Exhaled Breath Particles in Lung Transplantation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Exhaled Breath Particles as a Clinical Indicator for Acute and Chronic Rejection After Lung Transplantation

Conditions
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Lung Transplant Rejection, Primary Graft Dysfunction, Chronic Rejection of Lung Transplant

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have undergone LTx at Skåne University Hospital, SUS Lund Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LTx rejection<br>Lung transplanted patients with acute or chronic rejection | |
| LTx non-rejection<br>Lung transplanted patients without any form of rejection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of proteins in EBP | 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. | Pre-transplantation | 
| Concentration of proteins in EBP | 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. | Day 1-3 after lung transplantation | 
| Concentration of proteins in EBP | 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. | 1 month after lung transplantation | 
| Concentration of proteins in EBP | 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. | 3 months after lung transplantation | 
| Concentration of proteins in EBP | 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. | 6 months after lung transplantation | 
| Concentration of proteins in EBP | 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. | 9 months after lung transplantation | 
| Concentration of proteins in EBP | 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. | 12 months after lung transplantation | 
| Concentration of proteins in EBP | 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. | 18 months after lung transplantation | 
| Concentration of proteins in EBP | 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. | 2 years after lung transplantation | 
| Concentration of proteins in EBP | 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. | 3 years after lung transplantation | 
| Concentration of proteins in EBP | 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. | 4 years after lung transplantation | 
| Particle flow rate from the airways (PFR) | 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. | Day 1-3 after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 1 month after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 3 months after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 6 months after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 9 months after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 12 months after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 18 months after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 2 years after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 3 years after transplantation | 
| Particle flow rate from the airways (PFR) | 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. | 4 years after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | Pre-transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | Day 1 after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | Day 2 after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | Day 3 after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 1 month after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 3 months after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 6 months after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 9 months after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 12 months after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 18 months after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 2 years after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 3 years after lung transplantation | 
| Concentration of proteins and other biomarkers in plasma | Concentration and composition of proteins and other biomarkers will be analysed in plasma | 4 years after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | Day 1-3 after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 1 month after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 3 months after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 6 months after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 9 months after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 12 months after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 18 months after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 2 years after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 3 years after lung transplantation | 
| Concentration of proteins and other biomarkers in BAL | Concentration and composition of proteins and other biomarkers will be analysed in BAL | 4 years after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue. Both taken from the native lung and from the donor lung. | At the time of lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 1 months after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 3 months after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 6 months after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 9 months after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 12 months after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 18 months after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 2 years after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 3 years after lung transplantation | 
| Concentration of proteins and other biomarkers in lung tissue | Concentration and composition of proteins and other biomarkers will be analysed in lung tissue | 4 years after lung transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PExA, Exhaled Breath Particles, Lung transplantation, Primary Graft Dysfunction, Chronic Lug Allograft Dysfunction