Smoking pattern in men and women: A possible contributor to sex differences in smoke-related lung diseases

hoc test odds would be 0.076 [0.25 3 0.303] and corresponding to a post hoc test probability of 7.6% [0.076/(1 1 0.076)]) (8). We designed the classifier to assess organ quality for donor pool expansion strategies, to identify organs for possible rehabilitation on ex vivo lung perfusion, and to identify potential targets for directed therapies in clinical trials. The validation of the pathways identified in this transcript panel highlights the importance of the innate immune system in the development of PGD and identifies its constituent genes as potential therapeutic targets. This work builds on previous work identifying associated pathways and developing clinical predictors important in PGD to assess risk prior to procurement to facilitate decision making for potential therapeutics and advanced surgical therapies (3, 4, 7). Although these results are promising, there are limitations to consider. The cohort sample size was small, therefore reducing overall power. Nonetheless, this study represents a temporal validation in tissue of prior findings in blood and BAL using a conventional machine learning approach. Tissue biopsy is an invasive procedure with associated risks. We validated our classifier in tissue to ensure that all lung compartments were sampled (endothelial, epithelial, and lymphoid), and we acknowledge that further refinement will be necessary to scale to clinical practice. Additionally, translating gene expression prediction to the bedside will require development of point-of-care technologies using abbreviated gene sets, such as those using microfluidics (9). As this study cohort did not overlap with our prior cohorts, we were unable to assess interactions between blood, BAL, and tissue compartments. Although this work is supported by several other studies that show association (3, 4, 10), additional validation will be necessary to confirm discriminant and diagnostic validity and generalizability. In summary, we have demonstrated that transcript analysis of donor lung tissue, using an innate immunity pathway classifier, can be used in conjunction with clinical variables to predict PGD with excellent discrimination and precision. With the ability to identify organ risk, this panel has the potential to alter future PGD clinical trial designs and lead to the development of precision medical approaches. As PGD drives morbidity and mortality associated with lung transplant, further research in this area has the potential to improve outcomes following transplantation.