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Study Objectives: The prospective Self-Efficacy Measure for Sleep Apnea study (SEMSAS) is investigating thresholds for health literacy, self-efficacy and precariousness at obstructive sleep apnea (OSA) diagnosis to predict CPAP adherence. This paper describes the study protocol and presents baseline data from the ongoing study., Methods: Eligible individuals had confirmed OSA and were referred to a homecare provider for continuous positive airway pressure (CPAP) therapy initiation. Data on patient characteristics and comorbidities were collected, along with baseline evaluations of self-efficacy [15-item Self-Efficacy Measure for Sleep Apnea tool (SEMSA-15)], precariousness [Deprivation in Primary Care Questionnaire (DipCareQ)], and health literacy (Health Literacy Questionnaire). CPAP adherence over 12 months of follow-up will be determined using remote monitoring of CPAP device data. The primary objective is to define an optimal SEMSA-15 score threshold to predict CPAP adherence at 3- and 12-month follow-up., Results: Enrollment of 302 participants (71% male, median age 55 years, median body mass index 31.6 kg/m 2 ) is complete. Low self-efficacy (SEMSA-15 score ≤ 2.78) was found in 93/302 participants (31%), and 38 (12.6%) reported precariousness (DipCareQ score > 1); precariousness did not differ significantly between individuals with a SEMSA-15 score ≤ 2.78 versus >2.78. Health literacy was generally good, but was significantly lower in individuals with versus without precariousness, and with low versus high self-efficacy., Conclusion: SEMSAS is the first study using multidimensional baseline assessment of self-efficacy, health literacy and precariousness, plus other characteristics, to determine future adherence to CPAP, including CPAP adherence trajectories. Collection of follow-up data is underway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gentina, Gentina, Douay, Micoulaud-Franchi, Pépin and Bailly.)

Continuous positive airway pressure (CPAP) is the most efficient treatment of obstructive sleep apnea (OSA). Little is known about the impact of spousal relationship profiles on CPAP adherence. We aimed to identify clusters of couples of OSA patients, and their association with CPAP adherence 120 days after CPAP initiation. In a multicenter prospective study, OSA patients recently prescribed CPAP were enrolled with their spouses. Data about spousal relationships were collected at inclusion and at day 120. Latent class analysis was performed to determine homogeneous groups of spousal relationships. The 290 participants were predominantly males (77%), median age was 53 years and interquartile range (IQR) 46-62, median body mass index (BMI) was 32 kg/m² (IQR: 28.6-35.9) and median apnea-hypopnea index: 43 events per hour (IQR: 33-58). Three couple clusters were identified: 1) older retired couples, 2) young working couples, and 3) mature active couples. Patients in the older retired couples cluster presented the highest CPAP adherence ( p < 0.01) independently of initial complaints, OSA severity, and degree of improvement under CPAP. In a large cohort of OSA patients in whom clusters of couples were determined, there was a significant difference in CPAP adherence at day-120 after CPAP initiation.

Background: Continuous positive airway pressure (CPAP) is the first line therapy for obstructive sleep apnea (OSA) but its effectiveness requires high adherence. We aimed to assess the impacts of the spouse's/partner's involvement and the quality of the couple's relationship on CPAP adherence., Methods: In a multicenter prospective study conducted in France, patients reported their subjective views regarding their partner's engagement in their CPAP treatment and the quality of their marital relationship using the Quality of Marriage Index. A hierarchical linear model was built to assess the predictors of CPAP adherence at day 120. Structural equation modeling was performed to evaluate the direct and indirect effects of the spouse's/partner's engagement and the quality of the couple's relationship on CPAP adherence., Results: The 290 OSA patients were predominantly male (77%), with a median age of 53 years IQR: [46; 62], median BMI: 32 kg/m 2 [28.6; 35.9] and median apnea + hypopnea index: 43/per hour [33; 58]. Independent factors for CPAP adherence at day 120 were the partner's encouragement of CPAP usage and a stable relationship exceeding 30 years, although emotional support or collaboration were not associated with CPAP adherence. Structural equation modeling demonstrated that spouse's/partner's engagement is directly related to CPAP adherence and improvement of symptoms, and that CPAP adherence is a mediator of disease-specific health-related quality of life. Marital quality was a significant moderator of these interactions meaning that a spouse's/partner's engagement improved adherence only when the quality of marriage index was high., Conclusion: Future research and integrated OSA management should systematically include and document the role of the spouse/partner in CPAP adherence., (Copyright © 2018. Published by Elsevier B.V.)

Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, baclofen has been shown to decrease respiratory drive. In humans, however, use of baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic baclofen therapy for alcohol withdrawal. In one patient, baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with baclofen. Given the increasing number of patients receiving baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with baclofen usage., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Continuous positive airways pressure (CPAP) is the accepted therapy for obstructive sleep apnoea (OSA), but compliance is variable. We hypothesised that an auto bi-level device with pressure relief during exhalation (auto bi-level) would treat OSA as well as CPAP and that transitioning non-compliant CPAP patients without modifiable causes of poor compliance to this device would improve compliance and clinical outcomes., Materials and Methods: OSA patient's on positive airways pressure therapy with compliance below 4 h of use on ≥70% of nights over the past 3 months despite having no modifiable causes of poor compliance were transitioned onto an auto bi-level device for 10 weeks. Patients completed an Epworth sleepiness scale and Functional Outcomes of Sleep Questionnaire (FOSQ) at 15 days and 10 weeks and had their compliance and therapy data downloaded. Additionally, patients underwent polysomnography on their auto bi-level device at week 10., Results: Thirty-five patients were included. The apnoea-hypopnoea index, arousal index, sleep efficiency, total sleep time and sleep stage distribution were similar at baseline and week 10. Compliance, excessive daytime sleepiness and several FOSQ domains improved significantly at day 15 and week 10. Patients requiring an effective pressure ≥10 cmH(2)0 during the lead-in period on CPAP experienced greater significant improvements compliance than those requiring an effective pressure <10 cmH(2)0., Conclusions: Auto bi-level with pressure relief during exhalation treats OSA as effectively as CPAP without inducing additional arousals. Transitioning non-compliant CPAP patients without modifiable causes of poor compliance from their CPAP to this new device improves compliance and clinical outcomes over a 10-week period.

Introduction: This French, multicenter, randomized double-blind controlled trial tested the hypothesis that pressure reduction during exhalation (C-Flex; Respironics; Murrysville, PA) would improve continuous positive airway pressure (CPAP) compliance, comfort, and quality of life., Methods: Two hundred eighteen newly diagnosed sleep apnea patients (seven centers; mean [+/- SD] age, 55 +/- 11 years; mean body mass index, 31 +/- 6 kg/m(2); mean apnea-hypopnea index, 44 +/- 21 events/h) were randomly assigned to receive 3 months of treatment with CPAP (108 patients) or C-Flex (110 patients). Objective compliance, generic quality-of-life questionnaire (SF-36) scores, disease-specific quality-of-life questionnaire (Grenoble Sleep Apnea Quality of Life [GrenobleSAQOL]) scores, and visual analog scales for CPAP comfort and side effects were determined at baseline and after 3 months. After 3 months, patients in the CPAP arm were moved to the C-Flex arm for 3 additional months (open study)., Results: An intention-to-treat analysis demonstrated that there were no differences at 3 months between C-Flex and CPAP use in terms of compliance, the rate of side effects, and comfort. Low compliers receiving CPAP therapy (< 4 h of use) significantly improved this outcome during the open study (p = 0.04). There was a significant improvement in six of eight of the SF-36 domain scores and in all of the domains of the GrenobleSAQOL scores in both groups using either CPAP or C-Flex., Conclusion: In unselected sleep apnea patients, C-Flex was associated with similar outcomes to standard CPAP. Low compliers receiving CPAP therapy improved their adherence when moving to C-Flex., Trial Registration: ISRCTN Register Identifier: 08065291.

Endocan is a proteoglycan specifically secreted by endothelial cells. Through its glycan domains, endocan binds to hepatocyte growth factor and increases its mitogenic activity. Here, we show that human embryonic kidney 293 cells, which have been genetically engineered to overexpress endocan, form tumors when injected s.c. in SCID mice. Both the glycan and a phenylalanine-rich region of endocan are necessary for mediating tumor growth activity. Blocking the phenylalanine-rich region with a monoclonal antibody results in a marked reduction of tumor growth. Finally, we report that circulating levels of endocan are increased in mice with the endocan-expressing human embryonic kidney 293 cell tumors and in a series of adult patients with lung cancer. Taken together, these results suggest that (a) endothelial-derived endocan induces tumor growth, (b) antibodies to endocan may have therapeutic potential, and (c) circulating levels of endocan may eventually represent a novel marker for cancer.

