Identifying the Biomarkers for the Treatment of Severe Asthma - Episode 1

Type 2 Inflammation in Asthma

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Hello, and thank you for joining this MD Magazine® Peer Exchange titled “Identifying the Biomarkers for the Treatment of Severe Asthma.”

We now have a better understanding of the type 2 asthma pathway, including allergic and eosinophilic asthma, which are the causes of most asthma. In the last 2 decades, there has been a dramatic growth in the biologics market for the treatment of asthma. This highly selective treatment approach focuses on different inflammatory pathways and blocking those pathways.

We’ll dive into a closer look at the different biologics approved in the United States and their mechanisms of action. We will also gain a better understanding of identifying biomarkers that might aid in phenotyping to help individualize treatment for these patients.

I am Dr. Neal Jain. I’m the director of research at Arizona Allergy & Immunology Research. I’m also a co-owner of Arcadia Allergy & Asthma and San Tan Allergy & Asthma in Phoenix, Arizona. I’m a practicing allergist and immunologist clinician with an interest in severe asthma and biomarkers for the evaluation of asthma.

Participating today on our panel are: Dr. Nicola Hanania, associate professor of medicine and the Pulmonary, Critical Care, and Sleep Medicine Department at Baylor College of Medicine in Houston, Texas. He’s also the director of the Airways Clinical Research Center at Baylor College of Medicine in Houston, Texas, and the director of the Asthma and COPD Clinic at Ben Taub Hospital in Houston, Texas.

We also have Dr. Bradley Chipps. He is the former president of the American College of Allergy, Asthma & Immunology, and he is in practice in Sacramento, California.

Lastly, we have Dr. Aidan Long, an associate professor of medicine in the Department of Medicine at Massachusetts General Hospital in Boston, Massachusetts. Thank you for joining us. Let’s begin.

So to start off this discussion, I think it’s important to sort of take a step back and think about asthma from a more basic standpoint, before we get into a discussion about biologics and biomarkers. So I thought it might be helpful to just sort of start off and think a little bit about what happens pathophysiologically when we think about asthma. Aidan, do you want to lead us off?

Aidan A. Long, MD: Yeah. So asthma is a disease of airway obstruction—the airways that carry the air from outside to the alveoli get constricted, with a combination of muscle spasms. And predominantly, these days, we realize it’s a disease of inflammation. This is inflammatory cells getting in there. There’s swelling. There’s mucus production. So it’s a combination of 3 things: smooth muscle contraction, swelling, and increased mucus production. Together these things cause obstruction to the airways. The patient experiences difficulty moving air in and out—more moving out than in. When we breathe in, we have extra muscles that help us. When we breathe out, we are relaxed. So there’s nothing to help us breathe out. So it’s a disorder of moving air in and out. It feels uncomfortable. There is chest tightness, wheezing, and shortness of breath.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Sure. And so building upon that, we’ve learned a lot about the pathophysiology, obviously, in the last few decades. We started to begin to think about asthma as, sort of, what’s old is new. But we started to think about asthma again in terms of different types of inflammation. And so Brad, I’m just sort of curious, we are hearing more and more about this idea of type 2 [T2] inflammation. I was wondering if you could share some thoughts on what that means, as far as type 2 high versus type 2 low and how you think about that?

Bradley Chipps, MD: Well, as we think about how airway inflammation is modified by either a biologic or a steroid, we think about type 2 as mainly the poster child for that, driven by Th2 [T helper cell 2] lymphocytes or ILC2 [type 2 innate lymphoid cells]. They all drive increased eosinophil activity, which is a marker of disease activity or a disease that is potentially helpful with steroid treatment or with 1 of the currently approved biologics. The flip side of that, of course, being low T2 asthma, which is primarily, at least in part, neutrophil driven, which tends to be more refractory to therapy and is a bigger challenge for all of us. Now, whether T2 asthma is 50%, 60%, whether it stays persistent over time, there’s literature on both sides of that fence. And so I think we have to blend all those things together as we try to identify the patient who will respond by decreasing exacerbations, which are the reasons that all these currently available biologics were approved. And that is a big challenge we have. That’s why we all have a job.

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

Aidan A. Long, MD: I was struck by a study from a long time ago. In the 1920s, Francis Rackemann, who was the head of allergy at Massachusetts General, the first allergy clinic in the United States, published a paper saying, “I think there are 2 types of asthma. There’s extrinsic asthma and intrinsic asthma.” And the extrinsic he was referring to was allergic asthma, where outside triggers are driving it. I’m curious these days, because we have a similar dichotomy. We call it T2 high, which very largely seems to overlap, although not completely, with allergic asthma; and then the intrinsic, which we’re calling T2 low. So I think it’s intriguing. How far have we come?

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

Aidan A. Long, MD: Or have we come?

Bradley Chipps, MD: And the role of infection. People used to use a combined bacterial vaccine to treat asthma and try to downregulate infection, and now we’re gaining more information, and infectious processes may be a major factor in driving asthma.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Yeah. The microbiome, how that plays a role, and all these kinds of things.

Transcript edited for clarity.