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An Investigation of Tumor Necrosis Factor (TNF)-Alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01161303
Recruitment Status : Completed
First Posted : July 13, 2010
Last Update Posted : July 13, 2010
University of Southampton
Information provided by:
University Hospital Southampton NHS Foundation Trust

Brief Summary:

We have developed in vitro systems including primary epithelial cell cultures and explant cultures of bronchial tissues to study the interaction between the bronchial mucosa and allergens. This approach involves culturing bronchial biopsies under optimal conditions and stimulate them with allergens thus enabling us to perform a dynamic study without the need of performing several bronchoscopies and will allow the testing of unapproved substances, which could, otherwise, not be delivered, in vivo.

We wish to apply these ex vivo bronchial culture systems to assess cytokine release in moderately severe asthmatics and evaluate the effects of blocking TNF-alpha signalling using anti TNF-alpha monoclonal antibodies.

Condition or disease

Detailed Description:
Volunteers with moderately severe asthma will be recruited and carefully characterized in terms of lung function, asthma symptom scores, medication usage and allergen sensitivity (by blood and skin tests). If suitable, they will then be asked to withdraw their corticosteroids for a week with careful monitoring of the symptoms and peak flows before undergoing fibreoptic bronchoscopy as was carried out in the previous explant study. Bronchial brushings and biopsies will be carried out as per standard technique used in University medicine. Primary epithelial cell cultures will be established from bronchial brushings and will be used for optimising the dose of anti TNF-alpha required for inhibition of TNF-alpha induced responses. The biopsies will be placed in either culture medium alone, allergen extract or allergen extract plus anti TNF-alpha antibody and cultured for 24 hours. The biopsies will then be either snap frozen in liquid nitrogen for analysis of cytokines or processed for immunohistochemical analysis. The supernatants from each study will be recovered and analysed for cytokine (IL-5, IL-8, IL-13, MIP 1 alpha and RANTES) release by ELISA.

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Study Type : Observational
Actual Enrollment : 12 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Study to Investigate the Role of TNF-alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures
Study Start Date : July 2000
Actual Primary Completion Date : June 2003
Actual Study Completion Date : June 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Biopsy

Biospecimen Retention:   Samples With DNA
  • bronchial brushings and biopsies
  • Blood

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Primary care clinic

Inclusion Criteria:

  • Moderately severe asthmatics
  • Male or female
  • Uses inhaled beclomethasone 400-1000 mcg or equivalent
  • Documented positive skin test to common allergens and
  • FEV1 of >60% predicted

Exclusion criteria:

  • Smokers
  • Subjects with an acute asthmatic episode in the last 6 weeks
  • Other significant clinical illnesses
  • Pregnant women
  • Those sensitive to lignocaine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01161303

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United Kingdom
Southampton University Hospital Trust
Southampton, Hampshire, United Kingdom, SO16 6YD
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust
University of Southampton
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Principal Investigator: Stephen T Holgate, MD University of Southampton

Publications of Results:
Babu KS, Puddicombe S, Shaw TJ, Howell T, Wilson SJ, Holgate ST, Davies DE. Am J Respir Crit Care Med. 169 (7): A801, 2004

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Responsible Party: Professor S.T. Holgate, University of Southampton Identifier: NCT01161303     History of Changes
Other Study ID Numbers: SUHT-III-KSB
First Posted: July 13, 2010    Key Record Dates
Last Update Posted: July 13, 2010
Last Verified: July 2010

Keywords provided by University Hospital Southampton NHS Foundation Trust:
TNF alpha
epithelial cell culture

Additional relevant MeSH terms:
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Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases