Asthma is a Condition of Different Phenotypes with Targeted Treatments

Asthma is a chronic condition characterized by inflammation and hyperreactivity in the lung airways. The mainstay of asthma treatment is the use of inhaled steroid medications which help to control inflammation and treat the symptoms. Inhalers containing bronchodilator medications such as albuterol that work to rapidly open up the airways are used as rescue medications to treat acute symptoms. For patients with severe asthma symptoms, systemic steroids either in pill or injection forms may be used. However even when used intermittently, these medications are associated with multiple long-term side effects. Biologic medications which block specific inflammatory pathways are new and effective therapeutic options for severe asthma, without the long-term side effects common to systemic steroids.  For years, asthma specialists thought that all asthma was the same and treated all patients with asthma with similar treatment regimens. More recently, however, researchers and clinicians have learned that this is not the case.

There are different types of inflammation observed in the airways, known as endotypes, which can lead to differences in the clinical features of disease seen in patients, known as phenotypes. Identification of an individual’s specific asthma endotype and phenotype can help improve disease management. Rather than using the same treatment regimen for all patients, current strategies for asthma management focus on individualizing treatment based on a patient’s phenotype. This is known as personalized or precision medicine. There are several well-defined asthma phenotypes including: allergic, non-allergic, eosinophilic, neutrophilic, exercise-induced, and aspirin-induced.  Below is a brief description of some of the more commonly identified asthma phenotypes in children and adults and their potential treatments.

Allergic asthma is the most common asthma phenotype and has been described in about 40-50% of children and adults with asthma. In allergic asthma, exposure to environmental allergens such as pollens, animal dander, or dust mites trigger asthma symptoms. There are various tests that can be used to identify patients with an allergic phenotype including: allergy testing via skin or blood to look for environmental allergies or triggers, a complete blood count to look for an increase in a type of white blood cell called the eosinophil, increased blood levels of the allergy antibody IgE and exhaled nitric oxide testing to measures the amount of allergic inflammation in the airways. Patients with allergic asthma often respond well to medications containing an inhaled steroid. Reducing exposure to allergens in the home and controlling nasal allergy symptoms with medications such as intranasal steroids or antihistamines may also be important strategies in improving asthma control. Allergen immunotherapy, using either allergy shots or sublingual tablets, is a means of becoming less allergic to triggers and may also be recommended. More recently, biologic therapies such as omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab-ekko that target the specific immunologic pathways causing allergic inflammation have been developed to treat patients with poorly controlled allergic asthma.

In the non-allergic asthma phenotype, patients have asthma, but tests do not indicate that they have markers of allergic inflammation. In these individuals, testing for indoor and outdoor aeroallergens may be negative, eosinophil counts and IgE antibody levels are typically low, as is the exhaled nitric oxide level. Patients with non-allergic asthma often have other triggers for their asthma, such as infections or irritants. In patients with non-allergic asthma other types of medications may be prescribed in addition to inhaled steroid medications. For patients with uncontrolled asthma despite traditional therapies, tezepelumab-ekko a biologic medication targeting immunologic pathways of both allergic and non-allergic inflammation may be considered.

Another asthma phenotype is the eosinophilic phenotype. The eosinophil is a white blood cell that can be elevated in patients with allergies and asthma. Patients with eosinophilic asthma have increased levels of eosinophils in the blood and airways and an elevated exhaled nitric oxide level, but may not have positive allergy tests to indoor or outdoor allergens. In addition to inhaled steroid medications, biologic therapies including mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab-ekko can reduce eosinophils and are approved to treat eosinophilic asthma.

Neutrophilic asthma is an asthma phenotype described commonly among patients that have severe asthma. This type of asthma may be diagnosed by obtaining and examining a sputum sample containing saliva and mucus coughed up from the respiratory tract and observing a large number of white blood cells called neutrophils. In this type of asthma, the medication regimen may be modified to include additional types of inhalers or other medications such as macrolide antibiotics. There is currently no biologic therapy approved for neutrophilic asthma.

Exercise-induced asthma is a type of asthma where symptoms are triggered by exercise. The diagnosis of this type of asthma is typically made based on when during exercise or how strenuous the exercise is before symptoms occur. An exercise test consists of checking a breathing test called spirometry after exercising on a treadmill or in the clinic hallway and may be used to evaluate a drop in lung function. Patients with exercise-induced asthma may be treated with specific types of medications and/or may be instructed to use their asthma rescue inhaler 15 minutes before exercise to prevent an attack.

The aspirin-sensitive phenotype, known as aspirin-exacerbated respiratory disease (AERD) is a less common asthma phenotype observed in both children and adults. Patients with AERD will have asthma symptoms triggered after taking aspirin or a non-steroidal anti-inflammatory drug (NSAID). Patients with this asthma phenotype may also have symptoms of chronic rhinitis with nasal inflammation and nasal polyps. This type of asthma is identified mainly by history or an aspirin challenge in the clinic, but a blood count may also reveal an elevated eosinophil count. Patients with this type of asthma may benefit from medications such as leukotriene modifiers or certain biologic therapies that target the immunologic pathway induced by aspirin or NSAIDs. An aspirin desensitization procedure after which treatment with daily aspirin is continued may also be considered.

Although there is better recognition by asthma specialists of the different endotypes and phenotypes, it may still be difficult to accurately determine the asthma phenotype in certain patients. Not only can patients have overlapping asthma phenotypes, but for many phenotypes there are no reliable confirmatory tests. Additionally, phenotype identification may not lead to a significant change in medications since there is a lack of targeted treatments for many of the asthma phenotypes. More research is needed to understand asthma phenotypes, how they differ, how to identify them, and to continue to develop new medications that target each phenotype successfully.

There is no one test that accurately diagnoses asthma, but allergy/immunology physicians are experts in diagnosing, testing, and treating asthma. Your allergy/immunology physician will perform a history and physical exam and may use tests including allergy testing, blood testing, spirometry, and/or a chest x-ray to help make a diagnosis of asthma, while identifying your asthma phenotype and finding the best medications to personalize your treatment.  

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3/13/2024