Airway Remodeling in Cystic Fibrosis Is Heterogeneous

<b>Rationale:</b> Cystic fibrosis (CF) is characterized by bronchiectasis on imaging, while functionally evolving toward obstructive impairment. Despite its assumed importance in CF, small airway remodeling and its relation to bronchiectasis remains poorly understood. <b>Objectives:</b> The aim of our study was to explore both large and small airway disease morphometrically, by using detailed imaging techniques, such as <i>ex vivo</i> high-resolution computed tomography (HRCT) and micro-computed tomography (μCT), and histological analysis in advanced CF. <b>Methods:</b> On HRCT (600 μm; CF, <i>n</i> = 21; control, <i>n</i> = 6) and μCT (150 μm; CF, <i>n</i> = 3; control, <i>n</i> = 1) scans of inflated explanted lungs, the ratio of visible airway volume to total lung volume (AV%) was calculated as a marker of bronchiectasis, while airway segmentation was used for generation analysis. Clinical data were retrospectively collected. On μCT (8.5 μm) images of lung cores (±2.8 cm<sup>3</sup>), extracted randomly from each lobe (three per lobe), distal airway (DA) diameter, number of airway collapses, and number of open terminal bronchioles per milliliter were analyzed. Morphometric analysis was supplemented with histological analysis of DA collapse. <b>Results:</b> AV% on HRCT was heterogeneous among CF lungs (0.7-4.6%), overlapping with controls (0.4-1.2%). However, the pattern of airway loss on μCT was homogeneous among CF lungs and most pronounced from generations 9-16. AV% did not correlate with the number of open terminal bronchioles per milliliter or percentage predicted forced expiratory volume in 1 second, which correlated with each other. Open DAs in CF lungs were narrowed compared with DA in controls. On the other hand, collapsed DAs in CF lungs showed varying degrees of proximal dilation, with DA diameter correlating with AV%. On histology, collapsed CF DAs showed constrictive bronchiolitis. <b>Conclusions:</b> Airway remodeling in end-stage CF is heterogeneous, ranging from minimal bronchiectasis, overlapping with control lungs, to extensive bronchiectasis with small airway dilation. However, the degree of bronchiectasis is unrelated to functional impairment or the amount of small airway loss, underscoring the importance of small airway disease.

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Publication Details

Journal
Annals of the American Thoracic Society
Published
2024-12-19
DOI
https://doi.org/10.1513/annalsats.202404-446oc
Citations
2
Primary Topic
Cystic Fibrosis Research Advances
Type
article
Field-Weighted Citation Impact
0.84
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article

Airway Remodeling in Cystic Fibrosis Is Heterogeneous

Matthieu Boone, Emanuela Elsa Cortesi, Robin Vos, F. Vermeulen et al.
2 citations
Annals of the American Thoracic Society
Cystic Fibrosis Research Advances
0.84
article

Airway Remodeling in Cystic Fibrosis Is Heterogeneous

Matthieu Boone, Emanuela Elsa Cortesi, Robin Vos, F. Vermeulen, Dirk Van Raemdonck, Lynn Willems, Jan Van Slambrouck, Birgit Weynand, Janne Kaes, Janne Verhaegen, John E. McDonough, Hanne Beeckmans, Vincent Geudens, Charlotte Hooft, Bart M. Vanaudenaerde, Marijke Proesmans, Charlotte De Fays, Mieke Boon, Yousry Mohamady, Laurens J. Ceulemans, Pieterjan Kerckhof, Gitte Aerts, Lieven Dupont, Ghislaine Gayan‐Ramirez, Wim Wuyts, Astrid Vermaut, Lucia Aversa, Xin Jin
article en
2 citations

Abstract

<b>Rationale:</b> Cystic fibrosis (CF) is characterized by bronchiectasis on imaging, while functionally evolving toward obstructive impairment. Despite its assumed importance in CF, small airway remodeling and its relation to bronchiectasis remains poorly understood. <b>Objectives:</b> The aim of our study was to explore both large and small airway disease morphometrically, by using detailed imaging techniques, such as <i>ex vivo</i> high-resolution computed tomography (HRCT) and micro-computed tomography (μCT), and histological analysis in advanced CF. <b>Methods:</b> On HRCT (600 μm; CF, <i>n</i> = 21; control, <i>n</i> = 6) and μCT (150 μm; CF, <i>n</i> = 3; control, <i>n</i> = 1) scans of inflated explanted lungs, the ratio of visible airway volume to total lung volume (AV%) was calculated as a marker of bronchiectasis, while airway segmentation was used for generation analysis. Clinical data were retrospectively collected. On μCT (8.5 μm) images of lung cores (±2.8 cm<sup>3</sup>), extracted randomly from each lobe (three per lobe), distal airway (DA) diameter, number of airway collapses, and number of open terminal bronchioles per milliliter were analyzed. Morphometric analysis was supplemented with histological analysis of DA collapse. <b>Results:</b> AV% on HRCT was heterogeneous among CF lungs (0.7-4.6%), overlapping with controls (0.4-1.2%). However, the pattern of airway loss on μCT was homogeneous among CF lungs and most pronounced from generations 9-16. AV% did not correlate with the number of open terminal bronchioles per milliliter or percentage predicted forced expiratory volume in 1 second, which correlated with each other. Open DAs in CF lungs were narrowed compared with DA in controls. On the other hand, collapsed DAs in CF lungs showed varying degrees of proximal dilation, with DA diameter correlating with AV%. On histology, collapsed CF DAs showed constrictive bronchiolitis. <b>Conclusions:</b> Airway remodeling in end-stage CF is heterogeneous, ranging from minimal bronchiectasis, overlapping with control lungs, to extensive bronchiectasis with small airway dilation. However, the degree of bronchiectasis is unrelated to functional impairment or the amount of small airway loss, underscoring the importance of small airway disease.

Annals of the American Thoracic SocietyVol. 22(4)
HOGENT University of Applied Sciences and Arts (BE), Cystic Fibrosis Foundation (US), Cystic Fibrosis Trust (GB), Universitair Ziekenhuis Leuven (BE), Ghent University Hospital (BE), Ghent University (BE), Cystic Fibrosis Research Foundation (IT), Shenzhen Chronic Disease Prevention Center (CN), Clinica de Pneumologie Iaşi (RO), Health and Human Development (2HD) Research Network (CM), Eurogentec (Belgium) (BE), McMaster University (CA), KU Leuven (BE)
Openalex Percentile: Top 22%
Cystic Fibrosis Research Advances
0.84
DOISourceOpenAlex
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