Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.

Sleep disorders and COVID-19.

This chapter summarizes the known associations between COVID-19 and sleep dysfunction, including insomnia, excessive daytime sleepiness, restless legs syndrome and nightmares, and touches upon pandemic-related considerations for obstructive sleep apnea and continuous positive airway pressure treatment. Treatment strategies and management approaches are also briefly discussed.

Diagnostic accuracy and feasibility of portable sleep monitoring in patients with obstructive sleep apnea: Re-exploring the utility in the current COVID-19 pandemic.

Portable sleep monitoring (PSM) is a promising alternative diagnostic tool for Obstructive Sleep Apnea (OSA) especially in high burden resource limited settings. We aimed to determine the diagnostic accuracy and feasibility of PSM device-based studies in patients presenting for evaluation of OSA at a tertiary care hospital in North-India. PSM studies (using a Type-III PSM device) were compared for technical reliability and diagnostic accuracy with the standard laboratory-based Type-I polysomnography (PSG). Patients were also interviewed about their experience on undergoing an unsupervised PSM studies. Fifty patients (68% males) were enrolled in the study, of which only 30% patients expressed their concerns about undergoing unsupervised PSM studies which included safety issues, ease of use, diagnostic accuracy, etc. Technical acceptability criteria were easily met by the PSM studies with signal loss in 12% studies (complete data loss and inaccessible data in 6% studies), warranting repetition sleep studies in four patients. The overall sensitivity of PSM device (AHI ≥5) was 93.5% (area under curve; AUC: 0.87). The diagnostic accuracy was 68.5%, 80%, and 91.4% for mild, moderate, and severe cases of OSA, respectively. An overall strong correlation was observed between PSM-AHI (apnoea-hypopnoea index) and PSG (r>0.85, p≤0.001), especially in severe OSA. The observed sensitivity was >90% for AHI>20 (clinically significant OSA), with high specificity of 91% for severe OSA (AUC: 0.94, 0.97 for AHI>20, AHI>30 respectively). The overall Bland-Altman concordance analysis also demonstrated only a small dispersion for PSM studies with a Cronbach's coefficient of 0.95. Therefore, there is good diagnostic accuracy as well as feasibility of home-based portable sleep studies in Indian patients. It can be promoted for widespread use in high burden countries like India for diagnosing and managing appropriately selected stable patients with high clinical probability of OSA, especially during the ongoing crises of COVID-19 pandemic.

Contemporary Concise Review 2022: Sleep.

COVID-19 AND SLEEP: The COVID-19 pandemic is associated with an increase in insomnia and impaired sleep quality Health care workers are particularly susceptible and improved with cognitive behavioural therapy for insomnia (CBT-I) Long COVID has significant effects on sleep OSA impacts on the severity of acute COVID-19 illness OBSTRUCTIVE SLEEP APNOEA: Large trials of clinically representative patients confirm the cardiovascular benefits of CPAP treatment in OSA CPAP may improve long-term cognitive outcomes in OSA, but further research is needed Racial disparities in OSA prevalence and mortality risk are becoming evident Periodic evaluation of OSA risk in pregnancy is important as timing may be key for intervention to prevent or treat cardiovascular risk factors INSOMNIA: Comorbid insomnia and obstructive sleep apnoea (COMISA) can frequently co-exist and the combined negative effects of both may be deleterious, particularly to cardiovascular health There is evidence for effectiveness with novel orexin receptor antagonists.

The association between respiratory diseases and periodontitis: A systematic review and meta-analysis.

AIM: To evaluate (1) whether periodontitis has an influence on the prevalence/incidence of respiratory diseases (chronic obstructive pulmonary disease [COPD], asthma, community-acquired pneumonia [CAP], obstructive sleep apnoea [OSA] and COVID-19), and (2) what is the impact of periodontal therapy on the onset or progression of respiratory diseases. MATERIALS AND METHODS: An electronic search was performed on Pubmed, Cochrane Library and Scopus databases up to October 2021, to identify studies answering the PECOS and PICOS questions. RESULTS: Seventy-five articles were selected. Meta-analyses identified statistically significant associations of periodontitis with COPD (nstudies  = 12, odds ratio [OR] = 1.28, 95% confidence interval [CI] [1.16; 1.42], p < .001), and OSA (ns  = 6, OR = 1.65, 95% CI [1.21; 2.25], p = .001), but not for asthma (ns  = 9, OR = 1.53, 95% CI [0.82; 2.86], p = .181). For acute conditions, two studies were found for CAP, while for COVID-19, significant associations were found for the need of assisted ventilation (ns  = 2, OR = 6.24, 95% CI [2.78; 13.99], p < .001) and COVID-related mortality (ns  = 3, OR = 2.26, 95% CI [1.36, 3.77], p = .002). Only four intervention studies were found, showing positive effects of periodontal treatment on COPD, asthma and CAP. CONCLUSIONS: A positive association between periodontitis and COPD, OSA and COVID-19 complications has been found, while there is a lack of intervention studies.

