Upper Airway Resistance Syndrome (UARS): a common underlying cause for all "chronic complex illnesses"? (ME/CFS, fibro, GWI, etc.)

[Peter T]

Thank you for a prompt response, I had not expected it so soon given you are redrafting your initial post.

I agree that it is clinically sensible if a doctor identifies a sleep related issue with a well established treatment that they should provide that treatment independent of whether or not the patient also has another condition such as Fibromyalgia or even ME/CFS. Also I agree that a potential association between such as Fibromyalgia and specific sleep disorders is worth examining, but I would wary of any doctor currently claiming she/he could treat Fibromyalgia by treating IFL; I would be even more wary of any doctor claiming to treat an hypothesised issue of the limbic system with CPAP.

Though a potential model of ‘chronic complex illness’ (a phrase I am very uncomfortable with) involving sensitisation of a particular part of the brain) may be of academic interest, at present it should have no place in the clinic. We can see the harm that arises from such premature use of speculative theories in clinical settings, when we look at some of the truly dreadful materials issued by BACME for use with their patients in the UK specialist services.

(Added - I also accept current treatments for or understanding of sleep disorders may not be very sophisticated, we see that in lots of other conditions, for example this is often raised here in relation to thyroid issues.)

 

[Utsikt]

So essentially UARS is never being ruled out.

Then that is a big issue when you are trying to connect UARS and ME/CFS.

 

[nataliezzz]

Then that is a big issue when you are trying to connect UARS and ME/CFS.

True!

I think once you have spent as long reading and thinking about this as me and connecting it to personal experience, a lot of pieces that are not directly supported by evidence start to make intuitive sense, and because of that, I definitely overstated the evidence in my original post.

I don't see ME/CFS as a separate disorder from fibromyalgia, or GWI (considering how many people with fibro & GWI meet criteria for ME/CFS and have PEM, and how many people with ME/CFS meet criteria for fibro), I just see it as all these symptoms clustering in the same individuals in different combinations (there is nothing uniquely special about PEM); when my ME/CFS started, I had unrefreshing sleep and fatigue before PEM, OI and pain emerged as new symptoms (I don't think I developed a new disorder when these other symptoms emerged, but I wouldn't have met criteria for ME/CFS when my illness first started because I didn't have PEM).

And I had PEM without chronic fatigue as a kid (if I played really hard I would get a fever/exhaustion the next day and have to stay in bed - my mom called it my "overtired disease"); so I wouldn't have met criteria for ME/CFS as a kid even though I had the pathognomonic symptom (PEM) because I didn't have the other symptoms like chronic fatigue/reduced functional capacity (perhaps it's possible I had some degree of chronic fatigue and was just not aware of it due to not having a clear baseline, but if I did it didn't interfere with daily activities and life). I always thought it couldn't have been real PEM because I didn't have other ME/CFS symptoms, but I now think that's what it was.

Many people with ME/CFS (and fibro, GWI) have insomnia, and while one can argue that insomnia can be caused by various disorders (I agree), it appears that the majority of people with chronic insomnia have obstructive sleep-disordered breathing (& their chronic insomnia remits for many when treated with PAP).

I had issues with insomnia, and chronic anxiety, and cold hands/feet (esp. during sleep) before I developed full-blown ME/CFS (my ME/CFS had a rapid onset, by the way, I just didn't have PEM/OI/pain at first, it just started with fatigue & unrefreshing sleep).

So it reads like «UARS: the unifying theory of everything?» (a bit of hyperbole)

So yeah, as crazy as it sounds, I kind of think UARS could be a unifying underlying pathology for a ton of unexplained chronic ills (not only "chronic complex illnesses" where people tend to have many of these unexplained symptoms clustering together, but also the person with primary complaint of chronic insomnia, the person with classic SDB symptoms like sleepiness/fatigue and cognitive dysfunction, all of these people could have varying presentations of one underlying disorder.

Anyways, I'll try to stop now, cause I said I would lol.

 

[Utsikt]

For whenever you have time:

I think once you have spent as long reading and thinking about this as me and connecting it to personal experience, a lot of pieces that are not directly supported by evidence start to make intuitive sense, and because of that, I definitely overstated the evidence in my original post.

That’s fair enough. I still wonder if you’re too focused on trying to confirm your chosen theory rather than trying to see what we can know based on the current evidence.

I don't see ME/CFS as a separate disorder from fibromyalgia, or GWI (considering how many people with fibro & GWI meet criteria for ME/CFS and have PEM, and how many people with ME/CFS meet criteria for fibro), I just see it as all these symptoms clustering in the same individuals in different combinations (there is nothing uniquely special about PEM)

I don’t think there is any reason at all to believe that there are not separate disorders at play here. Similar generic symptoms does not in any way indicate similar causes.

