Impaired complement regulation drives chronic lung allograft dysfunction after lung transplantation. DOI Creative Commons
Hrishikesh S. Kulkarni, Laneshia K. Tague, Daniel R. Calabrese

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

ABSTRACT A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause mortality after transplantation, is needed to improve outcomes. The complement system links innate adaptive immune responses and activated early post-lung transplantation form C3 convertase, a critical enzyme that cleaves central component C3. We hypothesized LTx recipients with genetic predisposition enhanced activation have worse CLAD-free survival mediated through increased alloimmunity. interrogated known functional polymorphism (C3R102G) increases impaired convertase inactivation in two independent recipient cohorts. C3R102G, identified at least one out three recipients, was associated survival, particularly subset who developed donor-specific antibodies (DSA). In mouse orthotopic model, regulation resulted more severe obstructive airway lesions when compared wildtype controls, despite only moderate differences graft-infiltrating effector T cells. Impaired promoted intragraft accumulation memory B cells antibody-secreting cells, resulting DSA levels. summary, cell survival. BRIEF SUMMARY Lung transplant genetically predisposed demonstrate rejection-free This phenotype cell-activation antibodies.

Language: Английский

No tolerance for Pseudomonas in lung transplants DOI
Idaira M. Guerrero-Fonseca, Bryan G. Yipp

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(784)

Published: Feb. 5, 2025

Pseudomonas infection after lung transplantation induces acute intragraft lymphocytotoxicity that promotes antibody-mediated rejection in mice (Liao et al. , this issue).

Language: Английский

Citations

0
Exploring the Association Between Torquetenovirus Viral Load and Immunosuppressive Drug Exposure in Lung Transplantation DOI Creative Commons
Víctor Manuel Mora Cuesta,

Emilio Rodrigo,

David Iturbe‐Fernández

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 494 - 494

Published: March 27, 2025

To improve lung transplant recipient (LungTx) outcome, it would be of great interest to measure the net state immunosuppression avoid both infection and rejection. Measurement Torquetenovirus load (TTV load) has been proposed as a biomarker monitor solid organ transplantation, but its relationship with immunosuppressive drugs, particularly mycophenolic acid (MPA), is not well understood. We performed prospective study 53 LungTx, measuring TTV before at week 3, month 3. Tacrolimus MPA doses levels were recorded, an area under curve (AUC-MPA) was calculated third month. LungTx in fourth quartile exhibited low risk acute rejection (OR 0.113, 95% CI 0.013-0.953, p = 0.045) high opportunistic from 3 6 15.200, 1.525-151.511, 0.020), respectively. weakly related tacrolimus trough level (rho 0.283, 0.040). Neither blood nor AUC-MPA load, although only patients reduction dose 1 showed smaller increase (0.86, IQR 2.58 log10 copies/mL vs. 2.26, 3.02 copies/mL, 0.026). In conclusion, partially exposure drugs. Other variables, such inflammation, immunosenescence, frailty, may influence overall load.

Language: Английский

Citations

0
Triple role of exosomes in lung transplantation DOI Creative Commons
Dingyu Rao, Defa Huang, Zhihai Peng

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Exosomes are tiny vesicles secreted by the vast majority of cells and play an important role in physiological as well pathological processes body. Circulating exosomes Lung Transplant Recipients (LTxR) undergoing rejection contain mismatched Human Leukocyte Antigens (HLA) lung-associated autoantigens (e.g., K-alpha1 microtubule protein collagen V), which may induce autoantibodies, circulating trigger immune response that results lung transplant recipient. This article discusses transplantation from three perspectives: a biomarker for after transplantation; mechanism exosome-mediated activation response; potential therapeutic strategy.

Language: Английский

Citations

0
Management of pharmacotherapy in lung transplant candidates DOI

Katelyn N. Rudzik,

Haifa Lyster

Current Opinion in Pulmonary Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Purpose of review Lung transplantation is a common treatment for end-stage lung disease (ESLD). Patients present to evaluation on various medications that could impact their candidacy and posttransplant course. In this review, we will discuss pretransplant optimization pharmacotherapy minimize complications while waiting transplant increase success. We also important considerations immunosuppression, antimicrobial prophylaxis, complex drug interactions. Recent findings Prior transplantation, several should be optimized promote success including minimization corticosteroids, opioids, benzodiazepines. candidates up date vaccinations. Most ESLD are well tolerated continue until the point antifibrotics, CFTR modulators, pulmonary vasodilators. Mammalian target rapamycin inhibitors other immunosuppressants may need stopped or minimized before infection would healing complications. Medications risk bleeding, thrombosis, aspiration prior listing. Summary article, management Changes in done cautiously prevent worsening native transplantation.

