• Am. J. Respir. Crit. Care Med. · Mar 2013

    Interaction between Pseudomonas and CXC chemokines increases risk of bronchiolitis obliterans syndrome and death in lung transplantation.

    • Aric L Gregson, Xiaoyan Wang, S Sam Weigt, Vyacheslav Palchevskiy, Joseph P Lynch, David J Ross, Bernard M Kubak, Rajan Saggar, Michael C Fishbein, Abbas Ardehali, Gang Li, Robert Elashoff, and John A Belperio.
    • Division of Infectious Diseases, Department of Medicine, School of Public Health, University of California, Los Angeles, CA 90095, USA. a.gregson@ucla.edu
    • Am. J. Respir. Crit. Care Med.. 2013 Mar 1;187(5):518-26.

    RationalePseudomonas 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.ObjectivesTo 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.MethodsA 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.Measurements And Main ResultsThe 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.ConclusionsOur 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.

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