Serum Periostin at 1 y Is Associated With Subsequent Chronic Lung Allograft Dysfunction After Lung Transplantation: A Multicenter Validation Study

Background. Chronic lung allograft dysfunction (CLAD) remains the leading cause of late morbidity and mortality after lung transplantation, yet clinically useful biomarkers capable of identifying recipients at risk before overt functional decline are lacking. We previously identified serum periostin as a potential biomarker associated with bronchiolitis obliterans syndrome in a single-center cohort. Methods. In this multicenter validation study, we analyzed prospectively biobanked serum samples from the Korean Organ Transplant Registry. Serum periostin, transforming growth factor-beta 1, and interleukin-13 were measured in samples obtained 1 y after lung transplantation. Time-to-event analyses were landmarked at the 1-y biomarker measurement to evaluate associations with subsequent CLAD development. Cox proportional hazards models adjusted for prespecified clinical covariates were used. A periostin cutoff derived from the prior discovery cohort (66.2 ng/mL) was prespecified for validation. Results. Among 202 lung transplant recipients who survived to 1 y, 33 (16.3%) developed CLAD during follow-up. One-year periostin levels were significantly higher in recipients who developed CLAD than in those who remained CLAD-free (84.4 [73.0-114.6] versus 38.2 [26.6-54.3] ng/mL; P < 0.001). In multivariable analyses, higher periostin levels remained associated with increased CLAD risk (adjusted hazard ratio, 1.26 per SD increase; 95% confidence interval, 1.08-1.47; P = 0.003). The prespecified periostin cutoff effectively stratified CLAD-free survival. Conclusions. Serum periostin levels measured 1 y after lung transplantation were associated with subsequent CLAD development. These findings support serum periostin as a clinically informative biomarker for risk stratification among lung transplant recipients who survive the early posttransplant period.