Comparison of Alveolar Macrophages in Healthy Individuals Versus Individuals With COPD

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeffrey L. Curtis, University of Michigan
ClinicalTrials.gov Identifier:
NCT00281203
First received: January 20, 2006
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Procedure: blood drawing
Procedure: fiberoptic bronchoscopy

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Innate and Adaptive Immunity in COPD Exacerbations: Bronchoscopies on Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • alveolar macrophage functions in vitro [ Time Frame: day of bronchoscopy ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: September 2005
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
healthy smokers
Must be free of serious diseases that might make it dangerous to undergo bronchoscopy.
Procedure: blood drawing
blood will be drawn on the entry visit and will starting the intravenous (IV) line on the day of bronchoscopy
Procedure: fiberoptic bronchoscopy
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.

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:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Healthy volunteers

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281203

Locations
United States, Michigan
University of Michigan at Ann Arbor
Ann Arbor, Michigan, United States, 48105
Sponsors and Collaborators
University of Michigan
Investigators
Study Chair: Jeffrey L. Curtis University of Michigan at Ann Arbor
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jeffrey L. Curtis, Professor of Internal Medicine (Pulmonary & Critical Care Medicine), University of Michigan
ClinicalTrials.gov Identifier: NCT00281203     History of Changes
Other Study ID Numbers: 1327, R01HL082480
Study First Received: January 20, 2006
Last Updated: July 15, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Michigan:
Chronic Obstructive Pulmonary Disease
COPD

Additional relevant MeSH terms:
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 16, 2014