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Macrophage Phagocytosis in COPD

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ClinicalTrials.gov Identifier: NCT00298389
Recruitment Status : Completed
First Posted : March 2, 2006
Last Update Posted : March 20, 2014
Sponsor:
Information provided by (Responsible Party):
Imperial College London

March 1, 2006
March 2, 2006
March 20, 2014
October 2005
December 2010   (Final data collection date for primary outcome measure)
Measurement of phagocytosis [ Time Frame: 12 days ]
Measurement of phagocytosis in vitro
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Complete list of historical versions of study NCT00298389 on ClinicalTrials.gov Archive Site
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Macrophage Phagocytosis in COPD
Macrophage Phagocytosis in Chronic Obstructive Pulmonary Disease
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
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.
Observational
Observational Model: Case Control
Time Perspective: Prospective
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Non-Probability Sample
Healthy subjects, smokers without COPD and COPD patients
  • Chronic Obstructive Pulmonary Disease
  • Emphysema
  • Chronic Bronchitis
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
90
Same as current
December 2010
December 2010   (Final data collection date for primary outcome measure)

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.-

Sexes Eligible for Study: All
21 Years to 75 Years   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
 
NCT00298389
05/Q0404/111
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Imperial College London
Imperial College London
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Principal Investigator: Louise E Donnelly, PhD Imperial College London
Imperial College London
March 2006