Exhaled Breath Particles in Lung Transplantation

Recruiting

• Conditions: Primary Graft Dysfunction; Lung Transplant Rejection; Chronic Rejection of Lung Transplant

• Registration Number: NCT05375149
• Lead Sponsor: Lund University Hospital

Brief Summary

Lung transplantation (LTx) is the only effective treatment for patients with end stage lung disease. Of the major organs transplanted, survival following LTx is the lowest with a mean of 5 years. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and contributes to the development of chronic lung allograft dysfunction (CLAD) that remains the leading cause of late mortality. Earlier detection of rejection after LTx is of substantial importance as it would improve the possibilities of treatment and could increase survival.

The investigators have shown in previous work that exhaled breath particles (EBP) reflect the composition of respiratory tract lining fluid (RTLF). EBP and particle flow rate (PFR) can be used as non-invasive methods for early detection and monitoring of airway diseases such as acute respiratory distress syndrome (ARDS). It has also been shown that the particle flow prolife after lung transplantation differs between patients who develop PGD and those who do not and that the composition of EBP differs between patients with and without bronchiolitis obliterans syndrome (BOS), an obstructive form of CLAD.

Samples of EBP and measurements of PFR will be collected from lung transplanted patients. Membranes with EBP will be saved for molecular analysis. The investigators aim to identify potential particle flow patterns and biomarkers for earlier detection of rejection after lung transplantation.

Detailed Description

Samples of EBP and measurement of PFR will be done on patients undergoing lung transplantation at Skåne University Hospital (SUS) Lund. Measurements of EBP and PFR and collection of blood will be done repeatedly postoperatively when the patient is still in the hospital, at three months post-transplantation, at six months post-transplantation, at 12 months post-transplantation and annually after that. An additional preoperative blood sample will also be obtained. Furthermore, the investigators will collect bronchoalveolar lavage fluid (BALF) and lung biopsies when the patient is scheduled for routine bronchoscopies in the follow-up period.

This study involves measurements of EBP and PFR done by the particles in exhaled air (PExA) system on lung transplanted patients with and without acute or chronic rejection. The patients who do not develop any form of rejection will serve as a control group to the ones who develop rejection. Furthermore, each patient will serve as their own control.

The purpose of this study is to find better means of identifying rejection of transplanted lungs in earlier stages, and to explore candidate biomarkers. Earlier diagnosis of rejection of the transplanted organ can lead to better treatment possibilities and a positive impact on survival after LTx.

Study Timeline

• Study Start: 2018-09-18
• Status Verified: 2022-02
• Study First Submitted: 2022-05-10
• Study First Submitted QC: 2022-05-10
• Last Update Submitted: 2022-05-10
• Study First Posted: 2022-05-16
• Last Update Posted: 2022-05-16
• Primary Completion: 2024-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Patients who have undergone LTx at Skåne University Hospital, SUS Lund

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Concentration of proteins in EBP	4 years after lung transplantation	Proteins from exhaled air are collected onto a membrane for subsequently molecular analysis. Analysis aims to identify candidate biomarker for acute and chronic rejection of transplanted lungs.
Particle flow rate from the airways (PFR)	4 years after transplantation	PFR will be measured by the PExA device. The flow rate and the particle pattern will be analysed to find differences between groups of lung transplanted patients with and without rejection.

Secondary Outcome Measures

Name	Time	Method
Concentration of proteins and other biomarkers in BAL	4 years after lung transplantation	Concentration and composition of proteins and other biomarkers will be analysed in BAL
Concentration of proteins and other biomarkers in lung tissue	4 years after lung transplantation	Concentration and composition of proteins and other biomarkers will be analysed in lung tissue
Concentration of proteins and other biomarkers in plasma	4 years after lung transplantation	Concentration and composition of proteins and other biomarkers will be analysed in plasma

Trial Locations

Locations (1)

Skåne University Hospital; 🇸🇪 Lund, Skåne Län, Sweden