Special Issue "Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: 31 December 2019.

Special Issue Editors

Prof. Dr. Vsevolod Y. Polotsky
E-Mail Website
Guest Editor
Johns Hopkins University
Interests: obstructive sleep apnea; upper airway; control of breathing; intermittent hypoxia; animal model; obesity; metabolic syndrome; leptin; chemogenetics
Dr. Mihaela Teodorescu
E-Mail Website
Guest Editor
University of Wisconsin School of Medicine and Public Health
Interests: obstructive sleep apnea; intermittent hypoxia; upper airway; breathing control; asthma; lower airway inflammation; remodeling; animal model

Special Issue Information

Dear Colleagues,

Obstructive sleep apnea (OSA) is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep, which leads to intermittent hypoxia and sleep fragmentation. OSA is a common disorder affecting 25–30% of adult population and more than 50% of obese individuals. OSA leads to poor neurocognitive, cardiovascular, metabolic, and possibly even oncological outcomes, but OSA treatment remains a challenge. Continuous positive airway pressure (CPAP) is a highly efficacious treatment for OSA, but poor adherence severely limits its use. Mandibular advancement devices have better compliance, but are not as effective as CPAP. Hypoglossal nerve stimulation is a promising alternative in patients, who are unable to tolerate CPAP, but so far it has been effective only in a limited subset of patients. Until recently, there was no effective pharmacotherapy, but promising drug-candidates have been emerging over the last year.

For an upcoming Special Issue in the Journal of Clinical Medicine "Therapies for Obstructive Sleep Apnea", we invite investigators to contribute original research articles (including animal and human studies; clinical studies will be given priority), as well as review articles, that will stimulate continuing efforts to develop better therapies for OSA. Potential topics may include, but are not limited to, the following:

  • Novel aspects of CPAP treatment and interventions to improve CPAP adherence;
  • Oral appliances in OSA: state-of-the-art;
  • Hypoglossal nerve stimulation: novel approaches;
  • Emerging pharmacotherapy of OSA;
  • Pre-clinical studies of novel therapeutics in OSA;
  • Treatment of OSA in children.

Prof. Dr. Vsevolod Y. Polotsky
Dr. Mihaela Teodorescu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • obstructive sleep apnea
  • oral appliance
  • CPAP
  • hypoglossal nerve
  • paediatrics
  • adherence

Published Papers (8 papers)

