Abstract
Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities. Although recent years have seen considerable advances in identifying and categorizing these subgroups on the basis of clinical, functional and histomorphological changes, as well as susceptibility to medicinal treatment, this process is far from over. Since the actual pathophysiological mechanisms governing airway remodelling are still only poorly understood, diagnosis and therapy of chronic lung allograft dysfunction presents a major challenge to clinicians, radiologists and pathologists alike. Here, we review and discuss the current state of the literature on chronic lung allograft dysfunction and shed light on classification systems, corresponding clinical and morphological changes, key cellular players and underlying molecular pathways, as well as on emerging diagnostic and therapeutic approaches.
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Abbreviations
- ACR:
-
Acute cellular rejection
- AFE:
-
Alveolar fibroelastosis
- ARAD:
-
Azithromycin-responsive allograft dysfunction
- ATP:
-
Adenosintriphosphat
- BAL:
-
Bronchoalveolar lavage
- BMP:
-
Bone morphogenetic protein
- BO:
-
Bronchiolitis obliterans
- BOOP:
-
Bronchiolitis obliterans organizing pneumonia
- BOS:
-
Bronchiolitis obliterans syndrome
- CAV:
-
Cardiac allograft vasculopathy
- CLAD:
-
Chronic lung allograft dysfunction
- oCLAD:
-
Obstructive chronic lung allograft dysfunction
- rCLAD:
-
Restrictive chronic lung allograft dysfunction
- CLL:
-
Chronic lymphocytic leukemia
- CMV:
-
Cytomegalovirus
- CRISTAL:
-
Curing resin infiltrated samples for transparent analysis with light
- CT:
-
Computed tomography
- CXCL:
-
CXC-motive chemokine
- CXCR2:
-
CXC-motive chemokine receptor 2
- DSA:
-
Donor-specific antibodies
- ECM:
-
Extracellular matrix
- EMT:
-
Epithelial–mesenchymal transition
- FEV1:
-
Forced expiratory volume in 1 second
- FGF:
-
Fibroblast growth factor
- FVC:
-
Forced vital capacity
- GMCSF:
-
Granulocyte macrophage colony-stimulating factor
- HLA:
-
Human leukocyte antigens
- ICAM:
-
Intracellular adhesion molecule
- IL:
-
Interleukin
- IPF:
-
Idiopathic pulmonary fibrosis
- ISHLT:
-
International Society for Heart & Lung Transplantations
- LuTx:
-
Lung transplantation
- MCP:
-
Monocyte chemoattractant protein-1
- MMP:
-
Matrix metalloproteinase
- Mreg:
-
regulatory macrophage
- MRI:
-
Magnetic resonance imaging
- NK:
-
Natural killer cell
- NRAD:
-
Neutrophilic reversible allograft dysfunction
- OAR:
-
Obliterative airway remodelling
- OP:
-
Organizing pneumonia
- P2X7:
-
Purinergic receptor
- PGD:
-
Primary graft dysfunction
- PPFE:
-
Pleuroparenchymal fibroelastosis
- RAS:
-
Restrictive allograft syndrome
- RC:
-
Radio- and/or chemotherapy
- ROS:
-
Reactive oxygen species
- SMAD:
-
Sma- and Mad-related protein
- SMC:
-
Smooth muscle cell migration
- TGF-β:
-
Transforming growth factor β
- THBS1:
-
Thrombospondin 1
- TIMP:
-
Tissue inhibitor of metalloproteinases
- Tx:
-
Transplantation
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The authors thank Robert Blach, Adrian Anklamm and Gillian Teicke for editing the text and the Deutsche Forschungsgemeinschaft (DFG; grant SFB 738/3, project B09) for funding.
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Mark Kuehnel and Lavinia Maegel contributed equally to this work.
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Kuehnel, M., Maegel, L., Vogel-Claussen, J. et al. Airway remodelling in the transplanted lung. Cell Tissue Res 367, 663–675 (2017). https://doi.org/10.1007/s00441-016-2529-0
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DOI: https://doi.org/10.1007/s00441-016-2529-0