Macrophage Phagocytosis in COPD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT00298389
First received: March 1, 2006
Last updated: March 19, 2014
Last verified: March 2006
  Purpose

Patients with chronic obstructive pulmonary disease (COPD) that have frequent chest infections are the patients most likely to become worse over time. Why these people are more susceptible to chest infections is not known. One reason might be that the white cells in their lungs called macrophages do not work properly. Normally, these cells remove all the debris inhaled into the lung. This can also include bacteria. In patients with COPD, these macrophages are not able to remove these particles. The research question addresses why this happens


Condition
Chronic Obstructive Pulmonary Disease
Emphysema
Chronic Bronchitis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Macrophage Phagocytosis in Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Measurement of phagocytosis [ Time Frame: 12 days ] [ Designated as safety issue: No ]
    Measurement of phagocytosis in vitro


Enrollment: 90
Study Start Date: October 2005
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Detailed Description:

Chronic obstructive pulmonary disease (COPD) comprises chronic bronchitis, small airways disease and emphysema. The major risk factor for the development of COPD is cigarette smoking therefore, the prevalence of this disease is increasing. COPD accounts for increasing numbers of hospital admissions due to increased numbers of chest infections and exacerbations. This may be related to the reduced capacity of macrophages from COPD patients to phagocytose bacteria and apoptotic cells. The reasons for this defect in the innate immune response in these subjects is unclear but there are suggestions that scavenger receptors may be altered by oxidative stress and reduce the phagocytotic pathway. This would be relevant in COPD, as increased oxidative stress is associated with cigarette smoking. We have preliminary data that shows a similar reduce phagocytotic response in monocyte-derived macrophages (MDM) from COPD patients compared with smokers and non-smokers. As these cells have not been exposed to oxidative stress other mechanisms may play a role in reducing phagocytosis. Using this MDM model, by taking blood from patients with COPD, we aim to investigate the mechanism of defective phagocytosis in COPD. We will measure the expression and regulation of cell surface scavenger receptors in cells of disease patients and control subjects and examine the signalling pathways leading to actin polymerization and phagosome formation. Finally, we aim to identify novel therapeutic strategies to reverse this effect and augment phagocytosis of macrophages in patients with COPD. Such a strategy would reduce chest infections and exacerbations and hence improve quality of life.

  Eligibility

Ages Eligible for Study:   21 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Healthy subjects, smokers without COPD and COPD patients

Criteria

Inclusion Criteria:

Healthy non-smoking subjects:

All normal volunteers will meet the following criteria:

Age 21-75 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 35-75 years. A smoking history of at least 10 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.

Exclusion Criteria:

Subjects will not included in this study if they meet any of the following exclusion criteria:

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.-

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00298389

Locations
United Kingdom
Imperial College London
London, United Kingdom, SW3 6LY
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Louise E Donnelly, PhD Imperial College London
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00298389     History of Changes
Other Study ID Numbers: 05/Q0404/111
Study First Received: March 1, 2006
Last Updated: March 19, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
macrophage
phagocytosis
exacerbation

Additional relevant MeSH terms:
Bronchitis
Bronchitis, Chronic
Emphysema
Pulmonary Emphysema
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Pathologic Processes

ClinicalTrials.gov processed this record on July 31, 2014