Hi, I just wanted to say I definitely think that CPAP/BiPAP is the mainstay treatment for UARS, just that it does not appear to be a cure for most UARS patients. If you are sleeping nightly (through most of the night) with PAP that is properly titrated to resolve/significantly reduce inspiratory flow limitation for a few weeks and you are not feeling better, then you likely do not have UARS. However, "properly titrated..." almost never happens (supposedly the auto-titrating setting algorithms are targeted at flow limitation in addition to apneas/hypopneas, but from my time on UARS forums I'm not convinced that they actually do a good job with this). This is something that patients will just have to verify themselves for the moment - see my advice (Bluesky thread link) on how to do this.
In fact, spending a few weeks sleeping with properly titrated PAP is (IMO) the only way to know whether you actually have UARS/OSAS (there are other treatment options like a mandibular advancement device but this often doesn't fully resolve sleep-disordered breathing/inspiratory flow limitation and you would need to do a follow-up sleep study wearing it to confirm if it does). You can do a sleep study and get a diagnosis of OSA/UARS based on your AHI or RDI, but these factors don't actually correlate with symptoms/are not the cause of symptoms (at least until you get into the more severe OSA range), so the only way to confirm a diagnosis (IMO) is to try treating the sleep-disordered breathing and see if your symptoms improve.
Some people just don't tolerate PAP though, unfortunately. I didn't until I had a nasomaxillary/palate expansion procedure (I'm guessing just because my nasal airways were so narrow):
I was unable to tolerate CPAP or BiPAP prior to getting a nasomaxillary expansion surgery (EASE with Dr. Kasey Li) - I could fall asleep with it but could never stay asleep with it for more than 2-3 hours (I would wake up and have difficulty falling back asleep and end up just taking it off); immediately following the surgery I was able to sleep through the night on BiPAP. There was only ~1mm of expansion from the surgery itself; the rest of the expansion took place slowly over the course of ~9 months (photos of pre-surgery and end of expansion below - now I have braces to close the gaps between my teeth and correct the changes to my bite). I had a very narrow/high-arched palate, which corresponds to narrow nasal airways (since the roof of your mouth is the floor of your nose).
Studies relevant to the olfactory nerve - limbic system sensitization hypothesis of UARS (I'm going to make a thread discussing the hypothesis later, but this is just to share with people outside of S4ME for the moment):
I appreciate your tenacity @nataliezzz.
I've learnt a lot from reading this discussion and videos, such as how breathing efficiency can deteriorate to the point that SpO2 can dip at night more for people with UARS than not.
But it's chicken and egg when we have poor & loose diagnostic tests for UARS and EDS / hEDS and even POTS (the cutoff limit is quite arbitraty) and even those tests aren't routinely used in any situation. They aren't tested for because little can be done about them, but I feel as if they are clues being left scattered everywhere and not enough attention paid to them.
I do remember that my first symptoms of lacking available energy were attributed to lack of restorative sleep. Then in 2013 (from my Amazon history lol) I read "Steven Y. Park MD Sleep, Interrupted: A physician reveals the #1 reason why so many of us are sick and tired" and discovered what UARS was for the first time - And no UK respiratory specialists had even heard of it.
My 3 x Polysomnogram at London Sleep Clinic revealed "Alpha Wave Intrusion" which I understand is now associated with Fibromyalgia and ME.
At this time I hadn't met anyone who even suggested I might have ME, but I hadn't noticed at that time that it wasn't just lack of restorative sleep, but that I also had temperature dysregulation and some OI issues too.
My ME diagnosis wasn't confirmed until 2021 by which time I recognised the classic PEM symptoms had been going on for years, but I didn't realise how abnormal and defining they were.
So I'm still listening, and want to encourage rather than dismiss this train of thought, as if Sleep Disordered Breathing (associated with hEDS) could be a trigger for ME (or something indistinguishable from it), it may be that all roads lead do to Rome.
If so, each road is a clue that might help solve the whole problem of where and exactly what Rome is, in this case.
Notably there have been studies that have used a Polysomnography in ME/CFS, including the intramural study. There were no findings of relevance. Moreover a subset of those participants even underwent a 6 week trial of CPAP without there being any relevant improvements!
Hi, just following up on this old exchange. I can't find anything about a CPAP treatment trial for ME/CFS - not in the intramural study or anywhere else. Of course, if there is one, I'd love to have a look.
