347 Running out of Air: CLAD Phenotypes Post Lung Transplant

Abstract

Purpose: Survival following lung transplantation is limited by chronic lung allograft dysfunction (CLAD). Increasingly Bronchiolitis Obliterans Syndrome (BOS), characterized by an obstructive ventilatory defect, is recognized as not the only form of CLAD. As such, we sought to identify characteristic CLAD phenotypes in a large group of lung transplant recipients (LTR) managed at a single centre. Methods and Materials: CLAD was defined as an irreversible decline in FEV1 80% from baseline. 245 patients transplanted between January 2002 and June 2010 were retrospectively reviewed. Spirometry was used to identify CLAD phenotypes: obstructive (BOS), restrictive or a pattern showing both obstruction and reduction in FVC (mixed). Those displaying a restricted or mixed phenotype were further classified by the presence or absence of a persistent infiltrate on CT scan and by histopathology. Results: 119 of 245 LTR were identified as having CLAD: 43 (36%) obstructive, 46 (39%) restrictive and 30 (25%) mixed phenotype. Of those patients with a restrictive or mixed defect, an infiltrate was present in 31 (41%) Ante and post-mortem histological analysis of the lung allograft revealed a novel histopathological phenotype, fibrinoid organizing pneumonia (FOP) in 17 (55%) of these patients. FOP was characterized by obliteration of the alveolar luminae and respiratory bronchioles by fibrinoid material which was not responsive to conventional immunosuppressive regimens. Conclusions: The non-obstructive phenotypes of CLAD appear to have a worse prognosis with survival following FOP being universally poor with time from onset of CLAD to death being less than 12 months (median 215 days; IQR 100 – 282).