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Abstract

We evaluated whether lysyl oxidase-like 2 (LOXL2), which promotes cross-linking of collagen in pathologic stroma, was detectable in serum from idiopathic pulmonary fibrosis (IPF) patients, and assessed its relationship with IPF disease progression (DP).Patients from ARTEMIS-IPF (n=69) and the Genomic and Proteomic Analysis of Disease Progression in IPF (GAP) study (n=104) were analysed. Baseline serum LOXL2 levels were compared to baseline clinical and physiologic surrogates of disease severity, and the association with IPF DP was assessed using a classification and regression tree (CART) method.sLOXL2 correlated weakly with forced vital capacity and carbon monoxide diffusion capacity (r range -0.24 to 0.05) in both cohorts. CART-determined thresholds were similar: ARTEMIS-IPF 800 pg·mL-1, GAP 700 pg·mL-1. In ARTEMIS-IPF, higher sLOXL2 (>800 pg·mL-1) was associated with increased risk for DP (hazard ratio [HR] 5.41, 95% confidence interval [CI] 1.65-17.73). Among GAP subjects with baseline spirometric data (n=70), higher sLOXL2 levels (>700 pg·mL-1) were associated with more DP events (HR 1.78, 95% CI 1.01-3.11). Among all GAP subjects, higher sLOXL2 levels were associated with increased risk for mortality (HR 2.28, 95% CI 1.18-4.38).These results suggest that higher sLOXL2 levels are associated with increased risk for IPF DP. However, due to multiple limitations, these results require validation.