HAPE Study

[Eric Carter]

Hi Everyone,

 

I am a MSc Student up in Vancouver at UBC. I was hoping to share a few details of my research and find some potential participants.

 

I am very interested in what makes some individuals susceptible to High Altitude Pulmonary Edema (HAPE). Right now, the best way we have of predicting if you will get HAPE is if you had it on a previous occasion. Beyond this, we don't really know a whole lot for sure. Evidence suggests that high blood pressures within your pulmonary circulation are caused by altitude, cold, and exertion. These pressures literally squeeze fluid (blood) into the airspace of the lungs.

 

Last week, I began collecting data in two participants at Vancouver General Hospital. During a prior visit, basic medical information was taken and baseline VO2max (maximal work capacity) tests were completed.

 

Upon arrival at VGH, participants met our study team which included two medical doctors overseeing testing, three graduate students administering tests, two undergraduate subject handlers, and one technologist.

 

Then they performed a series of lung function tests using a Spirometer:

 

 

Above is a test measuring the Diffusion Capacity of Carbon Monoxide (DLCO). This is a good estimate of how well oxygen is able to go from the airspace of the lung, into the bloodstream. As you can imagine, in the case of HAPE, where fluid is occupying the airspace, oxygen has a hard time of getting to the bloodstream.

 

After this, participants undergo a pre-test computed tomography (CT) scan. This is a little different from your average scan and takes abut six minutes. Rather than scan the entire lung, we just look at three thin slices. Within these slices, we are able to evaluate the density of the lung tissue. Again, in the case of HAPE, we would expect more fluid and therefore, increased tissue density.

 

After all the pre-testing, participants head to our stationary bikes for a 45 min interval workout. This is designed to be HARD! You can see they are enjoying it:

 

 

We use a very cool bike called a Velotron. In the next picture you can see the laptop running the bikes. With the software we can monitor power output (watts) as well as all the other readouts you would see on a fancy bike computer. You can also see the subjects wearing monitors which read their heart rate and blood oxygen saturation.

 

 

After finishing the workout, the participants repeat all the pre-test measures. Below in the background you can see someone chest deep in the CT scanner. In the foreground our technologist is monitoring the computer screen which shows the real-time CT image. You can make out her lungs, heart, and spine.

 

 

After this, we wrap it up for the night!

 

My overall goal is that someday, simple exercise and a series of inexpensive lung function tests could predict the likelihood of experiencing HAPE. I also hope that the research provides some insight into the pathophysiology of high altitude illness.

 

Also, if you are interested in this research, check out http://www.environmentalphysiology.ca We are continually conducting experiments into high altitude illness.

 

Thanks!

 

-Eric

ecarter1 (@) interchange.ubc.ca

Edited March 18, 2011 by Eric Carter

[Chad_A]

Looks like a cool test to do; too bad I haven't had HAPE (yet). Good luck in your ventures.

[Rad]

Interesting. I doubt a CT scan administered by a radiologist is going to count as cheap by any measure. Not to mention concerns about radiation exposure. Blood or genetic markers would be better if you can find any. But I'm all for scientific experiments. Good luck.

[colt45]

That's an awesome project!! I imagine that the CT scan would not make it to the final HAPE susceptibility testing protocol for multiple reasons, although I have heard that there are simplified versions of spirometry that are cheap and that can be easily performed in a non-hospital setting.

 

For the purposes of the research study, it should be interesting to see whether the various physiologic parameters that are measured end up correlating with anatomic findings on the CT. Let us know what you find!

[Eric Carter]

You are right about the cost of the CT scans. They are expensive. Luckily I am supported by several grants. Regarding radiation, it is approximate to 1/2 the yearly background radiation in Vancouver. A trip to Denali would likely increase your risk of cancer much more.

 

I didn't mention the genetic aspect but we are taking DNA samples (using a cheek swab) from subjects as well. Several genes have been associated with HAPE and we will look to see if any of these are overrepresented in our "susceptible" group.

 

Colt45 has the right idea, but in reality, using any of my data to test for susceptibility is pretty far down the road. At this point, we are really trying to figure out what is going on.

