Asthma and obstructive sleep apnea: More than an association!

The purpose of this study is to conduct a systematic review and meta-analysis evaluating the effects of respiratory muscle therapy (ie, oropharyngeal exercises, speech therapy, breathing exercises, wind musical instruments) compared with control therapy or no treatment in improving apnea-hypopnea index ([AHI] primary outcome), sleepiness, and other polysomnographic outcomes for patients diagnosed with obstructive sleep apnea (OSA). Only randomized controlled trials with a placebo therapy or no treatment searched using PubMed, EMBASE, Cochrane, and Web of Science up to November 2018 were included, and assessment of risk of bias was completed using the Cochrane Handbook. Nine studies with 394 adults and children diagnosed with mild to severe OSA were included, all assessed at high risk of bias. Eight of the 9 studies measured AHI and showed a weighted average overall AHI improvement of 39.5% versus baselines after respiratory muscle therapy. Based on our meta-analyses in adult studies, respiratory muscle therapy yielded an improvement in AHI of -7.6 events/h (95% confidence interval [CI] = -11.7 to -3.5; P ≤ .001), apnea index of -4.2 events/h (95% CI = -7.7 to -0.8; P ≤ .016), Epworth Sleepiness Scale of -2.5 of 24 (95% CI= -5.1 to -0.1; P ≤ .066), Pittsburgh Sleep Quality Index of -1.3 of 21 (95% CI= -2.4 to -0.2; P ≤ .026), snoring frequency (P = .044) in intervention groups compared with controls. This systematic review highlights respiratory muscle therapy as an adjunct management for OSA but further studies are needed due to limitations including the nature and small number of studies, heterogeneity of the interventions, and high risk of bias with low quality of evidence.

This study evaluates the relationship between obstructive sleep apnea (OSA) and asthma. Literature search was carried out in several electronic databases and random effects meta-analyses were performed to obtain pooled estimates of the prevalence of OSA, OSA risk and sleep disordered breathing (SDB) in asthma patients and pooled odds ratios of the prevalence between asthma and non-asthma patients. In adult asthma patients, the prevalence [95% confidence interval] of OSA, OSA risk, and SDB was 49.50 [36.39, 62.60] %, 27.50 [19.31, 35.69] %, and 19.65 [14.84, 24.46] % respectively. The odds of having OSA, OS risk and SDB by the asthma patients were 2.64 [1.76, 3.52], 3.73 [2.90, 4.57] and 1.73 [1.11, 2.36] times higher (p < 0.00001 for all) in asthma than in non-asthma patients, respectively. Adult asthma patients with OSA had significantly higher BMI in comparison with asthma patients without OSA. This study reveals that the prevalence of OSA in asthma patients is considerably higher; even higher than OSA risk and SDB. Sleep studies should be performed in asthma patients with symptoms suggestive of OSA/OSA risk/SDB.

Obesity, obstructive sleep apnoea, and diabetes mellitus: anaesthetic implications

From Resistant Airway to Resistant Hypertension.

Background: Obstructive sleep apnea (OSA) is described as a disturbance of sleep presentingrepetitive (either total or partial) closure of the upper airway. Studies have demonstrated that OSA inthe middle-aged induces excessive daytime sleepiness; mood problems and poor quality of life. OSAis characterized by repetitive narrowing or obstruction of the upper airway during sleep, resultingin apnea or hypopnea. Patients with OSA have shown poor sleep quality. Purpose: To evaluate thepossible association between OSA and patients’ sleep quality. Literature review: OSA is a commonsleep disturbance classified by intermittent partial or total upper airway obstruction during sleep, causing intermittent hypoxemia, recurrent arousals, sleep fragmentation, and poor sleep quality. OSA is related to the quality of life, depression, and anxiety, but there were associations with acute stress which were reported by a few studies. Most of studies on OSA had collected data from moderate to severe sleep apnea in elderly patients and clinical settings. Continuous positive airway pressure (CPAP) therapy, which provides a mechanical pneumatic stent for the upper airway, is an effective treatment for OSA. As a rule, it is given via a nasal mask, and therefore patients should ideally keep their mouth closed during sleep. Conclusion: The literature review showed that there was a significant association between obstructive sleep apnea risk and sleep quality. The risk of increasing OSA among young people is associated with acute stress, and the relationship is mediated by sleep quality.Keywords: sleep apnea, continuous positive airway pressure, upper airway obstruction

