Asthma Phenotypes and Endotypes

Neal Jain, MD, FAAP, FAAAAI, FACAAI: You had mentioned, Brad, some different immune cells—type 2 [T2] innate lymphoid cells, eosinophils, mast cells. We’re starting to learn more about the roles of all these. I’m curious to know your opinion, Nic, regarding how these all play together. In my clinic, oftentimes I try to identify whether these patients have this steroid responsive, nonsteroid responsive, exacerbation prone, nonexacerbation prone types of asthma. And I think we’re all sort of, without maybe necessarily thinking about it, classifying our patients as T2 high or T2 low. If you see someone who doesn’t have that profile, do you immediately think that they have asthma or that there’s something else going on? How do you approach that?

Nicola A. Hanania, MD, MS: Well, Neal, for many years we thought about asthma as a 1-size-fits-all disease, and we know now it is a heterogeneous disease. As clinicians, we’ve seen patients who respond to 1 therapy versus the other. Patients can present late in the disease. I’m an adult pulmonologist, so I see patients who are older who never had asthma in their childhood but had asthma later on in life. And what drives the asthma in that population may be different from what drives asthma earlier on.

So now we have a new look at this old disease. And 1 way to look at it is clinically. How does it present? These are what we call phenotypes. A major phenotype, for example, is allergic asthma. This is a large population of asthmatics, and it starts early in life. But there are other phenotypes, and T2 low and T2 high may actually help if you use certain biomarkers. But clinically, how they present and the onset of the disease may help us sort of subdivide this disease.

And obviously, that may reflect a response to therapy. For example, in the T2-high bucket, we have the allergic asthma, the exercise-induced asthma, but we also have the late-onset, eosinophilic asthma. These are patients who are not allergic, but they have high eosinophils. That belongs to that population. On the other hand, in the T2 low, we have late-onset asthma that is noneosinophilic and is less responsive to treatment. Smokers with asthma and obesity-related asthma: These are some subtypes or clinical types. These are the phenotypes. But people are now saying, “OK, fine, phenotypes are good.” But within the phenotypes there are several other endotypes that actually reflect the mechanism of these phenotypes. And that’s probably where we need to go, to address targeted therapies. We’ll talk about that in a few minutes.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: And I think that becomes 1 of the big questions. Are you a grouper? Are you putting all these people together, or are you a splitter? And does that matter? I think that is sort of the question that all of us are challenged with, and we’re hearing a lot of buzz about that in our field. Is it helpful to sort of define, or is there significant overlap between these individuals who have allergic, eosinophilic, late onset, early onset. And these are the questions, I think, that we’re challenged with.

Nicola A. Hanania, MD, MS: I think with the mild population, or moderate asthma, maybe it doesn’t make a difference and treatment may be same way. But in more severe asthma, I think the splitters would win here.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Yeah.

Aidan A. Long, MD: I actually think that’s a really important point, and it’s driven in part by factors other than biology. It’s driven by factors such as cost. If there was not a cost issue, we might start splitting much earlier and going after individual phenotypes. But since some of these newer products come with an enormous expense, we tend to reserve them and start splitting in the severe group rather than mild and moderate groups. I agree with Nic on that.

Bradley Chipps, MD: And the question is, how far down the pharmacologic chain do you walk down before you decide a biologic is important? Do you add a third, fourth, and fifth long-term controller before you finally say that enough is enough and admit you need a biologic? I think that we’ll talk about that later, but it’s an important thing to keep in mind.

Transcript edited for clarity.