Local release of eosinophil peroxidase following segmental allergen provocation in asthma.

BACKGROUND: Eosinophil peroxidase (EPO) is an eosinophilic basic protein, which leads to increased permeability and damage of bronchial epithelial cells in asthma. OBJECTIVE: As little is known about its local expression and release in humans the intracellular expression in lung and peripheral eosinophils and the concentrations of EPO in bronchoalveolar lavage (BAL) fluid and serum was investigated in patients with asthma. METHODS: Twelve mild atopic asthmatic and nine control subjects underwent segmental sham and allergen challenge. EPO concentrations in BAL fluid and serum were determined by immunoassay and flow cytometry was used to determine the intracellular expression of EPO in BAL-derived and peripheral eosinophils. RESULTS: In asthmatic patients a large increase in BAL eosinophils--total cells: median 9.5 x 10(6) (range: 0.5 to 455.0 x 10(6)); relative: 38% (1 to 91%)--was detectable 24 h following allergen challenge, but peripheral blood eosinophil counts did not change. Concentrations of EPO in BAL fluid increased from 1 microg/L (1.0 to 6.8 microg/L) to 42 microg/L (5.6 to 379.6 microg/L; P < 0.01) after allergen but not after saline challenge (1.5 microg/L; 1.0 to 21.9 microg/L), whereas in control subjects all measurements were below the detection limit. Serum concentrations of EPO increased slightly from 18.3 microg/L (3.0 to 56.8 microg/L) to 27 microg/L (3.8 to 133.9 microg/L; P < 0.05) 24 h after allergen challenge in asthmatic patients. Furthermore, the intracellular expression of EPO (measured as mean fluorescence intensity) was decreased in BAL eosinophils compared with blood eosinophils (mean fluorescence intensity 29 (7 to 71) vs. 48 (20 to 85); P < 0.01) after allergen challenge. CONCLUSION: The finding of increased EPO concentrations in the BAL fluid and decreased intracellular EPO expression in pulmonary eosinophils of asthmatic patients reflects the allergen-triggered release of EPO into the bronchial space.

Effects of inhaled salbutamol in primary pulmonary hypertension.

Although lung function is grossly normal in patients with primary pulmonary hypertension (PPH), mild-to-moderate peripheral airflow obstruction can be found in the majority of patients with this disease. Therefore, beta2-agonists may affect pulmonary function, blood gases and haemodynamics in patients with PPH. Pulmonary function testing, blood gas measurements and right heart catheterisation was performed in 22 patients with PPH and the acute effects of inhaled salbutamol (0.2 mg) were measured. Salbutamol caused an increase in the forced expiratory volume in one second (FEV1) from 2446+/-704 to 2550+/-776 mL. The mean expiratory flow at 50% of the vital capacity (MEF50) rose from 58+/-17 to 66+/-21% pred. The pulmonary artery pressures remained unchanged after inhalation of salbutamol, but the cardiac output increased significantly from 3.9+/-1.4 to 4.2+/-1.4 L x min(-1) accompanied by significant increases in stroke volume and mixed venous oxygen saturation as well as a significant decrease in pulmonary vascular resistance. The arterial oxygen tension rose from 9+/-2.4 kPa (68+/-18 mmHg) at baseline to 9.7+/-2.8 kPa (73+/-21 mmHg) after inhalation of salbutamol, the alveolo-arterial oxygen gradient values improved from 6+/-2.5 kPa (45+/-19 mmHg) to 5.1+/-2.9 kPa (38+/-22 mmHg), respectively. Inhaled salbutamol has beneficial acute effects on pulmonary function, blood gases and haemodynamics in patients with primary pulmonary hypertension.

Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension.

