Desperate Mum to son with UARS seeking advice

[Illorum]

Sure! I'll start a writeup and go more in-depth than my reddit post, but tl;dr eliminate as many flow limitations as possible

[Geer1]

Illorum, do you have the cyclic flow rate phenomenon in your OSCAR data? I see you commented that these wouldnt be scored as a RERA in a sleep study but at least based on the example posted this should be fairly easy to determine from OSCAR data. Makes sense to me this would be the case because if your body is reacting enough to change sleep state then your breathing flow rate is most likely to be affected as well.

I'll look at data to confirm but I dont remember seeing obvious cyclical pattern like this in his data.

Bunnymummy, glad to hear you got in touch with a good sleep doctor that you can trust a bit more. I am learning a few more things about my situation and will share later as I think something similar could easily be happening with your son.

[BunnyMummy]

Illorum, do you have the cyclic flow rate phenomenon in your OSCAR data? I see you commented that these wouldnt be scored as a RERA in a sleep study but at least based on the example posted this should be fairly easy to determine from OSCAR data. Makes sense to me this would be the case because if your body is reacting enough to change sleep state then your breathing flow rate is most likely to be affected as well.

I'll look at data to confirm but I dont remember seeing obvious cyclical pattern like this in his data.

Bunnymummy, glad to hear you got in touch with a good sleep doctor that you can trust a bit more. I am learning a few more things about my situation and will share later as I think something similar could easily be happening with your son.

Thanks Geer1, sorry I never got around to replying to you did I. Struggling to keep on top of everything again... 

Based in my sons Oscar data do you think the cap thing could be a possibility for him?

[Illorum]

The Cyclic Alternating Pattern is not a respiratory phenomenon, it is an EEG phenomenon that is influenced by respiratory events and other sensory stimuli. 

The Cyclic Alternating Pattern is an EEG phenomenon that occurs in NREM sleep. It can be considered the "microstructure" of sleep, whereas sleep staging (REM, stage 1, 2, 3, etc) is the "macrostructure." It is an alternative paradigm to the AASM's current rigid definitions of "arousal." Only 1 in 9 apneas ends in AASM EEG arousal, while 1 in 3 hypopneas ends in arousal (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434561/). Clearly, some neurological phenomena must have occurred to reopen the airway upon the termination of these events. When analyzing patients with Sleep Apnea using CAP scoring, it was found that rather than ending in EEG arousals, 96% of apneas/hypopneas ends in a "phase change" of CAP (a proportion of which are considered AASM arousals). Thus, CAP phases can be considered the underlying phenomenon by which the body tries to reopen the collapsing airway.

CAP has two phases: the A phase and the B phase. The B phase can be thought of as background rhythm, while the A phase designates cerebral activity or increased arousal. Here are some images of it: https://imgur.com/a/g9HsDa5

CAP is a normal component of NREM sleep, but in patients with sleep disordered breathing, periods of apnea or hypopnea/flow limitation can lead to a phase change from background rhythm to the A phase. The A phase has three subtypes: A1, A2, and A3. All three EEG phenomenon terminate respiratory events, but only most of EEG phenomena in A3 and 60% of A2 are considered AASM "Arousals". Flow limitation events, apneas, and hypopneas lead to the constant reintroduction of CAP by forcing the brain to try to repeatedly fix the collapsing the airway. This increases the CAP rate and time spent in CAP, leading to poor sleep consolidation and excessive daytime sleepiness or fatigue.

