Guía de la Sociedad Española De Anestesiología, Reanimación y Terapéutica del Dolor (SEDAR), Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC) para el manejo de la vía aérea difícil. Parte I / Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR) Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part I

La sección de Vía Aérea de la Sociedad Española De Anestesiología, Reanimación y Terapéutica del Dolor (SEDAR), la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) y la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC) presentan la Guía para el manejo integral de la vía aérea difícil en el paciente adulto. Sus principios están focalizados en el factor humano, los procesos cognitivos para la toma de decisiones en situaciones críticas y la optimización en la progresión de la aplicación de estrategias para preservar una adecuada oxigenación alveolar con el objeto de mejorar la seguridad y la calidad asistencial. El documento proporciona recomendaciones basadas en la evidencia científica actual, herramientas teórico/educativas y herramientas de implementación, fundamentalmente ayudas cognitivas, aplicables al tratamiento de la vía aérea en el campo de la anestesiología, cuidados críticos, urgencias y medicina prehospitalaria. Para ello se realizó una amplia búsqueda bibliográfica según las directrices PRISMA-R y se analizó utilizando la metodología GRADE. Las recomendaciones se formularon de acuerdo con esta metodología. Las recomendaciones de aquellas secciones con evidencia de baja calidad se basaron en la opinión de expertos mediante consenso alcanzado a través de un cuestionario Delphi.(AU)

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factor, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.(AU)

Guía de la Sociedad Española De Anestesiología, Reanimación y Terapéutica del Dolor (SEDAR), Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC) para el manejo de la vía aérea difícil. Parte II / Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR) Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part II

La sección de Vía Aérea de la Sociedad Española De Anestesiología, Reanimación y Terapéutica del Dolor (SEDAR), la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) y la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC) presentan la Guía para el manejo integral de la vía aérea difícil en el paciente adulto. Sus principios están focalizados en el factor humano, los procesos cognitivos para la toma de decisiones en situaciones críticas y la optimización en la progresión de la aplicación de estrategias para preservar una adecuada oxigenación alveolar con el objeto de mejorar la seguridad y la calidad asistencial. El documento proporciona recomendaciones basadas en la evidencia científica actual, herramientas teórico/educativas y herramientas de implementación, fundamentalmente ayudas cognitivas, aplicables al tratamiento de la vía aérea en el campo de la anestesiología, cuidados críticos, urgencias y medicina prehospitalaria. Para ello se realizó una amplia búsqueda bibliográfica según las directrices PRISMA-R y se analizó utilizando la metodología GRADE. Las recomendaciones se formularon de acuerdo con esta metodología. Las recomendaciones de aquellas secciones con evidencia de baja calidad se basaron en la opinión de expertos mediante consenso alcanzado a través de un cuestionario Delphi.(AU)

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factor, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.(AU)

Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factor, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR) Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part II.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factor, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Effect of different therapeutic strategies on olfactory outcomes in patients with chronic rhinosinusitis with nasal polyps: a systematic review.

INTRODUCTION: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), yet the effect of the currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile the evidence on the impact of medical, surgical, and biological therapies on the olfactory outcomes in patients with CRSwNP. METHODS: This review was conducted by two reviewers, according to the Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) guidelines. The quality of evidence of all studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP). RESULTS: Forty-four studies were included in the qualitative synthesis (assessing sinonasal surgery [n = 23], biologics [n =15], and conventional medical treatment [n = 6]); most had moderate-to-high methodological quality. Overall, significant improvements in the sense of smell were detected with all analyzed interventions measured by either an objective or a subjective tool (or both). However, most studies used different outcome measurements, hindering comparisons between interventions, and data on clinically relevant changes were missing. CONCLUSION: Oral corticosteroids, biologics and sinonasal surgery improve olfactory impairment associated with CRSwNP, but the high variability among existing studies does not allow accurate comparisons.

The Influence of BMI in Asthma: Which Traits Are due to Obesity and Which to the Asthma and Obesity Phenotype?

