Link between OSA and the "beer gut"

[Muffy]

Right I think I know where some confusion lies. Going back to the Steier paper, they have defined their end-expiratory pressure as the peak value. End-expiration does not also equal start of next inspiration, and I think that's where my wires were getting crossed.

But it does. That is the only possible definition, namely

End-expiration is the point that immediately precedes the ensuing inspiration.

Muffy

[onesight1]

Hi all. This is my first post in this forum. I'm currently a PhD student working in the area of sleep apnoea. I have been looking at one potential mechanism which might explain why sleep apnoea is predominant in males.
While it is clear that the risk of developing sleep apnoea increases when you put on extra weight, the actual distribution of where this fat is stored is known to be a better predictor of sleep apnoea. For example, fat around the neck is a better predictor of sleep apnoea compared to your body mass index.

Alternatively, I have been looking at the link between abdominal obesity ("beer gut") and upper air collapsibility. The belief is that males who have a bigger belly have increased pressure inside the abdomen. This increased pressure is a likely force to push the diaphragm and airways upwards towards the head, making the upper airway more "floppy" and therefore easier to collapse. Sleep apnoea is known to generally be more severe when you're on your back.

Therefore, I looked at the effect of increased pressure inside the abdomen on upper airway collapsibility during sleep in obese male sleep apnoea patients. I increased pressure inside the abdomen by inflating a large pressure cuff (ala bloody pressure cuff) which was placed around the abdomen. I then assessed how collapsible the airway was with and without abdominal compression. In terms of the results, the airway was slightly more collapsible when there was increased pressure inside the abdomen. While the effect was small, I discovered a very strong relationship between pressure inside the stomach and upper airway collapsibility during times when the cuff wasn't inflated. Basically, this might mean that pressure inside the abdomen is perhaps an important predictor of how collapsible your airway is, but these effects cannot be simply simulated by using a cuff to simulate abdominal obesity.

Some food for thought

Daniel

which is why older males should check into TRT... they could have low testosterone, which adds to the fatigue and abdominal fat.

[split_city]

Right I think I know where some confusion lies. Going back to the Steier paper, they have defined their end-expiratory pressure as the peak value. End-expiration does not also equal start of next inspiration, and I think that's where my wires were getting crossed.

But it does. That is the only possible definition, namely

End-expiration is the point that immediately precedes the ensuing inspiration.

Muffy

What about if there is a pause after expiration before the start of the next inspiration? Is end-expiration still the same as start inspiration in this example?

Ok, so by what your saying, end-expiration = start inspiration. I still don't get where you are heading. Back to this figure:



You stated this earlier that

end-expiration (start inspiration) in these highly dynamic patients is at the end of the plateau

If that is the case, why does the first green line in the above example not correspond to the plateau for Pes? Even your second green line doesn't overlap the plateau. Are you still saying that the start inspiration Pes in the above example is ~20cmH20 i.e. end of plateau? If so, I will have to disagree based on other parameters e.g. mask and epiglottic pressure, diaphragm EMG and iPEEP (e.g. clearly shown by Steier et al). I still believe that Pes at start inspiration is ~7cmH20.



See above supine data. The Pes at start inspiration, as defined by start flow (or in the case above, dip in mask pressure), is below the end of the plateau in this example. That's what I'm saying is happening with the first figure. Inspiratory flow can't begin until there is a pressure gradient, such that there needs to negative pleural pressure. You're saying Pes at start inspiration is ~20cmH20. Taking into account the mediastinal artefact, true Pes would be about 13cmH20 at a guess. How will you generate inspiratory flow with that?? That's why these patients are showing iPEEP (see Steier). Inspiratory airflow can only commence when iPEEP is first overcome such that iPEEP reflects a “threshold load” on the respiratory system, increasing the work of breathing and impairing inspiratory function. In other words, patients need to overcome this positive airway pressure before flow i.e. start inspiration, can be established.

[split_city]

...Obese males tend to have greater intra-abdominal pressures versus BMI-matched obese females, again illustrating the difference in fat distribution.