The Utility of Home Sleep Apnea Testing in the Advanced Heart Failure Populations.

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.

Obstructive Sleep Apnea with COVID-19.

The novel coronavirus disease-2019 (COVID-19) and the ensuing pandemic have greatly impacted the global healthcare system due to its high infectiousness, associated high mortality, and a complete lack of immunity in the population. Globally, the COVID-19 pandemic has unleashed a health crisis that has not only seriously disrupted people's lives but also affected their normal sleep, along with physical and mental health; this situation is especially exacerbated in people suffering from pre-existing conditions, such as sleep apnea. A recent meta-analysis of 18 studies by Miller et al. (September 2020) showed that obstructive sleep apnea (OSA) is related to higher mortality and morbidity in patients with COVID-19 and is most likely independent of other risk factors. A recent meta-analysis indicated that COVID-19 patients with OSA are more severely affected than those without OSA, thereby providing further evidence that concurrent OSA may elevate the severity of COVID-19 infection, along with the risk of mortality. The COVID-19 pandemic has significantly impacted the diagnosis and therapeutic management of patients with OSA. Thus, it is necessary to identify and develop new diagnostic and therapeutic avenues in the future. In this context, the current study summarizes known associations between COVID-19 and OSA and the regular diagnostic and therapeutic strategies for OSA in the light of COVID-19 pandemic prevention and control.

Obstructive sleep apnoea and perioperative medicine: a growing concern.

Obstructive sleep apnoea represents a sizable public health and economic burden. Owing to rising obesity rates, the prevalence of obstructive sleep apnoea is increasing, and it is a condition that is significantly underdiagnosed. Exacerbated by the COVID-19 pandemic, the backlog of elective surgeries is also sizable and growing. A combination of these factors means that many patients due to have surgery will have obstructive sleep apnoea, either diagnosed or otherwise. Patients with obstructive sleep apnoea have a significantly increased risk of operative complications, but the evidence base for optimum perioperative management of these patients is limited. This article reviews sleep apnoea, its prevalence and its impact on operative management and perioperative outcomes for patients. The evidence base for screening and treating undiagnosed obstructive sleep apnoea is also comprehensively assessed. Finally, a pathway to manage patients with possible undiagnosed obstructive sleep apnoea is proposed, and areas for further research identified.

Obstructive Sleep Apnea and Cardiovascular Diseases: Sad Realities and Untold Truths regarding Care of Patients in 2022.

Obstructive sleep apnea (OSA) is one of the most common and serious sleep-related breathing disorders with a high prevalence among patients with cardiovascular (CV) diseases. Despite its widespread presence, OSA remains severely undiagnosed and untreated. CV mortality and morbidity are significantly increased in the presence of OSA as it is associated with an increased risk of resistant hypertension, heart failure, arrhythmias, and coronary artery disease. Evaluation and treatment of OSA should focus on recognizing patients at risk of developing OSA. The use of screening questionnaires should be routine, but a formal polysomnography sleep study is fundamental in establishing and classifying OSA. Recognition of OSA patients will allow for the institution of appropriate therapy that should alleviate OSA-related symptoms with the intent of decreasing adverse CV risk. In this review, we focus on the impact OSA has on CV disease and evaluate contemporary OSA treatments. Our goal is to heighten awareness among CV practitioners.

The Influence of SARS-CoV-2 Pandemic on TMJ Disorders, OSAS and BMI.

