Positioning of Tezepelumab in Severe Asthma / Posicionamento do Tezepelumabe na Asma Grave

Asthma is one of the most common chronic diseases and is estimated to be severe in 3%-10% of affected patients. There is a need for additional biologic treatments that are highly efficacious across the spectrum of severe uncontrolled asthma. Currently available drugs inhibit 1 or 2 specific cytokines or IgE antibodies and thus only partially suppress the complex type 2 (T2) inflammatory cascade. Biologics targeting more upstream molecules in the pathophysiological pathway of asthma could treat asthma more effectively. Tezepelumab is a human monoclonal immunoglobulin G2λ antibody that targets the cytokine thymic stromal lymphopoietin (TSLP). It is the first marketed biologic against an epithelial cell–derived cytokine, preventing binding of TSLP to its receptor and reducing the immune stimuli that TSLP can trigger in different asthma endotypes. Tezepelumab reduces downstream biomarkers of inflammation, such as blood and airway eosinophils, FeNO, IgE, IL-5, and IL-13. Tezepelumab provides a clinical benefit in severe asthma, reducing the annualized asthma exacerbation rate in patients with either high or low levels of biomarkers of T2 inflammation, although the effect is greater among those with high levels. The drug has been shown to improve asthma control, quality of life, and lung function and reduce airway hyperresponsiveness. Therefore, tezepelumab can be used across the spectrum of patients with severe uncontrolled asthma, especially in T2-high patients. This review includes a positioning statement by the authors, all of whom are members of the SEAIC Asthma Committee (AU)

A asma é uma das doenças crônicas mais comuns e estima-se que seja grave em 3% a 10% dos pacientes afetados. Há necessidade de tratamentos biológicos adicionais que sejam altamente eficazes em todo o espectro da asma grave não controlada. Os medicamentos atualmente disponíveis inibem 1 ou 2 citocinas específicas ou anticorpos IgE e, portanto, suprimem apenas parcialmente a cascata inflamatória complexa tipo 2 (T2). Os produtos biológicos que visam moléculas mais a montante na via fisiopatológica da asma poderiam tratar a asma de forma mais eficaz. Tezepelumab é um anticorpo monoclonal humano imunoglobulina G2λ que tem como alvo a citocina linfopoietina estromal tímica (TSLP). É o primeiro produto biológico comercializado contra uma citocina derivada de células epiteliais, impedindo a ligação da TSLP ao seu receptor e reduzindo os estímulos imunológicos que a TSLP pode desencadear em diferentes endótipos de asma. Tezepelumabe reduz biomarcadores de inflamação a jusante, como eosinófilos no sangue e nas vias aéreas, FeNO, IgE, IL-5 e IL-13. O tezepelumab proporciona um benefício clínico na asma grave, reduzindo a taxa anualizada de exacerbação da asma em pacientes com níveis elevados ou baixos de biomarcadores de inflamação T2, embora o efeito seja maior entre aqueles com níveis elevados. Foi demonstrado que o medicamento melhora o controle da asma, a qualidade de vida e a função pulmonar e reduz a hiperresponsividade das vias aéreas. Portanto, o tezepelumabe pode ser usado em todo o espectro de pacientes com asma grave não controlada, especialmente em pacientes com T2 elevado. Esta revisão inclui uma declaração de posicionamento dos autores, todos membros do Comitê de Asma da SEAIC (AU)

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)

Prevalence, T2 Biomarkers, and Cost of Severe Asthma in the Era of Biologics: The BRAVO-1 Study

Background: The last decade has seen new classifications of the pathophysiology of asthma that have changed the treatment options available. Objectives: To update data on the prevalence of T2 asthma, comorbidities, biomarker characterization, and costs of severe asthma in patients aged ≥12 years, taking into account new classifications and treatment options. Methods: Retrospective, observational, nationwide study using a top-down approach. Data were obtained from BIG-PAC®, an electronic medical record database of 1.7 million patients in Spain. The study population comprised patients aged ≥12 years who had received medical care during the period 2016-2017 and been diagnosed with asthma at least 1 year prior to the index date. Patients were followed for 1 year. Results: The prevalence of asthma was 5.5%. Asthma was severe in 3031 of these patients (7.7%), 81.2% of whom presented T2 asthma. Among patients with severe asthma, 64.1% had uncontrolled disease, 31.2% were oral corticosteroid–dependent (37% in the uncontrolled severe asthma group), and only 3.8% were receiving biologics. The most common T2 comorbidities were allergic rhinitis (66.1%), atopic dermatitis (29.1%), and chronic rhinosinusitis with nasal polyps (14.6%). Mortality rates in the total population and uncontrolled severe asthma groups were 4.2% and 5.5%, respectively. The total annual costs per patient with severe asthma were €5890 (uncontrolled) and €2841 (controlled). Conclusions: In the era of biologics, most severe asthma patients present T2 asthma. Despite the availability of new treatments, rates of oral corticosteroid–dependent patients with uncontrolled severe asthma remain high, although biologics continue to be underused. The costs of uncontrolled severe asthma are twice as high as those of controlled severe asthma. (AU)