I want to write down some vague recollections here before I forget them as it was approaching 15 years since I had my PSGs.
At that time, and I don’t think much has changed, UARS wasn’t a recognised condition or even acronym in the UK.
I became aware of it when I was reading Stephen Park’s book (Sleep Interrupted) which was fascinating. I want to write down what I think I recall of his findings:
1) He made no mention of ME as he seemed unfamiliar with it.
2) He mentioned that there were very distinct differences between UARS and Sleep Apnoea.
3) He noted that the SpO2 thresholds used in PSGs were used to diagnose Sleep Apnoea, not UARS, so PSG studies didn’t record SDB unless it met the Sleep Apnoea criteria.
4) He noted that people with Sleep Apnoea would snore and stop breathing with no awareness that anything was wrong. They had no conscious awareness that they had slept badly apart from Extreme Daytime Sleepiness / Fatigue.
5) People with UARS (detected by tiny changes in SpO2 even for short durations) would be unconsciously disturbed and waken much more easily.
6) People with UARS had more arousals into lighter sleep. They would hear and be easily disturbed by their own snoring, which people with Apnoea would sleep solidly through.
So UARS isn’t “Small Apnoea”. It’s totally different. For that reason:
a) He had little success treating UARS with CPAP, as most with UARS wouldn’t tolerate it. They would awaken at a pin drop and having something on their face meant they never fell asleep or were very disturbed by it during brief arousals.
b) His successes were with use of Mandibular Advancement Devices (MADs) that helped move to lower jaw forward to open up the airway enough that nothing else was needed - BUT this wouldn’t work for anyone with a strong overbite, where top teeth overlap lower ones. Pushing jaw forwards just jams lower teeth against top ones and TMJ can result (and is often already present, as natural body behaviour is to thrust the lower jaw when SpO2 drops.
c) UARS almost always resulted from narrow dental arches (as @Natalie also describes)
d) Surgeries that reduced turbinates, changed jaw geometry or widened dental arches often had dramatic effects. But turbinate reduction is usually quite temporary.
Park is/was a sleep surgeon but he only advised surgery in most extreme cases.
I think the major takeaway for me is how huge the difference is between Apnoea and UARS, especially in relation to a patient’s awareness during and after sleep, that something isn’t right.
I mention all of this because it’s taken 15 years before technology advanced enough for me to tolerate daily SpO2 measurement, in the form of an Oura Ring 4, which measured 93% average last night, which is on the lower edges of being acceptable. I’m going to see if more detail is available in the data (e.g. lowest and frequency).
If at some time in the past it was this bad or worse, I can imagine it may have contributed to my brain being in a more constantly aroused and vigilant state when asleep, and why I am always awoken by a dog barking when my partner sleeps solidly through.
I wonder if you are able to sleep through someone else snoring in the same room or if it would disturb your sleep too much / keep you awake? Remember that people who have Apnoea generally sleep right through their own snoring and gagging / choking as if nothing happened, and that definitely isn’t the case for anyone I’ve met who has ME.
Hi, just following up on this old exchange. I can't find anything about a CPAP treatment trial for ME/CFS - not in the intramural study or anywhere else. Of course, if there is one, I'd love to have a look.
All PI-ME/CFS participants underwent polysomnography in a sleep laboratory. Two had mild periodic limb movements (PLM Index ≥ 5, < 25), two had mild sleep apnea (Apnea Hypopnea Index ≥ 5, < 15 per hour), and one had moderate sleep apnea (Apnea Hypopnea Index ≥ 15, < 30 per hour). None of these individuals noted substantial improvement after a six-week trial of CPAP. Sleep fragmentation was noted in 10 PI-ME/CFS participants (three mild, five moderate, two severe). Thus, PI-ME/CFS participants reported moderate sleep dysfunction not explained by polysomnographic evaluation.
So 3/17 ME/CFS patients met criteria for OSA* and none of these 3 noted substantial improvement after a 6-week trial of CPAP -- that's all that's stated about it in the supplement. I had AI search the supplementary data ZIP folder (24 Excel spreadsheets) for any mention of a CPAP trial and it didn't find anything. So as far as I can tell, there were no official outcome measures used to assess changes in symptoms, no description of CPAP titration protocol, and no CPAP compliance data (how many hours a night/how many nights etc. the patients actually used CPAP). It seems like they were basically just using this as a way to rule out OSA as the actual cause of some patients' symptoms, expecting that if OSA was driving their symptoms they would all report dramatic improvement on CPAP.
