Obstructive Sleep Apnea Is a Distinct Physiological Endotype in Individuals with Comorbid Insomnia and Sleep Apnea.

Rationale: With up to 40% of individuals with either insomnia or obstructive sleep apnea (OSA) demonstrating clinically significant symptoms of the other disorder, the high degree of comorbidity among the two most common sleep disorders suggests a bidirectional relationship and/or shared underpinnings. Although the presence of insomnia disorder is believed to influence the underlying pathophysiology of OSA, this influence is yet to be examined directly. Objectives: To investigate whether the four OSA endotypes (upper airway collapsibility, muscle compensation, loop gain, and the arousal threshold) are different in patients with OSA with and without comorbid insomnia disorder. Methods: Using the ventilatory flow pattern captured from routine polysomnography, the four OSA endotypes were measured in 34 patients with OSA who met the diagnostic criteria for insomnia disorder (COMISA) and 34 patients with OSA without insomnia (OSA only). Patients demonstrated mild-to-severe OSA (apnea-hypopnea index, 25.8 ± 2.0 events/h) and were individually matched according to age (50.2 ± 1.5 yr), sex (42 male: 26 female), and body mass index (29.3 ± 0.6 kg/m2). Results: Compared with patients with OSA without comorbid insomnia, patients with COMISA demonstrated significantly lower respiratory arousal thresholds (128.9 [118.1 to 137.1] vs. 147.7 [132.3 to 165.0] % eupneic ventilation ([Formula: see text]); U = 261; 95% confidence interval [CI], -38.3 to -13.9; d = 1.1; P < 0.001), less collapsible upper airways (88.2 [85.5 to 94.6] vs. 72.9 [64.7 to 79.2] %[Formula: see text]; U = 1081; 95% CI, 14.0 to 26.7; d = 2.3; P < 0.001), and more stable ventilatory control (i.e., lower loop gain: 0.51 [0.44 to 0.56] vs. 0.58 [0.49 to 0.70]; U = 402; 95% CI, -0.2 to -0.01; d = 0.05; P = 0.03). Muscle compensation was similar between groups. Moderated linear regression revealed that the arousal threshold moderated the relationship between collapsibility and OSA severity in patients with COMISA but not in patients with OSA only. Conclusions: A low arousal threshold is an overrepresented endotypic trait in individuals with COMISA and may exhibit a greater relative contribution to OSA pathogenesis in these patients. Contrastingly, the prevalence of a highly collapsible upper airway in COMISA was low, suggesting that anatomical predisposition may contribute less to OSA development in COMISA. Based on our findings, we theorize that conditioned hyperarousal perpetuating insomnia may translate to a reduced arousal threshold to respiratory events, thereby increasing the risk or severity of OSA. Therapies that target increased nocturnal hyperarousal (e.g., through cognitive behavior therapy for insomnia) may be effective in individuals with COMISA. Clinical trial registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12616000586415).

Respiratory arousal threshold among patients with isolated sleep apnea and with comorbid insomnia (COMISA).

Insomnia and obstructive sleep apnea (OSA) are common sleep disorders and frequently coexist (COMISA). Arousals from sleep may be a common link explaining the frequent comorbidity of both disorders. Respiratory arousal threshold (AT) is a physiologic measurement of the level of respiratory effort to trigger an arousal from sleep. The impact of COMISA on AT is not known. We hypothesized that a low AT is more common among COMISA than among patients with OSA without insomnia. Participants referred for OSA diagnosis underwent a type 3 sleep study and answered the insomnia severity index (ISI) questionnaire and the Epworth sleepiness scale. Participants with an ISI score ≥ 15 were defined as having insomnia. Sleep apnea was defined as an apnea hypopnea index (AHI) ≥ 15 events/h. Low AT was determined using a previously validated score based on 3 polysomnography variables (AHI, nadir SpO2 and the frequency of hypopneas). OSA-only (n = 51) and COMISA (n = 52) participants had similar age (61[52-68] vs 60[53-65] years), body-mass index (31.3[27.7-36.2] vs 32.2[29.5-38.3] kg/m2) and OSA severity (40.2[27.5-60] vs 37.55[27.9-65.2] events/h): all p = NS. OSA-only group had significantly more males than the COMISA group (58% vs 33%, p = 0.013. The proportion of participants with a low AT among OSA-only and COMISA groups was similar (29 vs 33%, p = NS). The similar proportion of low AT among COMISA and patients with OSA suggests that the respiratory arousal threshold may not be related to the increased arousability of insomnia.

