Precision Prevention in Obstructive Sleep Apnea.

Sleep-related breathing disorders, encompassing snoring and obstructive sleep apnea (OSA), are highly prevalent worldwide, and there have been important advances in recent years regarding the understanding of underlying pathophysiology mechanisms, diagnosis, and improvement in therapeutic options. The precision medicine and person-centered approaches are based on the concept that every individual is unique and a myriad of elements influence the likelihood of developing the disease, the signs and symptoms expressed, the response to different treatment modalities, and the susceptibility to complications. Thus, health and disease are the result of phenotypic outcomes resulting from interactions between biological factors, environment, and lifestyle.

The Beginning of the AI-Enabled Preventative PAP Therapy Era: A First-in-Human Proof of Concept Interventional Study.

Positive Airway Pressure (PAP) therapy is the most common and efficacious treatment for Obstructive Sleep Apnea (OSA). However, it suffers from poor patient adherence due to discomfort and may not fully alleviate all adverse consequences of OSA. Identifying abnormal respiratory events before they have occurred may allow for improved management of PAP levels, leading to improved adherence and better patient outcomes. Our previous work has resulted in the successful development of a Machine-Learning (ML) algorithm for the prediction of future apneic events using existing airflow and air pressure sensors available internally to PAP devices. Although researchers have studied the use of ML for the prediction of apneas, research to date has focused primarily on using external polysomnography sensors that add to patient discomfort and has not investigated the use of internal-to-PAP sensors such as air pressure and airflow to predict and prevent respiratory events. We hypothesized that by using our predictive software, OSA events could be proactively prevented while maintaining patients' sleep quality. An intervention protocol was developed and applied to all patients to prevent OSA events. Although the protocol's cool-down period limited the number of prevention attempts, analysis of 11 participants revealed that our system improved many sleep parameters, which included a statistically significant 31.6% reduction in Apnea-Hypopnea Index, while maintaining sleep quality. Most importantly, our findings indicate the feasibility of unobtrusive identification and unique prevention of each respiratory event as well as paving the path to future truly personalized PAP therapy by further training of ML models on individual patients.

Association of adherence to the Mediterranean diet and physical activity habits with the presence of insomnia in patients with obstructive sleep apnea.

PURPOSE: Insomnia and obstructive sleep apnea (OSA) are among the most prevalent sleep disorders and frequently co-occur, defining the sleep apnea-insomnia syndrome. However, data exploring associations between insomnia and lifestyle habits in patients with OSA are lacking. Therefore, the aim of the present study was to investigate potential associations between insomnia presence and individual lifestyle parameters in patients with mild/moderate-to-severe OSA evaluated by attended polysomnography. METHODS: These are secondary analyses, using data from a cross-sectional study among 269 Greek patients with OSA. Clinical, anthropometric, socioeconomic, and lifestyle data were collected for all participants. Insomnia presence was evaluated through the validated psychometric instrument "Athens Insomnia Scale" (AIS). Adherence to the Mediterranean diet was estimated with the MedDietScale index and physical activity habits were assessed through a validated questionnaire. Backward stepwise multiple logistic regression analysis was used to estimate the association between lifestyle habits (i.e., adherence to the Mediterranean diet and physical activity) and the likelihood of having insomnia, while adjusting for potential confounders. RESULTS: Of 269 patients newly diagnosed with OSA (aged 21-70 years; 73% men), 146 (54%) were categorized as having insomnia. In multivariable models, higher adherence to the Mediterranean diet and engagement in physical activity for ≥ 30 min/day were both associated with a lower likelihood of having insomnia (odds ratio (95% confidence intervals): 0.40 (0.18-0.91) and 0.49 (0.28-0.86), respectively). CONCLUSIONS: Results add to the limited data on the role of lifestyle in insomnia and should be further explored both in epidemiological and clinical studies.

Clinical safety and hemodynamic, cardiac autonomic and inflammatory responses to a single session of inspiratory muscle training in obstructive sleep apnea.

