An observational study in Asthma, sponsored by Imperial College London. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-10-31.
Sponsored by Imperial College London · Observational
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.
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:
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
3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.
This study's enrollment of 18 is below the median of 150 across 970 observational studies indexed under Asthma.
Browse Asthma studies →Imperial College London is the lead sponsor of 824 studies on the registry; 178 are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 6 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
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
healthy volunteers
Other: bronchoscopy
mild asthmatics
Other: bronchoscopy
moderately-severe asthmatics
Other: bronchoscopy
severe asthmatics
Other: bronchoscopy
bronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies
Difference in ASM Mass Between Groups
Time frame: at time of bronchoscopy, an average of 1 hour
Difference in ASM Proliferation, Migration and Cytokine Release Between Groups
Time frame: at time of bronchoscopy, an average of 1 hour
Difference in Intracellular Oxidative Stress Mechanisms From ASM Between Groups
Expression of Nrf2 protein
Time frame: at time of bronchoscopy, an average of 1 hour
Correlation Between ASM Mass and Airway Hyper-responsiveness (PC20)
Time frame: at the time of bronchoscopy, an average of 1 hour
| Milestone | Healthy | Non-severe Asthma | Severe Asthma |
|---|---|---|---|
| Started | 5 | 6 | 7 |
| Completed | 5 | 6 | 7 |
| Not completed | 0 | 0 | 0 |
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Expression of Nrf2 protein
| relative expression unit | Healthy | Non-severe Asthma | Severe Asthma |
|---|---|---|---|
| Difference in Intracellular Oxidative Stress Mechanisms From ASM Between Groups | 2 (1.1 to 2.4) | 3 (1.1 to 3.6) | 3 (1.2 to 4.2) |
No measurements were reported for this outcome.
Collected over 2 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Healthy | 0/5 (0%) | 0/5 (0%) | 0/5 (0%) |
| Non-severe Asthma | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) |
| Severe Asthma | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) |
| Age, Continuous(years) | Healthy | Non-severe Asthma | Severe Asthma | Total |
|---|---|---|---|---|
| Mean | 34.67 ± 6.3 | 38.17 ± 8.5 | 36.67 ± 4.12 | 36.5 ± 6.3 |
| Sex: Female, Male(Participants) | Healthy | Non-severe Asthma | Severe Asthma | Total |
|---|---|---|---|---|
| Female | 1 | 1 | 2 | 4 |
| Male | 2 | 5 | 4 | 11 |
| Race and Ethnicity Not Collected(Participants) | Healthy | Non-severe Asthma | Severe Asthma | Total |
|---|---|---|---|---|
| Count of participants | — | — | — | 0 |
| Region of Enrollment(participants) | Healthy | Non-severe Asthma | Severe Asthma | Total |
|---|---|---|---|---|
| United Kingdom | 5 | 6 | 7 | 18 |
Plan to share: No
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Imperial College London