Influence of the device used for obstructive sleep apnea diagnosis on body position: a comparison between polysomnography and portable monitor.

PURPOSE: Different devices have been used for the diagnosis of obstructive sleep apnea (OSA), which differ in the number of sensors used. The numerous sensors used in more complex sleep studies such as in-lab polysomnography may influence body position during sleep. We hypothesized that patients submitted to in-lab polysomnography (PSG) would spend more time in the supine position than patients submitted to an ambulatory Portable Monitor (PM) sleep study. METHODS: Body position during PSG and PM studies was compared among two distinct groups of patients matched for age, body-mass index (BMI), apnea-hypopnea index (AHI), and gender. Predictors of time spent in the supine position were determined using a multiple linear regression model. RESULTS: Of 478 participants who underwent either PSG or PM studies, mean age: 61[43-66] years; males: 43.9%; BMI: 28.4[26.1-31.1]kg/m2; AHI 14[7-27] events/hour). Participants who underwent PSG studies spent more time in the supine position (41[16-68]% than participants who underwent PM studies (34[16-51]%), P = 0.014. Participants with OSA spent more time in the supine position than participants without OSA, both among the PSG and PM groups P < 0.05). Gender, BMI, OSA severity, and sleep study type were independent predictors of time spent in the supine position. CONCLUSION: In-lab PSG may increase time spent in the supine position and overestimate OSA severity compared to a PM sleep study. OSA diagnosis is also associated with increased time spent in the supine position. The potential influence on the sleeping position should be taken into account when choosing among the different sleep study types for OSA diagnosis.

Clinical Decision-making for Continuous Positive Airway Pressure Mask Selection.

Continuous positive airway pressure is the gold standard treatment for obstructive sleep apnea. Different interfaces with distinct characteristics, advantages, and disadvantages are available, which may influence long-term adherence. Oronasal masks have been increasingly used. However, recent evidence suggest that nasal masks are more effective when continuous positive airway pressure is used to treat obstructive sleep apnea. The main objective of this review is to describe the basis for the selection of the interface for the treatment of obstructive sleep apnea with continuous positive airway pressure.

Insomnia episodes, new-onset pharmacological treatments, and other sleep disturbances during the COVID-19 pandemic: a nationwide cross-sectional study in Brazilian health care professionals.

STUDY OBJECTIVES: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on insomnia and other sleep disturbances in health care professionals. METHODS: A survey was distributed using social media and organizational emails to Brazilian active health care professionals during the COVID-19 outbreak. We explored potential associated factors including age, sex, occupation, workplace, work hours, income, previous infection with COVID-19, recent/current contact with COVID-19 patients, regional number of incident deaths, anxiety, and burnout. We evaluated new-onset/previous insomnia worsening episodes (primary outcome), new pharmacological treatments, sleep quality, duration, nightmares, and snoring (secondary outcomes). RESULTS: A total of 4,384 health professionals from all regions of the country were included in the analysis (44 ± 12 years, 76% females, 53.8% physicians). Overall, 55.7% were assisting patients with COVID-19, and 9.2% had a previous COVID-19 infection. The primary outcome occurred in 32.9% of respondents in parallel to 13% new pharmacological treatments for insomnia. The sleep quality worsened for 61.4%, while 43.5% and 22.8% reported ≥ 1-hour sleep duration reduction and worsening or new-onset nightmares, respectively. Multivariate analyses showed that age (odds ratio [OR]: 1.008; 95% confidence interval [CI] 1.001-1.015), females (OR: 1.590; 95% CI 1.335-1.900), weight change (decrease: OR: 1.772; 95% CI 1.453-2.161; increase: OR: 1.468; 95% CI 1.249-1.728), prevalent anxiety (OR: 3.414; 95% CI 2.954-3.948), new-onset burnout (OR: 1.761; 95% CI 1.489-2.083), family income reduction > 30% (OR: 1.288; 95% CI 1.069-1.553), and assisting patients with COVID-19 (OR: 1.275; 95% CI 1.081-1.506) were independently associated with new-onset or worsening of previous insomnia episodes. CONCLUSIONS: We observed a huge burden of insomnia episodes and other sleep disturbances in health care professionals during the COVID-19 pandemic. CITATION: Drager LF, Pachito DV, Moreno CRC, et al. Insomnia episodes, new-onset pharmacological treatments, and other sleep disturbances during the COVID-19 pandemic: a nationwide cross-sectional study in Brazilian health care professionals. J Clin Sleep Med. 2022;18(2):373-382.

