So an important thing to understand is your lungs are the primary interface between the human body and the, and the outside world, so your lungs are constantly dealing with insults, we're inhaling viruses, we're inhaling bacterial particles, we're inhaling air pollutants constantly. So there's a constant turnover in the lungs, uh, of these things that we don't want, uh, and the, the two primary ways that the lungs get rid of things that we don't want in there are mucociliary clearance. Uh, particles are trapped by mucus and cleared through ciliary action and then expectorated, and through the immune system and particularly phagocytes, um, cells that eat foreign particles and break them down, macrophages and neutrophils, uh, and we're constantly dealing with and resolving these inflammatory insults to the lung. So what happens in bronchiectis and the best way to, to understand that is an insult to the lung happens. But rather than being able to clean that up and resolve the inflammation, the, the body fails to clear things, and that may be genetically determined, it may be because of the severity of the event that takes place, um, and that inflammation persists, the body is not able to clear those inflammatory cells, uh, and is not able to tidy up the insult that it's encountered. And so what you enter into is a self-perpetuating cycle, or sometimes we call it a vortex within bronchiectasis, where you have inflammation that's predominantly driven by neutrophils, uh, and those cells have been shown through extensive research to drive the other components of the disease. So neutrophils release chemicals, proteases that cause the body to make too much mucus, uh, that excessive mucus further impairs the clearance of, Uh, particles from the lungs, uh, and can set up the conditions required for infection, for bacteria to grow. Obstruction of the airways with mucus and the presence of infection do one thing, which is drive more inflammation. More inflammation means more mucus, means greater susceptibility to infection, and you can see how those things interact to create a self-perpetuating or a feed forward cycle. Those neutrophils that I'm talking about are also critical because the chemicals that they release are inherently toxic, they're there to destroy foreign particles like bacteria. You get enough of those proteases and those other chemicals, they will also cause significant damage to the lung. And bronchiexis is best thought of as, as a chronic damage to the airways, so you get destruction of the bronchial walls, distortion of the anatomy. That happens slowly over time because of the action of these, these proteases uh and other chemicals released from neutrophils. And so you can see how the neutrophil is foundational to the pathophysiology of bronchiectis. It drives the mucous hypersecretion, dysfunction. Of the neutrophils ultimately is what leads to failure to clear bacteria from the airways, and it's, uh those uh factors, particularly granule proteins that are released from neutrophils that ultimately damage the bronchial walls and lead uh to the permanent structural lung damage that we call bronchiectasis. And so at its core, bronchiectis is a, is an, a disorder of uh dysregulated inflammation and chronic inflammation.
Presenter
