Trajectories of FEV1 After Lung Transplantation (TRAJLUNG)

Trajectories of FEV1 After Lung Transplantation: Determinants and Clinical Outcomes

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Lung Transplant Failure and Rejection; Chronic Lung Allograft Dysfunction

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 2500

Contacts and Locations

Study Locations

• France
  • Suresnes, France
    • Foch Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients who received a bilateral lung transplantation

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

12

Cohorts and Interventions

Group / Cohort
Foch hospital; Lung recipients from Foch hospital, Suresnes, France
Bichat hospital; Lung recipients from Bichat hospital, Paris, France
Nantes hospital; Lung recipients from Nantes hospital, Nantes, France
San Antonio center; Lung recipients from Pulmonary hypertension center, San Antonio, Texas, US
Marie-Lannelongue hospital; Lung recipients from Marie-Lannelongue hospital, Le Plessis-Robinson, France
Bordeaux hospital; Lung recipients from Bordeaux hospital, Nantes, France
Marseille hospital; Lung recipients from Marseille hospital, Marseille, France
Toulouse hospital; Lung recipients from Toulouse hospital, Toulouse, France
Strasbourg hospital; Lung recipients from Strasbourg hospital, Strasbourg, France
Grenoble hospital; Lung recipients from Grenoble hospital, Grenoble, France
Cochin hospital; Lung recipients from Strasbourg hospital, Paris, France
Hospital center Mayenne North; Lung recipients from Hospital center Mayenne North, Mayenne, France

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Paris Translational Research Center for Organ Transplantation
• Investigators: Principal Investigator: Antoine Roux, MD, PhD, Foch Hospital

Publications and helpful links

General Publications

• GBD Chronic Respiratory Disease Collaborators. Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2020 Jun;8(6):585-596. doi: 10.1016/S2213-2600(20)30105-3.
• Li X, Cao X, Guo M, Xie M, Liu X. Trends and risk factors of mortality and disability adjusted life years for chronic respiratory diseases from 1990 to 2017: systematic analysis for the Global Burden of Disease Study 2017. BMJ. 2020 Feb 19;368:m234. doi: 10.1136/bmj.m234. Erratum In: BMJ. 2020 Aug 6;370:m3150.
• Brakema EA, Tabyshova A, van der Kleij RMJJ, Sooronbaev T, Lionis C, Anastasaki M, An PL, Nguyen LT, Kirenga B, Walusimbi S, Postma MJ, Chavannes NH, van Boven JFM; FRESH AIR collaborators. The socioeconomic burden of chronic lung disease in low-resource settings across the globe - an observational FRESH AIR study. Respir Res. 2019 Dec 21;20(1):291. doi: 10.1186/s12931-019-1255-z.
• Perch M, Hayes D Jr, Cherikh WS, Zuckermann A, Harhay MO, Hsich E, Potena L, Sadavarte A, Lindblad K, Singh TP, Stehlik J; International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-ninth adult lung transplantation report-2022; focus on lung transplant recipients with chronic obstructive pulmonary disease. J Heart Lung Transplant. 2022 Oct;41(10):1335-1347. doi: 10.1016/j.healun.2022.08.007. Epub 2022 Aug 20. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): January 1, 2021
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Lung trajectories; Unsupervised analysis; Determinants of FEV1 trajectories
• Other Study ID Numbers: TRAJLUNG001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data may be shared for research purpose upon reasonable request.
• IPD Sharing Time Frame: After publication
• IPD Sharing Access Criteria: Via email to the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No