 

I will definitely keep you posted.

 

Thanks!

 

-Eric

Edited March 18, 2011 by Eric Carter

[OlympicMtnBoy]

Cool, does this tie in to the studies Andy Luks has been doing down here? I went in for one of his studies but that was using ultrasound and measuring heart valve blood velocity. I ended up not being a candidate for the study but it was still kind of fun for the first round.

[iluka]

Cool, does this tie in to the studies Andy Luks has been doing down here? I went in for one of his studies but that was using ultrasound and measuring heart valve blood velocity. I ended up not being a candidate for the study but it was still kind of fun for the first round.

 

Completely independent study going on up there.

[iluka]

I have heard that there are simplified versions of spirometry that are cheap and that can be easily performed in a non-hospital setting.

 

There are certainly many simple ways to measure pulmonary function using spirometry devices but none of the information you get from spirometry has any utility in predicting who is susceptible and not susceptible to HAPE or other forms of altitude illness.

 

The key thing with people who get HAPE is that their pulmonary artery pressures (i.e., the blood pressures in the lungs) rise much higher in hypoxia (or exercise at sea-level for that matter) than people who are not susceptible to HAPE. Why that occurs is not clear but it's this marked rise in these pressures that is critical to the development of HAPE. Under these high pressures, fluids leaks out of the pulmonary capillaries into the lung tissues.

 

Finding an easy way to predict whether someone will have these pulmonary artery pressure responses has been a challenge.

 

It will be interesting to see the results of Eric's study.

 

[mneagle]

A few comments:

 

“Right now, the best way we have of predicting if you will get HAPE is if you had it on a previous occasion. Beyond this, we don't really know a whole lot for sure.”

 

Semi-true. We know for a fact that healthy young men who ignore advice about acclimatization are at much higher risk of getting HAPE. As this characterizes the majority of people on this site, you’ve come to the right place for high risk subjects.

 

 

 

“Above is a test measuring the Diffusion Capacity of Carbon Monoxide (DLCO). This is a good estimate of how well oxygen is able to go from the airspace of the lung, into the bloodstream.”

 

Mostly not true. Under normal physiologic conditions (except at extremely high altitudes), oxygen uptake is mostly perfusion limited, as opposed to diffusion limited.

 

 

 

“Again, in the case of HAPE, we would expect more fluid and therefore, increased tissue density.”

 

True, but heavy exertion has been shown to increase lung tissue density all by itself due to increased lung blood volume. This is at least one reason why DLCO also increases (transiently) due to exercise.

 

 

 

It seems what you are really doing is establishing baseline stats at low altitude for your subjects. To make any predictions about susceptibility to HAPE, the logical next step is to repeat your protocol at high altitude or in a hypobaric chamber. I’m pretty sure that a lot of this stuff has already been studied at that mountaintop lab in Europe (the name of which I can’t recall but I’ll bet Andy knows it). I would also be very cautious about potential selection bias and applying your findings too broadly. The risk factors for average people vs. those for established high altitude climbers may be very different.

 

Welcome to the fold.

 

[mneagle]

Found a reference:

 

Physiology experiment at Capanna Regina Margherita

 

Check out Google images of Capanna Regina Margherita. That's my idea of a proper high altitude lab.

[Eric Carter]

Thanks for the comments, hopefully my quotes worked so see below for my response and please correct if I am wrong.

 

Semi-true. We know for a fact that healthy young men who ignore advice about acclimatization are at much higher risk of getting HAPE..

 

Absolutely right - but these people are high-risk for a different reason presumably. This is a psychological factor rather than a physiological one. I am looking for the difference between the two climbers who acclimatize together and one is sick while the other is fine. As far as purely predicting altitude sickness you are definitely right, rate of ascent is a pretty good indicator.

 

Mostly not true. Under normal physiologic conditions (except at extremely high altitudes), oxygen uptake is mostly perfusion limited, as opposed to diffusion limited.