Would be interesting to know if the women who have sleep apnea also have reduced levels of these hormones.

Hhhmm, you raise a good point. I might need to look into that.

PS If you aren't aware, statins with their potential muscle damage contribute to sleep apnea in some individuals. As you are testing men who have been the targets for statin mfgs, it might be worth gathering that data and determining if muscle weakness from statins might also be contributory...

Another good point as I didn't exclude patients who were taking statins. Not quite sure of their effects on say, the genioglossus.

[Muse-Inc]

Results 1 - 10 of about 1,090 for statins "genioglossus"...happy surfing

[Muffy]

End-expiration is the point that immediately precedes the ensuing inspiration.

What about if there is a pause after expiration before the start of the next inspiration?

Not only does it make no difference, but how else could you be assured that the patient, has, in fact, stopped exhalation, and the effects of all forces have been accounted for, such as continued expiratory flow and the other factors that go to create that iPEEP thing you were talking about before? Too high a respiratory rate (whether it was patient- or machine-generated) or bronchospasm (from cardiac or pulmonary origin) could result in air-trapping because the patient was still activity exhaling at the point of inhalation. The only way that you could account for this is to define end-exhalation as previously noted. Not everybody is looking at 7 different channels to try to identify that moment, y'know.

Speaking of which, I also made the point about whether or not your channels were "synched". Different methodologies will report out in slightly different timeframes (i.e., a pressure or effort signal may come in at a slight delay compared to an electrical signal). So while it's great that you're microanalyzing down to 0.1 seconds to define these points, without seeing your biocals, I would say you could be miles off.

BTW, that was also why I asked if the "20 cmH2O patient" was on CPAP or not. Not only did that flow waveform look machine-generated, but there appeared to be a delay in reporting that signal as well.

If that is the case, why does the first green line in the above example not correspond to the plateau for Pes? Even your second green line doesn't overlap the plateau.

Well, among other reasons,

I went back to the original sleep file and carefully picked where I thought inspiration started based on flow, mask pressure, epiglottic pressure and diaphragm EMG activity. I haven't put in an arbitrary 7cmH20 because that's the Pes value where the lines are. The scale is quite broad as shown by an earlier snapshot.

You're sitten' there with a microscope and you've got me looking at a view from 5 miles away. You put up the microscope view and maybe I'll get a little closer (assuming that would even be necessary).

But if the margin of error of your acquired signals is like +/- 0.5 seconds, it makes no sense to try to analyze at the 0.1 second level.

Muffy

[split_city]

Are you or are you not suggesting that Pes at start inspiration is ~20cmH20? Regardles of whether the signals are in sync, this is what you are alluding to because you have stated end-expiration/start inspiration is at the end of the plateau. Taking away the mediastinal artefact, Pes is still going to be above atmospheric pressure at this point. How is the patient going to generate inspiratory flow? Again, Steier et al shows that the end of the plateau does not represent start of inspiration in the supine obese individual.

[Muffy]

Are you or are you not suggesting that Pes at start inspiration is ~20cmH20? Regardles of whether the signals are in sync, this is what you are alluding to because you have stated end-expiration/start inspiration is at the end of the plateau. Taking away the mediastinal artefact, Pes is still going to be above atmospheric pressure at this point. How is the patient going to generate inspiratory flow?

That's exactly what I'm saying, so as a scientist I would question the validity of your data including confounding factors and improper calibration techniques.

Again, Steier et al shows that the end of the plateau does not represent start of inspiration in the supine obese individual.

Since I haven't seen his biocals, I'm not ready to buy his gig either.

Muffy

[split_city]

Are you or are you not suggesting that Pes at start inspiration is ~20cmH20? Regardles of whether the signals are in sync, this is what you are alluding to because you have stated end-expiration/start inspiration is at the end of the plateau. Taking away the mediastinal artefact, Pes is still going to be above atmospheric pressure at this point. How is the patient going to generate inspiratory flow?

