TY - JOUR
T1 - Airway remodelling in the transplanted lung
AU - Kuehnel, Mark
AU - Maegel, Lavinia
AU - Vogel-Claussen, Jens
AU - Robertus, Jan Lukas
AU - Jonigk, Danny
N1 - Funding Information:
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.
Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Bronchiolitis obliterans
KW - Chronic lung allograft dysfunction
KW - Chronic rejection
KW - Lung transplantation
KW - Obliterative airway remodelling
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U2 - 10.1007/s00441-016-2529-0
DO - 10.1007/s00441-016-2529-0
M3 - Review article
C2 - 27837271
AN - SCOPUS:84994719173
VL - 367
SP - 663
EP - 675
JO - Zeitschrift für Zellforschung und mikroskopische Anatomie (Vienna, Austria : 1948)
JF - Zeitschrift für Zellforschung und mikroskopische Anatomie (Vienna, Austria : 1948)
SN - 0302-766X
IS - 3
ER -