If the AASM arousal is a sign of transient sleep discontinuity, the finding of phasic EEG delta activities during enhancement of autonomic functions indicates the possibility of physiological activation without sleep disruption. In effect, non-visible sleep fragmentation induced by acoustic tones has been seen to be associated with increased daytime sleepiness, indicating that the processes of sleep consolidation may be impaired - in this case by sensorial stimulation - without evidence of sleep discontinuity.40 In other words, slow EEG events (K-complexes and delta bursts) and AASM arousals (fast rhythms) share functional properties, and, despite their EEG differences, they may be included within the comprehensive term of activating complexes. Such a variety of EEG manifestations relies on specific gates which control the flow of internal and external inputs. The thalamic-basal forebrain gate is an ultimate step of resistance against arousing impulses. Initially the cortex tries to preserve sleep continuity with reinforcement of its gates that are indicated by the occurrence of K-complexes and delta bursts in the sleep EEG. However, when the thalamic gate cannot control the afferent inputs a cortical change is seen translated by an alpha mixed or an alpha/beta frequency burst.41 Anyway, the initial reaction of the cerebral cortex is a sleep-protective response as the majority of transient rapid activities are preceded by a slow high-amplitude EEG burst

Parrino, L., Ferri, R., Bruni, O., & Terzano, M. G. (2012). Cyclic alternating pattern (CAP): The marker of sleep instability. Sleep Medicine Reviews, 16(1), 27–45. doi:10.1016/j.smrv.2011.02.003 
You can read the whole thing here: https://sci-hub.tw/10.1016/j.smrv.2011.02.003



How does this relate to UARS? Since these flow limitation events lead in phase change events and not "arousal", the AASM does not consider them "RERAs." However, they still cause sleep disordered breathing symptoms. A study came out of Stanford 15 years ago investigating the sleep parameters of patients complaining of persisting chronic fatigue and exhaustion. When undergoing normal sleep studies, they had AHIs near 0 and RDIs < 5, pretty much the same as the control group. However, when using CAP scoring, it was found that the microstructure of their sleep and amounts of flow limitation significantly deviated from the control group. They spent twice as much time in CAP and had nearly half as much Slow Wave Sleep (delta). These patients that were fatigued/tired, normal AHI, RDI, and Arousal Index, improved on PAP, yet met no AASM definitions of sleep disordered breathing. You can read the whole thing here: https://sci-hub.tw/10.1016/j.sleep.2006.03.016

In older and heavier patients, the desaturation component of hypopnea scoring catches many of these events. However, young people rarely desaturate as they have responsive palatal nerves (more on that later) and often are not overweight/obese. How fast one will desaturate is a function of body mass, thus younger and thinner people will not have desaturation hypopneas.

For most people with OSA, this probably isn't very relevant as you are already diagnosed, but if your CPAP gave you PLMS, it's been shown that the elimination of flow limitations that end in CAP phases eliminates the PLMS. It's always been known that OSA can masquerade as PLMS, so it makes sense that PLMS may persist if under-titrated.

Eighty-one successively seen patients with PLMs during CPAP titration were investigated. Elimination of AASM-defined hypopnea was not sufficient to eliminate the PLMs observed during the titration; higher CPAP eliminated flow limitation and CAP phases A2 and A3 and persisting PLMs. PLMs were associated with simultaneous EMG bursts in expiratory abdominal muscles.

https://pubmed.ncbi.nlm.nih.gov/22241760/

The reason I had brought this up on reddit was because there were a number of people who had UARS symptoms yet had normal sleep studies. One had even tried out a BiPAP and had significant improvement. Sleep studies in the US (and other places I presume), even if RERAs are scored, unfortunately do not rule out sleep-disordered breathing. The only place I know that CAP scoring standard is Italy, though many university sleep clinics in other places have the capability.
One study out of Stanford 10 years ago found the AASM defined respiratory disturbances so lacking that it missed 80% of children with sleep disordered breathing, even though they had great improvement on PAP therapy. They devised an alternate hypopnea criteria based on CAP that accurately detected their SDB. 

The AASM scoring criteria classified 19% of subjects as having OSA while the Stanford criteria diagnosed 99% of the subjects with OSA who were referred for evaluation of suspected sleep disordered breathing. The primary factor differentiating the AASM and Stanford criteria was the scoring of hypopneas

https://sci-hub.tw/10.1016/j.sleep.2011.04.004

The reason mild respiratory disturbances hit young/UARS patients so much harder than OSA patients is thought to be caused by differences in the nerves in the palatal mucosa. OSA patients have local neuropathy that impairs their ability to effectively respond to flow limitation while UARS patients have intact nerves. This means they are able to "fight back" to a degree but still suffer the consequences. Changes to the nerves is thought to be caused by the long term effects of vibratory snores or GERD.

