Restrictive chronic lung allograft dysfunction: Where are we now?

Abstract

Chronic lung allograft dysfunction (CLAD) remains a frequent and troublesome complication after lung transplantation. Apart from bronchiolitis obliterans syndrome (BOS), a restrictive phenotype of CLAD (rCLAD) has recently been recognized, which occurs in approximately 30% of CLAD patients. The main characteristics of rCLAD include a restrictive pulmonary function pattern with a persistent decline in lung function (FEV1, FVC and TLC), persistent parenchymal infiltrates and (sub)pleural thickening on chest CT scan, as well as pleuroparenchymal fibroelastosis and obliterative bronchiolitis on histopathologic examination. Once diagnosed, median survival is only 6 to 18 months compared with 3 to 5 years with BOS. In this perspective we review the historic evidence for rCLAD and describe the different diagnostic criteria and prognosis. Furthermore, we elaborate on the typical radiologic and histopathologic presentations of rCLAD and highlight risk factors and mechanisms. Last, we summarize some opportunities for further research including the urgent need for adequate therapy. In this perspective we not only assess the current knowledge, but also clarify the existing gaps in understanding this increasingly recognized complication after lung transplantation.

Keywords: bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; lung transplantation; restriction; restrictive allograft syndrome.