PURPOSE: To determine clinical safety and cardiovascular, cardiac autonomic and inflammatory responses to a single session of inspiratory muscle training (IMT) in obstructive sleep apnea (OSA) subjects. METHODS: In a randomized controlled trial individuals of both sexes, aged between 30 and 70 years old with diagnosis of moderate to severe OSA were enrolled. Volunteers with OSA (n = 40) performed an IMT session with three sets of 30 repetitions with a 1-min interval between them. The IMT group (n = 20) used a load of 70% of the maximum inspiratory pressure (MIP), and the placebo group (n = 20) performed the IMT without load. Measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), heart rate variability (HRV), and inflammatory markers were performed pre, post-immediate and 1 h after the IMT session. RESULTS: No differences were shown in SBP, DBP, HRV, or inflammatory markers at any of the intervals analyzed. However, HR in the IMT group was lower ​​1 h after the IMT session compared to the pre-session values ​​(p = 0002). HR was higher in the placebo group when comparing pre × post-immediate (p < 0.001). HR decreased after the first hour in relation to the pre (p < 0.001) and post-immediate (p < 0.001) values. CONCLUSION: IMT sessions promote discreet hemodynamic, cardiac autonomic and inflammatory responses. Therefore, IMT is considered clinically safe and can be performed at home, guided but unsupervised, with lower cost and greater adherence to exercise program for subjects with OSA.

Cushing Syndrome is Associated with Increased Stage N2 Sleep and Decreased SWS Partially Reversible After Treatment.

The aim of the present study was to evaluate the sleep parameters of patients with Cushing syndrome (CS) at the time of diagnosis and 12-months after treatment. Thirty four newly diagnosed patients with endogenous CS (17 with ACTH-secreting pituitary adenoma, 17 with adrenal CS) and 23 controls with similar age were included in the study. Two polysomnography (PSG) recordings were performed; one at the time of diagnosis and the other 12 months after resolution of hypercortisolemia. Control group had only baseline PSG. Based on the PSG findings, stage N2 sleep was found to be prolonged, stage N3 and REM sleep were shortened in patients with CS. Average heart rate and mean Apnea Hypopnea Index (AHI) score were higher in patients with CS than the control subjects. Sixteen (47.1%) patients with CS and 4 (17.4%) controls had obstructive sleep apnea (OSA; AHI ≥5). There were no significant differences in sleep parameters of patients according to the etiology of CS (adrenal vs. pituitary) patients. Following 12-months of treatment, a significant decrease in stage N2 sleep and a significant increase in stage N3 sleep were detected, but there was no change in terms of AHI. In conclusion, Cushing syndrome has disturbing effects on sleep structure and these effects are at least partially reversible after treatment. However, the increased risk of OSA was not reversed a year after treatment indicating the importance of early diagnosis and treatment of CS.

Clusters of comorbidities in idiopathic pulmonary fibrosis.

INTRODUCTION: Comorbidities are common in patients with idiopathic pulmonary fibrosis (IPF) and negatively impact health-related quality of life, health-care costs and mortality. Retrospective studies have focused on individual comorbidities, but clusters of multiple comorbidities have rarely been analysed. This study aimed to comprehensively and prospectively assess comorbidities in a multicentre, real-world cohort of patients with IPF, including prespecified conditions of special interest and to analyse clusters of comorbidities and examine characteristics, disease course and mortality of the clusters. METHODS: Several measurements, questionnaires, medications and medical history were combined to assess comorbidities. Using self-organizing maps, clusters of comorbidities were identified and phenotypes characterized. Disease course was assessed using mixed effects models and mortality using Cox regression. RESULTS: One-hundred and fifty IPF patients were included prospectively. All except one patient suffered from at least one comorbidity and multimorbidity was common. Arterial hypertension, gastro-oesophageal reflux disease, hypercholesterolemia, emphysema and obstructive sleep apnea were most prevalent. Four comorbidity clusters were identified. Each cluster had distinct comorbidity profiles, patient characteristics, symptom burden and disease severity. Patients with fewer comorbidities had better exercise capacity and less dyspnea at baseline, but a trend towards faster deterioration was observed. Mortality analyses showed no significant differences between clusters. CONCLUSIONS: Multimorbidity is prevalent in patients with IPF. Four specific clusters of comorbidities may represent phenotypes in IPF. A trend towards faster decline in exercise capacity and dyspnea was observed in patients with fewer comorbidities. Increased knowledge of comorbidities facilitates prevention and treatment of comorbidities in patients with IPF.

