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

[nataliezzz]

How would leave a patient with minor UARS who's predominant ME/CFS symptom is PEM/PENE with delayed 48 - 72 onset plus the usual OI/POTs?

@SteveFifield I think you saw my informal case report above about the improvement in my orthostatic intolerance/POTS on BiPAP. I think this study provides good evidence for UARS being able to cause OI (all of the patients in the study had orthostatic hypotension [OH], but as you may know, it's been suggested that OH and POTS may both be responses to the same underlying problem [e.g. hypovolemia], and I and others have experienced both, even fluctuating within short time frames - e.g. I remember one time I was doing NASA lean tests on myself off meds for my ME/CFS doctor and I had hyperPOTS one day when I was doing more activity/"running on adrenaline" and OH literally the next day when in PEM)

How might PEM possibly be related to UARS? We don't have any evidence on that, but IMO it fits with the proposed theory of UARS being a stress response disorder of the limbic system. Aspects of PEM like the following fit nicely with that IMO: PEM severity does not necessarily correspond to actual energy expenditure, you can end up in an identical state of PEM from physical/cognitive/emotional/social exertion or even sensory input alone, PEM can be prevented/reduced for many patients by taking CNS depressants like benzos/DXM ahead of exertion (Vicodin - also a CNS depressant - works the same for me).

Feels like it's a co-morbity or possibly enhances susceptibility, just as appears to be the case for EDS and hEDS.

I think UARS is the cause of my ME/CFS. I find that much more plausible than that I have two disorders with all of these overlapping symptoms (the only core symptom of ME/CFS there's no link to in the UARS lit is PEM: unrefreshing sleep, fatigue, and cognitive dysfunction are well-recognized symptoms of UARS, and I think there's good evidence for myalgia and OI too). Many people, myself included, did not have PEM when our illness first started (and I don't think we developed a new/separate illness when PEM emerged); whatever ME/CFS is, I think you can have a form of it without PEM (yes, I know, by definition it's not ME/CFS then...)

All of my symptoms improved quite quickly when I got on BiPAP: my muscle pain was about 50% improved by the end of the first week, and ~3 weeks in I stopped the bupropion and my acute OI symptoms on standing were resolved.

Some might say the improvement in my symptoms was what was being caused by UARS, and everything left over is ME/CFS. I'm more inclined to believe that whatever was causing my symptoms before (a stress response to inspiratory flow limitation during sleep, according to the UARS theory), BiPAP is activating the same pathway, just to a lesser degree, since literally all of my ME/CFS symptoms - including PEM - improved on BiPAP (and I think this fits with the olfactory nerve hypothesis of UARS):

I think the partial (~35-50%) improvement that most "chronic complex illness" patients experience on properly titrated PAP fits with the olfactory nerve - limbic system sensitization hypothesis (the olfactory nerve has been shown to have mechanosensory properties, sensing changes in nasal airflow/pressure - see my OP), because if our limbic systems have become sensitized to changes in nasal airflow/pressure outside of "normal" breathing (i.e. IFL) during sleep, then we are probably going to react to having pressurized air blown up our noses as a stressor too lol.

I have a BlueSky thread on this topic.

Here is another study (The effects of nasal anesthesia on breathing during sleep) that supports the role of olfactory mechanosensory input to the brain: nasal anesthesia during sleep resulted in a fourfold increase in apneas (equally distributed between central and obstructive); the increase in central apneas suggests that olfactory mechanosensory input to the limbic system is involved in regulation/rhythmicity of breathing (central apnea = brain fails to send signals telling you to breathe). The increase in obstructive apneas could be because nasal anesthesia disrupts the nasal-respiratory reflex and suppresses the activity of muscles in the upper airway.