Relationship Between Intermittent Hypoxia, COPD and Comorbidities (Podcast)

Intermittent hypoxia in patients with chronic obstructive pulmonary disease (COPD) may matter more than clinicians once thought. A recent episode of Respiratory Exchange delves deeper into the connection between the conditions.

Patients with persistent hypoxia, defined as having an oxygen saturation of less than or equal to 88%, are known to have an increased risk for mortality. But the association with increased risk for mortality with intermittent or nocturnal hypoxia is not as clear.

“There seems to be a clear association of mortality if they're persistently hypoxemic,” explains Amy Attaway, MD, a staff pulmonologist at Cleveland Clinic and the episode’s guest. “But other studies haven't shown that intermittent episodes really seem to cause increased risk for mortality or morbidity in our patients…I think there's a lot more to know about hypoxemia and how it can affect our patients, and what the impact is in more longer-term studies.”

But, while intermittent hypoxia may not clearly affect mortality, it may still impact several other comorbidities, such as muscle loss, frailty, cognition and reduced function. One of Dr. Attaway’s research focuses has been on sarcopenia in COPD patients.

“What we’ve found is that there seems to be a general shift in COPD patients, where a lot of the muscle fibers, which maybe were Type 1 before, will start shifting to Type 2,” she explains. “We're not really sure why or how that happens, but it's believed to be that oxygen is a pretty big stimulus, especially if you have low oxygen. One of our hypotheses that we study in our lab is that perhaps these episodes of intermittent hypoxia in our COPD patients are stimulating these fibers to shift from the Type 1to the Type 2 fibers.”

To learn more about the connection between COPD and hypoxia, click the podcast player above to listen to the episode now, or read on for a short, edited excerpt.

More Respiratory Exchange episodes are available at https://my.clevelandclinic.org/podcasts/respiratory-exchange or wherever you get your podcasts.

Excerpt

Dan Culver, DO (host): So, what you're saying is that some of the sarcopenia and muscle loss we see in patients, and I think you noticed this even in patients who have a normal body mass index, when you look at their lean muscle mass, it's low. That's replaced a lot of the time by adipose tissue. And so, I suppose that that explains some of their functional incapacity, loss of exercise tolerance. Then I wonder what the role of pulmonary rehab is and the things we've kind of traditionally used to try to combat that. Is that not as effective if you have intermittent hypoxia?

Dr. Attaway: I think that's a great question. That's actually something that we're hoping to study further. It really hasn't been looked at before. But there is clear evidence in the literature that with pulmonary rehabilitation, there are responders and non-responders. Some patients do great with pulmonary rehab. They regain their muscle. They improve their physical performance and their functional capacity. And then some patients just don't seem to respond.

This is after these studies have all adjusted for patients' activity levels — they adjust for sedentary behavior. That's an important compounder in any of these studies. But, yes, there's clear evidence of non-responders to pulmonary rehab, and that's one of the things we're hoping to study, and understand if maybe intermittent hypoxemia is impacting that.

Dr. Culver: So, if I understand correctly, in people who have intermittent hypoxia, number one, we should be suspicious about people with differently pigmented skin and look a little bit more deeply, perhaps with blood gas or other techniques. But in people with intermittent hypoxia, it's not as clear-cut as just measuring mortality, that there are other long-term effects on various organs, including the muscles, and that what you've shown is that that has a direct effect on the myocytes, both the breathing muscles and the non-breathing muscles like the limb muscles, in a way that leads to decreased functional capacity and that seems to be oxygen-dependent. Is that a fair exposition?

Dr. Attaway: Yes, I'd say definitely. We were able to look at this in patients in a large sleep registry, which is Dr. Mira's registry, looking at patients with COPD who had nocturnal hypoxemia. They had reduced muscle mass and physical performance. This was an associative study. Then, at the bench, when we looked in the lab, we looked at the impact of intermittent hypoxia on skeletal muscle cells. We also looked at mouse models, and it did seem to impact performance and muscle mass. There were reductions in muscle mass. And it seemed to be clearly affected by episodes of the intermittent hype, or intermittent hypoxia model.

Dr. Culver: So, potentially, this is a pretty important observation insofar as I think we've traditionally dismissed intermittent hypoxia as a nuisance or a measurement artifact. Like many other things in medicine, we don't try to normalize everything back to how it was when we were 18. But this may have more profound, systemic consequences than we recognized before.

Dr. Attaway: I really do think that it's an important thing to recognize and to look at in our patients. I think COPD is a disease of comorbidities, and we don't have a clear explanation for why patients with COPD have more bone loss and muscle loss. They're at an increased risk of heart disease. It can affect almost every organ of your body. And in the past, a lot of times, we thought there was an inflammatory impact from COPD. But then we see our patients who maybe don't have evidence of a lot of inflammation. They're not having frequent exacerbations. But they still show this profound muscle loss, profound bone loss, and heart disease over time.

So, I think there's a lot more to study. I think it's important to understand what could be causing that. And one of our suspicions in our practice is that intermittent hypoxia could be playing a role in increasing the risk for these comorbidities in COPD.