Impact of histaminergic H3 receptor antagonist on hypoglossal nucleus in chronic intermittent hypoxia conditions.

RATIONALE: The hypoglossal nucleus (HN) controls the movement of the genioglossus (GG) muscle whose dysfunction leads to airway occlusion and occurrence of obstructive sleep apnea (OSA). Histamine produced by the tuberomammillary nucleus (TMN) has a potent excitatory action on GG muscle activity. OBJECTIVES: The aim of the study was to investigate the role histaminergic neurons play in the regulation of the genioglossus. METHODS: C57BL/6 mice were exposed to chronic intermittent hypoxia (CIH) for 3 weeks to resemble OSA. The histamine H3 receptor (H3R) antagonist ciproxifan was applied to increase histamine in the brain. Histamine levels and GG activity were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electromyogram (EMG) separately. Neuronal activity and repair ability of the HN and TMN and key proteins of histamine were analyzed by immunohistochemistry and western blots. RESULTS: Significant decline of histamine level and GG activity of the HN and TMN induced by CIH exposure could be ameliorated by ciproxifan. Application of ciproxifan could also partly reverse the decline of the histidine decarboxylase (HDC) by CIH. CONCLUSIONS: This investigation studied the impacts of ciproxifan on the HN and TMN in CIH conditions and revealed that the negative effects on the HN and TMN caused by CIH could be partly ameliorated by ciproxifan, which might open new perspectives for the development of pharmacological treatment for OSA.

Impact of short-acting vs. standard anaesthetic agents on obstructive sleep apnoea: a randomised, controlled, triple-blind trial.

Sleep apnoea is associated with negative outcomes following general anaesthesia. Current recommendations suggest using short-acting anaesthetic agents in preference to standard agents to reduce this risk, but there is currently no evidence to support this. This randomised controlled triple-blind trial tested the hypothesis that a combination of short-acting agents (desflurane-remifentanil) would reduce the postoperative impact of general anaesthesia on sleep apnoea severity compared with standard agents (sevoflurane-fentanyl). Sixty patients undergoing hip arthroplasty under general anaesthesia were randomised to anaesthesia with desflurane-remifentanil or sevoflurane-fentanyl. Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the supine apnoea-hypopnoea index on the first postoperative night. Secondary outcomes were the supine apnoea-hypopnoea index on the third postoperative night, and the oxygen desaturation index on the first and third postoperative nights. Additional outcomes included intravenous morphine equivalent consumption and pain scores on postoperative days 1, 2 and 3. Pre-operative sleep study data were similar between groups. Mean (95%CI) values for the supine apnoea-hypopnoea index on the first postoperative night were 18.9 (12.7-25.0) and 21.4 (14.2-28.7) events.h-1 , respectively, in the short-acting and standard anaesthesia groups (p = 0.64). Corresponding values on the third postoperative night were 28.1 (15.8-40.3) and 38.0 (18.3-57.6) events.h-1 (p = 0.34). Secondary sleep- and pain-related outcomes were generally similar in the two groups. In conclusion, short-acting anaesthetic agents did not reduce the impact of general anaesthesia on sleep apnoea severity compared with standard agents. These data should prompt an update of current recommendations.

Effect of water exercise in blood pressure and sleep quality of hypertensive adults.

BACKGROUND: Together with ageing there is an increase in blood pressure levels. However, physical activity is one of the most recommended strategies for preventing the increase of blood pressure. Water exercise involves numerous advantages, one of which is the comfort proportioned by water temperature. The aim of this study was to evaluate the effects of a water exercise program on blood pressure, physical fitness, quality of sleep and the likelihood of having sleep apnea (SA) in hypertensive adults. METHODS: We evaluated 21 sedentary hypertensive subjects of both sexes. The water exercise was conducted over 13 weeks, three times/week, 50 min/day. Resting blood pressure, height, body weight, waist and hip circumference, functional capability, as well as sleep quality and the likelihood of having sleep apnea were evaluated before and after the experimental period. RESULTS: There was a significant decrease in systolic and mean blood pressure. Significant increases in strength, muscular and aerobic endurance, coordination, agility, dynamic balance and flexibility were also seen. In addition, a reduction in the likelihood of sleep apnea was identified, despite a deterioration in sleep quality. CONCLUSIONS: Water exercise was effective in reducing systolic blood pressure, in improving functional capacity variables, and in reducing probability of sleep apnea in hypertensive subjects, however it promoted worsening of sleep quality.

