Ventilatory capacity in CLAD is driven by dysfunctional airway structure.
Airway tree
Bronchiolitis obliterans syndrome (BOS)
Chronic lung allograft dysfunction (CLAD)
Constrictive bronchiolitis
Obstruction
Restrictive allograft syndrome (RAS)
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
15
11
2023
revised:
05
02
2024
accepted:
07
02
2024
medline:
18
3
2024
pubmed:
24
2
2024
entrez:
23
2
2024
Statut:
ppublish
Résumé
Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood. A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung μCT and tissue-core μCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions. BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters. Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted. This research was funded with the National research fund Flanders (G060322N), received by R.V.
Sections du résumé
BACKGROUND
BACKGROUND
Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood.
METHODS
METHODS
A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung μCT and tissue-core μCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions.
FINDINGS
RESULTS
BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters.
INTERPRETATION
CONCLUSIONS
Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted.
FUNDING
BACKGROUND
This research was funded with the National research fund Flanders (G060322N), received by R.V.
Identifiants
pubmed: 38394744
pii: S2352-3964(24)00065-3
doi: 10.1016/j.ebiom.2024.105030
pmc: PMC10897920
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105030Informations de copyright
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests JK and VG and MV are junior research fellows of the Research Foundation Flanders (FWO; 1198920N and 1102020N and 1SE433N). MV received compensation from Sanofi for attending the ERS 2023 congress. GPLA is a supported by an European Respirology Society Clinical Fellowship Grant. SB is supported by the Paul Corris International Clinical Research Training Scholarship. LJDS (De Sadeleer) is supported by the European Union's Horizon Europe research and innovation programme as a Marie Sklodowska-Curie actions postdoctoral fellowship (grant agreement No. 101066289).