Here's some reasons why I don't necessarily think that is the case.
First of all, CPAP, as it is conventionally prescribed, does not actually seem to work that well for many OSA patients. In the European Sleep Apnea Database cohort of 4,853 CPAP-treated patients, Bonsignore et al. (2021) found that excessive daytime sleepiness (EDS, Epworth Sleepiness Scale >10) declined form 56% at baseline to 28.2% at follow-up (median 5 months), although longer treatment time made a difference: EDS was 40% at 0-3 month first follow-up visit and declined to 13–19% at 4 months - 2 years first follow-up visit. Incomplete resolution of apneas/hypopneas and/or poor CPAP adherence occurred with similar frequency in patients with and without persistent EDS, suggesting that residual symptoms are not simply a product of inadequate treatment hours or residual apnea/hypopnea events.
If you've been following along, you'll know that the Epworth Sleepiness Scale (ESS) actually measures a mix of objective sleepiness and fatigue, which are uncorrelated symptoms in OSA patients. I'll get into some reasons why I think CPAP may not work that well (at least on a shorter time scale) for many OSA patients with objective sleepiness in a later write-up, but that's not the type of OSA we are concerned with here when it comes to a potential connection to ME/CFS; we're concerned with the fatigue subtype of OSA (/UARS - there is no separate UARS), which is proposed to be driven by a physiological stress response to inspiratory flow limitation (IFL).
Which brings me to my next point: historically, CPAP titration protocols have been designed to eliminate apneas/hypopneas, but not necessarily IFL. There was one trial comparing a conventional titration protocol to an IFL-targeted titration protocol (see below), but considering ESS and Maintenance of Wakeful Test were the outcome measures -- and not fatigue/other symptoms relevant to this subtype of OSA -- I wouldn't put too much stock in the results, even though IFL-targeted titration did seem to result in better outcomes on some of the measures assessed.
Meurice et al. (1998) compared IFL-targeted vs. conventional titration and found that while mean Maintenance of Wakefulness Test (MWT: a measure of ability to sustain wakefulness sitting in a quiet, dimly lit environment) and ESS outcomes did not differ significantly between groups, conventional titration produced highly variable outcomes with 3 patients showing no MWT improvement whatsoever, while IFL-targeted titration produced uniformly improved scores and significantly better CPAP adherence (7.3 vs. 6.0 hours/night). Final MWT was uncorrelated with AHI, arousal index, or oxygen saturation, but correlated positively with CPAP adherence and residual IFL burden, suggesting that eliminating IFL may improve both treatment efficacy and tolerability.
If someone has the IFL-driven fatigue OSA subtype and they are titrated on CPAP to a pressure that only resolves apneas/hypopneas but not IFL, you would likely not expect them to feel significantly better; in fact, there's an argument that they might actually feel worse if they are now spending less time in apnea (complete cessation of airflow) and more time in IFL (and according to Dr. Gold's hypothesis of prolonged decreases in nasal pressure during IFL activating the limbic system, it's actually milder IFL that would be expected to activate the limbic system more than hypopnea [which is also a form of IFL] due to greater prolonged decreases in nasal pressure, as there is less airflow/negative nasal pressure during hypopnea than milder IFL). So CPAP potentially shifting people from hypopnea-dominant breathing to milder IFL-dominant breathing could also theoretically make things worse. You've also added the stress of CPAP (mask on your face, and potentially pressurized air itself -- especially in the case of CPAP over bilevel devices -- acting as a unique stressor too; see following thread for a discussion of that: Sleep-disordered breathing (UARS/OSA) and chronic insomnia).
The CPAP pressure baseline shift
Looking at Gold's Figure 5, the key thing to understand is that the y-axis represents airflow in ml/sec, with inspiration going downward (negative values) representing subatmospheric nasal pressure. This is at atmospheric baseline — no CPAP.
On CPAP, the entire pressure baseline is shifted upward by whatever the CPAP pressure is. So if someone is on 12 cmH₂O CPAP (which is the median optimal pressure in Parekh et al.), the nasal pressure during inspiration would need to generate a negative swing exceeding 12 cmH₂O just to reach atmospheric, let alone go subatmospheric. During IFL on CPAP, where peak inspiratory flow is constrained and effort-independent, it seems very unlikely that nasal pressure would actually go subatmospheric — the positive pressure is actively splinting the airway open and providing a pressurized airflow baseline.
