Asthma Is A Single Disease With MANY Root Causes
What is the root cause of asthma? The answer to this question has eluded physicians for over 2,400 years. Now, as researchers delve deep into the field of genetics, the complexity of our disease appears quite apparent, making it understandable that the root cause remains unknown. However, given what is now known about the connection between genetics and asthma, many researchers now think the better question might be: WHAT ARE THE ROOT CAUSES OF ASTHMA?
Think about that for a second. Since 1989, with the development of asthma guidelines, the topline recommendation for ALL people with asthma has been inhaled corticosteroids to prevent and control asthma. Yet some asthmatics, it is now known, respond poorly to inhaled corticosteroids. This was kind of a surprise to researchers, as they thought they had FINALLY come upon an ideal asthma medicine.
The revelation that corticosteroids did not work for about 10-15% of asthmatics lead them to up the ante as far as asthma research was concerned. This, and other evidence, lead researchers to the realization that, while asthma is a single disease, it has MANY causes. So, while asthma is a single disease, there are many subtypes of asthma, each one having a unique cause.
Making things even more complicated than this, researchers believe that every asthmatic has a unique combination of asthma genes randomly scattered along their genotypes, meaning that, even while two asthmatics may have the same subtype of asthma, their asthma presentations may still be different. This may explain why one person might have mild Allergic Asthma, while another person may have severe allergic asthma.
So if you thought this disease was complicated before, it just got severely complicated. It’s no wonder the root cause of our disease eluded great physicians like Hippocrates, and why they had to resort to theories to explain our disease.
Let’s put this into perspective. Some asthmatics have the following asthma genes: GATA3, TBX21, IL4, IL4RA, STAT6, and IL12B. All of these have the potential to impact T-helper (Th) cells, special white blood cells that recognize pathogens and initiate an immune response. They also release small proteins called cytokines that communicate with cells, telling them to do something.
So our example patient has one or more of these asthma genes along with a random sample of the other 100 plus asthma genes. They work together to cause a special type of Th cells called T-helper 2 cells to recognize harmless dust mites as harmful.
Th2 cells release a cytokine called Interleukin 13 (IL13). It is supposed to be released only in response to parasites. It causes blood vessels lining airways to release some of their fluid, resulting in inflammation of airway cells. The purpose of this response is to trap parasites.
This response was beneficial in the primitive world, where humans were commonly exposed to parasites. This response is no longer needed in our modern world where people are no longer exposed to parasites.
Researchers discovered that asthmatics had elevated Th2 and IL13 levels. It was learned that corticosteroids suppressed the effects of IL13, reducing airway inflammation. For a while, they believed they had the root cause and the treatment for our disease. Inhaled corticosteroids became a top of the line recommendation in most asthma guidelines to help asthmatics obtain ideal asthma control.
BUT, then it was discovered that some asthmatics responded poorly to corticosteroids. Upon further investigation, it was learned that these asthmatics had low levels of IL13 and elevated levels of Interleukin 17 (IL17), a cytokine that was supposed to only be released in response to fungus and bacteria. Corticosteroids did NOT suppress the effects of IL17.
So, you see, it was discoveries like this that lead to the realization that asthma is a single disease with more than one cause. This lead researchers to divide asthmatics with similar disease presentations into asthma subtypes, such as Allergic Asthma and Severe Asthma. Allergic asthmatics have asthma complicated by allergies, and severe asthmatics have asthma that does not respond to corticosteroids.
To make this even more complex, even Allergic Asthmatics can have different levels of severity, and this is because every asthmatic has a unique combination of asthma genes. So this may explain why some allergic asthmatics have mild asthma, and others have it more severe.
Anyway, all of these new revelations, along with many other discoveries, lead researchers to divide asthma into various subgroups, including allergic asthma, severe asthma, premenopausal asthma, obese asthma, severe asthma, asthma/COPD overlap syndrome, Aspirin sensitive, cough variant, etc.
Each of these are caused by unique gene combinations, meaning they probably all have a unique root cause. Researchers are still looking to learn more about specific root causes, the discovery of which may lead to more specific asthma treatments for each subgroup, leading to asthma guidelines specifically catered to each asthma subgroup. This should lead to better asthma control for all of the 334 million asthmatics around the world.
SO, WHAT ARE THE ROOT CAUSES OF ASTHMA? The answer is: WE STILL DO NOT KNOW. What we do know is that researchers will continue working overtime until they find all the answers we asthmatics yearn for, and ideally this will ultimately lead to a cure. Considering the complexity of this disease, it may take some time.
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