 

I'm not sure what you referring to when you say not true though my explanation of DLCO was admittedly short. DLCO is the rate (in ml*min*mmHg) at which CO can diffuse into the blood. Work by Ogilvie and Roughton (and others) determined that DLCO consists of two components, the capillary blood volume and the membrane diffusion. The test we use allows us to partition these components and determine if a change in DLCO was caused by the membrane or the volume component.

 

Many factors affect DLCO by changing the blood volume component including exercise and even body position (like you said, a change in perfusion) however interstitial or alveolar edema would effectively increase the membrane thickness and decrease permeability. In the case of my study, I hypothesize a small amount of sub-clinical edema will occur in susceptible subjects. This would be confirmed by a change in DLCO and its membrane component and no corresponding change in the blood volume component. Hopefully will have some data to share on this soon.

 

True, but heavy exertion has been shown to increase lung tissue density all by itself due to increased lung blood volume. This is at least one reason why DLCO also increases (transiently) due to exercise.

 

Absolutely, that is why I am comparing the HAPE susceptible group to the HAPE resistant group. The imaging methods we will use are designed to look specifically for extravascular water. This has already been shown to increase by O'Hare and McKenzie in healthy trained individual but again, this study is novel in that it will compare susceptible to non-susceptible.

 

It seems what you are really doing is establishing baseline stats at low altitude for your subjects. To make any predictions about susceptibility to HAPE, the logical next step is to repeat your protocol at high altitude or in a hypobaric chamber.

 

I would also be very cautious about potential selection bias and applying your findings too broadly. The risk factors for average people vs. those for established high altitude climbers may be very different.

 

Your pretty much right on there. When it comes down to it, at sea level, there must be something physiologically different than the fit climber who develops HAPE repeatedly despite a (normally) proper ascent plan and their healthy partner. This is what I am interested in. And as Andy said, more specifically: why do some people develop these higher pressures?

 

I may have been too hasty to add the bit about predicting susceptibility but I think it is important to have a goal to work toward. While I may have made it sound like a study goal, it would probably be better to call a career/lifetime one.

 

There are lots of directions to go from here. Repeating in hypobaria, with a right heart catheter, examining intra-pulmonary shunt, factors affecting endothelial permeability - all good PhD options

 

I would be happy to chat more so feel free to send me a message.

 

Eric

 

[mneagle]

Mostly not true. Under normal physiologic conditions (except at extremely high altitudes), oxygen uptake is mostly perfusion limited, as opposed to diffusion limited.

 

I'm not sure what you referring to when you say not true though my explanation of DLCO was admittedly short. DLCO is the rate (in ml*min*mmHg) at which CO can diffuse into the blood. Work by Ogilvie and Roughton (and others) determined that DLCO consists of two components, the capillary blood volume and the membrane diffusion. The test we use allows us to partition these components and determine if a change in DLCO was caused by the membrane or the volume component.

 

Many factors affect DLCO by changing the blood volume component including exercise and even body position (like you said, a change in perfusion) however interstitial or alveolar edema would effectively increase the membrane thickness and decrease permeability. In the case of my study, I hypothesize a small amount of sub-clinical edema will occur in susceptible subjects. This would be confirmed by a change in DLCO and its membrane component and no corresponding change in the blood volume component. Hopefully will have some data to share on this soon.

 

I was simply pointing out that your statement that DLCO is a good estimate of oxygen's ability to move from the airspace into the blood is not correct. Oxygen and carbon monoxide uptake are very different in the lung. Because of the enormous "sink" for CO in the blood, it is mostly diffusion limited while oxygen is perfusion limited except at very high altitude where diffusion can become a factor. DLCO measures CO uptake and estimates alveolar:capillary surface area but not oxygen uptake.

 

Keep in mind, if you have a pneumonectomy your DLCO will more or less be cut in half but the remaining lung's ability to transport oxygen into the blood stream is relatively unchanged from baseline.

 

This is fun stuff to think about. Not being in academics, I don't get to spend much time thinking about the difference between diffusion and perfusion limited gases anymore.

[Maine-iac]

Good article on pulmonary altitude issues:

 

MG Levitzky's Pulmonary Physiology- CH 11 "The Respiratory system under stress"

 

I would link you guys, but I'm logged on through a university so the link won't work.