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Background: Lung transplant is the fastest growing solid organ transplant procedure and venous thromboembolism has been described to occur in 8-29% of cases. This is much higher than any other solid organ and the exact incidence has yet to be determined. Risk factors for the development of venous thromboembolic disease (VTE) specific to lung transplant are not fully understood. Purpose: The purpose of this research was to describe the incidence and risk factors for VTE disease during the first year following lung transplant at a busy transplant center in the Southwest United States. Methods: A descriptive retrospective study design was used. Virchow's triad was used as a theoretical model to identify selected variables common to lung transplant in an effort to understand possible risk factors for the development of VTE in this patient population. Consecutive lung transplant cases between June 1, 2013 and May 31, 2014 at St. Joseph's Medical Center in Phoenix, Arizona were retrospectively reviewed and followed for exactly one year following the lung transplant date. Demographic variables, Virchow's triad variables, and variables previously identified in the literature as being risk factors for VTE were collected and analyzed using descriptive, frequency, t-test, chi-square, and logistic regression. Results: The incidence of VTE in this patient population was 25.8% and is consistent with findings from previous studies. Using the constructs of Virchow's triad did not yield any statistically significant predictors for VTE in this patient population. However, lung allocation score (LAS) (OR 1.109, CI 1.038-1.185), body mass index (BMI) (OR 1.362, CI 1.034-1.794), and time on the waitlist (OR 1.094, CI 1.023-1.171) did reach statistical significance as possible predictors for VTE following lung transplant in this patient sample. Conclusions: VTE is a common complication of lung transplant that has a high incidence during the first year following lung transplant. This study did identify LAS, BMI, and time on the waitlist as being possible risk factors for the development of VTE following lung transplant. LAS may be a useful surrogate to determine the risk for VTE in this population.

The purpose of this review was to identify the history of and advances in cystic fibrosis (CF). New treatment plans, medication developments, and a historical perspective of airway clearance therapy (ACT) will be presented. The importance of treatment compliance and time management in the care of cystic fibrosis patients will also be discussed. Furthermore, the development of cystic fibrosis clinics and the pivotal role they play in the treatment of the disease will be addressed. Lastly, a brief discussion concerning the need for and process of lung transplantation will be reported.

INTRODUCTION: Preoperative pulmonary rehabilitation (PPR) is an emerging therapy for transplant candidates who are awaiting surgery. Research indicates that PPR training has benefits for improving exercise tolerance, but little researcher exists on the association between PPR on post-transplant hospital outcomes. METHODS: The study was a non-probability cross-sectional analysis performed on data for post-transplant recipients who received either a single or bilateral lung transplant from February 8, 2007 to July 8, 2014. The study sample consisted of 207 transplant recipients. Analyses of the associations between independent variables: preoperative pulmonary rehabilitation and six-minute walk distance (6MWD) and covariates were performed by logistic regression analysis to examine the following outcomes: length of stay, hospital readmissions in the first 90 days post- transplant, and the number of hospital readmissions in the first 90 days. RESULTS: Transplant recipients who participated in preoperative pulmonary rehabilitation had 1.77 times greater odds of being readmitted in the first 90 days post-transplant compared to recipients who did not participated in preoperative pulmonary rehabilitation. Transplant recipients whose 6MWD was greater than 207 meters and who participated in preoperative pulmonary rehabilitation had 4.99 times greater odds of length of staying 12 days or less post- transplant surgery compared to transplant recipients whose walk distance was less than 207 meters and who did not participate in preoperative pulmonary rehabilitation. CONCLUSION: Pulmonary rehabilitation is an important part of the lung transplant. The results of this study indicate the importance of preoperative lung transplant on post-transplant outcomes for transplant recipients.

The use of lung transplantation, a life saving intervention, has been increasing over the last thirty years with a disappointing median survival of only 4.8 years. Despite the progress made in immunosuppressive therapies, allograft rejection following transplantation is the leading cause of death. As part of the immunosuppressive therapy, mycophenolate mofetil (MMF), the ester prodrug of mycophenolic acid (MPA) has proven its efficacy among heart, liver, kidney as well as lung transplanted patients. However, due to its rapid excretion, high daily doses are necessary and lead to serious side effects, forcing the patient to stop and change their course of treatment. Administration of drugs to the lungs is known to minimize local and systemic side effects by employing a lower amount of drug, to increase patient compliance and to improve the efficacy of the treatment. Therefore, developing novel MMF formulations for targeted delivery to the lungs will broaden the therapeutic options against lung transplant rejection. Within the framework of this dissertation, the development of an inhaled formulation of MMF was investigated. MMF must be metabolized by carboxylesterases to become active and its metabolism suffers from high inter- and intra-patient variability. The first objective of this dissertation was to investigate the occurrence of MMF hydrolysis in the lung. The second objective was to study the in vivo deposition,metabolism and distribution in rats, of an inhaled micron-size MMF suspension in comparison to inhaled IV Cellcept® and oral Cellcept®, the currently marketed products. According to the in vitro results, MMF is metabolized in human lung cells by carboxylesterases. The in vivo results showed an incomplete metabolism of MMF when delivered as a suspension due to the limited dissolution of the drug in the lungs. Following inhalation, the MMF suspension achieved higher and more prolonged concentration of the total drug in the lungs and lymphoid tissues as compared to the inhaled IV Cellcept®. The pulmonary delivery of the MMF suspension was able to achieve similar levels of drug in the lungs, higher levels in the lymphoid tissues and significantly lower levels in the systemic circulation when compared to the levels obtained from the oral gavage of oral Cellcept®. Ultimately, this dissertation demonstrated that the administration of micron-size MMF suspension offers a great potential for pulmonary administration. / text

