Asthma Subgroups: The 4 Types of Airway Inflammation

It is now understood that all asthmatics have some degree of chronic (it's always there) underlying airway inflammation. While it was once thought to be, all the same, researchers now understand there are 4 types of airway inflammation in asthma, each of which is now classified as a distinct asthma subgroup (which are really now called phenotypes), under which all the other subgroups fall.

Eosinophilic inflammation

This was once thought to be the sole source of airway inflammation in asthma and is still considered to be the most prevalent. You are allergic to something, hence you have allergic or intrinsic asthma. When exposed to your asthma triggers, your immune system responds by releasing a series of chemicals into your bloodstream.

These chemicals are called the mediators of inflammation, mainly because they are responsible for airway inflammation either directly or indirectly. Histamine and Leukotrienes are examples of mediators that directly cause inflammation. Interleukin 5 (IL5) is an example of a mediator that indirectly causes inflammation. It travels through the bloodstream and recruits white blood cells called eosinophils.3

Eosinophils are granulocytes, meaning they contain granules. These granules include many mediators of inflammation. They, in effect, enhance the inflammatory response, or make chronic underlying inflammation worse, resulting in asthma symptoms (asthma attacks).

In most cases, this response is only temporary, as eosinophil levels go back down to normal or near normal levels once you remove yourself from your asthma triggers. (allergic asthma or EIA).

How eosinophilic and severe asthma are linked

In some rare instances, eosinophil levels remain chronically elevated resulting in severe asthma (eosinophilic asthma or Churg-Strauss Syndrome). Sometimes it is triggered by a specific allergen called Aspirin or similar non-steroidal anti-inflammatory medicines, also resulting in severe asthma (AERD). Sometimes is it triggered by a mold (Aspergillosis).

Corticosteroids have been shown to reduce eosinophil levels, resulting in improved asthma control. Low to moderate doses of inhaled steroids usually work well for controlling allergic asthma and EIA. Eosinophilic, AERD, Churg-Strauss and Aspergillosis require the highest doses of inhaled steroids and occasional boosts of systemic steroids to obtain minimal control.

About 25% of untreated asthmatics and up to 50% of treated asthmatics have non-eosinophilic asthma. This is why it's important for researchers, and physicians, to be aware of the following types of airway inflammation.3,4

Neutrophilic inflammation

The quest to better understand severe asthma lead to the discovery that some asthmatics have elevated neutrophil levels in their airways (neutrophilic asthma). Those with this type of inflammatory response are usually non-allergic, and so they are described as having intrinsic asthma. Their asthma triggers generally include particulates in the air, pollutants, vi0nnruses and bacteria (infection-induced asthma). 3

Exposure to these asthma triggers trigger the release of mediators, the most significant of which is Interleukin 8 (IL8),3 which travels through the bloodstream and recruits neutrophils.

Neutrophils, like eosinophils, are granulocytes. Once they arrive in the airways, they release their contents (degranulate), which include many mediators of inflammation. They, like eosinophils, enhance the inflammatory effect, resulting in asthma symptoms. Since neutrophil levels are chronically elevated, asthma symptoms persist, resulting in some degree of shortness of breath even on good asthma days.

To make matters worse, neutrophils respond poorly, and sometimes not at all, to corticosteroids. This means that the highest doses of corticosteroids, and sometimes non-traditional asthma medicines (like COPD medicines) are needed to obtain minimal asthma control.

This subgroup of asthma is not as well understood as eosinophilic asthma. Smoking may cause it (asthma/ COPD overlap syndrome), chemicals in the air at your work may cause it (occupational asthma), and something unknown may cause it.3,5

Mixed neutrophilia and eosinophilia inflammation

This is the worse kind of asthma and is associated with refractory asthma (asthma not responsive to anything). One study found that they have the lowest lung function of all the asthma subgroups. They also had the highest frequency of daily wheezing and the highest healthcare utilization. They require frequent doctor visits, and an assortment of topline (corticosteroids, bronchodilators) and alternatives (such as COPD medicines) to obtain even minimal asthma control.5

Paucigranulocytic inflammation

Pauci means few. So, paucigranulocytic means few granulocytes. This is an unusual (and newly defined) subgroup of asthma associated with normal or near normal levels of eosinophils and neutrophils. It may also be called non-inflammatory asthma.3,5

Like neutrophilic asthma, this subgroup is not well understood. It is possible that there is some degree of eosinophilia, in which case corticosteroids may prove useful. Otherwise, typical and atypical asthma medicines may be indicated to obtain any degree of asthma control.6

A shift in the way asthma is phenotyped

Here you have four new asthma subgroups (phenotypes) based on the types of inflammatory cells, or lack of them, in asthmatic airways. This is a more specific form of phenotyping and is often referred to as cellular phenotyping.5 It is much more specific than traditional phenotyping, which is based on characteristics observed by physicians in the clinical setting (hence, allergic asthma, extrinsic asthma, EIA, occupational asthma, etc.1,2,5

Looking forward

The next goal of researchers is to learn what asthma genes, and what "biological pathways" are responsible for each of these inflammatory responses. And, of course, the ultimate goal is that research in this regard will lead to better treatment options to help all asthmatics obtain ideal asthma control.9

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