Multi-center safety and efficacy study of a negative-pressure intraoral device in obstructive sleep apnea.

BACKGROUND: Intraoral devices, with or without negative oral pressure, can stabilize the oropharynx and reduce obstructive sleep apneas. We tested the hypothesis that treatment with the iNAP® Sleep Therapy System, which applies negative oral pressure through an intra-oral appliance, would reduce the severity of obstructive sleep apnea in a multi-center, prospective, first-night-randomized-order cross-over study. METHODS/PATIENTS: 130 patients fulfilled the entry criteria (age <75, AHI 15-55, BMI <33), and 63 entered the primary endpoint cohort (Total Sleep Time ≥4 h/night on the baseline polysomnogram and an oral negative vacuum time maintained by iNAP® ≥ 4 h/night and total sleep time ≥4 h/night during the first treatment study). 54 patients completed a second treatment sleep study at least 28 days after the first sleep study. RESULTS: Among the primary endpoint cohort (n = 63, age = 53.2 ± 11.3, BMI = 27.1 ± 2.8), 33 patients (52 %; 95 % confidence interval = 40%-64 %, p < 0.001) responded to iNAP treatment according to the Sher criteria (>50 % reduction in AHI and an AHI ≤20 events/hr). The average oxy-hemoglobin saturation increased by 1-2%, and the average percent oxygen desaturation decreased (was less severe) by 1 % while using the iNAP device. The incidence of adverse events, all self-limited, was low. The reduction in the apnea-hypopnea index was durable over the 28-day study. Patients used iNAP on average 5.6 h per night during the study period. CONCLUSION: The iNAP® Sleep Therapy System achieved a durable benefit in more than half the patients with moderate to severe obstructive sleep apnea and may be considered in patients who object to or failed continuous positive airway pressure. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02698059.

Sex differences in polysomnographic findings in patients with obstructive sleep apnea.

BACKGROUND AND PURPOSE: Sex differences in the clinical findings and the polysomnographic presentation of patients with obstructive sleep apnea (OSA) are compelling current research issues. For example, patients suffering from obstructive sleep apnea are predominantly male. While women are older than men and tend to have a higher body mass index, men typically present with a more severe form of obstructive sleep apnea. Using polysomnography, we investigated a German cohort, subdivided per severity levels of obstructive sleep apnea (apnea-hypopnea index: ≥5 to < 15/h (mild), ≥15 to < 30/h (moderate), and ≥30/h (severe)) to provide a detailed analysis of breathing and sleep parameters, accounting for body position effects and severity of illness. A deeper understanding of sex differences may allow targeted diagnosis and treatment adjustment. PATIENTS AND METHODS: This retrospective study included a cohort of 1242 German patients (940 male, 302 female) who underwent overnight polysomnography at the private sleep laboratory "Intersom Köln", Center for Sleep Medicine and Sleep Research. In 1125 subjects (878 male, 247 female), obstructive sleep apnea was diagnosed. All patients were examined between January 01, 2018 and December 31, 2020, comparing anthropometric, sleep morphological, and respiratory polysomnographic findings. RESULTS: Female patients with obstructive sleep apnea were significantly older than male patients (60.9 ± 12.3 vs. 56.9 ± 12.5 years, P < .001), also among OSA subgroups per OSA severity. The body mass index was similar in male and female patients (29.6 ± 5.1 vs. 29.2 ± 7.3 kg/m2, P > .05), including the three subgroups. Men were more likely to have severe obstructive sleep apnea (46.9%) than women (35.2%). Women exhibited a higher proportion of slow-wave sleep than men (129.4 ± 52.8 vs. 104.2 ± 53.2 min; P < .001). The apnea-hypopnea index of total sleep time was significantly greater in male than female patients (32.9 ± 21.2 vs. 27.2 ± 20.2 per hour; P < .001). Female patients had a higher apnea-hypopnea index during rapid-eye-movement (REM) sleep (34.0 ± 23.8 vs. 31.8 ± 22.3 per hour; P = .171). A statistically significant difference in the apnea-hypopnea index during REM sleep between sexes was found when the obstructive sleep apnea severity was considered. Women had a lower apnea-hypopnea index in non-rapid eye-movement (NREM) sleep than men (25.7 ± 21.1 vs. 32.7 ± 22.3 per hour; P < .001). The oxygen desaturation index (29.9 ± 20.3 vs. 22.4 ± 19.4%; P < .001) and an oxygen desaturation below 90% (9.4 ± 14.0 vs. 6.8 ± 11.7%; P = .003) was greater in men than in women. In severe obstructive sleep apnea, the oxygen desaturation index was similar between the sexes (45.0 ± 17.8 vs. 41.1 ± 20.9%; P = .077). Male patients showed a higher supine apnea-hypopnea-index than female patients. (45.7 ± 26.7 vs 36.1 ± 22.7 per hour; P < .001). CONCLUSION: The present noninvasive, retrospective registry study is the first to examine sex differences in OSA in such a large German population in terms of respiratory and sleep parameters, taking into account the effects of body position and severity of the disease. We could confirm and extend observations from previous studies. Female patients were significantly older than the male patients. The apnea-hypopnea index was higher in male than in female patients. Women showed a higher apnea-hypopnea index in REM sleep and a lower one in NREM sleep. Men were desaturated more often and were more affected by supine-dependent obstructive sleep apnea than women. Contrary to the literature, there were no significant differences in body mass index (BMI) between the sexes. With increasing age and BMI, the gender differences become less significant.

