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Biomedical subjects

Rudolf Speich

Publications and source records attributed to Rudolf Speich.

At least 19 recordsLinked to original sources
PubMed2006

Itraconazole comedication increases systemic levels of inhaled fluticasone in lung transplant recipients.

BACKGROUND: After lung transplantation (LTx), inhaled corticosteroids may be prescribed and at the same time prophylaxis against fungal infections with itraconazole is common. In our center, the addition of inhaled fluticasone propionate to systemic immunosuppression resulted in clinical Cushing's syndrome in 4 lung transplant recipients on itraconazole comedication. OBJECTIVES: The current study was undertaken to compare systemic levels of inhaled fluticasone in patients with and without concomitant itraconazole therapy. METHODS: The single-center, prospective controlled study was performed in the LTx program in Zurich, Switzerland. Twenty stable recipients, 1-7 years after LTx, on a prednisone maintenance dose (5-7.5 mg/day) gave informed consent and were assigned to 2 groups: (A) without itraconazole comedication and (B) currently on itraconazole, being continued during the study period. The patients of both groups started inhalation of 1 mg fluticasone propionate twice daily for 14 days with a powder disc inhaler. Plasma fluticasone levels were measured before the start of the study and on day 14. RESULTS: Fluticasone levels before starting the treatment were below the detection limit in all 17 patients (7 in group A and 10 in group B) adhering to the study protocol. Baseline characteristics (underlying disease, age at LTx, time since LTx, FEV(1)) were comparable between the 2 groups. On study day 14, plasma fluticasone levels had increased to detectable levels in all patients (A: 273 +/- 124 pg/ml, B: 701 +/- 131 pg/ml), i.e. to significantly higher (p = 0.038) concentrations in patients on itraconazole. CONCLUSIONS: Itraconazole comedication substantially increases systemic levels of inhaled fluticasone, most likely by inhibiting the cytochrome P450 3A4 enzyme system and thus the clearance of fluticasone. Accumulation of fluticasone can result in increased systemic effects and therefore comedication has to be taken into consideration when inhaled fluticasone is prescribed.

Administration, Inhalation↗
PubMed2006

Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients.

BACKGROUND: There are no data on the effects of mycophenolate mofetil (MMF) on the incidence of bronchiolitis obliterans syndrome (BOS) in lung-transplant patients. This study attempted to determine whether MMF reduces the incidence of BOS in de novo lung transplant recipients compared with azathioprine (AZA). METHODS: This prospective, randomized, open-label, multicenter study compared the effects of MMF with AZA in combination with induction therapy, cyclosporine (Neoral) and corticosteroids in patients receiving their first lung transplant. Primary endpoint was incidence of BOS at 3 years. Secondary endpoints were incidence of acute rejection, time to first rejection event, and survival. RESULTS: The incidence of acute rejection and the time to first rejection event at 1 and 3 years did not differ between groups (54.1% vs. 53.8% and 56.6% vs. 60.3% for MMF and AZA respectively). Survival at 1 year tended to be better in patients receiving MMF (88 vs. 80%, P = 0.07). At year 3, there was no difference in survival or in the incidence, severity or time to acquisition of BOS between the two groups. Treatment was generally well tolerated, however more patients withdrew from AZA treatment than from MMF (59.6% vs. 46.5%, P = 0.02). As a result, there was an imbalance in the observation times of the two groups (876 +/- 395 vs. 947 +/- 326 days). CONCLUSIONS: No differences were seen in the incidence of acute rejection or BOS in lung transplant recipients treated with MMF or AZA. This null result may have been influenced by the shorter observation time for AZA patients.

Adolescent↗
PubMed2006

Long-term experience with oral or inhaled vasodilator combination therapy in patients with pulmonary hypertension.