Treatment with aerosolised iloprost, a prostacyclin analogue, has beneficial effects in patients with pulmonary arterial hypertension (PAH). It is unclear if patients, whose clinical condition deteriorates under treatment with aerosolised iloprost, benefit from switching to continuous intravenous iloprost. The current authors report on 16 patients with severe PAH who received continuous intravenous iloprost after primary or secondary failure of treatment with aerosolised iloprost. Determinants of efficacy were survival, New York Heart Association (NYHA) class, and walking distance in the 6-min walk test. Of 93 patients with PAH treated with aerosolised iloprost, 16 required switching to intravenous iloprost for clinical deterioration. These patients had severe right heart failure with a cardiac index of 1.6+/-0.2 L x min(-1) x m(-2) and a mixed-venous oxygen saturation of 52+/-6%. Five of these patients showed no improvement and eventually died. Three patients had further deterioration in NYHA class and exercise capacity; two of them underwent lung transplantation; the third patient is still alive. Eight patients showed marked clinical improvement; one underwent lung transplantation and the others are currently alive and stable. In the latter group of patients, the walking distance in the 6-min walk test increased from 205+/-94 to 329+/-59 m. It was not possible to identify clinical or haemodynamic factors that would predict whether switching from inhaled to intravenous iloprost would have a beneficial effect. In patients with pulmonary arterial hypertension who deteriorated while being treated with aerosolised iloprost, switching to continuous intravenous iloprost caused substantial improvement in exercise capacity in eight of 16 patients but could not prevent progression of pulmonary hypertension in the remaining eight patients. Since it was impossible to predict the individual effects of this approach, intravenous prostaglandin treatment should be considered in pulmonary arterial hypertension patients who deteriorate while receiving iloprost aerosol.

[An older female patient with refractory anemia and hemochromatosis]. / Eine ältere Patientin mit refraktärer Anämie und Hämochromatose.

CASE HISTORY AND CLINICAL FINDINGS: A 69-year-old woman was admitted because of a normocytic anemia. One year before an acute B19 parvovirus infection had been diagnosed, but the anemia was attributed to intestinal bleeding caused by a dysplastic colonic polyp. However, anemia persisted despite polypectomy. There was an excessive elevation of serum ferritin. ADDITIONAL EXAMINATIONS: A bone marrow biopsy and aspirate led to the diagnosis of a myelodysplastic syndrome (pure sideroblastic anemia). Ultrasound demonstrated advanced fibrosis of the liver. Fibrosis in association with severe parenchymatous siderosis was also demonstrated by histology. Analysis of the hemochromatosis gene (B-HFE, nt 845, G/A) was negative. DIAGNOSIS, THERAPY AND CLINICAL COURSE: The patient had secondary hemochromatosis due to a myelodysplastic syndrome. An acute infection with parvovirus B19 had been noted at the time of the first admission, one year before MDS was diagnosed. At that time, hemochromatosis had already caused fibrosis of the liver. However, complete regression of organ siderosis was achieved by deferoxamine administration. The myelodysplastic syndrome itself did not show any progression even 7 years after the diagnosis was established. CONCLUSION: Our case demonstrates the uncommon association between sideroblastic anemia and secondary hemochromatosis. Acute parvovirus infection may induce severe anemia in myelodysplastic syndromes. In acute B19 parvovirus infections an underlying hematologic disease should be excluded.

[Tracheobronchopathia osteochondroplastica: an uncommon cause of retention pneumonia in an elderly patient]. / Tracheobronchopathia osteochondroplastica: eine ungewöhnliche Ursache einer Retentionspneumonie.

A 79 years old patient without preexisting pulmonary disease was admitted due to pneumonia and hemoptysis. Despite intravenous antibiotic therapy he did not recover and still suffered from fever and dyspnea six days later. Fiberoptic bronchoscopia was performed in order to exclude poststenotic pneumonia. However, macroscopically a "rock-garden" trachea, the characteristic picture of osteochondroplastic tracheobronchopathy, was seen with multiple whitish irregularly shaped nodules in the trachea, except in the pars membranacea, involving both sides of the bronchial system and producing subtotal stenosis. Although cytologic examination suggested adenocarcinoma, histology confirmed the diagnosis of osteochondroplastic tracheobronchopathy. Repeated CT scans as well as control bronchoscopy served as a means of excluding simultaneous carcinoma. The case presented here demonstrates that even progressive tracheobronchopathy may remain asymptomatic for a long time until subtotal stenosis or impaired clearing mechanisms may lead to retention pneumonia. Cytologic examination may give false positive results suggesting malignant disease. However the typical macroscopic picture as well as histology should lead to the correct diagnosis.

Cytokine profile of bronchoalveolar lavage-derived CD4(+), CD8(+), and gammadelta T cells in people with asthma after segmental allergen challenge.

