Severe Asthma: What Is Airway Remodeling?

Severe Asthma: What Is Airway Remodeling?

About 5-10% of asthmatics have what is now understood to be Severe Asthma. 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.

What is a little history?

Researchers first recognized airway remodeling in asthmatics in 1922.1 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 current definition of airway remodeling?

It’s when abnormal changes occur in cells lining airways. This makes small airways 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 all known about airway remodeling?

Listed below are six phrases often used to describe airway remodeling. These are followed by what I think they mean 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 this 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 airways. They are usually bound snug 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 together. 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.1-2
  2. Goblet Cell Hyperplasia and mucus production. Goblet cells are randomly scattered throughout the airways and squeezed between epithelial cells. Hyperplasia means there is an abnormally large 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 traps unwanted particles and pathogens. Hypertrophied goblet cells may produce excessive amounts of secretions, especially during asthma attacks.1-5
  3. Smooth Muscle Cell (SMC) Hyperplasia. Wrapped around airways are bundles of smooth muscles. When these muscles are relaxed, airways remain open. When they constrict, airways become narrow. Perhaps also due proliferation, there is an abnormally large number of airway smooth muscles. This causes this smooth muscle to become hypertrophied (enlarged). This increases the mass of smooth muscles and may contribute to airway wall thickening. A potential treatment for SMC may be bronchial thermoplasty, where bronchial smooth muscles are burned away so they can no longer obstruct airways.1-7
  4. Thicker Smaller Airways. On the inside surfaces of your airways are 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, and this also makes airway walls thicker than normal. A technical term for this is subepithelial fibrosis. This makes airways abnormally narrow. The amount of thickening present has been directly correlated with increased asthma severity. 2-5, 8
  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 interstitial spaces (the spaces between cells) to cause airway inflammation and edema. This inflammation irritates cells and nerves in the area to cause asthma symptoms, or to make airways more hypersensitive.2-4

What to make of this?

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 will go over some strategies for preventing and treating airway remodeling.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The Asthma.net team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.
View References
  1. Keglowich, L.F., P. Borger, "The Three A's In Asthma -- Airway Smooth Muscle, Airway Remodelling & Angiogenesis," Open Respiratory Medicine Journal, 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475688/, accessed 8/9/17
  2. Berair, et al, "Origins of increased airway smooth muscle mass in asthma," BMC Medicine, 2013, https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-145, accessed 8/9/17
  3. Agmy, Gamal, "Asthma Phenotypes and Genotypes," 2014, Jan. 3., https://www.slideshare.net/GamalAgmy/asthma-phenotypes-and-endotypesStart on slide 9, accessed 9/13/17
  4. Rogers, Duncan, "Airway goblet cell hyperplasiain asthma: hyper-secretory and anti-inflammatory,Clinical and Experimental Allergy, 2002, August, http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2745.2002.01474.x/abstract?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+and+Sunday+i.e+16th+and+17th+September+at+3%3A00+EDT+%2F+8%3A00+BST+%2F+12%3A30+IST+%2F+15%3A00+SGT+for+5+hours+and+3hours+for+essential+maintenance.+Apologies+for+any+inconvenience+caused+, accessed 8/9/17
  5. Hyperplasia, Free Dictionary by Farlax, http://medical-dictionary.thefreedictionary.com/hyperplasia, accessed 8/9/17
  6. xBentley, J. Kelley, Marc B. Hershenson, "Airway Smooth Muscle Growth in Asthma," Proceedings of the American Thoracic Society, 2008, January, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645305/, accessed 8/9/17
  7. xLazarus, Stephen, "Airway remodelling in asthma," Medscape, 2017, September 14, http://www.medscape.org/viewarticle/420569, accessed 9/14/17
  8. Roche, W.R., "Subepithelial fibrosis in the bronchi of asthmatics," Lancet, 1989, https://www.ncbi.nlm.nih.gov/pubmed/2466184, accessed 8/11/17
  9. Mauad, et al., Abnormal Alveolar Attachments with Decreased Elastic Fiber Content in Distal Lung in Fatal Asthma," American Journal of Respiratory And Critical Care Medicine, 2004, http://www.atsjournals.org/doi/full/10.1164/rccm.200403-305OC, accessed 10/1

Comments

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  • lisat844
    5 months ago

    Up until my late 30s I had mild asthma. Then at some point, I acquired histoplasmosis, which left me with 14 nodules. My asthma went from mild to severe persistent, and I was wondering if having the histoplasmosis could have caused airway restructuring. My life has changed drastically and at 53, I still haven’t accepted the fact I may continue to get worse, since I’ve been getting worse for over a decade.
    I see a wonderful pulmonologist, who is very intelligent and knowledgeable, and has changed my controller(s) so many times. He tested my IgE levels, which were high, but Xolair only worked about 3 months. He’s now testing for eosinophils. It’s all so confusing.
    And now I’m wondering if the fungal infection has caused the kind of changes that would result in the acute changes in my lungs.

  • Leon Lebowitz, RRT moderator
    5 months ago

    Hi lisa844 and I’m so sorry for these health challenges you’ve described for us. It’s gratifying for us to hear you have a ‘wonderful pulmonologist’, and trust that he will guide you through your various conditions and be able to address all your concerns. Please do check back and let us know how you’re doing. Wishing you the best. Leon (site moderator)

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