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| Sponsors and Collaborators: |
Imperial College London Asthma UK Royal Brompton & Harefield NHS Foundation Trust |
|---|---|
| Information provided by: | Imperial College London |
| ClinicalTrials.gov Identifier: | NCT00779870 |
Purpose
Our hypothesis is that the severity of asthma is determined by the way in which airway smooth muscle cells grow and release inflammatory mediators. Our main objective is to establish how the properties of the airway smooth muscle cell varies with asthma severity. Environmental agents, such as cigarette smoke, and inflammation can give rise to oxidative stress - this is a process whereby harmful chemicals called free radicals are formed in the body and damage tissues. The damage caused can be limited/prevented by protective, or anti-oxidant mediators. We will also look at molecules involved in oxidative stress which may affect the way in which the airway smooth muscle grows and produces inflammatory mediators.
| Condition | Intervention |
|---|---|
|
Asthma |
Other: bronchoscopy |
| Study Type: | Observational |
| Study Design: | Cohort, Cross-Sectional |
| Official Title: | Evaluating the Role of Oxidant/Anti-Oxidant Balance and the Relationship of Asthma Severity on Airway Smooth Muscle Proliferation, Migration and Cytokine Release. |
endobronchial biopsies and cultured airway smooth muscle cells
| Estimated Enrollment: | 68 |
| Study Start Date: | October 2008 |
| Estimated Study Completion Date: | September 2011 |
| Estimated Primary Completion Date: | September 2011 (Final data collection date for primary outcome measure) |
| Groups/Cohorts | Assigned Interventions |
|---|---|
|
1
health volunteers
|
Other: bronchoscopy
bronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies
|
|
2
mild asthmatics
|
Other: bronchoscopy
bronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies
|
|
3
moderately-severe asthmatics
|
Other: bronchoscopy
bronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies
|
|
4
severe asthmatics
|
Other: bronchoscopy
bronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies
|
Aims and Objectives The objective of this study is to examine whether the severity of asthma is related to (and possibly caused by) ASM dysfunction. Severe asthmatics have been shown to have more ASM in bronchial biopsies than non-severe asthmatics16. Because ASM cells can be obtained from bronchial biopsies obtained via bronchoscopy, we will examine endobronchial biopsies from mild, moderate and severe asthmatics, and healthy non-asthmatic subjects to compare features of remodelling (severe asthmatic subjects will have been assessed through the Difficult Asthma Protocol at the Royal Brompton Hospital24). In particular, we will focus on ASM mass, proliferation and changes in expression of different contractile proteins (α-actin and myosin) and chemokines, and will assess in vitro the response of ASM cells to stimulation by TGF-β and IL-1β. We will also examine the effect of dexamethasone on chemokine release and induced proliferation in vitro. We will also study enzymes and anti-oxidants involved in oxidative stress, such as Nox4, MnSOD and catalase, to look at their role in regulating ASM cell proliferation and chemokine synthesis. We want to see if there is an oxidant-anti oxidant balance in ASM in severe asthma compared to non-severe asthma.
AIM:
1. To establish the difference in ASM phenotype in asthma patients of differing severity of disease in terms of ASM mass, proliferation, migration and chemokine release.
Study design There will be 3 study visits. In the first two visits, the subjects will undergo spirometry with reversibility testing, a methacholine challenge test (to assess degree of bronchial hyper-responsiveness), skin prick tests and IgE levels (to assess atopic status), measurement of exhaled nitric oxide (as a non-invasive marker of inflammation), and the asthmatic subjects will complete an Asthma Control Questionnaire and an Asthma Quality of Life Questionnaire. The third visit will be on the day admission for the bronchoscopy.
Study protocol:
Visit 1 - screening visit
Visit 2 - Methacholine challenge test
Visit 3 - Day admission for fibreoptic bronchoscopy
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
Mild, moderate and severe asthmatics, with a control group of healthy non-smoking volunteers
Inclusion criteria - Asthma Age 18-60 Physician diagnosis of asthma Intermittent/mild, moderate and severe asthma as per GINA guidelines [1]
For the severe asthma subjects, they will also have the following:
Major characteristics (at least one of the following criteria)
Requirement for treatment with high dose inhaled corticosteroids (ICS) Minor characteristics (at least 2 out of the following)
Near fatal asthma event in the past
Reference [1] GINA - The Global Initiative for Asthma. www.ginasthma.com
Exclusion criteria - Asthma Intubation for asthma within 6 months of entry into this study Current smokers, or less than 3 years since quitting smoking (< 5 pack/years) Less than 4 weeks from an exacerbation On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin Concomitant anti-IgE therapy On anti-platelet or anti-coagulant drugs Low platelet count Pregnancy or breast-feeding Previous bronchoscopy within three months of this study
Healthy volunteer subjects:
We are aiming for 5 atopic and 5 non-atopic healthy volunteers.
Inclusion criteria:
Age 18 - 60 Non smokers (or less than 5 pack/yrs if ex-smokers) Normal lung function
Exclusion criteria:
History of asthma or allergic rhinitis Any chronic illness Current smokers, or less than 3 years since quitting smoking (< 5 pack/years) PC20 less than 16mg/ml On anti-platelet or anti-coagulant drugs Low platelet count Pregnancy or breast-feeding Previous bronchoscopy within three months of this study
Contacts and Locations| Contact: Patricia Macedo, MBBS MRCP Msc | 00442073518051 | p.macedo@imperial.ac.uk |
| Contact: Florence Chow, RGN | 00442073518051 | florence.chow@imperial.ac.uk |
| United Kingdom | |
| Royal Brompton Hospital | Recruiting |
| London, United Kingdom, Sw3 6NP | |
| Contact: Florence Chow, RGN 00442073518051 florence.chow@imperial.ac.uk | |
| Principal Investigator: | Kian F Chung, MBBS MD FRCP DSc | Imperial College London |
More Information
| Responsible Party: | Imperial College London ( Professor Kian Fan Chung ) |
| Study ID Numbers: | 08/H0708/2 |
| Study First Received: | October 22, 2008 |
| Last Updated: | October 23, 2008 |
| ClinicalTrials.gov Identifier: | NCT00779870 History of Changes |
| Health Authority: | United Kingdom: National Health Service; United Kingdom: Research Ethics Committee |
|
asthma severity airway smooth muscle oxidative stress |
|
Hypersensitivity Lung Diseases, Obstructive Antioxidants Respiratory Tract Diseases Bronchial Diseases Lung Diseases |
Hypersensitivity, Immediate Anesthetics Stress Asthma Anesthetics, Local Respiratory Hypersensitivity |
|
Hypersensitivity Lung Diseases, Obstructive Immune System Diseases Respiratory Tract Diseases Bronchial Diseases |
Lung Diseases Hypersensitivity, Immediate Asthma Respiratory Hypersensitivity |
