But there is no agreed marker for PEM (2 day CPET proposed in past) no agreed identifying symptom (certain delay now promoted as key but that is just assertion). It is a disputable term as to what is entailed and sb who gets it after 14 hrs may be different from sb who gets it after7 or 24 in key aspects or not. We don't know. We don't know and defining PEM as unique by a specific descriptive feature e.g 24hr + delay is cart before horse if that means to deny commonalities with earlier onset post exertional malaises. 24 + PEM it may be researched separataely as e.g." Biomarkers in PEM with 24 hr + onset" but without any foregome conclusion re. the nature of those with earlier onset, though there must be some differences. presumably, but not necessarily key ones.
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New Forum Software Installed (Still a few issues but reopening the forum) More details.
Upper Airway Resistance Syndrome (UARS): a common underlying cause for all "chronic complex illnesses"? (ME/CFS, fibro, GWI, etc.)
- Thread starter nataliezzz
- Start date
Utsikt
Senior Member (Voting Rights)
I don’t think I’ve said anything about PEM needing a delay of 24 hours. I think I’ve only linked the factsheet that says «PEM usually starts hours or a day or two after it is triggered and can last for hours, days, weeks or longer.» And said something similar about how PEM is often/usually delayed.
If I’ve said something else, I’ll go back and edit it because that wasn’t my intention.
No worries I was just commenting generally on the uncertainties of PEM (or trying to). Sorry for any misunderstanding.
Utsikt
Senior Member (Voting Rights)
Ah, I see. No worries!
nataliezzz
Established Member (Voting Rights)
It's not a core symptom of ME/CFS, but some patients do experience excessive daytime sleepiness (and many patients experience excessive sleeping, like you said, of course). I had daytime sleepiness in addition to fatigue earlier on in my illness and the sleepiness went away.
Both sleepiness and fatigue are well recognized to be associated with UARS/OSAS; some people with these disorders complain of one more than the other. Other people with UARS/OSAS appear to have other complaints like insomnia as their primary complaint (chronic insomnia patients with excessive daytime sleepiness and other OSA signs & symptoms [obesity, witnessed apneas, etc.] were excluded in that study and 40/40 left were still diagnosed with OSA/UARS [90% OSA - the prevalence of OSA in the general population is ~20%]. Many experienced remission from chronic insomnia with PAP therapy). UARS/OSAS being able to cause chronic insomnia may not seem logical (aren't these patients supposed to be tired/sleepy?), but it fits with the stress response paradigm of sleep-disordered breathing: the brain reacting to sleep-disordered breathing as a stressor results in a state of somatic arousal -> chronic insomnia (I think it fits with the "tired but wired" feeling many of us know so well).
And I think the study and case reports I've cited support that for yet others, fibromyalgia/body pain may the dominant complaint. It seems the symptoms and combination of symptoms varies highly in different individuals with UARS/OSAS.
There is no universal pattern of how UARS (or OSAS) patients presents.
As I think I think I've convincingly argued above, a person with UARS/OSAS can present with sleepiness without insomnia, or insomnia without sleepiness, e.g.
No one knows if UARS could cause symptoms like PEM because no one has ever taken a group of people who meet strict criteria for ME/CFS, evaluated them for UARS, and treated those who may have it to see the effect on ME/CFS symptoms like PEM.
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nataliezzz
Established Member (Voting Rights)
Yes, I do want to do this at some point, the idea of it just sounds really exhausting at the moment, especially as I have already spent 10s of hours compiling it all into threads on Bluesky/etc. (but I know that's not an accessible option for people).
Yes, agreed.
No need to do everything at once. If there's a study that's central to the hypothesis, you can make a thread for just that one to start. Normally we don't add any color commentary in the first post either, just the abstract, so you don't have to add comments immediately either. Maybe others will make comments that you can later reply to if you want.
The thing is that if you fixed my frozen shoulder with an injection that took away the mobility issues and pain that meant it interrupted my sleep then
Insisted on not being incredibly careful what you were measuring and the time period.
