Trajectories of FEV1 After Lung Transplantation

Study Overview
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Brief Summary
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For individuals with ESLD, lung transplantation is the best, or only treatment option with increased pulmonary function and quality of life. The forced expiratory volume in one second (FEV1) is the standard to monitor the lung function after transplantation. The goal of this study is to identify and validate the FEV1 trajectories after lung transplantation, as well as their determinants and outcomes, using an international cohort of lung recipients.

Detailed Description
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Chronic lung diseases affect about 500 million individuals and are the third leading cause of death worldwide, accounting for 7% of all mortality. They drive the growing number of individuals with end stage lung disease (ESLD), a public health issue with socioeconomic consequences. For individuals with ESLD, lung transplantation is the best, or only treatment option with increased pulmonary function and quality of life. Lung recipients remain however particularly at risk, with a median patient survival of around five years, which is much lower than other organ recipients, such as kidney, heart or liver recipients. Adequate monitoring of the lung recipient is therefore crucial to optimize the allograft longevity. The forced expiratory volume in one second (FEV1) is the standard to monitor the lung function after transplantation, and is used to evaluate the stage and severity of lung allograft diseases. However, according to a literature review we performed, the very few studies that have investigated the FEV1 evolution, and its relationship with outcomes such as death or chronic lung allograft dysfunction, were commonly based on cohort with insufficient data variety and completeness. Importantly, these studies lacked external validation, multidimensional approach, and none has attempted to identify the main profiles of FEV1 trajectories and their associated parameters. As such, the determinants and long-term outcomes of FEV1 trajectories are still poorly understood. A multidimensional, trajectory-based approach may help unveil clinically relevant organ function profiles among lung recipients. Indeed, several studies have shown the potential existence of underlying trajectories of transplanted organs' function and diseases, and their associations with outcomes and relevance for patient management, such as in kidney or heart transplantation. These studies used a unsupervised approach, which permitted to erase any preconceived clinical ideas. Overall, this approach has shown its value in several medical specialties, in particular in image analysis, oncology, or cardiology. Therefore, the goal of this study was to identify and validate the FEV1 trajectories after lung transplantation, as well as their determinants and outcomes, using an international cohort of lung recipients, with a protocol-based collection of FEV1 repeated assessments and clinical, biological, histological and immunological data.

Official Title
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Trajectories of FEV1 After Lung Transplantation: Determinants and Clinical Outcomes

Conditions
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Lung Transplant Failure and Rejection, Chronic Lung Allograft Dysfunction

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Double lung transplant recipients Age 18 years or older at the time of transplant Transplant between January 1, 2010 and December 31, 2020 At least 2 PFTs available for analysis Exclusion Criteria: Did not consent to clinical data use for research purposes Multi-organ transplant

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Foch hospital<br>Lung recipients from Foch hospital, Suresnes, France | |
| Bichat hospital<br>Lung recipients from Bichat hospital, Paris, France | |
| Nantes hospital<br>Lung recipients from Nantes hospital, Nantes, France | |
| San Antonio center<br>Lung recipients from Pulmonary hypertension center, San Antonio, Texas, US | |
| Marie-Lannelongue hospital<br>Lung recipients from Marie-Lannelongue hospital, Le Plessis-Robinson, France | |
| Bordeaux hospital<br>Lung recipients from Bordeaux hospital, Nantes, France | |
| Marseille hospital<br>Lung recipients from Marseille hospital, Marseille, France | |
| Toulouse hospital<br>Lung recipients from Toulouse hospital, Toulouse, France | |
| Strasbourg hospital<br>Lung recipients from Strasbourg hospital, Strasbourg, France | |
| Grenoble hospital<br>Lung recipients from Grenoble hospital, Grenoble, France | |
| Cochin hospital<br>Lung recipients from Strasbourg hospital, Paris, France | |
| Hospital center Mayenne North<br>Lung recipients from Hospital center Mayenne North, Mayenne, France | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 trajectories | FEV1 trajectories of the lung recipient | Up to 10 years after lung transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient death | Patient death after lung transplantation | Up to 10 years after lung transplantation | 
| Allograft failure | Allograft failure after lung transplantation | Up to 10 years after lung transplantation | 
| Chronic lung allograft dysfunction | CLAD after lung transplantation | Up to 10 years after lung transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung trajectories, Unsupervised analysis, Determinants of FEV1 trajectories