@nataliezzz this would be evidence against your idea that OSA plays a role in ME/CFS if one was to believe the authors, right? Because the authors claim TNFalpha and IL-6 to be elevated in OSA and we know that they are not elevated in ME/CFS.
I just thought it was an interesting paper so I figured I would post it here (and I also had heard that Dr. Klimas was doing small pilot studies treating ME/CFS & GWI patients with etanercept [in conjunction with mifepristone] - not sure what the current status on that is).
I'm not aware of the research re: TNF-α and IL-6 in ME/CFS, maybe you can point me to that. The studies that these authors cite for their claim "We and others have shown that the inflammatory cytokines, TNF-α and IL-6, are elevated in sleep apnea and that this elevation is compounded with, but independent of, obesity (13–15)" appear to be small ones (
1,
2,
3 - at least the first two, the last one does not state a sample size) and even if it is generalizable to all patients with OSA + sleepiness (which is how OSA syndrome [OSAS] has historically been defined), I don't think we can make any generalizations to all people with symptomatic OSA (e.g. it may be that only people with OSA presenting primarily with excessive daytime sleepiness have these cytokines elevated, but if you looked at all people with symptomatic OSA - e.g. those with primarily fatigue, or insomnia, etc. rather than sleepiness as the primary complaint too - these effects would disappear). I do think there are many ways that UARS/OSAS can present (e.g. some people have sleepiness without insomnia, and some have insomnia without sleepiness - and both can be reduced/alleviated by PAP in some/many cases - see below). So there is no universal presentation for UARS/OSAS.
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).
Anyways, in the UARS thread, there was a general discussion about "Why are OSAS patients sleepy/fatigued/etc. if the majority of patients with OSA are asymptomatic?" so this paper may provide some insight on why at least some OSAS are sleepy. From the paper:
"We and others have shown that the inflammatory cytokines, TNF and IL-6, are elevated in sleep apnea and that this elevation is compounded with, but independent of, obesity (13–15). Also, these cytokines are elevated in experimentally induced sleepiness in healthy young adults after one or several nights of total sleep loss (16, 17) or partial sleep loss for 1 wk (18). There are several ways that peripheral cytokines can communicate and signal the brain to elicit central nervous system manifestation, e.g. sleepiness, including crossing the blood-brain barrier (19, 20) and through peripheral autonomic efferent nerves (21). Based on these findings, we have proposed that TNF-α and IL-6 might play a significant role in mediating sleepiness and fatigue in disorders of EDS [excessive daytime sleepiness] in humans (14–16). Furthermore, we and others have shown that there is a strong correlation between the degree of obesity and levels of TNF-α and IL-6, both of which induce peripheral insulin resistance (5, 14, 15, 22–27). Thus, we have proposed that inflammation is an important mechanism involved in the multifaceted association between sleep apnea and sleepiness."
