Eosinophilic airway inflammation (EAI) is a distinct immune response characterized by an excessive buildup of eosinophils, a specific type of white blood cell, within the respiratory tract. This buildup often signifies a Type 2 (T2-high) inflammatory pathway, driven by specific signaling molecules. EAI distinguishes a severe, chronic subtype of respiratory disease from other forms. Identifying this phenotype is necessary for selecting targeted therapies that effectively manage the condition.
Eosinophils: Immune Function and Airway Damage
Eosinophils are white blood cells that originate in the bone marrow and are normally present in low numbers in the bloodstream. Their primary role involves defending the body against parasitic infections and participating in allergic reactions. When the immune system is activated, specific chemical signals, particularly the cytokine Interleukin-5 (IL-5), drive the production, maturation, and recruitment of these cells to the airways. This process results in their pathological accumulation within the lung tissue and mucus.
Once recruited, activated eosinophils degranulate, releasing toxic proteins and mediators. These substances include Major Basic Protein (MBP), Eosinophil Cationic Protein (ECP), and various leukotrienes. The release of these cytotoxic granule proteins directly damages the respiratory epithelial lining. This damage contributes to the features of chronic airway disease, including increased mucus production, thickening of the basement membrane, and tissue remodeling that narrows the air passages.
Diseases Driven by Eosinophilic Inflammation
Eosinophilic inflammation is most commonly recognized as the underlying driver of a severe phenotype of asthma, often referred to as T2-high or eosinophilic asthma. This subtype affects patients whose symptoms persist despite standard treatment. Eosinophilic asthma is characterized by persistent inflammation and a higher risk of severe exacerbations. Elevated eosinophils in the blood or airways differentiate this disease from non-eosinophilic or T2-low asthma phenotypes.
The same inflammatory mechanism is central to other systemic conditions involving the lungs. Eosinophilic Granulomatosis with Polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a rare vasculitis where eosinophils inflame blood vessels throughout the body, frequently involving the respiratory system. Furthermore, a subset of patients with Chronic Obstructive Pulmonary Disease (COPD) exhibit an eosinophilic pattern, which predicts a favorable response to specific anti-inflammatory treatments.
Methods of Diagnosis and Monitoring
Quantifying the degree of EAI is necessary for personalizing treatment plans. The gold standard for directly measuring airway eosinophilia is the induced sputum eosinophil count, where a threshold of \(\ge 2-3\%\) of total inflammatory cells defines the eosinophilic phenotype. While this method provides the most direct measure of airway inflammation, it is often technically challenging and not widely available.
Less invasive, surrogate biomarkers are frequently utilized to infer the presence of EAI. The peripheral blood eosinophil count is a widely accessible test; a count of \(\ge 300\text{ cells}/\mu\text{L}\) often indicates systemic eosinophilia correlating with airway disease. Another non-invasive tool is the Fractional Exhaled Nitric Oxide (FeNO) test, which measures nitric oxide concentration in a patient’s breath. Elevated FeNO levels, typically over \(25\text{ parts per billion (ppb)}\), suggest T2-high inflammation because Interleukin-13 (IL-13) upregulates the enzyme responsible for nitric oxide production.
Specialized Treatment Strategies
Treatment for EAI is distinct from general respiratory care because it targets the specific pathways driving the inflammation. Inhaled corticosteroids (ICS) are the foundational anti-inflammatory treatment. Patients with EAI often require higher doses or the addition of short courses of oral corticosteroids to suppress persistent inflammation. The most significant advance involves specialized biologic therapies for managing severe EAI.
These biologics are monoclonal antibodies designed to interrupt the cytokine cascade that fuels eosinophil production and activity. Anti-Interleukin-5 (anti-IL-5) therapies, such as mepolizumab, reslizumab, and benralizumab, directly target the cytokine IL-5 or its receptor. By blocking IL-5 signaling, these medications inhibit the survival and maturation of eosinophils, leading to a marked reduction in their numbers in the blood and airways.
Other biologics target different points in the T2 inflammatory pathway. Dupilumab, for example, blocks the shared receptor component for both Interleukin-4 (IL-4) and Interleukin-13 (IL-13), two cytokines that promote the allergic response and airway inflammation. By disrupting these upstream signals, dupilumab indirectly reduces the overall T2 inflammatory environment, including eosinophil recruitment and activation. This precise, targeted approach offers effective control for patients with severe EAI.