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These two studies investigate the immune responses of lung and kidney transplant recipients to the influenza vaccine. The study involving kidney transplant recipients developed a novel flow cytometry assay to measure cell-mediated immunity in response to influenza vaccination. The activation of T-cells was assessed through the change in T-cell production of interferon gamma after vaccination. In lung transplant recipients, the study examined the formation of de novo anti-HLA antibodies following influenza vaccination. Anti-HLA antibodies were classified as donor-specific or not. The study in kidney transplant recipients found that the influenza vaccine is effective at stimulating the immune response and producing long-lived memory in these patients, as evidenced by high baseline T-cell activity. The study of lung transplant recipients found that receiving the influenza vaccine did not result in the production of anti-HLA antibodies. Both studies found vaccine to be safe for use in these populations. / Experimental Medicine

Despite decades of changes in allocation policies for lung transplantation, the field is plagued by outdated and ethically problematic processes that impact candidate selection. Transplant centers screen potential organ recipients with a psychosocial evaluation in an attempt to identify potential barriers to post transplant success. Professional guidelines note the problematic nature of basing transplant candidacy on social factors. The prohibitive nature of the process in conjunction with the coercive pressures of impending demise forces individuals and their social support systems to make concessions that directly impact their individual dignities. Precluding eligible candidates based upon nonadherence does not improve clinical outcomes and thus does not benefit the net population. Psychosocial evaluation needs to be reimagined. The current practice, as it stands, fails to meet national ethical standards, but with its diverse widespread utilization, the psychosocial evaluation can become a tool to identify potential gaps and empower transplant teams to support individuals in addressing perceived deficiencies. / Urban Bioethics

Acute lung injury (ALI) is a major cause of mortality after lung transplantation. Recent studies indicate protein kinase C delta (PKCδ) could be an effective target to treat ALI. We have developed a gold nanoparticle (GNP)-peptide hybrid that can inhibit PKCδ signaling. PKCδ inhibitor peptide (PKCi) and 95P2P4 stabilizing peptides were conjugated onto GNP. Physicochemical properties of the nanoformulations were examined. A lung transplant-simulated cell culture model was used to evaluate therapeutic efficacy in vitro. A pulmonary ischemia-reperfusion (IR) model was used to test therapeutic efficacy in vivo. GNP-Peptide hybrids showed good stability with high cellular uptake. GNP-PKCi formulations demonstrated anti-inflammatory and anti-apoptotic effects in vitro. When administered to rats under IR stress, GNP-PKCi formulation improved blood oxygenation, reduced pulmonary edema and histological lung injury. In conclusion, we have successfully formulated a clinically-applicable nanoparticle with therapeutic potential to ameliorate lung injury and inflammation. Our formulation strategy could be used to deliver other peptide-based drugs.

Acute lung injury (ALI) is a major cause of mortality after lung transplantation. Recent studies indicate protein kinase C delta (PKCδ) could be an effective target to treat ALI. We have developed a gold nanoparticle (GNP)-peptide hybrid that can inhibit PKCδ signaling. PKCδ inhibitor peptide (PKCi) and 95P2P4 stabilizing peptides were conjugated onto GNP. Physicochemical properties of the nanoformulations were examined. A lung transplant-simulated cell culture model was used to evaluate therapeutic efficacy in vitro. A pulmonary ischemia-reperfusion (IR) model was used to test therapeutic efficacy in vivo. GNP-Peptide hybrids showed good stability with high cellular uptake. GNP-PKCi formulations demonstrated anti-inflammatory and anti-apoptotic effects in vitro. When administered to rats under IR stress, GNP-PKCi formulation improved blood oxygenation, reduced pulmonary edema and histological lung injury. In conclusion, we have successfully formulated a clinically-applicable nanoparticle with therapeutic potential to ameliorate lung injury and inflammation. Our formulation strategy could be used to deliver other peptide-based drugs.