That's exactly what I'm saying, so as a scientist I would question the validity of your data including confounding factors and improper calibration techniques.

Again, Steier et al shows that the end of the plateau does not represent start of inspiration in the supine obese individual.

Since I haven't seen his biocals, I'm not ready to buy his gig either.

Muffy

First of all, by start inspiration, do you mean start of inspiratory effort or start of inspiratory flow? If you mean start of inspiratory effort, then yes, I agree that it's at the end of the plateau. As I and others have shown, there will be a delay between start inspiratory effort and start inspiratory flow because the individual needs to overcome the positive airway pressure before they can't generate flow i.e. due to iPEEP.

Pending your response, are you simply querying the validity of the ~20cmH20 at start inspiratory effort? As I showed earlier, the patient's end-expiratory (start inspiratory effort) Pes was much lower during "stable" breathing. The ~11cmH20 is consistent with that presented by Steier et al. Don't forget that the 11cmH20 includes mediastinal artefact.



However, the 20cmH20 period does not occur during stable breathing. There's increased expiratory drive which I believe is contributing to the rise in the peak Pes. The increase in peak Pes seems to relate to the increase in expiratory drive. As shown earlier, Carley et al also shows a rise in peak Pes (up to ~20cmH2O) during obstruction.



But please feel free to write a letter to the editor of Thorax expressing your concerns with the Steier article and perhaps also Journal of Applied Physiology in regards to the Carley paper.

[Muffy]

First of all, by start inspiration do you mean start of inspiratory effort or start of inspiratory flow? If you mean start of inspiratory effort, then yes, I agree that it's at the end of the plateau. As I and others have shown, there will be a delay between start inspiratory effort and start inspiratory flow because the individual needs to overcome the positive airway pressure before they can't generate flow i.e. due to iPEEP.

Now I should move my green lines to the left even a little more (and you have to move that red one):



so by this criteria, inspiratory start is now definitely at 20 cmH2O, and that's the end of iPEEP.

Pending your response, are you simply querying the validity of the ~20cmH20 at start inspiratory effort?

Right.

However, the 20cmH20 period does not occur during stable breathing. There's increased expiratory drive which I believe is contributing to the rise in the peak Pes. The increase in peak Pes seems to relate to the increase in expiratory drive. As shown earlier, Carley et al also shows a rise in peak Pes (up to ~20cmH2O) during obstruction.

Carley shows two, not the sustained 20 cmH2O baseline you demonstrated during stable breathing (and I'm calling this stable breathing because those respiratory variations appear to be central (this critical information could have/should have been supported by information from the RIP belts)):



and you're trying to compare this to obstruction as noted by Carley. This is apples and aardvarks. Look at the increasing effort during respiratory event in his Pes vs the sustained low effort which then increases during normal respiration in yours.

But please feel free to write a letter to the editor of Thorax expressing your concerns with the Steier article and perhaps also Journal of Applied Physiology in regards to the Carley paper.

Have their people call my people and I'll see if I can work them in, but you're the one who just bad-mouthed his iPEEP thing, not me.

Oooooh, is he ever gonna be mad.....

Muffy

[split_city]

First of all, by start inspiration do you mean start of inspiratory effort or start of inspiratory flow? If you mean start of inspiratory effort, then yes, I agree that it's at the end of the plateau. As I and others have shown, there will be a delay between start inspiratory effort and start inspiratory flow because the individual needs to overcome the positive airway pressure before they can't generate flow i.e. due to iPEEP.

Now I should move my green lines to the left even a little more (and you have to move that red one):

First of all, you put the red line in based on what you believed I thought was start inspiration. I never picked that as start inspiratory effort or inspiratory flow if we are going down that track.

so by this criteria, inspiratory start "effort" is now definitely at 20 cmH2O, and that's the end of iPEEP.

