Glucocorticoid Treatment in Severe Asthma

Area of Science:

• Pulmonology and Respiratory Medicine
• Clinical Pharmacology
• Immunology

Background:

• Severe asthma affects 3-10% of asthmatics, often requiring high-intensity therapy.
• Glucocorticoids (GCs) are standard but linked to toxicity and variable response based on inflammatory endotypes (T2 vs. non-T2).
• GC resistance mechanisms include GRβ overexpression and impaired GRα function.

Purpose of the Study:

• To review the challenges of chronic systemic glucocorticoid (GC) use in severe asthma.
• To evaluate the role of biologic therapies in reducing GC burden.
• To highlight the importance of precision medicine and steroid stewardship.

Main Methods:

• Literature review of severe asthma management strategies.
• Analysis of clinical trial data on biologic therapies.
• Discussion of molecular mechanisms of GC resistance and toxicity.

Main Results:

• Biologic therapies targeting IgE, IL-5, IL-4Rα, and TSLP demonstrate significant oral corticosteroid (OCS)-sparing effects.
• These therapies enable OCS dose reduction or discontinuation in steroid-dependent asthma patients.
• Biologics align with precision medicine, offering phenotype-specific treatment.

Conclusions:

• Minimizing chronic GC use is crucial in severe asthma management.
• Biologic therapies represent a transformative approach to reduce GC exposure and improve long-term outcomes.
• Future directions include biomarker-driven selection and enhanced steroid stewardship protocols.