So the honest answer to your direct question [is there still prolonged subatmospheric nasal pressure during IFL on CPAP?] is: probably not. IFL occurring at significantly elevated CPAP pressures is almost certainly not producing subatmospheric nasal pressure at the nares. The prolonged inspiratory duration and constrained flow plateau would still be present — the temporal signature of IFL — but the absolute nasal pressure environment is fundamentally different from atmospheric-baseline IFL.
Looking at the paper, the optimal CPAP pressure was a median of 12 cmH₂O, and suboptimal was 4 cmH₂O below that — so median 8 cmH₂O. Still well above atmospheric. And yet:
Sustained IFL (SIFL) at these pressures significantly increased K-complex density
K-complexes shifted from delta-dominant to alpha-dominant during SIFL periods
This shift explained 17% of additional PVT lapse variance, independent of AHI and arousal index
Crucially, there were no scorable cortical arousals and no oxygen desaturation during SIFL
This is a really striking finding for your framework — because it demonstrates that the CNS is detecting and responding to IFL even in the complete absence of subatmospheric nasal pressure. The brain is registering something about flow-limited breathing that is arousal-promoting at the microarchitectural level, without any of the classical triggers (hypoxia, cortical arousal, visible EEG disruption).
What this means for the olfactory-limbic hypothesis
This creates an interesting fork. Gold's olfactory-limbic mechanism is specifically about subatmospheric nasal pressure as the sensory input. But Parekh et al. demonstrate CNS activation during IFL at pressures where subatmospheric nasal pressure almost certainly isn't occurring.
This doesn't necessarily refute Gold's mechanism — it may simply mean the olfactory-limbic pathway is broader than the subatmospheric pressure framing suggests, and that additional pathways may operate in parallel:
The olfactory-limbic route — operative not only via prolonged subatmospheric nasal pressure but potentially via the distinctive temporal dynamics of IFL itself: the rapid early rise in inspiratory flow followed by a sustained plateau creates an airflow/pressure signature that is qualitatively different from normal breathing regardless of absolute pressure baseline, and could constitute a novel olfactory nerve stimulus even during CPAP-pressurized breathing. Whether Gold's proposed mechanism requires subatmospheric pressure specifically, or responds to abnormal flow dynamics more broadly, remains an open question worth clarifying with Dr. Gold directly.
Mechanoreceptor/respiratory effort signaling — the prolonged inspiratory effort itself, sensed via pulmonary stretch receptors or upper airway mechanoreceptors, which would operate regardless of CPAP pressure level.
So, in a discussion of a possible connection between sleep-disordered breathing and ME/CFS, I would say this finding is worth noting, but with context; for example: "3/17 patients in the intramural ME/CFS study trialed CPAP for 6 weeks (no description of titration protocol, no compliance data reported) and did not report substantial improvement (no specific outcome measures reported)."
*I've stopped placing much importance at all on % patients meeting criteria for OSA in various studies -- unless it is the same research group showing a difference in % meeting OSA criteria between different patient groups (blinded of course). I recently came across a large population-based study from Switzerland (n=2,121) that found using home PSG with nasal pressure transducers that 84% of men and 61% of women (ages 40-85) met criteria for OSA (AHI ≥5) when using the current recommended AASM scoring guidelines for hypopnea. See also Obstructive sleep apnea is a common disorder in the population—a review on the epidemiology of sleep apnea, 2015, Franklin et al for highly variable OSA prevalence rates between studies. Various factors likely contribute (beyond geographical population factors like obesity rates, craniofacial anatomy differences, etc.) including use of thermistors (less sensitive measure of airflow) vs. nasal pressure transducers (most clinics should probably be using pressure transducers by now) and use of different hypopnea criteria (to see an example of how different hypopnea criteria can dramatically affect OSA diagnosis rates, see this study).
