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      Innovative treatments for adults with obstructive sleep apnea

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          Abstract

          Obstructive sleep apnea (OSA) affects one in five adult males and is associated with significant comorbidity, cognitive impairment, excessive daytime sleepiness, and reduced quality of life. For over 25 years, the primary treatment has been continuous positive airway pressure, which introduces a column of air that serves as a pneumatic splint for the upper airway, preventing the airway collapse that is the physiologic definition of this syndrome. However, issues with patient tolerance and unacceptable levels of treatment adherence motivated the exploration of other potential treatments. With greater understanding of the physiologic mechanisms associated with OSA, novel interventions have emerged in the last 5 years. The purpose of this article is to describe new treatments for OSA and associated complex sleep apnea. New approaches to complex sleep apnea have included adaptive servoventilation. There is increased literature on the contribution of behavioral interventions to improve adherence with continuous positive airway pressure that have proven quite effective. New non-surgical treatments include oral pressure devices, improved mandibular advancement devices, nasal expiratory positive airway pressure, and newer approaches to positional therapy. Recent innovations in surgical interventions have included laser-assisted uvulopalatoplasty, radiofrequency ablation, palatal implants, and electrical stimulation of the upper airway muscles. No drugs have been approved to treat OSA, but potential drug therapies have centered on increasing ventilatory drive, altering the arousal threshold, modifying loop gain (a dimensionless value quantifying the stability of the ventilatory control system), or preventing airway collapse by affecting the surface tension. An emerging approach is the application of cannabinoids to increase upper airway tone.

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          Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets.

          The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized. To define carefully the proportion of key anatomic and nonanatomic contributions in a relatively large cohort of patients with OSA and control subjects to identify pathophysiologic targets for future novel therapies for OSA. Seventy-five men and women with and without OSA aged 20-65 years were studied on three separate nights. Initially, the apnea-hypopnea index was determined by polysomnography followed by determination of anatomic (passive critical closing pressure of the upper airway [Pcrit]) and nonanatomic (genioglossus muscle responsiveness, arousal threshold, and respiratory control stability; loop gain) contributions to OSA. Pathophysiologic traits varied substantially among participants. A total of 36% of patients with OSA had minimal genioglossus muscle responsiveness during sleep, 37% had a low arousal threshold, and 36% had high loop gain. A total of 28% had multiple nonanatomic features. Although overall the upper airway was more collapsible in patients with OSA (Pcrit, 0.3 [-1.5 to 1.9] vs. -6.2 [-12.4 to -3.6] cm H2O; P <0.01), 19% had a relatively noncollapsible upper airway similar to many of the control subjects (Pcrit, -2 to -5 cm H2O). In these patients, loop gain was almost twice as high as patients with a Pcrit greater than -2 cm H2O (-5.9 [-8.8 to -4.5] vs. -3.2 [-4.8 to -2.4] dimensionless; P = 0.01). A three-point scale for weighting the relative contribution of the traits is proposed. It suggests that nonanatomic features play an important role in 56% of patients with OSA. This study confirms that OSA is a heterogeneous disorder. Although Pcrit-anatomy is an important determinant, abnormalities in nonanatomic traits are also present in most patients with OSA.
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            Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning.

            Evidence suggests that, to maintain treatment effects, nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) needs to be used every night. What remains unknown is the nightly duration of use required to normalize functioning. This study, employing probit analyses and piecewise regression to estimate dose-response functions, estimated likelihoods of return to normal levels of sleepiness and daily functioning relative to nightly duration of CPAP. Multicenter, quasi-experimental study. Seven sleep centers in the United States and Canada. Patients with severe OSA (total cohort n = 149; the numbers of included participants from 85 - 120, depending on outcome analyzed.) CPAP. Before treatment and again after 3 months of therapy, participants completed a day of testing that included measures of objective and subjective daytime sleepiness and functional status. There were significant differences in mean nightly CPAP duration between treatment responders and nonresponders across outcomes. Thresholds above which further improvements were less likely relative to nightly duration of CPAP were identified for Epworth Sleepiness Scale score (4 hours), Multiple Sleep Latency Test (6 hours), and Functional Outcomes associated with Sleepiness Questionnaire (7.5 hours). A linear dose-response relationship (P < 0.01) between increased use and achieving normal levels was shown for objective and subjective daytime sleepiness, but only up to 7 hours use for functional status. Our analyses suggest that a greater percentage of patients will achieve normal functioning with longer nightly CPAP durations, but what constitutes adequate use varies between different outcomes.
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              A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions.

              Continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA) but adherence to the treatment limits its overall effectiveness across all age groups of patients. Factors that influence adherence to CPAP include disease and patient characteristics, treatment titration procedures, technological device factors and side effects, and psychological and social factors. These influential factors have guided the development of interventions to promote CPAP adherence. Various intervention strategies have been described and include educational, technological, psychosocial, pharmacological, and multi-dimensional approaches. Though evidence to date has led to innovative strategies that address adherence in CPAP-treated children, adults, and older adults, significant opportunities exist to develop and test interventions that are clinically applicable, specific to sub-groups of patients likely to demonstrate poor adherence, and address the multi-factorial nature of CPAP adherence. The translation of CPAP adherence promotion interventions to clinical practice is imperative to improve health and functional outcomes in all persons with CPAP-treated OSA. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Nat Sci Sleep
                Nat Sci Sleep
                Nature and Science of Sleep
                Nature and Science of Sleep
                Dove Medical Press
                1179-1608
                2014
                18 November 2014
                : 6
                : 137-147
                Affiliations
                [1 ]Biobehavioral Health Science Department, College of Nursing, University of Illinois at Chicago, Chicago, IL, USA
                [2 ]Center for Narcolepsy, Sleep and Health, University of Illinois at Chicago College of Nursing, Chicago, IL, USA
                [3 ]Department of Orthodontics, University of Illinois at Chicago College of Dentistry, Chicago, IL, USA
                [4 ]Sleep Center, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USA
                Author notes
                Correspondence: Terri E Weaver, University of Illinois at Chicago College of Nursing, 845 S Damen Ave MC 802, Chicago, IL 60612-7350, USA, Tel +1 708 771 5623, Fax +1 708 771 5673, Email teweaver@ 123456uic.edu
                Article
                nss-6-137
                10.2147/NSS.S46818
                4242689
                25429246
                5620c6d2-0f2f-4867-8981-b6849f64e2e1
                © 2014 Weaver et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                obstructive sleep apnea,innovative treatment,continuous positive airway pressure,oral appliance,nerve stimulation

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