Journal of Clinical Medicine

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13 pages, 303 KiB

Open AccessCommunication

Treatment of Obstructive Sleep Apnea in Children: Handling the Unknown with Precision

by David Gozal, Hui-Leng Tan and Leila Kheirandish-Gozal

J. Clin. Med. 2020, 9(3), 888; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030888 - 24 Mar 2020

Cited by 47 | Viewed by 5928

Abstract

Treatment approaches to pediatric obstructive sleep apnea (OSA) have remarkably evolved over the last two decades. From an a priori assumption that surgical removal of enlarged upper airway lymphadenoid tissues (T&A) was curative in the vast majority of patients as the recommended first-line [...] Read more.

Treatment approaches to pediatric obstructive sleep apnea (OSA) have remarkably evolved over the last two decades. From an a priori assumption that surgical removal of enlarged upper airway lymphadenoid tissues (T&A) was curative in the vast majority of patients as the recommended first-line treatment for pediatric OSA, residual respiratory abnormalities are frequent. Children likely to manifest persistent OSA after T&A include those with severe OSA, obese or older children, those with concurrent asthma or allergic rhinitis, children with predisposing oropharyngeal or maxillomandibular factors, and patients with underlying medical conditions. Furthermore, selection anti-inflammatory therapy or orthodontic interventions may be preferable in milder cases. The treatment options for residual OSA after T&A encompass a large spectrum of approaches, which may be complementary, and clearly require multidisciplinary cooperation. Among these, continuous positive airway pressure (CPAP), combined anti-inflammatory agents, rapid maxillary expansion, and myofunctional therapy are all part of the armamentarium, albeit with currently low-grade evidence supporting their efficacy. In this context, there is urgent need for prospective evidence that will readily identify the correct candidate for a specific intervention, and thus enable some degree of scientifically based precision in the current one approach fits all model of pediatric OSA medical care. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

17 pages, 1248 KiB

Open AccessArticle

Relationships Among and Predictive Values of Obesity, Inflammation Markers, and Disease Severity in Pediatric Patients with Obstructive Sleep Apnea Before and After Adenotonsillectomy

by Hai-Hua Chuang, Chung-Guei Huang, Li-Pang Chuang, Yu-Shu Huang, Ning-Hung Chen, Hsueh-Yu Li, Tuan-Jen Fang, Jen-Fu Hsu, Hsin-Chih Lai, Jau-Yuan Chen and Li-Ang Lee

J. Clin. Med. 2020, 9(2), 579; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020579 - 20 Feb 2020

Cited by 24 | Viewed by 3329

Abstract

Both obstructive sleep apnea (OSA) and obesity are major health issues that contribute to increased systemic inflammation in children. To date, adenotonsillectomy (AT) is still the first-line treatment for childhood OSA. However, the relationships among and predictive values of obesity, inflammation, and OSA [...] Read more.

Both obstructive sleep apnea (OSA) and obesity are major health issues that contribute to increased systemic inflammation in children. To date, adenotonsillectomy (AT) is still the first-line treatment for childhood OSA. However, the relationships among and predictive values of obesity, inflammation, and OSA severity have not been comprehensively investigated. This prospective study investigated body mass index (BMI), serum inflammatory markers, and OSA severity before and after AT in 60 pediatric patients with OSA. At baseline, differences in levels of interleukin-6, interleukin-9, basic fibroblast growth factor, platelet-derived growth factor-BB, as well as regulated on activation, normal T cell expressed and secreted (RANTES) were significant among the various weight status and OSA severity subgroups. After 3 months postoperatively, the differences in these inflammatory markers diminished along with a decrease in OSA severity while obesity persisted. The rate of surgical cure (defined as postoperative obstructive apnea-hypopnea index < 2.0 and obstructive apnea index < 1.0) was 62%. Multivariate analysis revealed that age, BMI z-score, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, and RANTES independently predicted surgical cure. Despite the significant reductions in inflammatory markers and OSA severity after AT, an inter-dependent relationship between obesity and OSA persisted. In addition to age and BMI, several inflammatory markers helped to precisely predict surgical cure. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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15 pages, 1627 KiB

Open AccessArticle

Socioeconomic Inequities in Adherence to Positive Airway Pressure Therapy in Population-Level Analysis

by Abhishek Pandey, Suresh Mereddy, Daniel Combs, Safal Shetty, Salma I. Patel, Saif Mashaq, Azizi Seixas, Kerry Littlewood, Girardin Jean-Luis and Sairam Parthasarathy

J. Clin. Med. 2020, 9(2), 442; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020442 - 6 Feb 2020

Cited by 31 | Viewed by 3256

Abstract

(a) Background: In patients with sleep apnea, poor adherence to positive airway pressure (PAP) therapy has been associated with mortality. Regional studies have suggested that lower socioeconomic status is associated with worse PAP adherence but population-level data is lacking. (b) Methods: De-identified data [...] Read more.