Repetitive airway occlusion during sleep in patients with obstructive sleep apnoea (OSA) results in the generation of negative intrathoracic pressures and ends in arousal, both of which may predispose to reflux during sleep (nocturnal reflux). We aimed to determine and compare the prevalence of nocturnal reflux symptoms and their sleep-associated risk factors in untreated OSA patients, OSA patients using continuous positive airway pressure (CPAP) therapy, and the general population. Gastro-oesophageal reflux and sleep questionnaires were completed by 1116 patients with polysomnography diagnosed OSA and by 1999 participants of the 2007 Busselton population health survey. Of the OSA patients, 137 completed the reflux questionnaire before and after treatment. Risk of OSA in the general population was assessed using the Berlin score. The prevalence of frequent (>weekly) nocturnal reflux symptoms was increased (P<0.001) in OSA patients (10.2%) versus the general population (5.5%), in individuals from the general population at high (8.7%) versus low risk (4.3%) of OSA and in patients with severe (13.9%) versus mild OSA (5.1%). Frequent nocturnal reflux symptoms were associated with high risk (general population) (OR 1.9, P<0.01) and severity of OSA (OSA population) OR 3.0, severe versus mild OSA, P<0.001) after correcting for age, gender and body mass index. Treatment with CPAP decreased the prevalence of reflux symptoms significantly. In conclusion, the prevalence of nocturnal reflux symptoms is increased in those with or suspected of having OSA. This association is independent of other risk factors including age, gender and body mass index, suggesting a causal relationship between OSA and nocturnal reflux.

Commentary on Zheng Y, Yee BJ, Wong K, Grunstein R, Piper A. A pilot randomized trial comparing CPAP versus bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease. J Clin Sleep Med. 20XX;XX(XX):XXX-XXX. doi:10.5664/jcsm.9506.

Background: Recent studies have found a high prevalence of obstructive sleep apnea (OSA) among responders of the World Trade Center (WTC) disaster. Exposure to particulate matter (PM) causing upper airway inflammation is considered a significant contributing factor in the pathogenesis of OSA. The Berlin Questionnaire (BQ) is a widely used questionnaire to screen for OSA with published sensitivity up to 86% and specificity of 87% for OSA risk. We aim to investigate whether a relationship exists between OSA risk using the BQ and exposure to PM using the Wisnevsky exposure score. Methodology: We evaluated 808 participants in the WTC-CHEST Program from January 2011 to September 2013. High risk for OSA was identified as 2 or more positive categories in the BQ. The subjects were categorized into four exposure groups: very high, high, intermediate and low (Wisnevsky exposure score). Chi-square and Binary Logistic Regression analyses were performed to determine if there was a significant relationship between OSA risk and PM exposure. Results: High risk for OSA is associated with PM exposure in the study population (p=0.002). Using a binary logistic regression adjusting for gender and age, high risk for OSA was still found to be significantly associated with PM exposure (p = 0.022). Conclusion: Prior investigations have demonstrated a link between PM exposure and pulmonary disease, digestive disorders and PTSD. These results provide strong evidence for the association of PM exposure and OSA. In fact, PM exposure in this cohort of WTC first responders is one of the most significant contributors to increased OSA risk. Assessment of both OSA risk and exposure to PM are important as both have been linked to an increase in cardiovascular risk.

