Asthma was once considered a single, though complex, disease. Now it’s recognized as a spectrum of diseases. Each type of asthma has a diversity that can result in different responses to treatment in people.
Severe asthma is one form of the disease. It’s estimated that 5-10 percent of people with asthma have severe asthma. Severe or difficult-to-treat asthma is broken up into subtypes that include allergic asthma, eosinophilic asthma and non-eosinophilic asthma.
Severe asthma is the diagnosis when…
- asthma symptoms are not well-controlled by high-dose inhaled corticosteroids (anti-inflammatory controller medications);
- the patient experiences two or more asthma attacks in a 12-month span requiring oral corticosteroids (pills that treat severe acute asthma symptoms).
Asthma is characterized by airway inflammation and airway hyper-responsiveness. This leads to asthma symptoms: coughing, wheezing, shortness of breath and chest tightness. Environmental and genetic factors often play a role in who develops asthma.
Recent medical breakthroughs involving severe asthma are transforming how it is diagnosed and treated. Airway inflammation is a particular focus. New medications focus on treating a specific type of inflammatory response called Type 2 inflammation. This can lead to poorly controlled asthma or uncontrolled asthma.
What is Type 2 inflammation in asthma?
Many people have allergic asthma in which their symptoms occur after exposure to allergens, irritants such as air pollution, or even weather changes. For others with asthma, an important contributor to severe or persistent asthma is inside their body. It’s a form of asthma called Type 2 inflammation.
As many as 50-70 percent of asthma patients have Type 2 inflammation. Type 2 inflammation is a systemic allergic response that involves the activation of immune cells, including eosinophils, mast cells and T-cells. These cells release inflammatory mediators called cytokines, chemokines and IgE antibodies.
This process results in inflammation in the airways. It can lead to an increased risk of asthma exacerbations and decreased lung function.
Cytokines, which are proteins that signal the body’s cells and begin an immune response, are major contributors to Type 2 inflammation.
Common asthma biomarkers are also present in Type 2 inflammation. These include:
- eosinophils (white blood cells involved in airway inflammation)
- Immunoglobulin E (IgE, the chemical associated with allergies)
- fractional exhaled nitric oxide (FeNO, chemicals in the breath produced by cells in an inflammatory response)
When there are too many eosinophils in the blood, it can cause eosinophilic inflammation and an increased risk of severe asthma flares. This is known as eosinophilic asthma.
Genetics also appear to play a role in Type 2 inflammation. Studies show that if one or both parents have Type 2 inflammation related to asthma, their child is four times more likely to have asthma or an allergic disease.
What are symptoms of Type 2 inflammation in asthma?
Symptoms of severe asthma with Type 2 inflammation are similar to those of regular asthma, but they are more severe and persistent. These symptoms may include:
- Frequent coughing, especially at night
- Shortness of breath, even during mild activity or at rest
- Wheezing that persists even with medication
- Difficulty sleeping or sleep disturbances due to asthma symptoms
- Increased use of quick-relief inhalers
Asthma patients with excessive Type 2 inflammation may have one or more Type 2 inflammatory diseases of varying levels of severity. These diseases may include:
- Chronic rhinosinusitis with nasal polyps (CRSwNP)
- Aspirin-exacerbated respiratory disease (AERD)
- Severe atopic dermatitis, or eczema
- Chronic idiopathic urticaria (CIU; also called chronic spontaneous urticaria)
- Eosinophilic esophagitis (EoE)
- Gastroesophageal reflux disease (GERD)
- Sleep apnea
What severe asthma treatments are available?
Doctors and scientists are getting a better understanding of severe asthma including Type 2 inflammation. This has led to new and innovative medications.
Treatment for severe asthma is more intensive than for mild or moderate asthma. The goal is to reduce airway inflammation and improve lung function. This can be done by medications that do the following:
- treat the airway inflammation and asthma symptoms;
- inhibit the source of Type 2 inflammation to lower the risk of asthma attacks and hospitalizations.
Talk with your doctor about which medications are right for you. Here are some common severe asthma medications that may reduce Type 2 inflammation:
Inhaled corticosteroids are a common treatment for asthma, but people with severe asthma may require higher doses to control symptoms. Because they are inhaled, these medications go directly to inflamed airways. Inhaled corticosteroids reduce inflammation in the airways and improve lung function. They can also reduce mucus production. Inhaled corticosteroids must be taken daily to prevent severe exacerbations.
Inhaled corticosteroids are different from oral corticosteroids. Oral corticosteroids are pills that treat severe acute asthma symptoms. They are typically prescribed for a short period of time (5-7 days). Oral corticosteroids have 10 times the dosage of inhaled corticosteroids. As a result, there is an increased risk of side effects such as headaches, easy bruising of the skin, weight gain, moodiness and depression. Long-term oral corticosteroid exposure can result in serious side effects that involve eye problems, diabetes, increased risk of infections, and thinning bones.
