Macrophage Phagocytosis in COPD

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

56 participants

Study Classification

OBSERVATIONAL

Study Start Date

2005-10-31

Study Completion Date

2010-12-31

Brief Summary

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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

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Detailed Description

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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.

Conditions

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Chronic Obstructive Pulmonary Disease Emphysema Chronic Bronchitis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Non smokers

Non smokers included no history of respiratory or allergic disease, normal baseline spirometry

No interventions assigned to this group

Smokers

Smoking history of at least 10 pack years

No interventions assigned to this group

COPD

Patients with stable COPD

No interventions assigned to this group

Eligibility Criteria

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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

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.-

Minimum Eligible Age

21 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes