@article{01HT4N8CMRFGXQWH82T7H36VP1,
  abstract     = {{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: 
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: 
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: 
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.}},
  articleno    = {{105030}},
  author       = {{Kerckhof, Pieterjan and Ambrocio, Gene P.L. and Beeckmans, Hanne and Kaes, Janne and Geudens, Vincent and Bos, Saskia and Willems, Lynn and Vermaut, Astrid and Vermant, Marie and Goos, Tinne and De Fays, Charlotte and Aversa, Lucia and Mohamady, Yousry and Vanstapel, Arno and Orlitová, Michaela and Van Slambrouck, Jan and Jin, Xin and Varghese, Vimi and Josipovic, Iván and Boone, Matthieu and Dupont, Lieven J. and Weynand, Birgit and Dubbeldam, Adriana and Van Raemdonck, Dirk E. and Ceulemans, Laurens J. and Gayan-Ramirez, Ghislaine and De Sadeleer, Laurens J. and McDonough, John E. and Vanaudenaerde, Bart M. and Vos, Robin}},
  issn         = {{2352-3964}},
  journal      = {{EBIOMEDICINE}},
  keywords     = {{General Biochemistry, Genetics and Molecular Biology,General Medicine,BRONCHIAL ARTERY REVASCULARIZATION,LUNG ALLOGRAFT DYSFUNCTION,OBLITERATIVE BRONCHIOLITIS,TRANSPLANTATION,PHENOTYPES,MORPHOLOGY}},
  language     = {{eng}},
  pages        = {{15}},
  title        = {{Ventilatory capacity in CLAD is driven by dysfunctional airway structure}},
  url          = {{http://doi.org/10.1016/j.ebiom.2024.105030}},
  volume       = {{101}},
  year         = {{2024}},
}

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