Regulation of the Release of Inflammatory Mediators From Lung Macrophages.

NCT00147017 | Completed Results

• 4 other identifiers: 01-093DHTAB PN1257DHTAB PC3608DHTAB P00134
• Study Type: observational
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate the mechanisms whereby specific white cells called macrophages found in the lung release inflammatory mediators or chemicals together with enzymes that destroy the surrounding lung tissue. The hypothesis is that in diseases such as chronic obstructive pulmonary disease (COPD), lung macrophages release either more or different types of inflammatory mediators and/or destructive enzymes compared to subjects without COPD. We will isolate macrophages from small pieces of lung parenchyma. These samples are derived from lobes resected for carcinoma of the lung. We would aim to examine the responses of tissue derived macrophages in three groups of subjects, namely (i) non-smoking controls (lung carcinoma as secondary metastasis), (ii) smokers without clinical or histological signs of COPD and (iii) smokers with COPD. The resected lung tissue will be cut into small pieces and washed in order to release the macrophages from the tissue. The macrophages will then be isolated from other cell types in the washings. We will then use these isolated cells in vitro to examine the cell surface receptors in order to compare these macrophage cells with macrophages reported from bronchoalveolar lavage and monocyte derived macrophage models. We will then examine inflammatory mediator synthesis and release following stimulation of these cells. We will also examine the regulation and release of enzymes known to damage lung tissue. Using these two models we will then examine the signal transduction pathways that lead to this activation of the macrophages and investigate the effects of novel therapeutic agents to inhibit inflammatory mediator and/or enzyme synthesis and release. The objective is to identify the mechanisms whereby macrophages respond to pro-inflammatory conditions seen in COPD with a view to identify novel targets for drug therapy.

Conditions

COPD; Chronic Bronchitis; Emphysema

Keywords

macrophage; inflammation; COPD

Outcome Measures

Primary Outcomes (3)

• Macrophage Activation, TNF-a

  measure release of inflammatory mediators from isolated macrophages

  20 hours

• Macrophage Activation, GM-CSF

  GM-CSF, granulocyte macrophage-colony stimulating factor

  20 hours

• Interleukin, IL-8

  20 hours

Study Arms (3)

Smokers

All subjects had a smoking history of \>15 pack years

Ex-smokers

Ex-smokers had ceased smoking for \>6 months.

Emphysema lung transplant

The emphysema subjects were all undergoing lung transplants.

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All subjects undergoing lung resection surgery

You may qualify if:

• \- All subjects undergoing surgical resection of the lung

You may not qualify if:

• \- Anyone unable to understand the consent form

Sponsors & Collaborators

• Imperial College London: lead
• Novartis: collaborator
• Boehringer Ingelheim: collaborator
• Royal Brompton & Harefield NHS Foundation Trust: collaborator

Study Sites (1)

Royal Brompton Hospital/NHLI Imperial College London

London, SW3 6LY, United Kingdom

Location

Related Publications (1)

• Smith SJ, Fenwick PS, Nicholson AG, Kirschenbaum F, Finney-Hayward TK, Higgins LS, Giembycz MA, Barnes PJ, Donnelly LE. Inhibitory effect of p38 mitogen-activated protein kinase inhibitors on cytokine release from human macrophages. Br J Pharmacol. 2006 Oct;149(4):393-404. doi: 10.1038/sj.bjp.0706885. Epub 2006 Sep 4.

  PMID: 16953188 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

protein samples have been retained

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic; Emphysema; Inflammation

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Results Point of Contact

• Title: Professor Louise Donnelly
• Organization: Imperial College London

l.donnelly@imperial.ac.uk

+442075947895

Study Officials

• Louise E Donnelly, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2005
• First Posted: September 7, 2005
• Study Start: June 1, 2001
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 10, 2019
• Results First Posted: November 27, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)