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Objectives: To study the impact of using the US Public Health Service broadened definition of "increased-risk" donors (2013) in comparison with "high-risk" (1994) and standard infectious risk donors on lung transplant recipient outcomes., Methods: Patients who underwent lung transplant between January 1, 2006, and May 31, 2017, in the Scientific Registry of Transplant Recipients were divided into 2 cohorts, recipients of: (1) high-risk donors: January 1, 2006, to October 1, 2013, and (2) increased-risk donors: January 1, 2014, to May 31, 2017, and compared with matched recipients who received standard-risk donors. Risks for acute rejection, patient, and graft survival using propensity score matched cohorts, multivariable logistic, and Cox models were examined., Results: In total, 18,490 lung transplant recipients were analyzed with 36% transplanted during the increased-risk donor definition period. The proportion of donors classified as nonstandard infectious risk increased with the definition change (8% high-risk donors vs 22% increased-risk donors; P < .001). In both cohorts, male patients with a lower forced expiratory volume in 1 second and greater creatinine were more likely to receive an organ from increased risk donors. Neither graft nor patient survival differed by donor type in either period. Acute treated rejection within 1 year did not differ by period for recipients of increased risk donors (odds ratio, 0.87; P = .23) or recipients of high-risk donors (odds ratio, 1.2; P = .27)., Conclusions: The 2013 broadened definition of donor risk increased the proportion of nonstandard infectious risk donors. Recipients of increased/high-risk donors had similar graft and patient survival compared with standard-risk donors., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Dysregulated expression of IL-4 has been linked with allergic diseases. IL-4 expression is controlled at the level of gene transcription by the coordinated action of multiple factors that bind regulatory promoter elements. In addition, alterations in chromatin structure are thought to play a role in regulating the expression of cytokines in the T(H)2 gene cluster, although the biochemical basis for these alterations in human T cells is not well understood., Objective: We sought to define the role of histone acetylation in the regulation of IL4 gene expression in human T cells., Methods: IL-4 protein production was measured by means of ELISA. IL-4 promoter activity was measured with luciferase-based reporter constructs transiently transfected into Jurkat T cells. The acetylation status of histones associated with the IL4 gene was analyzed with chromatin immunoprecipitation assays., Results: IL-4 production from activated peripheral blood T cells was enhanced by the histone deacetylase inhibitor trichostatin A. Overexpression of the type 1 histone deacetylases 1, 2, and 3 inhibited transcription driven by the IL-4 promoter in Jurkat T cells, whereas cotransfection of the histone acetyltransferase CREB-binding protein potentiated IL-4 promoter activity. Using chromatin immunoprecipitation assays, we show that nucleosomes in the proximal IL-4 promoter are acetylated on T-cell activation., Conclusion: Our results demonstrate that the acetylation state of histones associated with the IL-4 promoter is a key regulator of IL4 gene expression.