CLINICAL AND IMMUNOLOGICAL PREDICTORS OF UNCONTROLLED ALLERGIC DISEASES IN CHILDREN AND ADULTS: THE ROLE OF BIOMARKERS, MICROBIOME, AND PERSONALIZED THERAPY

Abstract

Allergic diseases (asthma, allergic rhinitis, atopic dermatitis, and food allergy) share epithelial barrier dysfunction, type 2 immune activation, microbial dysbiosis, and age-dependent trajectories. A major challenge is early identification of patients who remain uncontrolled despite guideline-based therapy, as uncontrolled disease increases exacerbations, sleep disturbance, school and work impairment, systemic corticosteroid exposure, and anxiety. This narrative review synthesizes clinical and immunological predictors of uncontrolled allergic disease in children and adults, emphasizing biomarkers, microbiome-related mechanisms, and personalized therapy. Current concepts from international guidelines and literature (2020–2026) were analyzed. Poor control is predicted by high baseline disease activity, early-onset multi-organ atopy, recurrent exacerbations, polysensitization, type 2-high inflammation, barrier impairment, comorbidities (rhinosinusitis, obesity), persistent environmental exposure, psychological stress, and non-adherence. Biomarkers improve risk stratification only when interpreted with clinical context: blood eosinophils and fractional exhaled nitric oxide are useful in asthma; allergen-specific IgE and molecular components refine diagnosis in rhinitis and food allergy; and skin, blood, and microbiome markers may phenotype atopic dermatitis. Microbiome dysbiosis helps explain how early-life exposures, antibiotics, diet, epithelial injury, and Staphylococcus aureus colonization shape allergic severity, although it is not a standalone diagnostic test. Personalized therapy integrates treatable-trait assessment, allergen immunotherapy, biologics targeting IgE, IL-5/IL-5R, IL-4Rα, IL-13, and TSLP, and anti-IgE-based risk reduction in selected food allergy patients. Future care requires a life-course model integrating phenotype, endotype, biomarkers, exposure history, and patient behavior.