Eosinophilic Asthma

Background

For decades physicians have understood that a diagnosis of asthma requires further description because attacks of wheezing and shortness of breath can be associated with several underlying diseases. For example, patients allergic to animal dander, such as cat dander, who have animals as pets, may suffer from chronic severe asthma. Identification of patients with this form of asthma (referred to as allergic asthma) is important because symptoms may improve strikingly if the offending animal is removed or the patient receives allergy immunotherapy.

Another form of asthma is associated with the eosinophil, a blood cell that stains intensely with the acidic dye, eosin. The association between asthma and elevation of blood eosinophils was established more than 100 years ago. By the middle of the last century, severe chronic asthma, often starting in adult life, ages 35-50, often showing marked elevations of blood and tissue eosinophils was a known clinical entity. Attention is now being focused on asthma-associated eosinophilia because of new effective asthma treatments that reduce eosinophils. These agents, described below in greater detail, demonstrate that reducing eosinophils benefits asthma and thus establish the eosinophil as an important cell responsible for tissue damage in asthma.

What is Eosinophilic Asthma?

Eosinophilic asthma is a subtype of asthma that is often severe. It is commonly seen in people who develop asthma in adulthood, although it may occur in children and young adults.

Watch this video on YouTubeAsthma is a chronic lung disease in which diseased airways are infiltrated by inflammatory cells (and thus thickened) and obstructed by fluid and mucous. This causes spasms in the bronchial tubes, making breathing difficult. Asthma may result from allergy or other hypersensitivities; however, many patients who have eosinophilic asthma do not have a history of allergic conditions (e.g., hay fever, food allergy, eczema, or other allergic conditions).

In eosinophilic asthma, the numbers of eosinophils are increased in blood, lung tissue, and mucus coughed up from the respiratory tract (known as sputum). The whole respiratory tract is involved in airflow obstruction from the sinuses to the small or distal airways. Patients with eosinophilic asthma frequently suffer from chronic sinus disease and nasal polyposis.

Research has shown that an elevated number of eosinophils in the blood correlates with future risk and severity of asthma attacks.

Asthma can range in severity and treatment may vary from patient to patient. To help outline the best course of treatment for an asthmatic patient, it is important for a health care provider to determine which subtype of asthma a person might have, because there are now new therapies that target specific subgroups of asthma, like eosinophilic asthma.

Causes

The cause of eosinophilic asthma is unknown. Patients with eosinophilic asthma do not typically have underlying allergies (e.g., pollen, dust mites, smoke, and pet dander) that trigger asthma symptoms.

Who is Affected?

The exact prevalence of eosinophilic asthma is unknown, however, it is estimated that approximately 10% of all asthma is categorized as severe. Eosinophilic asthma is most commonly diagnosed in adults 35-50 years old, although it is sometimes seen in even older adults and pediatric patients. Eosinophilic asthma equally affects males and females.

Symptoms

People with eosinophilic asthma typically have the following symptoms:

Wheezing
Coughing
Shortness of breath/difficulty breathing
Chest tightness
Lung function abnormalities (airflow obstruction)
Chronic rhinosinusitis with nasal polyps
Inflamed nasal mucous membrane

Symptoms are often severe and can be persistent.

Diagnosis

The diagnosis of eosinophilic asthma is made by measuring the number of eosinophils in a patient’s blood. Because other subsets of the eosinophil-associated disease may cause elevated blood eosinophils, including hypereosinophilic syndromes, results must be interpreted in context with the patient’s history, reported symptoms, and clinical evaluation. The blood draw (venipuncture) is a minimally invasive procedure and may be performed in a doctor’s office.

Eosinophilic asthma can also be diagnosed by examining a patient’s sputum sample under a microscope. To get the sample of sputum for testing, a patient coughs up a mucous sample. This procedure is non-invasive and may be performed in a doctor’s office.

A third way to diagnose eosinophilic asthma is by examining a bronchial biopsy or bronchial fluid from the lung. This procedure is invasive. To perform it, a doctor who specializes in lung disease (pulmonologist) performs a bronchoscopy by inserting an instrument called a bronchoscope through the nose or mouth. Several small samples of tissue (or fluid) are collected (biopsy) and are then analyzed to determine the infiltration of eosinophils. The procedure is performed under anesthesia and may require a hospital stay.

