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Marc Humbert

Publications and source records attributed to Marc Humbert.

63 records · Page 4Linked to original sources
PubMed2002

Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: The purpose of this study was to assess the efficacy and safety of beraprost sodium, an orally active prostacyclin analogue, in New York Heart Association (NYHA) functional class II and III patients with pulmonary arterial hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has been proven effective. However, this treatment is associated with serious complications arising from the complex delivery system. METHODS: In this double-blind, placebo-controlled study, 130 patients with PAH were randomized to the maximal tolerated dose of beraprost (median dose 80 microg four times a day) or to placebo for 12 weeks. The primary end point was the change in exercise capacity assessed by the 6-min walk test. Secondary end points included changes in Borg dyspnea index, cardiopulmonary hemodynamics and NYHA functional class. RESULTS: Patients treated with beraprost improved exercise capacity and symptoms. The difference between treatment groups in the mean change of 6-min walking distance at week 12 was 25.1 m (95% confidence interval [CI]: 1.8 to 48.3, p = 0.036). The difference in the mean change of Borg dyspnea index was -0.94 (95% CI: -1.63 to -0.24, p = 0.009). In the sub-group of patients with primary pulmonary hypertension, the difference in the mean change of 6-min walking distance was 46.1 m (95% CI: 3.0 to 89.3, p = 0.035). Cardiopulmonary hemodynamics and NYHA functional class had no statistically significant changes. Drug-related adverse events were common in the titration phase and decreased in the maintenance period. CONCLUSIONS: Beraprost improves exercise capacity and symptoms in NYHA functional class II and III patients with PAH and, in particular, in those with primary pulmonary hypertension.

Administration, Oral↗
PubMed2002

Chemokine RANTES in severe pulmonary arterial hypertension.

The recent discovery that sporadic and familial primary pulmonary hypertension can be associated with germline mutations of genes encoding receptor members of the transforming growth factor-beta family has focused much attention on cytokines and growth factors in pulmonary vascular disorders. Production of several cytokines has been demonstrated in severe pulmonary arterial hypertension, emphasizing the possible influence of inflammatory mechanisms in this condition. Moreover, perivascular inflammatory cell infiltrates composed of macrophages and lymphocytes have been detected in plexiform lesions of primary pulmonary hypertension. Chemokine RANTES is an important chemoattractant for monocytes and T cells. We therefore hypothesize that chemokine RANTES promotes cell recruitment in the lungs of patients displaying severe pulmonary arterial hypertension. Reverse transcriptase polymerase chain reaction demonstrated elevated RANTES mRNA expression in 10 lung samples from patients with severe pulmonary arterial hypertension, as compared with seven control subjects. In situ hybridization and immunohistochemistry confirmed that endothelial cells were the major source of RANTES within the pulmonary artery wall of the patients. Serial sections analysis showed that RANTES expression was associated with CD45+ inflammatory cell infiltrates. These results support the concept that inflammatory mechanisms play a role in the natural history of pulmonary arterial hypertension.

Adult↗
PubMed2002

Pulmonary artery pressure-flow relations after prostacyclin in primary pulmonary hypertension.

Exercise tolerance improves within a few weeks after prostacyclin initiation in patients with primary pulmonary hypertension even in the absence of significant changes in resting pulmonary vascular resistance and/or in patients who fail to respond to an acute vasodilator challenge. We tested the hypothesis that this early effect of prostacyclin may be ascribable to an improved pressure-flow response of the pulmonary circulation to exercise. Pulmonary hemodynamic variables at rest and during exercise and the 6-min walking distance were determined before and after 6 wk of continuous intravenous prostacyclin treatment (11 +/- 1.5 ng/kg/min) in seven patients unresponsive to an acute nitric oxide vasodilator test. Mean pulmonary arterial pressure/cardiac index coordinates obtained during exercise were pooled, and the slopes of these plots were compared using covariance analysis. All hemodynamic variables at rest were unchanged after prostacyclin. By contrast, the 6-min walking distance improved in all patients (mean increase, 81 m) and the slope of the mean pulmonary artery pressures/cardiac indexes plot decreased with prostacyclin, from 18.2 to 13.1 mm Hg/L/min/m(2) (p < 0.01). These results suggest that the improvement in exercise tolerance seen after 6 wk of prostacyclin therapy may be ascribable to a decrease in incremental pulmonary vascular resistance during exercise.

Antihypertensive Agents↗
PubMed2002

Pulmonary arterial hypertension: thin-section CT predictors of epoprostenol therapy failure.