Background: The characteristics of the asthma and obesity phenotype have been described in cluster studies but have not been subsequently confirmed. Specific characteristics of this phenotype have not been differentiated from those inherent to the patient’s body mass index (BMI). Objectives: This study aims to assess the effect of BMI on asthma in order to identify which traits could define the asthma and obesity phenotype and which are inherent to the patient's BMI. Methods: A real-life retrospective observational study was conducted based on data from 2514 patients with suspected asthma collected at the first visit to the allergy clinic between November 2014 and November 2017. All patients had to perform an appropriate spirometry maneuver. All BMI, sex, and age groups were represented. Results: The influence of BMI on asthma differed according to age group and sex. All spirometry results and FeNO were influenced by BMI. The only notable asthma characteristics were later onset of asthma with higher BMI values. No other differences were found between the BMI groups. Conclusions: The effect of BMI on asthma is age-dependent; therefore, it should be corrected for age. The most important variations are in FeNO and spirometry results. The specific characteristics of the asthma and obesity phenotype are a greater perception of symptoms with fewer alterations in respiratory function tests and a lower prevalence of atopy, rhinitis, and allergy, including allergic asthma. Other characteristics of this phenotype, such as a higher female prevalence or late-onset or noneosinophilic asthma, are nonspecific for this phenotype

Antecedentes : las características del fenotipo del asma y la obesidad se han descrito en estudios grupales, pero no se han confirmado posteriormente. Las características específicas de este fenotipo no se han diferenciado de las inherentes al índice de masa corporal (IMC) del paciente. Objetivos : Este estudio tiene como objetivo evaluar el efecto del IMC sobre el asma para identificar qué rasgos podrían definir el fenotipo del asma y la obesidad y cuáles son inherentes al IMC del paciente. Métodos : Se realizó un estudio observacional retrospectivo de la vida real basado en datos de 2514 pacientes con sospecha de asma recopilados en la primera visita a la clínica de alergia entre noviembre de 2014 y noviembre de 2017. Todos los pacientes tuvieron que realizar una maniobra de espirometría adecuada. Estuvieron representados todos los grupos de IMC, sexo y edad. Resultados : La influencia del IMC sobre el asma difirió según grupo de edad y sexo. Todos los resultados de la espirometría y el FeNO estuvieron influenciados por el IMC. Las únicas características notables del asma fueron la aparición tardía del asma con valores de IMC más altos. No se encontraron otras diferencias entre los grupos de IMC. Conclusiones : El efecto del IMC sobre el asma depende de la edad; por lo tanto, debe corregirse según la edad. Las variaciones más importantes se encuentran en los resultados de FeNO y espirometría. Las características específicas del fenotipo de asma y obesidad son una mayor percepción de los síntomas con menos alteraciones en las pruebas de función respiratoria y una menor prevalencia de atopia, rinitis y alergia, incluido el asma alérgica. Otras características de este fenotipo, como una mayor prevalencia femenina o asma de aparición tardía o no eosinofílica, no son específicas de este fenotipo (AU)

Clínica, epidemiología e imagenología del fibroma osificante y la displasia fibrosa del territorio cráneo-maxilofacial: revisión narrativa / Clinical, epidemiology and imaging of ossifiying fibroma and fibrous dysplasia of the cranio-maxillofacial territory: narrative review

