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Eosinophils and Asthma: What To Know (Part 2)

This article begins where my last article, “Eosinophils And Asthma: What To Know (Part 1)” left off. You may benefit from reading that article and then returning to this one.

So, let’s get back into explaining eosinophils. Here I will explain how eosinophils are responsible for more aggressive asthma attacks. These attacks may be more severe and harder to treat. They may also be responsible for severe asthma, particularly eosinophilic asthma. Allow me to explain.

Eosinophils begin arriving 4-6 hours after exposure to the trigger. In our example it’s dust mites, although it can be any asthma trigger. Here, eosinophils release their contents, which are hundreds of tiny granules.

What do eosinophils do?

These are the culprits that do all the damage, per se.

Eosinophils cause inflammation during the late phase. You do not have to remember these. There will be no test. I just want you to see how eosinophils work. This should help explain how eosinophils contribute to more aggressive asthma attacks and severe asthma. Here are the contents inside eosinophils:

  • Major basic protein (Proteoglycan 2, PRG2)

    It’s a protein controlled by the PRG2 gene. It causes mast cell degranulation. It’s meant to be a response to invading parasites.1

  • Eosinophil cationic protein (ribonuclease 3, ECP)

    It’s a protein controlled by the RNASE3 gene. It causes mast cell degranulation and inflammation of cells lining airways. Degranulation is a fancy word to mean that these cells release chemicals that may also include even more pro inflammatory mediators. So, in this way, cells can even cause their own damage.2

  • Eosinophil-derived neurotoxin (EDN)

    It’s an protein controlled by the RNASE 2 gene. They have antiviral properties and attract and stimulate the activation of dendritic cells, which recruit more Th2 cells, which release even more pro inflammatory mediators.3

  • Eosinophil peroxidase (EPX)

    It’s a protein controlled by the EPX gene. It’s meant to disintegrate the cellular walls of parasites to kill them.4 It causes gaps to develop on cellular walls, causing blood vessels to leak their fluid causing airway inflammation.5

  • Leukotriene

    Yes. These are released during the early phase. And, here, even more are released. These guys cause upper and lower airway inflammation. They can cause both allergy and asthma symptoms. They can even cause bronchospasm and asthma attacks. A treatment method for blocking their effects are anti leukotrien antagonists, such as Singulair.6

Eosinophils play a major role in asthma

All allergic asthmatics have increased eosinophil levels in their sputum. But, eosinophil levels tend to diminish and return to normal or close to normal levels between attacks.6

There are three ways eosinophil levels go down. These are the three ways that asthma attacks may end.

  1. Time

    Sometimes time alone will resolve asthma.

  2. Getting away from the trigger

    Sometimes, just getting away from the trigger is all that is needed to end the attack. Sometimes, a combination of time and getting away will resolve asthma attacks.

  3. Medicine

    There are lots of medicines used to reverse, and also to prevent, asthma attacks. Some are bronchodilators, which open airways to end asthma attacks fast. But, sometimes more aggressive treatment is needed, and this is where corticosteroids come in handy.

Eosinophilic inflammation responds well to corticosteroids

This is because corticosteroids work to reduce eosinophil levels. I don’t want to get into how this happens (not just yet). I just want you to now corticosteroids suppress the effects of eosinophils.

Systemic steroids help reverse asthma attacks and inhaled corticosteroids (ICS) help prevent asthma attacks or make them less severe when they do occur. They suppress eosinophils and reduce their numbers. They prevent them from doing their job, which is causing aggressive airway inflammation.

This is why inhaled corticosteroids are now considered top-line medicines for helping allergic asthmatics obtain good asthma control.6

There is an exception

However, certain genetic variations may stimulate higher eosinophil levels and severe asthma. In such cases, eosinophil levels may stay elevated even between asthma episodes. This makes asthma that tougher to control, even with corticosteroids. This often results in a diagnosis of severe asthma, perhaps including a diagnosis of eosinophilic asthma.6

In this case, your doctor may prescribe the highest doses of iCS. If you still continue to have poorly controlled asthma, this is where biologics come in handy. Most biologics available for asthma today block the effects of IL5. They either bind to IL5 or bind to its receptors. In either case, one of these biologics can essentially prevent the late phase asthma attack. These medicines have proven very helpful for helping severe asthmatics obtain good asthma control. This is especially true if you have eosinophilic asthma, AERD, or Eosinophilic Granulomatitis Polyangitis.

Eosinophils are responsible for persistent asthma

Eosinophils are the culprits responsible for more severe asthma attacks. This is because eosinophils may stick around for a long time. Therefore, they continue to release mediators for a long time. So, this is what makes late phase asthma attacks more severe.

Now, most asthma attacks are completely reversible. This can be done with time, removal from the trigger, and/ or treatment. For the more aggressive asthma attacks, systemic corticosteroids are helpful. But, for a few people these eosinophil levels persist despite treatment with corticosteroids. This is what leads to your more severe subgroups of asthma.

This is what causes persistent eosinophilic asthma. Here eosinophil levels remain high even between attacks. In a sense, these asthmatics are continuously experiencing late phase asthma symptoms. This subgroup of asthma can still be treated. But, it usually requires higher doses of inhaled corticosteroids. Sometimes treatment may require 2 or more asthma medicines.

What to make of this?

This article should answer the question, “What do eosinophils do?” You can see here how the presence of eosinophils can make asthma attacks more severe. They can even sometimes make asthma difficult to control. They can also cause severe asthma, such as eosinophilic asthma. The good news is that eosinophilic inflammation, no matter how severe, responds well to traditional asthma medicines.

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.

  1. GeneCards. PRG2 Gene. https://www.genecards.org/cgi-bin/carddisp.pl?gene=PRG2. Accessed 4/14/19.
  2. GeneCards. RNASE3 Gene. https://www.genecards.org/cgi-bin/carddisp.pl?gene=RNASE3. Accessed 4/14/19.
  3. Yang D, Chen Q, Bo S, et al. Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. Journal of Experimental Medicine. 2008;205(1):79-90. doi: 10.1084/jem.20062027.
  4. NCBI. EPX eosinophil peroxidase. http://www.ncbi.nlm.nih.gov/gene/8288. Accessed 4/14/19.
  5. Duguet A, Iljima H, Eum SY, Hamid Q, Eidelman DH. Eosinophil peroxidase mediates protein nitration in allergic airway inflammation in mice. American Thoracic Society. 2001:164(7);1119-1126. doi: 10.1164/ajrccm.164.7.2010085
  6. National Heart Lung And Blood Institute (NHLBI). Asthma guidelines. https://www.nhlbi.nih.gov/files/docs/guidelines/03_sec2_def.pdf. Accessed 4/14/19.

Comments

  • Shellzoo
    2 weeks ago

    As I sit here, my chin and eyelids itching and getting hives, I am enjoying understanding how eosinophils are responding and causing inflammation. Appreciate the detailed explanation that is easy to read and understand. Now to take some allergy meds and inhalers….

  • Leon Lebowitz, RRT moderator
    2 weeks ago

    Hi again, Shellzoo, and thanks for chiming in here. I’m sure John will appreciate you kind words about the material he has had published here.
    Wishing you well,
    Leon (site moderator)

  • Leon Lebowitz, RRT moderator
    1 week ago

    Hi John, and thanks for responding!!
    Leon (site moderator)

  • John Bottrell, RRT moderator author
    1 week ago

    John does appreciate it. 🙂 John. Site Moderator.

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