Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension

Background Pulmonary vasodilators in general and prostacyclin therapy in particular, have markedly improved the outcome of patients with pulmonary arterial hypertension (PAH). As endothelial dysfunction is a key feature of PAH, and as endothelial progenitor cells (EPC) may contribute to vascular repair in PAH, we suspected that prostacyclin therapy might enhance EPC numbers and functions. In the present study, objectives were to determine whether EPC may contribute to vasodilator treatment efficacy in PAH. Methods We quantified CD34+ cells, CFU-Hill and ECFC (endothelial colony forming cells) in peripheral blood from children with idiopathic PAH (n = 27) or PAH secondary to congenital heart disease (n = 52). CD34+ were enumerated by flow cytometry, CFU-Hill and ECFC by a culture assay. ECFC grown ex vivo were tested for their angiogenic capacities before and after prostacyclin analog therapy (subcutaneous treprostinil). Results ECFC counts were significantly enhanced in the 8 children treated with treprostinil, while no change was observed in children receiving oral therapy with endothelin antagonists and/or PDE5 inhibitors. CD34+ cell and CFU-Hill counts were unaffected. ECFC from patients treated with treprostinil had a hyperproliferative phenotype and showed enhanced angiogenic potential in a nude mouse preclinical model of limb ischemia. Conclusions ECFC may partly mediate the clinical benefits of prostanoids in pulmonary arterial hypertension

High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study

One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis

Contribution majeure de l'enquête environnementale au diagnostic de deux cas de pneumopathie d'hypersensibilité aux plumes d'oie

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

PHYSIOPATHOLOGIE DE LA BRONCHIOLITE OBLITERANTE CHEZ LES TRANSPLANTES PULMONAIRES (IMPLICATION DE 4 MEDIATEURS PROFIBROSANTS : TGF-BETA, IGF-1,ET-1 ET PDGF)

PARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Caractéristiques cliniques et pronostic des patients avec pneumopathie interstitielle diffuse admis en soins intensifs pour détresse respiratoire

Il n existe que peu de données sur le pronostic des patients présentant une pneumopathie interstitielle diffuse (PID) et admis en réanimation. Evaluer le devenir des patients avec PID admis en réanimation pour détresse respiratoire aiguë, avec un intérêt particulier pour ceux atteint de Fibrose Idiopathique (FI) ou de pneumopathie médicamenteuse. Identification rétrospective des patients avec PID admis en réanimation ou en soins continus pneumologiques à l HEGP entre 1993 et 2009. Le critère de jugement principal était la mortalité intra-hospitalière.72 patients ont été inclus, divisés en 3 groupes : FI, n=28 ; pneumopathie médicamenteuse (PM), n=20 et diverses PID, n=24. Les taux de mortalité étaient respectivement de 68, 40 et 25% pour les FI, les PM et les diverses PID (p=0,006). Ils atteignaient 100, 64 et 60% en cas de recours à la ventilation mécanique (p=0,007). En analyse multivariée, le recours à l assistance ventilatoire (invasive ou non invasive) (OR= 35; [95% IC, 5-255]), le type de PID (FI vs divers PID) (OR=22; [95% IC, 3-147]) et le traitement par corticoïdes à la phase aigue (OR=0.19; [95% IC, 0.04-0.99]) ont été identifiés comme facteurs prédictifs de mortalité. Cette étude confirme le mauvais pronostic des patients avec FI admis en réanimation et particulièrement en cas de ventilation mécanique. En revanche, les pneumopathies médicamenteuses ou autres formes de PID ont, malgré des critères de sévérité similaires à l entrée, un meilleur pronostic. Enfin, l instauration d une corticothérapie à la phase aigue apparaît comme un facteur protecteur quel que soit le type de PID.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

0304 : Treprostinil indirectly regulates endothelial colony forming cell angiogenic properties by increasing VEGF-A produced by mesenchymal stem cells

Prostacyclin therapy has markedly improved the outcome of patients with pulmonary hypertension (PH). Endothelial dysfunction is a key feature of PH, so the aim of our study was to determine how treprostinil contributes to the angiogenic functions of endothelial progenitors (ECFC). Treprostinil did not modify clonogenic properties nor endothelial differentiation potential from cord blood stem cells. Treprostinil treatment significantly increased the vessel-forming ability of ECFC combined with mesenchymal stem cells (MSC) in Matrigel implanted in nude mice. Silencing or blocking VEGF-A in MSC blocked the pro-angiogenic effect of treprostinil in vitro and in vivo. Clinical relevance was confirmed by the high level of VEGF-A detected in plasma from patients with pediatric pulmonary hypertension who had been treated with treprostinil. Our results suggest that VEGF-A level in patients could be a surrogate biomarker of treprostinil efficac