Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation

Abstract

Acute rejection (AR) is a common complication following lung transplantation and is an established risk factor for bronchiolitis obliterans syndrome (BOS). AR clinical presentation varies considerably and is sometimes associated with an acute decrease in forced expiratory volume in 1 s (FEV1). We hypothesized that lung transplant recipients who experience such spirometrically significant AR (SSAR), as defined by a ≥10% decline in FEV1 relative to the prior pulmonary function test, are subsequently at increased risk for BOS and worse overall survival. In a large single center cohort (n = 339), SSAR occurred in 79 subjects (23%) and significantly increased the risk for BOS (p < 0.0001, HR = 3.2, 95% CI 2.3-4.6) and death (p = 0.0001, HR = 2.3, 95% CI 1.5-3.5). These effects persisted after multivariate adjustment for pre-BOS AR and lymphocytic bronchiolitis burden. An analysis of the subset of patients who experienced severe SSAR (≥20% decline in FEV1) resulted in even greater hazards for BOS and death. Thus, we demonstrate a novel physiological measure that allows discrimination of patients at increased risk for worse posttransplant outcomes. Further studies are needed to determine mechanisms of airflow impairment and whether aggressive clinical interventions could improve post-SSAR outcomes.