This is part of the MD Magazine® Peer Exchange, “Precision Medicine in the Treatment of Severe Asthma.”Click here for Segment 5 and learn about the role of biomarkers in the evolution of asthma.
Peter Salgo, MD: We have come back to sort of lumping asthma together as a giant meatball of wheezing. Let’s take it apart. Let’s parse this out. It’s a heterogeneous disease. How do you start discussing different kinds of asthma and different triggers?
Neal Jain, MD: We’re starting to see and understated a lot more. I go back to the initial asthma work that was done in the 1950s. If you look back, there are some good data from the 1950s that suggested that we knew that if you had eosinophilic inflammation, you were apt to respond to corticosteroid therapy. We didn’t know how to look for it adequately. Biopsy studies and all kinds of things were done. We’re now at the point where we’re seeing these biomarkers. We’re understanding more about the heterogeneity of the disease. In a basic sense, there are these sort of 2 subtypes of asthma—this eosinophilic, allergic, T2-high type of disease, or elevated Th2 inflammation; and this T2 non—T2-high condition, which I would say is more of a trash bag or trash can diagnosis with a lot of different conditions...
Peter Salgo, MD: A lot of our asthma patients are really pleased to hear you describe them that way.
Neal Jain, MD: I think we’re learning more, and we’re starting to understand that if you don’t have this Th2-high disease, it’s unknown how to manage it.
Peter Salgo, MD: We hear about adaptive versus innate immune responses. What’s that?
Neal Jain, MD: That’s a tricky one. As our understanding of asthma pathology and heterogeneity is evolving, we’re also understanding that these are highly connected. We used to have this idea that IgE [immunoglobulin E] and allergic responses were really fundamental to this process. And now we’re understanding that a lot of the innate parts of our immune system (dendritic cells, antigen-presenting cells, type 2 innate lymphoid cells, and epithelium) are interplaying to sort of cause that adaptive immune response. This happens in some individuals but not all.
David Rosenstreich, MD: Fundamentally, asthma is inflammation of the bronchial airways. The point is that inflammation can come from many different pathways. We used to think, “Well, you have either allergic inflammation or nonallergic inflammation.” But it’s much more complicated than that. The idea is that you can have allergic-mediated inflammation. You can have neutrophilic inflammation. You can have inflammation coming from inhalation of airway pollutants that will generate from epidermal cells, etcetera. There are so many pathways that generate the final common pathway, which is the inflammation.
Peter Salgo, MD: Let me run down some very common factors that people see in their patients. And then I’d like to try to assess them in terms of their impact on asthma. Age of onset—important or not important?
Raffi Tachdjian, MD: It is quite important because we tend to see more Th2-high types of phenotypes in the younger population. As we know, 75% to 80% of asthma in that group is allergic in nature. That kind of helps us with the mechanism and helps us to understand the pathophysiology.
Peter Salgo, MD: What about an exacerbation history?
David Rosenstreich, MD: Past history is the best predictor of future behavior.
Peter Salgo, MD: What about triggers?
Neal Jain, MD: To an extent, it is seemingly, increasingly clear that viruses are one of the most fundamentally important triggers among asthma. It probably doesn’t matter what type of asthma you have, but exacerbations seem to be driven by viruses.
Peter Salgo, MD: Obesity? Body habitus?
David Rosenstreich, MD: The trick is that people should pay attention to what is predictable. When you have an asthmatic patient who comes down with a cold, you pretty much know that their asthma is going to be worse 4 to 7 days later. You have to prepare them for it. You have to educate them. You have to be prepared for it.
Neal Jain, MD: That can lead to exacerbations. But then you also have to take into account, as you had mentioned, allergens and allergies. In that younger population, especially, allergies are a driver of symptoms. For example, consider the kid who is playing soccer, who is allergic to the grass, who goes out and plays in the grass. This kid has an asthma attack because he or she is exposed to high amounts of grass.
David Rosenstreich, MD: But in terms of prediction, here in the Northeast, when the tree pollens start coming up, the asthma emergency department visits skyrocket. We can tell a patient that they’re going to get sick every year when the pollen is up. What they don’t understand is that at least here in the Northeast, there’s pollen when there’s snow on the ground. And so they say, “Well, it’s February. It can’t be from my allergies.” You have to, as a physician, educate them and say, “Look, every February the pollen goes up. You’re going to have a problem. Make sure you’re taking your controller medicines.”
Peter Salgo, MD: Obesity—does it matter?
Neal Jain, MD: Absolutely. When we talk about those different phenotypes of asthma, we see that there are those who have noninflammatory types of asthma that seem to be driven by obesity. And so I think that is a factor.
Peter Salgo, MD: We’ll get back to that because I’d like to talk about weight loss as therapy. We mentioned eosinophils, but what about neutrophilic inflammation?
Neal Jain, MD: There are some interesting data coming out about that as well. How we manage it—we don’t know. How you identify it is another question. There are some initiatives looking at chronic azithromycin therapy or other types of therapy in these people who have neutrophilic, primarily infection-driven asthma.
Peter Salgo, MD: Are there any phenotypes out there that will drive you directly to change your management therapy or recognize different types of asthma?
David Rosenstreich, MD: Well, the major phenotype that we can easily measure is eosinophilia. High levels of eosinophils in the blood indicate the allergic phenotype—the Th2-high phenotype. They’re the people who are going to respond to inhaled steroids and oral corticosteroids and respond better to many of these new biologics. So the single best biomarker that we have, that everybody can take advantage of, is blood eosinophilia.
Neal Jain, MD: I don’t know that I would agree entirely with that, only because I think that blood eosinophils are highly variable over time. I think it also depends, to an extent, on severity—looking at other biomarkers like FeNO [exhaled nitric oxide], IgE, allergen, and sensitivity. All those things, as a composite, especially once you get to higher levels of therapy, are important biomarkers to help identify…
David Rosenstreich, MD: But in terms of the primary care physician, if you have a single biomarker that you want to rely on, you should make sure you’re getting eosinophil counts.
Neal Jain, MD: Especially in individuals who are not on therapy, I think that is a helpful one.
Transcript edited for clarity.