title: Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection.
abstract: BACKGROUND
  Obliterative bronchiolitis (OB) remains one of the leading causes of death in lung transplant recipients after 2 years, and acute rejection (AR) of lung allograft is a major risk factor for OB. Treatment of AR may reduce the incidence of OB, although diagnosis of AR often requires bronchoscopic lung biopsy. In this study, we evaluated the utility of exhaled-breath biomarkers for the non-invasive diagnosis of AR.
  
  
  METHODS
  We obtained breath samples from 44 consecutive lung transplant recipients who attended ambulatory follow-up visits for the Johns Hopkins Lung Transplant Program. Bronchoscopy within 7 days of their breath samples showed histopathology in 21 of these patients, and we included them in our analysis. We measured hydrocarbon markers of pro-oxidant events (ethane and 1-pentane), isoprene, acetone, and sulfur-containing compounds (hydrogen sulfide and carbonyl sulfide) in exhaled breath and compared their levels to the lung histopathology, graded as stable (non-rejection) or AR. None of the study subjects were diagnosed with OB or infection at the time of the clinical bronchoscopy.
  
  
  RESULTS
  We found no significant difference in exhaled levels of hydrocarbons, acetone, or hydrogen sulfide between the stable and AR groups. However, we did find significant increase in exhaled carbonyl sulfide (COS) levels in AR subjects compared with stable subjects. We also observed a trend in 7 of 8 patients who had serial sets of breath and histopathology data that supported a role for COS as a breath biomarker of AR.
  
  
  CONCLUSIONS
  This study demonstrated elevations in exhaled COS levels in subjects with AR compared with stable subjects, suggesting a diagnostic role for this non-invasive biomarker. Further exploration of breath analysis in lung transplant recipients is warranted to complement fiberoptic bronchoscopy and obviate the need for this procedure in some patients.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. sean_studer@mssm.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Studer
authors.forename: J B
authors.initials: JB
authors.lastname: Orens
authors.forename: I
authors.initials: I
authors.lastname: Rosas
authors.forename: J A
authors.initials: JA
authors.lastname: Krishnan
authors.forename: K A
authors.initials: KA
authors.lastname: Cope
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: J V
authors.initials: JV
authors.lastname: Conte
authors.forename: P B
authors.initials: PB
authors.lastname: Becker
authors.forename: T H
authors.initials: TH
authors.lastname: Risby
mesh_terms: D000096:Acetone / Q000032:analysis; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D001944:Breath Tests; D002070:Butadienes / Q000032:analysis; D004980:Ethane / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D045782:Hemiterpenes; D006801:Humans; D006862:Hydrogen Sulfide / Q000032:analysis; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010420:Pentanes / Q000032:analysis; D013461:Sulfur Oxides / Q000032:analysis; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; D013461:Sulfur Oxides; C005059:isoprene; D000096:Acetone; C010063:carbonyl sulfide; D004980:Ethane; D006862:Hydrogen Sulfide