BackgroundThis retrospective cohort study aimed to determine if there are differences in cardiovascular co-morbidities, blood pressure (BP) and continuous positive airway pressure (CPAP) use between patients with positional-dependent and nonpositional-dependent obstructive sleep apnea (OSA).MethodsPatients who were referred for overnight polysomnography for suspected OSA between 2007 and 2011 were screened. A total of 371 patients with OSA were included for analysis and divided into six groups according to positional-dependency and severity of OSA: positional mild (n = 52), positional moderate (n = 29), positional severe (n = 24), non-positional mild (n = 18), non-positional moderate (n = 70) and non-positional severe group (n = 178). The six groups were compared for anthropometric and polysomnographic variables, presence of cardiovascular co-morbidities, morning and evening BP and the changes between evening and morning BP, and CPAP device usage patterns.ResultsDemographic and anthropometric variables showed non-positional severe OSA had poor sleep quality and higher morning blood pressures. Positional mild OSA had the lowest cardiovascular co-morbidities. Overall CPAP acceptance was 45.6%. Mild OSA patients had the lowest CPAP acceptance rate (10%), followed by moderate group (37.37%) and severe group (61.88%, P < 0.001). However, the significant difference in CPAP acceptance across OSA severity disappeared when the data was stratified by positional dependency.ConclusionsThis study found that positional mild OSA had less cardiovascular co-morbidities compared with subjects with positional severe OSA. Independent of posture, CPAP acceptance in patients with mild OSA was low, but CPAP compliance was similar in CPAP acceptors regardless of posture dependency of OSA. Since there are increasing evidences of greater cardiovascular risk for untreated mild OSA, improving CPAP acceptance among mild OSA patients may be clinically important regardless of posture dependency.

Are we underestimating the lifelong benefits of therapy for obstructive sleep apnea? Alec M Berman, Saurabh S Thosar, Steven A SheaOregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, USAObstructive sleep apnea (OSA) is a complex disorder involving the cardiovascular (CV), pulmonary, and metabolic systems. Characterized by marked daytime fatigue and reduced quality of life, OSA is independently associated with increased risk of hypertension,1 cardiovascular disease (CVD),2 including myocardial infarction (MI)3 and ischemic stroke,4 metabolic syndrome,5 and all-cause mortality.6 Currently, the most common treatment for OSA is continuous positive airway pressure (CPAP) during sleep, though its efficacy in reducing daytime fatigue and CVD risk factors depends largely on compliance to therapy, which is poor in the general population.7 Lamberts et al8 performed a large epidemiological study of OSA, using the Danish National Patient Registry (NPR; ∼4.5 million; including 25,389 people diagnosed with OSA), which confirmed associations between OSA and risk of ischemic stroke and MI. Yet, that study failed to show that CPAP reduces the incidence of these adverse CV events.8 On the other hand, a more recent study, which examined the same Danish NPR across a very similar time period, revealed that in people with OSA, CPAP reduces all-cause mortality.9 This editorial evaluates these seemingly conflicting results, whereby CPAP appears to reduce mortality but not two of the largest contributors to mortality: stroke and MI.

The Pharyngeal Airway: Is Bigger Really Better?

ABSTRACTIt has been shown that obstructive sleep apnea (OSA) is related to hypertension and cardiovascular disease; however, the prevalence of OSA in general population and the impact of it on blood pressure especially in Japan has not been well determined. We have conducted a screening test for OSA from 2003 to 2011. In addition, a cross-sectional analysis was performed in 2012 to determine the association of OSA and cardiovascular risk factors in Japanese men (18–69 years of age; mean age, 44.4 ± 0.2). The study group consisted of 2208 male employees, and OSA was evaluated by using the 4% oxygen desaturation index and apnea-hypopnea index (AHI). The prevalence of mild-to-moderate (5≤AHI<30) and severe (AHI≥30) OSA in the studied subjects were 7.1%, and 6.1%, respectively. Among the 135 severe OSA subjects, 105 (77.8%) had been treated with continuous positive airway pressure. Both systolic and diastolic blood pressures (DBP) were significantly increased in the subjects with severe OSA compared with those without OSA. These associations in DBP remained observed after adjustment for age, body mass index (BMI), estimated glomerular filtration rate, HbA1c, current alcohol intake, current smoking habits, and OSA treatment. DBP in severe OSA subjects were significantly increased in 1807 subjects who were not treated for hypertension or OSA. However, the levels of blood pressures were not decreased by OSA treatment. These results suggest that the prevalence of OSA is relatively high in middle-aged Japanese men and that blood pressures were elevated in the subjects with severe OSA.

