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Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.

Publication ,  Journal Article
Todd, JL; Weber, JM; Kelly, FL; Neely, ML; Nagler, A; Carmack, D; Frankel, CW; Brass, DM; Belperio, JA; Budev, MM; Hartwig, MG; Martinu, T ...
Published in: J Heart Lung Transplant
June 2023

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.

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Published In

J Heart Lung Transplant

DOI

EISSN

1557-3117

Publication Date

June 2023

Volume

42

Issue

6

Start / End Page

741 / 749

Location

United States

Related Subject Headings

  • Surgery
  • Retrospective Studies
  • Lung Transplantation
  • Lung
  • Humans
  • Bronchoalveolar Lavage Fluid
  • Biomarkers
  • Allografts
  • Adult
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Todd, J. L., Weber, J. M., Kelly, F. L., Neely, M. L., Nagler, A., Carmack, D., … Palmer, S. M. (2023). Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study. J Heart Lung Transplant, 42(6), 741–749. https://doi.org/10.1016/j.healun.2023.02.1495
Todd, Jamie L., Jeremy M. Weber, Francine L. Kelly, Megan L. Neely, Andrew Nagler, Dylan Carmack, Courtney W. Frankel, et al. “Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.J Heart Lung Transplant 42, no. 6 (June 2023): 741–49. https://doi.org/10.1016/j.healun.2023.02.1495.
Todd, Jamie L., et al. “Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.J Heart Lung Transplant, vol. 42, no. 6, June 2023, pp. 741–49. Pubmed, doi:10.1016/j.healun.2023.02.1495.
Todd JL, Weber JM, Kelly FL, Neely ML, Nagler A, Carmack D, Frankel CW, Brass DM, Belperio JA, Budev MM, Hartwig MG, Martinu T, Reynolds JM, Shah PD, Singer LG, Snyder LD, Weigt SS, Palmer SM. Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study. J Heart Lung Transplant. 2023 Jun;42(6):741–749.
Journal cover image

Published In

J Heart Lung Transplant

DOI

EISSN

1557-3117

Publication Date

June 2023

Volume

42

Issue

6

Start / End Page

741 / 749

Location

United States

Related Subject Headings

  • Surgery
  • Retrospective Studies
  • Lung Transplantation
  • Lung
  • Humans
  • Bronchoalveolar Lavage Fluid
  • Biomarkers
  • Allografts
  • Adult
  • 3202 Clinical sciences