title: Bile acid aspiration associated with lung chemical profile linked to other biomarkers of injury after lung transplantation.
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.
authors.affiliation: Emory Transplant Center, Emory University, Atlanta, GA.
authors.forename: D C
authors.initials: DC
authors.lastname: Neujahr
authors.forename: K
authors.initials: K
authors.lastname: Uppal
authors.forename: S D
authors.initials: SD
authors.lastname: Force
authors.forename: F
authors.initials: F
authors.lastname: Fernandez
authors.forename: C
authors.initials: C
authors.lastname: Lawrence
authors.forename: A
authors.initials: A
authors.lastname: Pickens
authors.forename: R
authors.initials: R
authors.lastname: Bag
authors.forename: C
authors.initials: C
authors.lastname: Lockard
authors.forename: A D
authors.initials: AD
authors.lastname: Kirk
authors.forename: V
authors.initials: V
authors.lastname: Tran
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: D P
authors.initials: DP
authors.lastname: Jones
authors.forename: Y
authors.initials: Y
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts; D015415:Biomarkers / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D019295:Computational Biology; D005260:Female; D005500:Follow-Up Studies; D005764:Gastroesophageal Reflux / Q000150:complications; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000473:pathology / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D025341:Principal Component Analysis; D011379:Prognosis; D053120:Respiratory Aspiration / Q000150:complications*; D012307:Risk Factors
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers
keywords: Aspiration; bile acid; lung transplantation; metabolomics