Severe Asthma: What Is Airway Remodeling?

About 5-10% of asthmatics have what is now understood to be severe asthma.¹ While there are a variety of reasons why someone might end up with severe asthma, one potential cause is airway remodeling. Here's what is presently known.

A little history of airway remodeling

Researchers first recognized airway remodeling in asthmatics in 1922.² They linked it with severe asthma during the early 1990s. So, while they have been researching this vigorously, their understanding of what their studies show is on the cutting edge. For this reason, there is no set, agreed-upon definition of it, and it remains poorly understood.

What is the definition of airway remodeling?

Airway remodeling occurs when abnormal changes take place in the cells lining the airways. This causes the small airways to become abnormally thick and scarred. These walls become extremely hypersensitive (twitchy) to asthma triggers. As it progresses, it can cause severe asthma. Similar names for remodeling you might see are structural changes, fibrosis, and scarring.

What is known about airway remodeling?

Listed below are 6 phrases often used to describe airway remodeling. These are followed by my interpretation, based on what I have read.

Note: Sometimes, in our quest to understand a complex disease like asthma, things can appear quite complicated. I think that's the case here. This is mainly because it is so new. So, keep this in mind as you read on. I will try to keep this as simple as possible. I promise, no test will follow.

1. Epithelial cell thickening and shedding. Epithelial cells are those cells that line the inside of the airways. They are usually bound snugly together. Asthmatic epithelial cells become damaged due to inflammation. They have trouble repairing themselves. For various reasons, this causes these cells to lose their ability to bind to each other. This causes some cells to become loose (shed). To help repair the damage, other cells are recruited to the area. The combination of these effects makes airways extra sensitive to asthma triggers.^2,3
2. Goblet cell hyperplasia and mucus production. Goblet cells are randomly scattered throughout the airways and squeezed between epithelial cells. Hyperplasia refers to an abnormal increase in the number of cells in a tissue. This may be caused by proliferation (cell replication or division) that occurs faster than normal. This causes goblet cells to become abnormally large (hypertrophied). Goblet cells (and submucosal cells, too) are cells that produce mucus to lubricate airways and trap unwanted particles and pathogens. Hypertrophied goblet cells may produce excessive amounts of secretions, especially during asthma attacks.^2-6
3. Smooth muscle cell (SMC) hyperplasia. Wrapped around the airways are bundles of smooth muscles. When these muscles are relaxed, airways remain open. When they constrict, airways become narrow. Perhaps also due to proliferation, there is an abnormally large number of airway smooth muscles. This causes the smooth muscle to become hypertrophied (enlarged). This increases the mass of smooth muscles and may contribute to the thickening of the airway wall. A potential treatment for SMC may be bronchial thermoplasty, where bronchial smooth muscles are burned away so they can no longer obstruct airways.^2-8
4. Thicker, smaller airways. The inner surfaces of your airways are lined with epithelial cells. Each epithelial cell is covered with cilia or fine, hairlike structures that move back and forth to move mucus up to the back of your throat to be swallowed. Under a single layer of epithelial cells (epithelium) is a basement membrane. This basement membrane becomes abnormally thick, which also makes the airway walls thicker than normal. A technical term for this is subepithelial fibrosis. This makes the airways abnormally narrow. The amount of thickening present has been directly correlated with increased asthma severity.^{3-6, 9}
5. Angiogenesis. Below the basement membrane is a submucosal layer, which contains connective tissue and blood vessels. Another thing that happens is an increase in the number of blood vessels that feed these cells. These vessels tend to be more permeable than non-asthmatic submucosal vessels. This can lead to small amounts of blood seeping into the interstitial spaces (the spaces between cells), causing airway inflammation and edema. This inflammation irritates cells and nerves in the area, causing asthma symptoms or making the airways more hypersensitive.^3-5

How is airway remodeling connected to severe asthma?

So, sorry if I got a little complicated there. It's just a complex subject. And, again, there will be no test. This is just for our information. Some of these may happen in all asthmatics, to some extent. However, the combination of them all happening together may be what is responsible for some cases of severe asthma. At least this is my understanding of the research. In my next post, I'll go over some strategies for preventing and treating airway remodeling.