BACKGROUND: Disease progression in pulmonary hypertension (PH) is common despite standard vasodilator monotherapy with iloprost, bosentan or sildenafil. OBJECTIVE: To investigate if the combination of these non-invasively applicable treatments is an effective option to address the multiple pathophysiological mechanisms present in PH. METHODS: We analysed the clinical course of 23 patients with PH, diagnosed as idiopathic (n = 15), chronic thromboembolic (n = 4), and associated with collagen vascular disease (n = 4), receiving combination vasodilator therapy at our institution. RESULTS: Vasodilator therapy before combination therapy consisted of inhaled iloprost (I; n = 12), or oral bosentan (B; n = 6) at a mean duration of 19 +/- 3 months. The combination therapy added was B (n = 8), sildenafil (S; n = 6) or I (n = 4) and in five patients, combination therapy was given from the beginning (3x BS, 1x IS, 1x IBS). Under combination therapy, the 6-minute walk distance (6MWD) increased significantly by 46.7 +/- 24.8 m (p = 0.02) after three months, and after six months it was still 38.3 +/- 28.3 m (p = 0.17) longer than before combination therapy. Respective changes in the Borg Scale and the NYHA functional class were -1.05 +/- 0.49 (p = 0.014) and -0.42 +/- 0.19 (p = 0.02) after three months and -0.21 +/- 0.65 (p = 0.61) and -0.38 +/- 0.29 (p = 0.26) after six months. Only minor side effects were reported. CONCLUSION: Combination vasodilator therapy in severe PH is safe and well tolerated. It significantly improves exercise capacity and stabilises the functional class in patients with severe PH deteriorating under single-agent therapy.

Administration, Inhalation↗
PubMed2006

Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation.

BACKGROUND: In this study, we prospectively analyzed the functional outcome and the survival after lung-volume reduction surgery (LVRS) in patients with end-stage emphysema who were initially potential candidates for lung transplantation (LTX), and investigated the impact of LVRS on posttransplant course in patients who underwent LTX after LVRS. METHODS: Of the 216 patients who underwent LVRS between 1994 and 2005, 58 were potential candidates for LTX at the time of LVRS (age 65 years or younger, forced expiratory volume in 1 second 25% of predicted or less; LVRS/LTX group). Lung-volume reduction surgery was performed by means of video-assisted, bilateral stapled resection of target areas. During the same period, 31 patients underwent primary LTX for end-stage emphysema (LTX group). Spirometry, plethysmography, carbon monoxide diffusing capacity, 6-minute walking distance, and dyspnea score were assessed preoperatively and at predetermined times after operation. Survival analysis was performed by use of the Kaplan-Meier method. RESULTS: All the functional variables significantly improved after LVRS and peaked within the first year. Subjective improvement was observed for up to 5 years after LVRS, and 53% (31 of 58) of the patients were still alive and had not undergone transplantation after a median follow-up of 44 months. Fourteen percent (8 of 58) of the patients underwent secondary LTX because of progressive worsening of the respiratory function after a median bridging time between LVRS and LTX of 33 months. Postoperative recovery after transplantation and median survival time were comparable between the 8 patients of the LVRS/LTX group and the 31 patients of the LTX group (96.5 months versus 118.5 months, p = 0.9). CONCLUSIONS: Lung-volume reduction surgery can significantly improve symptoms and lung function in selected patients who are initially potential candidates for LTX. Lung-volume reduction surgery can allow the postponement of LTX for up to 4 to 5 years and does not impair the chances for a subsequent successful LTX.

Adult↗
PubMed2006

Pretransplantation bone disease in patients with primary pulmonary hypertension.

INTRODUCTION: Osteoporosis is a common condition in patients with end-stage lung disease, but little attention has been given to bone disease in patients with primary pulmonary hypertension (PPH). The purposes of this study were as follows: (1) to determine the prevalence of osteoporosis in patients with severe PPH before lung transplantation, (2) to investigate whether generally accepted risk factors for osteoporosis would play a role in this special group of patients, and (3) to determine whether there is an association between functional parameters and pretransplantion bone mass. DESIGN: A retrospective analysis of 18 consecutive patients with PPH accepted for lung transplantation at the University Hospital of Zurich. MEASUREMENTS AND RESULTS: Decreased bone mineral density (BMD) [T score <- 1.0] was found in 11 of 18 patients (61%) at the femoral neck (FN) and 13 of 18 patients (72%) at the lumbar spine (LS). We did not find a significant difference of BMD in a gender- or age-specific manner. Body mass index (BMI) correlated significantly with BMD and T score at the FN and WT. Pulmonary vascular resistance (PVR) was notably linked with BMD at the FN. We found a positive association between walking distance in the 12-min walking test and BMD at the FN and WT. CONCLUSIONS: Low bone density is a very frequent condition in patients with severe PPH. In contrast to the general population, in our study group neither age nor female gender were significantly associated with lower bone mass. Body weight and BMI were highly coupled with BMD. Among the functional parameters, walking distance and PVR were correlated to BMD at the FN. Considering that patients with PPH may have an improved life expectancy in the future, the early diagnosis, prevention, and treatment of osteoporosis should receive high priority.

Adult↗
PubMed2006

Chronic thromboembolic and pulmonary arterial hypertension share acute vasoreactivity properties.

