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Asthma Subgroups: Non-Th2 Dominant Asthma

There was a time researchers thought 100 percent of asthma cases were allergic and Th2 dominant. Today they know that not all asthma is allergic. In fact, they’re are now aware of many asthma subgroups (phenotypes). They also now aware that about 50 percent of asthma cases are non-Th2 dominant. So, what is non-Th2 dominant Asthma? Here’s what to know.

So, what is non-Th2 dominant asthma?

Asthma is a lung disease. But, it affects much more than just the lungs. We now know this as a fact. In fact, while asthma effects the lungs, it’s actually a disease of an overactive immune system.

And it’s caused by abnormal genes that tell the immune system what to do. Sometimes genes undergo what is called single nucleotide polymorphisms (SNPs). A simpler term for this is mutation or change. These SNPs cause genes to do something abnormal. Researchers have discovered over 100 potential asthma genes.

T-helper 2 (Th2) cells are white blood cells (lymphocytles) that contain many granules. These grandules are called mediators of inflammation. They have a significant impact on mast cells lining airways. When told to do so, mast cells release their contents. The end result here is airway inflammation and asthma.

So, Th2 cells are responsible for Th2 dominant asthma. The type of inflammation is usually caused by eosinophils. It is very responsive to top-line asthma medicines like rescue medicine and corticosteroids. Most people with this phenotype are able to obtain good asthma control.

T-helper 1 (Th1) cells are also lymphocytes that contain many granules. Like Th2 cells, they are now thought to have an impact on mast cells. But they may also have an impact on cells themselves. They may cause cells to release their own mediators of inflammation, such as Interleukin 2 and IFN-g. These cause a more aggressive type of inflammation compared to Th2 inflammation. It is not very responsive to top-line asthma medicines. (6, Chen)

So, Th1 cells may be responsible for non-Th2 dominant asthma. The type of inflammation is not well understood.

What do researchers know about non-Th2 dominant asthma?

What researchers do understand is that non-Th2 dominant asthma tends to have an adult-onset, which is usually after the age of 40. It also occurs in individuals with no family history of allergies.1

While they meet the criteria for asthma, their airways are less sensitive and obstructed than those with Th2 dominant asthma. Their asthma also tends to be more persistent and less responsive to corticosteroids.1

This means they tend to also have a diagnosis of severe asthma.

Is there a genetic component?

There is a genetic component that differs from that of which causes Th2 dominant asthma. In the case of non-Th2 dominant asthma, certain asthma genes release proteins that are responsible for injury and repair of tissues. These proteins directly cause hyperactive airways that are far more reactive to asthma triggers than those who have Th2 dominant asthma. This causes narrow airways and loss of lung function (low FEV1).1

What causes one to develop this phenotype?

So, it would appear that non-Th2 dominant asthma is caused by gene mutations that are unique from those that are present in the Th2 dominant phenotype.

Those of us with a predisposition to developing asthma are born with our asthma genes. Most of these are turned off until some “key” turns them on. These “keys” are usually something in your environment that is inhaled. But they could also be things inside you.

This “key” for most people with Th2 dominant asthma are allergens. We are exposed to most allergens early in life. So, allergic asthma usually develops very early life.

The key for turning on genes responsible for the non-Th2 dominant response may be unique to keys that might turn on the Th2 dominant response. It may develop only when you’re exposed to these “keys” over a long-period of time. And this is what makes it typically adult-onset asthma.

Here are some examples.

A new asthma subgroup

So, this is basically what is known about non-Th2 dominant asthma. It’s a very new asthma subgroup, which may explain why so little is known. Researchers are working to better understand it. They are trying to discover better treatments for reversing and controlling it. All of this in an effort to help all asthmatics obtain ideal control.2

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. Wenzel, Sally, “Asthma phenotypes: the evolution from clinical to molecular approaches,” Nature Medicine, 2012, May, Vol. 18, No. 5, pages 716-725, http://www.healthylungs.com.au/resources/WenzelAstham-Phenotypes.pdf, accessed 10/31/16
  2. Chen, et al., “Stress and Inflammation in Exacerbations of Asthma,” 2007, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077080/#R24, accessed 10/31/16

Comments

  • RosieK
    1 month ago

    Thanks for this article.
    I have been diagnosed with Neutrophillic asthma, this year. I am 70 now.
    Didn’t start having asthma til mid 2014.
    It has had a huge impact on my life. It is present everyday at some level.
    I am responding less and less to steroids.
    Love a follow up on tips to manage this sort of asthma.

  • John Bottrell, RRT moderator author
    1 month ago

    Thank YOU! Glad to hear you found the article helpful. Great idea for a follow up post. At the present time, researchers are just beginning to understand neutrophilic asthma. Generally, it’s treated using a step up approach, where traditional asthma medicines are used, followed by second-line medicines and COPD medicines (https://asthma.net/living/asthma-medicine-finding-what-works-best-for-you/). There are also some medicines in the pipeline tailored specifically for this type of inflammation, one example is Danirixen (https://copd.net/uncategorized/danirixin-hope/). Have you discussed treatment strategies with your asthma doctor? Just curious. John. Site Moderator.

  • Shellzoo
    1 month ago

    I find the asthma subtypes fascinating. It seems right now that you get told you have asthma and get treated with very little details on type or how severe. I expect eventually we will get more details with our diagnosis and a very personalized plan for treatments based on the subtypes. Asthma seems like a very general term when there are so many ways asthma presents itself. I only know I have moderate persistent asthma because I looked at my bill and it was listed there. I think once I was told I have allergic asthma and it has been mentioned that I have asthma/COPD although my spirometry is finally improving. Here is a question: How much does/should a patient know about their condition? Is there a reason patients are not told what their subtype is? Good article on an interesting subject.

  • John Bottrell, RRT moderator author
    1 month ago

    I think you are correct. It will be neat (and exciting too) to see where this all comes out. All the best. John. Site Moderator.

  • Shellzoo
    1 month ago

    Now that I have good control, I don’t expect it to affect me as much but for those who struggle to get good control, I expect it will be a game changer. How is asthma research? Is it well funded? A priority?

  • John Bottrell, RRT moderator author
    1 month ago

    Great question. I think it is because asthma subgrouping is so new. I am not sure about this, but I think there are some doctors (whispering here so no one else hears this) who do not even know about asthma subgroups. And that’s no knock on them, as there is so much being learned so fast that it’s hard even for the best doctors to keep up with it all. But, yes, I am convinced that, maybe even within the next ten years or so, there will be a blood test that can tell you if you have COPD, asthma, and what subgroup. And this will lead to a specific treatment guideline. Of course, all of this is in theory. But that does seem to be where it’s headed. And the goal of all of this is to help all asthmatics obtain better asthma control. What do you think? John. Author/ Site Moderator.

  • Shellzoo
    1 month ago

    I think the subtypes can lead to better treatment as we learn what works best with each subtype but I suspect people can have more than 1 subtype. It could get rather complicated.

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