Mechanisms of Lung Allograft Rejection
Condition: Lung Transplant; Chronic Allograft Rejection
Study type: Observational

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.
    

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.
    

Keywords: Bronchoalveolar Lavage; Acute Rejection; Chronic Rejection; Genetic Polymorphisms; Innate Immunity; Lung Transplantation; Lung Allograft Rejection