Staphylococcus via an Interaction With the ELR+ CXC Chemokine ENA-78 Is Associated With BOS

Abstract

Staphylococcus aureus is the most commonly isolated gram-positive bacterium after lung transplantation and has been associated with poor post-transplant outcomes, but its effect on BOS and death in the context of the allograft inflammatory environment has not been studied. A three-state Cox semi-Markovian model was used to determine the influence of allograft S. aureus and the ELR+ CXC chemokines on the survival rates and cause-specific hazards for movement 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). Acute rejection, pseudomonas pneumonia, BALF CXCL5 and its interaction with S. aureus all increased the likelihood of transition from transplant to BOS. Transition to death from transplant was facilitated by pseudomonas infection and single lung transplant. Movement from BOS to death was affected by the interaction between aspergillus, pseudomonas and CXCL5, but not S. aureus. S. aureus isolation had state specific effects after lung transplantation and only in concert with elevated BALF CXCL5 concentrations did it augment the risk of BOS. Pseudomonas and elevated BALF concentrations of CXCL5 continued as significant risk factors for BOS and death after BOS in lung transplantation.

Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation

“…Additionally, we report that Pseudomonas aeruginosa isolation is associated with worse CLAD‐free survival, as is the cumulative number of positive cultures for Pseudomonas aeruginosa . Our multivariable analysis also identified Aspergillus isolation, and the development of DSA as risk factors for worse CLAD‐free survival on multivariable analysis, which is consistent with reports of them being risk factors for deleterious long‐term outcomes after lung transplantation . Our findings are consistent with those of the University of California, Los Angeles group who had previously reported that the likelihood of transition from transplant to chronic rejection and death is increased by the interactions between Pseudomonas aeruginosa, Aspergillus, and ELR + CXC chemokines derived from lung epithelial cells that can act via its receptor CXCR2 (IL‐8 receptor β) .…”

“…“DSA clearance” was defined as all DSA tests being negative after an initial positive result, and the time between the first positive and the negative result after which all other results remained negative was defined as the “time to DSA clearance”. A positive bacterial culture from a bronchial wash or BAL was defined as “bacterial isolation” . We did not attempt to distinguish between infection and colonization.…”

Graft Loss and CLAD-Onset Is Hastened by Viral Pneumonia After Lung Transplantation

“…1,2 A diverse group of both infectious and noninfectious posttransplant events are associated with an increased risk of subsequent CLAD. [3][4][5][6][7][8][9][10] Bacterial and viral infections, however, make up the bulk of identifiable posttransplant insults. 5,[11][12][13] The introduction of respiratory virus multiplex polymerase chain reaction (PCR) has increased the detection and awareness of the community acquired respiratory viruses (CARV).…”

Infectious Triggers of Chronic Lung Allograft Dysfunction

“…Gram-negative bacteria make up the majority of bacterial infections, with Pseudomonas aeruginosa being the most frequently isolated, between 25 and 58 % of the time [54,[63][64][65]. At our center, like others, Staphylococcus aureus is the most frequent gram-positive bacteria isolated in 14 to 30 % of cases (15 % of our recipients) [54,59,62,[64][65][66].…”