T cell-derived cytokines play an important role in the pathogenesis of allergic asthma, but little is known about the cytokine profile of their different subsets. The aim of the present study was to investigate the cytokine production potential of CD4(+), CD8(+), or gammadelta(+) T cells derived from the bronchoalveolar space of mild atopic asthmatic subjects (n = 11) and nonatopic control subjects (n = 9) before and 24 h after segmental allergen challenge. The cytokine production was determined using the technique of intracellular cytokine detection by flow cytometry. Comparing asthmatic with control subjects we found no difference in the percentage of CD4(+), CD8(+), or gammadelta T cells in the bronchoalveolar lavage fluid before and after allergen challenge. Before allergen challenge the proportion of cells producing the cytokines interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-13 was not different in CD4(+) and CD8(+) cells. The major difference between the groups was an increased percentage of positive-staining cells for the T helper-(Th)2-cytokines IL-5 and IL-13 in the gammadelta T-cell subset. After allergen challenge, all T-cell subsets revealed a decreased proportion of cells producing the Th1-type cytokines IFN-gamma and IL-2. The percentage of IL-4- and IL-5-positive cells did not change in all subsets, and there was a decreased proportion of IL-13- positive cells in the CD4(+) subset. These findings indicate an increased Th2-cytokine profile in gammadelta T cells. After allergen challenge, the dysbalance between Th1 and Th2 cytokines was further accentuated by a reduction in Th1 cytokine-producing T cells.

Transition of adult patients with cystic fibrosis from paediatric to adult care--the patients' perspective before and after start-up of an adult clinic.

UNLABELLED: Although most patients with cystic fibrosis (CF) survive into adulthood, many CF centres are still run by paediatricians. A transition programme from the paediatric CF unit to a newly established CF clinic at the Department of Internal Medicine was carried out for the whole group of patients > or =18 years. We aimed to evaluate our patients' opinion of the transition by analysing the results of two surveys performed before and after the transition. Nine months before the transition, we mailed an anonymous questionnaire. Statements regarding the forthcoming transition were to be answered on scales from 1 to 4, and the patients had to check a list of adjectives describing the current treatment in the paediatric CF centre as well as the presumed care in the adult unit. Fifteen months after the transition, a second survey with similar questions was carried out. RESULTS: 44 of 68 patients (65%) aged 18 to 33 years replied to the first and 56% of patients to the second questionnaire. Mean duration of treatment at the paediatric CF centre was 7.5 years (range: 1 to 22 years). Twelve patients each were classified as supporters or opponents of the transition, the remaining patients as intermediates. Older patients and those who had not required hospitalisation during the preceding year had a more positive attitude to the transition (p <0.05). There was a linear relationship between the transition attitude score and the presumed quality of care in the Internal Medicine Department (r = 0.62, p <0.001), but no relation to the quality of present paediatric care (r = -0.09, p = 0.59). In the second survey, patients rated the quality of care in the adult CF unit better than prior to the transition. CONCLUSIONS: The transition from paediatric to a newly established adult CF centre was accepted by most adult CF patients. Thorough training of all staff of the new adult unit and a close co-operation between both departments are pre-requisites to guarantee a smooth transition of all patients.

[A young man with adynamia, subepicardial ischemia and sleep apnea]. / Ein junger Mann mit Adynamie, Aussenschichtischämie und nächtlicher Apnoe.

HISTORY AND CLINICAL FINDINGS: A 44-year-old manager presented himself for the assessment of nocturnal apnoea. He reported increasing lack of drive and nightly angina pectoris. INVESTIGATIONS: Polysomnography indicated obstructive apnoea and hypopnoea with a respiratory disturbance index of 29.1, while the ECG showed T wave inversion in all leads. There was severe hypothyroidism with atrophic thyroid tissue. DIAGNOSIS, TREATMENT AND COURSE: The patient had an obstructive sleep apnoea syndrome (OSAS), hypothyroidism with myxoedema, hypopnoea and myocardial ischaemia. He was treated with negative peak airway pressure (nCPAP) ventilation, administration of L-thyroxine and initiation of anti-anginal medication, which relieved his symptoms. The severe hypothyroidism was thought to be the most important cause of his respiratory disorder and angina. CONCLUSION: This case illustrates the connection between hypothyroidism and OSAS. Hypothyroidism must be excluded in patients with OSAS, regardless of the patient's age.

[Long-term treatment of primary pulmonary hypertension with inhaled iloprost]. / Langfristige Behandlung der primären pulmonalen Hypertonie mit inhalativem Iloprost.