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Research

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Open AccessArticle
The Effects of Eplerenone on the Circadian Blood Pressure Pattern and Left Ventricular Hypertrophy in Patients with Obstructive Sleep Apnea and Resistant Hypertension—A Randomized, Controlled Trial
J. Clin. Med. 2019, 8(10), 1671; https://doi.org/10.3390/jcm8101671 - 13 Oct 2019
Abstract
The obstructive sleep apnea (OSA) is highly associated with various significant cardiovascular outcomes such as resistant hypertension (RAH). Despite this, as of now the relationship between high night-time blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with OSA and RAH is [...] Read more.
The obstructive sleep apnea (OSA) is highly associated with various significant cardiovascular outcomes such as resistant hypertension (RAH). Despite this, as of now the relationship between high night-time blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with OSA and RAH is not fully understood. The aim of this study was to assess the influence of the addition of eplerenone to a standard antihypertensive therapy on parameters of 24-h ambulatory blood pressure measurement (ABPM) as well as on the results of echocardiography and polysomnography in patients with OSA and RAH. The patients were randomly assigned to one of the two study groups: the treatment group, receiving 50 mg/d eplerenone orally for 6 months (n = 51) and the control group, remaining on their standard antihypertensive therapy (n = 51). After that period, a significant reduction in the night-time BP parameters in the treatment group including an increased night blood pressure fall from 4.6 to 8.9% was noted. Additionally, the number of non-dipper patients was reduced by 45.1%. The treatment group also revealed a decrease in left ventricular hypertrophy and in the apnea–hypopnea index (AHI) with a positive correlation being observed between these two parameters. This study is the first to report the improvement of the circadian BP profile and the improvement of the left ventricle geometry in patients with OSA and RAH following the addition of selective mineralocorticoid receptor antagonists to antihypertensive therapy. Full article
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Open AccessArticle
Alternations of Circadian Clock Genes Expression and Oscillation in Obstructive Sleep Apnea
J. Clin. Med. 2019, 8(10), 1634; https://doi.org/10.3390/jcm8101634 - 06 Oct 2019
Abstract
Circadian misalignment plays an important role in disease processes and can affect disease severity, treatment outcomes, and even survivorship. In this study, we aim to investigate whether expression and daily oscillation patterns of core circadian clock genes were disturbed in patients with obstructive [...] Read more.
Circadian misalignment plays an important role in disease processes and can affect disease severity, treatment outcomes, and even survivorship. In this study, we aim to investigate whether expression and daily oscillation patterns of core circadian clock genes were disturbed in patients with obstructive sleep apnea/hypopnea (OSA) syndrome. We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes in leukocytes of peripheral blood collected at 12 AM, 6 AM, 12 PM, and 6 PM from 133 patients with OSA and 11 normal controls. Daily expression patterns of the nine circadian clock genes were observed in normal controls, but three of these genes (BMAL1, CLOCK, CRY2) were disrupted in patients with OSA. The expressions of eight circadian clock genes (except PER1) at midnight were significantly downregulated in patients with severe OSA. Binary logistic regression analysis selected CRY1 and PER3 as independent factors for severe OSA and showed that the combined expressions of CRY1 and PER3 enhanced the capability of predicting severe OSA (Odds ratio, 5.800; 95% CI, 1.978 to 17.004; p = 0.001). Our results show that combined expressions of CRY1 and PER3 at midnight could be a potential predictor for severe OSA. Full article
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Open AccessArticle
Blood Pressure Non-Dipping and Obstructive Sleep Apnea Syndrome: A Meta-Analysis
J. Clin. Med. 2019, 8(9), 1367; https://doi.org/10.3390/jcm8091367 - 02 Sep 2019
Cited by 1
Abstract
Aim: We examined the reduced blood pressure (BP) nocturnal fall in patients with obstructive sleep apnea (OSA) by a meta-analysis including studies that provided data on prevalence rates of non-dipping (ND) pattern during 24-h ambulatory blood pressure monitoring (ABPM). Design: The PubMed, OVID-MEDLINE, [...] Read more.