[Rheumatological Diseases and Sleep: Somnological Aspects of Diagnostics and Therapy]. / Rheumatologische Erkrankungen und Schlaf ­ Schlafmedizinische Aspekte der Diagnostik und Therapie ­ Eine literaturbasierte Übersicht.

This PubMed-based review discusses primary and secondary sleep disorders associated with rheumatological diseases. It presents the pathophysiological interaction of sleep-related diseases and rheumatological disorders and summarises clinical symptoms, diagnostic investigation and therapies from a somnological perspective. EPIDEMIOLOGY: 70 % of patients suffering from rheumatological diseases report poor sleep quality, numerous awakenings at night and non-restorative sleep. More than 20 % of these patients are found to have primary sleep disorders such as obstructive sleep apnoea (OSA) and the restless legs syndrome (RLS). PATHOGENESIS: Primary and secondary sleep disorders may increase symptoms associated with rheumatological diseases, e. g. excessive daytime sleepiness, fatigue, depression, pain intensity, and disease activity. Vice versa, pain intensity and inflammatory markers worsen sleep quality. In patients with rheumatic diseases, obesity as well as disease-related skeletal characteristics may be predisposing factors for obstructive sleep apnoea. The restless legs syndrome, which frequently occurs in rheumatological diseases, lowers sleep quality due to a sensory stimulus and periodic leg movements causing sleep fragmentation. DIAGNOSTIC INVESTIGATION: Somnological diagnostic investigation consists of sleep-related questionnaires and scales. Objective tests are used to measure reaction time and vigilance. Sleep-related breathing and movement disorders can be identified with screening devices and polygrafic monitoring. A final polysomnografic sleep study is necessary to make the diagnosis and to initiate a specific treatment and follow-up examinations. TREATMENT: Sleep disorders associated with rheumatological diseases may be treated with behavioural and drug therapies. Drug therapy is commonly used in the management of insomnia and RLS. Most cases of OSAS can be treated with CPAP or UPS devices. Interdisciplinary cooperation in the fields of somnology and rheumatology may improve treatment in RA patients.

Upper-airway stimulation for obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea is associated with considerable health risks. Although continuous positive airway pressure (CPAP) can mitigate these risks, effectiveness can be reduced by inadequate adherence to treatment. We evaluated the clinical safety and effectiveness of upper-airway stimulation at 12 months for the treatment of moderate-to-severe obstructive sleep apnea. METHODS: Using a multicenter, prospective, single-group, cohort design, we surgically implanted an upper-airway stimulation device in patients with obstructive sleep apnea who had difficulty either accepting or adhering to CPAP therapy. The primary outcome measures were the apnea-hypopnea index (AHI; the number of apnea or hypopnea events per hour, with a score of ≥15 indicating moderate-to-severe apnea) and the oxygen desaturation index (ODI; the number of times per hour of sleep that the blood oxygen level drops by ≥4 percentage points from baseline). Secondary outcome measures were the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and the percentage of sleep time with the oxygen saturation less than 90%. Consecutive participants with a response were included in a randomized, controlled therapy-withdrawal trial. RESULTS: The study included 126 participants; 83% were men. The mean age was 54.5 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The median AHI score at 12 months decreased 68%, from 29.3 events per hour to 9.0 events per hour (P<0.001); the ODI score decreased 70%, from 25.4 events per hour to 7.4 events per hour (P<0.001). Secondary outcome measures showed a reduction in the effects of sleep apnea and improved quality of life. In the randomized phase, the mean AHI score did not differ significantly from the 12-month score in the nonrandomized phase among the 23 participants in the therapy-maintenance group (8.9 and 7.2 events per hour, respectively); the AHI score was significantly higher (indicating more severe apnea) among the 23 participants in the therapy-withdrawal group (25.8 vs. 7.6 events per hour, P<0.001). The ODI results followed a similar pattern. The rate of procedure-related serious adverse events was less than 2%. CONCLUSIONS: In this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea. (Funded by Inspire Medical Systems; STAR ClinicalTrials.gov number, NCT01161420.).

