The Pathopysiology of Asthma

The pathophysiology of asthma—that is, the processes it entails—involves multiple organs, systems, and mechanisms. While these differ somewhat from one type of asthma to the next, the end result is the same: bronchoconstriction, inflammation, and mucus overproduction that make it harder for you to breathe. What sets all of this into motion, asthma's pathogenesis, is equally complex.

Learning more about how asthma comes about can help you better understand how various treatments and management approaches can minimize asthma's impact on your life and why your doctor may recommend one over another.

Pathophysiology of Asthma

Pathophysiology is the way in which a disease alters the normal function of your body. The term is derived from Greek prefix pathos, meaning "suffering," and the root physiologia, meaning "natural philosophy."

The pathophysiology of asthma involves:

• Hypersensitivity
• Hyperresponsiveness to stimuli
• Bronchoconstriction and inflammation
• In severe cases, airway remodeling

Hypersensitivity

People with asthma are known to be hypersensitive to things called triggers. What this means is that the immune system incorrectly perceives certain stimuli, such as dust or pollen, to be harmful. This sensitivity is what causes allergies and sensitivities.

Common allergens include:

• Dust mites
• Animal dander or fur
• Mold
• Pollen
• Certain foods (e.g., peanuts, milk, eggs)
• Certain drugs (e.g., penicillin, cephalosporin antibiotics, anti-inflammatories)

Common sensitivities include:

• Smoke
• Dust
• Air pollution
• Strong odors
• Workplace chemicals

Hyperresponsiveness to Stimuli

In people without asthma, the airways relax when an irritant is breathed in to help expel it. In asthma, the airways don't relax and actually get smaller. This is called hyperresponsiveness, and it's somewhat like a twitch in your airways that's especially easy to induce.

The narrowing of the airways makes it more difficult to breathe. When you use your rescue inhaler, you feel better because the medication relaxes your airways and makes them larger so that air can flow more easily.

Bronchoconstriction and Inflammation

Hyperresponsiveness causes your bronchial tubes to contract. At the same time, inflammatory cells and chemicals flood your airways and cause inflammation, which further restricts your breathing and can become chronic.

Bronchoconstriction and inflammation combine with excess production of mucus, which exacerbates breathing difficulty and leads to a chronic cough that works to release the mucus.

Bronchospasm typically lasts for one to two hours before resolving. In some cases, however, it may appear to resolve only to have an attack occur up to 12 hours later.

Asthma symptoms may be present only on occasion or all the time, depending on your asthma severity. Asthma exacerbations, or attacks, involve a more extreme tightening of the airways that makes it hard to breathe and can be life-threatening.

Airway Remodeling

In more severe cases, chronic inflammation can lead to a process called airway remodeling in which the walls of the air passages thicken and harden, the glands enlarge, and networks of blood vessels grow rapidly and abnormally.

While less severe asthma is considered reversible with proper treatment and management, airway remodeling is currently irreversible. It's associated with worsened symptoms and more frequent and severe asthma attacks.

Pathogenesis of Asthma

Taking a step back, all of this begins with a changes that occur at the cellular level.

Hypersensitivity prompts an activation of the immune system and starts a complex chain reaction involving numerous cells and substances. This mechanism includes an early phase and a late phase.

The early phase begins when your immune system detects allergens or irritants in your body. In response, plasma cells release an antibody called immunoglobulin E (IgE). Antibodies are specialized cells that attack and try to destroy things your body perceives as threats.

The IgE then attaches itself to several types of white blood cells, which can vary due to the type of asthma.

Mast Cells

Mast cells are especially prevalent in certain areas of your body, including the lungs.

Once IgE attaches to a mast cell, that cell will respond to the presence of an allergen by releasing:

• Cytokines: Proteins that drive inflammatory processes through interferons, interleukins, and tumor necrosis factor-alpha (TNF-α)
• Histamine: A chemical messenger that dilates blood vessels, drives inflammation, causes symptoms of an allergic reaction (itchy, watery eyes and sore throat), and leads to bronchoconstriction and mucus production
• Prostaglandins: A compound involved in inflammation, mucus production, bronchoconstriction, and airway remodeling
• Leukotrienes: Chemicals that include highly potent bronchoconstrictors
• Platelet-activating factor (PAF): A substance tied to anaphylaxis, which is a severe and potentially life-threatening allergic reaction, and that may reduce the effectiveness of allergy medications

Basophils

Basophils perform a number of important functions, perhaps the most important of which is in certain inflammatory reactions, particularly those involving allergies.

Basophils are a part of the innate immune system, which triggers a non-specific reaction to anything the body considers harmful. Unlike adaptive immunity, which elicits a targeted response, innate immunity results in a generalized attack that involves inflammation, swelling, pain, fever, and fatigue.

Basophils, like mast cells, produce histamine, leukotrienes, and PAF. Having too many basophils in your blood (basophilia) can be a powerful driver of asthma symptoms, including:

• Severe inflammation of the lungs
• Bronchoconstriction
• Excessive production of mucus, causing coughing and respiratory obstruction

Basophils are especially implicated in allergic asthma.

Eosinophils

Eosinophils are less involved in allergic asthma and associated more with their own subtype, called eosinophilic asthma (e-asthma).

E-asthma is often severe and comes on most often in adulthood. While it involves an allergic response, many people with this type of asthma don't actually have allergies.