Aim: We examined the reduced blood pressure (BP) nocturnal fall in patients with obstructive sleep apnea (OSA) by a meta-analysis including studies that provided data on prevalence rates of non-dipping (ND) pattern during 24-h ambulatory blood pressure monitoring (ABPM). Design: The PubMed, OVID-MEDLINE, and Cochrane CENTRAL literature databases were searched for appropriate articles without temporal restriction up to April 2019 through focused and sensitive search methods. Studies were identified by crossing the search terms as follows: “obstructive sleep apnea”, “sleep quality”, “non dipping”, “reduced nocturnal BP fall”, “circadian BP variation”, “night-time BP”, and “ambulatory blood pressure monitoring”. Results: Meta-analysis included 1562 patients with OSA from different clinical settings and 957 non-OSA controls from 14 studies. ND pattern prevalence in patients with OSA widely varied among studies (36.0–90.0%). This was also the case for non-OSA controls (33.0% to 69.0%). Overall, the ND pattern, assessed as an event rate in the pooled OSA population, was 59.1% (confidence interval (CI): 52.0–65.0%). Meta-analysis of the seven studies comparing the prevalence of ND pattern in participants with OSA and controls showed that OSA entails a significantly increased risk of ND (Odds ratio (OR) = 1.47, CI: 1.07–1.89, p < 0.01). After the exclusion of patients with mild OSA, OR increased to 1.67 (CI: 1.21–2.28, p < 0.001). Conclusions: The present meta-analysis, extending previous information on the relationship between OSA and impaired BP dipping, based on single studies, suggests that this condition increases by approximately 1.5 times the likelihood of ND, which is a pattern associated with a greater cardiovascular risk than normal BP dipping. Full article
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Open AccessArticle
Clinical Characteristics of Obstructive Sleep Apnea in Psychiatric Disease
J. Clin. Med. 2019, 8(4), 534; https://doi.org/10.3390/jcm8040534 - 18 Apr 2019
Abstract
Patients with serious psychiatric diseases (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia and psychotic disorder) often complain about sleepiness during the day, fatigue, low energy, concentration problems, and insomnia; unfortunately, many of these symptoms are also frequent in patients with Obstructive [...] Read more.
Patients with serious psychiatric diseases (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia and psychotic disorder) often complain about sleepiness during the day, fatigue, low energy, concentration problems, and insomnia; unfortunately, many of these symptoms are also frequent in patients with Obstructive Sleep Apnea (OSA). However, existing data about the clinical appearance of OSA in Psychiatric Disease are generally missing. The aim of our study was a detailed and focused evaluation of OSA in Psychiatric Disease, in terms of symptoms, comorbidities, clinical characteristics, daytime respiratory function, and overnight polysomnography data. We examined 110 patients (56 males and 54 females) with stable Psychiatric Disease (Group A: 66 with MDD, Group B: 34 with BD, and Group C: 10 with schizophrenia). At baseline, each patient answered the STOP–Bang Questionnaire, Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Hospital Anxiety and Depression Scale (HADS) and underwent clinical examination, oximetry, spirometry, and overnight polysomnography. Body Mass Index (BMI), neck, waist, and hip circumferences, and arterial blood pressure values were also measured. The mean age of the whole population was 55.1 ± 10.6 years. The three groups had no statistically significant difference in age, BMI, hip circumference, and systolic and diastolic arterial blood pressure. Class II and III obesity with BMI > 35 kg/m2 was observed in 36 subjects (32.14%). A moderate main effect of psychiatric disease was observed in neck (p = 0.044, η2 = 0.064) and waist circumference (p = 0.021, η2 = 0.078), with the depression group showing the lowest values, and in pulmonary function (Forced Vital Capacity (FVC, %), p = 0.013, η2 = 0.084), with the psychotic group showing the lowest values. Intermediate to high risk of OSA was present in 87.37% of participants, according to the STOP–Bang Questionnaire (≥3 positive answers), and 70.87% responded positively for feeling tired or sleepy during the day. An Apnea–Hypopnea Index (AHI) ≥ 15 events per hour of sleep was recorded in 72.48% of our patients. AHI was associated positively with male sex, schizophrenia, neck, and waist circumferences, STOP–Bang and ESS scores, and negatively with respiratory function. A large main effect of psychiatric medications was observed in waist circumference (p = 0.046, η2 = 0.151), FVC (%) (p = 0.027, η2 = 0.165), and in time spend with SaO2 < 90% (p = 0.006, η2 = 0.211). Our study yielded that patients with Psychiatric Disease are at risk of OSA, especially men suffering from schizophrenia and psychotic disorders that complain about sleepiness and have central obesity and disturbed respiratory function. Screening for OSA is mandatory in this medical population, as psychiatric patients have significantly poorer physical health than the general population and the coexistence of the two diseases can further negatively impact several health outcomes. Full article

