Chronic lung allograft dysfunction (CLAD) is often associated with early ischemia-reperfusion injury and/or repetitive aspiration-related lung injury as a result of gastroesophageal reflux. Dr. Shu Lin’s laboratory has developed an experimental rat model of pulmonary orthotopic transplantation and experimentally induced chronic aspiration that captures the clinical milieu in several important aspects. His ongoing studies have revealed that the development of obliterative bronchiolitis in this model, a major cause of CLAD in patients, is dependent on a three-hit injury involving (a) ischemia-reperfusion injury, (b) alloimmunity, and (c) chronic aspiration.
Dr. Lin also conducts research into factors present in post-industrial society that lead to aberrant immune function. This work, in collaboration with Dr. William Parker at Duke, examines the role of the “human biome”, or life associated with the “ecosystem of the human body”, in regulating immune function in the development and progression of atherosclerosis in a genetically modified mouse model. This ongoing research examines ways in which non-infectious immune dysfunction might be averted by manipulation of the biome, particularly the fauna of the biome.
- The relationship between chronic lung allograft dysfunction and gastroesophageal relfux
- The role of mast cells in obliterative bronchiolitis–associated CLAD
- The effects of the biome on the development of atherosclerosis
- The effects of gastric fluid on the pulmonary microbiome
Chronic Aspiration-Induced Lung Injury
By using a rodent model of chronic gastric fluid aspiration, our laboratory has been able to investigate various aspects of chronic aspiration-induced lung injury in non-transplant settings. The associated pathology, the aspirate components necessary to reproduce this injury, and the manner in which the immune profile is shifted are some of the notable topics investigated in this line of work.
In clinical lung transplantation, gastroesophageal reflux-related chronic aspiration has been linked to chronic lung allograft dysfunction (CLAD) in the pathologic form of obliterative bronchiolitis (OB). Our laboratory has successfully recapitulated this pathology in an experimental model in the rat lung transplant. As a result, we have been able to investigate various issues centered around the development of OB-associated CLAD induced by chronic aspiration. For example, mast cells (as the cell type that is potentially involved in the pathogenesis) and the longer ischemic time (as a more conducive condition in which this pathology occurs) have been examined using this experimental animal model of lung transplantation.
Shu Lin, M.D., Ph.D.
Duke University Medical Center
DUMC Box 2605
Durham, NC 27710, USA