Prostacyclin treatment of pulmonary arterial hypertension (PAH) was cumbersome and limited to continuous intravenous (IV) or subcutaneous (SQ) infusion for years. Limited data exists regarding transition from injectable to inhaled prostanoid ever since its availability.

Mycobacterium chlorophenolicum is a nontuberculous mycobacterium that has previously been characterized as nonpathogenic. We describe a 44 year-old patient with a history of deceased donor renal transplant on sirolimus who was found to meet criteria.

Posaconazole is an attractive agent for fungal prophylaxis in lung transplant patients due to its broad spectrum of activity. The oral suspension (POS) formulation has poor bioavailability requiring low pH and dietary fat for adequate systemic exposure. In November 2013 the FDA approved a posaconazole extended-release tablet (PERT) formulation. Given its more predictable absorption and systemic exposure, we transitioned to the use of the new formulation. The aim of this study is to compare the likelihood of achieving therapeutic posaconazole levels (≥0.7 mg/L) using the two oral formulations of posaconazole. This is a retrospective, single center, cohort study of patients receiving a single or bilateral lung transplant at our center between 1/1/2013 and 10/9/2014. Patients received dual fungal prophylaxis with nebulized amphotericin B and either POS or PERT dosed per manufacturer recommendations for prophylaxis. Posaconazole was continued for 4 months after transplant. Data collected include patient demographic information, steady-state posaconazole levels, LFTs and fungal culture data. Baseline demographics were similar between the two groups (POS n=23, PERT n=16). Overall, 62% of patients had a bilateral transplant, 54% were male, and at time of transplant mean age and weight were 58 years and 73kg respectively. Eight-eight percent of patients receiving PERT prophylaxis achieved therapeutic levels of posaconazole compared to 39% of patients receiving POS (chi-squared P=0.002). Mean posaconazole levels were significantly higher in the PERT group, 1.94±1.09 mg/L, compared to the POS group, 0.65±0.38 mg/L (P=0.0003). Mean time from day of transplant to day of posaconazole level averaged 24 days for the entire cohort (P=0.63 between groups). No patient in the study required dose reduction or discontinuation of posaconazole due to LFT elevations. Fungal infections during the 4-month prophylaxis period were rare and no patient in the cohort died from invasive fungal infection. Posaconazole extended-release tablets more effectively achieved therapeutic blood levels for fungal prophylaxis in our lung transplant population and were well tolerated with no patient requiring dose reduction or discontinuation.

Historically, patients with pulmonary arterial hypertension (PAH) have been treated with bilateral lung translation (BLT) for physiologic reasons. However, some patients with PAH may not be candidates for BLT and it is unknown whether single lung transplantation (SLT) can be performed safely in those patients. Our study compared survival in SLT versus BLT patients stratified to differing levels of mean PAH. We reviewed the UNOS database for patients with emphysema, pulmonary fibrosis, and primary PAH transplanted since 2004. Propensity scores (PS) were generated to adjust for factors that could bias the type of transplant procedure.PS-adjusted Cox proportional hazards regression models were constructed to measure type of surgery and PAH effects (normal< 26mmHg, mild 26-35, moderate 35-45, severe>45). 6923 patients met criteria for analysis. 3139 (45%) patients underwent SLT versus 3784 (55%) BLT. PAH was classified as normal in 3757 (54%), mild in 2217 (32%), moderate in 554 (8%), and severe in 395 (6%) patients. There was a survival advantage for BLT versus SLT at 1,3,5 and 8 years (90.3%vs88.5%,72.8vs67. 2%, 60.5vs51.8%, 44vs34.1%, p<0.001). Full regression adjustment demonstrated a 14% decrease in risk of mortality in the BLT group (HR=0.86, 95% CI 0.78-0.95,p=0.004). Patients with severe PAH had increased mortality (HR=1.30, p=.016). There was no additional effect on survival when type of transplant was analyzed with varying degrees of PAH. (Table, Graph) Patients receiving BLT, compared to SLT, have a significant survival advantage independent of the degree of PAH and patients with severe PAH have overall worse survival compared to other recipients. Our study failed to show any interaction between the type of transplant performed and degree of PAH with respect to survival. This data suggests that it may be safe to perform SLT on patients with PAH whoare not felt to be candidates for BLT.TableInteraction of PAH and Type of Transplant on SurvivalModel TermUnadjustedPropensity Selection AdjustmentPropensity Full Regression AdjustmentFull RegressionAdjustmentDouble vs. Single0.99 (0.90-1.09) p=0.860.88 (0.90-0.98) p=0.0190.88 (0.79-0.97) p=0.0130.86 (0.78-0.95) p=0.004PAH: Mild vs. Normal0.99 (0.90-1.09) p=0.861.04 (0.94-1.15) p=0.441.04 (0.94-1.14) p=0.471.00 (0.91-1.11) p=0.93PAH: Moderate vs. Normal1.05 (0.89-1.24) p=0.591.14 (0.96-1.35) p=0.131.13 (0.96-1.35) p=0.151.03 (0.87-1.22) p=0.76PAH: Severe vs. Normal1.11 (0.91-1.35) p=0.291.27 (1.04-1.57) p=0.0221.26 (1.03-1.55) p=0.0271.30 (1.05-1.60) p=0.016PAH and SurgeryType:Evidence of InteractionNone, p=0.74None, p=0.80None, p=0.80None, p=0.72 Open table in a new tab