You can read more about that here: https://sci-hub.tw/10.1378/chest.122.3.866

I wanted to bring it up here since BunnyMummy's son has had a study that turned up normal - and if she needed help figuring out if it really truly is UARS plaguing her son, a sleep study with CAP analysis (and preferably coupled with esophageal manometry) could help convince his doctors her son has a sleep breathing disorder or rule out UARS.

Some more reading on the Cyclic Alternating Pattern:
https://journals.lww.com/clinicalneuroph..._in.5.aspx
https://cyber.sci-hub.tw/MTAuMTAxNi9qLnN...no2012.pdf
https://sci-hub.tw/10.1097/MCP.0000000000000100
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976911/

[Dormeo]

Illorum, that’s an incredibly helpful post. Thank you!

[Geer1]

Illorum, I think you need to be careful with what conclusions you draw from this data. These studies are simply showing that minor respiratory disturbances occur with CAP changes. They still don't understand why nor did I see explanations on how treating the breathing issue resolved the health issues.

I have been dealing with what I consider to be chronic fatigue as it is the closest thing that explains all my symptoms. Fatigue, nasal congestion, sleep disturbances, reflux, ibs, all of the symptoms commonly found in chronic fatigue patients. I have been through a number of the treatments, anxiety/depression, sleep apnea, reflux treatment, diets/digestive and I have finally started to improve after 1.5 years of slowly worsening symptoms.

Back in Mar/Apr I was at my worst. I was fatigued all the time and was having a hard time even working part time. I was having to use Dymista daily to try and provide minor relief from nasal congestion, polyethylene glycol (PEG) daily for constipation and abdominal tenderness, doctor tried me on a new antidepressant which didn't do much and then an internist recommend trying a low FODMAP diet to look into food intolerances and help with digestive symptoms. I then started talking with a dietician and also a naturopath. I was feeling a bit better on low FODMAP diet but was still having ups and downs that I was having trouble explaining. I was tested for SIBO which came back positive and I also started to notice a correlation with dairy products being the most obvious trigger of digestive symptoms (bloating, abdominal tenderness, constipation, reflux). I started on Candibactin (antimicrobial for treating SIBO and SIFO), NAC (supplement that helps with breaking down biofilms and chronic bronchitis) and removed dairy from my diet. This was 6 weeks ago now and during that time my health has started to improve. I am not sure if it is the removal of dairy or if it is the supplements or combination of the two but the results have been obvious. Digestive symptoms have improved, I no longer take PEG, I don't have obvious reflux, nasal congestion has improved significantly and I now forget/don't take Dymista about as often as I do think to take it, my fatigue has improved and I worked 55 hours last week and am on track for the same this week and I don't feel that tired.

My results aren't just based on how I feel though. There is data and physical changes to support improvement as well. I have lost 25 lbs (part of which was just from low FODMAP before dairy free/supplements and some after), a wart like thing on my finger had been there for 1.5 years and nitrogen frozen at least half a dozen times and also treated for over a month with actikeral (salycylic acid with chemotherapy drug) and never healed and now during these past few weeks is 90% healed. I was diagnosed with sleep apnea back in November and have been using CPAP since then and tracking my data with OSCAR. I had noticed worsening tidal volume and minute ventilation and I had started to develop a mouth breathing problem (I believe due to trouble breathing). Over the past 6 weeks my tidal volume and ventilation have now been improving as can be seen below.

So the question is, what caused what? I had disturbed breathing but was it the issue or a symptom? Did I have CAP problems? Possibly, my sleep was quite disturbed even when breathing looked fine in OSCAR data. The thing is that my results aren't uncommon either. For example here is a study done in 2016 in which they found that cows milk protein intolerance is common in young people with chronic fatigue and that removing dairy helps improve symptoms. Again the question is if the dairy is the problem or if it is simply making things worse? I have been drinking milk my whole life (did have an intolerance as a baby though) so why was I fine until now? Was it actually the dairy removal that helped or the supplements?

https://pubmed.ncbi.nlm.nih.gov/27177188/

"Cow's milk protein intolerance is a common problem in young people with chronic fatigue syndrome and is a treatable contributor to their symptoms."

