title: Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients.
abstract: Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases.
authors.affiliation: J. Craig Venter Institute, Rockville, MD.
authors.forename: J
authors.identifier: 0000-0002-3997-4561
authors.initials: J
authors.lastname: Shankar
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: M H
authors.initials: MH
authors.lastname: Nguyen
authors.affiliation: Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: M M
authors.initials: MM
authors.lastname: Crespo
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Kwak
authors.affiliation: J. Craig Venter Institute, Rockville, MD.
authors.forename: S K
authors.initials: SK
authors.lastname: Lucas
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: K J
authors.initials: KJ
authors.lastname: McHugh
authors.affiliation: J. Craig Venter Institute, Rockville, MD.
authors.forename: S
authors.initials: S
authors.lastname: Mounaud
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: J F
authors.initials: JF
authors.lastname: Alcorn
authors.affiliation: Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: J M
authors.initials: JM
authors.lastname: Pilewski
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA.
authors.forename: N
authors.initials: N
authors.lastname: Shigemura
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: J K
authors.initials: JK
authors.lastname: Kolls
authors.affiliation: J. Craig Venter Institute, Rockville, MD.
authors.forename: W C
authors.initials: WC
authors.lastname: Nierman
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.|VA Pittsburgh Healthcare System, Division of Infectious Diseases, Pittsburgh, PA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D001991:Bronchitis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D012189:Retrospective Studies; D014136:Tracheitis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D066027:Transplant Recipients
chemical_list: D016207:Cytokines