Spirometry Reference Values Mismeasurement for Women

Podcast Transcript

Raed Dweik, MD:

Hello and welcome to the Respiratory Exchange Podcast. I'm Raed Dweik, chairman of the Respiratory Institute and Cleveland Clinic. This podcast series of short, digestible episodes is intended for healthcare providers, and covers topics related to respiratory health and disease. My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, critical care, sleep, infectious disease and related disciplines. We will share information that will help you take better care of your patients today as well as the patients of tomorrow. I hope you enjoy today's episode.

Amy Attaway, MD:

Hello everyone. My name is Amy Attaway. I'm one of the pulmonary staff at Cleveland Clinic, and I'm very excited to introduce Dr. Philippe Haouzi, who we're going to having our podcast discussion with. So Dr. Haouzi is the medical director of Pulmonary Function Testing Lab, and he's also a physiologist who's very interested in the physiology of breathing. And he's a big part of the research community looking at that. And he has research commentary coming out in Lancet Respiratory. He's going to be talking more about that, but basically what they did is they reanalyzed different reference values for lung volumes comparing men and women. It's a very interesting and compelling article where he considers what the clinical implications of that is, which we're going to talk about.

And so as medical director of a pulmonary function lab, we do these tests on patients, almost 100,000 tests per year to measure their lung function or lung volumes, and we use Global Lung Initiative reference values. A lot of his commentary is considering the impact of sex on these reference values. So thank you, Dr. Haouzi, for being here. Why don't you tell us basically the context of the commentary and what it means to have reference value for human subjects?

Philippe Haouzi, MD:

Thank you, Dr. Attaway. As you mentioned, the measurement of lung volume is important information that we use routinely by pulmonologists to evaluate lung diseases and for the diagnosis as well. So the problem is always the same and has always been the same since we have measured this lung volume. There are different lung volumes, of course, that we can measure, and the question is: is a volume normal or low? If it's low, then it will affect a disease, needed treatment, et cetera, et cetera.

So to do that we use reference values that have been established in a large population of supposedly normal individuals all over the world. And as you mentioned in your introduction, this initiative is called the GLI, or Global Lung Initiative where all these data are available. And until very recently when we measured lung volume, we compare this lung volume to these reference values according to the age of the patient, the height of the patient, as you are taller, you have higher lung volume, if you get older your lung volumes are going down.

And two other parameters. One is the race and the other one is sex. Women versus men have different lung volumes according to the GLI regression.

Amy Attaway, MD:

Right, right. And so I think one of the really fascinating things that kind of laid the groundwork for your analysis of sex is that they've recently called to question the impact of race on these reference values. Do you wanna talk a little bit more about that?

Philippe Haouzi, MD:

Yeah, exactly. So, there was a debate going on in the medical community about using race as a criteria for lung volumes. We have realized over time is that, first of all, it's very difficult of course to define race. So, the criteria that were used to differentiate between these different groups were based on the color of the skin or the geographical origin of the patient. So, it was not very clear criteria.

And we also realized that the variability within the whole population is larger than the variability between each group. So eventually what happened is that a few months ago there was a decision made at the ATS, validated by the ERS, the European Respiratory Society, to get rid of race. So what we have now is that lung volumes, or predicted values for lung volumes according to age, height, and sex.

And the question is that when we look at the population, comparing the population of women and men, we see a very similar pattern to the pattern that was there when people were using race, meaning that if you compare the population describing the GLI criteria you immediately notice that a large number of women are above the, at the limit of normal, meaning well above what you expected for men. And the vast majority of women are above the lower limit of normal.

I mean that we don't see clear evidence why a given woman should be expected to have lower value than men. That's what we have now. So right now the only difference between the two groups is that women have 10 to 20% lower predicted values.

Amy Attaway, MD:

And I think that's, in your research commentary you actually look at our Cleveland Clinic population and you analyze using that. Do you wanna talk a little bit more about that?

Philippe Haouzi, MD:

Yes, so, again, what we saw is that the vast majority of women would not qualify for lower predicted values. There's no rationale for that.

