• Ariss DerHovanessian, Jamie L Todd, Alice Zhang, Ning Li, Aradhna Mayalall, C Ashley Finlen Copeland, Michael Shino, Elizabeth N Pavlisko, W Dean Wallace, Aric Gregson, David J Ross, Rajan Saggar, Joseph P Lynch, John Belperio, Laurie D Snyder, Scott M Palmer, and S Sam Weigt.
• 1 Division of Pulmonary and Critical Care Medicine.
• Ann Am Thorac Soc. 2016 May 1; 13 (5): 627-35.

RationaleThe clinical course of chronic lung allograft dysfunction (CLAD) is heterogeneous. Forced vital capacity (FVC) loss at onset, which may suggest a restrictive phenotype, was associated with worse survival for bilateral lung transplant recipients in one previously published single-center study.ObjectivesWe sought to replicate the significance of FVC loss in an independent, retrospectively identified cohort of bilateral lung transplant recipients and to investigate extended application of this approach to single lung recipients.MethodsFVC loss and other potential predictors of survival after the onset of CLAD were assessed using Kaplan-Meier and Cox proportional hazards models.Measurements And Main ResultsFVC loss at the onset of CLAD was associated with higher mortality in an independent cohort of bilateral lung transplant recipients (hazard ratio [HR], 2.75; 95% confidence interval [CI], 2.02-3.73; P < 0.0001) and in a multicenter cohort of single lung recipients (HR, 1.80; 95% CI, 1.09-2.98; P = 0.02). Including all subjects, the deleterious impact of FVC loss on survival persisted after adjustment for other relevant clinical variables (HR, 2.36; 95% CI, 1.77-3.15; P < 0.0001). In patients who develop CLAD without FVC loss, chest computed tomography features suggestive of pleural or parenchymal fibrosis also predicted worse survival in both bilateral (HR, 2.01; 95% CI, 1.16-5.20; P = 0.02) and single recipients (HR, 2.47; 95% CI, 1.24-10.57; P = 0.02).ConclusionsWe independently validated the prognostic significance of FVC loss for bilateral lung recipients and demonstrated that this approach to CLAD classification also confers prognostic information for single lung transplant recipients. Improved understanding of these discrete phenotypes is critical to the development of effective therapies.

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