BACKGROUND: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are the major classes of pulmonary hypertensive disorders according to the World Health Organization; both lead to right heart failure and death. A better understanding of disease mechanisms has led to the suggestion that the thromboembolic and nonthromboembolic types of pulmonary hypertension may share pathophysiologic features. We therefore compared acute vasoreactivity and proximal pulmonary artery compliance in patients with PAH and CTEPH during the initial diagnostic heart catheterization. METHODS: Right heart catheterization using a flow-directed Swan-Ganz catheter was performed in patients with CTEPH (n = 22) and PAH (n = 35). Pulmonary hemodynamics were assessed at baseline, during the inhalation of 40 ppm of nitric oxide, and 30 min after the inhalation of 10 mug of iloprost. To assess the proximal pulmonary artery compliance, the pulse pressure (PP) [systolic-diastolic pressure] and the fractional PP (PPf) [divided by the mean pressure] were calculated. RESULTS: Both vasodilators produced similar hemodynamic improvement, and the difference between CTEPH and PAH was not significant. The baseline PP and PPf did not vary between the two groups. CONCLUSION: Patients with PAH and CTEPH show similar acute vasoreactivity to inhaled nitric oxide and iloprost, and have similar pulmonary artery compliance. These findings support the presence of some shared pathophysiologic pathways in both disorders and may lead to therapeutic implications in patients with inoperable CTEPH.

Adult↗
PubMed2005

Clinical features of gamma-hydroxybutyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use.

OBJECTIVE: To describe the clinical features of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) toxicity. METHODS: Retrospective case-study of 65 GHB and GBL intoxications seen in an urban emergency department. RESULTS: 63% of intoxications occurred in male patients. The median age was 24 years (range 16-41 years). 65% co-ingested alcohol or illicit drugs, mostly MDMA and cocaine. 83% presented with coma. The mean+/-S.D. time to regain consciousness among comatose patients was 111+/-61 min and was significantly longer in patients who co-abused illicit drugs such as cocaine or MDMA (155+/-60 min). Bradycardia occurred in 38%, hypotension in 6% and hypothermia in 48%. Agitation was observed in 17% of all patients and was significantly more frequent in patients with alcohol co-use (29%). Vomiting occurred in 31% of all patients and tended to be more frequent in patients who co-used alcohol (39%). Management of GHB and GBL overdose was supportive. Four patients needed admission to an intensive care unit for mechanical ventilation (6%). CONCLUSIONS: Overdosing of GHB and GBL frequently results in non-reactive coma reflecting the severity of poisoning. Multiple drug use is common and significantly influences the clinical presentation.

4-Butyrolactone↗
PubMed2005

Extended donor lungs: eleven years experience in a consecutive series.

OBJECTIVE: The aim of this study was to delineate the profile of extended donor lungs in comparison to ideal donor lungs and to analyse their outcome. Particular attention was given to donor lungs with a low PaO(2) (<250mmHg) before harvesting or with multiple extended criteria. METHODS: Between 1993 and 2003, 148 patients (79 women, 69 men, mean age 39.9 years) underwent lung transplantation. Indications were cystic fibrosis in 35.8%, emphysema in 26.4%, pulmonary fibrosis in 12.2%, pulmonary hypertension in 9.5%, and others in 16.1%. Donor data and recipients medical files were reviewed. Criteria for donor lungs were considered extended if one or more of the following criteria were met: age >55 years, smoking >20 pack-years, PaO(2) before harvesting <300mmHg, pathologic chest X-ray, and purulent secretion at bronchoscopy. A comparison between recipients from ideal and from extended donor lungs was performed with respect to the median duration of mechanical ventilation, the median length of stay at the intensive care unit, postoperative complications, the 30-day and the 1-year survival, and the 6-month follow-up spirometry. RESULTS: Sixty-three (42.6%) donor lungs were considered extended and 20 (31.7%) met more than one criteria. Outcome comparison between recipients from ideal (I) and extended (II) donor lungs did not statistically differ in postoperative complications (18.8% (I) vs. 26.9% (II), P=0.32), mean duration of mechanical ventilation (d) (4.4+/-2.7 (I) vs. 2.6+/-2.1 (II), P=0.2), mean length of stay at the ICU (d) (11.5+/-8.8 (I) vs. 9.2+/-6.9 (II), P=0.4), 6-month pulmonary function (FEV1=83+/-23% of the predicted value (I) vs. 82+/-18% (II), P=0.81), 30-day survival (90.6% (I) vs. 93.7% (II), P=0.56), 1-year survival (83.5% (I) vs. 81% (II), P=0.83). Thirty-day survival was also comparable even in recipients from donor lungs with PaO(2)<250mmHg (n=8) (90.6% (I) vs. 87.5%, P=0.57). The number of extended criteria had no impact on the outcome. The combination of PaO(2)<300mmHg with purulent secretion at bronchoscopy seemed to influence the early outcome of recipients from extended donor lungs negatively. CONCLUSIONS: Our results suggest that the use of selected extended donor lungs does not compromise the outcome after transplantation. PaO(2) <250mmHg before harvesting of the lungs is not an absolute contra-indication for transplantation.

