Mechanisms of Rhinovirus Induced Asthma Exacerbations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01159782
Recruitment Status : Unknown
Verified July 2010 by Imperial College London.
Recruitment status was:  Recruiting
First Posted : July 9, 2010
Last Update Posted : July 23, 2010
Information provided by:
Imperial College London

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Rhinovirus Infection in Asthma Other: Rhinovirus infection Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Human Model of Rhinovirus Induced Acute Asthma Exacerbations
Study Start Date : October 2009
Estimated Primary Completion Date : April 2012
Estimated Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
U.S. FDA Resources

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

Primary Outcome Measures :
  1. differentially expressed genes in bronchial epithelial cells and alveolar macrophages from normal and asthmatic subjects before and during rhinovirus infection [ Time Frame: april 2012 ]

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria for atopic asthmatics:

  • Age 18-55 years
  • Doctor diagnosis of Asthma
  • PC20 < 8 µg/ml and worsening asthma symptoms with infection since last change in asthma therapy.
  • Atopic on skin testing
  • Treatment comprising short acting beta agonist (SABA) only (steroid naïve group) or SABA + inhaled corticosteroid (ICS) * (steroid treated group)

    • subjects on inhaled corticosteroids must be on a daily dose of between 100mcg and 1000mcg fluticasone or equivalent.

Exclusion Criteria:

  • Smoking history over past 6 months or > 5 py 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
  • Pregnant or breastfeeding women
  • Contact with infants or elderly at home or at work
  • Exacerbation or virus within the previous 6 weeks
  • Treatment with oral steroids now or in the previous 3 months
  • Current use of nasal spray, anti-histamine, anti-leukotriene
  • Antibodies to rhinovirus 16 in a titre >1:2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01159782

United Kingdom
National Heart and Lung Institute Recruiting
London, England, United Kingdom, W2 1PG
Contact: David Jackson   
Principal Investigator: Sebastian Johnston         
Sponsors and Collaborators
Imperial College London

Responsible Party: Professor Sebastian Johnston, Imperial College London Identifier: NCT01159782     History of Changes
Other Study ID Numbers: 09/H0712/59
First Posted: July 9, 2010    Key Record Dates
Last Update Posted: July 23, 2010
Last Verified: July 2010

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases