Transition from BOS to RAS Impairs Prognosis after Lung Transplantation - CLAD Subtype Analysis by CT-Volumetry

Abstract

Chronic lung allograft dysfunction (CLAD) is the most important reason for poor patient survival after lung transplantation. Of the two CLAD subtypes, restrictive allograft syndrome (RAS) has worse prognosis than bronchiolitis obliterans syndrome (BOS), but only limited information is available on the incidence and clinical effect of CLAD subtype change after CLAD onset. We set out to characterize CLAD subtype development by computed tomography (CT) volumetry after CLAD onset. 167 adult patients who underwent de novo lung transplantation in a nationwide transplant centre between 2003-2015 were retrospectively analyzed. CLAD subtype was determined by CT volumetry at CLAD onset. Lung volume decrease of <15% from baseline resulted in BOS and >15% in RAS classification. Patients were re-classified to BOS->RAS or RAS->BOS if persistent lung volume change was detected, and no other specific reasons for lung volume change were present. Radiologic findings of air trapping and fibrosis were linked to lung volume change. Seventy-one (43%) patients were diagnosed with CLAD which was classified as BOS in 63 (89%) and RAS in 8 (11%) patients. After CLAD onset, 6 (9.5%) of BOS patients were re-classified as BOS->RAS, and one (12.5%) RAS patient was re-classified as RAS->BOS whereas other patients remained in their original CLAD subtype. Class change from BOS to RAS occurred at a median of 515.5 days after CLAD onset. Recipient (Figure A, p= 0.002) and graft survival (Figure B, p= 0.003) after CLAD diagnosis was impaired in BOS->RAS group compared to patients remaining in the BOS category. Radiological evidence of both air trapping and fibrosis was seen in 83% of BOS->RAS patients, and fibrotic changes preceded the subtype change in 67% of patients. A significant proportion of BOS patients transform to RAS after CLAD diagnosis, which has an adverse effect on recipient and graft survival.