The neutrophil is, is a problem in bronchi. I mean, you, you can really talk to James Chalmers about it. I mean, he, he, years ago, he was telling me how he thought it was overactive neutrophils causing a problem, and I thought it was an interesting hyposis, um, but he, he and, you know, others really went forward and, and proved it, and he's, he's been the leader in this field, and I, I think this was probably even his idea, you know, 1520 years ago. So, Um, there's no question that, that, uh, he and other groups have shown there is neutrophil, uh, overactivity. Um, there is, uh, there are serum proteases, uh, there's nets. There, that neutrophilic inflammation, um, is correlated with, you know, poorer outcomes. Um, when you look at nets, uh, they correlate with exacerbation risk. You can see, You know, people with more serum protease, uh, activity or neutrophilastase activity do more poorly. They have more, um, progression of disease and higher risk of flares, exacerbations, etc. and poorer quality of life. So, um, it, you know, it, it does speak to the fact that these neutrophils seem to be, um, causing quite a bit of inflammation. Now, You know, I, I think it's always the chicken or the egg thing, right? I mean, is it because the bugs are there and, and the neutrophils are reacting appropriately, or, or maybe the neutrophils are overreacting? And I think the hypothesis was, you know, we, if we tame them down a bit, can we actually promote better homeostasis in the airway? And, you know, defined by less inflammation, less, um, less flare-ups, less exacerbation, and that's certainly what we're seeing. Uh, now with the output from the clinical trials with renzocadeb. So, you know, neutrophils, when they undergo maturation, they package various serine proteases. Um, these are young neutrophils, uh, in the, um, in the bone marrow. Um, so, if you, Target dipeptidal peptidase one, which is um really cathepsin C and uh you essentially. Minimize or inhibit the packaging or the activation of those, those serum proteases. So, those neutrophils mature and come out of the marrow as basically, um, you know, they're not carrying their sidearm anymore. I don't know the best way to put it, but they're dumbed down. I always say to patients, they're just not as active because they don't have those, uh, active, uh, activated serum proteases. So, and we can, of course, You know, measure that, uh, in these studies, you see decreased neutrophil elastase when patients are on that type of therapy. Um, and then, of course, we've seen the clinical outcome from those studies where, where we see a, um, association with less, less, uh, daily symptoms and less risk of exacerbation.
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