Who May Benefit From Diuretics in OSA?: A Propensity Score-Match Observational Study.

BACKGROUND: Diuretics have been reported as effective for reducing OSA severity by preventing fluid retention and reducing rostral fluid shift. The benefit of diuretics might vary depending on the OSA clinical phenotype and comorbidities. To test this hypothesis, we conducted a propensity score-matched cohort analysis of data from the French national sleep apnea registry "Observatoire Sommeil de la Fédération de Pneumologie." RESEARCH QUESTION: Which phenotypic subtypes of OSA may benefit from diuretics? STUDY DESIGN AND METHODS: A propensity score analysis was used to determine the impact of diuretics on OSA severity. Matching (ratio 1:4) was performed by using a 0.1 collider for the propensity score. Severe OSA was defined as an apnea-hypopnea index (AHI) > 30 events/h, and the usefulness of diuretics was assessed by using a logistic regression model. RESULTS: The 69,564 OSA patients studied in the OSFP prospective observational cohort had a median age of 56.9 years (interquartile range: 47.4; 65.6), 67% were men, and the median AHI was 28 (14; 43) events/h. Among them, 9,783 (14.1%) were treated with diuretics. Diuretics reduced OSA severity in overweight or moderately obese patients (P = .03) and in patients with hypertension (P < .01), particularly in patients with hypertension with a BMI between 25 and 35 (P < .01). Diuretics had no significant effect on OSA severity in patients with self-reported low physical activity or heart failure. INTERPRETATION: Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension. A prospective study is needed to confirm that diuretics are of interest in combined therapies for hypertensive patients with OSA.

Qualitative Assessment of the Effect of Continuous Positive Airway Pressure on the Nasal Cavity.

BACKGROUND: For patients with obstructive sleep apnea (OSA), there is a lack of knowledge regarding the impact of continuous positive airway pressure (CPAP) on the nasal cavity. There is a significant need for evidence-based recommendations regarding the appropriate use of CPAP following endoscopic sinus and skull base surgery. OBJECTIVE: The goal of this study is to translate a previously developed cadaveric model for evaluating CPAP pressures in the sinonasal cavity by showing safety in vivo and quantifying the effect of positive pressurized air flow on the nasal cavity of healthy individuals where physiologic effects are at play. METHODS: A previously validated cadaveric model using intracranial sensor catheters has proved to be a reliable technique for measuring sinonasal pressures. These sensors were placed in the nasal cavity of 18 healthy individuals. Pressure within the nose was recorded at increasing levels of CPAP. RESULTS: Overall, nasal cavity pressure was on average 85% of delivered CPAP. The amount of pressure delivered to the nasal cavity increased as the CPAP increased. The percentage of CPAP delivered was 77% for 5 cmH2O and increased to 89% at 20 cmH2O. There was a significant difference in mean intranasal pressures between all the levels of CPAP except 5 cmH2O and 8 cmH2O (P < .001). CONCLUSION: On average, only 85% of the pressure delivered by CPAP is transmitted to the nasal cavity. Higher CPAP pressures delivered a greater percentage of pressurized air to the nasal cavity floor. Our results are comparable to the cadaver model, which demonstrated similar pressure delivery even in the absence of anatomic factors such as lung compliance, nasal secretions, and edema. This study demonstrates the safety of using sensors in the human nasal cavity. This technology can also be utilized to evaluate the resiliency of various repair techniques for endoscopic skull base surgery with CPAP administration.

Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is very common but is frequently undiagnosed. Symptoms include loud snoring, nocturnal awakening, and daytime sleepiness. Motor vehicle accidents due to drowsy driving are a particular concern. Evaluation and treatment should focus on symptomatic patients, both to alleviate symptoms and to potentially decrease cardiovascular risk. In recent years, a strategy of home sleep apnea testing followed by initiation of autotitrating continuous positive airway pressure therapy in the home has greatly reduced barriers to diagnosis and treatment and has also facilitated routine management of OSA by primary care providers.

