Comparison of Alveolar Macrophages in Individuals With COPD Versus Smokers With Normal Pulmonary Function

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University of Michigan
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeffrey L. Curtis, University of Michigan
ClinicalTrials.gov Identifier:
NCT00281190
First received: January 20, 2006
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Procedure: Blood drawing
Procedure: Bronchoalveolar lavage during indicated bronchoscopy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Innate and Adaptive Immunity in COPD Exacerbations: Clinically-Indicated Bronchoscopies

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 ]

Estimated Enrollment: 16
Study Start Date: September 2005
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Healthy smokers
Smokers with normal pulmonary function
Procedure: Blood drawing
blood will be drawn at the time of starting the intravenous (IV) line for the procedure.
Procedure: Bronchoalveolar lavage during indicated bronchoscopy
A small amount of liquid will be introduced and immediately sucked back out of portions of the lung, and the cells that are recovered will be analyzed in the laboratory. All test will be solely for research, and there will be no results reported to the subject from that fluid.
Other Name: BAL
COPD patients
COPD patients
Procedure: Blood drawing
blood will be drawn at the time of starting the intravenous (IV) line for the procedure.
Procedure: Bronchoalveolar lavage during indicated bronchoscopy
A small amount of liquid will be introduced and immediately sucked back out of portions of the lung, and the cells that are recovered will be analyzed in the laboratory. All test will be solely for research, and there will be no results reported to the subject from that fluid.
Other Name: BAL

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 I:C. 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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Smokers with COPD or smokers with normal pulmonary function will be recruited from among subjects scheduled to undergo bronchoscopy for clinical indications.

Criteria

Inclusion criteria:

  • Diagnosis of COPD and/or chronic bronchitis (study group, following American Thoracic Society guidelines)
  • Willingness to participate in follow-up studies defined in the protocol
  • Ability to give informed consent
  • Already undergoing clinically indicated bronchoscopy

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: NCT00281190

Contacts
Contact: Jeffrey L. Curtis, M.D. 734-845-3457 jlcurtis@umich.edu
Contact: Lisa McCloskey, RRT 734-769-7100 ext 5-6180 lmcclosk@umich.edu

Locations
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    cgetty@med.umich.edu   
Contact: Lisa McCloskey, BA, RRT    734-769-7100 ext 5-3533    lmcclosk@med.umich.edu   
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.         
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: NCT00281190     History of Changes
Other Study ID Numbers: 1326, R01HL082480, R01 HL82480
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:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on October 01, 2014