And can you elaborate on the last part? I think it would be good if you can explain what you mean by PEM.

So yeah, as crazy as it sounds, I kind of think UARS could be a unifying underlying pathology for a ton of unexplained chronic ills (not only "chronic complex illnesses" where people tend to have many of these unexplained symptoms clustering together, but also the person with primary complaint of chronic insomnia, the person with classic SDB symptoms like sleepiness/fatigue and cognitive dysfunction, all of these people could have varying presentations of one underlying disorder.

If it sounds crazy, it probably is..

 

[nataliezzz]

That’s fair enough. I still wonder if you’re too focused on trying to confirm your chosen theory rather than trying to see what we can know based on the current evidence.

Yes, probably.

I don’t think there is any reason at all to believe that there are not separate disorders at play here. Similar generic symptoms does not in any way indicate similar causes.

PEM could just as easily be a "similar generic symptom" of multiple disorders as chronic widespread muscle pain/tenderness. There is no objective diagnostic test/biomarker for either confirming some kind of specific underlying pathophysiology (like I said, based on @ME/CFS Skeptic 's analysis of 2-day CPET data, I don't buy 2-day CPET as a diagnostic test/biomarker for PEM), so one can just as easily argue that PEM could be a symptom of multiple different disorders as chronic widespread muscle pain/tenderness.

And can you elaborate on the last part? I think it would be good if you can explain what you mean by PEM.

PEM: Significant and prolonged decline in baseline/exacerbation of existing symptoms (and often new symptoms) triggered by physical/cognitive/emotional/sensory/orthostatic exertion/stress, often with a delayed onset. That's just an informal definition from me though; is there one official definition we should be referring to?

If it sounds crazy, it probably is..

Perhaps. But people also thought hand washing preventing infections sounded crazy...

 

[nataliezzz]

I'd be mainly interested in things pertaining specifically to ME/CFS (for starters OSA has a sex ratio that is almost the opposite of ME/CFS so one has to explain the mechanisms that cause these things with different symptom constellations etc), rather than other conditions where I have no idea what those conditions are even supposed to be and I have no idea on how the literature might even look like, including negative findings.

OSA being more common in men does not mean that inspiratory flow limitation during sleep is more common in men, however (and even if it were, in this theory it's not just about presence of inspiratory flow limitation but how the brain reacts to it, so there may be sex differences there.)

Women with sleep-disordered breathing (SDB - OSA/snoring) actually have more excessive daytime sleepiness than men with SDB based on large epidemiological data (they only ever looked at sleepiness, not other symptoms recognized to be associated with SDB), but as I acknowledge here, it doesn't necessarily mean the increased sleepiness in women > men with SDB is because of SDB.



https://www.sciencedirect.com/science/article/abs/pii/S1389945722000478
The one attempted UARS prevalence study from the São Paulo Epidemiologic Sleep Study data found a higher prevalence in females: overall prevalence of 3.1% with 4.4% in females and 1.5% in males (UARS criteria was IFL time ≥5% of total sleep time, minimum SpO2 ≥92%, AHI < 5, and symptoms of excessive daytime sleepiness or fatigue) - I am not sure if people with diagnoses like ME/CFS were excluded as I couldn't access the full paper.

 

[Utsikt]

PEM could just as easily be a "similar generic symptom" of multiple disorders as chronic widespread muscle pain/tenderness. There is no objective diagnostic test/biomarker for either confirming some kind of specific underlying pathophysiology (like I said, based on @ME/CFS Skeptic 's analysis of 2-day CPET data, I don't buy 2-day CPET as a diagnostic test/biomarker for PEM), so one can just as easily argue that PEM could be a symptom of multiple different disorders as chronic widespread muscle pain/tenderness.

It isn’t as widespread or generic as chronic widespread pain, because that is probably the most common generic symptom (that is also caused by so many fundamentally different things).

There is a thread on description of PEM in other conditions, feel free to add any concrete examples there:

https://www.s4me.info/threads/pem-like-descriptions-and-accounts-in-non-me-illnesses.41456/

The current lack of a biomarker for ME/CFS does not make it more likely that PEM is generic because the basic research hasn’t been done yet.

PEM: Significant and prolonged decline in baseline/exacerbation of existing symptoms (and often new symptoms) triggered by physical/cognitive/emotional/sensory/orthostatic exertion/stress, often with a delayed onset. That's just an informal definition from me though; is there one official definition we should be referring to?