Then of course not being troubled by the shoulder on top of my me/cfs would mean overall I was in less pain and exhaustion - but you wouldn’t have been treating my me/cfs other than what should be happening if there was a real medical otidsssion dealing with us of making sure we don’t have other treatable issues on top exacerbating it because it’s bad enough having that if you aren’t already ill, then add in what losing a nights sleep does to someone with me/cfs
But it’s down to research design etc , or just finding the others who also have frozen shoulders and claiming that’s a ‘sample of me/cfs’ rather than ‘your ten cherry-picked frozen shoulder people’ whether/what it says much about me/cfs ?
Eg taking careful research to find out what the me/cfs was like before the shoulder issue started (not using just before it was injected as the starting point) and how it might have indeed struggled whilst carrying that extra burden and maybe even after that shoulder is dealt with the me/cfs doesn’t even improve back to where it was before because eg months of bad shoulder and fixing it took its toll.
Because obviously if starting at the day the shoulder was eg injected and calling any improvement in exhaustion in me/cfs from that day where someone had a bad shoulder impacting their life up to that day was ‘improvement’ would be fine if you were just demonstrating not leaving something else untreated takes its toll but inaccurate if you say treating a shoulder improves the me/cfs and then think the shoulder might be part of the cause of me/cfs rather than a comorbidities that didn’t help?
… and this is why I have big issues with even the ActuonforME big survey using the ‘does x symptoms improve with y treatment that isn’t for me/cfs but to therapy for toe pain’ definition of me/cfs . Why just those aspects selected and not also frozen shoulders, UTIs and other things people commonly have that ‘don’t help their cfs’ if that’s the claim?
The taking it to this next level by claiming HPA axis stuff then feels obscure and in order to try and put some squaring of s circle that isn’t there - there is only a connection in that those he’s found/sought out who have this and that then also have x other illness apparently have both , not ‘the population’ which would involve a representative sample?
Or have I missed where he’s taken a representative sample of me/cfs or fibro or whatnot?
There are a few layers here to look into what has been done to demonstrate which claims in what illnesses vs the theory?
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Does UARS cause significant hypercapnia.? If so this may be worth a look and may be relevant to ME improving on rapamycin.
nataliezzz
Established Member (Voting Rights)
No, UARS doesn't cause hypercapnia. By definition, there is no significant oxygen desaturation in UARS. There can be hypercapnia in obstructive sleep apnea (OSA), but I don't think it's the primary driver of symptoms like fatigue, sleepiness and cognitive dysfunction in people with OSA syndrome either, though it may contribute for some.Does UARS cause significant hypercapnia.? If so this may be worth a look and may be relevant to ME improving on rapamycin.
nataliezzz
Established Member (Voting Rights)
I'm going to try to make some individual threads for Dr. Gold's fibro & Gulf War illness studies at some point where I can discuss the methodology of how the samples were recruited, so I can let you know once I have done that so you can take a look.
However, here is one study of what I believe is fair to say a pretty representative sample of fibromyalgia patients where 23/23 had obstructive sleep apnea (OSA) - of course it's possible that those with more disturbed sleep were more likely to agree to undergo polysomnography (but even if that were the case, it would be difficult to explain all 23 having OSA based on prevalence of OSA in the general population):
But here is a study (not from Dr. Gold) where a rheumatology clinic offered polysomnography to consecutive female (ACR criteria meeting) fibromyalgia patients who were not specifically complaining of sleep disturbances; 40% (23) agreed and all 23 had OSA, with 19/23 (83%) having an AHI >15. That does not happen by chance - the prevalence of OSA (AHI ≥ 5) in women in the general population based on epidemiological studies is ~15-20%.
