Heterogeneity of Chronic Lung Allograft Dysfunction Phenotypes: Spirometric, Histopathologic and Imaging Associations over a 16-Year Experience

Background: The 2019 update by the ISHLT of classification for chronic lung allograph dysfunction (CLAD) includes a mixed and undefined phenotype. Objectives: Assess (a) frequency of phenotypes (per ISHLT) with emphasis on double lung transplants (DLTxs), (b) concordance of spirometry with imaging and transbronchial biopsy findings, (c) mortality rates amongst phenotypes. Methods: Single-center retrospective study of adult patients. Time from transplant to CLAD and mortality amongst phenotypes compared by ANOVA adjusted for age, gender and BMI. Results: Of 360 patients, 96 (27%) met criteria for CLAD (57 DLTx). Seventy-four (77%) experienced combined FEV1 and FVC decline. In DLTxs, onset of FEV1 decline (n=12) occurred 10 months earlier than for FVC (n=4) and 5 months before simultaneous onset of FVC and FEV1 decline (n=41). Amongst DLTxs, largest cohort was mixed group (n=30, 53%); RAS phenotype second largest (n=16, 28%). Median onset of CLAD: 30 months for BOS and mixed categories (combined n=34); 48 months for RAS (n=16). Time to death following DLTx: longest in BOS, shortest in RAS, intermediate in mixed phenotypes. Conclusion: CLAD occurs in more than one-quarter of patients; three-fourths exhibit concurrent decline in FEV1 and FVC. Imaging detects changes when biopsy findings are mild or not identified and often do not reflect spirometric changes