**Background:** The Spanish Guideline on the Management of Asthma (GEMA) is a multidisciplinary, evidence-based clinical practice guideline that has been updated annually for over 20 years. GEMA 5.3, published in 2023, involves 21 scientific societies from Spain, Latin America, and Portugal. Its primary objective is to improve asthma control and quality of life by providing healthcare professionals with simple, practical recommendations for routine clinical practice. The guideline covers diagnosis, classification, treatment, and management of asthma in both adults and children, including special circumstances such as pregnancy, occupational asthma, and comorbidities.
**Methods:** The update was based on a systematic literature review of articles published in 2022, selected by four expert reviewers from high-impact journals in pulmonology, allergology, pediatrics, family medicine, and internal medicine. The evidence was classified using an alphabetic system (A to D), and recommendations were categorized as robust (R1) or weak (R2) based on quality of evidence, risk-benefit balance, costs, and patient preferences. Consensus was achieved through a pyramidal system involving chapter authors, coordinators, and a final Delphi method among all authors and reviewers. The guideline was funded by pharmaceutical companies, but the authors declare that the funding bodies did not influence the content.
**Key Results:** The guideline presents several important updates. A new definition for severe uncontrolled asthma (SUA) is introduced: asthma that remains poorly controlled despite treatment with high-dose ICS/LABA/LAMA in the previous year, or requiring maintenance oral glucocorticoids for at least 6 months. Lack of control is defined by any of: ACT < 20 or ACQ > 1.5; ≥ 2 severe exacerbations or ≥ 2 courses of oral glucocorticoids (≥ 3 days each) in the previous year; ≥ 1 hospitalization for severe exacerbation in the previous year; or chronic airflow limitation (FEV1/FVC < 0.7 or FEV1 < 80% predicted). Theophylline is removed from the therapeutic armamentarium. Triple therapy with fluticasone/vilanterol/umeclidinium in a single inhaler is incorporated for severe asthma (approved in Hispanic America but not by European agencies). Tezepelumab is included in the therapeutic algorithm for severe uncontrolled asthma, and benralizumab is now indicated for T2 asthma with blood eosinophils between 150-300/μL. New recommended questionnaires include the Asthma Impairment and Risk Questionnaire (AIRQ) and the Sino-Nasal Outcome Test 22 (SNOT-22). The guideline also introduces a new tool: iaGEMA, a chatbot-type artificial intelligence application that provides GEMA recommendations in response to real clinical questions. The treatment algorithm for biologics in severe uncontrolled asthma is updated, with specific thresholds for eosinophils and FeNO. For example, dupilumab is recommended if eosinophils ≥ 300/μL and/or FeNO ≥ 50 ppb, and not recommended if eosinophils ≥ 1,500/μL. Mepolizumab is indicated if current eosinophils ≥ 150/μL and ≥ 300/μL in the previous 12 months. Benralizumab is indicated if current eosinophils ≥ 150/μL and nasal polyposis or ≥ 3 severe exacerbations in the previous year or FVC < 60%. The guideline also provides a detailed algorithm for tapering oral glucocorticoids in patients starting biologics.
**Clinical Implications:** GEMA 5.3 provides a comprehensive, updated framework for asthma management that emphasizes phenotype-directed therapy, particularly for severe uncontrolled asthma. The inclusion of new biologics and the refinement of treatment algorithms based on biomarkers (eosinophils, FeNO) allow for more personalized treatment. The introduction of iaGEMA, an AI-powered tool, aims to improve guideline implementation in clinical practice. The guideline also highlights the importance of addressing comorbidities, treatment adherence, and inhalation technique. The removal of theophylline and the emphasis on avoiding SABA overuse reflect current evidence on safety and efficacy. The updated definition of SUA and the new algorithms for corticosteroid-dependent asthma provide clearer guidance for managing the most challenging patients. Overall, GEMA 5.3 is positioned as a key reference for Spanish-speaking clinicians worldwide, aiming to improve asthma control and reduce exacerbations through evidence-based, practical recommendations.