JHLT open · 2025
Prognostic impact of restrictive ventilatory defects in chronic lung allograft dysfunction without restrictive allograft syndrome-like opacities: Stratification of emerging undefined and unclassified phenotypes.
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Fukuda Taiki, Nakamura Yusei, Ko Yuki, Tseng Shu-Chi, Gagne Staci M, Johkoh Takeshi, Li Yi, Christiani David C, Ojiri Hiroya, Sholl Lynette, Nishino Mizuki, Hatabu Hiroto
Аннотация
BACKGROUND: Chronic lung allograft dysfunction (CLAD) remains a critical factor affecting post-lung transplant prognosis. While RAS-like opacities (RLO) are established as poor prognostic indicators, prognostic stratification of non-RLO CLAD cases, including undefined and unclassified phenotypes per the 2019 International Society for Heart and Lung Transplantation (ISHLT) criteria, remains unexplored.
METHODS: We retrospectively analyzed 241 bilateral lung transplant recipients between 2005 and 2021. CLAD was diagnosed and classified per the 2019 ISHLT criteria. Non-RLO patients were stratified by restrictive ventilatory defects for survival analysis. Diaphragmatic elevation and pleural effusion were also evaluated as potential causes of restrictive physiology and their prognostic significance.
RESULTS: Of 83 CLAD patients, 61 (73.5%) had no RLO. In multivariable Cox analysis of non-RLO patients, restrictive ventilatory defects showed a trend toward worse outcomes (Hazard ratio [HR]: 2.56, 95% CI: 0.98-6.71; p = 0.055), while obstructive defects showed no association (HR: 0.88, p = 0.785). When accounting for retransplantation as a competing event using Fine-Gray regression, restrictive ventilatory defects were significantly associated with increased cumulative incidence of death (subdistribution HR: 2.96, 95% CI: 1.17-7.51; p = 0.022). Pleural effusion showed a trend toward association with restrictive defects (p = 0.063) and emerged as an independent prognostic factor (HR: 5.06, 95% CI: 1.57-16.27; p = 0.007).
CONCLUSIONS: Non-RLO CLAD patients with restrictive ventilatory defects demonstrated significantly increased cumulative incidence of death (retransplantation as a competing risk), challenging the assumption that all non-RLO cases follow a favorable BOS-like prognosis. Pleural effusion was identified as a significant independent prognostic marker.
METHODS: We retrospectively analyzed 241 bilateral lung transplant recipients between 2005 and 2021. CLAD was diagnosed and classified per the 2019 ISHLT criteria. Non-RLO patients were stratified by restrictive ventilatory defects for survival analysis. Diaphragmatic elevation and pleural effusion were also evaluated as potential causes of restrictive physiology and their prognostic significance.
RESULTS: Of 83 CLAD patients, 61 (73.5%) had no RLO. In multivariable Cox analysis of non-RLO patients, restrictive ventilatory defects showed a trend toward worse outcomes (Hazard ratio [HR]: 2.56, 95% CI: 0.98-6.71; p = 0.055), while obstructive defects showed no association (HR: 0.88, p = 0.785). When accounting for retransplantation as a competing event using Fine-Gray regression, restrictive ventilatory defects were significantly associated with increased cumulative incidence of death (subdistribution HR: 2.96, 95% CI: 1.17-7.51; p = 0.022). Pleural effusion showed a trend toward association with restrictive defects (p = 0.063) and emerged as an independent prognostic factor (HR: 5.06, 95% CI: 1.57-16.27; p = 0.007).
CONCLUSIONS: Non-RLO CLAD patients with restrictive ventilatory defects demonstrated significantly increased cumulative incidence of death (retransplantation as a competing risk), challenging the assumption that all non-RLO cases follow a favorable BOS-like prognosis. Pleural effusion was identified as a significant independent prognostic marker.