Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol.

INTRODUCTION: Obstructive sleep apnoea (OSA) is a prevalent disease associated with cardiovascular events. Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events. Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes, resulting in sympathetic overactivity and blood pressure (BP) elevation. Continuous positive airway pressure (CPAP) is the primary treatment for OSA and induces a small but significant reduction in BP. The use of auto-adjusting positive airway pressure (APAP) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities. However, the pathophysiological mechanisms implicated are not fully elucidated. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP. Therefore, this double-blind randomised controlled trial aims to compare muscle sympathetic nerve activity (MSNA) assessed by microneurography (reference method for measuring sympathetic activity) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients. This present manuscript describes the design of our study, no results are presented herein. and is registered under the below reference number. METHODS AND ANALYSIS: Adult subjects with newly diagnosed OSA (Apnoea-Hypopnoea Index >20/hour) will be randomised for treatment with APAP or fixed CPAP. Measurements of sympathetic activity by MSNA, heart rate variability and catecholamines will be obtained at baseline and after 30 days. The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats. Sample size calculation was performed with bilateral assumption. We will use the Student's t-test to compare changes in sympathetic tone between groups. ETHICS AND DISSEMINATION: The protocol was approved by The French Regional Ethics Committee. The study started in March 2018 with primary completion expected to March 2019. Dissemination plans of the results include presentations at conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03428516; Pre-results.

[Obstructive sleep apnea syndrome. Diagnostic strategies in various clinical settings]. / Syndrome d'apnées du sommeil. Stratégies diagnostiques dans les différents contextes cliniques.

Obstructive Sleep Apnea Syndrome (OSAS) is a common disease, whose prevalence and expression may vary depending on the associated pathology, age or gender. Thus, the prevalence of OSAS is up to 80% in case of refractory hypertension. This led up to individualize clinical presentation of clusters, although currently, the individualization of these different phenotypes did not conduct to a specific care or predict different evolution. Offering the best strategy for the right patient remains an important objective. However, the frequent association of OSAS and various metabolic diseases, and thus induced cardiovascular risk factors, is to be considered in the therapeutic care and judgment of the response to established treatments. By acting on all components in pathological cause in these patients with OSAS, a combined support will thus permit optimal beneficial effect.

Rebiopsy during disease progression in patients treated by TKI for oncogene-addicted NSCLC.

All lung cancer patients with mutant epidermal growth factor receptor (EGFR) or rearranged EML4-ALK eventually develop acquired resistance to treatment. Rebiopsy may give insight into the resistance mechanisms and direct further lines of treatment. Here, we evaluate the potential interest and limitations of rebiopsy. Patients with mutant EGFR or rearranged EML4-ALK non-small cell lung cancer (NSCLC) and acquired resistance to tyrosine kinase inhibitors were included in a retrospective study to determine the percentage of patients who underwent rebiopsy and whether rebiopsy would have been possible, or not, in the remaining patients. In a cohort of 84 patients from 6 institutions, a biopsy had been performed in 39 cases. Biopsy samples were sufficient for histopathological or cytological examination in 35 cases (89.7 %). Complete or partial response had been observed in 84.5 % of patients whose cancer further progressed and who underwent rebiopsy. A biopsy could have been considered in 30 of the 45 remaining patients. Those with brain (N = 9) and bone (N = 2) metastases and/or with contraindications (N = 6) were excluded (two patients had both brain metastases and a contraindication). The rebiopsy target was thoracic in 62 % of cases and on distant metastases in 38 % of cases. Patients with NSCLC and an activating mutation could undergo a rebiopsy in 72 % of cases. A response to treatment does not preclude the possibility of rebiopsy at the time of progression.