Eosinophil, basophil, and T helper 2 (TH2) cell recruitment into tissues is a characteristic feature of allergic diseases. These cells have in common the expression of the chemokine receptor CCR3, which may represent a specific pathway for their accumulation in vivo. Although animal models of allergic reactions are available, findings cannot always be extrapolated to man. To overcome these limitations, we have developed a humanized mouse model of allergic cutaneous reaction using severe combined immunodeficiency mice engrafted with skin and autologous peripheral blood mononuclear cells from allergic donors. Intradermal injection of the relevant allergen into human skin xenografts from allergic individuals induced a significant recruitment of human CD4(+) T cells, basophils, and TH2-type cytokine mRNA-expressing cells, as well as murine eosinophils. Human skin xenografts, atopic status, and autologous peripheral blood mononuclear cell reconstitution were all mandatory to induce the allergic reaction. Next, we addressed the role of CCR3 in the endogenous mechanisms involved in the inflammatory cell recruitment in this experimental model of allergic cutaneous reaction. In vivo administration of an anti-human CCR3-blocking antibody selectively reduced accumulation of eosinophils but not that of CD4(+) cells, basophils, or cells expressing mRNA for TH2-type cytokines. These findings establish a new in vivo model of humanized allergic reaction and suggest that eosinophil migration is mediated mainly through CCR3. Finally, these results suggest that this model might be useful to test human-specific antiallergic modulators.

Proteoglycans that modulate the activities of growth factors, chemokines, and coagulation factors regulate in turn the vascular endothelium with respect to processes such as inflammation, hemostasis, and angiogenesis. Endothelial cell-specific molecule-1 is mainly expressed by endothelial cells and regulated by pro-inflammatory cytokines (Lassalle, P., Molet, S., Janin, A., Heyden, J. V., Tavernier, J., Fiers, W., Devos, R., and Tonnel, A. B. (1996) J. Biol. Chem. 271, 20458-20464). We demonstrate that this molecule is secreted as a soluble dermatan sulfate (DS) proteoglycan. This proteoglycan represents the major form either secreted by cell lines or circulating in the human bloodstream. Because this proteoglycan is specifically secreted by endothelial cells, we propose to name it endocan. The glycosaminoglycan component of endocan consists of a single DS chain covalently attached to serine 137. Endocan dose-dependently increased the hepatocyte growth factor/scatter factor (HGF/SF)-mediated proliferation of human embryonic kidney cells, whereas the nonglycanated form of endocan did not. Moreover, DS chains purified from endocan mimicked the endocan-mediated increase of cell proliferation in the presence of HGF/SF. Overall, our results demonstrate that endocan is a novel soluble dermatan sulfate proteoglycan produced by endothelial cells. Endocan regulates HGF/SF-mediated mitogenic activity and may support the function of HGF/SF not only in embryogenesis and tissue repair after injury but also in tumor progression.

ICAMs are ligands for LFA-1, a major integrin of mononuclear cells involved in the immune and inflammatory processes. We previously showed that endothelial cell specific molecule-1 (ESM-1) is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. Here, we demonstrate that ESM-1 binds directly to LFA-1 onto the cell surface of human blood lymphocytes, monocytes, and Jurkat cells. The binding of ESM-1 was equally dependent on Ca(2+), Mg(2+), or Mn(2+) divalent ions, which are specific, saturable, and sensitive to temperature. An anti-CD11a mAb or PMA induced a transient increase in binding, peaking 5 min after activation. Direct binding of ESM-1 to LFA-1 integrin was demonstrated by specific coimmunoprecipitation by CD11a and CD18 mAbs. A cell-free system using a Biacore biosensor confirmed that ESM-1 and LFA-1 dynamically interacted in real time with high affinity (K(d) = 18.7 nM). ESM-1 consistently inhibited the specific binding of soluble ICAM-1 to Jurkat cells in a dose-dependent manner. These results suggest that ESM-1 and ICAM-1 interact with LFA-1 on binding sites very close to but distinct from the I domain of CD11a. Through this mechanism, ESM-1 could be implicated in the regulation of the LFA-1/ICAM-1 pathway and may therefore influence both the recruitment of circulating lymphocytes to inflammatory sites and LFA-1-dependent leukocyte adhesion and activation.