PURPOSE: To correlate pretherapeutic thin-section computed tomographic (CT) findings in patients with pulmonary hypertension with the risk of fatality with treatment with epoprostenol. MATERIALS AND METHODS: Seventy-three consecutive patients with severe pulmonary hypertension treated with epoprostenol were retrospectively separated into two groups. The first group included 12 patients who had a fatal outcome with epoprostenol therapy. The second group (n = 61) was a reference group of patients with epoprostenol-induced clinical improvement. Pretherapeutic thin-section CT scans of each patient were reviewed. RESULTS: Poorly defined nodular opacities (P =.003), septal lines (P =.04), pleural effusion (P =.01), and adenopathy (P =.009) strongly correlated with a risk of clinical worsening with treatment. In six patients in group 1, postmortem examination of the lung revealed either pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. CONCLUSION: On pretherapeutic thin-section CT scans, poorly defined nodular opacities, septal lines, pleural effusion, and adenopathy should raise suspicion for pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis and provoke possible further evaluation before epoprostenol therapy.

Adult↗
PubMed2002

[Mutations of genes coding for TGF-beta receptors (BMPR2 and ALK-1) in primary pulmonary arterial hypertension].

Pulmonary hypertension is defined by an elevation in pulmonary artery pressure leading to progressive right heart failure and death. Primary (idiopathic) pulmonary hypertension (PPH) is a rare disease with an estimated incidence of 2 per million inhabitants per year in France. Abnormal pulmonary artery angiogenesis is a characteristic feature of this condition including endothelial and smooth muscle cell proliferation in small to medium-sized pulmonary arteries. The recent discovery of germline mutations of genes coding for receptor members of TGF-beta (BMPR-2 et ALK-1) in PPH represents a considerable progress in the understanding of this pulmonary orphan disease. This review summarizes the current genetic data obtained in this condition.

Activin Receptors, Type I↗
PubMed2002

[Pulmonary hypertension associated with systemic sclerosis].

Pulmonary hypertension is a rare but well known life-threatening complication of scleroderma and particularly in its limited variant, the CREST syndrome (Calcification, Raynaud phenomenon, Esophageal dysmotility, Sclerodactily, Telangiectasia). The aim of this article is to analyze the available literature and to report the experience of a center for pulmonary vascular diseases. Dyspnea is the main symptom and is frequently severe. Echocardiography is an excellent tool to detect pulmonary hypertension. However, right-heart catheterization is necessary to confirm the diagnosis of pulmonary hypertension and to test vasoreactivity with a potent vasodilator such as nitric oxide. Hemodynamic parameters are less severe in patients with connective tissue diseases perhaps because of an earlier diagnosis. A significant lower proportion of patients presents an acute vasodilator response suggesting an early constitution of irreversible pulmonary vascular lesions. Continuous intravenous epoprostenol therapy seems to be less effective as compared with patients with primitive pulmonary hypertension and does not improve survival. In our experience, immunosuppressive therapy does not improve hemodynamic or clinical data. Novel therapies including oral, sub-cutaneous or inhaled stable prostacyclin analogues and endothelin receptor antagonists are currently evaluated in large placebo-controlled trials.

Antihypertensive Agents↗
PubMedDate not supplied

Primary pulmonary hypertension: Current therapy.

Because the causes of primary pulmonary hypertension (PPH) remains unknown, the therapeutic approach of the disease can be only empirical, based on the pathology and pathobiology of pulmonary circulation. Despite the inability to cure the disease, therapeutic advances over the past 20 years have contributed to an improvement of quality of life and prolonged survival in PPH patients. Current therapeutic approach of PPH mostly includes limitation of physical activity, long-term anticoagulation, and vasodilator therapy. Among all tested oral vasodilators, calcium-channel blockers are the most efficient long-term therapies by improving symptoms and hemodynamics in a subset of PPH patients (10% to 15%) who acutely respond to such drugs. Acute pulmonary vasodilator response to inhalation of nitric oxide can predict acute and chronic responses to oral calcium-channel blockers. A better understanding of the pathogenesis of PPH has changed the focus of medical treatments from purely chronic vasodilator therapy to the evaluation of agents, such as prostaglandins, that may reverse the proliferation of pulmonary vascular cells and result in regression of the pulmonary vascular hypertrophy and remodeling. Long-term treatment with intravenous epoprostenol (prostaglandin I(2) or prostacyclin) improves exercise capacity, hemodynamics and survival in most patients with PPH in functional class NYHA III or IV, and may be currently considered as the "gold standard" therapy for severe patients. However, response to long-term epoprostenol therapy may be incomplete, adverse effects are common, and survival remains unsatisfactory (55% at 5 years). In such patients with severe pulmonary hypertension refractory to medical therapy, atrioseptostomy and lung transplantation can be indicated.

Anticoagulants↗