Effects of exercise on sleep symptoms in patients with severe obstructive sleep apnea.

OBJECTIVE: To investigate the extent to which exercise is associated with symptoms in patients with severe obstructive sleep apnea (OSA). METHODS: We included subjects with an apnea-hypopnea index (AHI) > 30 events/h who completed validated sleep and exercise questionnaires. We compared symptom frequency/scores between exercisers and nonexercisers, adjusting for the usual confounders. RESULTS: The sample included 907 nonexercisers and 488 exercisers (mean age, 49 ± 14 years; mean AHI, 53 ± 20 events/h; 81% men). Nonexercisers and exercisers differed significantly in terms of obesity (72% vs. 54%), the mean proportion of sleep in non-rapid eye movement stage 3 sleep (9 ± 8% vs. 11 ± 6%), and tiredness (78% vs. 68%). Nonexercisers had a higher symptom frequency/scores and poorer sleep quality. Adjustment for exercise weakened the associations between individual symptoms and the AHI, indicating that exercise has a mitigating effect. In binary logistic models, exercise was associated with approximately 30% lower adjusted questionnaire1 score > 2, tiredness; poor-quality sleep, unrefreshing sleep, and negative mood on awakening. Although the odds of an Epworth Sleepiness Scale score > 10 were lower in exercisers, that association did not withstand adjustment for confounders. CONCLUSIONS: Exercise is associated with lower frequency/intensity of symptoms in patients with severe OSA. Because up to one third of patients with severe OSA might exercise regularly and therefore be mildly symptomatic, it is important not to rule out a diagnosis of OSA in such patients.

Intensive Continuous Positive Airway Pressure Adherence Program During Stroke Rehabilitation.

Background and Purpose- Continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea may improve stroke recovery, but adherence is poor. We assessed the effectiveness of an intensive CPAP adherence program during and after inpatient stroke rehabilitation on 3-month adherence and stroke recovery. Methods- In a single-arm study, 90 stroke rehabilitation patients were enrolled into an intensive CPAP adherence program. CPAP was continued after a run-in among qualifying patients with evidence of obstructive sleep apnea. The primary outcome was CPAP adherence, defined as ≥4 hours of use on ≥70% of days, over 3 months. Results- A total of 62 patients qualified for continued CPAP and 52 of these were willing to continue CPAP after discharge from rehabilitation. At 3 months, the average daily CPAP use was 4.7 hours (SD 2.6), and 32/52 (62%) patients were adherent. Factors significantly associated with adherence included more severe stroke, aphasia, and white race. Compared with nonadherent patients, adherent patients experienced greater improvements in the cognitive component of the Functional Independence Measure ( P=0.02) and in the National Institutes of Health Stroke Scale ( P=0.03). Conclusions- This intensive CPAP adherence program initiated during stroke rehabilitation can lead to CPAP adherence in the majority of patients with evidence of obstructive sleep apnea, including those with more severe stroke and aphasia, and may promote recovery. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02809430.

The effect of opioid therapy on sleep quality in patients with chronic non-malignant pain: A systematic review and exploratory meta-analysis.

Current guidelines recommend opioid therapy to chronic non-malignant pain (CNP) patients when the benefits for pain and function outweigh risks. This systematic review examined the effects of opioid therapy on sleep - a valued functional outcome- in CNP. Electronic and hand searches of relevant studies up through July 2017 identified 18 eligible studies providing data from 3,746 CNP patients for analysis. Twelve of these studies were randomised controlled trials of up to 12-month in duration. Morphine sulfate, oxycodone and transdermal fentanyl were the most tested therapies (n = 4 each). Only two studies used objective sleep measures in addition to self-report ratings, questionnaires or sleep diaries. Whilst calmer sleep with less body/leg movements and fewer awakenings could be achieved following opioid therapy, these might occur with increased sleep-disordered breathing and a much-shortened rapid eye movement (REM) sleep latency. Both the narrative synthesis and exploratory meta-analysis suggest that opioid therapy in CNP is associated with improved self-reported sleep quality. However, the effect is inconsistent, small (Standardised Mean Difference = 0.36), and may be accompanied by excessive daytime sleepiness. As a Cochrane-recommended assessment revealed "unclear" or "high" overall risk of bias for all studies, future opioid trials of stronger methodology and better reporting are needed to confirm and elucidate the effect.

