No description available.

Class of 2012 Abstract / Specific Aims: The purpose of this study was to evaluate the effectiveness of various post-operative prophylaxis methods in lung transplant patients by comparing the incidence of venous thromboembolism (VTE) before and after the implementation of a standardized hospital order set at the University of Arizona Medical Center (UAMC) in April 2007. Methods: Paper and electronic medical charts were retrospectively reviewed if patients had a lung transplant date between October 31, 2003 – October 31, 2010. A computerized database was used to collect demographic data, length of stay (LOS), comorbid conditions, prophylaxis type (including dose/frequency), and date/type of thromboembolic events in the post-operative period prior to discharge and up to 1-year post- discharge. Main Results: Ninety-two patient charts were included in the study with 35 charts in the pre-order set (“Before”) group and 57 charts in the post- order set (“After”) group. All baseline characteristics were similar between groups except age (mean age difference 8.1 yrs, p=0.003), use of mycophenolate (Before n=24, After n=54; p=0.002), and use of medications that increase risk of VTE (Before n=6, After n=2; p=0.05). The April 2007 protocol significantly increased the number of patients receiving any method of prophylaxis (p<0.0001). However, receiving prophlyaxis did not significantly reduce event rates or readmissions due to VTE. Conclusions: Although implementation of the April 2007 protocol did not significantly reduce VTE event rates and readmissions, VTE prophylaxis should continue to remain a priority. Adherence to the implemented protocol may reduce the number of patients left without effective methods of prophylaxis.

Bone marrow-derived progenitor cell populations have been implicated in tissue regeneration and also in human disease pathology. This thesis investigated the hypothesis that Clara Cell Secretory Protein positive (CCSP+) epithelial-like progenitor cells and circulating fibrocyte numbers are altered in human lung disease and injury, and aimed to determine the predictive value of these cell profiles. It was found that cystic fibrosis patients have an increased number of CCSP+ cells in their bone marrow and peripheral blood, while patients with bronchiolitis obliterans syndrome (BOS) have a decreased number. In addition, BOS and pulmonary fibrosis patients have increased circulating fibrocytes. In response to ischemia reperfusion injury, an increase in CCSP+ cells in the peripheral blood was found at 24 hrs following lung transplant. Lastly, in patients studied greater than 1-year from transplant, those diagnosed with BOS had a higher number of fibrocytes and a loss of CCSP+ peripheral blood cells when compared to patients with stable lung function, with increased fibrocytes being associated with time post-transplant. In these patients, the ratio of fibrocytes-to-CCSP+ cells was predictive of lung function. Multiplex protein arrays were used to investigate corresponding patient plasma, aiming to elucidate key mediators of progenitor cell recruitment. While differences in various cytokines were found between end-stage diseases, a specific relationship between Stem Cell Growth Factor- and CCSP+ cells was identified and between Monocyte Chemotactic Protein-1 and fibrocytes. Conversely, response of CCSP+ cells following transplant appears to be mediated by known mobilizing factors SDF-1 and GM-CSF. Interestingly, in patients followed long-term after transplant, MCP-1 was associated with the number of CCSP+ cells, while SDF-1 correlated with fibrocyte numbers. These observations suggest common pathways acting on both populations that may be altered by the microenvironment, and may further suggest a common origin. This work contributes important information regarding changes in lung progenitor cells and their association with human disease and tissue repair, which could ultimately support future directions that directly advance therapy and improve patient care.

Bone marrow-derived progenitor cell populations have been implicated in tissue regeneration and also in human disease pathology. This thesis investigated the hypothesis that Clara Cell Secretory Protein positive (CCSP+) epithelial-like progenitor cells and circulating fibrocyte numbers are altered in human lung disease and injury, and aimed to determine the predictive value of these cell profiles. It was found that cystic fibrosis patients have an increased number of CCSP+ cells in their bone marrow and peripheral blood, while patients with bronchiolitis obliterans syndrome (BOS) have a decreased number. In addition, BOS and pulmonary fibrosis patients have increased circulating fibrocytes. In response to ischemia reperfusion injury, an increase in CCSP+ cells in the peripheral blood was found at 24 hrs following lung transplant. Lastly, in patients studied greater than 1-year from transplant, those diagnosed with BOS had a higher number of fibrocytes and a loss of CCSP+ peripheral blood cells when compared to patients with stable lung function, with increased fibrocytes being associated with time post-transplant. In these patients, the ratio of fibrocytes-to-CCSP+ cells was predictive of lung function. Multiplex protein arrays were used to investigate corresponding patient plasma, aiming to elucidate key mediators of progenitor cell recruitment. While differences in various cytokines were found between end-stage diseases, a specific relationship between Stem Cell Growth Factor- and CCSP+ cells was identified and between Monocyte Chemotactic Protein-1 and fibrocytes. Conversely, response of CCSP+ cells following transplant appears to be mediated by known mobilizing factors SDF-1 and GM-CSF. Interestingly, in patients followed long-term after transplant, MCP-1 was associated with the number of CCSP+ cells, while SDF-1 correlated with fibrocyte numbers. These observations suggest common pathways acting on both populations that may be altered by the microenvironment, and may further suggest a common origin. This work contributes important information regarding changes in lung progenitor cells and their association with human disease and tissue repair, which could ultimately support future directions that directly advance therapy and improve patient care.