Back to BunnyMummy and her son's situation. Her son has almost every symptom of some sort of underlying allergy/intolerance. I wouldn't be surprised in the slightest if it is the problem or at a minimum making things worse. The hard part is determining what the allergy/intolerance is, the only accurate way is long tedious elimination diets removing known irritants for multiple weeks then reintroducing and looking for symptoms. FODMAP is a proven diet that can provide significant improvement but I think it is more effective with digestive symptoms and maybe not as effective with fatigue etc. Chronic fatigue and these other issues in my research seem to be more related to things like gluten, dairy, soy, peanuts, in short the most common allergens. It is like many people that don't have true IGE reactions can still be prone to some sort of other issue with these foods. 

   

Anyways just some food for thought. It is easy to get tied on a single issue/symptom (sleep disturbed breathing etc) and not as easy to understand if it is the cause or a symptom. As the Guilleminault study says 

"The challenges now are to understand why similar breathing disorders during sleep lead to different clinical presentations".

The other question in BunnyMummy's case is that if breathing is the cause why does treating this (with both CPAP and now BiPAP) not provide significant improvement?

[Illorum]

Illorum, I think you need to be careful with what conclusions you draw from this data. These studies are simply showing that minor respiratory disturbances occur with CAP changes. They still don't understand why nor did I see explanations on how treating the breathing issue resolved the health issues.

Did you read... anything?

PAP therapy stabilizes the cyclic alternating pattern in both UARS and OSA patients. 

Eighty-one successively seen patients with PLMs during CPAP titration were investigated. Elimination of AASM-defined hypopnea was not sufficient to eliminate the PLMs observed during the titration; higher CPAP eliminated flow limitation and CAP phases A2 and A3 and persisting PLMs. PLMs were associated with simultaneous EMG bursts in expiratory abdominal muscles.

https://pubmed.ncbi.nlm.nih.gov/22241760/

In OSAS patients effectively treated with nasal CPAP, therapy induces a significant reduction of CAP instability as well as daytime sleepiness. The improvement is associated with a robust curtailment of A3 subtypes and an expansion of A1 percentage [53]. Further studies will better clarify the relationship between sleep microstructure and diurnal performance.

https://sci-hub.tw/10.1097/MCP.0000000000000100

The first night of ventilatory therapy was characterized by a remarkable expansion of stages 3 and 4 and of REM sleep. In addition, NCPAP suppressed the presence of cyclic alternating pattern (CAP) in REM sleep and induced an impressive rebound of arousals and of certain CAP variables—i.e., CAP rate, CAP time, number of CAP cycles—which dropped well below the physiologic values expressed by controls. A normal duration of phases A and B was re-established starting the first treatment night. When we matched sleep variables with the indices of daytime function, a significant correlation emerged only between the variations of CAP rate and VAS scores. In particular, improvement of daytime sleepiness was less evident when the ventilatory-induced drop of CAP rate was more pronounced.

https://n.neurology.org/content/54/8/1633.short

Forty-five patients completed PAP titration. The oxygen saturation nadir improved from 89.5 ± 4.6 to 91.8 ± 4.3 percent (p = 0.001). Stanford AHI was significantly reduced from 18.6 ± 8.6 to 2.2 ± 1.5 (p = 0.0001). Forty-four other patients returned for follow-up PSG 3–6 months after completion of tonsillectomy and adenoidectomy with/without radiofrequency treatment of turbinates. Overall, Stanford AHI was significantly reduced from 15.5 ± 9.5 to 11.54 ± 7.3 events/h (p = 0.033).

https://sci-hub.tw/10.1016/j.sleep.2011.04.004

This is not controversial. I am not drawing broad conclusions. The science is there: CAP is a fundamental part of sleep and sensory stimuli (like flow limitation) induce phase changes. Elimination of the flow limitation pattern normalizes CAP. This is not obscure science either. This is a commonplace practice in Europe and Latin America. In fact, every sleep center in Italy has the capacity for CAP analysis. The only thing you seem to be interested in is essential oil naturopathy and some crusade against milk. I am not saying BunnyMummy's son definitively is suffering from CAP-related UARS. I'm saying it's something that is worth ruling out considering his level of impairment. 

