本期胸小星将为大家带来人肺移植术后CLAD的病理学特征谱；无临床表现，供体来源细胞游离DNA的极端升高仍增加了CLAD和死亡的风险，一起来看看吧！
2017·EATTS
01
Spectrum of chronic lung allograft dysfunction pathology in human lung transplantation
Benjamin Renaud-Picard1,2,3, Gregory Berra1,2,4, David Hwang5, Ella Huszti6, Ei Miyamoto1,2, Gerald J Berry7, Prodipto Pal8, Stephen Juvet1,2,9, Shaf Keshavjee1,2,9, Tereza Martinu1,2,9
1 Latner Thoracic Research Laboratories, Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
2 Toronto Lung Transplant Program, Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada.
3 INSERM Unité mixte de recherche 1260, Regenerative nanomedicine, University of Strasbourg, Strasbourg, France.
4 Service de pneumologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
5 Department of Pathology, Sunnybrook Hospital, Toronto, Ontario, Canada.
6 Biostatistics Research Unit, University Health Network, Toronto, ON, Canada.
7 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
8 Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
9 University of Toronto, Toronto, Ontario, Canada.
Background:
Long-term survival after lung transplantation (LTx) remains limited by Chronic Lung Allograft Dysfunction (CLAD), which includes two 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, as well as 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 pathological 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 towards 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 pathological 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 pathological assessments.
[CITATION]:Renaud-Picard B, Berra G, Hwang D, et al. Spectrum of chronic lung allograft dysfunction pathology in human lung transplantation. J Heart Lung Transplant. 2024 Apr 23:S1053-2498(24)01563-8.
[DOI]:10.1016/j.healun.2024.04.002
[IF]:8.9
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人肺移植术后慢性移植肺功能障碍的病理学特征谱
胸“星”外科学术团队兴趣小队成员 陈嘉玲 译
背景
方法
结果
结论
Figure 2.Histological parameters used for the grading system assessing the pathological spectrum in chronic lung allograft dysfunction.
Figure 3. Overlap between BOS and RAS samples in pathological features except for
Parenchymal fibrosis and vascular fibrosis.
2017·EATTS
02
Extreme elevations of donor-derived cell-free DNA increases the risk of chronic lung allograft dysfunction and death, even without clinical manifestations of disease
Michael B. Keller1,2,3,4, David Newman5, Muhtadi Alnababteh1,2,3, Lucia Ponor2,6, Pali Shah2,4, Joby Matthews2,4, Hyesik Kong1,2, Temesgen Andargie1,2, Woojin Park1,2, Ananth Charya7, Helen Luikart8,9, Shambhu Aryal, Steven D. Nathan2,10, Jonathan B. Orens2,4, Kiran K. Khush8, Moon Jang1,2, Sean Agbor Enoh1,2,4
1 Laborarory of Applied Precision Omics (APO) National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health
2 Genomic Research Alliance for Transplantation (GRAfT)
3 Critical Care Medicine Department, Clinical Center, National Institutes of Health
4 Pulmonary and Critical Care Medicine, Johns Hopkins Hospital
5 College of Nursing, Florida Atlantic University, FL
6 Division of Hospital Medicine, Johns Hopkins Bayview Medical Center
7 Division of Pulmonary and Critical Care Medicine, University of Maryland Medical Center
8 Division of Cardiovascular Medicine
9 Department of Pathology, Stanford University School of Medicine, Palo Alto, CA
10 Inova Fairfax Hospital, Falls Church, VA
Background:
Lung transplant recipients are traditionally monitored with pulmonary function testing (PFT) and lung biopsy to detect post-transplant complications and guide treatment. Plasma donor-derived cell free DNA (dd-cfDNA) is a novel molecular approach of assessing allograft injury, including subclinical allograft dysfunction. The aim of this study was to determine if episodes of extreme molecular injury (EMI) in lung transplant recipients increases the risk of CLAD or death.
Methods:
This multicenter prospective cohort study included 238 lung transplant recipients. Serial plasma samples were collected for dd-cfDNA measurement by shotgun sequencing. EMI was defined as a dd-cfDNA above the third quartile of levels observed for acute rejection (dd-cfDNA level of ≥ 5% occurring after 45 days post-transplant). EMI was categorized as Secondary if associated with co-existing acute rejection, infection or PFT decline; or Primary if not associated to these conditions.
Results:
EMI developed in 16% of patients at a median 343.5 (IQR: 177.3-535.5) days post-transplant. Over 50% of EMI episodes were classified as Primary. EMI was associated with an increased risk of severe CLAD or death (HR: 2.52, 95%CI: 1.10-3.82, P = 0.024). The risk remained consistent for Primary EMI (HR: 2.34, 95%CI 1.18-4.85, P = 0.015). Time to first EMI episode was a significant predictor of the likelihood of developing CLAD or death (AUC = 0.856, 95%CI = 0.805-908, P < 0.001).
Conclusions:
Episodes of EMI in lung transplant recipients are often isolated and not detectable with traditional clinical monitoring approaches. EMI is associated with an increased risk of severe CLAD or death, independent of concomitant transplant complications.
[CITATION]:Keller MB, Newman D, Alnababteh M, et al. Extreme elevations of donor-derived cell-free DNA increases the risk of chronic lung allograft dysfunction and death, even without clinical manifestations of disease. J Heart Lung Transplant. 2024 May 3:S1053-2498(24)01644-9.
[DOI]:10.1016/j.healun.2024.04.064
[IF]: 8.9
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胸“星”外科学术团队兴趣小队成员 陈星月 译
背景
方法
结果
结论
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2017·EATTS
