Diagnostic and Therapeutic Applications of Microarrays in Lung Transplantation

Study Overview
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Brief Summary
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Objective: To evaluate the potential impact of molecular phenotyping of transbronchial biopsies in lung transplant recipients with allograft dysfunction, and the potential for developing a safer endobronchial mucosal biopsy format.

Detailed Description
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The current standard for biopsy-based diagnoses of dysfunction of lung transplants is the International Society of Heart and Lung Transplantation (ISHLT) classification applied to transbronchial biopsies, which represents an arbitrary international consensus. Recent data-driven approaches using molecular and conventional technologies indicate that this system produces frequently incorrect diagnoses with potential harm to patients due to inappropriate treatment. especially in relationship to the correct diagnosis of chronic lung allograft dysfunction is a pressing need. To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype. The MMDx, developed first in kidney transplant biopsies with thoroughly established phenotypes, will now be adapted to lung transplant transbronchial biopsies (TBBs). Microarray analysis of lung allograft biopsy specimens will be compared to conventional allograft phenotyping, including clinical, physiologic, radiographic and histological assessment. The present study will use the MMDx™ system to assess and report TBBs, and validate and refine this system in 300 unselected prospectively collected lung TBBs. A subset of the study will examine the third bifurcation mucosal endobronchial biopsies (3BMBs) paired with TBBs from 50 patients to see if the safer 3BMBs can substitute for the TBB to be used by MMDx™. Due to a considerable interest and support from participating Centers, the study is further extended and collected 1010 TBBs and 585 3BMBs from 853 patients. We plan to collect 300 more TBBS and 300 more 3BMBs.This this is the extension of the INTERLUNG study - INTERLUNGEX.

Official Title
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Multi-Centric Observational Study to Analyze the Diagnostic Molecular Features in the Clinical Setting of Lung Allograft Biopsies

Conditions
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Lung Transplant Rejection

Intervention / Treatment
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* Procedure: Lung transplant biopsy bites.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All lung transplant recipients undergoing a biopsy as determined by their surgeon or physician. Exclusion Criteria: Patients who declined participation or unable to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Procedure: Lung transplant biopsy bites.|In the second phase of the study, two biopsy bites from the same patient will be collected to assess tissue sampling variability.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Report the molecular scores (probability) of lung transplant disease in a reference set of 600 transbronchial biopsies. | Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction. | two years | 
| Report the molecular diagnoses of the MMDx-TBB system | Compare MMDx readings to standard-of-care TBB histology and clinical diagnosis of CLAD. | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Report the molecular scores (probability) of lung transplant disease in a reference set of 600 mucosal endobronchial biopsies. | Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction. | two years | 
| Report the molecular diagnoses of the MMDx-3BMB system | Compare MMDx-3BMB readings to MMDx-TBB readings and clinical diagnosis of CLAD | two years | 
| Report the molecular changes over time in medically indicated follow-up biopsies | Predict and monitor response to anti-rejection treatment. | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibody mediated rejection, T cell mediated rejection