BACKGROUND: Continuous intravenous infusion of prostacyclin is an effective treatment for primary pulmonary hypertension. This approach, however, requires the insertion of a permanent central venous catheter with the potential risk of serious complications. Recently, administration of aerosolized iloprost, a stable prostacyclin analogue, has been introduced as an alternative therapy for severe pulmonary hypertension. METHODS: We evaluated the effects of treatment with aerosolized iloprost over a one-year period on exercise capacity and hemodynamic variables in patients with primary pulmonary hypertension. RESULTS: Twenty-four patients with primary pulmonary hypertension received aerosolized iloprost at a cumulative daily dose of 100 to 150 micrograms for at least one year. The mean (+/- SD) walking distance in the 6-min-walk test increased from 278 +/- 96 meters at base line to 363 +/- 135 meters after 12 months (P < 0.0001). During the same period, the mean pulmonary artery pressure declined from 59 +/- 10 mmHg to 52 +/- 15 mmHg (P = 0.006), the cardiac output increased from 3.8 +/- 1.4 l/min to 4.4 +/- 1.3 l/min (P = 0.02), and the pulmonary vascular resistance declined from 1.205 +/- 467 dynes.s.cm-5 to 925 +/- 469 dynes.s.cm-5 (P = 0.0003). Treatment was generally well tolerated and except for mild coughing, minor headache and jaw pain in some patients, no side effects occurred. CONCLUSIONS: Long-term treatment with aerosolized iloprost is safe and has sustained effects on exercise capacity and pulmonary hemodynamics in patients with primary pulmonary hypertension.

Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice.

A method for the noninvasive measurement of airway responsiveness was validated in allergic BALB/c mice. With head-out body plethysmography and the decrease in tidal midexpiratory flow (EF(50)) as an indicator of airway obstruction, responses to inhaled methacholine (MCh) and the allergen ovalbumin were measured in conscious mice. Allergen-sensitized and -challenged mice developed airway hyperresponsiveness as measured by EF(50) to aerosolized MCh compared with that in control animals. This response was associated with increased allergen-specific IgE and IgG1 production, increased levels of interleukin-4 and interleukin-5 in bronchoalveolar lavage fluid and eosinophilic lung inflammation. Ovalbumin aerosol challenge elicited no acute bronchoconstriction but resulted in a significant decline in EF(50) baseline values 24 h after challenge in allergic mice. The decline in EF(50) to MCh challenge correlated closely with simultaneous decreases in pulmonary conductance and dynamic compliance. The decrease in EF(50) was partly inhibited by pretreatment with the inhaled beta(2)-agonist salbutamol. We conclude that measurement of EF(50) to inhaled bronchoconstrictors by head-out body plethysmography is a valid measure of airway hyperresponsiveness in mice.

Azathioprine withdrawal in stable lung and heart/lung recipients receiving cyclosporine-based immunosuppression.

BACKGROUND: Chronic rejection is the leading cause of graft failure after (heart-) lung transplantation. Therefore, many centers maintain a triple immunosuppressive cyclosporine-based regimen including azathioprine (AZA) during the long-term course after lung transplantation. However, an increased risk of malignancies has been attributed to prolonged immunosuppression, and there is evidence that less intensive immunosuppressive regimens are feasible in the long-term course after other solid organ transplantation. Therefore, we investigated the effects of AZA withdrawal in stable lung transplant recipients. METHODS: A prospective study was performed to assess the effects of AZA withdrawal in patients who received a lung transplant more than 4 years ago with stable graft function defined by absence of rejection episodes for at least 2 years and no evidence of bronchiolitis obliterans. RESULTS: A total of 24 patients qualified for the study and 7 discontinued AZA. Despite the small number of patients, termination of the study became necessary after 12 months because significantly more grafts showed deteriorating function after withdrawing AZA (4 of 7) compared to recipients continuing a triple therapy (1 of 17; P<0.05). In recipients with deteriorating graft function conventional treatment with high-dose corticosteroids and reinstitution of AZA failed to stop the development of obliterative bronchiolitis. CONCLUSIONS: Our data reinforce the importance of a potent immunosuppressive regimen for the maintenance of stable graft function after lung transplantation.

Interleukin 16 and T-cell chemoattractant activity in bronchoalveolar lavage 24 hours after allergen challenge in asthma.