The other question in BunnyMummy's case is that if breathing is the cause why does treating this (with both CPAP and now BiPAP) not provide significant improvement?

If the diagnostic criteria for sleep disordered breathing was based on one's ability to self titrate, tolerate, and see significant improvement on PAP therapy then I suspect a significant proportion of the people on this board would be glad to hear from you they don't have SDB.

[Geer1]

This is not controversial. I am not drawing broad conclusions. The science is there: CAP is a fundamental part of sleep and sensory stimuli induce phase changes. Elimination of the flow limitation pattern normalizes CAP. This is not obscure science either. This is a commonplace practice in Europe and Latin America. In fact, every sleep center in Italy has the capacity for CAP analysis. The only thing you seem to be interested in is essential oil naturopathy and some crusade against milk. I am not saying BunnyMummy's son definitively is suffering from this. I'm saying it's something that is worth ruling out considering his level of impairment. 

The other question in BunnyMummy's case is that if breathing is the cause why does treating this (with both CPAP and now BiPAP) not provide significant improvement?

If the diagnostic criteria for sleep disordered breathing was based on one's ability to self titrate, tolerate, and see significant improvement on PAP therapy then I suspect a significant proportion of the people on this board would be glad to hear from you they don't have SDB.

I honestly think my naturopath is half useless but something whether it was the dairy or supplements helped while CPAP has not provided obvious improvement. 

You are right that CAP appears that it can be improved by CPAP at least in some cases but simply put having CAP doesn't mean you definitively have untreated sleep disordered breathing which is likely why it hasn't been adopted as a diagnostic or treatment criteria. It is an indicator that something is wrong with sleep, then you have to try and diagnose what.

Imo you are over simplifying that if he has CAP that he has an untreated sleep disordered breathing but even if you had data to support CAP how do you propose fixing it? He has the best bilevel available, what settings do you recommend? Higher EPAP? Higher PS? Frankly I don't think CAP is the problem (even if it is present). I have seen his data at different settings and his breathing is far from ideal but doesn't obviously respond to EPAP or PS and they feel he sleeps worse when trying what should help for UARS. If breathing is the issue you have to treat the cause and imo that is more likely related to the asthma and other allergy like symptoms than a physical deformity etc.

Just my opinion though...

[Illorum]

You are right that CAP appears that it can be improved by CPAP at least in some cases 

Wanna show me studies showing CAP doesn't change with OSA treatment? I've seen nothing remotely resembling that. That's like saying PAP therapy doesn't affect Arousal Index. I'm more inclined to believe 30 years of peer reviewed research and giants of sleep medicine like Christian Guilleminault than you, who hasn't cited anything.

but simply put having CAP doesn't mean you definitively have untreated sleep disordered breathing which is likely why it hasn't been adopted as a diagnostic or treatment criteria. It is an indicator that something is wrong with sleep, then you have to try and diagnose what

And I never claimed that. I literally said "CAP is a normal component of NREM sleep" in my post. In fact, if you'd bothered to read the studies, you would know that normal individuals spend ~27% of sleep in CAP. It's the 50% increase in time spent in CAP that is concerning in the chronically fatigued patients, and even more in the sleep apnea patients.

He has the best bilevel available, what settings do you recommend? Higher EPAP? Higher PS? Frankly I don't think CAP is the problem (even if it is present). I have seen his data at different settings and his breathing is far from ideal but doesn't obviously respond to EPAP or PS and they feel he sleeps worse when trying what should help for UARS. If breathing is the issue you have to treat the cause and imo that is more likely related to the asthma and other allergy like symptoms than a physical deformity etc.

