학술논문
Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.
Document Type
Academic Journal
Author
Todd JL; Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina. Electronic address: jamie.todd@duke.edu.; Weber JM; Duke Clinical Research Institute, Durham, North Carolina.; Kelly FL; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Neely ML; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina.; Nagler A; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Carmack D; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Frankel CW; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Brass DM; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Belperio JA; David Geffen School of Medicine, University of California, Los Angeles, California.; Budev MM; Cleveland Clinic, Cleveland, Ohio.; Hartwig MG; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Martinu T; Toronto General Hospital Research Institute, Toronto, Ontario, Canada.; Reynolds JM; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Shah PD; Johns Hopkins University School of Medicine, Baltimore, Maryland.; Singer LG; Toronto General Hospital Research Institute, Toronto, Ontario, Canada.; Snyder LD; Department of Medicine, Duke University Medical Center, Durham, North Carolina.; Weigt SS; David Geffen School of Medicine, University of California, Los Angeles, California.; Palmer SM; Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 9102703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3117 (Electronic) Linking ISSN: 10532498 NLM ISO Abbreviation: J Heart Lung Transplant Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Chronic lung allograft dysfunction (CLAD) increases morbidity and mortality for lung transplant recipients. Club cell secretory protein (CCSP), produced by airway club cells, is reduced in the bronchoalveolar lavage fluid (BALF) of lung recipients with CLAD. We sought to understand the relationship between BALF CCSP and early posttransplant allograft injury and determine if early posttransplant BALF CCSP reductions indicate later CLAD risk.
Methods: We quantified CCSP and total protein in 1606 BALF samples collected over the first posttransplant year from 392 adult lung recipients at 5 centers. Generalized estimating equation models were used to examine the correlation of allograft histology or infection events with protein-normalized BALF CCSP. We performed multivariable Cox regression to determine the association between a time-dependent binary indicator of normalized BALF CCSP level below the median in the first posttransplant year and development of probable CLAD.
Results: Normalized BALF CCSP concentrations were 19% to 48% lower among samples corresponding to histological allograft injury as compared with healthy samples. Patients who experienced any occurrence of a normalized BALF CCSP level below the median over the first posttransplant year had a significant increase in probable CLAD risk independent of other factors previously linked to CLAD (adjusted hazard ratio 1.95; p = 0.035).
Conclusions: We discovered a threshold for reduced BALF CCSP to discriminate future CLAD risk; supporting the utility of BALF CCSP as a tool for early posttransplant risk stratification. Additionally, our finding that low CCSP associates with future CLAD underscores a role for club cell injury in CLAD pathobiology.
Competing Interests: Disclosure statement None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
(Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
Methods: We quantified CCSP and total protein in 1606 BALF samples collected over the first posttransplant year from 392 adult lung recipients at 5 centers. Generalized estimating equation models were used to examine the correlation of allograft histology or infection events with protein-normalized BALF CCSP. We performed multivariable Cox regression to determine the association between a time-dependent binary indicator of normalized BALF CCSP level below the median in the first posttransplant year and development of probable CLAD.
Results: Normalized BALF CCSP concentrations were 19% to 48% lower among samples corresponding to histological allograft injury as compared with healthy samples. Patients who experienced any occurrence of a normalized BALF CCSP level below the median over the first posttransplant year had a significant increase in probable CLAD risk independent of other factors previously linked to CLAD (adjusted hazard ratio 1.95; p = 0.035).
Conclusions: We discovered a threshold for reduced BALF CCSP to discriminate future CLAD risk; supporting the utility of BALF CCSP as a tool for early posttransplant risk stratification. Additionally, our finding that low CCSP associates with future CLAD underscores a role for club cell injury in CLAD pathobiology.
Competing Interests: Disclosure statement None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
(Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)