IL-16 has been shown to be one of the earliest CD4(+) cell chemoattractants present in BAL 4-6 h after antigen challenge but little is known about its persistence and biological activity after 6 h. We determined the concentration of IL-16 using ELISA and the T-cell chemoattractant activity using a modified Boyden chamber assay in unconcentrated BAL fluid from 13 patients with mild asthma and 9 nonatopic control subjects at baseline and 24 h after segmental allergen or saline challenge. Furthermore, the percentage of IL-16-producing T cells was determined in the different samples of BAL fluid using a flow cytometric intracellular cytokine assay. Although no substantial levels of IL-16 protein were detectable in BAL fluid from control subjects and patients with asthma at baseline and after saline challenge, IL-16 concentrations were significantly elevated in patients with asthma after allergen challenge (median, 97 pg/ml; range, 38-362 pg/ml; p < 0.01). Furthermore, there was an increased T-cell chemoattractant activity after allergen challenge in patients with asthma (p < 0.01), which could be blocked by preincubation with anti-IL-16 antibodies and which correlated significantly with the IL-16 protein levels (R = 0.90, p < 0.01) and with the level of Fas ligand expression on BAL CD4(+) cells (R = 0. 80, p < 0.05). A high percentage (mean 70-90%) of CD4(+) and CD8(+) cells stained positively for IL-16 in both patients with asthma and control subjects without differences after allergen or saline challenge. These data demonstrate that the increased chemotactic activity for T cells in patients with asthma is mainly attributable to IL-16. Although T cells by themselves are able to produce IL-16, other cells, such as epithelial cells, have to be considered as further sources for this cytokine in patients with asthma.

Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue.

BACKGROUND: Continuous intravenous infusion of epoprostenol (prostacyclin) is an effective treatment for primary pulmonary hypertension. This approach requires the insertion of a permanent central venous catheter, with the associated risk of serious complications. Recently, aerosolized iloprost, a stable prostacyclin analogue, has been introduced as an alternative therapy for severe pulmonary hypertension. METHODS: We evaluated the effects of aerosolized iloprost on exercise capacity and hemodynamic variables over a one-year period in patients with primary pulmonary hypertension. RESULTS: Twenty-four patients with primary pulmonary hypertension received aerosolized iloprost at a daily dose of 100 or 150 microg for at least one year. The mean (+/-SD) distance covered in the six-minute walk test increased from 278+/-96 m at base line to 363+/-135 m after 12 months (P<0.001). During the same period, the mean pulmonary arterial pressure before the inhalation of iloprost declined from 59+/-10 mm Hg to 52+/-15 mm Hg (P=0.006), cardiac output increased from 3.8+/-1.4 liters per minute to 4.4+/-1.3 liters per minute (P=0.02), and pulmonary vascular resistance declined from 1205+/-467 dyn x sec x cm(-5) to 925+/-469 dyn x sec x cm(-5) (P<0.001). The treatment was generally well tolerated, except for mild coughing, minor headache, and jaw pain in some patients. CONCLUSIONS: Long-term treatment with aerosolized iloprost is safe and has sustained effects on exercise capacity and pulmonary hemodynamics in patients with primary pulmonary hypertension.

Sarcoidosis and common variable immunodeficiency. A case of a malignant course of sarcoidosis in conjunction with severe impairment of the cellular and humoral immune system.

The occurrence of sarcoidosis in combination with common variable immunodeficiency (CVID) has been described in a small number of patients. In these patients, sarcoidosis consisted of lymphadenopathy, mild to moderate pulmonary involvement and hepatosplenomegaly. However, severe and rapidly progressive pulmonary fibrosis in combination with a severe defect of the cellular and humoral immune system has not been described yet. In our patient, defects of the T and B cell system resulted in severe immunodeficiency. The defect of the humoral immune system was characterized by the impairment of specific antibody production in vivo. In addition, hypogammaglobulinemia with missing IgA and IgE along with a marked defect in IgM and IgG production was noted. There was a progressively reduced lymphocyte proliferation in response to T cell mitogens, while proliferation after specific IL-2 stimulation was normal. A Th1 lymphocyte-subset-like profile might thus play a role in the pathogenesis and might form the connecting link between sarcoidosis and CVID. This is the report of a so far new and unique combination of severe immunodeficiency and sarcoidosis also associated with a congenital dysmorphia consisting of a palatal cleft. The findings of the 40 patients with CVID and sarcoidosis reported so far are discussed in order to point out the typical features of patients with this uncommon syndrome.

A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group.