It also has to be triggered by exertion/stimuli that was easily tolerated previously, and the length and severity of the episode must be out of proportion to the trigger(s). And it’s not rapid fatigability, DOMS, etc.

We recently made a PEM factsheet.

It’s not a formal definition, though. The motivation for making it (if I understood things correctly) was the lack of good info on PEM.

There is a discussion thread here in case you have any thoughts so I don’t derail this thread any further.

You can also read the discussion leading up to the final version here.

Perhaps. But people also thought hand washing preventing infections sounded crazy...

If you read up on how that hypothesis was created, you’ll see that Semmelweis noticed a clear correlation (less deaths of birthing mothers from childbed fever in wards staffed by midwives compared to by doctors/students), and he then went on to rule out possible explanations through controlled experiments.

Spoiler: Summary of Semmelweis’s discovery

He stumbled upon more data when a pathologist died of the same illness as the person they autopsied - childbed fever. This proved that anyone could get it, and not just women giving birth.

He hypothesised that small parts of the corpse got transferred to patients via doctors/students that also worked on cadavers and made them sick. So he instructed the staff to start cleaning their hands and instruments with chlorine (he was aiming for getting rid of the smell, but lucked out with a very effective disinfectant).

The doctors were upset because they didn’t want to be the ones to blame for the deaths. They did not call it crazy because the data didn’t make sense. They just didn’t like the implication.

Comparing that to Gold’s theory, you’ve already decided on what the answer should be, and you’re looking for things that line up with that instead of doing the basic science first. It’s the complete opposite approach.

 

[nataliezzz]

If you read up on how that hypothesis was created, you’ll see that Semmelweis noticed a clear correlation (less deaths of birthing mothers from childbed fever in wards staffed by midwives compared to by doctors/students), and he then went on to rule out possible explanations through controlled experiments.

Comparing that to Gold’s theory, you’ve already decided on what the answer should be, and you’re looking for things that line up with that instead of doing the basic science first. It’s the complete opposite approach.
[/SPOILER]

Gold noticed an objective finding - alpha-delta sleep (as I keeps stating, the only consistently replicable objective finding in fibromyalgia besides SFN perhaps) in many of his UARS patients without a fibromyalgia diagnosis. He then identified a statistically significant inverse correlation between presence of alpha-delta sleep and AHI in a small study of consecutive SDB patients, and performed a small controlled experiment treating GWI patients with CPAP in which improvement in GWI symptoms were correlated with an objective finding - decreased sleep stage shifts. There is also a published case report (not from Dr. Gold) of alpha-delta sleep disappearing along with fibromyalgia symptoms with treatment of sleep-disordered breathing. These are the kinds of findings I believe warrant calling for larger controlled trials (which is part of the reason I'm spending my time doing what I'm doing), though apparently most people disagree. Dr. Gold is a practicing clinician, not primarily a researcher. He published his theory in Sleep Medicine Reviews in 2011 (which included many other supporting data points from other research studies in addition to the above) so people in a position to carry out larger controlled studies would; as I've stated, I don't think we can assert that sleep medicine ignoring/rejecting it means they have in any way seriously considered the evidence when leaders in the field like Naresh Punjabi state that there is no need for experimental or even observational data to confirm the validity of the prevailing sleep fragmentation paradigm of SDB.

 

[nataliezzz]

It isn’t as widespread or generic as chronic widespread pain, because that is probably the most common generic symptom (that is also caused by so many fundamentally different things).

There is a thread on description of PEM in other conditions, feel free to add any concrete examples there:

https://www.s4me.info/threads/pem-like-descriptions-and-accounts-in-non-me-illnesses.41456/

The current lack of a biomarker for ME/CFS does not make it more likely that PEM is generic because the basic research hasn’t been done yet.

It also has to be triggered by exertion/stimuli that was easily tolerated previously, and the length and severity of the episode must be out of proportion to the trigger(s). And it’s not rapid fatigability, DOMS, etc.

We recently made a PEM factsheet.

It’s not a formal definition, though. The motivation for making it (if I understood things correctly) was the lack of good info on PEM.

There is a discussion thread here in case you have any thoughts so I don’t derail this thread any further.

You can also read the discussion leading up to the final version here.

Thank you for sharing the resources on PEM. I actually would agree that true delayed-onset PEM associated with severe/prolonged decreases in baseline is probably unique to ME/CFS (and some cases of CCI, as I discuss here - I know some people here will cringe to hear me say that, and I will acknowledge I'm just going off of informal case reports [Jen Brea & Jeff Wood], though I'd say they were pretty well documented. I do find it really interesting that Jen Brea never experienced a wired/running on adrenaline feeling since "tired but wired" seems to be such a universal feature of PEM in ME/CFS).