Is Laryngeal Descent Associated With Increased Risk for Obstructive Sleep Apnea?

Sleep quality in patients studied with laboratory-based polysomnography may differ from sleep quality in patients studied at home but remains clinically relevant and important to describe. We assessed objective sleep quality and explored factors associated with poor sleep in patients undergoing laboratory-based polysomnography. We reviewed diagnostic polysomnography studies from a 10-year period at a single sleep center. Total sleep time (TST) and sleep efficiency (SE) were assessed as markers of sleep quality. Poor sleep was defined as TST ≤ 4 hours or SE ≤ 50%. Multivariable analysis was performed to determine associations between objective sleep quality as an outcome and multiple candidate predictors including age, sex, race, body mass index, comorbidities, severity of obstructive sleep apnea, and central nervous system medications. Among 4957 patients (age 53 ± 15 years), average TST and median SE were 5.8 hours and 79%, respectively. There were 556 (11%) and 406 (8%) patients who had poor sleep based on TST and SE, respectively. In multivariable analysis, those who were older (per 10 years: 1.48 [1.34, 1.63]), male (1.38 [1.14,1.68]), and had severe obstructive sleep apnea (1.76 [1.28, 2.43]) were more likely to have short sleep. Antidepressant use was associated with lower odds of short sleep (0.77 [0.59,1.00]). Older age (per 10 years: 1.48 [1.34, 1.62]), male sex (1.34 [1.07,1.68]), and severe obstructive sleep apnea (2.16 [1.47, 3.21]) were associated with higher odds of poor SE. We describe TST and SE from a single sleep center cohort. Multiple demographic characteristics were associated with poor objective sleep in patients during laboratory-based polysomnography. Harrison EI, Roth RH, Lobo JM, et al. Sleep time and efficiency in patients undergoing laboratory-based polysomnography. J Clin Sleep Med. 2021;17(8):1591-1598.

