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To evaluate the effect of cold ischemic time (CIT) on donor pathogen transmission after lung transplantation (LTx). We reviewed data of 59 patients from 2011 to 2018 and analyzed the cultures results of donor bronchial aspirate (DBA), graft endobronchial bacterial swab (GEBS), recipient bacterial status before transplantation (RBT) and postoperative recipient bronchial aspirate (RBA) in relation to donor hospital length of stay (LOS), CIT and to recipient intubation time, Intensive Care Unit (ICU) and hospital LOS, perioperative and infection related deaths. The groups were compared using Mann-Withney U test and Fisher's exact test, death risk was analyzed as hazard ratio with 95% CI. Single LTx was in 17 cases, bilateral LTx in 42. First/only lung CIT1 was 403±107 min, second lung CIT2 - 541±114 min (the data are shown as mean ± Standard Deviation). Cultures were positive in 42,2% DBA, 83,1% GEBS, 79,7% RTB, 33,9% RBA. Longer donor hospital LOS (132±52 v.100±79 hrs) was associated with isolation of DBA Gram-negative bacteria (n=16), especially A. baumannii). Longer CIT2 (600±109 v. 518±108 min) was related to Gram-positive bacteria other than MSSA in GEBS and it caused recipient's longer ICU LOS (21±18 v. 10±13 days). Longer CIT1 (476±113 v. 388±100 min) and CIT2 (613±91 v. 522±113 min) was associated with growing the new pathogens in RBA. Longer CIT1 (440±102 v. 374±102 min) and CIT2 (584±101 v. 498±111 min) caused prolonged recipient intubation time above 3 days (n=26) and CIT2 (607±93 v. 521±113 min) was related to recipient perioperative death (n=10), but these two factors were not affected by positive DBA, GEBS nor RBA.. Recipient infection deaths (n=4), recipient ICU LOS above 7 days (n=21) and hospital LOS above 30 days (n=30) were not related to DBA, GEBS nor RBA. Positive DBA, GEBS and RBA did not increase recipient death risk - HR 0,690; 0,348 and 1,369 respectively. The cultures GEBS brought more information than DBA. Longer CIT increased Gram-positive bacteria load other than MSSA in GEBS. Donor hospital LOS was correlated with Gram-negative bacteria colonization. Positive cultures of DBA, GEBS, RBA did not affect recipient intubation time, ICU and hospital LOS, perioperative or infection related deaths. [ABSTRACT FROM AUTHOR]

The molecular pathogenesis of chronic lung allograft dysfunction (CLAD) is poorly understood. We hypothesized that microarray analysis of TBBs and mucosal biopsies from the third bronchial bifurcation (3BMBs) would provide insight into biological pathways through gene ontology (GO) analysis. We performed gene expression microarray analysis of 498 TBBs and 324 3BMBs from 10 international centers, comparing CLAD+ and CLAD- cases. CLAD was defined per 2019 ISHLT guidelines. Bayes-moderated t-tests were used to identify CLAD-associated genes. We performed GO biological process analysis with CLAD-associated genes with false discovery rate < 0.05. We also identified CLAD-associated transcripts after correcting for time post-transplant and excluding biopsies from patients diagnosed with rejection or infection. In TBBs CLAD-associated GO terms described lung development regulation, injury response, epithelial proliferation, epithelial-mesenchymal transition, and angiogenesis (Fig. 1A). In 3BMBs the GO terms included endocytosis and intracellular trafficking, cell-cell/cell-substrate adhesion, collagen/matrix metabolism, but unlike TBBs included immunity (Fig. 1B). Time correction did not affect transcript associations with CLAD in TBBs but diminished them in 3BMBs. Excluding biopsies with coexistent rejection or infection removed associations in TBBs but strengthened them in 3BMBs even after correcting for time post-transplant. In our biopsy set the molecular CLAD phenotype resembles a parenchymal response to wounding that overlaps other pathologies. CLAD-associated molecular changes were independent of time in TBBs but not 3BMBs, suggesting that CLAD is primarily a time dependent airway process involving injury and either adaptive or innate immunity. Unlike TBBs, molecular changes in 3BMBs were identifiable despite coexistent rejection or infection, suggesting this biopsy format may better capture CLAD information. [ABSTRACT FROM AUTHOR]