Adult↗
PubMed2005

Inflammation patterns in allogeneic and autologous airway tissue of lung transplant recipients.

Inflammatory injuries directed toward airway structures play a key role in lung allograft rejection. However, data relating to the inflammation patterns of large airways are scarce and, in particular, the relation between autologous and allogeneic parts is unknown. For the first time, in this study, simultaneously collected endobronchial biopsies from the main (autologous) and upper lobe (allogeneic) carina of lung transplant recipients were assessed immunohistologically. A total of 27 pairs of EBBs were taken. Twelve endoscopies documented acute rejection and four examinations of patients with BOS were performed. Patients with acute rejection had more CD8-positive cells in the allogeneic parts compared with patients without acute rejection. Patients with BOS had more CD4- and CD45-positive cells in the autologous airways than stable patients. We conclude that distinct inflammatory changes do occur in large airways of lung transplant recipients and are not limited to the donor parts of airways.

Adult↗
PubMed2005

Iron accumulation in lung allografts is associated with acute rejection but not with adverse outcome.

BACKGROUND: Iron content in lung allografts is increased after transplantation. It was hypothesized that this may lead to fibrosis and posttransplant bronchiolitis obliterans syndrome (BOS). METHODS: In a prospective study, we evaluated 399 BAL fluid (BALF) and transbronchial lung biopsy samples obtained concurrently from 72 consecutive lung transplant recipients. RESULTS: The hemosiderin scores (HSs) of the BALF samples increased steadily during the postoperative period (p < 0.001). Patients with at least one acute rejection episode (AR) grade > or = A2 event had higher mean HSs, the difference being significant after the second (p < 0.008) and the sixth postoperative months (p < 0.05). The HS correlated with the number of ARs (p < 0.004), and it significantly increased after the first AR (p < 0.04). Except for oral anticoagulation, no other risk factors for elevated iron content were found. There was no correlation between HS or number of ARs and the development of BOS or survival, respectively. CONCLUSIONS: Progressive iron accumulation in lung allografts seems to be caused mainly by an AR, possibly due to perivascular leakage of erythrocytes. Neither increased HS nor the frequency of ARs were risk factors for subsequent development of BOS. Early detection and treatment of ARs might uncouple their association with BOS.

Acute Disease↗
PubMed2004

Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension.

Clinical studies have shown the importance of endothelin as a pathogenic mediator in pulmonary arterial hypertension (PAH). We describe the effects of bosentan, an oral dual endothelin receptor antagonist, in patients with PAH associated with human immunodeficiency virus (HIV) infection. In this prospective study, 16 patients with PAH associated with HIV infection in stable condition received bosentan for 16 weeks. Efficacy endpoints included exercise capacity, cardiopulmonary hemodynamics, Doppler echocardiography, New York Heart Association functional class, and quality of life (SF-36 and EQ-5D). Safety was assessed by laboratory tests, vital signs, and adverse events. Improvements were observed from baseline to Week 16 in all efficacy parameters: 6-minute walk distance (+91 +/- 60 m, p < 0.001), New York Heart Association class (14 patients improved), hemodynamics (cardiac index: +0.9 +/- 0.7 L/minute/m(2), p < 0.001), Doppler echocardiographic variables, and quality of life. During the study, no patient died and none required epoprostenol treatment. Hepatic tolerability was similar to that reported in patients with PAH. Bosentan had no negative impact on control of HIV infection. Although limited by uncontrolled design, small sample size and short duration, this study suggests that bosentan may benefit patients with PAH associated with HIV infection, and that endothelin is an important pathogenic mediator in this disease.

Adult↗
PubMed2004

Clinical classification of pulmonary hypertension.