Purpose In chronic viral infections, CD4 exhaustion correlates with poor containment of virus. We predicted that high levels of CD4 exhaustion would be beneficial in lung transplantation. Methods and Materials A retrospective review was performed on 96 lung transplant recipients from Feb 2006 to April 2010 with at least 1 bronchoscopy or peripheral blood (PB) in the first post transplant year. CD4 exhaustion was measured using the sample closest to the 1-year post transplant date. CD4 cells in bronchoalveolar lavage fluid (BALF) and peripheral blood were assessed by flow cytometry and considered exhausted if PD1hi, CD127lo, and GranzymeB negative. Samples were analyzed for the association between exhausted CD4 cells and survival and developing chronic rejection. We performed univariate Kaplan-Meier analyses between CD4 exhaustion and chronic rejection or death. Chronic rejection was defined as BOS 1 or higher by ISHLT criteria. Results A modest rejection free benefit was associated with lower CD4 exhaustion. There was a statistically significant increased freedom from rejection in the patients with a lower degree of CD4 exhaustion in the BALF (p=.04 by Log Rank). Conclusions We hypothesized that high levels of CD4 exhaustion would be fortuitous as this would serve as a biomarker for anergy toward the lung allograft. Our findings indicate that CD4 exhaustion is in fact a negative predictor of lung function. We predict that high levels of CD4 exhaustion are associated with substantial defects in protective immunity thereby leading to impaired pathogen containment. Our findings are consistent with prior reports showing an association with low humoral immunity and chronic rejection. 1-, 3-, and 5-year Rate of Survival and Chronic Rejection Free in Different Levels of Exhausted CD4 in BALF and PB Survival Rate (%) Chronic Rejection Free (%) Exhausted CD4 Frequency 1-year 3-year 5-year 1-year 3-year 5-year Low in BALF 90.6 77.4 65.8 98.1 81.0 67.5 High in BALF 100 84.7 67.8 93.9 63.6 50.0 Low in PB 91.8 77.0 64.6 95.1 73.5 56.6 High in PB 100 86.2 56.6 100 72.4 67.2

Cytomegalovirus (CMV) causes significant morbidity and mortality after solid organ transplantation. The mammalian target of rapamycin (mTOR) inhibitors have been associated with lower rates of CMV infection in cardiac and renal transplant patients. This study compares the rates of CMV infection in lung transplant patients randomized to either sirolimus (SIR) or azathioprine (AZA) as part of a tacrolimus (TAC) based immunosuppressive regimen.