Targeted Pathology for the Treatment of Asthma

Transcript:

Stanley Goldstein, MD: When you’re thinking about getting into a biologic, I think it would be helpful to define whowhat are those type of patients, who just by definition of a patient that would potentially need a biologic. We have in the literature, just to point that out, is the ERS, [European Respiratory Society], and ATS definition of what a severe asthma patient is. Severe asthma patient is a patient that would require high-dose inhaled corticosteroids, plus another controller medicine, or may require oral corticosteroids for 50% of the year or greater and still be in control. So, that may define a severe asthma patient. Then you have those patients who are taking all those controller medicines or oral corticosteroids and continue to be poorly uncontrolled. TI think these are the patients that we’re referring to when you think about the need for a biologic either because they continue to be uncontrolled on their inhaled medications or even controlled on oral corticosteroids.

Since we now begin to now talk about biologic and they are referred to allergists and pulmonologists, let’s think about the pathology of asthma. I think Shahzad, you pointed this out before as you were talking about asthma as a syndrome and all the other types of asthma underneath that. If you could just address some of the pathology of asthma, when you think about the different inflammatory processes.

Shahzad Mustafa, MD: Sure. Dr. Mosnaim mentioned earlier, we have bronchoconstriction and inflammation. On, and overly simplistically in asthma, we’re really thinking about eosinophilic inflammation or Th2 [T helper Type 2] inflammation, which kind of varies and compares to COPD emphysema, which we think of as a predominately is neutrophilic inflammation. But nothing is binary, so there are shades of gray here. But we’re classically thinking of eosinophilic inflammation, and many, in fact, I think all of the biologics currently that are FDA approved for asthma are all really addressing that type of inflammation. WSo wanting to know what type of inflammation an individual has, whether it’s eosinophilic or neutrophilic, is important, and how are ways you can do that?

In the office, looking at the background, the patient’s background, are they allergic? If they have a lot of allergic conditions, then they’re more likely to be eosinophilic versus not. We can check for exhaled nitric oxide, which is a validated biomarker for eosinophilic airway inflammation. And although many of us are not doing lung function testing and spirometry because of the risk for aerosolization and risk of potential spreading of infection for people with COVID right now, checking exhaled nitric oxide is a non-aerosolized procedure. So, that’s a tool we can use even amongst this global pandemic.

Then when we’re thinking about these biologics, we can also check for eosinophils with a simple blood count, a CBC [complete blood count] with differential. There we’re using the eosinophils in the blood, peripheral eosinophilia as a surrogate for airway eosinophilia. T So trying to understand what type of inflammation an individual has is very, very important because the biologics we have are really directed at eosinophilic inflammation.

Stanley Goldstein, MD: In the literature, we all talk about phenotype and endotype. I think it’s would be important to discuss what is meant by a phenotype, because when you look at a group of researchers called the SARP, [Severe Asthma Research Program], they look at patients, they first try to put patients in buckets, and those buckets are based upon the patient’s phenotype. When we talk about phenotype, it means the observable characteristics of that person. What do you see in that person as far as what’s similar? SoSo, you put them in buckets. But we know when we think about phenotype, it doesn’t help define what type of biologics you would use, it may put them in buckets. Then it’s important to think about the endotype, which is . What is the endotype? It’s the inflammatory process that we’ve all been referring to, that occurs in that specific patient. Let’s discuss about, I know you brought it up already, Shahzad, but the different endotypes that may be related to some of these phenotypes, or maybe discuss the different phenotypes of asthma patients.

Shahzad Mustafa, MD: I like starting with phenotypes, and Dr. Mosnaim can chime in as well., too. TI think the first important thing is we can even start(?) the phenotype for asthmatics without ever talking to them, by just looking at them from across the room. Age is important. Younger asthmatics tend to be more Th2 or eosinophilic versus a later onset asthmatics, who may be more neutrophilic. Race is very important. We talk about health care disparities in America. But even outcomes and responses to medications. , we know thereThere are racial differences in responses to asthma medications. So thinking about that. Body habitus, body mass index, obesity is important. Obesity in addition to this potential physical restriction also affects your response to medications for asthma. Obesity impacts your response to inhaled corticosteroids. So, just looking at an individual starts to teaches you about their phenotype.

And then in the office, in our specialist office, at an allergist’s office, there’s a lot of testing we can do. Giselle, Dr. Mosnaim mentioned skin testing for allergic rhinitis and comorbidities. Skin testing tells us a lot about lung health and has a lot to do with asthma outcomes., we know that. Lung function testing, are they reversible with a bronchodilator, are they not reversible? Do they have high exhaled nitric oxide for eosinophilic disease versus non-eosinophilic disease? SoSo, there’s those phenotypes, and then we can order tests. For blood work,, many of us are ordering blood work— pulmonologists, allergists, and other specialists. We can check for eosinophils with a CBC, [a complete blood count] with differential. We can check for total IgE [Immunoglobulin E] levels, which again these are going to help us understand the patient’s particular asthma. There may be a role for imaging. So we have all these tools to better understand someone’s asthma, which can then hopefully better help us personalize their medical regimen that suits them most.

Transcript Edited for Clarity