Mechanisms of Interplay Between Allergy and Viruses in Asthma

Imperial College London

Status

Completed

Conditions

Rhinovirus Infection in Asthma

Treatments

Other: Rhinovirus Infection

Study type

Interventional

Funder types

Other

Identifiers

NCT01773590

12/LO/1278 (Other Identifier)

Details and patient eligibility

About

The aim of this study is to investigate the mechanisms of interplay between allergy (IgE and Th2 mediated inflammation) and virus infection in the development of asthma, as well as the risk and severity of acute exacerbations of asthma. Understanding these mechanisms should identify new approaches for novel therapies for the prevention of asthma development and for prevention/treatment of asthma exacerbations. Such treatment has potential to have a major impact on patient quality of life and to result in enormous reductions in health care costs.

A human model will be used to identify dysregulated genes/proteins and determine relationships with disease outcomes. This study will compare lower airway responses between asthmatic and healthy control subjects undergoing rhinovirus (RV) experimental infection (subjects will be infected with rhinovirus as part of the study). This will have the dual advantage of investigating mechanisms in the most natural model possible, as well as developing a better model for testing novel therapeutic approaches. The investigators will analyse the samples from both subject groups, to determine their relevance to the human disease. Any genes/proteins shown to be dysregulated and related to disease outcomes in the human model will be very strong candidates for immediate translation into human intervention studies.

Up to 12 asthmatic and/or healthy subjects will be recruited for a preliminary pilot study. These subjects will be ineligible to enter the main study due to the presence of neutralizing antibody to RV16 (~50% of subjects otherwise suitable for the study). These subjects will meet all other inclusion/exclusion criteria for the main study. The 12 participants will undergo tests including a single bronchoscopy, nasal sampling and blood tests allowing for optimisation of all sample processing techniques. They will not be infected with RV-16.

In the main study the investigators will aim to study up to 15 healthy volunteers and 15 volunteers with moderate asthma (all on inhaled steroid treatment). Subjects will undergo a single baseline bronchoscopy 2 weeks prior to inoculation with the RV16 virus. Following infection with the virus participants will be required to attend for regular sample collection including 2 further bronchoscopies post-infection. Patients will be followed until convalescence 6 weeks post infection.

Enrollment

43 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Inclusion criteria for Asthmatic subjects:

Age 18-55 years
Doctor diagnosis of Asthma
Histamine PC20 < 8 µg/ml (or <12 µg/ml and bronchodilator response ≥ 12%) and worsening asthma symptoms with infection since last change in asthma therapy
Atopic on skin testing
Treatment comprising ICS or combination inhaler (LABA+ICS)

*subjects on inhaled corticosteroids must be on a daily dose of 400mcg fluticasone or equivalent.
An Asthma Control Questionnaire (ACQ) score of > 0.75.

Inclusion criteria for healthy controls:

Age 18-55 years
No history or clinical diagnosis of asthma
No history of allergic rhinitis or eczema
Negative responses on skin prick testing
PC20 > 8 µg/ml and bronchodilator response <12%
Absence of current or previous history of significant respiratory disease
Absence of significant systemic disease

Exclusion criteria

Exclusion criteria for Asthmatic subjects:

Smoking history over past 6 months
Negative skin prick tests
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
Asthma exacerbation or viral illness within the previous 6 weeks
Treatment with oral steroids now or in the previous 3 months
Current use of nasal spray, anti-histamine, anti-leukotrienes
Antibodies to rhinovirus 16 in a titre >1:2

Exclusion criteria for healthy controls:

Any clinically relevant abnormality on screening or detected significant systemic disease
A current or previous diagnosis of asthma
Any positive skin prick test
Current symptoms of allergic rhinitis
History of eczema or allergic rhinitis
Pregnant or nursing women
Common cold within the previous 8 weeks
Treatment with oral or inhaled steroids now or in the previous 3 months; current use of long-acting β-agonists, nasal spray, anti-histamine, leukotrienes or tiotropium.
Shortness of breath score at screening over 1 or total lower respiratory tract score over 7
Antibodies to rhinovirus 16 in a titre >1:2