Abstract
Upper airway resistance syndrome (UARS) is a condition where the apnea-hypopnea index is less than 5 and respiratory-effort related arousal index is more than 10. The clinical presentation of UARS may be the same as obstructive sleep apnea-hypopnea syndrome (OSAS); it sometimes shows up with symptoms hardly suggestive of a sleep-disordered breathing. A 17 year-old male patient had applied to a local psychiatry clinic and complained of chronic fatigue, insomnia, behavioral and academic problems and was treated for anxiety and depression. After a period of unresponsive treatment, he was sent to a sleep center for evaluation of insomnia, which turned out to be a fragmented, unrefreshing sleep episode. Polysomnographical evaluation revealed that he had UARS without OSAS. His complaints decreased dramatically after he received CPAP treatment. This case shows that UARS should be considered in young patients with functional somatic syndromes even if the clinical presentation does not apparently imply the condition.
My summary: 17-year-old male with chronic fatigue, insomnia, social and academic problems (and diagnoses of depression and anxiety); "irregular treatment" with hypnotics, sedatives and antidepressants during a 2-year period did not ameliorate his symptoms. He was referred for polysomnography (PSG) due to insomnia (primarily sleep-maintenance insomnia). PSG findings "suggested UARS": AHI 4.5; RERA index 10.5, and "a pathognomonic inspiratory flow contour obtained from nasal cannula." He was titrated on CPAP to ameliorate RERA index to <5 (7 cm H2O). "At the end of his first night of continual sleep he reported positive changes in mood and behavior, i.e. refreshing sleep and a renewed sense of confidence. Follow-up visits proved that his complaints resolved dramatically, and no further complaints about fatigue from the patient were observed."
Continuing the discussion from above about outcomes on CPAP, these case reports highlight some of the variability. All of these patients ostensibly had the same problem (although they had variable symptom profiles) and experienced complete symptom resolution through some form of treatment of sleep-disordered breathing, though only 2/6 experienced complete symptom resolution from CPAP; one experienced modest improvement on CPAP but complete symptom resolution from maxillomandibular advancement (double jaw surgery), and 3 patients did not tolerate CPAP at all but experienced complete symptom resolution from mandibular advancement device (n=1) or maxillomandibular advancement surgery (n=2).
Abstract
...A 17 year-old male patient had applied to a local psychiatry clinic and complained of chronic fatigue, insomnia, behavioral and academic problems and was treated for anxiety and depression. After a period of unresponsive treatment, he was sent to a sleep center for evaluation of insomnia, which turned out to be a fragmented, unrefreshing sleep episode. Polysomnographical evaluation revealed that he had UARS without OSAS. His complaints decreased dramatically after he received CPAP treatment. This case shows that UARS should be considered in young patients with functional somatic syndromes even if the clinical presentation does not apparently imply the condition.
Abstract
Fibromyalgia syndrome (FMS) is characterized by chronic widespread musculoskeletal pain, stiffness and tenderness at multiple points. Sleep disturbances are common in FMS and patients usually complain about nonrestorative sleep...Herein we present a female patient with diagnosis of FMS for 10 years who had complaints of morning fatigue, restless sleep, sleepiness during day and snoring besides musculoskeletal symptoms. Severe OSAS was diagnosed after polysomnographic analysis and FMS symptoms were totally improved with nasal continuous positive airway pressure treatment.
Case presentations: Our three Caucasians patients each presented with severe, chronic insomnia associated with somatic arousal and fatigue occurring either alone, in association with bipolar disorder, or with temporomandibular joint syndrome. Polysomnography revealed that each patient also had mild obstructive sleep apnea, despite only one snoring audibly. One patient experienced a modest improvement in her somatic arousal, insomnia severity, and fatigue with autotitrating nasal continuous positive airway pressure, but the other two did not tolerate nasal continuous positive airway pressure. None of the patients received treatment for insomnia. All three patients subsequently underwent maxillomandibular advancement to treat mild obstructive sleep apnea and experienced prolonged, complete resolution of somatic arousal, chronic insomnia, and fatigue. The patient with bipolar disorder also experienced complete remission of his symptoms of depression during the 1 year he was followed postoperatively.
Abstract
Fibromyalgia (FM) is a chronic, often disabling disorder characterized by multisite pain along with sleep problems and fatigue. Pain and sleep exhibit a reciprocal relationship. When FM and obstructive sleep apnea/hypopnea (OSA) co-exist, treatment options include continuous positive airway pressure or mandibular advancement device. We present a patient experiencing fibromyalgia and OSA whose symptoms vanished wearing a Mandibular Advancement Device (MAD) during sleep. To our knowledge, this is the first documented case of FM symptom resolution by MAD treatment.
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