Eosinophilic Asthma: Symptoms, Diagnosis, And Treatment

Healthcare professionals have typically thought of asthma as a single condition. But medical science reveals there is more to the narrative.

Asthma is now known as a collection of conditions with differences in age of onset, symptoms, and treatment strategies. Among these conditions is eosinophilic asthma.

Asthma is a chronic respiratory condition characterized by inflammation and narrowing of the lung's airways. It often results from allergic triggers such as dust mites, pet dander, etc. But when a person has eosinophilic asthma, the inflammation in the respiratory system is caused by eosinophils.

These are types of white blood cells that help fight disease but may also cause swelling. Therefore, you may suffer eosinophilic asthma even if you don't have a history of allergies or allergic conditions such as eczema, food allergy, hay fever, etc.   

Eosinophilic asthma vs. normal asthma

Eosinophilic asthma refers to a particular asthma phenotype, defined by inflammation or the swelling of the airway mucosa and increased eosinophil levels in blood and sputum. Eosinophils are a critical part of the immune system when at normal levels. They fight bacteria and protect against infections.

But when eosinophil levels in the blood increase to more than 500/mm3, they may lead to asthma complications due to induced swelling in the airways. 

Eosinophilic asthma presents itself in three distinct phenotypes. The first one is allergen-exacerbated asthma, where those affected show atopy (allergen sensitization) alongside allergic rhinitis and exacerbated symptoms of allergen exposure, often in early-onset asthma. 

Idiopathic eosinophilic asthma is another phenotype and manifests in people whose eosinophilic swelling is a prominent pathology that can present at any age, especially in adulthood. Idiopathic eosinophilic asthma sufferers are nonatopic. The third phenotype is an aspirin-exacerbated respiratory disease with distinct features, including chronic rhinosinusitis (CRS) with nasal polyps and aspirin sensitivity. It usually presents in adults and nonatopic people. 

Medical professionals now realize there is no 'normal/regular asthma' but rather ‘classic’ asthma that occurs in childhood. It is the type of asthma often triggered by allergens such as molds, pollen, pet dander, and dust mites. The body's immune system of people with this type of asthma produces immunoglobulin E (IgE) when coming into contact with allergens. 

IgE is an antibody that attaches to particular cells and makes them release chemicals that lead to an allergic reaction. This includes severe allergic reactions (anaphylaxis), wheezing, itchy or watery eyes, sneezing, and increased airway sensitivity. It begins during childhood and usually responds well to inhaled corticosteroid therapy. 

On the other hand, eosinophilic asthma tends to present during adulthood and causes inflammation in the entire respiratory system. You might not recognize it as asthma since the main symptom is usually shortness of breath rather than wheezing. It may also not respond well to inhaled corticosteroids, even when administered in high doses. 

Symptoms of eosinophilic asthma

Common symptoms of eosinophilic asthma include:

Shortness of breath

An adult weighing 150-pounds has an average breathing rate of 14 breaths per minute when resting. When you experience shortness of breath or dyspnea, your breathing rate is below average. Those with eosinophilic asthma may experience this symptom due to the narrowing of airways resulting from inflammation. 

Nasal polyps

These are non-cancerous growths on the inner lining of the nasal cavity. The soft growths hang on the lining like teardrops and are usually painless. Typically, nasal polyps are not serious but may continue to grow and block your nose if left untreated. 

Wheezing

You may produce a whistling sound as you breathe through narrowed airways. Wheezing is common during exhalation or when breathing air out of the lungs. 

Cough

Another symptom of eosinophilic asthma is coughing. The cough usually lasts for a long time. 

Chest tightness

You may feel discomfort between your upper abdomen and lower neck. The unpleasant sensation makes you feel like there is a weight on your chest. You may feel this in one or many spots on your chest and sometimes all through the chest.

Chronic rhinosinusitis

Your sinuses may swell, leading to other symptoms such as clogged nasal passages, loss of smell, runny nose, and facial pain and pressure. 