(a) Background: In patients with sleep apnea, poor adherence to positive airway pressure (PAP) therapy has been associated with mortality. Regional studies have suggested that lower socioeconomic status is associated with worse PAP adherence but population-level data is lacking. (b) Methods: De-identified data from a nationally representative database of PAP devices was geo-linked to sociodemographic information. (c) Results: In 170,641 patients, those in the lowest quartile of median household income had lower PAP adherence (4.1 + 2.6 hrs/night; 39.6% adherent by Medicare criteria) than those in neighborhoods with highest quartile median household income (4.5 + 2.5 hrs/night; 47% adherent by Medicare criteria; p < 0.0001). In multivariate regression, individuals in neighborhoods with the highest income quartile were more adherent to PAP therapy than those in the lowest income quartile after adjusting for various confounders (adjusted Odds Ratio (adjOR) 1.18; 95% confidence interval (CI) 1.14, 1.21; p < 0.0001). Over the past decade, PAP adherence improved over time (adjOR 1.96; 95%CI 1.94, 2.01), but health inequities in PAP adherence remained even after the Affordable Care Act was passed. (d) Conclusion: In a nationally representative population, disparities in PAP adherence persist despite Medicaid expansion. Interventions aimed at promoting health equity in sleep apnea need to be undertaken. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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12 pages, 1050 KiB

Open AccessArticle

Nocturnal Hypoxemia Impacts Right Ventricle Diastolic Function in Obstructive Sleep Apnea: A Retrospective Observational Study

by Carla Scotti, Roberto Porta, Adriana Olivares, Laura Comini, Angelo Cinelli, Simonetta Scalvini and Michele Vitacca

J. Clin. Med. 2020, 9(1), 162; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9010162 - 7 Jan 2020

Cited by 4 | Viewed by 2526

Abstract

Obstructive sleep apnea (OSA), although a growing healthcare problem and documented risk factor for cardiovascular diseases, is still under-diagnosed in cardiac patients. To investigate the correlation between OSA and echocardiographic parameters of right ventricle diastolic (RVD) dysfunction, in particular trans-tricuspid E-wave deceleration time [...] Read more.

Obstructive sleep apnea (OSA), although a growing healthcare problem and documented risk factor for cardiovascular diseases, is still under-diagnosed in cardiac patients. To investigate the correlation between OSA and echocardiographic parameters of right ventricle diastolic (RVD) dysfunction, in particular trans-tricuspid E-wave deceleration time (EDT), we retrospectively analyzed data of 103 pure (comorbidity-free) OSA patients with comprehensive echocardiographic examination (ETT). Apnea/hypopnea index (AHI), oxygen desaturation index (ODI), mean nighttime oxyhemoglobin saturation (SpO₂), time elapsed with SpO₂ < 90% (T90) and mean peak desaturation of nocturnal events (Mdes, graded as mild, medium or severe) were compared with echocardiographic parameters. We found RVD dysfunction present in 58.3% of patients. Altered EDT correlated significantly with mean SpO₂, T90, and Mdes (p < 0.01, all). Nocturnal desaturators had a significantly worse EDT than non-desaturators (p = 0.027) and a higher risk of prolonged EDT (odds ratio, OR = 2.86). EDT differed significantly according to Mdes severity (p = 0.005) with a higher risk of prolonged EDT in medium/severe vs. mild Mdes (OR = 3.44). EDT detected the presence of RVD dysfunction in 58.3% of our pure OSA patients. It correlated poorly with AHI severity but strongly with nocturnal desaturation severity, independently of age. This ETT marker may be useful for deciding appropriate diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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10 pages, 435 KiB

Open AccessArticle

Impact of Positive Airway Pressure on International Restless Legs Syndrome Score in Sleep Disordered Breathing

by Seetha Lakshmanan, Nicolas R. Thompson, Maeve Pascoe, Reena Mehra, Nancy Foldvary-Schaefer, Irene L. Katzan and Harneet K. Walia

J. Clin. Med. 2019, 8(12), 2212; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8122212 - 14 Dec 2019

Cited by 3 | Viewed by 2707

Abstract

Study Objective: Studies have shown increased prevalence of restless legs syndrome (RLS) in sleep disordered breathing (SDB), however limited data have focused on the impact of SDB therapy on RLS. We hypothesize that positive airway pressure (PAP) will improve the International Restless Legs [...] Read more.