If we are going by what others have said:

Steier et al 2009 "Intrinsic positive end-expiratory pressure (PEEPi) as defined by change of oesophageal pressure (DPoes) from end-expiratory
baseline prior to inspiratory flow (vertical dashed line) in the supine posture in a morbidly obese subject." (From figure 1)

Lotti et al 2005 "The difference in esophageal pressure between end-expiration and the initiation of inspiratory flow was considered as an expression of dynamic positive end-expiratory alveolar pressure (PEEPi)."

Figure from Pankow et al



...then yes, the 20cmH20 represents start inspiratory effort. All these studies were conducted during wakefulness under stable breathing conditions. Whether the end of the plateau represents start inspiratory effort when expiratory drive is high, such is the case in my example, is another question. I assume it would but I'm not positive about it. Which comes to my next point...

Carley shows two, not the sustained 20 cmH2O baseline you demonstrated during stable breathing (and I'm calling this stable breathing because those respiratory variations appear to be central (this critical information could have/should have been supported by information from the RIP belts)):

and you're trying to compare this to obstruction as noted by Carley. This is apples and aardvarks. Look at the increasing effort during respiratory event in his Pes vs the sustained low effort which then increases during normal respiration in yours.

Hang on, which figure are you having issues with? The one above or this one (which is the one we have been primarily looking at) OR BOTH?



So to first of those two figures. Stable breathing? In what sense? Stable, as in the same what would be happening during wakefulness? Stable, as in not having any respiratory events? He maybe stable to you but it doesn't discount the fact that the individual is demonstrating increased drive. For example, the figure below shows an extended period (~3mins) of the first figure. It's a mixture of stage 2 and 3 sleep (sorry, EEG data was recorded on different computer but I have referred back to the stage data). You classify this as stable breathing? Perhaps, but the patient is certainly demonstrating increased drive (large swings in Pes and Pepi). Inspiratory phasic GG activity is certainly elevated. Upper airway resistance is high. Lots of snoring seen in the mask pressure channel. Importantly, not one EEG arousal was scored during this whole period despite the presence of respiratory events (again, EEG data not recorded on same computer). It has been speculated that arousals are potentially a necessary outcome to dissipate high drive, such is the case during respiratory events. Without arousals, this patient seems to a) overcome respiratory events and b) continues to maintain a high level of drive. But more to the point, call it "stable" breathing if you wish, but don't ignore the fact that they are experiencing high drive. During periods of less drive, end-expiratory Pes was much closer to 10cmH20.



Back to this end-expiratory 20cmH20 Pes. Unfortunately, we had technical difficulties with the gastric balloon catheter in this patient displaying the data above, so I am unable to comment on whether increased expiratory swings in gastric pressure were occurring at the same time during this period of increased drive. However, back to figure 2 (the one we have mostly been looking at).



Stable breathing?? Again, maybe but again, high drive state. I mean, just look at those expiratory gastric pressure swings!! I reckon this guy must have a rock hard six-pack under his shirt given the constant abdo crunches he does at night!! He constantly demonstrated these expiratory swings throughout the night. So, in essence, this might be "normal" to him but certainly not normal to most of the other patients I have studied.

Back to a previous point, it appears that this end-expiratory Pes increases as expiratory gastric pressure swings rise (figure below). Are they related? Is the increased abdo crunching contributing to the increased end-expiratory Pes?



It's a bummer that the Carley and co. didn't measure gastric pressure. It would have been interesting to see if the rise in end-expiratory Pes followed similar trends in expiratory gastric pressure swings.

Oh, what the heck. I'll do it for them. From a different patient, similar to Carley and co., end-expiratory Pes is on the rise during an obstruction. BUT, more importantly, look at those increments in expiratory gastric pressure swings towards the end of the event. They look nice. End-expiratory Pes appears to rise in line with increasing expiratory gastric pressure swings. What's more, the peak in expiratory gastric pressure corresponds pretty much to the peak of Pes.



So, in this example, this patient develops expiratory drive during obstruction which coincides with the increase in end-expiratory Pes. Our other 20cmH20 patient appears to have increased expiratory drive even during so called "stable" breathing. So what's to say the maintenance of expiratory gastric pressure swings is contributing to the increased end-expiratory Pes during the period of increase drive? I have already shown that end-expiratory Pes is much less in this patient when he is having normal Pes and Pga pressure swings.