Language: Английский

Citations

0
Donor Lung Weight a Novel Predictor for Primary Graft Dysfunction DOI Creative Commons

Arne Martinsson,

Anders Thorén,

Sven‐Erik Ricksten

et al.

JHLT Open, Journal Year: 2025, Volume and Issue: unknown, P. 100271 - 100271

Published: April 1, 2025

Language: Английский

Citations

0
Infections and lung transplantation: key considerations for eligibility, management, and posttransplant care DOI
Jonathan Huang,

Rachel Friedman‐Moraco,

Stephanie M. Pouch

et al.

Current Opinion in Pulmonary Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Purpose of review Lung transplantation is a critical and evolving therapy for patients with end-stage lung disease. As the need increases, careful candidate selection vital to maximizing outcomes ensuring appropriate organ allocation. A key challenge in transplant candidates colonization or infection lungs by environmental upper airway pathogens. These pathogens, along other chronic infections, can lead posttransplant complications high mortality an increased risk graft failure. Recent findings Major infectious considerations include multidrug-resistant bacteria (including Burkholderia cepacia complex), nontuberculous mycobacteria, molds, viral infections. By recognizing epidemiology, diagnosis, management these infections peri-transplant period, providers better mitigate risks improve success. Similarly, advancements diagnostics therapeutics offer novel approaches managing previously challenging Summary experience grows treating difficult syndromes, more are becoming eligible transplantation. thorough understanding essential improving selection, reducing complications, expanding eligibility.

Language: Английский

Citations

0
Pulmonary Hypertension and Lung Transplantation DOI

S. Kruszona,

K. Aburahma, Nunzio Davide de Manna

et al.

Zentralblatt für Chirurgie - Zeitschrift für Allgemeine Viszeral- Thorax- und Gefäßchirurgie, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Abstract Pulmonary artery hypertension (PAH), a subtype of pulmonary hypertension, is rare end-stage lung disease. Bilateral and combined heart transplantation have long been considered as gold standard therapy for PAH. This manuscript reviewed the most up-to-date literature on PAH, focusing particularly risk stratification, donor allocation, bridging to (BTT), intra- postoperative management in both adult pediatric patients. The last two decades witnessed an important shift transplant indications strategy Newly introduced antihypertensive drugs postponed time eligible patients, thus reserving severely ill high-risk patients triple therapy. Furthermore, widespread peritransplant use veno-arterial extracorporeal membrane oxygenation (ECMO) enables cardiac remodeling after bilateral transplantation. change from renders more organs available era organ shortage. ECMO-bridging life-saving tool selected PAH although associated with higher complications. Better allocation at high decompensation may reduce need further improve outcomes.

Language: Английский

Citations

0
Caring for the Transplant Patient for Non-transplant Anesthesia DOI

Jarva Chow,

Amanda Walborn, Kerilyn Petrucci

et al.

International Anesthesiology Clinics, Journal Year: 2025, Volume and Issue: unknown

Published: May 22, 2025

Language: Английский

Citations

0
Lung Transplantation DOI
Jason D. Christie, Dirk Van Raemdonck, Andrew J. Fisher

et al.

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: 392(7), P. 727 - 727

Published: Feb. 12, 2025

Citations

0
A randomized trial of open lung protective ventilation compared to conventional mechanical ventilation in deceased organ donors DOI Creative Commons
Lorraine B. Ware, Tatsuki Koyama, Ciara M. Shaver

et al.

The Journal of Heart and Lung Transplantation, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

We conducted a randomized trial of open lung protective ventilation (OLPV) compared to conventional (CV) in deceased donors. The primary outcome was utilization for transplantation. Eligible donors were ≥13 years with PaO2/FiO2 between 150 and 400 mmHg. Donors volume control OLPV [tidal (TV) 8 ml/kg, PEEP 10 cmH2O, protocolized recruitment maneuvers (RM)] or CV [TV 10ml/kg, 5 cm H2O, RM only after vent disconnect] duration donor management. Lungs evaluated transplantation on standardized ventilator settings both arms FiO2 1.0]. 153 (74 OLPV, 79 CV) included the final analysis. Median treatment 50 hours did not differ by arm. Donor 23% arm 22% arm, P = 0.85. Change from randomization procurement treatment; median increase (quartiles) versus 68 mmHg (18, 127) vs 74 (-27 170), 0.72. There no difference need vasopressors serious adverse events arms. Among 28 recipients whom detailed outcomes available, mechanical ventilation, ICU stay hospital different An strategy safe but improve oxygenation population US organ NCT03439995.

Language: Английский

Citations

0