The Importance of Mask Selection on Continuous Positive Airway Pressure Outcomes for Obstructive Sleep Apnea. An Official American Thoracic Society Workshop Report.

Continuous positive airway pressure (CPAP) remains the major treatment option for obstructive sleep apnea (OSA). The American Thoracic Society organized a workshop to discuss the importance of mask selection for OSA treatment with CPAP. In this workshop report, we summarize available evidence about the breathing route during nasal and oronasal CPAP and the importance of nasal symptoms for CPAP outcomes. We explore the mechanisms of air leaks during CPAP treatment and possible alternatives for leak control. The impact of nasal and oronasal CPAP on adherence, residual apnea-hypopnea index, unintentional leaks, and pressure requirements are also compared. Finally, recommendations for patient and partner involvement in mask selection are presented, and future directions to promote personalized mask selection are discussed.

Discriminating the severity of pharyngeal collapsibility in men using anthropometric and polysomnographic indices.

STUDY OBJECTIVES: Although obstructive sleep apnea results from the combination of different pathophysiologic mechanisms, the degree of anatomical compromise remains the main responsible factor. The passive pharyngeal critical closing pressure (Pcrit) is a technique used to assess the collapsibility of the upper airway and is often used as a surrogate measure of this anatomical compromise. Patients with a low Pcrit (ie, less collapsible airway) are potential candidates for non-continuous positive airway pressure therapies. However, Pcrit determination is a technically complex method not available in clinical practice. We hypothesized that the discrimination between low and high Pcrit can be estimated from simple anthropometric and polysomnographic indices. METHODS: Men with and without obstructive sleep apnea underwent Pcrit determination and full polysomnography. Receiver operating characteristics analysis was performed to select the best cutoff of each variable to predict a high Pcrit (Pcrit ≥ 2.5 cmH2O). Multiple logistic regression analysis was performed to create a clinical score to predict a high Pcrit. RESULTS: We studied 81 men, 48 ± 13 years of age, with an apnea-hypopnea index of 32 [14-60], range 1-96 events/h), and Pcrit of -0.7 ± 3.1 (range, -9.1 to +7.2 cmH2O). A high and low Pcrit could be accurately identified by polysomnographic and anthropometric indices. A score to discriminate Pcrit showed good performance (area under the curve = 0.96; 95% confidence interval, 0.91-1.00) and included waist circumference, non-rapid eye movement obstructive apnea index/apnea-hypopnea index, mean obstructive apnea duration, and rapid eye movement apnea-hypopnea index. CONCLUSIONS: A low Pcrit (less collapsible) can be estimated from a simple clinical score. This approach may identify candidates more likely to respond to non-continuous positive airway pressure therapies for obstructive sleep apnea.

Structure and severity of pharyngeal obstruction determine oral appliance efficacy in sleep apnoea.

KEY POINTS: •Some patients with obstructive sleep apnoea (OSA) respond well to oral appliance therapy, whereas others do not for reasons that are unclear. •In the present study, we used gold-standard measurements to demonstrate that patients with a posteriorly-located tongue (natural sleep endoscopy) exhibit a preferential improvement in collapsibility (lowered critical closing pressure) with oral appliances. •We also show that patients with both posteriorly-located tongue and less severe collapsibility (predicted responder phenotype) exhibit greater improvements in severity of obstructive sleep apnoea (i.e. reduction in event frequency by 83%, in contrast to 48% in predicted non-responders). •The present study suggests that the structure and severity of pharyngeal obstruction determine the phenotype of sleep apnoea patients who benefit maximally from oral appliance efficacy. ABSTRACT: A major limitation to the administration of oral appliance therapy for obstructive sleep apnoea (OSA) is that therapeutic responses remain unpredictable. In the present study, we tested the hypotheses that oral appliance therapy (i) reduces pharyngeal collapsibility preferentially in patients with posteriorly-located tongue and (ii) is most efficacious (reduction in apnoea-hypopnea index; AHI) in patients with a posteriorly-located tongue and less-severe baseline pharyngeal collapsibility. Twenty-five OSA patients underwent upper airway endoscopy during natural sleep to assess tongue position (type I: vallecula entirely visible; type II: vallecula obscured; type III: vallecula and glottis obscured), as well as obstruction as a result of other pharyngeal structures (e.g. epiglottis). Additional sleep studies with and without oral appliance were performed to measure collapsibility (critical closing pressure; Pcrit) and assess treatment efficacy. Overall, oral appliance therapy reduced Pcrit by 3.9 ± 2.4 cmH2 O (mean ± SD) and AHI by 69 ± 19%. Therapy lowered Pcrit by an additional 2.7 ± 0.9 cmH2 O in patients with posteriorly-located tongue (types II and III) compared to those without (type I) (P < 0.008). Posteriorly-located tongue (p = 0.03) and lower collapsibility (p = 0.04) at baseline were significant determinants of (greater-than-average) treatment efficacy. Predicted responders (type II and III and Pcrit < 1 cmH2 O) exhibited a greater reduction in the AHI (83 ± 9 vs. 48 ± 8% baseline, P < 0.001) and a lower treatment AHI (9 ± 6 vs. 32 ± 15 events h-1 , P < 0.001) than predicted non-responders. The site and severity of pharyngeal collapse combine to determine oral appliance efficacy. Specifically, patients with a posteriorly-located tongue plus less-severe collapsibility are the strongest candidates for oral appliance therapy.

