Research Group

  • Dr Peter Hopkins, Principal Investigator
  • Dr Bruce Kenneth, Co-Investigator
  • Dr Rogers Geraint Rogers, Research Scientist

Location

  • The Prince Charles Hospital, Brisbane, Australia

Title

  • Non-cultured Bacteria Hold the Key to Development and Progression of Rejection in Lung Transplant Patients

Lung transplantation is a surgical option for a select group of individuals with end-stage lung disease. The major impediments to long-term survival post-lung transplantation are obliterative bronchiolitis or chronic rejection, with an incidence of 50-60 percent at 5-years post-transplant. The clinical correlate of chronic rejection is Bronchiolitis Obliterans Syndrome (BOS), as defined according to forced expiration volume (FEV1), a lung volume measurement. The exact pathogenesis of BOS is unknown, although the initiating event is almost certainly centred on the small-airway epithelium leading to abnormal tissue repair and fibrogenesis. Along with allo-immune factors, non-immune factors may injure the epithelium; including infection (CMV, respiratory viruses, bacterial species), gastroesophageal reflux and ischaemia reperfusion injury. Infection perpetuates obliterative bronchiolitis by inducing further airway injury and promoting inflammation, which manifests as clinical deterioration with loss in lung function. Lung transplant recipients undergo routine assessment of their transplanted organ by way of bronchoscopy. Specimens obtained include bronchial washings and bronchoalveolar lavage (BAL) for culture and transbronchial lung biopsies for histology. Current techniques involve culturing for known pathogenic bacteria using selective media. However, this selectivity restricts the ability to identify unsuspected bacteria or those not considered to be pathogenic. Molecular techniques such as terminal restriction fragment length polymorphism (TRFLP) are more sensitive since they utilise bacterial DNA and RNA to obtain a unique genetic fingerprint in any given environment. Our primary aim is to obtain BAL from lung transplant recipients with or without BOS and compare standard culture to TRFLP analysis. Our preliminary data indicates BOS patients have multiple bacterial species on TRFLP, previously undetected using traditional culture media, with the most frequent species isolated from the genus Sphingomonas. We believe our new approach to the characterisation of the pulmonary flora in lung transplant patients will give a more accurate profile of relevant pathogens, identify novel species and lead to the development of new therapies for the disabling complication of obliterative bronchiolitis.

Progress Report

Final Report