Expert-presentatie: de impact van type-2-inflammatie bij COPD

My name is Surya Bhatt. I'm a professor of Medicine at the University of Alabama at Birmingham and I'm a COPD researcher. This talk is sponsored by Sanofi and Regeneron and you won't get any (CME) credit. In response to any kind of insult. For example, cigarette smoke, viral infections, bacterial infections, pollution, there is some element of epithelial injury and epithelial damage. And the first response to this usually is once there is enough epithelial damage, there is release of damage associated molecular patterns or (DAMPs) which are now perhaps more popularly called alarmins and these are IL-33, IL-25 and TSLP or thymic stromal lymphopoietin. So all these can be released and they all have specific roles in terms of furthering inflammation. And IL-33 is perhaps best understood and some people consider it the master inflammation switch where once it's activated, it stays activated for a long time. It promotes both type 1 and type 3 inflammation as well as type 2 inflammation. The traditional thinking has been that the prime driver of type two inflammation is IL-5, which causes eosinophilic inflammation. But now we understand that both IL-4 and IL-13 are important in driving type 2 inflammation. And here's a list of all the things that they can do.

lL-4 and IL-13:

• Can both cause epithelial barrier disruption.
• They can cause B cell class switching and enhance an increased production of IgE
• They can cause mast cell degranulation
• They can cause basophil degranulation
• And also eosinophilic inflammation just like IL-5.
• They can also result in goblet cell hyperplasia and mucus production especially IL-13.

And as a consequence of these, they can cause significant airway remodeling as well as alveolar destruction.

IL-4 and IL-13 levels are also elevated during an acute exacerbation as opposed to in the stable state or patients without COPD. So this is also important to note that these pathways are activated in patients with acute exacerbation of COPD and they present and important in COPD.

And then, you know, we all know that there's been a lot of understanding of mucin and mucus production in COPD. And one of the prime drivers of that is MUC5A and IL-4 can induce increased expression of MUC5AC in human epithelial cells. And there's also a dose dependent response almost of IL-13 on MUC5A as well as increased mucus production. So, especially IL-13 has been found to be an important driver of mucus production in patients with COPD.

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