Introducción: En la última década se han concadenado una serie de clasificaciones de la fisiopatología del asma que han cambiado las opciones de tratamientos disponibles. Objetivos: Actualizar los datos de prevalencia del asma T2, comorbilidades, caracterización de biomarcadores y costes del asma grave en pacientes ≥12 años en esta nueva situación. Métodos: Estudio retrospectivo, observacional y de ámbito nacional con un enfoque descendente. Los datos se obtuvieron de BIG-PAC®, una base de datos de historias clínicas electrónicas de 1,7 millones de pacientes en España. Se incluyeron pacientes ≥12 años que habían recibido atención médica durante el periodo 2016-2017 y que habían sido diagnosticados de asma al menos un año antes de la fecha índice y fueron seguidos durante un año. Resultados: La prevalencia del asma fue del 5,5%. De estos pacientes, 3.031 presentaban asma grave (7,7%), de los cuales el 81,2% presentaba asma T2. Entre los pacientes con asma grave, el 64,1% no estaban controlados, el 31,2% eran dependientes de corticosteroides orales (37% en el grupo de asma grave no controlada) y solo el 3,8% estaban en tratamiento con biológicos. Las comorbilidades T2 más frecuentes fueron la rinitis alérgica (66,1%), la dermatitis atópica (29,1%) y la rinosinusitis crónica con poliposis nasal (14,6%). Las tasas de mortalidad en los grupos de asma grave total y no controlada fueron del 4,2% y del 5,5%, respectivamente. Los costes totales anuales por paciente con asma grave fueron de 5.890 euros (no controlado) y 2.841 euros (controlado). Conclusiones: En la era de los biológicos, la mayoría de los pacientes con asma grave presentan asma T2. A pesar de la disponibilidad de nuevos tratamientos, las tasas de pacientes con asma grave no controlados y dependientes de corticosteroides orales siguen siendo altas, y los biológicos siguen estando infrautilizados. Los costes del asma grave no controlada duplican los del asma grave controlada. (AU)

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma

Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. Methods: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. Results: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤−0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. Conclusion: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH. (AU)

Antecedentes: En el asma bronquial, la hiperinsuflación pulmonar estática (SLH) medida mediante pletismografía corporal (Pleth) se asocia a un peor pronóstico. La gravedad de la SLH podría estar asociada con la disfunción de las vías respiratorias pequeñas (SAD), que puede medirse mediante la oscilometría de impulsos (IOS). Objetivo: Este estudio pretende determinar la correlación entre el SLH y la SAD en pacientes con asma grave, y la mejora de ambos parámetros en respuesta al tratamiento. Métodos: Se analizaron los datos de los pacientes que se inscribieron en el Registro de Asma Grave de Taiwán, una cohorte observacional prospectiva. Se realizaron periódicamente mediciones de Pleth e IOS. Se determinó la relación entre los parámetros espirométricos e IOS. Se analizaron los cambios en los parámetros clínicos y funcionales en respuesta al tratamiento. Resultados: De una muestra de 107 pacientes con asma grave, 83 (77,6%) presentaban SLH, definida mediante una relación volumen residual/capacidad pulmonar total (VR/CTP) aumentada. La mayoría de los pacientes eran mujeres de edad avanzada con peor función pulmonar y SAD, en comparación con los que no tenían SLH. El SAD por aumento de la resistencia/reactancia de las vías respiratorias se correlacionó significativamente con el SLH. La reactancia de las vías respiratorias a 5 Hz (X5) ≤-0,21 [kPa/(L/s)] detectó el SLH con un área bajo la curva ROC de 0,84 (p < 0,0001, sensibilidad = 85,2% y especificidad = 83,3%). Después de 12 meses, los pacientes que recibieron tratamiento biológico adicional presentaron una reducción significativa de las exacerbaciones, del nivel de óxido nítrico exhalado, del recuento de eosinófilos en sangre, una mejora del volumen espiratorio forzado en el primer segundo, de la X5, y una tendencia a la reducción del cociente RV/TLC en comparación con los que no recibieron tratamiento biológico... (AU)

[Control de asma grave predominantemente eosinofílica con el uso de anti IL-5].

Background: Asthma is a chronic inflammatory disease of the airways, caused by inflammatory cells and mediators, associated with smooth muscle dysfunction, causing variable airflow obstruction. With high, low and mixed type 2 immunoinflammatory mechanisms (endotypes). Severe asthma is that which requires step 4 or 5 of treatment (GINA 2023). The TH2 High phenotype, non-allergic with eosinophilia and FENO, is the second most common. It affects 300 million people around the world. Objetive: Describe asthma biomarkers after the use of antiinterleukin 5, Benralizumab, in adults with severe asthma. Methods: Case report, descriptive study. Patients with severe eosinophilic asthma and chronic polyposis rhinosinusitis under treatment with anti-IL5 were included, evaluating inflammatory biomarkers. Results: Serum eosinophils, FENO, ACT, spirometry, and exacerbations were measured in 8 patients at baseline and 6 months after treatment. The FEV1-FVC was 51% with improvement up to 95% later. 5 patients had FENO > 45 ppm subsequently only 3 continued to be inflamed. Eosinophilia 150 cells and subsequently only 1 patient persisted with eosinophilia 200 cells. Initial ACT < 19 in 7 patients Final ACT >19 in 7 patients. Exacerbations 8 patients with 2 or more exacerba- tions subsequently only 1 patient presented exacerbation. Conclusion: The use of anti-interleukin 5 (benralizumab) does reduce inflammatory markers, improves control and number of exacerbations in the short term. Monoclonal antibodies (Anti IL-5), if they improve inflammatory biomarkers, if clinical characteristics and inflammatory biomarkers are taken into account, it favors adequate asthma control.

