Bile Acid Aspiration Associated With Lung Chemical Profile Linked to Other Biomarkers of Injury After Lung Transplantation

作者: D. C. Neujahr , K. Uppal , S. D. Force , F. Fernandez , C. Lawrence

DOI: 10.1111/AJT.12631

关键词: Lung transplantationBronchoalveolar lavageMetabolomicsGranzyme BBile acidCXCL9Lung injuryImmunologyLungMedicineImmunology and AllergyPharmacology (medical)Transplantation

摘要: Aspiration of gastrointestinal contents has been linked to worse outcomes following lung transplantation but uncertainty exists about underlying mechanisms. We applied high-resolution metabolomics bronchoalveolar lavage fluid (BALF) in patients with episodic aspiration (defined by bile acids the BALF) identify potential metabolic changes associated aspiration. Paired samples, one and another without, from 29 stable transplant were studied. Liquid chromatography coupled mass spectroscopy was used interrogate metabolomic these samples. Data obtained for 7068 ions representing intermediary metabolites, environmental agents chemicals microbial colonization. A substantial number (2302) differed between acid positive negative samples when analyzed false discovery rate at q = 0.01. These included pathways metabolism. Hierarchical cluster analysis defined clusters that correlated previously reported biomarkers injury including T cell granzyme B level chemoattractants CXCL9 CXCL10. data specifically link presence allografts inflammatory known segregate worsening allograft outcome, provide additional mechanistic insight into association reflux injury.

参考文章(31)
Benjamin D. Medoff, John C. Wain, Edward Seung, Ryan Jackobek, Terry K. Means, Leo C. Ginns, Joshua M. Farber, Andrew D. Luster, CXCR3 and its ligands in a murine model of obliterative bronchiolitis: regulation and function. Journal of Immunology. ,vol. 176, pp. 7087- 7095 ,(2006) , 10.4049/JIMMUNOL.176.11.7087
D. C. Neujahr, S. D. Perez, A. Mohammed, O. Ulukpo, E. C. Lawrence, F. Fernandez, A. Pickens, S. D. Force, M. Song, C. P. Larsen, A. D. Kirk, Cumulative exposure to gamma interferon-dependent chemokines CXCL9 and CXCL10 correlates with worse outcome after lung transplant. American Journal of Transplantation. ,vol. 12, pp. 438- 446 ,(2012) , 10.1111/J.1600-6143.2011.03857.X
J. A. Jackson, E. J. Kim, B. Begley, J. Cheeseman, T. Harden, S. D. Perez, S. Thomas, B. Warshaw, A. D. Kirk, Urinary Chemokines CXCL9 and CXCL10 Are Noninvasive Markers of Renal Allograft Rejection and BK Viral Infection American Journal of Transplantation. ,vol. 11, pp. 2228- 2234 ,(2011) , 10.1111/J.1600-6143.2011.03680.X
Rachel Stovold, Ian A. Forrest, Paul A. Corris, Desmond M. Murphy, Jaclyn A. Smith, Sam Decalmer, Gail E. Johnson, John H. Dark, Jeffrey P. Pearson, Chris Ward, Pepsin, a biomarker of gastric aspiration in lung allografts: A putative association with rejection American Journal of Respiratory and Critical Care Medicine. ,vol. 175, pp. 1298- 1303 ,(2007) , 10.1164/RCCM.200610-1485OC
F D'Ovidio, S Keshavjee, Gastroesophageal reflux and lung transplantation. Diseases of The Esophagus. ,vol. 19, pp. 315- 320 ,(2006) , 10.1111/J.1442-2050.2006.00603.X
Frank D’Ovidio, Marco Mura, Melanie Tsang, Thomas K. Waddell, Michael A. Hutcheon, Lianne G. Singer, Denis Hadjiliadis, Cecilia Chaparro, Carlos Gutierrez, Andrew Pierre, Gail Darling, Mingyao Liu, Shaf Keshavjee, Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation. The Journal of Thoracic and Cardiovascular Surgery. ,vol. 129, pp. 1144- 1152 ,(2005) , 10.1016/J.JTCVS.2004.10.035
Jennifer M. Johnson, Tianwei Yu, Frederick H. Strobel, Dean P. Jones, A practical approach to detect unique metabolic patterns for personalized medicine Analyst. ,vol. 135, pp. 2864- 2870 ,(2010) , 10.1039/C0AN00333F
David C. Neujahr, Adriana C. Cardona, Onome Ulukpo, Mark Rigby, Andres Pelaez, Allan Ramirez, Anthony A. Gal, Seth D. Force, E Clinton Lawrence, Allan D. Kirk, Christian P. Larsen, Dynamics of Human Regulatory T Cells in Lung Lavages of Lung Transplant Recipients Transplantation. ,vol. 88, pp. 521- 527 ,(2009) , 10.1097/TP.0B013E3181B0E719
Xin Chen, Tadayuki Oshima, Toshihiko Tomita, Hirokazu Fukui, Jiro Watari, Takayuki Matsumoto, Hiroto Miwa, Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins. American Journal of Physiology-gastrointestinal and Liver Physiology. ,vol. 301, ,(2011) , 10.1152/AJPGI.00096.2011
Jo Rae Wright, Immunoregulatory functions of surfactant proteins. Nature Reviews Immunology. ,vol. 5, pp. 58- 68 ,(2005) , 10.1038/NRI1528