However, theoretically PEM could be a symptom of multiple disorders just like symptoms you consider to be more vague. I do believe many factors about PEM (and the medications it often responds to, etc.) suggest a CNS process, so perhaps there are multiple disorders affecting the CNS that could cause PEM, right? As I stated, I had PEM as a school-aged kid (it went away in middle school) without other ME/CFS symptoms (that I was aware of) - it just took a high threshold of activity to trigger it. Is it possible I had a different disorder back then for which PEM is a feature?

 

[Utsikt]

(and possibly CCI, as I discuss here - I know some people here will cringe to hear me say that, and I will acknowledge I'm just going off of informal case reports [Jen Brea & Jeff Wood], though I'd say they were pretty well documented. I do find it really interesting that Jen Brea never experienced a wired/running on adrenaline feeling since "tired but wired" seems to be such a universal feature of PEM in ME/CFS).

I think she has stated she never had ME/CFS. But the thread for discussing that is here (I linked the start of the most recent discussions).

However, theoretically PEM could be a symptom of multiple disorders just like symptoms you consider to be more vague. I do believe many factors about PEM (and the medications it often responds to, etc.) suggest a CNS process, so perhaps there are multiple disorders affecting the CNS that could cause PEM, right? As I stated, I had PEM as a school-aged kid (it went away in middle school) without other ME/CFS symptoms. Is it possible I had a different disorder back then for which PEM is a feature?

There are no medications that PEM in general responds to. There are anecdotes both for and agains various medications and supplements, but nothing substantial or backed by any kind of studies.

I think most people here would agree that the CNS is involved in PEM simply based on the symptoms. But that doesn’t mean the root cause lies in the CNS. And even if it did, we have no hard clues about how it actually works. But that’s a discussion for elsewhere.

These are the kinds of findings I believe warrant calling for larger controlled trials (which is part of the reason I'm spending my time doing what I'm doing), though apparently most people disagree.

I think this is where we need to take a close look at the evidence you cite. So I’m going to leave you to it with updating everything. As Trish mentioned earlier, we create individual threads for papers instead of discussion many in one thread. Makes it a lot easier to keep track of.

Maybe our time is best spent by leaving this thread be for now, and you can create threads for the studies one by one over the coming days/weeks/what fits you?

There is a pinned post at the top of each research subforum with instructions for how to create threads:
Considering posting a study here? Here's the best way to do it

If you cannot manage posting it yourself, go to this thread for help from others:
Thread for members to request a paper be posted

 

[nataliezzz]

I think she has stated she never had ME/CFS. But the thread for discussing that is here (I linked the start of the most recent discussions).

Thanks. I believe she still refers to it as "my ME" when discussing it and up until not too long ago, was making posts about #MESpine on Twitter, and is supposedly working on a film about the connection between neurosurgical diagnoses and ME/CFS & related disorders (this is her pinned profile post on Twitter):

I think this is where we need to take a close look at the evidence you cite. So I’m going to leave you to it with updating everything. As Trish mentioned earlier, we create individual threads for papers instead of discussion many in one thread. Makes it a lot easier to keep track of.

Maybe our time is best spent by leaving this thread be for now, and you can create threads for the studies one by one over the coming days/weeks/what fits you?

There is a pinned post at the top of each research subforum with instructions for how to create threads:
Considering posting a study here? Here's the best way to do it

If you cannot manage posting it yourself, go to this thread for help from others:
Thread for members to request a paper be posted

Thank you. Yes, good idea leaving the thread be for now. I of course want to respond to people's comments (and I appreciate people at least engaging with me on it here like most people refuse to do on Twitter), so the conversation keeps going when it would be best just to come back to it when I have the information laid out in more depth/more accessible format. I'll leave this here again

THREAD IN PROCESS OF BEING UPDATED. CHECK BACK ON 8/1 IF YOU ARE INTERESTED IN UARS.

-Natalie

 

[Peter T]

ON 8/1

Sorry I am being slow on the uptake, are you meaning the first of August, using the American convention?

 

[Utsikt]

Thanks. I believe she still refers to it as "my ME" when discussing it and up until not too long ago, was making posts about #MESpine on Twitter, and is supposedly working on a film about the connection between neurosurgical diagnoses and ME/CFS & related disorders (this is her pinned profile post on Twitter):

Shoot, I might have confused different people here. I can’t find the posts I was thinking about, so don’t take my word for anything here.