Combination medications combine two medicines into one inhaler. Your doctor may prescribe an inhaler that contains an anti-inflammatory corticosteroid and a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). They reduce inflammation in the airways, improve lung function and can relieve cough, wheeze and shortness of breath. Combination inhalers must be taken daily to prevent asthma symptoms.
In recent years, scientists have developed medications called biologics. These medications treat a variety of diseases including asthma. They are typically reserved for people with moderate to severe asthma that is not well controlled with inhaled corticosteroids.
Biologics are designed to treat the source of symptoms rather than the symptoms themselves. They target the cells and pathways that lead to allergic inflammation and breathing problems for people with asthma. They work by interrupting the process that causes inflammation, thus reducing asthma symptoms.
Biologics are often called “precision medicine” because they are designed for particular types of a disease. Some biologics target eosinophils and IgE while others target cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13.
Biologics are often used in combination or as an add-on therapy with other asthma medications. Types of biologics that can help with Type 2 inflammation include:
This medication blocks the antibody IgE, which triggers asthma symptoms. It is typically used for people with allergic airway inflammation.
This medication targets IL-5 and work by decreasing the number of eosinophils in the blood. This reduces airway inflammation and lung inflammation.
This medication blocks IL-4 and IL-13 that play a role in asthma inflammation. It is prescribed to people who have high levels of eosinophils and/or a history of allergies.
This medication targets IL-5 to prevent the activation of eosinophils that can cause inflamed airways.
This medication also targets IL-5 and works to decrease eosinophils. It is used to treat severe asthma in people with high levels of eosinophils in their blood.
If you have severe or persistent asthma that is difficult to control despite medication, talk with your doctor about Type 2 inflammation. You may want to ask whether stepping up medications to a biologic is right for you.
How do you manage asthma with Type 2 inflammation?
Managing asthma with Type 2 inflammation involves a comprehensive approach that addresses both the underlying causes and the symptoms of the condition.
Medications are likely to be part of your asthma management plan. Talk with your physician about your medication options – including inhaled corticosteroids and biologics – and decide together which is best for you. Lifestyle factors that can impact asthma – exercise, diet, stress and sleep, among others – are also evaluated and addressed.
Some strategies to help with asthma management and Type 2 inflammation include:
Identify and avoid triggers
Asthma symptoms can be triggered by a variety of factors, including allergen exposure, pollutants, and cold and flu viruses. Identifying and avoiding these triggers can reduce the frequency and severity of asthma symptoms.
Take controller medications as prescribed
If you’re prescribed a controller medications such as an inhaled corticosteroid, it’s important to take it daily, even if you feel well. Inhaled corticosteroids are designed to reduce airway inflammation and prevent asthma symptoms from occurring.
Use quick-relief medications as needed
Quick-relief albuterol inhalers can provide immediate relief of asthma symptoms. These medications should be used as needed, but it is important to talk to your doctor if you are using them frequently. If you are using them more than twice a week, this is a sign of severe or uncontrolled persistent asthma.
Monitor your asthma symptoms
Keeping track of your asthma symptoms can help you identify triggers and determine if your treatment plan is working effectively. Work with your doctor to develop an Asthma Action Plan. This is a personalized document that takes into account that each person’s asthma is unique and responds to treatments differently. It spells out how to treat your asthma daily and what to do if symptoms get worse.
Make Lifestyle Changes
Lifestyle changes are often overlooked in asthma management but they can play an important role in improving symptoms. Regular exercise, maintaining a healthy weight, reducing stress, getting enough sleep and avoidance of smoking or secondhand smoke can improve your breathing and quality of life.
People with allergic asthma may want to consider allergen immunotherapy, also known as allergy shots. Allergen immunotherapy involved receiving regular injections of small amounts of your allergen over several months or years. This can help desensitize your immune system to the allergens that trigger your asthma symptoms. Allergen immunotherapy is not a cure. When successful, it can reduce your immune response pattern to allergens and significantly improve quality of life.
Other conditions that involve Type 2 inflammation include:
- Atopic dermatitis, or eczema
- Nasal polyps
- Chronic rhinosinusitis with nasal polyps
- Aspirin-exacerbated respiratory disease (AERD)
- Gastroesophageal reflux disease (GERD)
- Sleep apnea
Bradley Chipps, MD, FACAAI, is a board-certified allergist and pediatric pulmonologist with Capital Allergy and Respiratory Disease Center in Sacramento, California. He earned his medical degree from University of Texas Medical Branch in Galveston in 1972. He is Past President of the American College of Allergy, Asthma and Immunology (ACAAI).