The Late Phase Asthma Attack
Earlier I explained how asthma is an abnormal immune response. I showed how this abnormal immune response makes your body sensitized to asthma triggers. I explained what happens during the early phase of an asthma attack. Here, I aim to show what happens during the late phase of an asthma attack. Ready? Here we go.
The process involved in the asthma immune response
I want to explain that the biological processes involved in the asthma immune response vary depending on what asthma subgroup you have. So, for our case, we are using an allergic asthmatic. Our asthmatic was exposed to dust mites, was sensitized, and experienced the early phase of an asthma attack. Now, our asthmatic enters the late phase.
The late phase asthma attack
About 60% of asthmatics who experience the early phase will experience this late phase. This is your body’s natural response when you are constantly exposed to an asthma trigger like dust mites, or a high dose of them.
During the early phase, mediators of inflammation are released. Some immediately cause inflammation. This is what causes your early phase asthma attack. The rest travel through your bloodstream and recruit reinforcements.
The reinforcements start arriving 4-8 hours after initial exposure to an antigen (dust mites, in our case). When they arrive, the late phase asthma attack begins. These reinforcements cause persistent airway inflammation. This makes airways increasingly hypersensitive (twitchy) to asthma triggers. This response prolongs the asthma attack. It also increases the risk for future asthma attacks. It may last 12-24 hours . It may last even longer.1,2
Here is what happens. These are the reinforcements that are now inside your airways. They are meant to kill pathogens. Although in our case, they are abnormally recruited to kill harmless dust mites.
Interleukin 5 (IL5). It's a cytokine released by Th2 cells during the early phase asthma attack. Its role is to travel through your bloodstream and recruit eosinophils.
Eosinophils. They’re leukocytes that are attracted to and kill parasites. They also play the most significant role in the late phase. They were recruited in the early phase when Th2 cells released Interleukin 5 (IL5). In a way, many researchers say that IL5 leads the charge during the late phase of an asthma attack.1
When eosinophils come into contact with airway cells they degranulate. This means they release their contents. These contents include a variety of chemicals. I won't list any of them here. I will save that for a future post.
These chemicals are responsible for airways inflammation
But, it's these chemicals that are responsible for more aggressive airway inflammation. This inflammation tends to make asthma attacks more severe and difficult to treat.
The good news is that eosinophils respond nicely to corticosteroids. This is what makes steroids a top-line treatment for asthma. But, in a small number of asthmatics, eosinophil levels stay high. This is what causes a special type of asthma called eosinophilic asthma. This is responsible for your more severe asthma.
Severe asthma responds less well to corticosteroids. A new line of treatments called biologics come in handy here. Three newer biologics target IL5. Nucala and Cinqair bind with IL5 to render it harmless. Fesenra binds with IL5 receptors on eosinophils, making IL5 unable to communicate with them.
Biologics target the late phase asthma attack
In either case, these biologics target the late phase asthma attack. Their job is to make IL5 unable to recruit eosinophils. The goal here is that eosinophil levels will decrease. And this will improve asthma control.
Basophils. They are another white blood cell (leukocytes) with a high affinity for IgE antibodies. In our case, dust mite IgE antibodies bind with basophils. This causes them to release their contents. These contents include histamine and cytokines. Two cytokines secreted are IL4 and IL13. These same cytokines contributed to sensitization and the early phase asthma attack.3,4
Interleukine 4 (IL4). They are cytokines that tell cells to make IgE antibodies.
Interleukine 13 (IL13). They are cytokines that directly cause airway inflammation.
A biologic called dupilumab binds with IL4 receptors. It renders IL4 and IL13 harmless. It was originally approved by the FDA for atopic dermatitis. But, more recently it has been approved for moderate or severe asthma.
What to make of this?
The late phase is a lot more complex than I make it out to be here. But, this is all you need to know for now. It's this late phase that causes your more severe asthma attacks. It's usually the reason people get to the point they need to seek help for asthma. And many of our newer asthma medicines are aimed at this late phase.
What has your experience with Singulair been like?