To determine if the application of continuous negative external pressure (cNEP) is effective and safe in individuals with obstructive sleep apnea (OSA) during an overnight in-laboratory sleep study.
A prospective, open-label pilot study in subjects with documented OSA recruited from the patient population at one sleep clinic. The intervention was application and titration of cNEP during overnight polysomnography.
Of the 15 subjects studied (mean apnea-hypopnea index [AHI] at baseline, 43.9 events/h), 13 (87%) were responders to cNEP: 9 had an excellent response (AHI < 5 events/h) and 4 had a partial response (AHI < 50% baseline and < 15 events/h). Three minor, self-limited adverse events occurred, which appeared related to contact pressure of the cNEP device on the skin.
In this pilot study, cNEP appears to be safe and effective during short-term use in subjects with OSA. Further studies are warranted.
Kram JA, Woidtke RV, Klein KB, Rose RM. Evaluation of continuous negative external pressure (cNEP) for the treatment of obstructive sleep apnea: a pilot study. J Clin Sleep Med. 2017;13(8):1009–1012.
Obstructive sleep apnea (OSA) is a common, chronic condition frequently associated with daytime sleepiness, cognitive dys-function, and other comorbidities.1–3 Current treatments such as continuous positive airway pressure (CPAP) and mandibular advancement devices may be effective but are often not well tolerated. Despite advances in product design and acclimation methods for such devices, a substantial proportion of individuals with OSA still do not receive effective therapy.4 Thus there is a need for new treatments that are both effective and acceptable to users.
The application of external pressure over the thorax is an acknowledged form of noninvasive ventilation.5 First used by Drinker and Shaw in 1929 for the treatment of a polio victim, the “iron lung” became a mainstay of supportive care for those with chronic respiratory failure.6 In this pilot study, we evaluated a novel investigational device that applies continuous negative external pressure (cNEP) over the upper airway (Figure 1). The cNEP sleep system consists of a soft silicone collar fitted over the anterior surface of the neck that is attached by a flexible tube to an adjustable vacuum pump. When a negative pressure is created within the collar, the spatial relationships of the soft-tissue structures comprising the pharyngeal airway are altered in a manner that retards structural collapse during sleep (Figure 2). Because the collar does not intrude on facial structures or force air into the airway, it may be easier for patients to acclimate to the device and may improve long-term adherence compared with current therapies.
The cNEP collar fitted over the upper airway.
cNEP = continuous negative external pressure.
The cNEP collar fitted over the upper airway.
(A) cNEP is at the minimum negative pressure setting required to maintain its position on the neck, and therefore the posterior airway space is still subject to occlusion during sleep, resulting in an obstructive apnea. (B) cNEP has been titrated to sufficient negative pressure such that the posterior airway space remains patent during sleep, preventing an apnea. cNEP = continuous negative external pressure.
(A) cNEP is at the minimum negative pressure setting required to maintain its position on the neck...
Previous studies indicate that cNEP favorably affects the critical airway closing pressure in humans7 and is effective in preventing obstructive apneas in those undergoing mild to moderate sedation.8 The United States Food and Drug Administration cleared the cNEP collar for this use in December 2015. This study is the first to test the clinical performance of cNEP in those with OSA.
This was a prospective, open-label pilot study. Patients with known OSA were enrolled from a population followed at an American Academy of Sleep Medicine (AASM) accredited sleep laboratory. Subjects were recruited from the clinic patient database, or by means of a research flyer in the waiting area. Males or females aged 22 to 70 years were eligible for enrollment if they met the following criteria: polysomnography (PSG) or home sleep apnea testing in the prior 6 months documenting the presence of OSA as indicated by an apneahypopnea index (AHI) > 15 events/h where less than 20% of apneas were central; absence of severe cardiopulmonary, neurologic, or carotid disease; absence of anatomic abnormalities of the cervical region and absence of excessive facial hair in the region where the cNEP sleep collar is positioned. All subjects were using CPAP or autotitrating positive airway pressure at the time of study enrollment.
