Comparison of Alveolar Macrophages in Healthy Individuals Versus Individuals With COPD

NCT00281203 | Completed

• 2 other identifiers: 1327R01HL082480
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive

Keywords

Chronic Obstructive Pulmonary Disease; COPD

Outcome Measures

Primary Outcomes (1)

• alveolar macrophage functions in vitro

  day of bronchoscopy

Study Arms (1)

healthy smokers

Must be free of serious diseases that might make it dangerous to undergo bronchoscopy.

Procedure: blood drawing; Procedure: fiberoptic bronchoscopy

Interventions

blood drawing PROCEDURE

blood will be drawn on the entry visit and will starting the intravenous (IV) line on the day of bronchoscopy

healthy smokers

fiberoptic bronchoscopy PROCEDURE

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.

healthy smokers

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers

You may qualify if:

• Healthy individuals with normal pulmonary function as defined by AmericanThoracic Society criteria (entry spirometry)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Michigan at Ann Arbor

Ann Arbor, Michigan, 48105, United States

Location

Related Publications (9)

• Freeman CM, Curtis JL, Chensue SW. CC chemokine receptor 5 and CXC chemokine receptor 6 expression by lung CD8+ cells correlates with chronic obstructive pulmonary disease severity. Am J Pathol. 2007 Sep;171(3):767-76. doi: 10.2353/ajpath.2007.061177. Epub 2007 Jul 19.

  PMID: 17640964 BACKGROUND

• Freeman CM, Han MK, Martinez FJ, Murray S, Liu LX, Chensue SW, Polak TJ, Sonstein J, Todt JC, Ames TM, Arenberg DA, Meldrum CA, Getty C, McCloskey L, Curtis JL. Cytotoxic potential of lung CD8(+) T cells increases with chronic obstructive pulmonary disease severity and with in vitro stimulation by IL-18 or IL-15. J Immunol. 2010 Jun 1;184(11):6504-13. doi: 10.4049/jimmunol.1000006. Epub 2010 Apr 28.

  PMID: 20427767 BACKGROUND

• Freeman CM, Martinez FJ, Han MK, Ames TM, Chensue SW, Todt JC, Arenberg DA, Meldrum CA, Getty C, McCloskey L, Curtis JL. Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009 Dec 15;180(12):1179-88. doi: 10.1164/rccm.200904-0552OC. Epub 2009 Sep 3.

  PMID: 19729666 BACKGROUND

• Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, Macnee W, Make BJ, Rabe KF, Rennard SI, Sciurba FC, Silverman EK, Vestbo J, Washko GR, Wouters EF, Martinez FJ. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010 Sep 1;182(5):598-604. doi: 10.1164/rccm.200912-1843CC. Epub 2010 Jun 3.

  PMID: 20522794 BACKGROUND

• Curtis JL, Todt JC, Hu B, Osterholzer JJ, Freeman CM. Tyro3 receptor tyrosine kinases in the heterogeneity of apoptotic cell uptake. Front Biosci (Landmark Ed). 2009 Jan 1;14(7):2631-46. doi: 10.2741/3401.

  PMID: 19273223 BACKGROUND

• Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc. 2007 Oct 1;4(7):512-21. doi: 10.1513/pats.200701-002FM.

  PMID: 17878463 BACKGROUND

• Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, Young VB, Toews GB, Curtis JL, Sundaram B, Martinez FJ, Huffnagle GB. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS One. 2011 Feb 22;6(2):e16384. doi: 10.1371/journal.pone.0016384.

  PMID: 21364979 RESULT

• Punturieri A, Copper P, Polak T, Christensen PJ, Curtis JL. Conserved nontypeable Haemophilus influenzae-derived TLR2-binding lipopeptides synergize with IFN-beta to increase cytokine production by resident murine and human alveolar macrophages. J Immunol. 2006 Jul 1;177(1):673-80. doi: 10.4049/jimmunol.177.1.673.

  PMID: 16785566 RESULT

• Todt JC, Freeman CM, Brown JP, Sonstein J, Ames TM, McCubbrey AL, Martinez FJ, Chensue SW, Beck JM, Curtis JL. Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression. Respir Res. 2013 Mar 9;14(1):33. doi: 10.1186/1465-9921-14-33.

  PMID: 23497334 DERIVED

Related Links

• COPD Foundation
• Training Grant in Lung Diseases
• Graduate Program in Immunology

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jeffrey L. Curtis

  University of Michigan at Ann Arbor

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Internal Medicine (Pulmonary & Critical Care Medicine)

Study Record Dates

• First Submitted: January 20, 2006
• First Posted: January 24, 2006
• Study Start: September 1, 2005
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: July 16, 2013

Record last verified: 2013-07

Locations

US (1)