Examining the Heterogeneity of COPD

Peter Salgo, MD: Let’s take a look at chronic obstructive pulmonary disease (COPD) for a moment. If you look at individuals, it’s a heterogeneous group. The disease seems to present in a heterogeneous way, right? You’ve got rapid versus low progression. You’ve got mild to severe symptoms and variability. How do you parse all of this out, Byron?

Byron Thomashow, MD: Part of the problem is that for far too long, we’ve looked at COPD cases as the same and have treated it all the same. That’s clearly not the case. We would never, at this point in time, view all cancers as the same. We shouldn’t be viewing all COPD cases as the same. As you said, Peter, there are frequent exacerbated and infrequent exacerbated scenarios. There are eosinophilic exacerbators. There are the chronic bronchitis or bronchiectatic patients. The subsets deserve specific therapy that is aimed at them.

Earlier, Jim mentioned lung volume reduction surgery. Not all emphysema is the same. We’ve learned that for those patients who have upper lobe—predominant emphysema, if they meet certain criteria, they may very well be candidates for either a surgical procedure or perhaps a bronchoscopic procedure that can potentially improve quality of life and survival. We need to look at the individuals, and we need to move away from treating them all the same way. I think that’s going to be a part of the focus, going forward. I assume, Antonio, that GOLD [Global Initiative for Chronic Obstructive Lung Disease] is looking at that, as well?

Peter Salgo, MD: When you take a look at COPD, I was taught that COPD was COPD. One size fits all. “Here’s how you treat it.” It’s probably been detrimental, right?

Barbara P. Yawn, MD, MSc, FAAFP: I think it has been detrimental to assume that it looks the same in everyone and that you should start the same in every patient. In primary care, “frequently the same” means that you start with the same drugs that you start with in asthma, for example. And we really have to highlight that asthma and COPD are very different. The primary therapies are very different. We also need to start being honest about things. The diagnosis that I dislike the most is acute bronchitis. People keep having acute bronchitis. Maybe they’re having exacerbations of their COPD. We can’t just put a Band-Aid on what’s happening today. We need to be thinking about what this means in the context of the patient’s whole course.

James F. Donohue, MD: In addition to what Barbara was just saying, one of the things that has really been leading research is the idea that people achieve a certain level of lung growth. They come into adulthood, and some lose lung function at a predictable rate. Others, if they smoke, lose it more rapidly. It turns out that life events occurring in utero, in early life, or maybe even with asthma have a profound effect on what your lung function is by age 50. We have many people who have normal lung growth here, who then smoke and lose function. And we have this other very important group who never achieved anywhere near normal lung function. They have much less to lose, and they can have much more severe disease. We’re only beginning to touch on the natural history of this disease—trying to learn about these different patterns and trying to design therapies and remedies for them.

Peter Salgo, MD: And, again, I want to come back to this normalization of symptoms.

James F. Donohue, MD: Correct.

Peter Salgo, MD: Patients tend to pull back, right? They’re not going to tell you what’s going on unless somebody asks them about it, right?

Antonio Anzueto, MD: Peter, the important thing now is that we have cohorts. We have data. We have patient information that we didn’t have 20 years ago, to better understand the disease. We look at COPD and genes. We are learning that it’s probably not about how many packs you smoke or for how long you smoke. We have Uncle Joe. He smoked. He was 90 years of age, and nothing happened with him. But, you know, Uncle Joe probably has good genes or something.

Peter Salgo, MD: We’ve all seen that story on the local news of the woman who’s 107 years old. They say, “To what do you owe your longevity?” She says, “Two packs of cigarettes and good scotch.” Everyone else who did that is dead at age 50, but she made it. That’s a bad role model, don’t you think?

Barbara P. Yawn, MD, MSc, FAAFP: For many years, women didn’t get COPD. Maybe this was because of who we studied. But, women do get COPD. They get COPD at a younger age. It is more severe. It progresses more rapidly, in general. And so, you need to think about women and COPD as almost a phenotype. We need to be serious about identifying those women who are just as bad as men, who say, “Oh, nothing’s going on. I’m just fine. I’m just out of shape.”

Peter Salgo, MD: If anything, in my clinical experience, women are worse. They’re called upon to provide all of the support, and they can’t admit that they can’t do it. The kids have got to go to school and, “We’ve got to do this.” And, “You’ve got to do that.” They’re not going to give that up.

Barbara P. Yawn, MD, MSc, FAAFP: That’s right. And so, we need to really be very supportive.

James F. Donohue, MD: That’s reminiscent of the scenario from a few years ago where a group of physicians were given patient characteristics and were asked, “Is this asthma or COPD?” And dependent on the gender with this characteristic, if it’s a man, it’s COPD. If it’s a woman, it’s called asthma. That can lead to changes. You might use a drug like a leukotriene antagonist in a woman. That’s not good for COPD, for example. Gender is extremely important.

Byron Thomashow, MD: There’s even some evidence suggesting that women are more susceptible to some of these factors, whether it is cigarette smoke or biomass fuel. As Antonio was saying, biomass fuels are a staggering issue around the world. Much of that exposure is with women and children.

Barbara P. Yawn, MD, MSc, FAAFP: Also, their comorbidities are at a higher rate. If you have all of these exposures, you are also more likely to get heart disease. Osteoporosis is certainly more common in women, especially in those who are postmenopausal. Depression and anxiety are also more common in women. So, comorbidities are, perhaps, even more important in women.

Peter Salgo, MD: I was trying to get at that, because depression is always listed in all of these bullet points with COPD.

Barbara P. Yawn, MD, MSc, FAAFP: Yes.

Peter Salgo, MD: And osteoporosis is listed, all the time, in all of these bullet points. Is it causal? Is COPD causal for these two? Or, are they fellow travelers? Do we know?

Barbara P. Yawn, MD, MSc, FAAFP: I don’t think we entirely know. I think that inflammation, as you commented on before, is very important. It affects all of these cases. I have to believe that depression and anxiety are made worse by the symptoms and the impact of COPD on your life, in addition to inflammation.

Transcript edited for clarity.