Introducción: El fibroma osificante (FO) y la displasia fibrosa (DF) tienen características imagenológicas e histopatológicas similares que dificultan el diagnóstico diferencial. El propósito de la presente revisión narrativa es analizar las características clínicas, epidemiológicas e imagenológicas del FO y la DF, y evaluar la relación entre las características imagenológicas y las variantes histopatológicas del FO, en reportes y series de casos publicados.Materiales y métodos:Se realizó una búsqueda de reportes y series de casos de FO y DF entre 2017-2021 en PubMed, Scopus y Web of Science. Los casos debían tener suficiente información clínica, epidemiológica, histopatológica e imagenológica.Resultados:Se incluyeron 23 artículos con 25 lesiones: 17 FO y 8 DF. El tiempo de evolución de DF es más prolongado que FO. FO se ubica con mayor tendencia en complejo osteomeatal en comparación con DF. Sólo FO presentó alteraciones en piel, radiolucidez/hipodensidad periférica, perforación ósea y rizalisis externa, además, tuvo mayor tendencia al avance a espacios anatómicos adyacentes y a generar asimetría facial y/o craneal. FO psammomatoide y FO trabecular comparten patrones imagenológicos y tienen límites definidos corticalizados. FO convencional tuvo mayor tendencia a perforar corticales. DF puede tener límites mal definidos y definidos corticalizados. El FO mostró características imagenológicas de mayor agresividad que la DF.Conclusiones:La histología e imagenología por sí solas no son decisivas en el diagnóstico de FO y DF. Es imprescindible considerar conjuntamente clínica, imagenología e histopatología, enfatizando en las características que orienten el diagnóstico diferencial.(AU)

Introduction: Ossifying fibroma (OF) and fibrous dysplasia (FD) have similar imaging and histopathological characteristics, which make differential diagnosis difficult. The aim of this narrative review was to analyze the clinical, epidemiological and imaging characteristics of OF and FD, as well as to evaluate the relationship between imaging characteristics and histopathologic variants of OF, in reports and case series published.Materials and methods:A search of reports and case series of OF and FD between 2017-2021 in PubMed, Scopus and Web of Science was performed. The cases had to have enough clinical, epidemiological, histopathological and imaging information.Results:23 articles with 25 lesions were included: 17 OF and 8 FD. FD had a longer time of evolution than OF. OF is more likely to be in osteomeatal complex compared to FD. Only OF had skin alterations, peripheral radiolucency/hypodensity, bone perforation and external root resorption, in addition, it had a greater tendency to advance to adjacent anatomical spaces and generate facial and/or cranial asymmetry. Psammomatoid OF and trabecular OF share imaging patterns and have defined and corticated margins. Conventional OF had a greater tendency to cortical perforation. DF can have ill-defined and defined and corticated margins. OF has imaging characteristics of greater aggressiveness than FD.Conclusion:Histology and imaging alone are not decisive in OF and FD diagnosis. It is essential to consider clinical, imaging and histopathological evaluations as a whole, emphasizing in the characteristics that guide the differential diagnosis.(AU)

Improvement in Smell Using Monoclonal Antibodies Among Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review.

BACKGROUND: Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP. METHODS: We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received. RESULTS: Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell. CONCLUSION: Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab.

Adherence to inhaled corticosteroids and long-acting ß2-agonists in asthma: A MASK-air study.

INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting ß2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.

Spanish Consensus on the Management of Chronic Rhinosinusitis With Nasal Polyps (POLIposis NAsal/POLINA 2.0).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent and burdensome disease for both individuals and health systems. Its management involves many specialties, including otorhinolaryngology, allergology, pulmonology, primary care, pharmacy, and pediatrics. A multidisciplinary approach and the participation of the patient in decision-making are essential, both for diagnosis and for therapy. The authors of the consensus aim to translate current knowledge into an easy-to-read practical guide and emphasize those aspects requiring further discussion or with unmet needs owing to the lack of appropriate scientific evidence. An iterative approach for the development of an evidence-based systematic review with recommendations was followed using a standard quality assessment approach (Scottish Intercollegiate Guidelines Network [SIGN] and National Institute for Health and Care Excellence [NICE]). The guideline was critically evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) and Recommendation Excellence (AGREE REX) instruments. Consequently, POLINA has been considered a high-quality guideline by an independent agency. The POLINA consensus provides new definitions of control, therapeutic management (including surgery and evaluation of severity), indications for use of biologics, and response. Finally, this guideline focuses on unmet research needs in CRSwNP.

Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials.

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.