Review

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Open AccessReview
Resistant/Refractory Hypertension and Sleep Apnoea: Current Knowledge and Future Challenges
J. Clin. Med. 2019, 8(11), 1872; https://doi.org/10.3390/jcm8111872 - 05 Nov 2019
Abstract
Hypertension is one of the most frequent cardiovascular risk factors. The population of hypertensive patients includes some phenotypes whose blood pressure levels are particularly difficult to control, thus putting them at greater cardiovascular risk. This is especially true of so-called resistant hypertension (RH) [...] Read more.
Hypertension is one of the most frequent cardiovascular risk factors. The population of hypertensive patients includes some phenotypes whose blood pressure levels are particularly difficult to control, thus putting them at greater cardiovascular risk. This is especially true of so-called resistant hypertension (RH) and refractory hypertension (RfH). Recent findings suggest that the former may be due to an alteration in the renin–angiotensin–aldosterone axis, while the latter seems to be more closely related to sympathetic hyper-activation. Both these pathophysiological mechanisms are also activated in patients with obstructive sleep apnoea (OSA). It is not surprising, therefore, that the prevalence of OSA in RH and RfH patients is very high (as reflected in several studies) and that treatment with continuous positive airway pressure (CPAP) manages to reduce blood pressure levels in a clinically significant way in both these groups of hypertensive patients. It is therefore necessary to incorporate into the multidimensional treatment of patients with RH and RfH (changes in lifestyle, control of obesity and drug treatment) a study of the possible existence of OSA, as this is a potentially treatable disease. There are many questions that remain to be answered, especially regarding the ideal combination of treatment in patients with RH/RfH and OSA (drugs, renal denervation, CPAP treatment) and patients’ varying response to CPAP treatment. Full article
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Open AccessReview
Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature
J. Clin. Med. 2019, 8(11), 1846; https://doi.org/10.3390/jcm8111846 - 02 Nov 2019
Abstract
Obstructive sleep apnea (OSA) is a highly prevalent condition with few therapeutic options. To date there is no approved pharmacotherapy for this disorder, but several attempts have been made in the past and are currently ongoing to find one. The recent identification of [...] Read more.
Obstructive sleep apnea (OSA) is a highly prevalent condition with few therapeutic options. To date there is no approved pharmacotherapy for this disorder, but several attempts have been made in the past and are currently ongoing to find one. The recent identification of multiple endotypes underlying this disorder has oriented the pharmacological research towards tailored therapies targeting specific pathophysiological traits that contribute differently to cause OSA in each patient. In this review we retrospectively analyze the literature on OSA pharmacotherapy dividing the medications tested on the basis of the four main endotypes: anatomy, upper airway muscle activity, arousal threshold and ventilatory instability (loop gain). We show how recently introduced drugs for weight loss that modify upper airway anatomy may play an important role in the management of OSA in the near future, and promising results have been obtained with drugs that increase upper airway muscle activity during sleep and reduce loop gain. The lack of a medication that can effectively increase the arousal threshold makes this strategy less encouraging, although recent studies have shown that the use of certain sedatives do not worsen OSA severity and could actually improve patients’ sleep quality. Full article
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Open AccessReview
Obstructive Sleep Apnea: Emerging Treatments Targeting the Genioglossus Muscle
J. Clin. Med. 2019, 8(10), 1754; https://doi.org/10.3390/jcm8101754 - 22 Oct 2019
Abstract
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus [...] Read more.
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus (GG) is the main upper airway dilator muscle. Currently, continuous positive airway pressure is the first-line treatment for OSA. Nevertheless, problems related to poor adherence have been described in some groups of patients. In recent years, new OSA treatment strategies have been developed to improve GG function. (A) Hypoglossal nerve electrical stimulation leads to significant improvements in objective (apnea-hypopnea index, or AHI) and subjective measurements of OSA severity, but its invasive nature limits its application. (B) A recently introduced combination of drugs administered orally before bedtime reduces AHI and improves the responsiveness of the GG. (C) Finally, myofunctional therapy also decreases AHI, and it might be considered in combination with other treatments. Our objective is to review these therapies in order to advance current understanding of the prospects for alternative OSA treatments. Full article
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Other

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Open AccessBrief Report
Effects of Continuous Positive Airway Pressure on Body Composition in Individuals with Obstructive Sleep Apnea: A Non-Randomized, Matched Before-After Study
J. Clin. Med. 2019, 8(8), 1195; https://doi.org/10.3390/jcm8081195 - 10 Aug 2019
Abstract
A reciprocal relationship between obesity and obstructive sleep apnea (OSA) likely exists, wherein obesity contributes to OSA, and OSA-related sleep disturbances promote weight gain. It remains unclear whether continuous positive airway pressure (CPAP) affects body composition. We conducted an open-label, parallel-arm, non-randomized, matched [...] Read more.
A reciprocal relationship between obesity and obstructive sleep apnea (OSA) likely exists, wherein obesity contributes to OSA, and OSA-related sleep disturbances promote weight gain. It remains unclear whether continuous positive airway pressure (CPAP) affects body composition. We conducted an open-label, parallel-arm, non-randomized, matched before-after study in individuals with OSA who were starting CPAP use (n = 12) and who were not (n = 12) to examine the effects of CPAP on total body composition (via air displacement plethysmography) including fat and fat-free mass. CPAP users (n = 12) were studied at baseline and after 8 weeks of CPAP use, and 12 age- and sex-matched non-CPAP OSA controls were studied at baseline and after an 8 week period. Statistically significant group x time interactions were seen for body weight, fat-free mass, and fat-mass, such that body weight and fat-free mass were increased, and fat mass decreased, at 8-week follow-up in the CPAP group compared to baseline. Body weight and body composition measures were unchanged in the non-CPAP control group. These findings are consistent with prior studies showing CPAP-induced weight gain, and suggest that weight gain observed following CPAP may be driven primarily by increases in fat-free mass. An increase in lean mass (and decrease in fat mass), despite an overall increase in body weight, can be considered a favorable metabolic outcome in response to CPAP use. Full article
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