Clinical symptoms and how well a patient responds to treatments also guide the diagnosis.

Eosinophilic asthma may be misdiagnosed as chronic obstructive pulmonary disease (COPD), which is characteristic of cigarette smokers.

Treatment

When treating eosinophilic asthma, the goal is to reduce the eosinophils in the airways and control a person’s breathing. Many patients who have eosinophilic asthma respond to typical asthma therapies, including inhaled and/or oral corticosteroids. Other patients may have symptoms that are resistant to these therapies.

Biologic therapies that target eosinophils may also be prescribed to treat eosinophilic asthma. Biologics that are currently approved for use in the U.S. include the following:

Benralizumab is a humanized monoclonal antibody. It blocks the action of interleukin-5 (IL-5), a signaling protein that is part of the immune system. It binds to the IL-5 receptor on eosinophils. It also targets natural killer cells, which are a type of white blood cell, to deplete eosinophils. It is approved for use in the U.S. for the add-on maintenance treatment of patients with severe asthma aged 12 and older with an eosinophilic phenotype of asthma. It is used in combination with other asthma medications.
Dupilumab is an interleukin-4 (IL-4) and interleukin-13 (IL-13) inhibitor. It binds to the IL-4 alpha receptor. It is approved as add-on maintenance therapy in patients with moderate-to-severe asthma aged 6 years and older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. It is also approved for those with severe atopic dermatitis and/or chronic sinusitis with nasal polyposis.
Mepolizumab is a humanized monoclonal antibody. It recognizes and blocks IL-5. It is approved for use in the U.S. to treat patients aged 6 or older who have eosinophilic asthma. It is used in combination with other asthma medications.
Reslizumab is another anti-IL-5 monoclonal antibody. It is approved for use in the U.S. as an add-on treatment for patients aged 18 years or older who have eosinophilic asthma.

In contrast to the above therapies that directly reduce the ability of the bone marrow to produce eosinophils, omalizumab is a monoclonal antibody directed against the allergy antibody, IgE, that results in reduction of eosinophilia because of lessening of allergic reactivity (and, in fact, parts of omalizumab’s benefit might be due to this reduction). While not approved for eosinophilic asthma, omalizumab has shown positive benefit in patients with eosinophilic asthma, with greater success in patients with higher eosinophil counts. It is approved for use in the U.S. to treat moderate to severe persistent allergic asthma in patients aged 6 years or older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with corticosteroids. However, most patients with the eosinophilic subtype of asthma do not have IgE-mediated allergy, and therefore, most will not benefit from omalizumab.

Prognosis

People who have asthma may experience a decline in lung function faster than people who do not have asthma. This is particularly true for people who smoke and those who have not managed their asthma well.

Death from asthma is rare, especially if a person is receiving proper treatment. Most asthma fatalities are preventable.

Asthma can be debilitating and asthma-related episodes can be frightening. Uncontrolled asthma may interfere with daily activities, such as school and work.

Many patients with eosinophilic asthma are able to manage their symptoms with inhaled or oral steroids; however, some patients experience persistent asthma attacks that are relatively resistant to typical treatments. New and emerging biologics that target eosinophils may help these patients to fully control their asthma.

As with other subsets of asthma, patients who have eosinophilic asthma should receive ongoing medical care to maintain optimum health.

Preparing for a Doctor’s Appointment

Patients with asthma or suspected asthma will likely be referred to an allergist or a pulmonologist. These tips may help you be more prepared for your appointment:

Keep a log of symptoms you are having, even if they are seemingly unrelated.
Bring a list of any prescription or over-the-counter medications you are taking. Don’t forget to list vitamins and supplements, too.
Jot down a list of questions, such as:
What tests or procedures will be performed?
- How will my asthma be monitored?
- How should I use my medications? How should they be stored?
- What triggers might cause my asthma to flare? Is there anything I can/should do to reduce my risk of having an asthma attack?
- Will I have an asthma action plan?
- How often do I need follow-up care?