OBJECTIVE: We sought to compare the acute hemodynamic effects of inhaled nitric oxide (NO) and aerosolized iloprost in primary pulmonary hypertension (PPH). BACKGROUND: Inhalation of the stable prostacyclin analogue iloprost has recently been described as a novel therapeutic strategy for PPH and may offer an alternative to continuous intravenous infusion of prostacyclin or inhalation of NO. METHODS: During right heart catheterization, 35 patients with PPH sequentially inhaled 40 ppm of NO and 14 to 17 microg of iloprost, and the effects on hemodynamics and blood gases were monitored. RESULTS: Both NO and iloprost caused significant increases in cardiac output, mixed-venous oxygen saturation and stroke volume as well as significant decreases in pulmonary artery pressure and pulmonary vascular resistance, whereas only inhaled iloprost significantly increased the arterial PO2 (p = 0.01). Compared with inhaled NO, aerosolized iloprost was more effective in reducing pulmonary artery pressure (-8.3 +/- 7.5 mm Hg vs. -4.3 +/- 8.8 mm Hg; p = 0.0001) and the pulmonary vascular resistance (-447 +/- 340 dynes x s x cm(-5) vs. -183 +/- 305 dyne x s x cm(-5); p < 0.0001). Furthermore, aerosolized iloprost caused a significantly greater increase of the cardiac output compared with NO (+0.7 +/- 0.6 liter/min vs. +0.3 +/- 0.4 liter/min; p = 0.0002) and had a more pronounced effect on the mixed-venous oxygen saturation (p = 0.003). CONCLUSIONS: During acute drug testing, aerosolized iloprost was more potent than inhaled NO as a pulmonary vasodilator in PPH at the doses used in this study.

Lung transplantation--10-year experience.

OBJECTIVE: The experience at our institution with various forms of lung transplantation (heart-lung, double lung and single lung) from December 1987 to September 1998 is reviewed and discussed. METHODS: During this decade, 282 procedures (46 heart-lungs (HLTx), 142 double lungs (DLTx) and 94 single lungs (SLTx)) have been performed in 258 patients (140 male, 118 female; age: 38 +/- 13 years). Major indications included pulmonary fibrosis (n = 73), obstructive lung disease (n = 55), cystic fibrosis (n = 48), primary pulmonary hypertension (n = 36), secondary pulmonary hypertension (majority Eisenmenger's syndrome) (n = 30), and retransplantation (n = 24). RESULTS: Early postoperative mortality (<90 days) was 13.9% (n = 36). The 1-, 3-, and 5-year survival rates in all recipients was 77, 70 and 63%, respectively. There was no significant difference in 1-year survival rates between the different procedures (HLTx: 78%, DLTx: 77%, SLTx: 77%). Significantly better 1-year survival was achieved in patients with cystic fibrosis (89%), pulmonary fibrosis (81%), obstructive lung disease (74%), and Eisenmenger's syndrome (83%) when compared to patients with primary pulmonary hypertension (55%). Survival rates remained unchanged during this period despite expanding indications during the last years. Causes of death in 90 recipients (HLTx: n = 19, DLTx: n = 37, SLTx: n = 34) included sepsis (n = 42), obliterative bronchiolitis (n = 28), cardiac failure (n = 5), and early allograft dysfunction (n = 2). Freedom from bronchiolitis obliterans syndrome (BOS) (>stage I ISHLT) was 80% at 1 year and 45% at 5 years. CONCLUSIONS: Lung transplantation offers a true therapeutic option with good early and midterm results. Yet, chronic graft dysfunction represents a major obstacle for long-term benefit of this procedure.

Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension.

Assessment of cardiac output is an important part of the management of patients with pulmonary hypertension. The accuracy of the thermodilution technique in patients with low cardiac output or severe tricuspid regurgitation has been questioned. To address this issue, we simultaneously compared 105 cardiac output measurements by the Fick method and thermodilution in 35 patients with pulmonary hypertension. Moreover, we evaluated the acetylene rebreathing technique, a noninvasive method of determining cardiac output. The mean difference +/- 95% limit of agreement between thermodilution and the Fick method was +0.01 +/- 1.1 L/min. The mean difference +/- 95% limit of agreement between acetylene rebreathing and the Fick method was -0.23 +/- 1.14 L/min. Neither the mean agreement nor the 95% limits of agreement of both thermodilution and acetylene rebreathing with the Fick method were affected by the presence of low cardiac output or severe tricuspid regurgitation. We conclude that thermodilution and acetylene rebreathing are useful tools for assessing cardiac output in patients with pulmonary hypertension, even in the presence of low cardiac output or severe tricuspid regurgitation.