Influence of human leukocyte antigen mismatching on bronchiolitis obliterans syndrome in lung transplantation

Don Hayes, Sylvester M. Black, Joseph D. Tobias, Benjamin T. Kopp, Stephen E. Kirkby, Heidi - Mansour, Bryan A. Whitson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Methods The UNOS database was queried for the period 1997 to 2013 to examine HLA mismatching and its association with BOS in LTx. Results Of 16,959 first-time adult LTx recipients, 16,854 were included in the univariate Cox analysis and Kaplan-Meier survival function evaluation, and 14,578 were included in multivariate Cox models. Multivariate Cox analysis showed that the number of total HLA mismatches was significantly associated with greater hazard of BOS (HR = 1.060; 95% CI 1.013 to 1.108; p = 0.011), as was the presence of 2 HLA-A mismatches, when compared with 0 or 1 mismatch at that locus (HR = 1.128; 95% CI 1.026 to 1.240; p = 0.012). These results were confirmed using competing-risks regression models that adjusted for death before BOS diagnosis. Multivariate Cox models identified no significant association with BOS hazard for HLA-B (HR = 1.014; 95% CI 0.914 to 1.126; p = 0.785) or HLA-DR (HR = 1.085; 95% CI 0.987 to 1.193; p = 0.090) mismatches. Higher body mass index was associated with increased risk for BOS, whereas older age was protective against BOS. Induction with alemtuzumab (HR = 0.343; 95% CI 0.252 to 0.467; p <0.001) or basiliximab (HR = 0.862; 95% CI 0.758 to 0.980; p = 0.023) and longer ischemic time (HR = 0.909; 95% CI 0.877 to 0.942; p <0.001) were associated with lower hazard of BOS. Conclusions Total HLA mismatches are associated with increased risk for BOS, specifically at the A locus. Induction with alemtuzumab or basiliximab reduced the risk, whereas greater ischemic time appears to also be protective.

Original languageEnglish (US)
Pages (from-to)186-194
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume35
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Bronchiolitis Obliterans
Lung Transplantation
HLA Antigens
Proportional Hazards Models
Kaplan-Meier Estimate
Body Mass Index
Multivariate Analysis
Databases

Keywords

  • bronchiolitis obliterans syndrome
  • hazard risk
  • human leukocyte antigen
  • induction therapy
  • lung transplantation
  • mismatch
  • obliterative bronchiolitis
  • survival

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Influence of human leukocyte antigen mismatching on bronchiolitis obliterans syndrome in lung transplantation. / Hayes, Don; Black, Sylvester M.; Tobias, Joseph D.; Kopp, Benjamin T.; Kirkby, Stephen E.; Mansour, Heidi -; Whitson, Bryan A.

In: Journal of Heart and Lung Transplantation, Vol. 35, No. 2, 01.02.2016, p. 186-194.

Research output: Contribution to journalArticle

Hayes, Don ; Black, Sylvester M. ; Tobias, Joseph D. ; Kopp, Benjamin T. ; Kirkby, Stephen E. ; Mansour, Heidi - ; Whitson, Bryan A. / Influence of human leukocyte antigen mismatching on bronchiolitis obliterans syndrome in lung transplantation. In: Journal of Heart and Lung Transplantation. 2016 ; Vol. 35, No. 2. pp. 186-194.
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abstract = "Background Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Methods The UNOS database was queried for the period 1997 to 2013 to examine HLA mismatching and its association with BOS in LTx. Results Of 16,959 first-time adult LTx recipients, 16,854 were included in the univariate Cox analysis and Kaplan-Meier survival function evaluation, and 14,578 were included in multivariate Cox models. Multivariate Cox analysis showed that the number of total HLA mismatches was significantly associated with greater hazard of BOS (HR = 1.060; 95{\%} CI 1.013 to 1.108; p = 0.011), as was the presence of 2 HLA-A mismatches, when compared with 0 or 1 mismatch at that locus (HR = 1.128; 95{\%} CI 1.026 to 1.240; p = 0.012). These results were confirmed using competing-risks regression models that adjusted for death before BOS diagnosis. Multivariate Cox models identified no significant association with BOS hazard for HLA-B (HR = 1.014; 95{\%} CI 0.914 to 1.126; p = 0.785) or HLA-DR (HR = 1.085; 95{\%} CI 0.987 to 1.193; p = 0.090) mismatches. Higher body mass index was associated with increased risk for BOS, whereas older age was protective against BOS. Induction with alemtuzumab (HR = 0.343; 95{\%} CI 0.252 to 0.467; p <0.001) or basiliximab (HR = 0.862; 95{\%} CI 0.758 to 0.980; p = 0.023) and longer ischemic time (HR = 0.909; 95{\%} CI 0.877 to 0.942; p <0.001) were associated with lower hazard of BOS. Conclusions Total HLA mismatches are associated with increased risk for BOS, specifically at the A locus. Induction with alemtuzumab or basiliximab reduced the risk, whereas greater ischemic time appears to also be protective.",
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AU - Mansour, Heidi -

