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Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation

Bronchiolitis obliterans syndrome (BOS) is considered an airway-centered disease, with bronchiolitis obliterans (BO) as pathologic hallmark. However, the histologic spectrum of pure clinical BOS remains poorly characterized. We provide the first in-depth histopathologic description of well-character...

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Autores principales: Vanstapel, Arno, Verleden, Stijn E., Verbeken, Eric K., Braubach, Peter, Goos, Tinne, De Sadeleer, Laurens, Kaes, Janne, Vanaudenaerde, Bart M., Jonigk, Danny, Ackermann, Maximilian, Ceulemans, Laurens J., Van Raemdonck, Dirk E., Neyrinck, Arne P., Vos, Robin, Verleden, Geert M., Weynand, Birgit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745215/
https://www.ncbi.nlm.nih.gov/pubmed/35011851
http://dx.doi.org/10.3390/jcm11010111
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author Vanstapel, Arno
Verleden, Stijn E.
Verbeken, Eric K.
Braubach, Peter
Goos, Tinne
De Sadeleer, Laurens
Kaes, Janne
Vanaudenaerde, Bart M.
Jonigk, Danny
Ackermann, Maximilian
Ceulemans, Laurens J.
Van Raemdonck, Dirk E.
Neyrinck, Arne P.
Vos, Robin
Verleden, Geert M.
Weynand, Birgit
author_facet Vanstapel, Arno
Verleden, Stijn E.
Verbeken, Eric K.
Braubach, Peter
Goos, Tinne
De Sadeleer, Laurens
Kaes, Janne
Vanaudenaerde, Bart M.
Jonigk, Danny
Ackermann, Maximilian
Ceulemans, Laurens J.
Van Raemdonck, Dirk E.
Neyrinck, Arne P.
Vos, Robin
Verleden, Geert M.
Weynand, Birgit
author_sort Vanstapel, Arno
collection PubMed
description Bronchiolitis obliterans syndrome (BOS) is considered an airway-centered disease, with bronchiolitis obliterans (BO) as pathologic hallmark. However, the histologic spectrum of pure clinical BOS remains poorly characterized. We provide the first in-depth histopathologic description of well-characterized BOS patients and patients without chronic lung allograft dysfunction (CLAD), defined according to the recent consensus guidelines. Explant lung tissue from 52 clinically-defined BOS and 26 non-CLAD patients (collected 1993–2018) was analyzed for histologic parameters, including but not limited to airway lesions, vasculopathy and fibrosis. In BOS, BO lesions were evident in 38 (73%) patients and varied from concentric sub-epithelial fibrotic BO to inflammatory BO, while 10/14 patients without BO displayed ‘vanishing airways’, defined by a discordance between arteries and airways. Chronic vascular abnormalities were detected in 22 (42%) patients. Ashcroft fibrosis scores revealed a median of 43% (IQR: 23–69) of normal lung parenchyma per patient; 26% (IQR: 18–37) of minimal alveolar fibrous thickening; and 11% (IQR: 4–18) of moderate alveolar thickening without architectural damage. Patchy areas of definite fibrotic damage to the lung structure (i.e., Ashcroft score ≥5) were present in 28 (54%) patients. Fibrosis was classified as bronchocentric (n = 21/28, 75%), paraseptal (n = 17/28, 61%) and subpleural (n = 15/28, 54%). In non-CLAD patients, BO lesions were absent, chronic vascular abnormalities present in 1 (4%) patient and mean Ashcroft scores were significantly lower compared to BOS (p = 0.0038) with 78% (IQR: 64–88) normally preserved lung parenchyma. BOS explant lungs revealed evidence of various histopathologic findings, including vasculopathy and fibrotic changes, which may contribute to the pathophysiology of BOS.
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spelling pubmed-87452152022-01-11 Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation Vanstapel, Arno Verleden, Stijn E. Verbeken, Eric K. Braubach, Peter Goos, Tinne De Sadeleer, Laurens Kaes, Janne Vanaudenaerde, Bart M. Jonigk, Danny Ackermann, Maximilian Ceulemans, Laurens J. Van Raemdonck, Dirk E. Neyrinck, Arne P. Vos, Robin Verleden, Geert M. Weynand, Birgit J Clin Med Article Bronchiolitis obliterans syndrome (BOS) is considered an airway-centered disease, with bronchiolitis obliterans (BO) as pathologic hallmark. However, the histologic spectrum of pure clinical BOS remains poorly characterized. We provide the first in-depth histopathologic description of well-characterized BOS patients and patients without chronic lung allograft dysfunction (CLAD), defined according to the recent consensus guidelines. Explant lung tissue from 52 clinically-defined BOS and 26 non-CLAD patients (collected 1993–2018) was analyzed for histologic parameters, including but not limited to airway lesions, vasculopathy and fibrosis. In BOS, BO lesions were evident in 38 (73%) patients and varied from concentric sub-epithelial fibrotic BO to inflammatory BO, while 10/14 patients without BO displayed ‘vanishing airways’, defined by a discordance between arteries and airways. Chronic vascular abnormalities were detected in 22 (42%) patients. Ashcroft fibrosis scores revealed a median of 43% (IQR: 23–69) of normal lung parenchyma per patient; 26% (IQR: 18–37) of minimal alveolar fibrous thickening; and 11% (IQR: 4–18) of moderate alveolar thickening without architectural damage. Patchy areas of definite fibrotic damage to the lung structure (i.e., Ashcroft score ≥5) were present in 28 (54%) patients. Fibrosis was classified as bronchocentric (n = 21/28, 75%), paraseptal (n = 17/28, 61%) and subpleural (n = 15/28, 54%). In non-CLAD patients, BO lesions were absent, chronic vascular abnormalities present in 1 (4%) patient and mean Ashcroft scores were significantly lower compared to BOS (p = 0.0038) with 78% (IQR: 64–88) normally preserved lung parenchyma. BOS explant lungs revealed evidence of various histopathologic findings, including vasculopathy and fibrotic changes, which may contribute to the pathophysiology of BOS. MDPI 2021-12-27 /pmc/articles/PMC8745215/ /pubmed/35011851 http://dx.doi.org/10.3390/jcm11010111 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vanstapel, Arno
Verleden, Stijn E.
Verbeken, Eric K.
Braubach, Peter
Goos, Tinne
De Sadeleer, Laurens
Kaes, Janne
Vanaudenaerde, Bart M.
Jonigk, Danny
Ackermann, Maximilian
Ceulemans, Laurens J.
Van Raemdonck, Dirk E.
Neyrinck, Arne P.
Vos, Robin
Verleden, Geert M.
Weynand, Birgit
Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation
title Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation
title_full Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation
title_fullStr Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation
title_full_unstemmed Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation
title_short Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation
title_sort beyond bronchiolitis obliterans: in-depth histopathologic characterization of bronchiolitis obliterans syndrome after lung transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745215/
https://www.ncbi.nlm.nih.gov/pubmed/35011851
http://dx.doi.org/10.3390/jcm11010111
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