As someone with an RDI of 16 and AHI of 5 verified on in labs, I also self titrated for months have not found significant improvement through PAP therapy. The biggest change for me came from my recent surgery. Some people simply aren't successful on PAP therapy. PAP failure is not uncommon. Residual SDB is also very common on PAP therapy. It's very hard to replace the body's own ventilation.

[Geer1]

You are right that CAP appears that it can be improved by CPAP at least in some cases 

Wanna show me studies showing CAP doesn't change with OSA treatment? I've seen nothing remotely resembling that. That's like saying PAP therapy doesn't affect Arousal Index. I'm more inclined to believe 30 years of peer reviewed research and giants of sleep medicine like Christian Guilleminault than you, who hasn't cited anything.

but simply put having CAP doesn't mean you definitively have untreated sleep disordered breathing which is likely why it hasn't been adopted as a diagnostic or treatment criteria. It is an indicator that something is wrong with sleep, then you have to try and diagnose what

And I never claimed that. I literally said "CAP is a normal component of NREM sleep" in my post. In fact, if you'd bothered to read the studies, you would know that normal individuals spend ~27% of sleep in CAP. It's the 50% increase in time spent in CAP that is concerning in the chronically fatigued patients, and even more in the sleep apnea patients.

He has the best bilevel available, what settings do you recommend? Higher EPAP? Higher PS? Frankly I don't think CAP is the problem (even if it is present). I have seen his data at different settings and his breathing is far from ideal but doesn't obviously respond to EPAP or PS and they feel he sleeps worse when trying what should help for UARS. If breathing is the issue you have to treat the cause and imo that is more likely related to the asthma and other allergy like symptoms than a physical deformity etc.

As someone with an RDI of 16 and AHI of 5 verified on in labs, I also self titrated for months have not found significant improvement through PAP therapy. The biggest change for me came from my recent surgery. Some people simply aren't successful on PAP therapy. PAP failure is not uncommon. Residual SDB is also very common on PAP therapy. It's very hard to replace the body's own ventilation.

Pap therapy doesnt affect arousal rates when arousals aren't due to sdb... CAP is not a measure of SDB, it is a measure of EEG as you mentioned earlier and even in my few minutes of research it is clear that there are lots of things that affect CAP structure and SDB is only one of the variables involved.

For example studies like this one where they use simple sleep aids to treat CAP, this wouldnt work if it was only due to SDB.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954706/

Disrupted CAP is a symptom, a sign of an underlying issue atfecting sleep quality and finding the underlying issue is what fixes a person. 

I dont know what surgery you had done but let's say it might have been turbinate reduction. This is a common improvement surgery for those with disrupted sleep and it can help lots of people but it doesnt actually treat the cause of swelling turbinates it just helps a person live with them by allowing them to breath easier. It is like slapping a bandaid on a wound, it might stop the bleeding but it isn't what heals the wound. 

In my case CPAP did help and I am sure that it improved my sleep quality and likely my CAP rate. But it didnt fix the underlying problem nor did it stop my symptoms from slowly getting worse. Without it I slept even worse but just a couple nights ago I slept without it and didnt feel that bad the next morning. I dont know that I have actually found and treated my underlying issue but I have seen significant improvement for the first time in 1.5 years. 

I challenge anyone struggling with similar issues(especially when symptoms like nasal congestion, asthma, skin reactions, etc are involved) to look into allergies/intolerances as they are common and can cause all sorts of issues. My doctors were pretty much useless at diagnosing this stuff but my dietician was very helpful and sees it regularly. It can be very hard to diagnose though. 

In bunnymummy's son's case he has all the symptoms of some sort of underlying allergy/intolerance/immune system dysfunction and I almost guarantee it is having a huge effect. I dont know what is causing it but it isn't a coincidence that his sleep, fatigue and anxiety are all getting worse at the same time his asthma, eczema and other symptoms are too. His entire body is screaming that something is wrong, the hard part is figuring out what it is. We have already spent months looking at and trying CPAP and BiPAP, keep digging if you feel like but imo time would better be spent looking into other causes. Jmo.