Biologic therapies target specific inflammatory pathways in severe uncontrolled asthma when conventional step-up therapy (high-dose ICS/LABA ± LAMA) fails. The NP must phenotype asthma to select the appropriate biologic: (1) Allergic phenotype with elevated total IgE (30-1500 IU/mL): omalizumab (anti-IgE) binds free IgE, preventing mast cell degranulation and type I hypersensitivity. (2) Eosinophilic phenotype with blood eosinophils ≥150-300/µL: mepolizumab (anti-IL-5) depletes eosinophils by blocking IL-5 survival signal; benralizumab (anti-IL-5Rα) directly depletes eosinophils via ADCC; both reduce exacerbations by 50%. (3) Type 2 inflammation with elevated eosinophils AND/OR elevated FeNO ≥25 ppb: dupilumab (anti-IL-4Rα) blocks both IL-4 and IL-13 signaling, reducing eosinophilic and IgE-driven inflammation, mucus hypersecretion, and airway remodeling. Tezepelumab (anti-TSLP) blocks the most upstream alarmin, effective regardless of inflammatory phenotype. The NP initiates biologics after confirming: adherence to high-dose ICS/LABA, correct inhaler technique, treatment of comorbidities (GERD, sinusitis, OSA), and environmental trigger avoidance. Biologic selection requires blood eosinophils, total IgE, FeNO, and allergy testing. All biologics require initial in-office administration with 30-minute post-injection monitoring for anaphylaxis (epinephrine must be available); subsequent doses may transition to home self-injection for some...