T Lymphocyte Cells in Individuals Experiencing an Acute Exacerbation of Chronic Obstructive Pulmonary Disease
The purpose of this study is to determine whether the lungs of individuals with chronic obstructive pulmonary disease (COPD) contain resident memory T lymphocytes that can produce a combination of cytokines that induce the symptoms of an acute exacerbation of COPD (AE-COPD). Specifically, the study will determine cell-surface receptors of lung T cells in comparison with blood T cells from the same subject, and will examine anti-CD3-activated blood or lung T cells for interleukin (IL)-6 and interferon-gamma production in response to IL-18, and for IL-17A production in response to recombinant IL-23.
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: Surgical Volunteers|
- phenotype and in vitro functions of lung lymphocytes [ Time Frame: within 3 days of surgery ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
COPD is one of the most pressing healthcare problems facing our nation. AE-COPD is 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.
The research protocol involves isolating lung lymphocytes from surgical specimens of patients already undergoing clinically indicated lung resections. Surgical lung resections may be performed either by open thoracotomy or by video-assisted thoracoscopic surgery (VATS), and could include pneumonectomies, lobectomies, or wedge-excisions, as dictated by clinical care of the patient. This protocol will exclusively use tissue that is of excess after a clinical diagnosis is established. The setting is the operating rooms at the Ann Arbor VA Hospital or the University of Michigan Hospital System. Subjects will be recruited from the outpatient clinics, but will be inpatients at the time of surgery.
Subjects will not undergo any additional procedures beyond routine clinical care as a result of participating in this protocol. However, it is anticipated that the study will have access to the medical record to extract results of demographic data, including occupational exposures and smoking history, pulmonary function testing, and results of imaging and other staging studies.
|Contact: Jeffrey L. Curtis, M.D.||firstname.lastname@example.org|
|Contact: Lisa McCloskey, RRT||734-769-7100 ext email@example.com|
|United States, Michigan|
|University of Michigan at Ann Arbor||Recruiting|
|Ann Arbor, Michigan, United States, 48105|
|Contact: Catherine Meldrum, B.S, R.N. 734-764-7388 firstname.lastname@example.org|
|Contact: Lisa McCloskey, RRT 734-769-7100 ext 5-3533 email@example.com|
|Principal Investigator: Jeffrey L. L Curtis, M.D.|
|Sub-Investigator: Fernando J Martinez, M.D., M.S.|
|Sub-Investigator: MeiLan K Han, M.D., M.S.|
|VA Ann Arbor Healthcare System||Recruiting|
|Ann Arbor, Michigan, United States, 48105|
|Contact: Lisa McCloskey, RRT 734-769-7100 ext 5-6180 firstname.lastname@example.org|
|Principal Investigator: Jeffrey L. Curtis, M.D.|
|Principal Investigator:||Jeffrey L. Curtis, M.D||University of Michigan at Ann Arbor|