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

• Type of Material: Article
• Authors: David Neujahr, Emory University; Karan Uppal, Emory University; Seth Force, Emory University; Felix Fernandez, Emory University; E Clinton Lawrence, Emory University; Allan Pickens, Emory University; Remzi Bag, Emory University; C. Lockard, Emory University; Allan Kirk, Emory University; V. Tran, Emory University; K. Lee, Hanyang University; Dean Jones, Emory University; Y. Park, Emory University
• Language: English
• Date: 2014-04-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons
• Final Published Version (URL): http://dx.doi.org/10.1111/ajt.12631
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 14
• Issue: 4
• Start Page: 841
• End Page: 848
• Grant/Funding Information: DCN is supported by an NIH career development grant: 5K08AI079166.
• Keywords: T-CELLS; lung transplantation; CHEMOKINE BIOLOGY; EPITHELIAL BARRIER FUNCTION; bile acid; SURGERY; Life Sciences & Biomedicine; Surgery; BRONCHIOLITIS OBLITERANS SYNDROME; LAPAROSCOPIC ANTIREFLUX SURGERY; CUMULATIVE EXPOSURE; TIGHT JUNCTION PROTEINS; TRANSPLANTATION; SURFACTANT; Transplantation; ALLOGRAFT-REJECTION; metabolomics; Aspiration; Science & Technology; GASTROESOPHAGEAL-REFLUX DISEASE
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, General

Abstract

Aspiration of gastrointestinal contents has been linked to worse outcomes following lung transplantation but uncertainty exists about underlying mechanisms. We applied high-resolution metabolomics of bronchoalveolar lavage fluid (BALF) in patients with episodic aspiration (defined by bile acids in the BALF) to identify potential metabolic changes associated with aspiration. Paired samples, one with bile acids and another without, from 29 stable lung transplant patients were studied. Liquid chromatography coupled to high-resolution mass spectroscopy was used to interrogate metabolomic contents of these samples. Data were obtained for 7068 ions representing intermediary metabolites, environmental agents and chemicals associated with microbial colonization. A substantial number (2302) differed between bile acid positive and negative samples when analyzed by false discovery rate at q=0.01. These included pathways associated with microbial metabolism. Hierarchical cluster analysis defined clusters of chemicals associated with bile acid aspiration that were correlated to previously reported biomarkers of lung injury including T cell granzyme B level and the chemoattractants CXCL9 and CXCL10. These data specifically link bile acids presence in lung allografts to inflammatory pathways known to segregate with worsening allograft outcome, and provide additional mechanistic insight into the association between reflux and lung allograft injury. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.