Inflammation and Corticosteroid Responsiveness in Severe Asthma

NCT00180661 | Completed Results DMC

• 1 other identifier: HL-69155
• Study Type: observational
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Some patients with mild asthma may develop severe asthma. It is not known what makes patients with mild asthma become severe, and we plan to find out why this happens. Patients with severe asthma may have a different type of inflammation in the airway tubes. Patients with severe asthma do not get as much benefit from taking steroid inhalers or tablets compared to asthma patients with mild disease. The study hypothesis is that the inflammation in severe asthma is such that it makes steroids less effective in treating asthma. We will find out what possible abnormalities there are in the blood cells and the bronchoalveolar macrophage cells in the lungs of patients with severe asthma compared to those with mild or moderate asthma.

Conditions

Asthma

Keywords

Severe asthma; corticosteroid responsiveness

Outcome Measures

Primary Outcomes (3)

• Lung Function FEV1

  FEV1, or forced expiratory volume, is a measurement taken from a pulmonary function test. It calculates the amount of air that a person can force out of their lungs in 1 second.

  1 day

• Suppression of Monocyte Activation and Alveolar Macrophage Activation by Dexamethasone Ex-vivo

  IL8 - Interleukin-8 (IL-8) is a cytokine produced by many normal cells including monocytes, neutrophils, fibroblasts, and endothelial cells

  1 day

• Effect of Corticosteroids on Release of Cytokines From Macrophages

  Once

Secondary Outcomes (3)

• Exhaled NO

  1 day

• Biopsy Eosinophils

  Once

• Sputum Eosinophils

  Once

Study Arms (3)

Severe Asthma

Patients under Steps 4/5 of Asthma Treatment - SIGN/BTS Guidelines

Moderate Asthma

Asthma patients on steps 2/3 of Asthma treatment according to SIGN/BTS Guidelines

Mild Asthma

Asthma patients on steps 1 of asthma treatment (steroid naive).

Eligibility Criteria

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

Study Population

Asthma population living in the UK - ranging in severity (from mild, to severe).

You may qualify if:

• The final diagnosis of severe asthma will be made according to the screening steps we have set up. The definition will require the presence of one or both major criteria (treatment with continuous or near continuous oral corticosteroids and/or requirement for treatment with high dose inhaled steroids) and two minor criteria.
• Patients who do not fit the criteria of severe asthma will not be entered into the study.
• Age 18-60; both sexes.
• Post-bronchodilator FEV1 greater than 40% on the day of the bronchoscopy
• No evidence of an exacerbation of asthma within the past 4 weeks.
• Ability to cooperate with procedures
• Ability to give consent
• Current smokers, and ex-smokers with greater than 10 pack years history of smoking.

You may not qualify if:

• Pregnancy or unreliable contraceptive measures in child-bearing woman. he bronchoscopist has determined the subject is clinically appropriate for bronchoscopy

Sponsors & Collaborators

• Imperial College London: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Royal Brompton Hospital

London, SW3 6HP, United Kingdom

Location

Related Publications (2)

• Chung KF, Godard P, Adelroth E, Ayres J, Barnes N, Barnes P, Bel E, Burney P, Chanez P, Connett G, Corrigan C, de Blic J, Fabbri L, Holgate ST, Ind P, Joos G, Kerstjens H, Leuenberger P, Lofdahl CG, McKenzie S, Magnussen H, Postma D, Saetta M, Salmeron S, Sterk P. Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma. European Respiratory Society. Eur Respir J. 1999 May;13(5):1198-208. doi: 10.1034/j.1399-3003.1999.13e43.x. No abstract available.

  PMID: 10414427 BACKGROUND

• Bhavsar P, Hew M, Khorasani N, Torrego A, Barnes PJ, Adcock I, Chung KF. Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma. Thorax. 2008 Sep;63(9):784-90. doi: 10.1136/thx.2007.090027. Epub 2008 May 20.

  PMID: 18492738 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

endobronchial biopsies and blood specimens.

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

f.chung@imperial.ac.uk

00442075947954

Study Officials

• Kian Fan Chung, MD

  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: September 12, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2003
• Primary Completion: February 1, 2008
• Study Completion: May 1, 2008
• Last Updated: October 4, 2019
• Results First Posted: October 4, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)