Trajectories of FEV1 after lung transplantation and patient outcomes

Abstract

Background: The forced expiratory volume in one second (FEV₁) is the standard measure used to monitor the lung function after lung transplantation. However, little is known about the FEV₁ trajectories post transplantation, and their associations with clinical outcomes.

Methods: Adult patients who received a bilateral lung transplant between January 1, 2010 and January 1, 2021 were included from 15 centers in France, Belgium, Austria and the US. Three French centers formed the development cohort and the remaining centers formed the external validation cohorts. All centers performed routine spirometry measurements commencing shortly after lung transplantation and continuing at regular intervals of maximum three months afterwards. Recipient, donor and transplant characteristics were collected. Latent class mixed models were used to identify FEV₁ trajectories. The number of FEV₁ trajectories was defined according to the Akaike Information Criterion, Bayesian Information Criterion, the discrimination, the entropy and the interpretability of the model.

Findings: A total of 2305 patients were included with 59 034 FEV₁ measurements collected. The median follow-up post-transplantation was 4.3 years (IQR 2.3-6.2). In the development cohort (n=605), the best latent class mixed model identified seven clinically meaningful FEV₁ trajectories. Trajectory #1 (25.6%) was characterized by patients with moderate and stable lung function (3-year patient survival = 79.9%); trajectory #2 (24.0%) and #3 (27.3%) were characterized by patients with moderate/high and stable lung function (3-year patient survival = 96.6% and 95.7% respectively); trajectory #4 (3.8%) was characterized by patients with increasing lung function (3-year patient survival = 69.6%); trajectory #5 (11.7%) was characterized by patients with a slow decline (3-year patient survival = 90.1%); and trajectory #6 (3.0%) and #7 (4.6%) were characterized by patients with accelerated decline (3-year patient survival = 33.3% and 59.5% respectively). Patients belonging to trajectories were associated with gender (p=0.020) and underlying disease (p=0.004). Similar FEV₁ trajectories and patient outcomes were identified in the external validation cohorts on the basis of independent analyses. The trajectories were also confirmed in a series of subpopulations. Last, FEV₁ value and slope at 1 year post transplant were strongly associated with FEV₁ trajectories, in both the development cohort and the external validation cohorts.

Interpretation: We identified and validated FEV₁ trajectories that capture different clinical scenarios associated with post-transplant recipient outcomes. Our results may provide the basis for a trajectory-based risk assessment of lung transplant recipients.

Funding: "Vaincre la mucoviscidose" grant, the association Grégory Lemarchal, ANR grant, PHRC grant, the FP7 collaborative project, IRSRPL grant, the Fondation du Souffle and PLUTO DITCAP grant from Vaincre la Mucoviscidose and Association Grégory Lemarchal.

Keywords: FEV1; Lung; Outcomes; Trajectories; Transplantation.