Similar to the graft survival models, we tested whether patient factors or other biomarker transformations could alter the HR of CXCL9 or CXCL10 AUC. As shown Z-VAD-FMK clinical trial
in Table 4, several patient factors did alter the HR of CXCL9 or CXCL10 AUC by more than 10% (although the last biomarker measures did not), but did not change the overall finding that the AUC of these biomarkers was associated with BOS. One of the determinants to longevity and quality of life after transplant is the stability and robustness of the lung function after transplantation. There are multiple factors that affect the degree of improvement following transplant, which include the type of disease for which the recipient is transplanted, the nature of the transplant (bilateral vs. single), the age and size of the transplant recipient and the number of episodes of acute rejection. Galunisertib purchase
We assessed the ability of the BALF biomarkers to correlate with FEV1 using both univariate and multivariate models. As shown in Table 5, multiple transformations of the biomarkers were associated with FEV1 function, with the running CXCL9 having the strongest negative association with FEV1. We were interested to test how other factors and biomarker transformations would alter the association between CXCL9 and CXCL10 AUC. In lung function multivariate models, we found no patient or transplant characteristics to be confounders of the association between biomarker AUC and FEV1. In the case of CXCL10 AUC, we found that the last measured biomarker taken closest to the FEV1 could significantly alter the AUC association with FEV1, but for CXCL9 AUC the last measured CXCL9 did not have Cabozantinib
a large impact. In the CXCL10 model, the AUC transformation was not even significant any longer when controlling for the last measure. This suggests for CXCL9, the biomarker was associated with both cumulative effects on lung function as well as instantaneous effects, but for CXCL10, the instantaneous effect was larger and more important than cumulative effects. Because the presence of acute rejection is one predictor of the risk of developing BO, we next assessed how CXCL9 and CXCL10 BALF levels tracked in the setting of acute rejection compared to quiescence. Because of a relatively small number of rejection episodes, we defined rejection as any evidence of venulitis or bronchiolitis (A or B score) by ISHLT criteria as determined by the pulmonary pathologist. In total, 29 of 40 patients had, at least, one episode of rejection and 16 of 29 patients only had minimal (grade 1) rejection as their highest rejection grade. In a paired manner, we compared each patient who had a period of nonrejection to an episode of rejection. For the 22 patients who met this criterion, CXCL10 was elevated in the setting of rejection compared with the previous nonrejection period (median 43.4 pg/mL vs. 13.9, p < 0.01 by Wilcoxon Rank test, Figure 3A).