The pandemic of the 21st century had a significant influence on the lives of the world population in a negative way. This situation determined a change of lifestyle; it caused the necessity of social isolation for a great number of people. In fact, people tended to avoid crowded environments, social events, to reduce medical checks and sports activities, favoring sedentary life because of fear of the virus. This social attitude brought a high level of stress that worsened many health conditions. This study has the aim of evaluating the possible influence of the pandemic on temporomandibular joint (TMJ) disorders, obstructive sleep apnea syndrome (OSAS) and body mass index (BMI). An anonymized survey, available in two languages (Italian and English), was given to 208 patients from different private dental practices. In this questionnaire, the patients shared experiences about their life during the pandemic. The article highlighted that during this health emergency, there was an increase in body weight in the considered sample. This brought a worsening of OSAS in 65% of patients with a previous diagnosis. Eventually, an increase in TMJ disorders and orofacial pain was reported.

COVID-19 Pandemic-Related Sleep and Mental Health Disparities among Students at a Hispanic and Minority-Serving Institution.

BACKGROUND: The COVID-19 pandemic has impacted nearly all sectors of our population, including college students, who continue to share disproportionate rate of disparities. In this study, we aimed to identity key sleep health characteristics, including markers for obstructive sleep apnea, as well as its relation to mental health, physical health, and academic performance. METHODS: A cross-sectional study design with online survey dissemination was used. Descriptive, bivariate, and multivariable binary logistic regression analyses were conducted among a predominantly minority population. RESULTS: Results show that nearly 78% of the population reported that the pandemic impacted their mental or physical health, while over 83% reported daytime tiredness/fatigue/sleepiness, and another 61% reported sleeping less than seven hours during weekdays. Among other associations, pandemic-related poor sleep health, including sleeping less than seven hours, was associated with daytime tiredness/fatigue/sleepiness, psychological distress, as well as low mental health and physical health. A severe marker for obstructive sleep apnea, having stopped breathing during sleep, was also associated with psychological distress during the pandemic. CONCLUSIONS: Sleep health interventions are critical for optimizing college student health and well-being, including improving mental health outcomes.

Sleep health and the circadian rest-activity pattern four months after COVID-19.

OBJECTIVE: To describe the prevalence and severity of sleep disorders and circadian alterations in COVID-19 patients four months after the acute phase of the disease. METHODS: This was a cross-sectional observational prospective study of patients with mild COVID-19, moderate COVID-19 (requiring hospitalization but no mechanical ventilation), or severe COVID-19 (with ARDS) four months after the acute phase of the disease. All patients underwent a home sleep apnea test and seven-day wrist actigraphy, as well as completing questionnaires to assess sleep quality and mental health. Differences among the three groups of patients were evaluated by ANOVA and the chi-square test. RESULTS: A total of 60 patients were included in the study. Of those, 17 were in the mild COVID-19 group, 18 were in the moderate COVID-19 group, and 25 were in the severe COVID-19 group. Sleep quality, as assessed by satisfaction, alertness, timing, efficiency, and duration scale scores, was found to be impaired in all three groups, which also had a high prevalence of unhealthy sleep, as assessed by the Pittsburgh Sleep Quality Index. The prevalence of insomnia was increased in all three groups, as assessed by the Insomnia Severity Index. The home sleep apnea test showed that the overall prevalence of obstructive sleep apnea was 60%, and seven-day wrist actigraphy showed that total sleep time was < 7 h in all three groups. Changes in quality of life and in the circadian rest-activity pattern were observed in all three groups. CONCLUSIONS: Sleep-related symptoms, changes in the circadian rest-activity pattern, and impaired mental health appear to be common in COVID-19 patients four months after the acute phase of the disease, severe COVID-19 being associated with a higher prevalence of obstructive sleep apnea.

Running a paediatric ambulatory sleep service in a pandemic and beyond.

OBJECTIVES: In response COVID-19, re-establishing safe elective services was prioritised in the UK. We assess the impact on face-to-face hospital attendance, cost and efficiency of implementing a virtual sleep clinic (intervention 1) to screen for children requiring level 3 ambulatory sleep studies using newly implemented ENT-UK guidelines for obstructive sleep apnoea (OSA) investigation (intervention 2). OBJECTIVES: (1) compare the proportion of children attending sleep clinic undertaking a sleep study before and after implementation of these interventions; (2) compare clinic cancellations and first-time success rates of sleep studies before and after intervention. DESIGN: Retrospective analysis. SETTING: District general hospital paediatric sleep clinic. PARTICIPANTS: Children aged 3 months to 16 years referred to sleep clinic by ENT for investigation of OSA over 3 months immediately following interventions (1 June 2020 - 1 September 2020) to the same period in the previous year (1 June 2019 - 1 September 2019). MAIN OUTCOME MEASURES: Number of children attending sleep clinic, date of birth/age of children attending sleep clinic, number of children undergoing sleep study, diagnostic outcomes, number of appointment cancellations, number of first-time sleep study failures. RESULTS: Post intervention, there was a significant reduction in the proportion of children undertaking ambulatory sleep studies, and nonsignificant reductions in appointment cancellations and in first-time sleep study failures. CONCLUSIONS: The introduction of the virtual sleep clinic meant that only those children requiring a sleep study attended a face-to-face appointment, which led to reduced face-to-face attendance. There were also unintended cost-effectiveness and efficiency benefits, with potential longer-term learning implications for the wider sleep community and other diagnostic services.

