Clinical trial NCT05375149: Exhaled Breath Particles in Lung Transplantation
Official title: Exhaled Breath Particles as a Clinical Indicator for Acute and Chronic Rejection After Lung Transplantation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Transplant Rejection
Primary Graft Dysfunction
Chronic Rejection of Lung Transplant
Keywords: Exhaled Breath Particles
PExA
Lung transplantation
Primary Graft Dysfunction
Chronic Lug Allograft Dysfunction
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
First posted: 2022-05-16
Enrollment: 150
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients undergoing lung transplantation at Skåne University Hospital, SUS Lund.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* None

Primary outcomes:
measure: Concentration of proteins in EBP
timeFrame: Pre-transplantation
measure: Concentration of proteins in EBP
timeFrame: Day 1-3 after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 1 month after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 3 months after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 6 months after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 9 months after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 12 months after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 18 months after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 2 years after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 3 years after lung transplantation
measure: Concentration of proteins in EBP
timeFrame: 4 years after lung transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: Day 1-3 after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 1 month after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 3 months after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 6 months after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 9 months after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 12 months after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 18 months after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 2 years after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 3 years after transplantation
measure: Particle flow rate from the airways (PFR)
timeFrame: 4 years after transplantation
Secondary outcomes:
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: Pre-transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: Day 1 after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: Day 2 after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: Day 3 after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 1 month after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 3 months after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 6 months after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 9 months after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 12 months after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 18 months after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 2 years after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 3 years after lung transplantation
measure: Concentration of proteins and other biomarkers in plasma
timeFrame: 4 years after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: Day 1-3 after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 1 month after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 3 months after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 6 months after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 9 months after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 12 months after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 18 months after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 2 years after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 3 years after lung transplantation
measure: Concentration of proteins and other biomarkers in BAL
timeFrame: 4 years after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: At the time of lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 1 months after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 3 months after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 6 months after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 9 months after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 12 months after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 18 months after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 2 years after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 3 years after lung transplantation
measure: Concentration of proteins and other biomarkers in lung tissue
timeFrame: 4 years after lung transplantation
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skåne University Hospital
state: Skåne Län
Study officials:
affiliation: Region Skåne, Lund University
name: Sandra Lindstedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ericson PA, Mirgorodskaya E, Hammar OS, Viklund EA, Almstrand AR, Larsson PJ, Riise GC, Olin AC. Low Levels of Exhaled Surfactant Protein A Associated With BOS After Lung Transplantation. Transplant Direct. 2016 Aug 26;2(9):e103. doi: 10.1097/TXD.0000000000000615. eCollection 2016 Sep.
citation: Stenlo M, Hyllen S, Silva IAN, Bolukbas DA, Pierre L, Hallgren O, Wagner DE, Lindstedt S. Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2020 Mar 1;318(3):L510-L517. doi: 10.1152/ajplung.00524.2019. Epub 2020 Jan 29.
citation: Broberg E, Hyllen S, Algotsson L, Wagner DE, Lindstedt S. Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction. Exp Clin Transplant. 2019 Dec;17(6):803-812. doi: 10.6002/ect.2019.0187. Epub 2019 Oct 11.
citation: Behndig AF, Mirgorodskaya E, Blomberg A, Olin AC. Surfactant Protein A in particles in exhaled air (PExA), bronchial lavage and bronchial wash - a methodological comparison. Respir Res. 2019 Sep 26;20(1):214. doi: 10.1186/s12931-019-1172-1.