Understanding the Role of the Allergic Cascade in Asthma Attacks

I remember the first time I ever heard the term, "allergic cascade," was in the early 2000s. It came up while I was talking to a doctor I worked with about a long-lasting and increasingly more severe allergy/asthma attack I was having. I was having trouble understanding why allergy and asthma symptoms had ratcheted up to another level hours after being exposed to one of my triggers. She explained how the allergic cascade causes this to happen after allergen exposure. The term, and her description of how it worked reminded me of a multi-level waterfall, with the water cascading ever stronger from ledge to ledge.

If you've never heard of this allergic cascade, it's not surprising. I don't think it's a term most laypeople would have heard. I'm not sure how many healthcare professionals even know what it is. I mean, I didn't before that discussion, and I'd already been a nurse for almost 20 years at that point.

Most asthma is allergic

In the U.S., more than 26 million people have asthma. And most of those people, as many as 60%, have the allergic type of asthma.¹ What this means, if you're like most of us, is that the things that trigger your asthma symptoms are allergens. Allergens are normally harmless substances that your immune system treats as health threats. They can include:

• Pollen
• Dust mites
• Mold
• Pet dander, saliva and urine
• Insect droppings

As a result, your immune system releases a substance called immunoglobulin E (or IgE for short). IgE then causes an inflammatory response in your airways. And that results in allergy symptoms such as sneezing, runny nose and congestion, in addition to common asthma symptoms such as:

• Wheezing
• Shortness of breath
• Coughing
• Chest tightness

The allergic cascade is progressive

Back to the idea of the allergic cascade--when doctors use this term, they are referring to a progressive sensitization and response to allergens. There are 3 stages:²

• Sensitization, or induction
• Early phase
• Late phase

During all 3 of these phases, there are different body cells and hormones or chemicals in play. For example, as mentioned above, initially IgE kicks off the allergic reaction. Later on, cells called eosinophils take a larger role. Chemicals called mediators also interact with these immune system cells during these stages.³

Sensitization

We all come into contact with hundreds of substances in the environment every single day. But in certain people, being exposed to some of these things, such as pollen, for the first time causes the immune system to overreact and become "sensitive" to that substance from then on.

When this happens, a cascade of reactions among immune cells occurs, for example:

• T helper cytokines stimulate B cells
• B cells become plasma cells that start making IgE antibodies
• IgE antibodies bind to mast cells

In most cases, all this occurs somewhat silently. This means that although the allergic process has been triggered inside your body, you will probably not have any noticeable symptoms this first time around. Complete sensitization could happen after only one contact with an allergen. In some people, though, it might take a few exposures to become fully sensitized.

Early phase

Once you are fully sensitized, when you come into contact with that allergen again, your body knows it is a (supposed) threat and is armed and ready to fight it off. In essence, your immune system reacts in a similar way to how it fights off germs such as bacteria and viruses that cause infections.

Think of those combination IgE antibodies and mast cells formed during the sensitization phase as soldiers. They release weapons called mediators to travel throughout the body and fight off the invaders, such as pollen. One of the most common mediators is histamine.

The early phase reaction can begin within minutes after exposure to an allergen, and then may continue for 3-4 hours. During this time, you will notice some of all of the allergy and asthma symptoms detailed above.⁴

Late phase

This is the phase that got me talking to my doctor friend all those years ago. After an intense allergy and asthma attack from pollen, my symptoms started to subside after a couple of hours. But then, they got worse again. The late phase of the cascade is the reason why this happens.

The immune system response labeled as late phase begins at the same time as the early phase. However, the changes it causes don't actually cause symptoms right away. In this phase, the "soldiers" mobilized in the early phase recruit helpers, inflammatory cells that include:⁴

• Eosinophils
• Neutrophils
• Basophils
• Monocytes
• Lymphocytes

These cells cause further and continued inflammation of the airways. As a result, symptoms from this phase will begin about 4 hours after exposure to your allergen, and then can continue for 6-12 hours. That's no fun, right?

Fighting the allergic cascade

Current asthma treatments are designed to address the various stages of the allergic cascade. Allergy shots, also called immunotherapy, work to make you less sensitive to an allergen. In other words, they work against the first phase. Other medications, such as antihistamines, disrupt the mediators released in the early phase of the cascade. Bronchodilators also fight the effects of the early phase.

Other medications, such as inhaled steroids, aim to decrease the inflammation common to late phase.

In summary

Understanding the allergic cascade isn't going to result in earth-shattering changes in how you manage your asthma or in your asthma control. However, if you're a science nerd like me, it may go a long way toward figuring out why your body reacts the way it does to the world around you. That can help you be better prepared for the whole allergic cascade effect. Be sure you always have your allergy and asthma medication easily accessible!