Study Objective: Studies have shown increased prevalence of restless legs syndrome (RLS) in sleep disordered breathing (SDB), however limited data have focused on the impact of SDB therapy on RLS. We hypothesize that positive airway pressure (PAP) will improve the International Restless Legs Syndrome (IRLS) score among SDB patients compared to patients without PAP. Methods: Patients with AHI ≥ 5 who responded positively to a RLS qualifier question from January 2010 to May 2015 were included in this retrospective study. IRLS score was used to measure RLS symptom severity. Two-sample t-tests and one-way analysis of variance were used to compare changes in IRLS score and linear regression models were created to examine IRLS change with PAP use and PAP adherence (PAP usage ≥4 h nightly for ≥70% of nights), adjusting for potential confounders. Results: In 434 patients (51.9 ± 13.4years, 50.5% female, 77.6% Caucasian; 325 PAP, 109 control), IRLS scores improved from baseline to follow-up, with the PAP group achieving significant improvement after adjustment for covariates (difference in IRLS: −1.8 (CI −3.6,0.00), p = 0.050). In self-reported PAP adherent patients, IRLS improvement was greater than controls (−5.3 ± 7.4 vs. −2.7 ± 7.6 respectively, p = 0.045), and comparable to non-adherent patients (−5.3 ± 7.4 vs. −3.0 ± 7.0, p = 0.091). Conclusions: Among SDB patients with a positive RLS qualifier, those who used PAP therapy achieved significantly greater improvement in IRLS scores than patients who did not use PAP, with more significant changes in the PAP adherent group. This is the first large clinical study to examine these relationships, providing a basis for future prospective interventional trials and informing clinicians of expected improvement in IRLS score in PAP treated SDB populations. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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17 pages, 1717 KiB

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

by Beata Krasińska, Szczepan Cofta, Ludwina Szczepaniak-Chicheł, Piotr Rzymski, Tomasz Trafas, Lech Paluszkiewicz, Andrzej Tykarski and Zbigniew Krasiński

J. Clin. Med. 2019, 8(10), 1671; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8101671 - 13 Oct 2019

Cited by 16 | Viewed by 3325

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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11 pages, 1673 KiB

Open AccessArticle

Alternations of Circadian Clock Genes Expression and Oscillation in Obstructive Sleep Apnea

by Ming-Yu Yang, Pei-Wen Lin, Hsin-Ching Lin, Pai-Mei Lin, I-Ya Chen, Michael Friedman, Chi-Fa Hung, Anna M. Salapatas, Meng-Chih Lin and Sheng-Fung Lin

J. Clin. Med. 2019, 8(10), 1634; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8101634 - 6 Oct 2019

Cited by 35 | Viewed by 3312

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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12 pages, 2256 KiB

Open AccessArticle

Blood Pressure Non-Dipping and Obstructive Sleep Apnea Syndrome: A Meta-Analysis

by Cesare Cuspidi, Marijana Tadic, Carla Sala, Elisa Gherbesi, Guido Grassi and Giuseppe Mancia

J. Clin. Med. 2019, 8(9), 1367; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8091367 - 2 Sep 2019

Cited by 57 | Viewed by 4142

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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12 pages, 241 KiB

Open AccessArticle

Clinical Characteristics of Obstructive Sleep Apnea in Psychiatric Disease

by Beat Knechtle, Nicholas-Tiberio Economou, Pantelis T. Nikolaidis, Lemonia Velentza, Anastasios Kallianos, Paschalis Steiropoulos, Dimitrios Koutsompolis, Thomas Rosemann and Georgia Trakada

J. Clin. Med. 2019, 8(4), 534; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8040534 - 18 Apr 2019

Cited by 18 | Viewed by 5814

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

Review

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13 pages, 1127 KiB

Open AccessReview

Sleep Disordered Breathing in Hypertrophic Cardiomyopathy—Current State and Future Directions

by Shreyas Venkataraman, Shahid Karim, Aiswarya Rajendran, C. Anwar A. Chahal and Virend K. Somers