Predictors of oronasal breathing among obstructive sleep apnea patients and controls.

Oronasal breathing may adversely impact obstructive sleep apnea (OSA) patients either by increasing upper airway collapsibility or by influencing continuous positive airway pressure (CPAP) treatment outcomes. Predicting a preferential breathing route would be helpful to guide CPAP interface prescription. We hypothesized that anthropometric measurements but not self-reported oronasal breathing are predictors of objectively measured oronasal breathing. Seventeen OSA patients and nine healthy subjects underwent overnight polysomnography with an oronasal mask with two sealed compartments attached to independent pneumotacographs. Subjects answered questionnaires about nasal symptoms and perceived breathing route. Oronasal breathing was more common (P = <0.001) among OSA patients than controls while awake (62 ± 44 vs. 5 ± 6%) and during sleep (59 ± 39 vs. 25 ± 21%, respectively). Oronasal breathing was associated with OSA severity (P = 0.009), age (P = 0.005), body mass index (P = 0.044), and neck circumference (P = 0.004). There was no agreement between objective measurement and self-reported breathing route among OSA patients while awake (κ = -0.12) and asleep (κ = -0.02). The breathing route remained unchanged after 92% of obstructive apneas. These results suggest that oronasal breathing is more common among OSA patients than controls during both wakefulness and sleep and is associated with OSA severity and anthropometric measures. Self-reporting is not a reliable predictor of oronasal breathing and should not be considered an indication for oronasal CPAP.NEW & NOTEWORTHY Continuous positive airway pressure (CPAP) interface choice for obstructive sleep apnea (OSA) patients is often guided by nasal symptoms and self-reported breathing route. We showed that oronasal breathing can be predicted by anthropometric measurements and OSA severity but not by self-reported oronasal breathing. Self-reported breathing and nasal symptoms should not be considered for CPAP interface choice.

Transmission of Oral Pressure Compromises Oronasal CPAP Efficacy in the Treatment of OSA.

BACKGROUND: An oronasal mask is frequently used to treat OSA. In contrast to nasal CPAP, the effectiveness of oronasal CPAP varies by unknown mechanisms. We hypothesized that oral breathing and pressure transmission through the mouth compromises oronasal CPAP efficacy. METHODS: Thirteen patients with OSA, well adapted to oronasal CPAP, were monitored by full polysomnography, pharyngeal pressure catheter, and nasoendoscope. Patients slept with low doses of midazolam, using an oronasal mask with sealed nasal and oral compartments. CPAP was titrated during administration by the oronasal and nasal routes, and was then reduced to induce stable flow limitation and abruptly switched to the alternate route. In addition, tape sealing the mouth was used to block pressure transmission to the oral cavity. RESULTS: Best titrated CPAP was significantly higher by the oronasal route rather than the nasal route (P = .005), and patients with > 25% oral breathing (n = 5) failed to achieve stable breathing during oronasal CPAP. During stable flow limitation, inspiratory peak flow was lower, driving pressure was higher, upper airway inspiratory resistance was higher, and retropalatal and retroglossal area were smaller by the oronasal rather than nasal route (P < .05 for all comparisons). Differences were observed even among patients with no oral flow and were abolished when tape sealing the mouth was used (n = 6). CONCLUSIONS: Oral breathing and transmission of positive pressure through the mouth compromise oronasal CPAP.

