Faculty Bibliography

Lung transplantation is a viable treatment option for select patients with end-stage lung disease. Two issues hamper progress in transplantation: first, donor shortage is a major limitation to increasing the number of transplants performed. Secondly, recipient outcomes remain disappointing when compared with other solid organ transplant results. Outcomes are limited by primary graft dysfunction (PGD), the posttransplant acute lung injury that increases both short-and long-term mortality. Attempts to overcome donor shortage have included aggressively managing solid organ donors to increase the number of donor lungs suitable for transplantation. Yet, the quality of the lung donor is likely to be related to the probability of the recipient experiencing PGD. PGD is the culmination of a series of insults, hemodynamic, metabolic, and inflammatory, that begin with the brain dead donor and result in poor recipient outcomes. Understanding the mechanism of donor lung injury resulting from brain death and the possible treatment strategies for its inhibition could help to increase the number of usable lungs and decrease the rate of PGD in the recipient. Here we present a review of the key pathways which result in donor lung injury, and follow this with a brief review of recent biomarkers that are proving to be instrumental to our ability to predict truly unsuitable lungs, and our ability to predict and hopefully prevent or treat recipients with subsequent lung injury.

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients. This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality. Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.

BACKGROUND: As early as the 1920's, researchers noted a relationship between caloric restriction, weight loss and a decreased incidence of hypertension (Terry 1922, Preble 1923, Bauman 1928, Master 1929). In 1988 a meta-analysis of aggregate data from 12 prospective studies, including 5 randomized controlled trials (RCTs), found that on average each 1 kilogram decrease in body weight in obese hypertensive patients was associated with a 2.4 mm Hg systolic and 1.5 mm Hg diastolic decrease in blood pressure (Staessen 1988). Blood pressure reductions were not dependent upon degree of baseline obesity.This review aims to: 1) update the work of Staessen (Staessen 1988) looking specifically at randomized controlled trials, and 2) assess whether any of the trials assess effects of weight-reducing diets on clinical outcomes such as quality of life, morbidity or mortality. OBJECTIVES: Evaluate whether weight-loss diets are more effective than regular diets or other antihypertensive therapies in controlling blood pressure and preventing morbidity and mortality in hypertensive adults. SEARCH STRATEGY: MEDLINE and The Cochrane Library were searched through November 1997. Trials known to experts in the field were included through June 1998. SELECTION CRITERIA: For inclusion in the review, trials were required to meet each of the following criteria: 1) randomized controlled trials with one group assigned to a weight-loss diet and the other group assigned to either normal diet or antihypertensive therapy; 2) ambulatory adults with a mean blood pressure of at least 140 mm Hg systolic and/or 90 mm Hg diastolic; 3) active intervention consisting of a calorie-restricted diet intended to produce weight loss (excluded studies simultaneously implementing multiple lifestyle interventions where the effects of weight loss could not be disaggregated); and 4) outcome measures included weight loss and blood pressure. DATA COLLECTION AND ANALYSIS: Studies were dual abstracted by two independent reviewers using a standardized form designed specifically for this review. The primary mode of analysis was qualitative; graphs of effect sizes for individual studies were also used. MAIN RESULTS: Eighteen trials were found. Only one small study of inadequate power reported morbidity and mortality outcomes. None addressed quality of life or general well being issues. In general, participants assigned to weight-reduction groups lost weight compared to control groups.Six trials involving 361 participants assessed a weight-reducing diet versus a normal diet. The data suggested weight loss in the range of 4% to 8% of body weight was associated with a decrease in blood pressure in the range of 3 mm Hg systolic and diastolic. Three trials involving 363 participants assessed a weight-reducing diet versus treatment with antihypertensive medications. These suggested that a stepped-care approach with antihypertensive medications produced greater decreases in blood pressure (in the range of 6/5 mm Hg systolic/diastolic) than did a weight-loss diet. Trials that allowed adjustment of participants' antihypertensive regimens suggested that patients required less intensive antihypertensive drug therapy if they followed a weight-reducing diet. Data was insufficient to determine the relative efficacy of weight-reduction versus changes in sodium or potassium intake or exercise. AUTHORS' CONCLUSIONS: Weight-reducing diets in overweight hypertensive persons can affect modest weight loss in the range of 3-9% of body weight and are probably associated with modest blood pressure decreases of roughly 3 mm Hg systolic and diastolic. Weight-reducing diets may decrease dosage requirements of persons taking antihypertensive medications.