J. Clin. Med. 2020, 9(4), 901; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9040901 - 25 Mar 2020

Cited by 4 | Viewed by 3328

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and sleep disordered breathing (SDB) is a treatable risk factor that has been seen to occur concurrently, and is known to propagate mortality and morbidity in a number of cardiovascular disease states including heart [...] Read more.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and sleep disordered breathing (SDB) is a treatable risk factor that has been seen to occur concurrently, and is known to propagate mortality and morbidity in a number of cardiovascular disease states including heart failure, and indeed hypertrophic cardiomyopathy. In this review, we summarize past studies that explored the simultaneous occurrence of HCM and SDB, and the pathophysiology of SDB in relation to heart failure, arrhythmias, cardiac ischemia and pulmonary hypertension in HCM. The current therapeutic modalities, with the effect of obstructive sleep apnea (OSA) treatment on HCM, are then discussed along with potential future directions. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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13 pages, 602 KiB

Open AccessReview

Treatment with CPAP in Elderly Patients with Obstructive Sleep Apnoea

by Tomas Posadas, Grace Oscullo, Enrique Zaldívar, Alberto Garcia-Ortega, José Daniel Gómez-Olivas, Manuela Monteagudo and Miguel Angel Martínez-García

J. Clin. Med. 2020, 9(2), 546; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020546 - 17 Feb 2020

Cited by 14 | Viewed by 3442

Abstract

The population pyramid is changing as a result of the ever-increasing life expectancy, which makes it crucial to acquire an in-depth understanding of the diseases that most often affect the elderly. Obstructive sleep apnoea (OSA) affects 15%–20% of the population aged over 65 [...] Read more.

The population pyramid is changing as a result of the ever-increasing life expectancy, which makes it crucial to acquire an in-depth understanding of the diseases that most often affect the elderly. Obstructive sleep apnoea (OSA) affects 15%–20% of the population aged over 65 years. Despite this prevalence, there have been very few specific studies on the management of OSA in this age group, even though over 60% of the patients aged over 65-70 years who attend sleep units with suspicion of OSA receive treatment with continuous positive airway pressure (CPAP), on the basis of an extrapolation of the positive results achieved by CPAP in clinical trials involving middle-aged males. However, the latter’s form of presentation, evolution and, probably, prognosis comparing with OSA are not the same as those of elderly patients. Recent clinical trials performed on an exclusive series of elderly patients have shed light on the possible role of CPAP treatment in elderly patients with OSA, but there are still many questions that need to be answered. The physiological increase in the number of sleep-related disorders with the passing of years, and the lack of validated diagnostic and therapeutic tools for this age group are probably the greatest obstacles to define, diagnose and treat OSA in the elderly. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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24 pages, 1987 KiB

Open AccessReview

Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment

by Annie C. Lajoie, Anne-Louise Lafontaine, R. John Kimoff and Marta Kaminska

J. Clin. Med. 2020, 9(2), 297; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020297 - 21 Jan 2020

Cited by 52 | Viewed by 5614

Abstract

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent upper airway obstruction during sleep resulting in intermittent hypoxemia and sleep fragmentation. Research has recently increasingly focused on the impact of OSA on the brain’s structure and function, in particular as this [...] Read more.

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent upper airway obstruction during sleep resulting in intermittent hypoxemia and sleep fragmentation. Research has recently increasingly focused on the impact of OSA on the brain’s structure and function, in particular as this relates to neurodegenerative diseases. This article reviews the links between OSA and neurodegenerative disease, focusing on Parkinson’s disease, including proposed pathogenic mechanisms and current knowledge on the effects of treatment. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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9 pages, 477 KiB

Open AccessReview

Continuous Positive Airway Pressure Treatment in Patients with Alzheimer’s Disease: A Systematic Review

by Veronica Perez-Cabezas, Carmen Ruiz-Molinero, Jose Jesus Jimenez-Rejano, Gloria Gonzalez-Medina, Alejandro Galan-Mercant and Rocio Martin-Valero

J. Clin. Med. 2020, 9(1), 181; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9010181 - 9 Jan 2020

Cited by 9 | Viewed by 3048

Abstract

Background: Epidemiological studies have suggested a pathophysiological relationship between obstructive sleep apnea syndrome (OSAS) and Alzheimer’s disease (AD). The aim of this study is to evaluate the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in AD and its relationship [...] Read more.

