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Macrophage Phagocytosis in COPD

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: NCT00298389
Recruitment Status : Completed
First Posted : March 2, 2006
Results First Posted : November 22, 2019
Last Update Posted : December 3, 2019
Information provided by (Responsible Party):
Imperial College London

Brief Summary:
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 or disease
Chronic Obstructive Pulmonary Disease Emphysema Chronic Bronchitis

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.

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Study Type : Observational
Actual Enrollment : 56 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Macrophage Phagocytosis in Chronic Obstructive Pulmonary Disease
Actual Study Start Date : October 2005
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Non smokers
Non smokers included no history of respiratory or allergic disease, normal baseline spirometry
Smoking history of at least 10 pack years
Patients with stable COPD

Primary Outcome Measures :
  1. Phagocytosis of H. Influenzae Concentration [ Time Frame: 1 hour ]
    Measurement of phagocytosis in vitro, Phagocytosis of H. influenzae concentration

  2. Phagocytosis of S. Pneumoniae Concentration [ Time Frame: 1 hour ]
    Measurement of phagocytosis in vitro, Phagocytosis of S. pneumoniae concentration

Biospecimen Retention:   Samples With DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy subjects, smokers without COPD and COPD patients

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.-

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): NCT00298389

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

Publications of Results:
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Responsible Party: Imperial College London Identifier: NCT00298389    
Other Study ID Numbers: 05/Q0404/111
First Posted: March 2, 2006    Key Record Dates
Results First Posted: November 22, 2019
Last Update Posted: December 3, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Bronchitis, Chronic
Respiratory Tract Diseases
Pathologic Processes
Bronchial Diseases
Respiratory Tract Infections