Endothelial Dysfunction and Specific Inflammation in Obesity Hypoventilation Syndrome

BACKGROUND: Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown. QUESTION: To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients. METHODOLOGY: 14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays. PRINCIPAL FINDINGS: OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11). CONCLUSIONS: Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00603096

Multi-detector CT evaluation in patients suspected of tracheobronchomalacia: Comparison of end-expiratory with dynamic expiratory volumetric acquisitions.

International audiencePURPOSE: The aim of this study was to compare dynamic expiratory imaging and end-expiratory imaging using multi-detector CT (MDCT) of the central airways in patients suspected of tracheobronchomalacia (TBM). METHODS: This study had local ethical committee approval. Seventy patients suspected of TBM were prospectively included. All patients underwent evaluation of central airways by three different low-dose MDCT acquisitions: end inspiration, end expiration, and dynamic expiration. Degree of airway collapse was measured by calculating the percentage change in the area and diameter of the airways between inspiratory and the two expiratory techniques at three levels of the trachea and in the sagittal diameter of the right and left main bronchi. Three threshold levels of percentage reduction in diameter or area (30%, 50%, and 70%) for defining TBM were evaluated. RESULTS: In the entire population, the mean percentage of airway collapse was significantly greater with dynamic expiratory imaging than with the end-expiratory imaging at three different levels: lower thoracic trachea (26% vs. 16.6%, p<0.009), right (25.2% vs. 14%, p<0.01) and left main (24.7% vs. 13.3%, p<0.01) bronchus. Whatever the threshold value for defining TBM, dynamic expiratory imaging always resulted in diagnosing TBM in more patients than end-expiratory imaging. CONCLUSIONS: Dynamic expiratory imaging shows a significantly greater degree and a significantly greater extent of airway collapse than standard end-expiratory imaging in patients suspected of TBM. Further evaluation of the clinical relevance of such findings is warranted

Évaluation pronostique de biomarqueurs dans l'hypertension artérielle pulmonaire. Justification et plan expérimental

National audienceCurrent situation Pulmonary arterial hypertension (PAH) is a serious disease. Its prognostic is based on the functional status quantified by the NYHA class and the 6-min walking test, and the hemodynamic data. The algorithms of treatment are solely based on the hemodynamic data and the functional status. The main objective is to test whether basal concentrations of isoprostanes, Big endotheline 1, ADMA, high sensitivity CRP, NT-Pro-BNP and cardiac troponin T are a 3-year prognostic factor in PAH using a combined criterion: death from any cause and pulmonary or cardiopulmonary transplantation. Materials and methods This is a multicenter, prospective, prognostic, single blinded study (plasma and urinary samples being blinded). The study started in november 2003, running for 2 years, with a 3 year follow-up for each patient. The main inclusion criterion is PAH. The data analysis will use a multivariable Cox model, taking into account the functional and hemodynamic parameters. Expected results This study will determine whether any of the biomarkers tested provides additional prognostic information in PAH in addition to the functional and hemodynamic parameters.Position du problème L'hypertension artérielle pulmonaire (HTAP) est une pathologie grave dont l'évaluation du pronostic repose sur l'étude du retentissement fonctionnel et sur les données hémodynamiques obtenues par cathétérisme. L'algorithme de prise en charge thérapeutique est exclusivement basé sur les données du cathétérisme et du retentissement fonctionnel. L'objectif principal est de tester l'hypothèse selon laquelle les concentrations basales d'isoprostanes, de Big endothéline 1, d'ADMA, de CRP ultrasensible, de NT-Pro-BNP et de troponine T cardiaque sont un facteur pronostique dans l'HTAP à 3 ans à l'aide d'un critère combiné comprenant la mortalité et la transplantation pulmonaire ou cardio-pulmonaire. Matériel et méthodes Il s'agit d'une étude multicentrique, prospective, pronostique, en simple-insu (échantillons urinaires et plasmatiques dosés en aveugle). L'étude a débuté en novembre 2003, avec un suivi de 3 ans prévu par patient, et une durée d'inclusion de 2 ans. Le principal critère d'inclusion est la présence d'une hypertension artérielle pulmonaire. Un modèle de Cox sera mis en œuvre en analyse multivariée afin d'identifier un éventuel facteur pronostique, en tenant compte des paramètres fonctionnels et hémodynamiques. Résultats attendus Cette étude prospective permettra de déterminer si l'un des biomarqueurs étudiés présente un intérêt pronostique indépendamment des paramètres pronostiques fonctionnels et hémodynamiques connus