Are there any new treatments specifically for UARS?

I received a diagnosis of UARS in 1995. I use an automated CPAP for it now, which is much better than CPAP I had used in the past. Though even with the Auto CPAP I still don't feel as good as I think I should. My question is are there any new treatments specifically for UARS? 

APAP often yields some improvement in upper airway resistance syndrome (UARS) cases for the simple and obvious reason that no one really sleeps all night long in one position or one stage of sleep; thus chances are variable pressure needs would benefit every patient. As such, it’s safe to say UARS, aka “respiratory effort-related arousals” (RERAs), worsens during the night perhaps in REM or supine sleep or possibly in the final third of the night as the body weakens from struggling to breathe against an obstructed airway regardless of whether the airway resistance is mild or severe. If these points are valid, and many sleep physicians believe them so, then we must ask why an APAP device does not yield better outcomes, either subjectively or objectively?

The answer as best we can tell from our clinical work and research investigations is that an APAP device does not eliminate UARS. Or the next likely answer starts with the premise that APAP may eliminate UARS, but then we must surmise the device causes a side-effect that worsens sleep. As I implied in responding to the initial questions for this Expert Insight column, the pressure needed to maintain airflow during inspiration is higher than pressure needed to maintain airway patency on expiration. During the titration, pressurized air is increased to convert an apnea to a hypopnea and then again increased to convert a hypopnea to a RERA. Thus, it should be apparent the highest pressure attained during any titration is the pressure level needed to convert RERAs to a normal, rounded airflow signal. Taken together, any pressure that treats inspiration is automatically too much pressure to apply on expiration and will produce the objective problem of expiratory pressure intolerance (EPI). EPI is not only an irregularity of the airflow signal, but it may also trigger interruptions or arousals from sleep.

Due to this physiology or pathophysiology, an APAP device will frequently produce one of two effects in the treatment of UARS. First, if the pressure is just right to eliminate inspiratory flattening, then by the facts above the pressure will be too high and EPI emerges. If, however, the pressure is lowered to prevent EPI from developing, then the pressure will not be high enough on inspiration to eliminate UARS.

For these reasons, our sleep medical center stopped prescribing auto-CPAP devices in 2005. More recently, some APAP devices added expiratory pressure relief (EPR), which equates to a mini-bilevel mode, and which may resolve the problems described above. As a first step, individuals with an APAP device with an EPR setting should start using the EPR mode to clarify whether they achieve improved outcomes. I am aware of centers who report that patients attain success with APAP/EPR devices; but we have not seen a consistent elimination of UARS without triggering EPI in patients using APAP/EPR.

Our experience has focused on auto-adjusting bilevel devices, including ABPAP, ASV, and IVAPS devices, which create a larger pressure gradient between inspiration and expiration. In our lab, we observe that ASV devices yield the most consistent results in eliminating RERAs and preventing EPI. (1) I recommend these devices highly for any patient suffering from residual UARS. However, most sleep centers have surmised incorrectly that the auto-adjusting algorithms on these devices are sufficiently reliable to address the patient’s sleep-disordered breathing without the necessity of a “manual” titration to fine-tune the settings. Some centers send patients home with an ABPAP device without conducting an in-lab titration while other centers may conduct the titration yet just set the device to “auto” instead of letting the tech manipulate pressures.

One good explanation for these constrained approaches would be a belief that apneas and hypopneas are the only breathing events to treat. While you (the questioner) may not be aware of the policies from the American Academy of Sleep Medicine (AASM), unfortunately this institution created a conundrum in the field a few years back by first declaring that scoring UARS or RERA events was optional (2,3) but then a few years later declared RERAs needed to be eliminated on a titration study.(4) On this topic, we have an extended commentary that has been accepted for publication in the Journal of Clinical Sleep Medicine, and we express the opinion that RERAs should always be scored and treated.

Going forward, you will need to find a center that shows interest in accurately assessing the UARS component of sleep-disordered breathing as well as having the capacity to use advanced PAP technology devices to eliminate RERA events during a titration. This skill set may prove difficult to locate given the current deterioration in our field as it tumbles head first toward home testing devices, which neither accurately diagnose UARS (let alone score RERAs properly) nor effectively treat UARS in a manner consistent with AASM policies to eliminate RERAs.(4) For these reasons, we established a 2nd Opinion Program at our center, details of which can be found at:

Unfortunately, these points were not covered in the recent Sleep Review piece by my friend and colleague, Dr Lawrence Epstein, when he wrote incisively on current trends and future predictions regarding the expansion of home testing in the sleep market.(5) By not addressing the impact of UARS in titrating patients, Epstein among many others beg the question when they address the utility of home versus in-lab testing. Even the two papers cited in his commentary (6,7) by Kuna et al (2011) and Rosen et al (2012) reported no information about the full RDI in their works; only AHI data were presented, which may have contributed to the mediocre adherence results, an effect often seen in studies that ignore the diagnosis and treatment of UARS in SDB patients. Suffice to say, it remains a serious concern that such research almost never reports the limitation of failing to follow AASM consensus guidelines that mandate the need to eliminate not only apneas and hypopneas but also RERAs.(4)

Summing up, I am reminded of an excerpt from Richard Heckler’s book about how we understand depression: “[Maslow] asks, How can we help people regain their health and happiness unless we truly understand what health and happiness look and feel like?”(8) The identical question must be asked of the professional sleep community: “what does normal sleep look and feel like?” I am persuaded many members of our field including sleep physicians and technologists may not have a clear or precise picture of normal sleep. Certainly, a component of normal sleep is normal breathing in most circumstances. If UARS manifests on the airflow signal, it is difficult to imagine how sleep could be normal, at least as far as we have observed. Sadly, it seems accurate to say that in your quest to treat your UARS, you may run across many obstructions in your path while attempting to resolve the obstructions in your airway.


(1) Krakow B, Ulibarri VA, Romero EA, Thomas RJ, McIver ND. Adaptive servo-ventilation therapy in a case series of patients with co-morbid insomnia and sleep apnea. Journal of Sleep Disorders: Treatment and Care. 2013;2(1):1-10.
(2) Redline S, Budhiraja R, Kapur V, Marcus CL, Mateika JH, Mehra R, et al. The scoring of respiratory events in sleep: reliability and validity. J Clin Sleep Med. 2007;3(2):169-200.
(3) Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2012;8(5):597-619.
(4) Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, et al. Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J Clin Sleep Med. 2008; 4(2):157-171.
(5) Epstein LJ. Sleep benefits management programs. Sleep Review: The Journal for Sleep Specialists.  10-1-2013;14(8):12-15.
(6) Rosen CL, Auckley D, Benca R, Foldvary-Schaefer N, Iber C, Kapur V, et al. A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: the HomePAP study. Sleep. 2012;35(6):757-767.
(7) Kuna ST, Gurubhagavatula I, Maislin G, Hin S, Hartwig KC, McCloskey S, et al. Noninferiority of functional outcome in ambulatory management of obstructive sleep apnea. Am J Respir Crit Care Med. 2011;183(9):1238-1244.
(8) Heckler RA. Waking Up Alive: The descent, the suicide attempt, and the return to life. New York: Ballantine Books; 1994.

Barry Krakow MD


Dr Krakow’s 27 years of sleep research have focused on the complex relationship between physiological and psychological sleep disorders. Dr Krakow currently operates private sleep medical center, Maimonides Sleep Arts & Sciences, Ltd., and serves as Classic SleepCare’s paid Medical Director.

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