Precision Medicine in Severe Asthma: Practical Phenotyping and Evidence-Based Selection of Biologic Therapy

Precision Medicine in Severe Asthma: Practical Phenotyping and Evidence-Based Selection of Biologic Therapy Article Type: Review Author : Zouheir J. Alameh, MD, DSc, FCCP Affiliation: Alameh Clinic, Aley, Lebanon Corresponding Author: Zouheir J. Alameh, MD, DSc, FCCP; Alameh Clinic, Aley, Lebanon; Email: alamehclinic@gmail.com Manuscript Word Count (approx.): 7745 Abstract Word Count: 230 Abstract Severe asthma is a heterogeneous syndrome in which persistent symptoms and recurrent exacerbations continue despite optimized high-dose inhaled corticosteroids and additional controller therapy. Biologic agents now offer targeted treatment for patients with Type 2 airway inflammation, but real-world selection remains challenging because phenotypes overlap, biomarkers fluctuate, and head-to-head trials are limited. This narrative review synthesizes contemporary guideline frameworks and pivotal randomized trials into a clinic-ready phenotyping workflow and a practical selection approach for currently available biologics. We outline a stepwise pathway that begins with confirmation of the asthma diagnosis and identification of modifiable drivers of poor control (adherence, inhaler technique, exposures, and comorbidities), followed by structured assessment of Type 2 biomarkers and treatable traits. Key signals used to align therapy include exacerbation burden, maintenance oral corticosteroid dependence, allergic sensitization with total immunoglobulin E eligibility, blood eosinophil counts, and fractional exhaled nitric oxide, interpreted in the context of systemic steroid exposure and comorbid disease (e.g., chronic rhinosinusitis with nasal polyps or atopic dermatitis). We summarize practical selection cues for anti-IgE, anti-interleukin-5/interleukin-5 receptor alpha, anti-interleukin-4 receptor alpha, and upstream epithelial cytokine blockade, and propose treat-to-target reassessment at 4-6 months using predefined response domains (exacerbations, steroid reduction, symptom control, lung function, and comorbidity outcomes). A structured, auditable precision-medicine pathway can improve biologic matching, support safer steroid tapering, and guide timely continuation or mechanism switching when response is inadequate.