On a side note, it's interesting that this individual (figure above) is able to still achieve some expiratory flow during obstruction without any inspiratory flow i.e. continues to lose lung volume.

But please feel free to write a letter to the editor of Thorax expressing your concerns with the Steier article and perhaps also Journal of Applied Physiology in regards to the Carley paper.

Have their people call my people and I'll see if I can work them in, but you're the one who just bad-mouthed his iPEEP thing, not me.

Oooooh, is he ever gonna be mad.....

Muffy

What you talking about willis? Nope, I didn't bad mouth it at all. I keep referring to it to support my work. You're the one expressing concerns with their data. You follow it up with him. Why not send an email directly to Steier to ask him for his biocals?

[split_city]

By the way, your style is very similar to StillAnotherGuest (SAG). Even your photobucket links are awfully similar...just saying

[Muffy]

First of all, you put the red line in based on what you believed I thought was start inspiration.

NFS.

If we are going by what others have said:

Steier et al 2009 "Intrinsic positive end-expiratory pressure (PEEPi) as defined by change of oesophageal pressure (DPoes) from end-expiratory
baseline prior to inspiratory flow (vertical dashed line) in the supine posture in a morbidly obese subject." (From figure 1)

Lotti et al 2005 "The difference in esophageal pressure between end-expiration and the initiation of inspiratory flow was considered as an expression of dynamic positive end-expiratory alveolar pressure (PEEPi).

OK, I'm gonna go real slow here. Has this not been correctly transcribed?

First of all, by start inspiration do you mean start of inspiratory effort or start of inspiratory flow? If you mean start of inspiratory effort, then yes, I agree that it's at the end of the plateau. As I and others have shown, there will be a delay between start inspiratory effort and start inspiratory flow because the individual needs to overcome the positive airway pressure before they can't generate flow i.e. due to iPEEP.

Muffy

[Muffy]

Right.

You can see it coming, but you can't stop it.

Muffy

[split_city]

Cool, very constructive points there...

...anyways, news just in.....expiratory gastric pressure swings contribute to iPEEP



Figure from Ninane et al 1993.

and I qoute "This suggested that the presence of PEEPi was related at least in part to the expiratory contraction of the transversus abdominus."

Taken from Lotti et al 2005 "One concern with PEEPi being an expression of preinspiratory muscle activity (decrease in Pes) is the concomitance of expiratory abdominal muscle contraction and then relaxation . Because of this we subtracted the decrease in Pga from the concomitant change in Pes before the beginning of inspiratory flow."

Look at the relationship again. The highest expiratory rise in gastric pressure was ~7cmH20. Going back to our 20cmH20 end-expiratory Pes guy (below). He is having much larger expiratory swings than that. The * swing is ~20cmH20. No wonder why his end-expiratory Pes and iPEEP are high even when considering mediastinal artefact. Does this satisfy you query as to why end-expiratory Pes is elevated to this level? Probably not, but oh well.



Now I must confess, that iPEEP vs rise in gastric pressure data came from COPD patients who were awake and seated. But again, my point is that expiratory gastric pressure swings contribute to end-expiratory Pes and it appears that the level of end-expiratory Pes is related to the rise in expiratory gastric pressure. But, coming back to an earlier point...is my 20cmH20 guy an obstructed airways patient? After looking at his spirometry results, he had an FEV1 of 87% predicted and FVC of 80% predicted so maybe something there. Mind you, all spirometry testing was done upright. However, unlike the COPD patients from the data above, my 20cmH20 guy did not demonstrate expiratory gastric pressure swings during wakefulness and end-expiratory Pes was closer to the "norm" in obese patients in the supine posture. He only tended to develop these expiratory swings when breathing became unstable and/or flow limited. Whatever the case, certainly an interesting individual. Perhaps I should talk about some of his data at a case conference....

That's the end of the news bulletin for this evening.