Exhaled Breath Particles in Lung Transplantation

NCT ID: NCT05375149

Last Updated: 2022-05-16

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-09-18
• Study Completion Date: 2026-09-30

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.

Conditions

Lung Transplant Rejection; Primary Graft Dysfunction; Chronic Rejection of Lung Transplant

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

LTx rejection

Lung transplanted patients with acute or chronic rejection

No interventions assigned to this group

LTx non-rejection

Lung transplanted patients without any form of rejection

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• None

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lund University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandra Lindstedt, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Region Skåne, Lund University

Locations

Skåne University Hospital

Lund, Skåne County, Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Sandra Lindstedt, MD, PhD

Role: CONTACT

sandra.lindstedt_ingemansson@med.lu.se

+46737220580

Facility Contacts

Sandra Lindstedt, MD, PhD

Role: primary

sandra.lindstedt_ingemansson@med.lu.se

0737220580

References

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.

Reference Type: BACKGROUND

PMID: 27795995 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31994907 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31615381 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31558154 (View on PubMed)

Other Identifiers

LTxPEx

Identifier Type: -

Identifier Source: org_study_id