In 1998, during the Second World Symposium on Pulmonary Hypertension (PH) held in Evian, France, a clinical classification of PH was proposed. The aim of the Evian classification was to individualize different categories sharing similarities in pathophysiological mechanisms, clinical presentation, and therapeutic options. The Evian classification is now well accepted and widely used in clinical practice, especially in specialized centers. In addition, this classification has been used by the U.S. Food and Drug Administration and the European Agency for Drug Evaluation for the labeling of newly approved medications in PH. In 2003, during the Third World Symposium on Pulmonary Arterial Hypertension held in Venice, Italy, it was decided to maintain the general architecture and philosophy of the Evian classification. However, some modifications have been proposed, mainly to abandon the term "primary pulmonary hypertension" and to replace it with "idiopathic pulmonary hypertension"; to reclassify pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis; to update risk factors and associated conditions for pulmonary arterial hypertension and to propose guidelines in order to improve the classification of congenital systemic-to-pulmonary shunts.

Genetic Predisposition to Disease↗
PubMed2004

Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy.

This study aimed to assess the long-term course of pulmonary arterial hypertension related to infection with human immunodeficiency virus (PAHRH) and the influence of antiretroviral therapy (ART) on its characteristics. We retrospectively analyzed all 47 patients in the Swiss HIV Cohort Study in whom PAHRH was diagnosed. Among 35 patients who underwent follow-up Doppler echocardiography, the right ventricular systolic pressure over right atrial pressure gradient increased by a median of 25 mm Hg in 9 patients who had not received ART, decreased by a median of 3 mm Hg in 12 patients who had received nucleoside analogs, and decreased by a median of 21 mm Hg in 14 patients who had received highly active ART (HAART) (P<.005). Among all 47 patients, median duration of survival after PAHRH diagnosis was 2.7 years. HAART significantly decreased mortality due to PAHRH as well as other causes. This study suggests a beneficial effect of combination ART in patients with PAHRH.

Adult↗
PubMed2004

Effects of sinus surgery in patients with cystic fibrosis after lung transplantation: a 10-year experience.

Chronic infectious rhinosinusitis with Pseudomonas aeruginosa is common in cystic fibrosis and may result in allograft infection after lung transplantation. Sinus surgery followed by nasal care may reduce these adverse effects. Sinus surgery was performed in 37 patients with cystic fibrosis after transplantation. Bacteriology of sinus aspirates (n=771) and bronchoalveolar lavage (BAL) (n=256) was correlated with clinical data. Sinus surgery was successful in 54% and partially successful in 27% of patients. A significant correlation between negative sinus aspirates and negative BAL and between positive sinus aspirates and positive BAL (P<0.0001) was found. Successful sinus management led to a lower incidence of tracheobronchitis and pneumonia (P=0.009) and a trend toward a lower incidence of bronchiolitis obliterans syndrome (P=0.23). Sinus surgery followed by daily nasal douching may control posttransplant lower airway colonization and infection. In the long term, this concept may lead to less bronchiolitis obliterans syndrome by decreasing bronchiolar inflammation.

Adolescent↗
PubMed2004

Ten years of lung transplantation in Switzerland: results of the Swiss Lung Transplant Registry.

OBJECTIVE: Lung transplantation has evolved from an experimental procedure to a viable therapeutic option in many countries. In Switzerland, the first lung transplant was performed in November 1992, more than ten years after the first successful procedure world-wide. Thenceforward, a prospective national lung transplant registry was established, principally to enable quality control. PATIENTS: The data of all patients transplanted in the two Swiss Lung Transplant centres Zurich University Hospital and Centre de Romandie (Geneva-Lausanne) were analysed. RESULTS: In 10 years 242 lung transplants have been performed. Underlying lung diseases were cystic fibrosis including bronchiectasis (32%), emphysema (32%), parenchymal disorders (19%), pulmonary hypertension (11%) and lymphangioleiomyomatosis (3%). There were only 3% redo procedures. The 1, 5 and 9 year survival rates were 77% (95% CI 72-82), 64% (95% CI 57-71) and 56% (95% CI 45-67), respectively. The 5 year survival rate of patients transplanted since 1998 was 72% (95% CI 64-80). Multivariate Cox regression analysis revealed that survival was significantly better in this group compared to those transplanted before 1998 (HR 0.44, 0.26-0.75). Patients aged 60 years and older (HR 5.67, 95% CI 2.50-12.89) and those with pulmonary hypertension (HR 2.01, 95% CI 1.10-3.65) had a significantly worse prognosis The most frequent causes of death were infections (29%), bronchiolitis obliterans syndrome (25%) and multiple organ failure (14%). CONCLUSION: The 10-year Swiss experience of lung transplantation compares favourably with the international data. The best results are obtained in cystic fibrosis, pulmonary emphysema and parenchymal disorders.

Adolescent↗