Article Text
PDF
Abstract
Background Chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) is the main cause of death beyond 1-year post-lung transplantation. The disease-initiating triggers as well as the molecular changes leading to fibrotic alterations in the transplanted lung are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS.
Methods Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen University hospital between 2005 and 2006, with or without development of BOS in a 5-year follow-up, were obtained 3 and 12 months after transplantation. Biopsies were assessed for total collagen, collagen type IV and biglycan in the alveolar and small airway compartments using Masson's Trichrome staining and immunohistochemistry.
Results A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months.
Conclusions Patients with future BOS displayed distinct ECM changes compared with patients without BOS. Our data indicate an involvement of alveolar and small airway compartments in post-transplantation changes in the development of BOS.
- Lung Transplantation
- Histology/Cytology
- Airway Epithelium
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Statistics from Altmetric.com
Footnotes
Contributors CM wrote the manuscript, performed immunohistochemistry, analysed and quantified the outcome of the IHC and histological stainings and interpreted them in relation to clinical data. HHS, CBA and MI provided clinical expertise, patient material and clinical data. CBA graded the patient material with regard to acute and chronic rejection and provided Masson's Trichrome stained tissue sections. AA-S and LTE provided clinical expertise and contributed to the interpretation of the data. AA-S, MI and GW-T designed the overall concept of the study. All authors participated in the study design, contributed to all manuscript versions and approved the final version of the manuscript.
Funding This study was supported by the Swedish Medical Research Council (11550), the Evy and Gunnar Sandberg Foundation, the Swedish Heart-Lung Foundation, the Alfred Österlund Foundation, the Royal Physiographic Society in Lund, the Swedish Foundation for Strategic Research, ALF (Government Public Health Grant) and the Medical Faculty of Lund University. HHS received a research grant from the Research Council at The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark and from Scandiatransplant.
Competing interests None declared.
Ethics approval The Danish Data Protection Agency.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.