Impact of the Ex-vivo Pulmonary Perfusion System on the Microbiome of Lung Grafts and Their Inflammatory Reaction.

Summary

It is known that the interactions of the graft and recipient microbiome are capable of modulating immune responses, inducing resilience or exacerbation of various inflammatory or fibrotic processes, therefore variations in the lung microbiome are associated with immunological changes in the transplanted lung.

The main objective is to understand the impact of new systems for conditioning and improving suboptimal lung grafts with ex vivo perfusion(EVLP) on the lung microbiome and its association with tissue inflammation.

The hypothesis is that manipulation of lung grafts and perfusion with broad-spectrum antibiotics during EVLP conditioning changes the lung microbiome, conditioning a less pro-inflammatory environment.

The methodology: This is a single-center prospective observational study. 7 consecutive brain-dead donors who do not meet the criteria to be lung donors will be included in the study. They will be carried out:

* P1. Detection: The donor without criteria to be a lung donor or rejected by all the transplant teams.
* P2. Extraction.
* P3. Cold preservation: The left lung will be cold-preserved
* P4. EVLP Conservation: The right lung will be prepared and conditioned for 3 hours using EVLP

The following samples will be taken at two times:

* T0: At the end of the extraction
* Bronchoalveolar lavage (BAL): Before tracheal clamping, BAL will be taken from the left main bronchus using bronchoscopy. The BAL will be performed on the right lung just before starting P4.
* Lung biopsy: Lung biopsy of the lower lobe of both grafts will be performed
* Preservation liquid or Perfusion liquid: 20 mL of preservation liquid that is in contact with the left graft before storage, as a sterility control (P3) and 20 mL of perfusion liquid before conditioning, as a sterility control (P4).
* T1: At the end of the conservation protocols (P3 or P4).
* B.A.L.
* Lung biopsy: left lower lobe.
* Preservation liquid or Infusion liquid: 20 mL of preservation liquid that is in contact with the left graft or 20 mL of perfusion fluid.

Due to the manipulation of the grafts during extraction and use of the technique, which involves extubating the donor and subsequently intubated again the grafts, as well as perfusion for a minimum of 3 hours with antibiotics, the use of EVLP could alter the microbiome of the grafts. This alteration could impact the obtaining of viable organs for transplant, in the immediate postoperative period as well as in the long-term results. There are no studies that analyse the change in the microbiome after conditioning with EVLP or its relationship with inflammatory parameters.

Conditions

• Lung Transplant Failure

Interventions

DEVICE

EVLP

The right lung will be perfused for 3h with EVLP

DEVICE

Cold preservation

The left lung will be cold preserved as usual protocol

Sponsors & Collaborators

• Hospital Clinic of Barcelona

  collaborator OTHER

• Vall d'Hebron Institute Research

  lead OTHER

Principal Investigators

• Irene Bello Rodríguez, Professor · Hospital Clinic of Barcelona

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-01

Primary Completion

2024-04-30

Completion

2024-06-30

Countries

• Spain

Study Locations