Severe Asthma

Understand what severe asthma is and how it is diagnosed and treated.

People with asthma always have some underlying inflammation in the airway that can usually be treated with a combination of quick-relief and long-term controller medicines. But some people may not respond well to inhaled corticosteroids or other long-term controller medicines, a sign that they may be suffering from severe asthma. This inflammation may be more difficult to treat and requires testing to find the root cause of the inflammation. By working with your physician, you should be able to develop a custom approach for treating your asthma.

Diagnosis

Diagnosing Severe Asthma

People with asthma may have ongoing symptoms and flare-ups, but that doesn’t necessarily mean they have severe asthma. Of the more than 25 million people in the U.S. living with asthma, only about 5-10% suffer from severe asthma. That is why it is important to talk to your doctor to determine if your symptoms signal severe asthma or are just uncontrolled asthma.

Uncontrolled asthma is often defined by the frequency of symptoms. For example:

  • Daytime asthma symptoms (e.g., shortness of breath, chest tightness, cough) more than twice a week
  • Waking up at night with asthma symptoms more than twice a month
  • Using quick-relief medicine for symptoms more than twice a week
  • Limiting activity because of asthma
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Uncontrolled vs. Severe Asthma

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Having three or more of these issues puts people with asthma into the uncontrolled category. These individuals could better control their symptoms by working with their asthma healthcare provider and discussing any issues with medication, reviewing inhalation techniques for medicines, and determining asthma triggers. Together, they should develop a plan to limit or avoid triggers and adjust their asthma treatment plan, such as adding a long-term controller medicine. 

Difficult to Treat Asthma

People whose asthma remains uncontrolled despite using high dose controller medicines are described as having difficult to treat asthma. Factors that may make an asthma patient more difficult to treat are having another chronic health condition, incorrect inhaler technique, and/or inconsistent use of prescription medicine.

Severe Asthma

Patients with severe asthma use the highest dose of inhaled corticosteroids plus a second controller and/or oral corticosteroids. However, despite using high dose medicines, reducing risks, and following their treatment plan, many times their asthma remains uncontrolled. Severe asthma is categorized into three types: allergic asthma, eosinophilic asthma and non-eosinophilic asthma.

Do you have uncontrolled asthma or severe asthma symptoms?

Take this assessment to help understand if your asthma is under control and access a downloadable summary to take with you to your next doctor’s appointment.
My Asthma Control Assessment
Testing

Testing for Severe Asthma

Before you can be tested for severe asthma, you will need a referral from your primary healthcare asthma provider to either an asthma specialist (pulmonologist) or allergy specialist (allergist). The specialist will review your medical history, your current asthma treatment plan and do a physical exam to assess your symptoms. If the specialist thinks you may have severe asthma, they will discuss additional testing with you to determine your specific type. This often starts with testing to identify a biomarker.

Biomarkers help determine what is causing the inflammation in your airways. Taking a blood sample, analyzing a mucus sample (sputum) or taking a breathing test that measure substances in your breath droplets are all common tests doctors use. These tests are performed in a doctor’s office or an outpatient clinic setting. Your specialist will recommend one or more of these tests based on your medical history and current symptoms.

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The underlying inflammation of a severe asthma patient’s lungs may be more difficult to treat and requires testing to identify biomarkers causing the inflammation.

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Once the biomarkers are identified, your doctor can determine the type of severe asthma and the different treatment options that are available to treat that specific type.

Your physician should discuss the tests and treatment options with you so together, you can make a decision based on what you both agree will work best for you.

Below is a chart that describes the biomarkers for severe asthma, the testing method, the type (or phenotype) and the available possible treatment options for targeted therapy.

Biomarker

Testing methodPhenotypeAvailable treatments

IgE*

Blood
Skin

Allergic (early onset)

Omalizumab

Eosinophil

Blood
Sputum
Breath (FeNO)

Eosinophilic (late onset)
—allergic and non-allergic

Mepolizumab
Reslizumab
Benralizumab
Dupilumab

Neutrophil

Sputum

Neutrophilic

Antibiotics
Lifestyle changes

*IgE - immunoglobulin E

Types

Types of Severe Asthma

There are two main categories of severe asthma—Type-2 inflammation and Non-Type-2 inflammation. These categories are based on a person’s response to treatment. Type-2 inflammation includes allergic asthma and eosinophilic asthma (or e-asthma) and Non-Type-2 inflammation includes non-eosinophilic asthma. For example, allergic asthma and e-asthma respond to treatment with inhaled corticosteroids and IgE (biomarker immunoglobulin E)-directed therapy or other biologics listed in the above table. Patients with Non-Type-2 inflammation, including non-eosinophilic asthma, generally do not respond well to inhaled corticosteroids. Allergic asthma and e-asthma have distinct biomarkers and treatment options available today. Treatments for non-eosinophilic asthma are currently being developed.

Tree chart showing the branches of the 2 main types of severe asthma: Type-2 inflammation and Non-type-2 inflammation

Allergic asthma is caused by exposure to allergens such as pollen, pet dander, molds, etc. Most people diagnosed with allergic asthma will also have a diagnosis of hay fever or rhinitis. For these patients, exposure to allergens causes the body’s immune system to produce immunoglobulin E(IgE), an antibody that attaches to certain cells and causes them to release chemicals creating an allergic reaction. When this happens, common symptoms are sneezing, itchy/watery eyes, severe allergic reactions (anaphylaxis), and increased airway sensitivity.

Eosinophilic asthma (E-asthma) is characterized by having an increase in eosinophils, a type of white blood cell that helps fight disease and infections. However, in some people, a high number of eosinophils can have a negative effect and results in inflammation of the airways which in turn causes asthma symptoms. An increase in the number of eosinophils can also be the result of an allergic reaction, a parasitic disease or a reaction to certain medications.