No description available.

Lung transplantation is a treatment for patients with end stage lung disease; they will not survive without such surgery. A caregiver is essential for a patient to become eligible for a lung transplant and the caregiver plays an essential role in the transplant recipient’s care both before and after transplant surgery. Most caregiver research has been conducted on caregivers of persons with Alzheimer’s disease, dementia or on elderly patients, however, it is important to examine caregivers’ experiences caring for other patient groups with disabling conditions. Caregivers of transplant recipients are one such group. The purpose of this qualitative study, using a hermeneutic phenomenological approach, was to examine the lived experiences of caregivers of lung transplant recipients pre- and post-lung transplantation. The study used semi- structured, face to face, tape recorded in- depth interviews to document the experiences of a purposive sampling of 20 caregivers of lung transplant recipients. Interviews (English, Spanish) were transcribed verbatim and analyzed for emerging themes. The resulting 4 themes and 12 sub themes were: 1) Establishing the diagnosis; 2) Caregivers roles; 3) Caregivers psychological and psychosocial Issues; and 4) Support. The 12 sub themes were:1) Caregivers reaction to transplant option; 2) Caregivers’ lack of basic knowledge as related to lung transplant 3) Disease progression: Reality of unanticipated changes/fear of death; 4) Pre- transplant experiences; 5) Hospital course; 6) Home care; 7) Lifestyle changes and Social activities;8) Physical health and Emotional health ; 9) Financial and Employment issues;10) Family/Friends;11) Professional support; 12) Support groups. Study results demonstrated caregivers’ lack of knowledge about transplantation, dramatic changes in caregivers ‘family life, social activities, employment, and often financial status. Results also demonstrated a need for health care providers and policy makers to recognize caregivers’ stressful life changes and implement informational, psychological and emotional interventions and policies to assist these caregivers during their stressful and tedious experiences.

Since the discovery of cyclosporine in 1971, calcineurin inhibitors have played a critical role in the therapeutic suppression of the immune response. Patients receiving solid organ transplants rely heavily on these medications to prevent the acute and chronic rejection of allografted tissue. Introduction of tacrolimus, the most frequently prescribed calcineurin inhibitor, has lead to improved clinical outcomes for organ transplant recipients; however, little improvement has been noted in lung transplantation. Difficulties with current oral dosing regimens for lung transplant patients stem primarily from drug systemic toxicity, heightened risk of invasive infection, and erratic oral bioavailability. We have proposed that pulmonary delivery of a tacrolimus formulation with improved solubility can provide high lung concentrations, while limiting corresponding systemic levels associated with toxicity. Chapter 2 investigates the pulmonary administration of tacrolimus dispersion for nebulization to lung transplanted rats. Resulting lung and blood levels were determined by appropriate bioanalytical methods. Limited systemic absorption was seen after pulmonary delivery, resulting in a 50 to 1 lung to blood concentration ratio. A 28 day safety and stability evaluation of tacrolimus dispersion for nebulization was conducted in Chapter 3. Results showed no signs of toxicity in Sprague Dawley rats and proved the stability of tacrolimus powder for dispersion for 3 months. For cases of severe asthma, immunosuppression is also necessary to restore normal lungs function and is typically treated with corticosteroids. Corticosteroids, however, are well known for their untoward side effects and can prove ineffective in severe asthmatics that have developed corticosteroid resistance. Chapter 4 investigates the use of tacrolimus dispersion for nebulization for prophylactic treatment of asthma. Efficacy was determined in an asthma-induced animal model by quantification of inflammatory cells and signaling chemicals. In Chapter 5, tacrolimus powder for inhalation is investigated in a novel dry powder inhalation platform. Respirable particles are produced when bulk particles (500 [micrometer]) comprising a matrix of drug/excipient are sheared apart by a marketed inhalation device to produce particles of the appropriate geometric diameter (50 [micrometer]). Biocompatible material with brittle properties were found to produce fine particle fractions (FPF) up to 70.3% and total emitted doses (TED) higher than 95%. / text