Background: Epidemiological studies have suggested a pathophysiological relationship between obstructive sleep apnea syndrome (OSAS) and Alzheimer’s disease (AD). The aim of this study is to evaluate the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in AD and its relationship with neurocognitive function improvement. Methods: Systematic review conducted following PRISMA’s statements. Relevant studies were searched in MEDLINE, PEDro, SCOPUS, PsycINFO, Web of Science, CINAHL and SportDicus. Original studies in which CPAP treatment was developel in AD patients have been included. Results: 5 studies, 3 RCTs (Randomized controlled trials) and 2 pilot studies. In all RCTs the CPAP intervention was six weeks; 3 weeks of therapeutic CPAP vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. The two pilot studies conducted a follow-up in which the impact on cognitive impairment was measured. Conclusions: CPAP treatment in AD patients decreases excessive daytime sleepiness and improves sleep quality. There are indications that cognitive deterioration function measured with the Mini Mental Scale decreases or evolves to a lesser extent in Alzheimer’s patients treated with CPAP. Caregivers observe stabilization in disease progression with integration of CPAP. More research is needed on the topic presented. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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8 pages, 207 KiB

Open AccessReview

Novel Aspects of CPAP Treatment and Interventions to Improve CPAP Adherence

by Terri E. Weaver

J. Clin. Med. 2019, 8(12), 2220; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8122220 - 16 Dec 2019

Cited by 55 | Viewed by 5332

Abstract

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea. However, the success of this treatment is hampered by nonadherence in half of the treated patients. Moreover, in clinical trials, poor adherence reduces adequate exposure required to determine its true [...] Read more.

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea. However, the success of this treatment is hampered by nonadherence in half of the treated patients. Moreover, in clinical trials, poor adherence reduces adequate exposure required to determine its true effect. There is growing evidence that behavioral interventions, in addition to education, are a promising approach to improving adherence. Behavioral interventions include the use of cognitive behavioral therapy and motivational enhancement therapy designed to elevate a patient’s self-efficacy. The abundance of data obtained by CPAP tracking systems enables daily surveillance of use, and this telemonitoring along with telehealth allows the provider to quickly intervene when nightly CPAP use falls below thresholds or mask leaks are present. Telehealth reaches a large number of patients who may not be able to regularly attend a clinic, providing support and reinforcement. Peer support may also be useful in improving adherence. Not all obstructive sleep apnea patients present with the same phenotype, and can, therefore, be clustered into several groupings. Which intervention is most successful with a given phenotype or cluster remains unexplored. Comprehensive adherence management requires a team approach with the unique contribution of different professionals. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

17 pages, 880 KiB

Open AccessReview

Oral Appliance Therapy for Obstructive Sleep Apnoea: State of the Art

by Kate Sutherland and Peter A. Cistulli

J. Clin. Med. 2019, 8(12), 2121; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8122121 - 2 Dec 2019

Cited by 24 | Viewed by 10274

Abstract

Obstructive sleep apnoea (OSA) represents a significant global health burden, with impact on cardiometabolic health, chronic disease, productivity loss and accident risk. Oral appliances (OA) are an effective therapy for OSA and work by enlarging and stabilising the pharyngeal airway to prevent breathing [...] Read more.

Obstructive sleep apnoea (OSA) represents a significant global health burden, with impact on cardiometabolic health, chronic disease, productivity loss and accident risk. Oral appliances (OA) are an effective therapy for OSA and work by enlarging and stabilising the pharyngeal airway to prevent breathing obstructions during sleep. Although recommended in clinical guidelines for OSA therapy, they are often considered only as second-line therapy following positive airway pressure (PAP) therapy failure. There has been a long-standing barrier to selecting OA over PAP therapy due to the inability to be certain about the level of efficacy in individual OSA patients. A range of methods to select OSA patients for OA therapy, based on the outcome of a single sleep study night, have been proposed, although none has been widely validated for clinical use. Emergent health outcome data suggest that equivalent apnoea–hypopnea index reduction may not be necessary to produce the same health benefits of PAP. This may be related to the more favourable adherence to OA therapy, which can now be objectively verified. Data on longer term health outcomes are needed, and there are additional opportunities for device improvement and combination therapy approaches. OAs have an important role in precision care of OSA as a chronic disorder through a multi-disciplinary care team. Future studies on real-world health outcomes following OA therapy are needed. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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13 pages, 1621 KiB

Open AccessReview

Transition to Adult Care for Obstructive Sleep Apnea

by Austin Heffernan, Uzair Malik, Russell Cheng, Shaun Yo, Indra Narang and Clodagh M. Ryan

J. Clin. Med. 2019, 8(12), 2120; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8122120 - 2 Dec 2019

Cited by 7 | Viewed by 5017

Abstract

Obstructive sleep apnea may occur throughout the lifespan, with peak occurrences in early childhood and during middle and older age. Onset in childhood is overwhelmingly due to adeno-tonsillar hypertrophy, while in adulthood, contributors include risk factors, such as obesity, male sex, and aging. [...] Read more.