Sleep-disordered breathing among women with fibromyalgia syndrome
Obstructive sleep apnea is a common disorder in the population—a review on the epidemiology of sleep apnea
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shak8
Senior Member (Voting Rights)
Sited in the post 7/20/25 @nataliezzz is Sleep-disordered breathing among women with fibromyalgia syndrome (Journal of Clinical Rheumatology, 2006)
journals.lww.com
Full-text is pay-walled.
****************************************************************************************************************************
I can personally attest to fragmented sleep. But what is the significance of this correlation (if there is one--I don't know if there was a control group, I don't know if the average BMI matches an invisible assumed control.)
Sleep-Disordered Breathing Among Women With Fibromyalgia... : JCR: Journal of Clinical Rheumatology
The authors conducted a chart review of one rheumatologist’s community-based practice where polysomnograms were offered routinely to all women who met the American College of Rheumatology criteria for fibromyalgia. Interpretation of these standardized protocol-based polysomnograms was performed...
journals.lww.com
Full-text is pay-walled.
Results:
Mean age of the study subjects (n = 23) was 45 (standard deviation, 7.8) years. Median body mass index was 27 kg/m2 (interquartile range 20–48). These women had poor sleep with many arousals (median arousal index 23), apnea–hypopneas (median apnea–hypopnea index 22, interquartile range 17–30). Desaturation was common with half the patients having nadir oxygen saturation less than 87%. Restless legs were detected in polysomnograms among many women who clinically denied it (mean leg movement index 5.8).Conclusions:
A large proportion of women with fibromyalgia in a general rheumatology practice had sleep-disordered breathing, which can be detected using sleep polysomnograms. Studies are needed to examine if treatment of the commonly detected sleep apnea will have a beneficial effect on symptoms of fibromyalgia.****************************************************************************************************************************
I can personally attest to fragmented sleep. But what is the significance of this correlation (if there is one--I don't know if there was a control group, I don't know if the average BMI matches an invisible assumed control.)
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shak8
Senior Member (Voting Rights)
I found a meta-analysis on Pub-Med by searching for sleep apnea and fibromyalgia.
pubmed.ncbi.nlm.nih.gov
Results: Fourteen studies met the inclusion criteria. This study showed that 21% of patients with OSAHS experienced FM. Subgroup analyses were performed based on race, age, sex, body mass index, and diagnostic criteria for patients with OSAHS. These findings indicate that obese patients with OSAHS have a higher risk of FM, similar to females with OSAHS. Regarding most sleep monitoring indicators, there were no discernible differences between patients with OSAHS with positive FM and those with negative FM. However, patients with positive FM had marginally lower minimum arterial oxygen saturation levels than those with negative FM. The current literature suggests that patients with OSAHS have a high incidence of FM (21%), and FM has little effect on polysomnographic indicators of OSAHS.
Fibromyalgia in obstructive sleep apnea-hypopnea syndrome: a systematic review and meta-analysis
Fibromyalgia in obstructive sleep apnea-hypopnea syndrome: a systematic review and meta-analysis - PubMed
<span><b>Introduction:</b> Fibromyalgia (FM) is a common condition in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). This meta-analysis aimed to evaluate differences in sleep monitoring indicators between patients with OSAHS and positive FM and patients with OSAHS and negative...
pubmed.ncbi.nlm.nih.gov
Results: Fourteen studies met the inclusion criteria. This study showed that 21% of patients with OSAHS experienced FM. Subgroup analyses were performed based on race, age, sex, body mass index, and diagnostic criteria for patients with OSAHS. These findings indicate that obese patients with OSAHS have a higher risk of FM, similar to females with OSAHS. Regarding most sleep monitoring indicators, there were no discernible differences between patients with OSAHS with positive FM and those with negative FM. However, patients with positive FM had marginally lower minimum arterial oxygen saturation levels than those with negative FM. The current literature suggests that patients with OSAHS have a high incidence of FM (21%), and FM has little effect on polysomnographic indicators of OSAHS.
