Biomarkers in Shifting the Treatment Paradigm of Asthma - Episode 5

Effect of Eosinophils on Treatment of Allergic Asthma

Transcript: Thomas Casale, MD: If you do blood eosinophils, and they're low, 50 to 100, and the pheno is low, is that patient going to respond to inhaled corticosteroids? What do you do? How do you treat them? That's for anybody.

Stanley Goldstein, MD: That's the major problem. They have those biomarkers you just mentioned. I think we have a lack of anything to really say this is what will help that person. Obviously, we try different things, and we know, like you said, they don't respond well to inhaled corticosteroids. They have significant decrease in their airway function. They may have comorbid conditions, such as obesity. That type of patient would have that potential of biomarker, as you just discussed. I think we need to research each to continue in that T2-low asthma, because it's not a one-type of patient. It's sort of a conglomerate of different patients to find paucigranulocytic no cells. You can find neutrophils. Or, you may find in another patient neutrophils and eosinophils. That’s the conundrum of those types of patients.

Thomas Casale, MD: Geoff, I'll pick on you. What do you do if you have someone that you’re convinced doesn't have an eosinophilic-driven asthma? How do you treat them?

Geoffrey L. Chupp, MD: I think these patients can be very challenging. I agree that they are a mixed group of individuals from a disease-driver standpoint. A lot of these patients I think are the ones that we are often concerned have some comorbidity that’s driving their symptomatology. When you see a patient that really has no evidence of T2 inflammation by eosinophil or allergy testing, then we start to think about reflux potentially contributing to their disease and often silent reflux that still requires a good motility workup. Sometimes, these patients can have vocal cord dysfunction. Once you are really convinced that this is an airway disease, asthmatic, obstructive airway disease, we sometimes try non-T2 treatments, nonsteroidal treatments, such as macrolides in these patients. That can be successful in controlling their disease. Bronchial thermoplasty, as well, which we do at our center, can be effective in these individuals as well.

Generally, we make sure we’re not missing other diseases here, like we do with all asthmatics, but sometimes search a little harder in this subset of individuals and move toward non—T2-type therapies for asthma, which are very limited at the moment. No particular biologic is available on the market right now to treat non-T2 disease.

Michael E. Wechsler, MD, MMSc: Of course, Geoff, in the context of patients who are on oral corticosteroids, I would say that all bets are off in terms of biomarkers.

Geoffrey L. Chupp, MD: That's right.

Michael E. Wechsler, MD, MMSc: We know that systemic corticosteroids blunt the type 2 biomarker signals that we see, for the most part. For patients who are on oral corticosteroids and systemic corticosteroids, the GINA [Global Initiative for Asthma] guidelines actually recommend us to assume that they have underlying type 2 inflammation, and we can go ahead and treat those patients with some of the biologics that we’ve discussed.

Geoffrey L. Chupp, MD: I agree with that fully, which is that patients who are systemic steroid dependent, meaning that they respond to systemic steroids, and that is the only thing that keeps them under control, I consider those to be T2 patients. By most experiences, I think the truly non-T2 patients are generally not steroid responsive to systemic steroids or inhaled steroids.

Syed Shahzad Mustafa, MD: I obviously completely agree with everyone with what was said about people on chronic steroids. I think it is safe to assume if they’re responding and feel better on them that they are likely to [have] T2-high [asthma]. But, we see a small subset come through the office every so often who are on a significant dose of systemic steroids and still very symptomatic, and I just reiterate what Geoff said. I think it’s particularly important to revisit the diagnosis there, because if you’re not responding there, it’s even more important to make sure we’re not missing any other comorbidities or other driving conditions.

Transcript Edited for Clarity