Pascaline Priou

Long-Term Outcome of Noninvasive Positive Pressure Ventilation for Obesity Hypoventilation Syndrome

BACKGROUNDnFew data are available on the long-term outcome of noninvasive positive pressure ventilation (NPPV) for obesity hypoventilation syndrome (OHS). This study was designed to determine long-term survival, treatment adherence, and prognostic factors in patients with OHS in whom NPPV was initiated in an acute setting vs under stable clinical conditions.nnnMETHODSnOne hundred thirty consecutive patients with OHS (56 women) who started NPPV between January 1995 and December 2006 either under stable conditions (stable group, n = 92) or during ICU management of acute hypercapnic exacerbation (acute group, n = 38) were retrospectively analyzed.nnnRESULTSnArterial blood gases and the Epworth sleepiness scale were both significantly improved after 6 months of NPPV. With a mean follow-up of 4.1 +/- 2.9 years, 24 (18.5%) patients died and 24 (18.5%) discontinued NPPV. On Kaplan-Meier analysis, 1-, 2-, 3-, and 5-year survival probabilities were 97.5%, 93%, 88.3%, and 77.3%, respectively. Mortality was lower than that described in a previous series of patients with untreated OHS. Supplemental oxygen therapy was the only independent predictor of mortality. The probability of continuing NPPV was 80% at 3 years with a high rate of daily use ( > 7 h). Female sex was predictive of lower long-term adherence to NPPV. The acute and stable groups did not differ in terms of arterial blood gases and Epworth sleepiness scale at 6 months, long-term survival, and treatment adherence.nnnCONCLUSIONSnThe results of this study support long-term NPPV as an effective and well-tolerated treatment of OHS whether initiated in the acute or chronic setting.

Endothelial Dysfunction and Circulating Microparticles from Patients with Obstructive Sleep Apnea

Endothelial dysfunction is involved in vascular complications of obstructive sleep apnea (OSA). In this study, circulating microparticles (MPs) from patients with OSA-induced nocturnal desaturations were characterized and their effects on endothelial function were evaluated. Two age-matched groups of patients undergoing polysomnography for OSA were compared: 35 desaturators with a 3% oxyhemoglobin desaturation index (ODI) > or = 10 events per hour of sleep and 27 nondesaturators with ODI <10 events per hour. MPs were characterized by flow cytometry and then either used to treat in vitro human endothelial cells or to study endothelial function in mice. Circulating MPs did not differ between groups, but MPs from granulocytes and activated leukocytes (CD62L(+)) were found at higher levels in desaturators. In vitro, MPs from desaturators reduced endothelial nitric oxide (NO) production by enhancing phosphorylation of endothelial NO synthase at the site of inhibition and expression of caveolin-1. CD62L(+) MPs positively correlated with ODI. Endothelial NO production negatively correlated with both CD62L(+) MPs and ODI. MPs from desaturators increased expression of endothelial adhesion molecules including E-selectin, ICAM-1 and ITGA5, and cyclooxygenase 2. Moreover, injection of MPs from desaturators into mice impaired endothelium-dependent relaxation in aorta and flow-induced dilation in small mesenteric arteries. This study demonstrates an association between endothelial dysfunction and increased circulating levels of CD62L(+) MPs. This may initiate atherogenic processes in patients with OSA and severe nighttime hypoxia.

Impact of Mandibular Advancement Therapy on Endothelial Function in Severe Obstructive Sleep Apnea

Rationale: Endothelial dysfunction, a major predictor of late cardiovascular events, is linked to the severity of obstructive sleep apnea (OSA). Objectives: To determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. Methods: In this trial, we randomized patients with severe OSA and no overt cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on an intention‐to‐treat basis. An embedded microsensor objectively measured treatment compliance. Measurements and Main Results: A total of 150 patients (86% males; mean [SD] age, 54 [10] yr; median [interquartile range] apnea‐hypopnea index, 41 [35‐53]; mean [SD] Epworth sleepiness scale, 9.3 [4.2]) were randomized to effective mandibular advancement device (n = 75) or sham device (n = 75). On intention‐to‐treat analysis, effective mandibular advancement device therapy was not associated with improvement of endothelial function compared with the sham device. Office and ambulatory blood pressure outcomes did not differ between the two groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea‐hypopnea index (P < 0.001); microarousal index (P = 0.008); and symptoms of snoring, fatigue, and sleepiness (P < 0.001). Mean (SD) objective compliance was 6.6 (1.4) h/night with the effective mandibular advancement device versus 5.6 (2.3) h/night with the sham device (P = 0.006). Conclusions: In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms but had no effect on endothelial function and blood pressure despite high treatment compliance. Clinical trial registered with www.clinicaltrials.gov (NCT 01426607).