Non-eosinophilic asthma includes neutrophilic, smooth-muscle mediated and mixed cells. People in this subgroup have few to no eosinophils in test results, and do not respond well to inhaled corticosteroids.

Neutrophilic asthma is a type of non-eosinophilic asthma. Neutrophils are the most common white blood cell in the body that help fight infections. Having too many neutrophils can cause Non-Type-2 inflammation in the airway, resulting in increased asthma symptoms. This type of asthma does not respond well to inhaled corticosteroids and using them may cause an increase in neutrophils. Neutrophilic asthma is associated with chronic bacterial or viral infections, obesity, smoking, and airway smooth muscle abnormalities.

Talk to Your Doctor

The best way to determine what type of severe asthma you may have is to talk to your asthma healthcare provider. You can also use our Severe Asthma Treatment Planning Tool and download the Severe Asthma Treatment Decision-Making Worksheet to help you start a discussion with your asthma specialist.

Treatment

How to Treat Severe Asthma

Once your asthma specialist has determined the type of severe asthma you are suffering from, they can tailor treatment based on your specific type.

Basic treatment for severe persistent asthma consists of inhaled corticosteroids. Additional long-term controller medicines, such as long-acting beta 2 agonists (LABA), montelukast or theophylline, are added if asthma is still uncontrolled. Oral corticosteroids can be added on to treatment if patients are still experiencing symptoms and flare-ups.

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Treating Severe Asthma

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A personalized treatment plan may include:

Macrolide antibiotics are used to help the body fight infection. These medicines control the number of white blood cells (or neutrophils) found in your airways. One study showed positive results using macrolide antibiotics in people with high counts of neutrophils in blood or sputum samples. Doctors don’t suggest these medications be used long term though because side effects, such as antibiotic resistance, can be very serious.

Oral corticosteroids are medicines that help to control inflammation. While experts recommend these medicines only for short-term use, doctors may prescribe them long-term for people with more frequent asthma flare-ups. Severe asthma patients use these medications in combination with quick-relief medicine, high-dose inhaled corticosteroids and long-acting bronchodilators. Side effects from using oral corticosteroids can pose a risk to the function of other bodily organs, but the benefits may at times outweigh the risk. The hope is that by using these powerful drugs for a short period of time, patients can gain better control and will eventually not need them at all. This treatment option is approved for adults and children, although long-term use in children is not recommended due to the higher risk side effects. If symptoms are still not controlled with long-term use of an oral corticosteroid, another treatment option should be considered and may include targeted therapies such as biologics.

Biologic medicines for moderate-to-severe asthma help block the response to airway triggers that cause inflammation, specifically targeting the cells that are part of the body’s immune system. Biological products include a wide range of medicines that are delivered either by an injection in your doctor’s office, IV infusion in a clinic or hospital or self-injection at home. People taking biologics receive treatment every 2-8 weeks depending on the particular biologic. Biologics are approved for people 18 years or older, and several are available for children as young as 6 years old. Pharmaceutical companies have been researching and developing these new biologic medicines with more on the way. Like most medicines, people taking biologics can experience side effects. However, this treatment option is worth discussing with your specialist to see if one of these may be right for you.

Bronchial Thermoplasty (BT) is a procedure that involves using radio frequency energy to apply mild heat to the smooth muscle tissue in the airway. The heat reduces the amount of smooth muscle tissue, causing less airway constriction and reducing flareups. BT is an option but is generally limited to those patients whose severe asthma does not respond well to inhaled corticosteroids and/or long-acting bronchodilator medications and also rely on oral-corticosteroids more than twice a year to manage asthma attacks or take an oral corticosteroid for daily maintenance. This treatment option is only available to adults and not recommended for patients that have other health conditions besides severe asthma.

Smoking, obesity, GERD and exposure to environmental triggers are linked to Non-Type-2 inflammation. This type of inflammation is mostly associated with the presence of neutrophils and few to no eosinophils in the airways. Neutrophils are white blood cells that the body produces to fight infection. Quitting smoking, changing diet, exercising, and reducing exposure to environmental triggers are strategies that may help to improve this (Non-Type 2) type of asthma. 

New treatments are available for patients with severe persistent asthma whose asthma is not controlled with inhaled corticosteroids and long-acting bronchodilators. Below are types of severe persistent asthma and their available treatments.



Type of severe asthma

Available treatment

Atopic or allergic asthma

Anti-IgE (omalizumab)

Blocks IL-4 and IL-13 (dupilumab)

Eosinophilic asthma

Blocks IL-5 (mepolizumab, reslizumab and benralizumab)

Blocks TSLP (tezepelumab)

Hyperreactive asthma

Bronchial thermoplasty

Treatments for allergic or eosinophilic asthma are given as an injection or IV every two to eight weeks depending upon the dose and medication required. Bronchial thermoplasty is a treatment given through an outpatient procedure called a bronchoscopy (a flexible tube with a light on the end of it). The bronchoscopy allows a pulmonologist to introduce a catheter that applies heat to the inside of your bronchial tubes. This heat causes the smooth muscle around your bronchial tubes to decrease by 60-70 percent and your airways become "less twitchy" to triggers.

Download the Severe Asthma Treatment Decision-Making Worksheet and use our Severe Asthma Treatment Planning Tool to help you start a discussion with your specialist.

PrecISE Clinical Study

PrecISE is a clinical study that uses precision medicine for severe asthma. Precision medicine is an approach to the prevention and treatment of disease that uses information about an individual's or group's specific disease process, symptoms, and treatment responses, to identify the medicines and therapies that are most likely to be effective for them.
Learn more

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