Asthma attacks

Inflammation, contraction of muscles around the airways, and increased mucus production may cause the narrowing of airways, which may result in asthma attacks. 

Changes in lung function

Eosinophilic asthma may cause changes in lung function similar to those present when a person has a chronic obstructive pulmonary disease (COPD). That is why people usually confuse eosinophilic asthma with COPD.

Symptoms of hypereosinophilic syndrome

This syndrome¹ is rare but usually occurs when eosinophil levels are extremely high. It causes symptoms such as mouth sores, rashes, and fatigue. People with eosinophilic asthma may also experience these symptoms.   

Who is affected by eosinophilic asthma?

Eosinophilic asthma usually affects adults aged 35 to 50, even if they have previously been asthma and allergy-free. It may also present in older adults and pediatric cases. This subset of asthma affects men and women at about the same rate. 

Although the exact prevalence is unknown, some studies² show that it affects about 5% of adults with asthma. Other studies³ suggest that severe eosinophilic asthma could have a higher prevalence than experts have previously known. 

Causes of eosinophilic asthma

The exact cause of eosinophilic asthma is still unclear. Many individuals with asthma usually have underlying allergies. Exposure to allergens such as animal dander, dust, molds, etc., triggers an inflammatory response that leads to an asthma attack. But people with eosinophilic asthma often don't have a history of allergies.

Diagnosing eosinophilic asthma

People with eosinophilic asthma have a high eosinophil count in their pulmonary mucous (sputum), lungs, and bloodstream. That is why diagnostic tests for the condition revolve around these three, except for the FeNo test and other tests still under investigation, which examine the gas released from the cells involved in the inflammation. 

Eosinophilic asthma diagnostic tests include:

Blood eosinophil count

This diagnostic test involves counting the number of eosinophils in your blood. Blood eosinophil count won't typically require preparation, but you should inform your doctor about any medications you are taking, as they might impact the results. When you go for this test, the doctor prepares your skin by swapping it with an antiseptic and putting an elastic band around the arm to find the vein.

The healthcare provider then inserts a needle into your vein and draws blood. 

This testing process is fairly quick, but it may take several days or a week to get the results. The laboratory technician counts the number of eosinophils present to give the result. An adult has a normal eosinophil count of up to 500/mm3 in their blood. 

An abnormal result is when the eosinophil count is too low or too high. However, you may have eosinophilic asthma when you have a higher-than-normal eosinophil count. The condition can be mild (500–1,500 cells/mm3), moderate (1,500–5,000 cells/mm3), or severe (greater than 5,000 cells/mm3). 

Sputum eosinophil count

Another way to diagnose eosinophilic asthma is by counting eosinophils in sputum. Simple coughing often does not bring up the sputum from inside the chest. Therefore, your doctor will need to perform sputum induction.

The doctor may give you an inhaler filled with fast-acting bronchodilator medication to relax and widen your airway. You may also inhale saline mist for 5-20 minutes to ensure nothing clogs the air path. 

After that, you can cough and spit mucus into a cup. Once your specimen is in the laboratory, the technician counts the white blood cells, including macrophages, neutrophils, lymphocytes, and eosinophils. A healthy sputum specimen usually has 1% eosinophils per cell and below.

The doctor may diagnose you with eosinophilic asthma if the count is above 2-3%⁴.

Bronchial biopsy test

This diagnostic test involves examining the lungs under a microscope and is more invasive. A healthcare professional inserts a bronchoscope (thin tube) through the mouth or nose to collect small fluid or tissue samples. An analysis of the biopsy establishes the infiltration of eosinophils.

Although the doctor performs the procedure under general or local anesthesia, it does not require hospitalization. 

Fractional exhaled nitric oxide test (FeNO test)

The cells involved in the swellings associated with eosinophilic asthma produce nitric oxide gas. The FeNO test⁵ measures the amount of this gas in parts per billion (PPB) in the air you exhale out of your lungs. When you have eosinophilic asthma, sometimes you may feel like you are breathing normally and without any difficulties.