Home Non-Invasive Ventilation Fails to Improve Quality of Life in the Elderly: Results from a Multicenter Cohort Study

Background Home non-invasive ventilation (NIV) is a widely used treatment for chronic hypoventilation but little is known on its impact in the elderly. In a multicenter prospective cohort study, we studied tolerance and efficacy of domiciliary NIV in patients aged 75 or more compared to younger ones. Methods and Results 264 patients with at least a six-month follow-up were analyzed. Among them, 82 were elderly. In the elderly and the younger, we found an improvement of arterial blood gas, the Epworth sleepiness scale and the Pittsburgh sleep quality index at 6 months. Mean daily use of NIV at 6 months was 7 hours and the rate of non-adherent patients was similar in both group. Health-related quality of life (HRQL) assessed by SF-36 questionnaires did not change significantly after NIV initiation in the elderly whereas HRQL improved in the less than 75. On univariate analysis, we found that diabetes was a predictive factor for non-adherence in the elderly (Odds ratio: 3.95% confidence interval: 1.06–8.52). Conclusion NIV was efficient in the elderly while evaluation at 6 months showed a good adherence but failed to improve HRQL.

Pneumopathie médicamenteuse sous traitement par venlafaxine et propranolol

Introduction La venlafaxine et le propranolol ont ete isolement incrimines dans de rares observations de pneumopathies medicamenteuses. Nous rapportons un cas de pneumopathie diffuse imputee a l’association des 2 molecules et discutons leur possible interaction. Observation Une patiente de 55 ans sous venlafaxine depuis 1†an etait admise en reanimation pour une insuffisance respiratoire aigue, 1 mois apres introduction d’un traitement par propranolol, dans un contexte de cirrhose decompensee. Une pneumopathie a Mycoplasma pneumoniae etait diagnostiquee. Apres une evolution favorable sous antibiotiques, une nouvelle degradation respiratoire survenait apres reintroduction de la venlafaxine et du propranolol, suivie d’une amelioration spontanee a l’arret du traitement. Le propranolol repris seul n’entrainait pas de recidive a 3 mois. Les 2 molecules etant metabolisees par le meme isoenzyme (CYP2D6) du cytochrome P450, la toxicite pulmonaire a pu provenir d’une competition entre les deux medicaments sur leur voie de degradation enzymatique. L’insuffisance hepatocellulaire a pu egalement contribuer au surdosage et a la toxicite pulmonaire medicamenteuse. Conclusions La venlafaxine et le propranolol ont une voie commune de degradation enzymatique. Leur association peut etre compliquee de pneumopathie medicamenteuse.

Effect of mandibular advancement therapy on inflammatory and metabolic biomarkers in patients with severe obstructive sleep apnoea: a randomised controlled trial

Systemic inflammation and metabolic disorders are among the mechanisms linking obstructive sleep apnoea (OSA) and cardiovascular disease (CVD). In 109 patients with severe OSA and no overt CVD, biomarkers of inflammation (C reactive protein, interleukin-6, tumour necrosis factor-α and its receptors, adiponectin, leptin and P-selectin), glucose and lipid metabolism, and N-terminal pro-brain natriuretic peptide, were measured before and after 2 months of treatment with a mandibular advancement device (MAD) (n=55) or a sham device (n=54). MAD reduced the Apnoea–Hypopnoea Index (p<0.001) but had no effect on circulating biomarkers compared with the sham device, despite high treatment adherence (6.6u2009hour/night). Trial registration number NCT01426607.

Impact of mandibular advancement therapy on endothelial function in severe obstructive sleep apnoea

This study aimed to determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. We randomized patients with severe OSA and no medical history of cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on intention-to-treat bases. An embedded micro sensor objectively measured treatment compliance. 150 patients [86% males; mean (SD) age, 54 (10); median [IQR] apnea-hypopnoea index, 41 [35-53]; mean Epworth sleepiness scale, 9.3 (4.2)] were randomized to effective mandibular advancement device (n=75) or sham device (n=75). In the intention-to-treat analysis, effective mandibular advancement device therapy was not associated with an improvement in endothelial function when compared to sham device. Office and ambulatory blood pressure outcomes did not differ between the 2 groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea-hypopnea index (p vs 5.6 (2.3) h/night with sham device (p=0.006). Conclusion In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms with no effect on endothelial function and blood pressure despite high treatment compliance.