title: Airway remodelling in the transplanted lung.
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.
authors.affiliation: Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, D-30625, Hanover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), The German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Hanover, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Kuehnel
authors.affiliation: Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, D-30625, Hanover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), The German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Hanover, Germany.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Maegel
authors.affiliation: Institute of Radiology, MHH, Hanover, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Vogel-Claussen
authors.affiliation: Royal Brompton & Harefield NHS Foundation Trust, Department of Histopathology, Hanover, Germany.
authors.forename: Jan Lukas
authors.initials: JL
authors.lastname: Robertus
authors.affiliation: Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, D-30625, Hanover, Germany. jonigk.danny@mh-hannover.de.
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
mesh_terms: D056151:Airway Remodeling; D064591:Allografts / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000503:physiopathology*; D016040:Lung Transplantation; D066253:Vascular Remodeling
keywords: Bronchiolitis obliterans; Chronic lung allograft dysfunction; Chronic rejection; Lung transplantation; Obliterative airway remodelling