T Lymphocyte Cells in Individuals Experiencing an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

June 13, 2019 updated by: Jeffrey L. Curtis, University of Michigan

Innate and Adaptive Immunity in COPD Exacerbations: Surgical Volunteers

The purpose of this study is to determine whether the lungs of individuals with chronic obstructive pulmonary disease (COPD) contain resident memory T lymphocytes that can produce a combination of cytokines that induce the symptoms of an acute exacerbation of COPD (AE-COPD). Specifically, the study will determine cell-surface receptors of lung T cells in comparison with blood T cells from the same subject, and will examine anti-CD3-activated blood or lung T cells for interleukin (IL)-6 and interferon-gamma production in response to IL-18, and for IL-17A production in response to recombinant IL-23.

Study Overview

Detailed Description

BACKGROUND:

COPD is one of the most pressing healthcare problems facing our nation. AE-COPD is 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 research protocol involves isolating lung lymphocytes from surgical specimens of patients already undergoing clinically indicated lung resections. Surgical lung resections may be performed either by open thoracotomy or by video-assisted thoracoscopic surgery (VATS), and could include pneumonectomies, lobectomies, or wedge-excisions, as dictated by clinical care of the patient. This protocol will exclusively use tissue that is of excess after a clinical diagnosis is established. The setting is the operating rooms at the Ann Arbor VA Hospital or the University of Michigan Hospital System. Subjects will be recruited from the outpatient clinics, but will be inpatients at the time of surgery.

Subjects will not undergo any additional procedures beyond routine clinical care as a result of participating in this protocol. However, it is anticipated that the study will have access to the medical record to extract results of demographic data, including occupational exposures and smoking history, pulmonary function testing, and results of imaging and other staging studies.

Study Type

Observational

Enrollment (Actual)

481

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

    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • VA Ann Arbor Healthcare System
      • 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

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects undergoing clinically indicated lung resections.

Description

Inclusion criteria:

  • Diagnosis of COPD AND underwent lung resection for malignancy OR lung volume reduction surgery OR lung transplantation OR lung resection for nodules and masses

Exclusion criteria:

  • Mental incompetence or active psychiatric illness
  • Currently using more than 20 mg/day of Prednisone
  • Asthma as primary clinical pulmonary diagnosis
  • Cystic fibrosis
  • Clinically significant bronchiectasis
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
phenotype and in vitro functions of lung lymphocytes
Time Frame: within 3 days of surgery
within 3 days of surgery

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Jeffrey L. Curtis, M.D, University of Michigan at Ann Arbor

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)

September 1, 2014

Study Completion (Actual)

January 1, 2015

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 (Actual)

June 17, 2019

Last Update Submitted That Met QC Criteria

June 13, 2019

Last Verified

January 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • 1328
  • 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.

Clinical Trials on Lung Diseases, Obstructive

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