However, a test on exhaled nitric oxide may reveal that you are exhaling significantly high levels of the gas, and you might need a slightly higher dosage of inhaled steroids to suppress the inflammation. 

Diagnosing eosinophilic asthma is critical in primary, secondary, and tertiary treatments. General practitioners typically use the tests even after primary diagnosis to know whether to initialize inhaled corticosteroids. 

Although people with eosinophilic asthma may respond to inhaled corticosteroids, these medications should be used when there is airway eosinophilia. Moreover, recognizing airway eosinophilia is critical since those with severe eosinophilia are vulnerable to chronic problems and airway remodeling, even if they take oral or inhaled corticosteroids.

Eosinophilic asthma treatment

Corticosteroids

Doctors usually give inhaled corticosteroids as the first line of treatment for asthma. These medications reduce airway swelling, which leads to constriction, thus enabling you to breathe without difficulties. However, those with eosinophilic asthma may not respond well to corticosteroids. 

The medications may not control their asthma adequately, causing frequent and severe asthma attacks. Typically, people with eosinophilic asthma require a high inhaled corticosteroid dosage. These may help if the symptoms are severe.

However, oral steroids may lead to long-term side effects, such as weight gain, osteoporosis, and diabetes mellitus. 

Fast-acting inhalers

Rescue inhalers may not be long-term treatment solutions. But it is critical to have them on hand when you have eosinophilic asthma. The quick-relief inhalers introduce medications that alleviate symptoms of flare-ups and open your airways to prevent asthma attacks. 

However, they don't prevent asthma symptoms the way long-term controllers do. As you rely on fast-acting inhalers, they become less effective since your lungs get accustomed to them. Reach out to your primary caregiver if you are using fast-acting inhalers multiple times a week. 

Leukotriene modifiers

Leukotriene modifiers reduce leukotrienes in the body. These are lipid mediators extracted from arachidonic acid and released by leukocytes and other cells, including those in the lungs. They contribute to the inflammatory cascade that leads to asthma. 

Leukotriene modifiers used in treating asthma work by hindering leukotrienes from binding to their receptors (Zafirlukast and montelukast) or by blocking enzyme 5-lipoxygenase, thus inhibiting the arachidonic acid metabolism's lipoxygenase pathway (zileuton).

Inhibitors of 5-lipoxygenase

Inhibitors of enzyme 5-lipoxygenase directly block it, thus preventing arachidonic acid metabolism to the LTA4. An orally active 5-lipoxygenase inhibitor (zileuton) boosts pulmonary function and reduces asthma symptoms. 

Cysteinyl leukotriene-receptor antagonists

Cysteinyl leukotriene-receptor antagonists hinder the actions of cysteinyl leukotrienes on target cells such as mucus and smooth muscle cells. Zafirlukast and montelukast are orally active cysteinyl leukotriene-receptors antagonists and boost pulmonary function while reducing asthma symptoms. 

Inhibitors of FLAP

Flap inhibitors prevent arachidonic acid metabolism to LTA4 by binding to FLAP, so it does not bind to 5-lipoxygenase. However, the agents are still in their early stages of development. Therefore, your doctor may prescribe one of the three leukotriene modifiers available for eosinophilic asthma treatment, which include zafirlukast (Accolate), montelukast sodium (Singulair), and zileuton (Zyflo).

Biologic therapies

Your doctor may also prescribe biological therapies to treat eosinophilic asthma. These include:

Benralizumab

This biological therapy, administered as a shot, collaborates with your body to attract immune cells that reduce eosinophils. Benralizumab is FDA approved to treat eosinophilic asthmatics ages 12 years and above as an add-on maintenance treatment. 

Reslizumab

You receive Reslizumab intravenously as an add-on treatment for eosinophilic asthma. It is FDA-approved for those ages 18 and above who have the condition at a dosage of 3mg/kg over 20-50 minutes every four weeks. Reslizumab is safe and well-tolerated by most people. 