Background: Studies evaluating the possible health-promoting effects of sound nutrition in heart and lung transplant recipients are currently lacking. Despite advances in drug treatment and patient monitoring, lifestyle-associated complications such as obesity, diabetes and cardiovascular disease occur frequently. Following transplantation, a low-fat eating pattern is currently viewed as best standard care. However, a Mediterranean diet based on a varied range of fresh unprocessed foods and supplemented with extra virgin olive oil has demonstrated clinical benefit in various non-transplant populations. The aim of this study was to evaluate the feasibility and acceptability of a Mediterranean vs a low-fat diet intervention in heart and lung transplant recipients, and to assess clinical and biochemical outcomes. Methods: This was a randomised controlled feasibility trial to evaluate a Mediterranean diet supplemented with extra-virgin olive oil, vs a modified low-fat diet in heart and lung transplant recipients at a single centre. In total, 41 clinically stable male and female (median age 55 years) transplant recipients were randomly assigned (1:1) in two separate 12-month waves (n=24 and n=17) to one of these diet interventions. A range of validated food frequency and adherence questionnaires captured changes in participants' reported eating habits to 6 weeks post-study. Clinical and biochemical analysis was conducted at baseline, 25 and 52 weeks. Telephone and outpatient contact provided a support mechanism to reinforce dietary behavioural change. Caloric intake and physical exercise awareness were discussed, but not promoted. Results: Thirty nine participants completed the trial (95%). Adherence to both interventions improved significantly at week 25, and was maintained at 52 and 58 weeks. Compared with baseline, waist circumference decreased in both groups at week 25 (p=0.024). A decrease in blood pressure and heart rate occurred at 52 weeks in the low-fat group only. At 52 weeks, higher adherence resulted in significant improvements in fasting glucose in the Mediterranean (< 4.8%) and low-fat (< 5%) groups. This respective pattern was also observed with total cholesterol (≤ 9% and ≤ 7%), triglycerides (≤ 9% and ≤ 20%) and IGF-1 (≤ 9% and ≤ 15%). A significant decrease in the LDL/HDL ratio (≤ 12%) occurred in the Mediterranean group only. Moreover, clinically relevant lipid and glucose regulation changes were observed in each intervention. Conclusions: The implementation of a prospective 12-month Mediterranean or low-fat diet is feasible and acceptable in a heart and lung transplant outpatient setting. Both interventions were positively associated with improvements in lipid and blood glucose regulation and circulating IGF-1. As part of a multidisciplinary framework, these findings offer an additional therapeutic strategy to optimise outpatient care.

Class of 2012 Abstract / Specific Aims: The purpose of this study was to evaluate the effectiveness of various post-operative prophylaxis methods in lung transplant patients by comparing the incidence of venous thromboembolism (VTE) before and after the implementation of a standardized hospital order set at the University of Arizona Medical Center (UAMC) in April 2007. Methods: Paper and electronic medical charts were retrospectively reviewed if patients had a lung transplant date between October 31, 2003 – October 31, 2010. A computerized database was used to collect demographic data, length of stay (LOS), comorbid conditions, prophylaxis type (including dose/frequency), and date/type of thromboembolic events in the post-operative period prior to discharge and up to 1-year post-discharge. Main Results: Ninety-two patient charts were included in the study with 35 charts in the pre-order set (“Before”) group and 57 charts in the post-order set (“After”) group. All baseline characteristics were similar between groups except age (mean age difference 8.1 yrs, p=0.003), use of mycophenolate (Before n=24, After n=54; p=0.002), and use of medications that increase risk of VTE (Before n=6, After n=2; p=0.05). The April 2007 protocol significantly increased the number of patients receiving any method of prophylaxis (p<0.0001). However, receiving prophlyaxis did not significantly reduce event rates or readmissions due to VTE. Conclusions: Although implementation of the April 2007 protocol did not significantly reduce VTE event rates and readmissions, VTE prophylaxis should continue to remain a priority. Adherence to the implemented protocol may reduce the number of patients left without effective methods of prophylaxis.

No description available.