1. Spectrum of chronic lung allograft dysfunction pathology in human lung transplantation.
- Author
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Renaud-Picard B, Berra G, Hwang D, Huszti E, Miyamoto E, Berry GJ, Pal P, Juvet S, Keshavjee S, and Martinu T
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Chronic Disease, Primary Graft Dysfunction pathology, Lung pathology, Aged, Graft Rejection pathology, Lung Transplantation, Allografts pathology, Bronchiolitis Obliterans pathology
- Abstract
Background: Long-term survival after lung transplantation (LTx) remains limited by chronic lung allograft dysfunction (CLAD), which includes 2 main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), with possible overlap. We aimed to detail and quantify pathological features of these CLAD sub-types., Methods: Peripheral and central paraffin-embedded explanted lung samples were obtained from 20 consecutive patients undergoing a second LTx for CLAD, from 3 lobes. Thirteen lung samples, collected from non-transplant lobectomies or donor lungs, were used as controls. Blinded semi-quantitative grading was performed to assess airway fibrotic changes, parenchymal and pleural fibrosis, and epithelial and vascular abnormalities., Results: CLAD lung samples had higher scores for all airway- and lung-related parameters compared to controls. There was a notable overlap in histologic scores between BOS and RAS, with a wide range of scores in both conditions. Parenchymal and vascular fibrosis scores were significantly higher in RAS compared to BOS (p = 0.003 for both). We observed a significant positive correlation between the degree of inflammation around each airway, the severity of epithelial changes, and airway fibrosis. Immunofluorescence staining demonstrated a trend toward a lower frequency of club cells in CLAD and a higher frequency of apoptotic club cells in BOS samples (p = 0.01)., Conclusions: CLAD is a spectrum of airway, parenchymal, and pleural fibrosis, as well as epithelial, vascular, and inflammatory pathologic changes, where BOS and RAS overlap significantly. Our semi-quantitative grading score showed a generally high inter-reader reliability and may be useful for future CLAD histologic assessments., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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