title: Clinical-radiological, histological and genetic analyses in a lung transplant recipient with Mounier-Kuhn syndrome and end-stage chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  The Mounier-Kuhn syndrome (MKS) is a rare disease characterized by a pathological dilation of the trachea and the bronchial system. The etiology of the disorder remains elusive, but genetic alterations and degradation of elastic fibers are thought to be involved in the pathogenesis. No causative treatment is available although transplantation is an option for end-stage disease. Here, we describe a patient suffering from MKS who received a double lung transplant at our department.
  
  
  METHODS
  Since a familial clustering of MKS is discussed in the literature, we performed a chromosomal analysis and an array-comparative genomic hybridization (CGH) to search for genetic abnormalities. At the time of transplantation, we collected samples from the bronchi and performed hematoxylin and eosin (HE), Elastic von-Gieson (EVG) and immunohistochemical stains of the explanted MKS bronchus, a control bronchus and of the inflammatory infiltrates. Specimens of main bronchi from the donor lung harvested for transplant served as control. Bronchial smears were taken from both main bronchi of the recipient for microbiological cultures.
  
  
  RESULTS
  No genetic alterations could be found in chromosomal analysis and in array-CGH. Histological analysis revealed a strong reduction of elastic fibers in the submucosal connective tissue and a diffuse inflammatory infiltrate, mainly comprised of CD4+ cells. In addition, immunohistochemistry showed increased matrix metalloproteinases (MMPs) protein expression of MMP-1, 2, 3 and 9.
  
  
  CONCLUSIONS
  Based on our findings, we hypothesize that MKS is a chronic inflammatory disease characterized by an MMP-mediated degradation of submucosal elastic fibers.
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mitterbauer
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.affiliation: Department of Radiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Prosch
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh
authors.initials: S
authors.lastname: Taghavi
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D000328:Adult; D055028:Comparative Genomic Hybridization; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D014057:Tomography, X-Ray Computed; D014137:Tracheobronchomegaly / Q000150:complications* / Q000175:diagnosis / Q000601:surgery
keywords: immunology; inflammation; lung transplantation; pathophysiology; tracheomalacia