Predictors of survival and transplantation outcomes in Japanese patients with interstitial lung disease referred for lung transplantation: a retrospective single-center study

Lung transplantation is a vital therapeutic option for patients with advanced interstitial lung diseases (ILDs) unresponsive to conventional treatments. In Japan, challenges for this treatment include a long waiting period (average, 2.5 year) and the absence of a comprehensive scoring system. Identifying predictors of survival and transplantation outcomes is critical for improving patient management and optimizing donor lung allocation. This study aimed to examine the clinical characteristics and outcomes of Japanese ILD patients referred for lung transplantation, focusing on factors associated with death and transplantation as competing risks. This retrospective, single-center study included patients with ILD referred to a lung transplant clinic between April 2009 and March 2020. Patients were followed until death or study-end censoring. Diagnoses were established through multidisciplinary discussion, incorporating surgical lung biopsy, bronchoscopic examinations, and high-resolution computed tomography. Statistical analyses (R 4.4.2) treated death and transplantation as competing events. Univariate and multivariate Fine–Gray models were used to evaluate factors influencing the subdistribution hazard ratio (sHR) for death. Cumulative incidence functions for death and transplantation were compared using the Gray test. Among 65 patients (mean age, 52.0 ± 7.9 years; 66% male), 15% underwent transplantation and 42% died before transplantation. The median time to transplantation was 585 days. Univariate Fine–Gray analysis showed that log-transformed C-reactive protein (CRP_ln) was significantly associated with increased mortality risk, whereas partial pressure of oxygen in arterial blood (PaO₂) and percent predicted diffusing capacity of the lung for carbon monoxide (%DLCO) were significantly associated with low mortality risk. Multivariate analysis confirmed that CRP_ln and PaO2 independently influenced mortality. Significant differences in the cumulative incidence of death were observed for PaO₂ (cutoff, 80 Torr), %DLCO (cutoff, 40%), and home oxygen therapy. For transplantation probability, Krebs von den Lungen-6 (KL-6; cutoff, 1,400 U/mL) showed a significant difference (p = 0.03). In Japanese ILD patients referred for lung transplantation, PaO₂, %DLCO, and CRP_ln were independent predictors of mortality. KL-6 was associated with transplantation probability. Continuous monitoring of these biomarkers could aid in the efficient allocation of donor lungs, given the scarcity of donors and prolonged waiting times in Japan.