Comparison of Alveolar Macrophages in Healthy Individuals Versus Individuals With COPD

July 15, 2013 updated by: Jeffrey L. Curtis, University of Michigan

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

32

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan at Ann Arbor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Healthy volunteers

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
alveolar macrophage functions in vitro
Time Frame: day of bronchoscopy
day of bronchoscopy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

January 20, 2006

First Submitted That Met QC Criteria

January 20, 2006

First Posted (Estimate)

January 24, 2006

Study Record Updates

Last Update Posted (Estimate)

July 16, 2013

Last Update Submitted That Met QC Criteria

July 15, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1327
  • R01HL082480 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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