Abstract
We evaluated whether lysyl oxidase-like 2 (LOXL2), which promotes cross-linking of collagen in pathological stroma, was detectable in serum from idiopathic pulmonary fibrosis (IPF) patients, and assessed its relationship with IPF disease progression.
Patients from the ARTEMIS-IPF (n=69) and the Genomic and Proteomic Analysis of Disease Progression in IPF (GAP) (n=104) studies were analysed. Baseline serum LOXL2 (sLOXL2) levels were compared with baseline clinical and physiological surrogates of disease severity, and the association with IPF disease progression was assessed using a classification and regression tree (CART) method.
sLOXL2 correlated weakly with forced vital capacity and carbon monoxide diffusion capacity (r -0.24–0.05) in both cohorts. CART-determined thresholds were similar: ARTEMIS-IPF 800 pg·mL−1 and GAP 700 pg·mL−1. In ARTEMIS-IPF, higher sLOXL2 (>800 pg·mL−1) was associated with increased risk for disease progression (hazard ratio (HR) 5.41, 95% 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 disease progression 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 disease progression. However, due to multiple limitations, these results require validation.
Abstract
Higher baseline sLOXL2 levels: no correlation with IPF severity, but association with disease progression http://ow.ly/sEbGW
Footnotes
For editorial comments see page 1233.
This article has supplementary material available from www.erj.ersjournals.com
Clinical trial: This study is registered at www.ClinicalTrials.gov with identifier number NCT00768300 and NCT 00373841.
Support statement: This work was funded by Gilead Sciences Inc. and a National Institutes of Health grant (grant number P50HL084932).
Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com
- Received May 8, 2013.
- Accepted September 19, 2013.
- ©ERS 2014