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

• Published in: Journal of clinical medicine 2022-01, Vol.11 (1), p.111
• Main Authors: 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, On Behalf Of The Leuven Lung Transplant Group
• Format: Article
• Language: English
• Subjects: Autopsies; Biopsy; Clinical medicine; Hyperplasia; Lung transplants; Patients; Pneumonia
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm11010111

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 ( = 21/28, 75%), paraseptal ( = 17/28, 61%) and subpleural ( = 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 ( = 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.