Amy Attaway, MD:

Mm-hmm.

Philippe Haouzi, MD:

Also when we look at the literature how people would justify a difference in lung volume, the data are not very solid. There is no clear evidence that even if there are some differences in some group of women versus men in terms of the anatomy, which needs to be really demonstrated at this point, we, it's still not clear. But let's say the data are there published in the literature... well, it does- we don't even know if this would translate into a measurable difference in lung function.

Amy Attaway, MD:

Hm.

Philippe Haouzi, MD:

So again coming back to our first comment that the popular, vast majority of women would not have lower reference lung volume than men. So for this reason we think it's time to, just like, it was done for race that the different society-

Amy Attaway, MD:

Mm-hmm.

Philippe Haouzi, MD:

... the ATS, the ERS, look at this question and re-address this question to know what to do with these numbers. Or these reference values.

Amy Attaway, MD:

Yeah, I think we were talking earlier about what the clinical implications were. So you gave the example of maybe a patient with COPD, or chronic obstructive pulmonary disease, like, what that would mean-

Philippe Haouzi, MD:

Yeah. So, for example, if we take this population where one volume is of interest like FEV1, the forced expiratory volume in one second. It's used as a criteria for the severity of the disease or even for the diagnosis sometimes. So women would need to go to a much lower level of FEV1 to be diagnosed as being, you know, obstructive. Same thing if you want to introduce a new treatment, this may delay the treatment. So there are implications. 10 to 20% is not a big difference but it is enough if one used very strict cutoff to mischaracterize a lung problem. So again, you know, for all of these reasons, it may have an important implication in women when we consider, you know, a diagnosis or the treatment of an obstructive disease.

Amy Attaway, MD:

Right, right. And so I think, we were talking about the next steps. You mentioned that we should maybe be reconsidering these reference values, what it could mean at the society level. Is-

Philippe Haouzi, MD:

Absolutely, uh, doctor. We are at... At this point it's important at least to revisit this question. And there should be a clear statement whether we should continue using lower reference values, and if so, why, from the society, different societies, you know, or revisiting on a regular basis our, the recommendation for normal values. Or if we should just get rid of them, or modify these reference values, and if so to which level. So until we do that, we still are stuck with these differences.

I think one of the implications is that, which is true for every test we do, we should avoid using too strict a cutoff when it comes to very important decisions. And, again, this is a very trivial comment but I think the clinical judgment should the one dictating, you know, both diagnosis and treatment using these lung volumes as a help or as a support when the decision is not clear. But forming our entire reasoning around strict cutoff may lead to disastrous decisions.

Amy Attaway, MD:

Right, exactly. I think we were talking about that, you know, lung volumes that we measure, they're a tool that can help with your clinical judgment. But if you have a patient who is borderline or maybe just above a cutoff that maybe we should consider that the, where these reference values are being revisited, they're subject to debate and that ultimately, we should really put the context of the test and what the best decisions for our patients-

Philippe Haouzi, MD:

Yeah, absolutely.

Amy Attaway, MD:

... right?

Philippe Haouzi, MD:

A 10-, 20% difference between a man and a woman can make the difference between someone who is obstructive or not. So, based on the current evidence that have produced in literature, it's not clear that we should keep this difference.

Amy Attaway, MD:

Okay. Great! We're so excited to see this commentary coming out in Lancet Respiratory. Do we have a date?

Philippe Haouzi, MD:

The next issue, which would be in May [2024].

Amy Attaway, MD:

Oh, great. And then I think just the, thinking about future implications at the society level for our patients, I think this has just been a really wonderful conversation to kind of put all that in context. Thank you so much, Dr. Haouzi.

Philippe Haouzi, MD:

Thank you, Dr. Attaway.

Raed Dweik, MD:

Thank you for listening to this episode Respiratory Exchange Podcast. For more stories and information from the Cleveland Clinic Respiratory Institute you can follow me on Twitter [X] @raeddweikmd.