Obstructive sleep apnea may occur throughout the lifespan, with peak occurrences in early childhood and during middle and older age. Onset in childhood is overwhelmingly due to adeno-tonsillar hypertrophy, while in adulthood, contributors include risk factors, such as obesity, male sex, and aging. More recently, there has been a precipitous increase in the prevalence of obstructive sleep apnea in youth. Drivers of this phenomenon include both increasing obesity and the survival of children with complex medical conditions into adulthood. Appropriate treatment and long-term management of obstructive sleep apnea is critical to ensure that these youth maintain well-being unfettered by secondary comorbidities. To this end, patient engagement and seamless transition of care from pediatric to adult health care systems is of paramount importance. To date, this is an unacknowledged and unmet need in most sleep programs. This article highlights the need for guideline-driven sleep disorder transition processes and illustrates the authors’ experience with the development of a program for sleep apnea. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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15 pages, 633 KiB

Open AccessReview

The Role of Animal Models in Developing Pharmacotherapy for Obstructive Sleep Apnea

by Lenise Jihe Kim, Carla Freire, Thomaz Fleury Curado, Jonathan C. Jun and Vsevolod Y. Polotsky

J. Clin. Med. 2019, 8(12), 2049; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8122049 - 22 Nov 2019

Cited by 12 | Viewed by 6277

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent closure of the upper airway during sleep. It has a complex pathophysiology involving four main phenotypes. An abnormal upper airway anatomy is the key factor that predisposes to sleep-related collapse of [...] Read more.

Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent closure of the upper airway during sleep. It has a complex pathophysiology involving four main phenotypes. An abnormal upper airway anatomy is the key factor that predisposes to sleep-related collapse of the pharynx, but it may not be sufficient for OSA development. Non-anatomical traits, including (1) a compromised neuromuscular response of the upper airway to obstruction, (2) an unstable respiratory control (high loop gain), and (3) a low arousal threshold, predict the development of OSA in association with anatomical abnormalities. Current therapies for OSA, such as continuous positive airway pressure (CPAP) and oral appliances, have poor adherence or variable efficacy among patients. The search for novel therapeutic approaches for OSA, including pharmacological agents, has been pursued over the past years. New insights into OSA pharmacotherapy have been provided by preclinical studies, which highlight the importance of appropriate use of animal models of OSA, their applicability, and limitations. In the present review, we discuss potential pharmacological targets for OSA discovered using animal models. Full article

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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19 pages, 935 KiB

Open AccessReview

Resistant/Refractory Hypertension and Sleep Apnoea: Current Knowledge and Future Challenges

by Grace Oscullo, Gerard Torres, Francisco Campos-Rodriguez, Tomás Posadas, Angela Reina-González, Esther Sapiña-Beltrán, Ferrán Barbé and Miguel Angel Martinez-Garcia

J. Clin. Med. 2019, 8(11), 1872; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8111872 - 5 Nov 2019

Cited by 22 | Viewed by 3981

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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26 pages, 2499 KiB

Open AccessReview

Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature

by Luigi Taranto-Montemurro, Ludovico Messineo and Andrew Wellman

J. Clin. Med. 2019, 8(11), 1846; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8111846 - 2 Nov 2019

Cited by 62 | Viewed by 8118

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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18 pages, 4456 KiB

Open AccessReview

Obstructive Sleep Apnea: Emerging Treatments Targeting the Genioglossus Muscle

by Olga Mediano, Sofia Romero-Peralta, Pilar Resano, Irene Cano-Pumarega, Manuel Sánchez-de-la-Torre, María Castillo-García, Ana Belén Martínez-Sánchez, Ana Ortigado and Francisco García-Río

J. Clin. Med. 2019, 8(10), 1754; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8101754 - 22 Oct 2019

Cited by 36 | Viewed by 15273

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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5 pages, 192 KiB

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

by Ari Shechter, Michael Airo, Jordan Valentin, Nicholas C. Dugas, Marwah Abdalla, Marie-Pierre St-Onge and Irene K. Louh

J. Clin. Med. 2019, 8(8), 1195; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8081195 - 10 Aug 2019

Cited by 9 | Viewed by 2749

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

(This article belongs to the Special Issue Treatment of Obstructive Sleep Apnea: State-of-the-Art and Future Directions)

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