Implanted upper airway stimulation device for obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: Previous feasibility studies have shown that electrical stimulation of the hypoglossal nerve can improve obstructive sleep apnea (OSA). The current study examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success. STUDY DESIGN: Two consecutive open prospective studies. METHODS: UAS systems were implanted in patients with moderate to severe OSA who failed or were intolerant of continuous positive airway pressure (CPAP). The study was conducted in 2 parts. In part 1, patients were enrolled with broad selection criteria. Apnea hypopnea index (AHI) was collected using laboratory-based polysomnography at preimplant and postimplant visits. Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also collected. In part 2, patients were enrolled using selection criteria derived from the experience in part 1. RESULTS: In part 1, 20 of 22 enrolled patients (two exited the study) were examined for factors predictive of therapy response. Responders had both a body mass index ≤32 and AHI ≤50 (P < .05) and did not have complete concentric palatal collapse. Part 2 patients (n = 8) were selected using responder criteria and showed an improvement on AHI from baseline, from 38.9 ± 9.8 to 10.0 ± 11.0 (P < .01) at 6 months postimplant. Both ESS and FOSQ improved significantly in part 1 and 2 subjects. CONCLUSIONS: The current study has demonstrated that therapy with upper airway stimulation is safe and efficacious in a select group of patients with moderate to severe OSA who cannot or will not use CPAP as primary treatment.

Differences in clinical features of upper airway resistance syndrome, primary snoring, and obstructive sleep apnea/hypopnea syndrome.

BACKGROUND: The clinical features of patients with upper airway resistance syndrome (UARS) have previously been compared to patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). No data regarding differences between patients with primary snoring (PS) or patients with obstructive sleep apnea/hypopnea without daytime sleepiness (OSAH) are available. We conducted a study to investigate clinical features of UARS, comparing them to those in patients with PS, OSAH, and OSAHS. METHODS: Retrospective chart analysis of 157 patients with PS, 424 patients with UARS, 562 patients with OSAH, and 1610 patients with OSAHS seen in two sleep disorders clinics between 1996 and 2006. All patients had a diagnostic polysomnography (PSG) and a comprehensive clinical history taken by board-certified sleep specialists. RESULTS: PS and UARS patients were significantly younger, less overweight and had lower weight gain during the past 5years. The female-to-male ratio was highest in the UARS group. UARS patients had significantly less stage non-rapid eye movement sleep (NREM) 1 and NREM 2 and significantly more NREM 3 and NREM 4 sleep than OSAH and OSAHS patients. Arousal indices between PS/UARS and OSAH/OSAHS patients were significantly lower, with no significant difference within these diagnostic categories. Patients with UARS presented the highest degree of subjective impairment. CONCLUSIONS: UARS patients share some clinical features of patients with OSAHS and PS, although these two groups differ in their presentation of clinical sleepiness. Patients with UARS were most impaired in terms of their daily functioning and perception of sleep quality. This finding could not be corroborated by objective measures.

Comparison of pleural pressure and transcutaneous diaphragmatic electromyogram in obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Based on studies of the impact of esophageal pressure on cardiovascular variables during sleep, this signal can be used to refine the severity level in the clinical diagnosis of obstructive sleep apnea syndrome. We hypothesized that relative changes in diaphragmatic electromyogram (EMG) can reflect short-term changes in esophageal pressure durng obstructive apneas and hypopneas. DESIGN: Diaphragmatic EMG was sampled at 0.25 kHz; diaphragmatic EMG waveform was band-pass filtered and digitally converted; the electrocardiogram artifact was eliminated; using a gating procedure, the waveform was fast-Fourier transformed and digitally rectified; and a moving average of 200 milliseconds was calculated. For each inspiratory effort during apnea or hypopnea, we calculated maximum diaphragmatic EMG and esophageal pressure. Data were normalized calculating the percentage difference between the first obstructed and each subsequent inspiratory effort during the respiratory event. SETTING: Sleep disorders laboratory. PATIENTS: 9 patients with moderate obstructive sleep apnea syndrome presenting with apneas and hypopneas during sleep. INTERVENTION: None. MEASUREMENTS AND RESULTS: 861 respiratory events were scored, and the evolution between esophageal pressure and diaphragmatic EMG were compared. Normalized data showed a good correlation between the 2 measures during apneas and hypopneas. There was a significant difference between the percentage increase in esophageal pressure and diaphragmatic EMG for apneas and hypopneas (esophageal pressure, apnea: 118.1% +/- 118.5%, hypopnea: 76.1% +/- 74.3%, P = .000; diaphragmatic EMG, 123.5% +/- 131.7%, hypopnea: 73.3% +/- 74.2%, P = .000). No significant differences for apnea or hypopnea were noted between the 2 measures under investigation. CONCLUSION: Diaphragmatic EMG may be clinically useful to describe relative changes in respiratory effort under conditions of apnea and hypopnea during sleep and to reliably dissociate central from obstructive events where esophageal pressure monitoring is not readily available.