Late Phase Asthma Attack, Part II
It's been a while since I wrote "Late Phase Asthma Attack." It's been a while since I wrote about something complicated or since I made something complex seem simple. So, I figured it's about time to expound upon what I wrote in part 1. So, here, without further ado, is some additional information researchers are learning about the late phase asthma attack.
What is the late phase?
The early phase asthma attack is what happens when you are first exposed to an asthma trigger. It also happens when you are exposed to something you are allergic to. The late phase and early phase are also used to describe allergy attacks. The early phase generally presents with mild symptoms.1
The late phase happens a while later. It’s what causes asthma attacks to become severe. It’s what causes severe asthma. The main culprits here are eosinophils. These are white blood cells that cause very aggressive airway inflammation. This is what makes asthma hard to treat.1
And do check out the links in this article. All the links here are purposefully placed so you can click them to get more information on this topic. This is all in an effort to learn as much as we can about this disease. We are learning lots about asthma, so there are lots of links here.
There's more to late phase asthma
I tried to keep part 1 pretty basic. Yet there is a lot more to the late phase that researchers are learning. There appear to be different cells and chemicals suspected to be involved in the late phase asthma attack. This is what researchers suspect is the cause of the late phase. They suspect that this is what may cause severe asthma attacks and severe asthma.2
So, this is what researchers are thinking. This is getting deep. But this is also a testament to how hard researchers are working, and how much they are learning, about our complex disease called asthma.
In our example in part 1, we used the asthma trigger dust mites. You inhale a lot of dust mites, and a reaction happens. You go through phase one. Then you go through phase 2. So, here are some more cells and chemicals researchers think are involved in the late phase of asthma.
Late phase cells
Th1 Cells. As noted in my post, “What is Sensitization?” they are another T-Cell that may play a role in allergic asthma, and probably in the late phase. Its exact role is yet unknown. They may also play a role in other more severe subgroups of asthma.3
Interleukine 17 (IL17). This is a cytokine released by Th1 cells. One study in mice found that its levels were increased in mice that were IgE sensitized. Other studies have correlated increased IL17 in asthmatics with poorly controlled asthma.4-6
Future medicine may block its effects. This is me talking here. Still, it’s a possibility. It’s a possible future medicine that may prevent or control severe asthma.
Th2 cells. They played a key role in the early phase. Here, in the late phase, they are still dominating, and this is why this entire process is often referred to as Th2 dominant asthma. I will describe this in more detail in an upcoming post. For now, they release more pro-inflammatory cytokines, including more IL5, IL13, and more IL 4.6
Interleukin 4 (IL4). It recruits even more Th2-cells, which release even more IL 4. This results in an ongoing loop that prolongs the inflammatory response.7
T-regulatory cells (Tregs). They are leukocytes that suppress the activity of Th2 cells and therefore suppress the allergy and asthma response. After dendritic cells present antigens to T-cells, they migrate to the lymph nodes and cause a reduction in Tregs and they activate NK cells.7
Natural killer (NK) cells. They work independently of antigens and are able to identify, bind with, and destroy cells infected with viruses, bacteria, or cancer. Their production is increased during the late phase asthma response as they secrete lots of Th2 cytokines. A genetic defect in this area can lead to severe allergies. A genetic defect may also lead to severe inflammation leading to airway scarring and severe asthma. Along with activating them, Tregs have also been shown to suppress their effects, perhaps so they don’t get carried away and cause harm.6,8
Interleukin 10 (IL10). It’s an anti-inflammatory cytokine created by the IL10 gene and released mainly by Th2 cells, mast cells, and Tregs. It acts to suppress dendritic and Th2 cells to prevent inflammation and to prevent autoimmune disorders. However, it has also been shown to prolong the life of B-cells and inhibit the production of IFNγ.5,8
Interferon (IFNγ). It’s a cytokine secreted by natural killer cells and Th1 cells and inhibits B-cells from making IgE antibodies. IL10 essentially blocks their effect so that IL4 can go ahead and tell B-cells to make dust mite IgE antibodies. IFNγ is also important to the destruction of pathogens that have been ingested and broken down (phagocytosis) by certain white blood cells.5
Before we go on, a quick refresher is needed. Dendritic cells are leukocytes (white blood cells) that recognize antigens (in our case dust mites) and present them to Th2 Cells, which run the show here.9
A sample patient
So, our sample patient here has allergic asthma. The early phase occurred 4-8 hours ago. Reinforcements are arriving. In part 1, I listed some of these reinforcements. Here is the rest.
CD4 Gene. It contains the recipe for a glycoprotein called CD4. (Can this gene be shut off or fixed with some future medicine?).5
CD4. It attaches to the surface of dendritic and T-Cells, also referred to as CD4 T-cells.
As noted in my Sensitization post linked to above, these are usually referred to as T-cells. There are four types of CD4 T-cells: Th1, Th2, Th17, and T-Regs. They all control adaptive immunity by releasing cytokines that activate other immune cells. They all play some role in allergic asthma, although Th2 plays the most significant role (see "Th2 Dominant Asthma"). Th2 cells release lots of Th2 cytokines, and they are the main instigators of the Th2 dominant inflammatory response that causes allergy and asthma symptoms. Th1 and Th17 may play a more significant role in the other more severe subgroups of asthma.6,7,10
A flaw in the CD4 gene may cause naive (immature) CD4, which may be responsible for causing dendritic and Th2 cells to recognize harmless antigens as harmful, thereby initiating the Th2 dominant inflammatory response. This causes allergy and/or asthma attacks. So, you can kind of see how this information is useful. A future medicine or biologic may block the effects of CD4 and prevent this response. It may help people obtain better asthma control.6,7,10
What to make of this?
What to make of this is researchers are getting deep. They are learning more and more every day about our disease. So, by the late phase, we are into a full-fledged asthma attack. This usually continues until your body succeeds at getting rid of the trigger. In this case, it's dust mites. When they are gone, all of these chemicals will decline to normal or near-normal levels and symptoms will subside. The process of resolving symptoms may naturally subside on their own, although they often require medical intervention.11
Do you get muscle cramps caused by your asthma medicine?