Radiological distribution patterns in restrictive chronic lung allograft dysfunction: Impact on survival across all phenotypes
Taiki Fukuda, MD, PhD,
Yusei Nakamura, MD,
Shu-Chi Tseng, MD,
Yuki Ko, MD, PhD,
Staci M. Gagne, MD,
Takeshi Johkoh, MD, PhD,
Yi Li, PhD,
David C. Christiani, MD, MPH, MS,
Hiroya Ojiri, MD, PhD,
Lynette Sholl, MD,
Mizuki Nishino, MD, MPH,
Hiroto Hatabu, MD, PhD
Affiliations
Taiki Fukuda, MD, PhD
Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; Department of Radiology, The Jikei University School of Medicine, Tokyo, Japan; Corresponding author: Taiki Fukuda, MD, PhD, Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115.
Yusei Nakamura, MD
Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Shu-Chi Tseng, MD
Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan City, Taiwan
Yuki Ko, MD, PhD
Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Staci M. Gagne, MD
Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts
Takeshi Johkoh, MD, PhD
Department of Radiology, Kansai Rosai Hospital, Hyogo, Japan
Yi Li, PhD
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
David C. Christiani, MD, MPH, MS
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, Massachusetts
Hiroya Ojiri, MD, PhD
Department of Radiology, The Jikei University School of Medicine, Tokyo, Japan
Lynette Sholl, MD
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Mizuki Nishino, MD, MPH
Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts
Hiroto Hatabu, MD, PhD
Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Background: Restrictive chronic lung allograft dysfunction (CLAD) demonstrates poor outcomes after lung transplantation. However, the impact of radiological patterns on survival within a restrictive CLAD under the new International Society for Heart and Lung Transplantation (ISHLT) criteria remains unclear. Methods: We analyzed retrospectively 241 bilateral lung transplant recipients between 2005 and 2021. CLAD was diagnosed and classified per the 2019 ISHLT criteria. Restrictive phenotype included restrictive allograft syndrome (RAS) and mixed phenotype. In these cases, RAS-like opacities (RLOs) were evaluated both qualitatively and semiquantitatively on computed tomography at CLAD diagnosis. RLOs were classified into upper-predominant and diffuse/lower-predominant distribution groups. Overall survival after CLAD diagnosis was assessed using Kaplan-Meier method with log-rank test and Cox proportional hazards models. Results: Eighty-three patients were diagnosed with CLAD after transplantation. Twenty-one (25.3%) had restrictive phenotype, which showed shorter survival compared to bronchiolitis obliterans syndrome (median survival: 19.8 vs 68.1 months; hazard ratio [HR], 4.53; 95% confidence interval [CI], 1.96-10.49; p < 0.001). Within the restrictive phenotype, the upper-predominant group demonstrated longer survival than the diffuse/lower-predominant group (median survival: 61.1 vs 15.5 months; p = 0.008). The diffuse/lower-predominant group had shorter survival compared to any other CLAD phenotype (HR, 8.45; 95% CI, 3.40-21.04; p < 0.001). The extent of RLOs within each distribution pattern was not significantly associated with survival. Conclusions: In restrictive phenotype CLAD, RLO distribution patterns determined survival outcomes, with diffuse/lower-predominant showing the poorest prognosis, while the extent of RLOs within each pattern did not correlate with prognosis.
