Ignite Creation Date:
2024-05-05 @ 4:38 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00281190
Status:
COMPLETED
Last Update Posted:
2014-12-16
First Post:
2006-01-20
Brief Title:
Comparison of Alveolar Macrophages in Individuals With COPD Versus Smokers With Normal Pulmonary Function
Sponsor:
University of Michigan
Organization:
University of Michigan
Study Overview
Official Title:
Innate and Adaptive Immunity in COPD Exacerbations Clinically-Indicated Bronchoscopies
Status:
COMPLETED
Status Verified Date:
2014-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether the alveolar macrophages AMø of patients with chronic obstructive pulmonary disease COPD show abnormal responsiveness to bacterial and viral products relative to smokers with normal pulmonary function Participation in this study will be offered to patients already scheduled to undergo a bronchoscopy for clinical indications
Detailed Description:
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
The purpose of this experiment is to determine whether the AMø of patients with COPD show abnormal responsiveness to bacterial and viral products relative to smokers with normal pulmonary function Specifically the study will determine the dose-response characteristics of AMø from these two groups of subjects 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 IC These stimuli mimic the response to Gram-negative bacteria Gram-positive bacteria and RNA viruses respectively
This research protocol involves adding a research bronchoalveolar lavage BAL to clinically indicated bronchoscopy that is being performed for evaluation of lung nodules suspected to possibly be malignant The research BAL will be performed during the same procedure but on the opposite lung from the radiographic lesion that motivated the bronchoscopy Subjects will be COPD patients or smokers with normal pulmonary function recruited from the Pulmonary Clinic Smoking history will be taken to mean at least 20 pack-years exposure and could include current or ex-smokers Bronchoscopy will be performed under conscious sedation using a fiberoptic bronchoscope in almost all cases on outpatients although stable inpatients could be considered for consent if they otherwise meet eligibility criteria The setting is the Endoscopy suite at the Ann Arbor VA Hospital
The procedures in this protocol involve the following upon enrollment bronchoalveolar lavage 200 ml maximal instilled volume and collection of blood for hematocrit serum albumin C-reactive protein and IL-6
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
The purpose of this experiment is to determine whether the AMø of patients with COPD show abnormal responsiveness to bacterial and viral products relative to smokers with normal pulmonary function Specifically the study will determine the dose-response characteristics of AMø from these two groups of subjects 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 IC These stimuli mimic the response to Gram-negative bacteria Gram-positive bacteria and RNA viruses respectively
This research protocol involves adding a research bronchoalveolar lavage BAL to clinically indicated bronchoscopy that is being performed for evaluation of lung nodules suspected to possibly be malignant The research BAL will be performed during the same procedure but on the opposite lung from the radiographic lesion that motivated the bronchoscopy Subjects will be COPD patients or smokers with normal pulmonary function recruited from the Pulmonary Clinic Smoking history will be taken to mean at least 20 pack-years exposure and could include current or ex-smokers Bronchoscopy will be performed under conscious sedation using a fiberoptic bronchoscope in almost all cases on outpatients although stable inpatients could be considered for consent if they otherwise meet eligibility criteria The setting is the Endoscopy suite at the Ann Arbor VA Hospital
The procedures in this protocol involve the following upon enrollment bronchoalveolar lavage 200 ml maximal instilled volume and collection of blood for hematocrit serum albumin C-reactive protein and IL-6
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL082480 | NIH | None | httpsreporternihgovquickSearchR01HL082480 |