Hi @nataliee,
please don’t feel the need to answer now, but I think some more information on IFL would be good since you’ve seen this as the key point. I’ve tried to get a very rough first understanding at IFL. It seems to me there have been negative results:
This small study of people with UARS found no difference in events of flow limitation in people with UARS vs controls (https://www.atsjournals.org/doi/10.1164/ajrccm.162.4.9908052#_i14).
You had previously cited a Sao Paolo study for prevalence estimates of UARS. What that study also showed is that low levels of FL alone does not indicate disease, it’s a physiologic phenomenon and mild IFL seems both common and normal (https://www.sciencedirect.com/science/article/abs/pii/S1389945722000478). The same seems to be established in other studies but I’ve been having a tougher time finding those (Rapoport, D. M., et al. "Flow limitation during sleep in normal subjects." Am J Respir Crit Care Med 149 (1994): A493., Rappoport, D. M., and R. G. Norman. "Inspiratory flow limitation (FL) and sleep fragmentation in normal subjects." Am J Respir Crit Care Med 151 (1995): A153.)
You have argued that CPAP not reliably working has to do with insufficient implementation that doesn’t address the FL issue sufficiently, with the titrated setup of Dr. Gold being able to overcome such problems. I had a look at the following meta-analysis on CPAP in UARS https://www.sciencedirect.com/science/article/pii/S1984006315000127?via=ihub, without looking at it deeply it seems to suggest that there isn’t a strong correlation between CPAPs addressing FL vs those not addressing FL when it comes to outcomes of patients (allegedly there was no relationship in studies such as https://publications.ersnet.org/content/erj/11/5/1121).
Regarding FL as “objective measure” I wonder whether it really is as objective as you’ve suggested, at a first glance it seems to me that maybe some of the same problems, that say occur for SFN, might also be occurring here (most people wouldn’t accept SFN as an objective measure for anything due to various biases). At a first glance it doesn’t always seem that things are standardised and maybe some other biases also coming into play (waveform interpretation, it’s also unclear to me in the GWI study what cut-off was used for the titration w.r.t PSG etc.).
please don’t feel the need to answer now, but I think some more information on IFL would be good since you’ve seen this as the key point. I’ve tried to get a very rough first understanding at IFL. It seems to me there have been negative results:
This small study of people with UARS found no difference in events of flow limitation in people with UARS vs controls (https://www.atsjournals.org/doi/10.1164/ajrccm.162.4.9908052#_i14).
You had previously cited a Sao Paolo study for prevalence estimates of UARS. What that study also showed is that low levels of FL alone does not indicate disease, it’s a physiologic phenomenon and mild IFL seems both common and normal (https://www.sciencedirect.com/science/article/abs/pii/S1389945722000478). The same seems to be established in other studies but I’ve been having a tougher time finding those (Rapoport, D. M., et al. "Flow limitation during sleep in normal subjects." Am J Respir Crit Care Med 149 (1994): A493., Rappoport, D. M., and R. G. Norman. "Inspiratory flow limitation (FL) and sleep fragmentation in normal subjects." Am J Respir Crit Care Med 151 (1995): A153.)
You have argued that CPAP not reliably working has to do with insufficient implementation that doesn’t address the FL issue sufficiently, with the titrated setup of Dr. Gold being able to overcome such problems. I had a look at the following meta-analysis on CPAP in UARS https://www.sciencedirect.com/science/article/pii/S1984006315000127?via=ihub, without looking at it deeply it seems to suggest that there isn’t a strong correlation between CPAPs addressing FL vs those not addressing FL when it comes to outcomes of patients (allegedly there was no relationship in studies such as https://publications.ersnet.org/content/erj/11/5/1121).