Retropalatal and retroglossal airway compliance in patients with obstructive sleep apnea.

OBJECTIVES: We hypothesized that preferential retropalatal as compared to retroglossal collapse in patients with obstructive sleep apnea was due to a narrower retropalatal area and a higher retropalatal compliance. Patients with a greater retropalatal compliance would exhibit a recognizable increase in negative effort dependence (NED). METHODS: Fourteen patients underwent upper airway endoscopy with simultaneous recordings of airflow and pharyngeal pressure during natural sleep. Airway areas were obtained by manually outlining the lumen. Compliance was calculated by the change of airway area from end-expiration to a pressure swing of -5 cm H2O. NED was quantified for each breath as [peak inspiratory flow minus flow at -5 cm H2O]/[peak flow] × 100. RESULTS: Compared to the retroglossal airway, the retropalatal airway was smaller at end-expiration (p < 0.001), and had greater absolute and relative compliances (p < 0.001). NED was positively associated with retropalatal relative area change (r = 0.47; p < 0.001). CONCLUSIONS: Retropalatal airway is narrower and more collapsible than retroglossal airway. Retropalatal compliance is reflected in the clinically-available NED value.

Palatal prolapse as a signature of expiratory flow limitation and inspiratory palatal collapse in patients with obstructive sleep apnoea.

In some individuals with obstructive sleep apnoea (OSA), the palate prolapses into the velopharynx during expiration, limiting airflow through the nose or shunting it out of the mouth. We hypothesised that this phenomenon causes expiratory flow limitation (EFL) and is associated with inspiratory "isolated" palatal collapse. We also wanted to provide a robust noninvasive means to identify this mechanism of obstruction.Using natural sleep endoscopy, 1211 breaths from 22 OSA patients were scored as having or not having palatal prolapse. The patient-level site of collapse (tongue-related, isolated palate, pharyngeal lateral walls and epiglottis) was also characterised. EFL was quantified using expiratory resistance at maximal epiglottic pressure. A noninvasive EFL index (EFLI) was developed to detect the presence of palatal prolapse and EFL using the flow signal alone. In addition, the validity of using nasal pressure was assessed.A cut-off value of EFLI >0.8 detected the presence of palatal prolapse and EFL with an accuracy of >95% and 82%, respectively. The proportion of breaths with palatal prolapse predicted isolated inspiratory palatal collapse with 90% accuracy.This study demonstrates that expiratory palatal prolapse can be quantified noninvasively, is associated with EFL and predicts the presence of inspiratory isolated palatal collapse.

Nasal vs Oronasal CPAP for OSA Treatment: A Meta-Analysis.

BACKGROUND: Nasal CPAP is the "gold standard" treatment for OSA. However, oronasal masks are frequently used in clinical practice. The aim of this study was to perform a meta-analysis of all randomized and nonrandomized trials that compared nasal vs oronasal masks on CPAP level, residual apnea-hypopnea index (AHI), and CPAP adherence to treat OSA. METHODS: The Cochrane Central Register of Controlled Trials, Medline, and Web of Science were searched for relevant studies in any language with the following terms: "sleep apnea" and "CPAP" or "sleep apnea" and "oronasal mask" or "OSA" and "oronasal CPAP" or "oronasal mask" and "adherence." Studies on CPAP treatment for OSA were included, based on the following criteria: (1) original article; (2) randomized or nonrandomized trials; and (3) comparison between nasal and oronasal CPAP including pressure level, and/or residual AHI, and/or CPAP adherence. RESULTS: We identified five randomized and eight nonrandomized trials (4,563 patients) that reported CPAP level and/or residual AHI and/or CPAP adherence. Overall, the random-effects meta-analysis revealed that as compared with nasal, oronasal masks were associated with a significantly higher CPAP level (Hedges' g, -0.59; 95% CI, -0.82 to -0.37; P < .001) (on average, +1.5 cm H2O), higher residual AHI (Hedges' g, -0.34; 95% CI, -0.52 to -0.17; P < .001) (+2.8 events/h), and a poorer adherence (Hedges' g, 0.50; 95% CI, 0.21-0.79; P = .001) (-48 min/night). CONCLUSIONS: Oronasal masks are associated with a higher CPAP level, higher residual AHI, and poorer adherence than nasal masks. TRIAL REGISTRY: PROSPERO database; No.: CRD42017064584; URL: https://www.crd.york.ac.uk/prospero/.