Transplant International (Apr 2024)

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

  • Anna Niroomand,
  • Anna Niroomand,
  • Anna Niroomand,
  • Anna Niroomand,
  • Gabriel Hirdman,
  • Gabriel Hirdman,
  • Gabriel Hirdman,
  • Nicholas Bèchet,
  • Nicholas Bèchet,
  • Nicholas Bèchet,
  • Haider Ghaidan,
  • Haider Ghaidan,
  • Haider Ghaidan,
  • Haider Ghaidan,
  • Martin Stenlo,
  • Martin Stenlo,
  • Martin Stenlo,
  • Martin Stenlo,
  • Sven Kjellström,
  • Marc Isaksson,
  • Ellen Broberg,
  • Ellen Broberg,
  • Ellen Broberg,
  • Ellen Broberg,
  • Leif Pierre,
  • Leif Pierre,
  • Leif Pierre,
  • Leif Pierre,
  • Snejana Hyllén,
  • Snejana Hyllén,
  • Snejana Hyllén,
  • Snejana Hyllén,
  • Franziska Olm,
  • Franziska Olm,
  • Franziska Olm,
  • Sandra Lindstedt,
  • Sandra Lindstedt,
  • Sandra Lindstedt,
  • Sandra Lindstedt

DOI
https://doi.org/10.3389/ti.2024.12298
Journal volume & issue
Vol. 37

Abstract

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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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