Asthma is a chronic inflammatory disorder of the airways, characterized by recurring symptoms like wheezing, shortness of breath, and coughing. It is now understood that asthma is not a single disease but a collection of different subtypes, or phenotypes, each driven by distinct biological mechanisms. Eosinophilic asthma (E-Asthma) is one such distinct phenotype, named for the type of immune cell—the eosinophil—that drives the underlying inflammation. Identifying these specific subtypes is fundamental for effective, personalized treatment.
The Biological Mechanism of Eosinophilic Asthma
E-Asthma is defined by the presence of elevated levels of eosinophils, a specific type of white blood cell, within the lungs and airways. Eosinophils are part of the immune system, traditionally helping the body fight off parasitic infections. In E-Asthma, these cells are overproduced and recruited to the respiratory tract, where their accumulation causes chronic inflammation and tissue damage.
The direction and growth of these cells are primarily controlled by the signaling protein Interleukin-5 (IL-5). IL-5 is a cytokine that acts as the primary regulator for eosinophils, promoting their differentiation from bone marrow stem cells and stimulating their proliferation and survival. This process allows a sustained, high concentration of eosinophils to build up within the airway lining.
Once activated, these surplus eosinophils release a potent mix of toxic substances, including cationic proteins, enzymes, and reactive oxygen species, directly into the airway tissue. This chemical attack damages the epithelial layer, the lining of the airways, leading to swelling, excessive mucus production, and thickening of the airway walls. This combination of effects results in the severe and persistent airway narrowing characteristic of E-Asthma.
The inflammation in E-Asthma is driven internally by this specific immune pathway, often referred to as Type 2 inflammation. The persistent presence of these activated cells contributes to airway remodeling, which is the structural change in the bronchial tubes that makes airflow limitation less reversible. Understanding the central role of IL-5 and eosinophils in this inflammatory cascade has become the basis for developing highly targeted treatments.
How E-Asthma Differs From Other Types
Eosinophilic asthma exhibits several distinct clinical characteristics that set it apart from other asthma phenotypes. This subtype is frequently categorized as severe asthma, meaning it remains poorly controlled despite the use of high-dose standard treatments. A significant differentiating factor is that E-Asthma often presents as late-onset disease, typically appearing for the first time in adulthood, usually between the ages of 35 and 50.
Unlike allergic asthma, which is typically triggered by external allergens through an immunoglobulin E (IgE) response, E-Asthma is frequently non-allergic. It often does not respond well to inhaled corticosteroids (ICS), the standard maintenance medication for most other asthma types, even at high doses. This lack of response necessitates alternative therapeutic approaches to manage persistent symptoms and frequent exacerbations.
Diagnosis of E-Asthma relies on specific laboratory tests that confirm the elevated presence of eosinophils. A simple blood test measures the peripheral blood eosinophil count, with a high count often suggesting this phenotype. Furthermore, a sputum eosinophil count, which examines cells directly from the airway mucus, provides a highly accurate measure of airway inflammation.
Another diagnostic tool is the fractional exhaled nitric oxide (FeNO) test, which measures a gas produced by inflammatory cells in the lungs. High FeNO levels often correlate with eosinophilic-driven inflammation, helping clinicians confirm the presence of Type 2 inflammation. E-Asthma is also associated with inflammation throughout the entire respiratory tract, which can manifest as coexisting conditions such as chronic rhinosinusitis and nasal polyps.
Specific Therapies for Eosinophilic Asthma
Because E-Asthma is often severe and shows poor responsiveness to traditional inhaled corticosteroids, its management has been revolutionized by a class of treatments known as biologics. These specialized medications, typically monoclonal antibodies, are engineered to precisely target the specific inflammatory molecules that drive the disease.
The most established biologics for E-Asthma interrupt the IL-5 pathway, thereby reducing the number of circulating and tissue-bound eosinophils. Mepolizumab (Nucala) and Reslizumab (Cinqair) are monoclonal antibodies that bind directly to the IL-5 cytokine itself. By neutralizing IL-5, these drugs prevent the signaling molecule from attaching to its receptor on the eosinophil surface, disrupting the production and survival of the inflammatory cells.
A different approach is taken by Benralizumab (Fasenra), a monoclonal antibody that targets the alpha subunit of the IL-5 receptor (IL-5Rα). By blocking this receptor, Benralizumab prevents IL-5 from initiating its signaling cascade. Furthermore, this medication triggers antibody-dependent cell-mediated cytotoxicity, which directly causes the near-complete programmed death (apoptosis) of the eosinophils.
Other biologics target different components of the Type 2 inflammatory response. Dupilumab (Dupixent) works by blocking the shared receptor component for both Interleukin-4 (IL-4) and Interleukin-13 (IL-13), two other cytokines involved in the inflammatory process. Tezepelumab (Tezspire) targets thymic stromal lymphopoietin (TSLP), a molecule that acts further upstream in the inflammatory cascade, blocking the initial release of multiple downstream cytokines, including IL-5, IL-4, and IL-13.
These targeted therapies offer significant benefits by reducing severe asthma exacerbations, improving lung function, and allowing many patients to reduce or eliminate their reliance on oral corticosteroids, which carry substantial side effects. The selection of a specific biologic is often based on the patient’s precise biomarker levels (e.g., eosinophil count or FeNO levels), ensuring the chosen treatment aligns with the patient’s individual inflammatory profile.