Regulation of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease

NCT00147095 | Completed

• 2 other identifiers: 02-207DHTAB PN1259
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate the mechanisms whereby lung function is decreased in COPD. The hypothesis is that in diseases such as COPD, inflammatory cells including neutrophils, macrophages and lymphocytes migrate to the lung and release either more or different types of inflammatory mediators and/or destructive enzymes compared to subjects without COPD. We aim to investigate these separate cell types in the blood of subjects with COPD and identify which genes are more highly expressed when compared to cells obtained from patients without COPD. We will also investigate the lung macrophages from these subjects to identify whether the same or different genes are expressed in these cells. We will isolate different leukocyte populations from the blood and extract ribonucleic acid (RNA) from these samples. The type and quantity of RNA in these samples is a reflection of the specific genes expressed in these cells. This RNA will be sent to Gene Logic and this company will test these samples to identify which genes have been expressed. Similar experiments will be performed using macrophages obtained following bronchoalveolar lavage of these subjects. We would aim to examine the responses of leukocytes from three groups of subjects, namely (i) non-smoking controls (ii) smokers without clinical or histological signs of COPD and (iii) smokers with COPD. The isolated leukocytes will either be immediately solubilized in solutions to purify RNA or we will then use these isolated cells in vitro and following stimulation investigate whether different genes are expressed or at a differential rate in the disease state. The objective is to identify which genes are specifically expressed in patients with COPD with a view to identify novel targets for drug therapy. We will examine both leukocytes derived from peripheral blood and macrophages obtained from bronchoalveolar lavage with the aim to determine whether differences attributable to disease can be identified in both circulating cells and those at the site of disease. This is a preliminary study to determine the profile of inflammatory mediator expression from leukocytes and as such power calculations to determine the number of subjects is not appropriate.

Conditions

COPD; Emphysema

Keywords

macrophages; neutrophils; lymphocytes

Study Arms (3)

HEALTHY NON-SMOKER

Healthy non-smoker participants

HEALTHY SMOKER

Healthy smoker participants

COPD and smoking

Smoking participants with COPD

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Healthy non-smoking and smoking subjects, smoking participants with COPD

You may qualify if:

• Healthy non-smoking subjects
• All normal volunteers will meet the following criteria:
• Age 21-70 years.
• No history of respiratory or allergic disease.
• Normal baseline spirometry as predicted for age, sex and height.
• Non-smokers.
• No history of upper respiratory tract infection in the preceding six weeks.
• Not taking regular medication
• COPD subjects COPD is diagnosed according to American Thoracic Society, European Respiratory Society and British Thoracic Society guidelines by the doctors in Professor Barnes' COPD clinic.
• All COPD volunteers will meet the following criteria:
• Age between 40-75 years.
• A smoking history of at least 20 pack years. ( 1 pack year = 20 cigarettes per day for 1 year)
• FEV1:FVC ratio of \<0.7, post-bronchodilator FEV1 of \<85% predicted, reversibility with inhaled beta2-agonist of \<15% of predicted FEV1: all three criteria are required.
• Current smokers or smokers who had ceased smoking for at least 6 months.
• No history of exacerbation, oral steroid or antibiotic use within the preceding 6 weeks.

You may not qualify if:

• Clinically significant findings in the medical history or on physical examination other than those of COPD in the COPD group.
• Pregnant women or mothers who are breastfeeding.
• Subjects who are unable to give informed consent.

Sponsors & Collaborators

• Imperial College London: lead
• Gene Logic: collaborator

Study Sites (1)

Royal Brompton Hospital/NHLI Imperial College London

London, SW3 6LY, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

RNA was isolated and sent to GeneLogic

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema

Condition Hierarchy (Ancestors)

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

Study Officials

• Louise E Donnelly, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 7, 2005
• Study Start: February 1, 2003
• Primary Completion: February 1, 2005
• Study Completion: February 1, 2005
• Last Updated: November 14, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)