Surrogate Markers and Risk Factors for Chronic Lung Allograft Dysfunction

Abstract

Obliterative bronchiolitis (OB) is the histologic correlate of chronic allograft dysfunction in pulmonary transplantation. The histologic diagnosis of OB is challenging, therefore a physiologic definition, bronchiolitis obliterans syndrome (BOS) based on pulmonary function tests has been used as a surrogate marker for OB for the last decade. BOS has proven to be the best available surrogate marker for OB and is predictive of the ultimate endpoints of graft and patient survival. Multiple other clinical markers have been reported and proposed as alternates for or complements to BOS grade, but all need further evaluation and validation in large, prospective clinical trials. Lastly, given the early occurrence and high incidence of chronic allograft dysfunction, the easily measurable endpoint of BOS grade, and our lack of understanding of ways to prevent or alter the course of BOS, lung transplant recipients represent an ideal population for clinical trials targeting prevention and treatment of chronic allograft dysfunction.

Primary Graft Dysfunction and Long-term Pulmonary Function After Lung Transplantation

“…The effect of PGD on short-term 3-5,7,11 and long-term 3,12 survival rates has been described by our group and by others, and risk factors for the development of PGD have also been identified. 6,8,13,14 Although many late deaths after lung transplant result from chronic lung rejection (BOS), 9 the association of early PGD and BOS has not been studied extensively. Previously identified risk factors for developing BOS include multiple episodes of acute rejection and gastroesophageal reflux disease (GERD).…”

Pharmacogenomics and lung transplantation: clinical implications

“…78 The clinical biomarkers for patient outcomes following lung transplantation are listed in Table 3, many of which have been inconsistently associated with the development of BOS. 79 The exceptions to the old biomarkers are a very recent study of FoxP3 in renal transplant patients 80 and the pharmacogenomic CARGO and LAR-GO studies. The Cardiac Allograft Rejection Gene Expression Observational (CARGO) and Lung Allograft Rejection Gene Expression Observational (LARGO) studies are the first ventures into identifying and screening large numbers of expressed mRNAs in peripheral blood as biomarkers for clinical status in cardiac and lung transplant patients, respectively.…”

Mesenchymal Stromal Cells in Bronchoalveolar Lavage as Predictors of Bronchiolitis Obliterans Syndrome

“…Bronchoalveolar lavage (BAL) offers a unique tool to sample the internal milieu of the lung and its cellular and molecular components have been evaluated to investigate markers and predictors of BOS (6,7). Proinflammatory cytokines (IL-8; regulated upon activation normal T-cell expressed and secreted; monocyte chemoattractant protein-1) (8)(9)(10)(11), profibrotic growth factors (transforming growth factor-b, platelet-derived growth factor) (10,12), and markers of extracellular matrix remodeling, such as matrix metalloproteases (13), have been reported to be increased in the BAL fluid in presence of BOS.…”