosteroids in the previous 3 months Current use of any nasal medication, anti-histamine, anti-leukotrienes, LABA, or anti-IgE therapy Presence of serum neutralising antibodies to rhinovirus-16 at screening Pregnant or breastfeeding women Contact with infants or elderly at home or at work

Exclusion criteria for healthy subjects:

History of atopy, asthma or any significant respiratory disease Smoking history over past 6 months or > 5 pack year history Current symptoms of rhinitis Any clinically relevant abnormality on screening or detected significant systemic disease Viral illness within the previous 6 weeks Current use of any nasal medication or anti-histamine Presence of serum neutralising antibodies to rhinovirus-16 at screening Pregnant or breastfeeding women Contact with infants or elderly at home or at work

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Asthma, Healthy
Asthmatics or Healthy Volunteers
Other: Rhinovirus infection
All subjects (asthmatic and non asthmatic healthy)will be infected with Rhinovirus 16.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Differentially expressed genes in bronchial epithelial cells and alveolar macrophages from normal and asthmatic subjects before and during rhinovirus infection
Time Frame: april 2012
april 2012

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 12, 2011

Primary Completion (Actual)

April 30, 2014

Study Completion (Actual)

April 30, 2014

Study Registration Dates

First Submitted

July 8, 2010

First Submitted That Met QC Criteria

July 8, 2010

First Posted (Estimated)

July 9, 2010

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 3, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09/H0712/59

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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