Clinical trial NCT05934617: Trajectories of FEV1 After Lung Transplantation
Official title: Trajectories of FEV1 After Lung Transplantation: Determinants and Clinical Outcomes
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Lung Transplant Failure and Rejection
Chronic Lung Allograft Dysfunction
Keywords: Lung trajectories
Unsupervised analysis
Determinants of FEV1 trajectories
Lead sponsor: Paris Translational Research Center for Organ Transplantation
Sponsor class: OTHER
First posted: 2023-07-07
Enrollment: 2500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients who received a bilateral lung transplantation

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: FEV1 trajectories
timeFrame: Up to 10 years after lung transplantation
Secondary outcomes:
measure: Patient death
timeFrame: Up to 10 years after lung transplantation
measure: Allograft failure
timeFrame: Up to 10 years after lung transplantation
measure: Chronic lung allograft dysfunction
timeFrame: Up to 10 years after lung transplantation
Other outcomes:
Locations:
city: Suresnes
country: France
facility: Foch hospital
Study officials:
affiliation: Foch hospital
name: Antoine Roux, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.