Frequently Asked Questions

1. What type of doctor treats eosinophilic asthma?
Pulmonologists, allergists, and immunologists all treat eosinophilic asthma; more pulmonologists may treat this subtype of asthma because it is less likely to be related to allergies. On the other hand, the occurrence of allergies needs to be determined so that it can be properly managed. Allergists/immunologists specialize in treating allergic diseases, including asthma. A pulmonologist is a specialist that focuses on conditions affecting the lungs and respiratory tract, which also include asthma. The type of doctor an asthmatic patient is seen by may depend on a variety of factors, such as the subtype of asthma they were diagnosed with, or their access to local specialists.

2. What therapies are FDA-approved to treat eosinophilic asthma?
For patients with eosinophilic asthma who do not respond to steroids and long-acting bronchodilators, other FDA-approved add-on options are omalizumab, mepolizumab, and reslizumab. Omalizumab is an anti-IgE therapy that reduces airway and blood eosinophils, but as most eosinophilic asthma patients are not allergic, it is not useful to most. Mepolizumab and reslizumab are anti-IL-5 therapies that target eosinophils and are often effective in treating eosinophilic asthma.

3. Is research being conducted for eosinophilic asthma?
Several clinical trials are currently underway, many of which focus on emerging biologic therapies to control the symptoms of eosinophilic asthma.

4. Will eosinophilic inflammation damage my airways?
Eosinophils are increased as a feature of persistent inflammation, which in turn has been associated with an increased number of asthma attacks and the decline of lung function. However, the relationship between eosinophilic inflammation and airflow obstruction and hyper-responsiveness is not yet well understood. Patients who have eosinophilic asthma should receive ongoing care to maintain optimum health.

Educational Videos

Managing Severe Asthma: Identifying and Treating Eosinophilic Asthma
Asthma can be a manageable condition, when diagnosed and treated properly. In this program, real patient, Andrew, shares his story about how pulmonary specialist, Dr. Mario Castro, M.D., M.P.H., with Washington University School of Medicine in St. Louis, Missouri, found the answers he desperately needed to get his severe asthma under control.

Physicians across many practice areas see these patients come through their practice, and this program is intended to help raise awareness of the signs and symptoms of severe asthma – including unmanageable symptoms, such as recurring colds, chest tightness and persistent cough — and specifically, the involvement of eosinophils, in both proper diagnosis and treatment of some severe asthma patients. This educational program was made possible thanks to a generous grant from Teva.

APFED is proud to have partnered with PVI, PeerView Institute for Medical Education, and Icahn School of Medicine at Mount Sinai to educate patients and providers about eosinophilic asthma. Support for the development of these resources was provided by an unrestricted educational grant to PVI, PeerView Institute for Medical Education, and Icahn School of Medicine at Mount Sinai from Teva Pharmaceuticals.

Other Resources

References

de Groot JC, ten Brinke A, Bel EHD. “Management of the patient with eosinophilic asthma: A new era begins.” Eur Respir J Open Res 2015; 1: 00024-2016.
Nair P. “What is an ‘eosinophilic phenotype’ of asthma?” J Allergy Clin Immunol 2013 Jul: 132(1): 81-83.
Simpson JL, Scott R, Boyle MJ, et al. “Inflammatory subtypes in asthma: assessment and identification using induced sputum.” Respirology 11 (2006): 54-61.
van Veen IH, Ten Brinke A, Gauw SA, et al. “Consistency of sputum eosinophilia in difficult-to-treat asthma: a 5-year follow-up study.” J Allergy Clin Immunol 2009; 124: 615-617.
Walford HH, and Doherty TA. “Diagnosis and management of eosinophilic asthma: A U.S. perspective.” Journal of Asthma and Allergy 7 (2014): 53-65.

Contributors and reviewers: Gerald Gleich, MD; Kate Nelson, PhD; Michael Wechsler, MD; Praveen Akuthota, MD; Marissa Shams, MD; Jonathan Spergel, MD, PhD

Updated March 2020.