Regarding FL as “objective measure” I wonder whether it really is as objective as you’ve suggested, at a first glance it seems to me that maybe some of the same problems, that say occur for SFN, might also be occurring here (most people wouldn’t accept SFN as an objective measure for anything due to various biases). At a first glance it doesn’t always seem that things are standardised and maybe some other biases also coming into play (waveform interpretation, it’s also unclear to me in the GWI study what cut-off was used for the titration w.r.t PSG etc.).
nataliezzz
Established Member (Voting Rights)
You are bringing up all the right points. Plenty of people have insp. flow limitation without symptoms, just like plenty of people have OSA without symptoms. Yet both snoring (which almost always = insp. flow limitation) in the absence of OSA (AHI ≥5) and OSA (almost everyone with OSA snores) have been shown in large epidemiological studies to be associated with sleepiness (I have linked them in my OP). And there are studies showing that CPAP reduces sleepiness in these individuals (people in this thread have previously asked me to provide the actual studies showing this, so I will try to do that at some point). So clearly narrowing/collapse of the airway is in some way a causal factor in the sleepiness in these individuals, yet it is not sufficient, since the majority of people with snoring/OSA do not have excessive daytime sleepiness (I am just talking about sleepiness because that is the only symptom these large population-based sleep studies looked at; I don't actually believe other well-recognized symptoms of OSAS like fatigue and cognitive dysfunction have a different underlying etiology, I think it's more just about individual variation in how people respond).
This is where Dr. Gold's paradigm comes in, providing an explanation for why snoring/inaudible insp. flow limitation is necessary but not sufficient to lead to symptoms like sleepiness, fatigue, cognitive dysfunction, insomnia and pain in sleep-disordered breathing patients. I have provided a better explanation of his theory in my OP now; take a look (results from studies like the one that showed a statistically significant inverse correlation between AHI and alpha-delta sleep, sleep-onset insomnia, headaches & IBS in sleep-disordered breathing patients provide support for the theory - as frequency of apneas [complete cessation of airflow] increases, there is less exposure to inspiratory flow limitation).
Thank you for sending me these! I plan to look at them in detail later.
It did look like the authors of the second study concluded "These results tend to show that correcting flow limitation is associated with a higher observance and a more important efficiency in normalizing daytime vigilance than with conventional nasal continuous positive airway pressure," so that seems to support the notion that eliminating flow limitation leads to better outcomes.
I emailed Dr. Gold again to ask him about his clinical experience over the years with fibromyalgia patients (he has seen hundreds, 100% of whom in clinical practice have had inspiratory flow limitation during sleep - the 1/28 in his study who didn't may have been because of the esophageal pressure catheter used in the study, which has been shown in other studies to prevent airway narrowing/collapse in some individuals.)
This is what he said:
"In Medicine, nothing is 100%. Not everyone with FM who I diagnose chooses to use nasal CPAP, Of those who do, not everyone uses it 100% of their nights in bed or for their entire time asleep on the nights they use it. Then, even if they use it whenever they are asleep, many of them have been prescribed SSRI's, anxiolytics, and such that cause fatigue when combined with CPAP and so confound the evaluation of their symptoms. What I can say after 20 years is that the outcomes you see in the 2004 paper are pretty much what I still see."
(i.e. his clinical experience with hundreds of fibro patients confirms that fibro patients typically experience ~35-50% improvement in their symptoms on CPAP).
As far as I know, Dr. Gold only uses CPAP. Dr. Barry Krakow thinks BiPAP/ASV leads to better outcomes in most individuals, especially those with milder SDB (see talk from him below) - he attributes this to expiratory pressure intolerance, and has shown that objective signals in the airflow improve along with subjective comfort when people are switched from CPAP to BiPAP/ASV. He has published a study of chronic insomnia patients showing that ASV lead to higher rate of remission from chronic insomnia than CPAP.
Even when it comes to BiPAP/ASV, which seems more tolerable and beneficial for many, I don't think it is typically curative when it comes to conditions like fibromyalgia (although we did see the case report of the woman whose fibro symptoms were "totally improved" with nasal CPAP); I do think breathing pressurized air is likely acting as a stressor too, explaining the failure of PAP to fully resolve the symptoms of these disorders in many individuals (in my opinion - and Dr. Gold's too).
Fair. Criteria for determining presence/absence of flow limitation may vary from study to study.
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