title: Interaction between Pseudomonas and CXC chemokines increases risk of bronchiolitis obliterans syndrome and death in lung transplantation.
abstract: BACKGROUND
  Pseudomonas aeruginosa is the most commonly isolated gram-negative bacterium after lung transplantation and has been shown to up-regulate glutamic acid-leucine-arginine-positive (ELR(+)) CXC chemokines associated with bronchiolitis obliterans syndrome (BOS), but the effect of pseudomonas on BOS and death has not been well defined.
  
  
  OBJECTIVE
  To determine if the influence of pseudomonas isolation and ELR(+) CXC chemokines on the subsequent development of BOS and the occurrence of death is time dependent.
  
  
  METHODS
  A three-state model was developed to assess the likelihood of transitioning from lung transplant (state 1) to BOS (state 2), from transplant (state 1) to death (state 3), and from BOS (state 2) to death (state 3). This Cox semi-Markovian approach determines state survival rates and cause-specific hazards for movement from one state to another.
  
  
  RESULTS
  The likelihood of transition from transplant to BOS was increased by acute rejection, CXCL5, and the interaction between pseudomonas and CXCL1. The pseudomonas effect in this transition was due to infection rather than colonization. Movement from transplant to death was facilitated by pseudomonas infection and single lung transplant. Transition from BOS to death was affected by the length of time in state 1 and by the interactions between any pseudomonas isolation and CXCL5 and aspergillus, either independently or in combination.
  
  
  CONCLUSIONS
  Our model demonstrates that common post-transplantation events drive movement from one post-transplantation state to another and influence outcomes differently depending upon when after transplantation they occur. Pseudomonas and the ELR(+) CXC chemokines may interact to negatively influence lung transplant outcomes.
authors: Division of Infectious Diseases, Department of Medicine, School of Public Health, University of California, Los Angeles, CA 90095, USA. a.gregson@ucla.edu
authors: Aric L
authors: AL
authors: Gregson
authors: Xiaoyan
authors: X
authors: Wang
authors: S Sam
authors: SS
authors: Weigt
authors: Vyacheslav
authors: V
authors: Palchevskiy
authors: Joseph P
authors: JP
authors: Lynch
authors: David J
authors: DJ
authors: Ross
authors: Bernard M
authors: BM
authors: Kubak
authors: Rajan
authors: R
authors: Saggar
authors: Michael C
authors: MC
authors: Fishbein
authors: Abbas
authors: A
authors: Ardehali
authors: Gang
authors: G
authors: Li
authors: Robert
authors: R
authors: Elashoff
authors: John A
authors: JA
authors: Belperio
mesh_terms: D001989:Bronchiolitis Obliterans / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D002353:Carrier State / Q000453:epidemiology*; D019743:Chemokines, CXC / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015141:Los Angeles / Q000453:epidemiology; D016040:Lung Transplantation / Q000401:mortality*; D008390:Markov Chains; D011379:Prognosis; D016016:Proportional Hazards Models; D011552:Pseudomonas Infections / Q000453:epidemiology*; D011550:Pseudomonas aeruginosa; D012307:Risk Factors
chemical_list: D019743:Chemokines, CXC