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Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath

Niroomand, Anna LU ; Hirdman, Gabriel LU ; Bèchet, Nicholas LU ; Ghaidan, Haider LU orcid ; Stenlo, Martin LU ; Kjellström, Sven LU ; Isaksson, Marc LU ; Broberg, Ellen LU ; Pierre, Leif LU and Hyllén, Snejana LU , et al. (2024) In Transplant International 37.
Abstract

Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had... (More)

Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had significantly higher PFR [686.4 (449.7–8,824.0) particles per minute (ppm)] compared to recipients without PGD [116.6 (79.7–307.4) ppm, p = 0.0005]. Porcine and human EBP proteins recapitulated proteins found in the BAL, demonstrating its utility instead of more invasive techniques. Furthermore, adherens and tight junction proteins were underexpressed in PGD tissue. Histological and proteomic analysis found significant changes to the alveolar-capillary barrier explaining the high PFR in PGD. Exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD.

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Contribution to journal
publication status
published
subject
keywords
exhaled breath particles, lung transplantation, mass spectrometry, particle flow rate, primary graft dysfunction
in
Transplant International
volume
37
article number
12298
publisher
Springer
external identifiers
  • scopus:85191076759
ISSN
0934-0874
DOI
10.3389/ti.2024.12298
language
English
LU publication?
yes
id
e064001a-b7b1-4f76-bb3d-90b587023f3a
date added to LUP
2024-05-08 10:32:01
date last changed
2024-05-08 10:32:28
@article{e064001a-b7b1-4f76-bb3d-90b587023f3a,
  abstract     = {{<p>Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had significantly higher PFR [686.4 (449.7–8,824.0) particles per minute (ppm)] compared to recipients without PGD [116.6 (79.7–307.4) ppm, p = 0.0005]. Porcine and human EBP proteins recapitulated proteins found in the BAL, demonstrating its utility instead of more invasive techniques. Furthermore, adherens and tight junction proteins were underexpressed in PGD tissue. Histological and proteomic analysis found significant changes to the alveolar-capillary barrier explaining the high PFR in PGD. Exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD.</p>}},
  author       = {{Niroomand, Anna and Hirdman, Gabriel and Bèchet, Nicholas and Ghaidan, Haider and Stenlo, Martin and Kjellström, Sven and Isaksson, Marc and Broberg, Ellen and Pierre, Leif and Hyllén, Snejana and Olm, Franziska and Lindstedt, Sandra}},
  issn         = {{0934-0874}},
  keywords     = {{exhaled breath particles; lung transplantation; mass spectrometry; particle flow rate; primary graft dysfunction}},
  language     = {{eng}},
  publisher    = {{Springer}},
  series       = {{Transplant International}},
  title        = {{Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath}},
  url          = {{http://dx.doi.org/10.3389/ti.2024.12298}},
  doi          = {{10.3389/ti.2024.12298}},
  volume       = {{37}},
  year         = {{2024}},
}