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.

  • Occupational Asthma. Chronic exposure to chemicals, fumes, or gases in the air at your work.
  • Asthma / COPD Overlap Syndrome. Chronic exposure to chemicals in cigarette smoke.
  • Obesity Associated Asthma. Chronic exposure to chemicals released from adipose (fat) tissue or exposure to fatty foods.
  • Virus Induced Asthma. Exposure to a massive lung infection.
  • Neutrophilic Asthma. Inflammation caused by neutrophils.
  • Paucigrranulocytic Asthma. Inflammation caused directly by cellular changes.

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

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