Comparison of Alveolar Macrophages in Healthy Individuals Versus Individuals With COPD
Recruitment status was Recruiting
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 LPS, 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.
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Innate and Adaptive Immunity in COPD Exacerbations: Bronchoscopies on Healthy Volunteers|
|Study Start Date:||September 2005|
|Estimated Study Completion Date:||July 2010|
|Estimated Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
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.
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.
|United States, Michigan|
|University of Michigan at Ann Arbor||Recruiting|
|Ann Arbor, Michigan, United States, 48105|
|Contact: Christi Getty, RRT 734-769-7100 ext 5-6180 firstname.lastname@example.org|
|Contact: Lisa McCloskey, BA, RRT 734-769-7100 ext 5-3533 email@example.com|
|Principal Investigator: Jeffrey L. Curtis, M.D.|
|Sub-Investigator: Fernando J Martinez, M.D., M.S.|
|Sub-Investigator: MeiLan K Han, M.D., M.S.|
|Study Chair:||Jeffrey L. Curtis||University of Michigan at Ann Arbor|