Mechanisms of Lung Allograft Rejection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00340418
Recruitment Status : Completed
First Posted : June 21, 2006
Last Update Posted : July 2, 2017
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This study will explore the ways in which lung transplants are rejected. A series of experiments will evaluate the differences in airway gene expression. Lung transplantation has become an important option for patients with advanced lung disease. More than 10,000 patients have received them to date, and about 1,200 transplant operations are performed worldwide each year. Although short-term survival has continued to improve, the 5-year survival rate is less than 50%. Most posttransplant deaths are directly or directly caused by chronic lung rejection, a condition of scarring that worsens lung function. .

Patients ages 18 and older who have received lung transplants, who are undergoing bronchoscopy as part of the usual care after transplant, and who are not pregnant may be eligible for this study.

Bronchoscopy and other procedures performed during this study are done only by doctors with special training. They will take a total of 30 to 60 minutes. During a bronchoscopy, patients will lie on a flat bed. They will be awake and follow instructions. First they will breathe Xylocaine (lidocaine), an anesthetic mist, for 8 to 10 minutes. That will lessen the discomfort of a small flexible tube called a bronchoscope that will be guided through the back of the patient's mouth or nose and into the breathing tubes. When the flexible tube is placed, patients will not be able to speak. They will receive the medication Versed (midazolam), to make them relaxed and not remember most of the procedure, and fentanyl, to decrease the possibility of feeling pain. These medications will be given through a narrow tube feeding into a small needle placed into a vein in the arm. The risks of the tube placed in the vein include bleeding, swelling, redness, and pain. Side effects from the medications may include stomach upset, heart palpitations (awareness of heartbeat), and changes in blood pressure. Patients will be carefully monitored for heart rate, blood pressure, breathing, and oxygen levels.

During the bronchoscopy, a procedure called bronchoalveolar lavage is done, in which a small amount of germ-free salt water is injected into through the bronchoscope into the lung and immediately suctioned back, thus washing the lining of the airways and checking for infection and rejection of the transplanted lungs. About 1 or 2 tablespoons of fluid will be collected for analysis. Also, an endobronchial brush biopsy may be performed. A small brush removes some of the cells from the surface of the airway. These cells will be sent to a laboratory at Duke University Health system to analyze the signals from the cells that may eventually led to scarring and chronic rejection of the lungs. Then, an endobronchial forceps biopsy is performed, in which one or two small pieces, each about the size of a grain of rice, of the lining of the lung's large airways is removed. A small surgical tool like tweezers is passed into the lung. Risks of biopsies may include bleeding, injury to the lung, or an air leak in the lung.

This study will not have a direct benefit for participants. However, it is hoped that information gathered will enhance researchers' understanding of how lung rejection occurs.

Condition or disease
Lung Transplant Chronic Allograft Rejection

Detailed Description:
Lung transplantation has emerged as a viable therapeutic option in the care of patients with advanced pulmonary parenchymal and pulmonary vascular disease. Currently, over 10,000 patients have received lung transplantation with approximately 1200 transplant operations performed worldwide each year. Short term survival after lung transplantation has continued to improve since the widespread application of this procedure and one-year survival at most centers now approaches 80%. Unfortunately, long-term outcomes after lung transplantation are disappointing with five-year survival below 50%. Most posttransplant deaths are due directly or indirectly to the development of chronic allograft rejection, which affects approximately 50% of all five-year survivors. Acute rejection is the major risk factor for the development of chronic rejection. Chronic lung rejection leads to a condition of irreversible fibrosis and obliteration of the small to medium size bronchioles known as obliterative bronchiolitis (OB). Very little is known about the pathogenic mechanisms that lead to the development of OB. Furthermore, it is unclear why acute rejection leads to the development of chronic rejection in some but not all patients. In order to better understand the mechanisms of OB we propose a series of experiments designed to evaluate differences in airway gene expression in a series of lung transplant recipients with and without acute rejection.

Study Type : Observational
Enrollment : 120 participants
Official Title: Mechanisms of Lung Allograft Rejection
Study Start Date : June 23, 2005
Study Completion Date : April 13, 2007

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

All adult (18 and older) lung transplant recipients who are undergoing bronchoscopy as part of the usual posttransplant care will be eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00340418

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
NIEHS, Research Triangle Park
Research Triangle Park, North Carolina, United States, 27709
Sponsors and Collaborators
National Institute of Environmental Health Sciences (NIEHS)

Publications: Identifier: NCT00340418     History of Changes
Other Study ID Numbers: 999905182
First Posted: June 21, 2006    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: April 13, 2007

Keywords provided by National Institutes of Health Clinical Center (CC):
Bronchoalveolar Lavage
Acute Rejection
Chronic Rejection
Genetic Polymorphisms
Innate Immunity
Lung Transplantation
Lung Allograft Rejection