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Terminal bronchioles decrease before emphysematous destruction and adaptive immune response in human explant lungs with COPD

C de Fays, H Beeckmans, P Kerckhof, V Geudens, A Vermaut, I Gyselinck, T Goos, M Vermant, J Kaes, C Aelbrecht, K Maes, Y Mohamady, L Aversa, S Everaerts, J E Mcdonough, L J De Sadeleer, S Gohy, J Ambroise, W A Wuyts, W Janssens, L J Ceulemans, D E Van Raemdonck, R Vos, N Kaminski, C Pilette, G Gayan-Ramirez, B M Vanaudenaerde
European Respiratory Journal 2022 60: 4646; DOI: 10.1183/13993003.congress-2022.4646
C de Fays
1Pole of Pneumology, ENT, and Dermatology, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium
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H Beeckmans
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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P Kerckhof
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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V Geudens
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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A Vermaut
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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I Gyselinck
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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T Goos
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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M Vermant
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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J Kaes
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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C Aelbrecht
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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K Maes
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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Y Mohamady
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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L Aversa
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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S Everaerts
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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J E Mcdonough
3Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven CT, USA
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L J De Sadeleer
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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S Gohy
1Pole of Pneumology, ENT, and Dermatology, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium
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J Ambroise
4Centre de Technologies Molécularaires Appliquées, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
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W A Wuyts
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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W Janssens
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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L J Ceulemans
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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D E Van Raemdonck
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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R Vos
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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N Kaminski
3Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven CT, USA
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C Pilette
1Pole of Pneumology, ENT, and Dermatology, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium
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G Gayan-Ramirez
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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B M Vanaudenaerde
2Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium
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Abstract

Emphysema, chronic bronchitis and small airways destruction characterize COPD of which the chronology remains elusive. Our aim was to study the morphological changes of COPD by microCT (number of terminal bronchioles/TB, alveolar surface density and tissue density) in combination with the innate and adaptive immune response by cellular deconvolution of tissue RNA profiling.

A total of 13 control (non-used donor) and 11 COPD (end-stage) explant lungs frozen at TLC were selected and of each 4 samples were imaged by microCT and underwent tissue RNA profiling (Ion Amplyseq Technology). MicroCT images were used to quantify the COPD samples in mild, moderate and severe based on tissue percentage (T%) and alveolar surface density, reflecting the degree of emphysema (Fig 1A). Normalized gene expression data were imputed in the xCell R package for cell type enrichment analysis into structural, innate and adaptive cells.

TB already decreased in mild COPD cores (p=0.0059 vs control), while T% and alveolar surface density gradually decreased (Fig 1B). Innate (dendritic cells) and adaptive immune cells (Th cells, Tc cells and B cells) only appeared in moderate and severe COPD cores (Fig 1C).

Within end-stage COPD lungs, terminal bronchioles decrease already in mild affected cores and prior to alveolar tissue destruction and innate/adaptive Immune response which starts in the moderate stage.

 

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  • COPD - mechanism
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Footnotes

Cite this article as Eur Respir J 2022; 60: Suppl. 66, 4646.

This article was presented at the 2022 ERS International Congress, in session “-”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2022
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Terminal bronchioles decrease before emphysematous destruction and adaptive immune response in human explant lungs with COPD
C de Fays, H Beeckmans, P Kerckhof, V Geudens, A Vermaut, I Gyselinck, T Goos, M Vermant, J Kaes, C Aelbrecht, K Maes, Y Mohamady, L Aversa, S Everaerts, J E Mcdonough, L J De Sadeleer, S Gohy, J Ambroise, W A Wuyts, W Janssens, L J Ceulemans, D E Van Raemdonck, R Vos, N Kaminski, C Pilette, G Gayan-Ramirez, B M Vanaudenaerde
European Respiratory Journal Sep 2022, 60 (suppl 66) 4646; DOI: 10.1183/13993003.congress-2022.4646

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Terminal bronchioles decrease before emphysematous destruction and adaptive immune response in human explant lungs with COPD
C de Fays, H Beeckmans, P Kerckhof, V Geudens, A Vermaut, I Gyselinck, T Goos, M Vermant, J Kaes, C Aelbrecht, K Maes, Y Mohamady, L Aversa, S Everaerts, J E Mcdonough, L J De Sadeleer, S Gohy, J Ambroise, W A Wuyts, W Janssens, L J Ceulemans, D E Van Raemdonck, R Vos, N Kaminski, C Pilette, G Gayan-Ramirez, B M Vanaudenaerde
European Respiratory Journal Sep 2022, 60 (suppl 66) 4646; DOI: 10.1183/13993003.congress-2022.4646
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