Standard AASM protocols for the conduct and scoring of PSG were employed.10 Hypopnea was assessed using the 2012 AASM scoring criteria when peak flow declined by > 30% from baseline for a duration of ≥ 10 seconds and was associated with a decrease in oxygen saturation of > 4%. Response to cNEP was characterized in a manner similar to AASM standards for CPAP9: cNEP was titrated from -20 to -45 centimeters of water (cm H2O) to determine the pressure that resulted in the lowest AHI. This was accomplished by graded increases in negative pressure of 2 to 3 cm H2O every 20 to 30 minutes in a manner analogous to an in-laboratory CPAP titration.9 Response to cNEP was categorized in a manner similar to AASM standards for CPAP9: an “excellent response” was defined as an AHI < 5 events/h and a “partial response” was defined as a reduction of AHI of > 50% from baseline and a AHI of < 15 events/h. Subjects who did not meet either criteria were considered non-responders. Adverse events were assessed by clinical observation and direct subject query. In this pilot study, subjective responses to cNEP in the study participants were not systematically evaluated.
The study protocol and informed consent form were approved by the Western Institutional Review Board on July 25, 2014 (approval no. 20141204) and cNEP was considered to be a nonsignificant risk device. All subjects provided written informed consent.
Fifteen subjects underwent cNEP titration. None discontinued the study prematurely. The characteristics of the study subjects are summarized in Table 1. Eight were male and seven were female. The mean age was 55.5 years, and the mean body mass index (BMI) 34.8 kg/m2. The mean AHI prior to the application of cNEP was 43.9 events/h, with a range of 15.5 to 79.6 events/h.
Demographic characteristics of subjects.
Demographic characteristics of subjects.
The results of the cNEP titration are shown in Table 2. Thirteen subjects (87%) responded to cNEP: nine (60%) exhibited an excellent response and four (27%) had a partial response. Two subjects (13%) did not respond. For responders, the mean negative pressure required to minimize the AHI during cNEP titration was 29.2 cm H2O. No subject characteristics (eg, age, sex, BMI, baseline AHI) appeared to predict whether a subject would respond to cNEP (data not shown).
Results of cNEP titration.
Adverse events were observed in three subjects: two had mild cutaneous erythema where the cNEP collar was in contact with skin and one had mild blistering at the contact site. All adverse events resolved without the need for clinical intervention.
This pilot study suggests that cNEP is effective at reducing AHI during an in-laboratory titration PSG. Most subjects (60%) exhibited an excellent response to cNEP (AHI < 5 events/h whereas 27% had a partial response (AHI < 50% of baseline and < 15 events/h). These findings are particularly noteworthy in this population with a mean baseline AHI of 43.9 events/h and mean BMI of 34.8 kg/m2.
Adverse events related to cNEP occurred in a small number of subjects. These appeared to be related to contact pressure between the collar and underlying skin. It is expected that such events will be reduced by future improvements in cNEP collar design.
This first pilot study, which was meant to determine if there was evidence that cNEP might be effective in the treatment of OSA, has a number of limitations: The sample size was quite small. So that we could evaluate the effects of a full range of negative pressures in each subject, it was not possible to maintain a given pressure for more than 30 minutes, nor was it possible to determine any relationship between cNEP and body position or sleep stage. Although it could be that the lack of a CPAP washout period may have biased the results, it is unlikely to have accounted for the magnitude of AHI decline we observed.11 Unfortunately, given the nature of the cNEP collar, a sham control was not feasible, because without applied vacuum, the collar will not remain adherent to the neck.
Despite such limitations, further research appears warranted because the proportion of favorable responses in this pilot study is encouraging and suggests the possibility that cNEP could be a treatment option for those with OSA of all levels of severity. Future clinical trials will need to address the durability of cNEP responses, the tolerability of cNEP beyond a single study night, define the possible effects of cNEP on upper airway pressure and dimension, and identify any effect of body position and sleep stage, among other things.
All authors have seen and approve this manuscript. Study site: California Center for Sleep Disorders, Alameda, California. This research of an investigational device was sponsored by Sommetrics, Inc. Drs. Kram and Klein and Ms. Woidtke report being consultants to Sommetrics, Inc; Drs. Kram and Klein report being shareholders in Sommetrics, Inc. Dr. Rose reports being an employee of Sommetrics, Inc., and owning stock in Sommetrics, Inc.
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