(Table 3) Table 3: Relationship between mechanistic endpoints and composite endpoint (N=28)(N=33)Syndome / Obliterative Bronchiolitis) within 24m(N=28)(N=33)relationship between infection and the composite endpoint (including an absence of statistical trends), we feel this study provides strong evidence rejecting the original hypothesis. (3 years). The primary endpoint was met in 46% of patients. CARV was detected in 156 patient visits (74% enterovirus/rhinovirus). We did not find a relationship between CARV recovery from respiratory specimens and the primary endpoint (HR 0.64 (0.25, 1.59), P=0.335) or between CARV and the development of allo- or autoimmune humoral or cellular responses. These findings raise the possibility that the immunologic impact of CARV following pediatric lung transplant is different than that Roscovitine (Seliciclib) observed in adults. Introduction Advancements in recipient selection, surgical techniques, evolving immunosuppressive regimens and more effective infection prophylaxis over the past 25 years have led to improved perioperative survival in pediatric lung transplant recipients (LTRs). However, long- term graft and patient survival has not improved substantially over the same period and remains significantly worse than outcomes for recipients of heart, liver and kidney allografts. Beyond the first post-transplant year, chronic lung allograft dysfunction (CLAD) is the most common cause of graft failure. The incidence of bronchiolitis obliterans syndrome (BOS), the most common form of CLAD, is 50% at 5 years in children and roughly 80% between 5 and 10 years in adults 1-3. Between 25 and 40% of lung transplant recipients will die directly or indirectly from CLAD 3. Although re-transplantation for CLAD is feasible, its utility is limited by organ availability and poorer survival after second transplant 4-6. Although the etiology of CLAD remains unclear, a common theme throughout the spectrum of clinical risk factors including primary graft dysfunction, recurrent and/or severe acute cellular rejection (ACR), viral infections including cytomegalovirus (CMV), bacterial infection (particularly Endpoint Yes(N=28) Endpoint No(N=33)K1T-reactive cellular immunity, we did not observe relationships between either of these parameters and the composite endpoint (Table 3). Nor did we observe significant correlations between the composite endpoint (or its components) and the presence of post-transplant humoral or cellular reactivity to either allo- or autoantigens whether or not. (Table 3) Table 3: Relationship between mechanistic endpoints and composite endpoint (N=28)(N=33)Syndome / Obliterative Bronchiolitis) within 24m(N=28)(N=33)relationship between infection and the composite endpoint (including an absence of statistical trends), we feel this study provides strong evidence rejecting the original hypothesis. The absence of a relationship between allo- and autoimmune responses and the composite endpoint may also reflect inadequate power. The relatively short 2-year follow-up period may have also limited our ability to identify the development of BOS, which is often diagnosed beyond 2 years post-transplant. We plan to obtain 5-year clinical follow-up data to assess this possibility. Because we did not collect data about patients who met exclusion criteria, we cannot rule out a recruitment bias in that regard. A final limitation to our study is that it was performed using BOS rather than CLAD criteria. It is possible that our findings would have been different had we collected sufficient data to characterize patients using current CLAD criteria and Roscovitine (Seliciclib) chosen a composite endpoint based on one of the CLAD subtypes. Nonetheless, in contrast to the adult population 21,44-46, respiratory viral infections in pediatric LTRs do not appear to be a predictor for poor outcome. Coupled with the observation that high immunosuppression based on ELISPOT reactivity was associated with Roscovitine (Seliciclib) viral infection, and the observation that Roscovitine (Seliciclib) a subset of our subjects had persistent rhinovirus infection 62 it is possible that viral infection was a ITGAL surrogate for immunosuppression in this population. The finding, in a companion study using samples from this population, that low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death and the composite outcome supports this hypothesis63. In summary, this comprehensive prospective analysis of pediatric LTRs found comparable outcomes to the most recent ISHLT registry report 3 Roscovitine (Seliciclib) but did not identify relationships among primary graft dysfunction, ACR, or CARV.