Twenty-year follow-up of children with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in children is associated with acute metabolic, cardiovascular, and neurocognitive abnormalities. The long-term outcomes of childhood OSA into adulthood have not been established. We performed a 20-year follow-up of patients with polysomnography-documented OSA in childhood compared to a healthy control group to evaluate the long-term anthropometric, sleep, cognitive, and cardiovascular outcomes. METHODS: Children diagnosed with severe OSA between ages 1 and 17 years (mean, 4.87 ± 2.77) were prospectively contacted by telephone as young adults after approximately 20 years. Data collected included reported anthropometric information, educational level, health history, and Berlin questionnaire scores. RESULTS: Young adults with confirmed severe OSA in childhood had significantly higher adulthood body mass index (P = .038), fewer academic degrees (P < .001), and more snoring (P = .045) compared to control patients. The apnea-hypopnea index during childhood trended toward predicting cardiovascular outcomes and the results of the Berlin questionnaire in adulthood. CONCLUSIONS: Adults with a history of severe childhood OSA have a high risk of snoring, elevated body mass index, and lower academic achievement in adulthood. Thus, children with severe OSA may be at increased risk of chronic diseases later in life. The intervening coronavirus disease 2019 (COVID-19) pandemic has introduced considerable additional neurobehavioral morbidity complicating the identification of the full long-term consequences of childhood OSA. CITATION: Nosetti L, Zaffanello M, Katz ES, et al. Twenty-year follow-up of children with obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1573-1581.

Obstructive sleep apnea is an independent risk factor for severe COVID-19: a population-based study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been proposed as a risk factor for severe COVID-19. Confounding is an important consideration as OSA is associated with several known risk factors for severe COVID-19. Our aim was to assess the association of OSA with hospitalization due to COVID-19 using a population-based cohort with detailed information on OSA and comorbidities. METHODS: Included were all community-dwelling Icelandic citizens 18 years of age and older diagnosed with SARS-CoV-2 infection in 2020. Data on demographics, comorbidities, and outcomes of COVID-19 was obtained from centralized national registries. Diagnosis of OSA was retrieved from the centralized Sleep Department Registry at Landspitali - The National University Hospital. Severe COVID-19 was defined as the composite outcome of hospitalization and death. The associations between OSA and the outcome were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), calculated using logistic regression models and inverse probability weighting. RESULTS: A total of 4,756 individuals diagnosed with SARS-CoV-2 infection in Iceland were included in the study (1.3% of the Icelandic population), of whom 185 had a diagnosis of OSA. In total, 238 were hospitalized or died, 38 of whom had OSA. Adjusted for age, sex, and BMI, OSA was associated with poor outcome (OR 2.2, 95% CI 1.4-3.5). This association was slightly attenuated (OR 2.0, 95% CI 2.0, 1.2-3.2) when adjusted for demographic characteristics and various comorbidities. CONCLUSIONS: OSA was associated with twofold increase in risk of severe COVID-19, and the association was not explained by obesity or other comorbidities.

Association between the degree of obstructive sleep apnea and the severity of COVID-19: An explorative retrospective cross-sectional study.

