Airway Smooth Muscle and Asthma Severity

NCT00779870 | Completed Results

• 1 other identifier: 08/H0708/2
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma

Keywords

asthma severity; airway smooth muscle; oxidative stress

Outcome Measures

Primary Outcomes (3)

• Difference in ASM Mass Between Groups

  at time of bronchoscopy, an average of 1 hour

• Difference in ASM Proliferation, Migration and Cytokine Release Between Groups

  at time of bronchoscopy, an average of 1 hour

• Difference in Intracellular Oxidative Stress Mechanisms From ASM Between Groups

  Expression of Nrf2 protein

  at time of bronchoscopy, an average of 1 hour

Secondary Outcomes (1)

• Correlation Between ASM Mass and Airway Hyper-responsiveness (PC20)

  at the time of bronchoscopy, an average of 1 hour

Study Arms (4)

1

healthy volunteers

Other: bronchoscopy

2

mild asthmatics

Other: bronchoscopy

3

moderately-severe asthmatics

Other: bronchoscopy

4

severe asthmatics

Other: bronchoscopy

Interventions

bronchoscopy OTHER

bronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Mild, moderate and severe asthmatics, with a control group of healthy non-smoking volunteers

You may qualify if:

• For the severe asthma subjects, they will also have the following:
• Major characteristics (at least one of the following criteria)
• Treatment with continuous or near continuous (\>50% of year) oral corticosteroids
• Requirement for treatment with high dose inhaled corticosteroids (ICS) Minor characteristics (at least 2 out of the following)
• Requirement for daily treatment with a controller medication in addition to ICS e.g. LABA, theophylline, leukotriene antagonist
• Asthma symptoms requiring SABA on a daily or near daily basis
• Persistent airways obstruction (FEV1 \<80% predicted, diurnal PEF variation \>20%)
• One or more emergency care visits for asthma per year
• or more steroid "bursts" per year
• Prompt deterioration with ≤ 25% reduction in oral or ICS
• Near fatal asthma event in the past
• Reference \[1\] GINA - The Global Initiative for Asthma. www.ginasthma.com

You may not qualify if:

• Healthy volunteer subjects:
• We are aiming for 5 atopic and 5 non-atopic healthy volunteers.
• Age 18 - 60 Non smokers (or less than 5 pack/yrs if ex-smokers) Normal lung function
• 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

Sponsors & Collaborators

• Imperial College London: lead
• Asthma UK: collaborator
• Royal Brompton & Harefield NHS Foundation Trust: collaborator

Study Sites (1)

Royal Brompton Hospital

London, Sw3 6NP, United Kingdom

Location

Related Publications (1)

• Michaeloudes C, Chang PJ, Petrou M, Chung KF. Transforming growth factor-beta and nuclear factor E2-related factor 2 regulate antioxidant responses in airway smooth muscle cells: role in asthma. Am J Respir Crit Care Med. 2011 Oct 15;184(8):894-903. doi: 10.1164/rccm.201011-1780OC.

  PMID: 21799075 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

endobronchial biopsies and cultured airway smooth muscle cells

MeSH Terms

Conditions

Asthma

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Results Point of Contact

• Title: Prof Fan Chung
• Organization: Imperial College London

f.chung@imperial.ac.uk

00442075947954

Study Officials

• Kian F Chung, MBBS MD FRCP DSc

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 22, 2008
• First Posted: October 24, 2008
• Study Start: October 1, 2008
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 31, 2019
• Results First Posted: October 31, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)