SEVERAL CONCEPTS HAVE RECENTLY EMERGED REGARDING OUR THINKING ABOUT THE PATHOGENESIS OF OBSTRUCTIVE SLEEP APNEA (OSA). First, considerable evidence now suggests that several variables may interactively contribute to the development of OSA.1 Although some patients have primarily an anatomical problem, with little contribution from other factors, others may have dysfunction of upper airway dilator muscles or instability in ventilatory control that exacerbates otherwise minor anatomical deficits. Some patients clearly have combinations of abnormalities that yield repetitive obstructive apnea. As such, measuring a single variable in isolation, as has been done historically, is unlikely to be illuminating. Second, the concept of tailored therapy suggests that measures to influence underlying pathophysiology are likely to be successful in some, but not all, patients with OSA. For example, the subgroup of patients with OSA that responds well to uvulopalatopharyngoplasty is likely to have primarily velopharyngeal anatomical compromise. Additionally, the subgroup of patients that responds well to oxygen is likely to have unstable ventilatory control as a major contributing factor.2 Similarly, a theoretic agent to augment hypoglossal motor output3, 4 may benefit some patients with OSA (with dysfunctional upper airway muscles) but may be deleterious in others (with unstable ventilatory control in whom airway dilation may promote important hypocapnia5). Given the need for therapeutic advances in OSA, an individualized approach that targets underlying mechanism (or combination of mechanisms) would seem worthwhile. Third, Younes6 has recently emphasized that even patients with severe OSA have some periods of stable breathing during sleep. Jordan et al7 have observed that these stable breathing periods are associated with marked genioglossus muscle activity. These data suggest that the upper airway dilator muscles are necessary and sufficient to stabilize breathing spontaneously in patients with OSA. Although these dilator muscles are known to have robust recruitment with respiratory stimuli during wakefulness, more marked or prolonged stimulation (or combinations of stimuli) are required for muscle activation during sleep.8 As a result, the arousal threshold becomes a critical factor, since individuals who wake up easily (low arousal threshold) will have unstable airway mechanics due to an inability to accumulate adequate respiratory stimuli to activate dilator muscles.9–11 Conversely a very high arousal threshold (hard to wake up) would be predicted to be deleterious in some patients, since profound hypoxemia or hypercapnia may occur prior to arousal (see Figure 1). Thus, strategies to manipulate arousal threshold (or any other variable) must be carefully individualized since a “one-size-fits-all” approach is unlikely to be fruitful in OSA. Figure 1 Schematic figure to illustrate the potential variability in response to a manipulation. The black lines illustrate the changes in ventilation which occur with increasing ventilatory drive. On the left is an individual with a relatively low recruitment ... In this issue of SLEEP, Loewen and colleagues12 have characterized critical pathophysiological variables in patients with OSA before and after therapy. The authors have helped to move us beyond the simple AHI by demonstrating the feasibility of a comprehensive assessment of multiple pathophysiological variables in one overnight study to determine important factors critical to the presence or absence of apnea. Ultimately, simplification or automation of these measurements would be useful to define the mechanisms underlying apnea in a given individual. Alternatively, demographic variables, polysomnography characteristics, or biomarkers may help to predict mechanistic variables with sufficient accuracy to determine why an individual does or does not have disease. The authors define an important conceptual model of the interactions among various respiratory parameters in a particular individual. However, it is unclear how “abnormal” a particular variable must be, or even whether an increase or decrease in a particular factor might be favorable. For example, an increase in the arousal threshold may be good or bad (depending on the upper airway recruitment threshold), or a significant reduction in the dynamic ventilator response (chemoresponsiveness) might be undesirable if chemical drive fails to recruit upper airway dilators. To answer these sorts of questions, quantitative models are needed to define more precisely how the different pathophysiologic factors interact in a particular individual.13 Such an approach would seem crucial given the lack of utility of a single variable (eg, arousal threshold) in isolation. These experiments12 provide insight into the question regarding whether observed abnormalities are intrinsic or acquired in patients with OSA. Although a change in a variable following continuous positive airway pressure (CPAP) is consistent with OSA causing the abnormality, a stable value of a variable following CPAP might suggest that the observed value is either intrinsic to these patients (eg, genetically determined or not directly OSA related) or perhaps an irreversible consequence of disease. A repeat assessment of the AHI in the Loewen study12 may have provided insight into the pathophysiologic importance of the observed changes with CPAP. For example, if a marked fall in dynamic ventilatory response were observed (as documented by the authors) despite a stable AHI, one could argue that this measure of dynamic ventilatory response is not a major factor in predicting AHI, at least in that individual. Thus, the authors have raised important questions that are worth pursuing. Of note, the authors12 demonstrate that the arousal threshold to respiratory stimuli decreases (patients wake up more easily) following CPAP therapy, suggesting that the observed elevation in arousal threshold in OSA10 maybe a disease consequence (rather than a cause), ostensibly due to sleep fragmentation. This finding is interesting, since a high arousal threshold should protect against apnea in those with robust upper airway muscle responsiveness. In theory, the arousal threshold may change over time adaptively to stabilize breathing. Clearly, excessive elevations in arousal threshold may become maladaptive if profound hypoxemia occurs prior to arousal. Another new finding12 is the observation that dynamic ventilatory response (a surrogate for ventilatory control instability) is markedly suppressed following CPAP therapy as compared with before CPAP. Because chemosensitivity may be blunted by sleep deprivation,14 the finding of increased dynamic ventilatory response in untreated OSA is somewhat surprising. The mechanism underlying this observation is unclear but may represent a form of long-term facilitation—that is, alterations in blood gases have sustained effects on control of breathing,15 a phenomenon that has been questioned in humans. Thus, further study is required. We applaud the authors and would advocate for further work using a comprehensive analysis of multiple pathophysiological variables integrated into a patient-specific quantitative model to identify mechanisms underlying apnea. Such individualized approaches should pave the way to targeted OSA therapy based on underlying mechanism.