Eosinophils:

• Contain inflammatory chemicals
• Create leukotrienes (which increase bronchoconstriction)
• Express numerous cytokines (which drive inflammation)

E-asthma is believed to be associated with a set of symptoms not present with other asthma types, including:

• Chronic rhinosinusitis
• Nasal polyps
• Enlarged mucus membranes in the nasal passages
• Loss of smell

When chronic rhinosinusitis and nasal polyps accompany asthma, they can predispose you to aspirin-induced asthma. When all three conditions are present, they are collectively known as Samter's Triad.

Neutrophils

People with severe asthma that doesn't respond well to treatment with corticosteroid medications often have high levels of neutrophils. Their condition is sometimes referred to as neutrophilic asthma.

Produced in the bone marrow, neutrophils are first-line responders. They destroy allergens and other invading organisms (viruses, bacteria) by surrounding and ingesting them.

Neutrophils are part of an acute inflammatory response. They:

• Activate and regulate several immune cells
• Support chronic inflammation
• Release an array of cytokines and PAF
• Release thromboxane, a hormone that constricts the smooth muscles of the airways

They're involved in both the innate and adaptive immune response as well.

T Helper 2 Cells

T helper 2 (Th2) cells do as their name suggests: They support other cells in several ways, including assisting with their activation. Of course, in asthma, these key players in the immune response are what help trigger asthma symptoms:

• GM-CSF: This cytokine tells stem cells to produce basophils, eosinophils, and neutrophils, which help sustain inflammation.
• Interleukins: These immune-response regulators help keep basophils and eosinophils alive; one of them contributes to airway remodeling and thickening.

Macrophages

Like neutrophils, macrophages are made in your bone marrow and engulf foreign substances to destroy them. In asthma, macrophages release substances that initiate and prolong hyperresponsiveness of the airways, increase mucus production and swelling, and attract eosinophils to the lung.

These substances include:

• PAF
• Prostaglandins
• Thromboxane

Macrophages can ultimately increase asthma symptoms.

Late Phase

The late phase of asthma occurs over the next few hours, as many of these cells make their way to the lungs, causing increased bronchoconstriction and inflammation, which makes it harder for you to breathe.

Neutrophils, eosinophils, and Th2 cells are especially believed to be a part of the late-phase response. These cells can be found in the sputum of people with asthma and may be associated with severe exacerbations.

Impact on Asthma Treatment

While there is no cure for asthma, treatments can control its symptoms and slow (if not entirely stop) its progression. With the pathogenesis and pathophysiology of asthma in mind, doctors can recommend strategies to either minimize or normalize the response, or prevent it from happening.

Certain medications target specific cells and the processes they're involved in, which is why it's so important for doctors to pinpoint exactly what's going on in the body, including the minute cellular changes and the broader system-wide effects.

Some classes of medications used for treating asthma include:

• Mast cell stabilizers
• Leukotriene modifiers
• Antihistamines
• Bronchodilators

Mast Cell Stabilizers

Mast cell stabilizers are medications for allergic asthma that reduce inflammation by preventing mast cells from releasing histamine and other inflammatory chemicals.

Some mast cell stabilizers used as asthma treatment are:

• Intal/Gastocrom (cromolyn)
• Tilade (nedocromil)

Leukotriene Modifiers

Leukotrienes directly influence bronchoconstriction and airway inflammation as part of the body's allergic response, and leukotriene modifiers prevent that from happening.

Some common leukotriene modifiers prescribed for asthma include:

• Accolate (zafirlukast)
• Singulair (motelukast)
• Zyflo (zileuton)

Antihistamines

The most common medications for allergies are antihistamines, and these drugs can play a role in treating allergic asthma, as well.

Primarily, antihistamines are used to prevent the allergic responses that can lead to asthma attacks. Because antihistamines aren't the only chemicals involved in the inflammation and bronchoconstriction of asthma, they're generally not the only treatment needed for complete asthma control.

Antihistamines are available by prescription or over-the-counter. Some common antihistamines include:

• Allegra (fexofenadine)
• Benadryl (diphenhydramine)
• Clarinex (desloratadine) 
• Claritin (loratadine)
• Xyzal (levocetirizine)
• Zyrtec (cetirizine)

Bronchodilators

Bronchodilator medications help relax the muscles of the airways. Short-acting bronchodilators, often called rescue inhalers, are used to end asthma attacks or to prevent EIB. Long-acting bronchodilators are taken regularly to prevent attacks.

These medications, and especially rescue inhalers, are a mainstay of asthma treatment, regardless of type, because all types include bronchoconstriction.

Common short-acting bronchodilators include:

• Ventolin/Proair/Proventil (albuterol)
• Xopenex (levalbuterol)

Some long-acting bronchodilators are:

• Salmetrol (available in the combination drug Advair)
• Performomist (formoterol)
• Atrovent (ipratropium)
• Theochron (theophylline)

Taking Control of Asthma

In the end, the course of the disease is not inevitable and can be altered with the appropriate use of medications and lifestyle management, including:

• Taking long-term control medications as prescribed
• Keeping your rescue inhaler handy for when you need it
• Avoiding triggers that cause asthma attacks
• Getting vaccinated against the flu or pneumonia (so symptoms aren't compounded by other causes of breathing difficulties)
• Making lifestyle choices that improve lung function, including diet, exercise, and not smoking
• Visiting your doctor regularly so they can monitor your respiratory health and manage medications to keep your asthma well controlled

A Word From Verywell

The nitty-gritty about what makes asthma come about may ultimately seem most relevant to your doctor. And to a large extent, that is true. That said, it hopefully gives you a better sense of what is happening in your body and why certain treatments and management approaches are working (and worth committing to) and why others are not.

Doing what you can to influence the early part of the cascade of events that bring about asthma symptoms can help you live well with your condition.