AU - Whitson, Bryan A.

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N2 - Background Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Methods The UNOS database was queried for the period 1997 to 2013 to examine HLA mismatching and its association with BOS in LTx. Results Of 16,959 first-time adult LTx recipients, 16,854 were included in the univariate Cox analysis and Kaplan-Meier survival function evaluation, and 14,578 were included in multivariate Cox models. Multivariate Cox analysis showed that the number of total HLA mismatches was significantly associated with greater hazard of BOS (HR = 1.060; 95% CI 1.013 to 1.108; p = 0.011), as was the presence of 2 HLA-A mismatches, when compared with 0 or 1 mismatch at that locus (HR = 1.128; 95% CI 1.026 to 1.240; p = 0.012). These results were confirmed using competing-risks regression models that adjusted for death before BOS diagnosis. Multivariate Cox models identified no significant association with BOS hazard for HLA-B (HR = 1.014; 95% CI 0.914 to 1.126; p = 0.785) or HLA-DR (HR = 1.085; 95% CI 0.987 to 1.193; p = 0.090) mismatches. Higher body mass index was associated with increased risk for BOS, whereas older age was protective against BOS. Induction with alemtuzumab (HR = 0.343; 95% CI 0.252 to 0.467; p <0.001) or basiliximab (HR = 0.862; 95% CI 0.758 to 0.980; p = 0.023) and longer ischemic time (HR = 0.909; 95% CI 0.877 to 0.942; p <0.001) were associated with lower hazard of BOS. Conclusions Total HLA mismatches are associated with increased risk for BOS, specifically at the A locus. Induction with alemtuzumab or basiliximab reduced the risk, whereas greater ischemic time appears to also be protective.

AB - Background Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Methods The UNOS database was queried for the period 1997 to 2013 to examine HLA mismatching and its association with BOS in LTx. Results Of 16,959 first-time adult LTx recipients, 16,854 were included in the univariate Cox analysis and Kaplan-Meier survival function evaluation, and 14,578 were included in multivariate Cox models. Multivariate Cox analysis showed that the number of total HLA mismatches was significantly associated with greater hazard of BOS (HR = 1.060; 95% CI 1.013 to 1.108; p = 0.011), as was the presence of 2 HLA-A mismatches, when compared with 0 or 1 mismatch at that locus (HR = 1.128; 95% CI 1.026 to 1.240; p = 0.012). These results were confirmed using competing-risks regression models that adjusted for death before BOS diagnosis. Multivariate Cox models identified no significant association with BOS hazard for HLA-B (HR = 1.014; 95% CI 0.914 to 1.126; p = 0.785) or HLA-DR (HR = 1.085; 95% CI 0.987 to 1.193; p = 0.090) mismatches. Higher body mass index was associated with increased risk for BOS, whereas older age was protective against BOS. Induction with alemtuzumab (HR = 0.343; 95% CI 0.252 to 0.467; p <0.001) or basiliximab (HR = 0.862; 95% CI 0.758 to 0.980; p = 0.023) and longer ischemic time (HR = 0.909; 95% CI 0.877 to 0.942; p <0.001) were associated with lower hazard of BOS. Conclusions Total HLA mismatches are associated with increased risk for BOS, specifically at the A locus. Induction with alemtuzumab or basiliximab reduced the risk, whereas greater ischemic time appears to also be protective.

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