Obstructive sleep apnea: personal, societal, public health, and legal implications.

Introduction Obstructive sleep apnea (OSA) is a widely prevalent sleep-related breathing disorder, which leads to several life-threatening diseases. OSA has systemic effects on various organ systems. Untreated OSA is associated with long-term health consequences including hypertension, heart disease, diabetes, depression, metabolic disorders, and stroke. In addition, untreated OSA is reported to be associated with cognitive dysfunction, impaired productivity at the workplace and in an increased risk of motor vehicle accidents (MVAs) resulting in injury and fatality. Other consequences of OSA include, but are not limited to, impaired vigilance, daytime somnolence, performance deficits, morning headaches, mood disturbances, neurobehavioral impairments, and general malaise. Additionally, OSA has become an economic burden on most health systems all over the world. Many driving license regulations have been developed to reduce MVAs among OSA patients. Methods Studies of the personal, societal, public health, and legal aspects of OSA are reviewed. Data were collected through the following databases: MEDLINE, Google Scholar, Scopus, SAGE Research Methods, and ScienceDirect. Conclusion OSA leads to worsening of patients' personal relationships, decreasing work productivity, and increasing occupational accidents as well as MVAs. The costs of undiagnosed and untreated OSA to healthcare organizations are excessive. Thus, proper management of OSA will benefit not only the patient but will also provide widespread benefits to the society as a whole.

Longitudinal Sleep Outcomes in Neonates With Pierre Robin Sequence Treated Conservatively.

STUDY OBJECTIVES: Although Pierre Robin sequence (PRS) is a major cause of neonatal obstructive sleep apnea (OSA), longitudinal studies reporting evolution with age are lacking. This study aimed to describe changes in sleep-related respiratory parameters and sleep architecture in neonates with PRS treated conservatively (defined for this paper as treatment without tracheostomy or mandibular distraction). METHODS: A retrospective, 14-year, single-institution study of neonates with PRS who underwent diagnostic polysomnography (PSG) and at least one follow-up PSG. Those treated with surgery were excluded. Data were analyzed using a mixed-effects model with subject-specific random effect. RESULTS: In a cohort of 21 infants, baseline PSG (mean age 0.9 ± 0.7 months) showed a total apnea-hypopnea index (AHI) of 24.3 ± 3.6 events/h, obstructive apnea-hypopnea index (OAHI) of 13.4 ± 1.6 events/h, central apnea index of 10.2 ± 3.2 events/h, and an arousal index of 28.3 ± 1.3 events/h (variables reported as least square means ± standard error of the mean). There was a significant reduction in AHI, OAHI, arousal index, and percentage of REM sleep with advancing age. Although 71% of infants achieved full oral feeds by one month of age, some infants remained underweight during infancy. CONCLUSIONS: These neonates with PRS and OSA, treated conservatively, had an improvement in OAHI with advancing age with the median age of OSA resolution at 15 months. Factors potentially responsible include craniofacial growth and maturational changes of respiratory control. Further studies are necessary to determine the long-term effects of conservative management on growth and neurodevelopmental outcomes in these infants.

Sleep-Disordered Breathing, Orofacial Growth, and Prevention of Obstructive Sleep Apnea.

Abnormal breathing during sleep is related to intrinsic and extrinsic factors that are present early in life. Investigation of fetal development and early-in-life orofacial growth allows recognition of risk factors that lead to change in upper airway patency, which leads to abnormal upper airway resistance, abnormal inspiratory efforts, and further increase in resistance and progressive narrowing of the collapsible upper airway. Such evolution can be recognized by appropriate clinical evaluation, specific polysomnographic patterns, and orofacial imaging. Recognition of the problems should lead to appropriate treatments and prevention of obstructive sleep apnea and its comorbidities.