Comparison of Alveolar Macrophages in Healthy Individuals Versus Individuals With COPD

Study Overview
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Brief Summary
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This study group forms the normal subject control group in an experiment designed to determine whether the alveolar macrophages (AMø) of patients with chronic obstructive pulmonary disease (COPD) show abnormal responsiveness to bacterial and viral products. Specifically, the study will determine the dose-response characteristics of AMø for production of interleukin (IL)-6, IL-18, and IL-23 (pro-inflammatory cytokines) on stimulation by purified lipopolysaccharide, a synthetic lipopeptide (PAM3-Cys), or poly I:C. These stimuli mimic the response to Gram-negative bacteria, Gram-positive bacteria, and RNA viruses, respectively. Results of the AMø from these healthy volunteers will be compared with AMø of COPD patients and smokers (or ex-smokers) with normal pulmonary function; those samples are being obtained during clinically indicated bronchoscopies under a separate consent form.

Detailed Description
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BACKGROUND: COPD is one of the most pressing healthcare problems facing our nation. Acute exacerbations of COPD (AE-COPD) are responsible for the bulk of healthcare costs, and much of the morbidity and decline in health status among individuals with this common disease. The lack of accepted animal models of AE-COPD necessitates novel approaches using human samples. Advances in the understanding of the pathogenesis have been slowed, in part, due to controversy as to how exacerbations should be defined. The prevailing paradigm has defined AE-COPD as event-based. Such definitions clearly identify groups of patients with accelerated loss of pulmonary function and increased mortality. However, limited data show that symptom-based definitions of AE-COPD also capture episodes inducing significant morbidity and functional decline, and hence of concern to patients. Fundamental mechanisms are lacking to explain AE-COPD defined by either means. Controversy also surrounds triggers of AE-COPD. Bacteria and viruses are involved in some episodes, but the relative importance of each is intertwined with disputes over the definition of AE-COPD. Progress at linking specific pathogens to molecular pathogenesis has been slow, both due to their diversity, and to the high rates of bacterial colonization of patients with COPD, even in the stable state. Moreover, in many AE-COPD cases, no pathogen can be identified. Without negating the value of analyzing infections with specific species of pathogens, it appears that progress in molecular pathogenesis could be accelerated by focusing on unifying features of the pulmonary immune response during AE-COPD. DESIGN NARRATIVE: Bronchoscopies will be performed on healthy volunteers. Subjects are reimbursed $30 for the initial visit and $150 at completion of the bronchoscopy to help defray travel expenses and for the time spent participating as a volunteer.

Official Title
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Innate and Adaptive Immunity in COPD Exacerbations: Bronchoscopies on Healthy Volunteers

Conditions
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Pulmonary Disease, Chronic Obstructive, Lung Diseases, Obstructive

Intervention / Treatment
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* Procedure: blood drawing
* Procedure: fiberoptic bronchoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy individuals with normal pulmonary function as defined by AmericanThoracic Society criteria (entry spirometry) Exclusion criteria: Unstable cardiovascular disease Other systemic disease in which survival of more than 2 years is unlikely Mental incompetence or active psychiatric illness Currently taking more than 20 mg/day of Prednisone Participation in another experimental protocol within 6 weeks of study entry Asthma Cystic fibrosis Clinically significant bronchiectasis Lung cancer Other inflammatory or fibrotic lung disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| healthy smokers<br>Must be free of serious diseases that might make it dangerous to undergo bronchoscopy. | Procedure: blood drawing<br>* blood will be drawn on the entry visit and will starting the intravenous (IV) line on the day of bronchoscopy<br>Procedure: fiberoptic bronchoscopy<br>* A flexible instrument will be passed through the mouth and into the lungs. Portions of the lungs will be washed, by injecting and immediately suctioning out a small amount of fluid. The entire return will be used for research purposes, and no results will be reported to the participant. Bronchoscopy is performed once.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alveolar macrophage functions in vitro |  | day of bronchoscopy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, COPD