Obstructive sleep apnea (OSA) on its own, as well as its risk factors, have been found to be associated with the outcome of Coronavirus disease 2019 (COVID-19). However, the association between the degree of OSA and COVID-19 severity is unclear. Therefore, the aim of the study was to evaluate whether or not parameters to clinically evaluate OSA severity and the type of OSA treatment are associated with COVID-19 severity. Patient data from OSA patients diagnosed with COVID-19 were reviewed from outpatients from the Isala Hospital and patients admitted to the Isala Hospital, starting from March until December 2020. Baseline patient data, sleep study parameters, OSA treatment information and hospital admission data were collected. Apnea hypopnea index (AHI), low oxyhemoglobin desaturation (LSAT), oxygen desaturation index (ODI), respiratory disturbance index (RDI), and the type of OSA treatment were regarded as the independent variables. COVID-19 severity-based on hospital or intensive care unit (ICU) admission, the number of days of hospitalization, and number of intubation and mechanical ventilation days-were regarded as the outcome variables. Multinomial regression analysis, binary logistic regression analysis, and zero-inflated negative binomial regression analysis were used to assess the association between the parameters to clinically evaluate OSA severity and COVID-19 severity. A total of 137 patients were included. Only LSAT was found to be significantly associated with the COVID-19 severity (p<0.05) when COVID-19 severity was dichotomized as non-hospitalized or hospitalized and ICU admission or death. Therefore, our findings showed that LSAT seems to be a significant risk factor for COVID-19 severity. However, the degree of OSA-based on AHI, ODI, and RDI-and OSA treatment were not found to be risk factors for COVID-19 severity when looking at hospital or ICU admission, the number of days of hospitalization, and number of intubation and mechanical ventilation days.

Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019: A Multicenter, Prospective, Observational Clinical Trial.

Rationale: Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. Objectives: To determine the effect of OSA on clinical outcomes in patients with COVID-19. Methods: The current prospective observational study was conducted in three hospitals in Istanbul, Turkey from March 10 to June 22, 2020. The participants were categorized as high-risk or low-risk OSA according to the Berlin questionnaire that was administered in the out-patient clinic, in hospital, or shortly after discharge from hospital blinded to the clinical outcomes. A modified high-risk (mHR)-OSA score based on the snoring patterns (intensity and/or frequency), breathing pauses, and morning/daytime sleepiness, without taking obesity and hypertension into account, were used in the regression models. Results: The primary outcome was the clinical improvement defined as a decline of two categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death) on Days 7, 14, 21, and 28, respectively. Secondary outcomes included clinical worsening (an increase of 1 category), need for hospitalization, supplemental oxygen, and intensive care. In total, 320 eligible patients (median [interquartile range] age, 53.2 [41.3-63.0] yr; 45.9% female) were enrolled. In all, 121 (37.8%) were categorized as known (n = 3) or high-risk OSA (n = 118). According to the modified scoring, 70 (21.9%) had mHR-OSA. Among 242 patients requiring hospitalization, clinical improvement within 2 weeks occurred in 75.4% of the mHR-OSA group compared with 88.4% of the modified low-risk-OSA group (P = 0.014). In multivariate regression analyses, mHR-OSA (adjusted odds ratio [OR], 0.42; 95% confidence interval [CI], 0.19-0.92) and male sex (OR, 0.39; 95% CI, 0.17-0.86) predicted the delayed clinical improvement. In the entire study population (n = 320), including the nonhospitalized patients, mHR-OSA was associated with clinical worsening (adjusted hazard ratio, 1.55; 95% CI, 1.00-2.39) and with the need for supplemental oxygen (OR, 1.95; 95% CI, 1.06-3.59). Snoring patterns, especially louder snoring, significantly predicted delayed clinical improvement, worsening, need for hospitalization, supplemental oxygen, and intensive care. Conclusions: Adults with mHR-OSA in our COVID-19 cohort had poorer clinical outcomes than those with modified low-risk OSA independent of age, sex, and comorbidities. Clinical trial registered with www.clinicaltrials.gov (NCT04363333).

An organ systems-based review of outcomes associated with sleep apnea in hospitalized patients.

ABSTRACT: The current global health crisis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the medical community to investigate the effects of underlying medical conditions, including sleep-disordered breathing, on inpatient care. Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing that may complicate numerous acquired conditions, particularly in inpatient and critical care settings. Viral pneumonia is a major contributor to intensive care unit (ICU) admissions and often presents more severely in patients with underlying pulmonary disease, especially those with obesity and OSA. This review summarizes the most recent data regarding complications of both OSA and obesity and highlights their impact on clinical outcomes in hospitalized patients. Additionally, it will highlight pertinent evidence for the complications of OSA in an organ-systems approach. Finally, this review will also discuss impatient treatment approaches for OSA, particularly in relation to the SARS-CoV-2 pandemic.