Mepolizumab

This biological treatment reduces the eosinophils count in the blood by binding to interleukin-5. People receive this medication as a shot. It is FDA-approved to treat eosinophilic asthmatics ages six years or older in combination with other asthma drugs. 

Dupilumab

This medication binds to the interleukin-4 receptor, thus reducing swelling in the lungs. The doctor prescribes this biological therapy as an add-on maintenance therapy for eosinophilic asthma. It is FDA-approved to treat the condition in those ages 12 years and above.

Omalizumab

The FDA approved omalizumab to treat severe asthma in 2003. It was the first monoclonal antibody to receive approval. It lowers the ability of the bone marrow to make eosinophils. The reduced allergic reactivity makes it beneficial for asthma treatment.

Omalizumab helps reduce airway inflammation and eosinophil counts in people with severe asthma and is safe and well-tolerated by most with the condition. 

What are the potential complications of eosinophilic asthma?

Ear infections

When you have eosinophilic asthma, the inflammation may extend to the ears and lead to eosinophilic otitis media (EOM). This middle ear infection is characterized by the build-up of eosinophils in the middle ear effusion and mucosa. When the cells undergo cytolysis, they pour out high levels of granule proteins which are toxic to tissues. 

Therefore, they may cause epithelial damage in the middle ear effusion and reduce mucus transport in the Eustachian tube. The thick fluid in the ears may increase the risk of gradual perceptive hearing loss. Also, the resulting ear infections may be resistant to standard treatments. 

Nasal polyps

Nasal polyps are abnormal benign growths that form in the inner side of the nasal cavity or sinuses. The non-cancerous growths vary in size. They may form in clusters or on their own. Nasal polyps may not cause any symptoms when small and few.

But when they enlarge or form in clusters, they can lead to breathing difficulties since they block airways and contribute to congestion, loss of smell, sinus infections, and other symptoms. They are potential complications of eosinophilic asthma and other types of asthma too. 

Chronic sinus infections

Eosinophilic asthma may also contribute to the swelling and infection of the linings of the sinuses. Typically, sinuses release thin mucus as a filtration system to keep the nose clean and bacteria-free. When the fluid fills and blocks the sinuses, infections can occur.

Sometimes sinuses infections are acute, lasting less than four weeks and resolving with minimal or no medical intervention. However, eosinophilic asthma often contributes to chronic sinus infections, which persist for a long time, even with treatment. 

Aspirin-exacerbated respiratory disease (AERD)

Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, are commonly used to treat pain and headaches. However, these medicines may trigger or worsen symptoms such as wheezing, stuffiness, and congestion in some people. This condition is an aspirin-exacerbated respiratory disease and a potential complication of eosinophilic asthma and other types of asthma. 

When to visit your doctor

You should visit a doctor if you experience eosinophilic asthma symptoms regularly or if the condition interferes with your daily activities. The doctor may prescribe stronger, long-term treatment to help improve your symptoms and quality of life. 

When visiting your healthcare provider, ensure you have a log of all symptoms you have been experiencing, even if they appear unrelated. In addition, carry a list of any over-the-counter, prescription medications, vitamins, and supplements you may be taking. 

How to manage eosinophilic asthma

When you have any subset of asthma, your lung function may decline faster than individuals without the condition. Therefore, you should manage the condition well and avoid unhealthy habits such as smoking. Management of eosinophilic asthma symptoms can help reduce the risk of lung scarring and other potential chronic complications.

Some overall lifestyle habits, such as healthy eating, stress management, and adequate sleep, may help manage eosinophilic asthma and improve your treatment outcome. Asthma fatalities are rare if you receive proper treatment; most that occur are preventable.

The lowdown

Eosinophilic asthma requires medical intervention. If left untreated, irreversible changes in the airways’ structure may cause chronic airway obstruction. See your primary care physician if you have symptoms that you suspect could be those of eosinophilic asthma.

The health professional can establish your condition's true nature and its extent, and make treatment recommendations. If the symptoms are severe, seek emergency medical intervention.