Antecedentes: El asma es una enfermedad inflamatoria crónica de vías respiratorias, provocada por células y mediadores inflamatorios, asociado a disfunción del músculo liso, provocando obstrucción variable del flujo aereo. Con mecanismos inmunoinflamatorios tipo 2 altos, bajos y mixtos (endotipos). Asma grave es aquella que requiere paso 4 o 5 de tratamiento (GINA 2023). El fenotipo TH2 Alto, no alergico con eosinofilia y FENO, es el segundo más común. Afecta a 300 millones de personas alrededor del mundo. Objetivo: Describir biomarcadores de asma, posterior al uso de antiinterleucina 5, Benralizumab, en adultos con asma grave. Métodos: Reporte de casos, estudio descriptivo. Se incluyeron pacientes con asma grave eosinofilica y rinosinusitis crónica poliposica en tratamiento con an- ti-IL5, evaluando biomarcadores inflamatorios Resultados: En 8 pacientes se midieron eosinófilos séricos, FENO, ACT, espirometría y exacerbaciones al inicio y 6 meses después del tratamiento. El FEV1-FVC fue 51% con mejoría hasta 95% después. 5 pacientes tenían FENO >45 ppm posteriormente solo 3 continuron inflamados. Eosinofilia 150 células y posterior- mente solo 1 paciente persistió con eosinofilia 200 células. ACT inicial < 19 en 7 pacientes ACT final > 19 en 7 pacientes. Exacerbaciones 8 pacientes con 2 o más exacerbaciones posteriormente solo 1 paciente presentó exacerbación. Conclusión: El uso de antiinterleucina 5 (Benralizumab) si disminuye marcadores inflamatorios, mejora el control y número de exacerbaciones a corto plazo. Los anticuerpos monoclonales (Anti IL-5), si mejoran biomarcadores inflamatorios si se toman en cuenta caracteristicas clínicas y biomarcadores inflamatorios favorece adecuado control de asma.

[Perfilamiento del paciente con asma grave eosinofílica para el tratamiento biológico con Mepolizumab y su efectividad en el control de la enfermedad].

Background: Management of severe eosinophilic asthma includes typing to identify allergic, eosinophilic and non-HT2 phenotypes. Elevated eosinophil levels are associated with higher IL-5 levels. Eosinophils during their migration to target tissues secrete proteins that damage the activated bronchial epithelium and correlate with asthma severity. Mepolizumab, a humanized monoclonal antibody that binds and neutralizes IL-5. Objectives: To describe experience with the use of biological anti interleukin 5 Mepolizumab. Methods: Case report, descriptive study. We included patients with severe uncontrolled asthma, a history of rhinosinusitis with nasal polyposis and/or EREA. Eosinophils 150 cells/µL, FeNO 25 ppb and spirometry with obstructive pattern. Results: 6 women with a diagnosis of severe asthma were included. Initial eosinophil values of 180 - 630 cél/µL, IgE 176 - 2500 Ui/ml, FENO 23 -39, ACT at 2, 4 and 6 months of use, minimum of 9 and maximum end of 25. Significant improvement in the ACT test from the first two months of use, decreased inhaled steroid and 0 to 2 exacerbations in 6 months. Conclusions: There are multiple studies, there are no statistically significant reports to demonstrate superiority with the use of a specific biological, together with the different economic limitations that exist in the country. It is necessary to identify target populations with phenotypes In Mexico there are few hospitals with these therapies, it is necessary to continue with the constant evaluation and contribution of information to find the right treatment for the Mexican population. that will respond to a specific therapy and direct treatment.

Antecedentes: El manejo del asma grave eosinofílica incluye tipificación para identificar fenotipos alérgicos, eosinofílicos y no TH2. Niveles elevados de eosi- nófilos se asocia a mayor nivel de IL-5. Los eosinófilos durante su migración a los tejidos diana, secretan proteínas que dañan el epitelio bronquial activado y se correlacionan con la gravedad del asma. Mepolizumab, anticuerpo monoclonal humanizado que se une y neutraliza la IL-5. Métodos: Describir experiencia con el uso de biológico anti-interleucina 5 Mepolizumab. Objetivos: Reporte de casos, estudio descriptivo. Se incluyeron pacientes con asma grave descontrolada, antecedente de Rinosinusitis con poliposis nasal y/o EREA. Eosinófilos ≥150 células/µL, FeNO ≥25 ppb y espirometría con patrón obstructivo. Resultados: Se incluyeron 6 pacientes mujeres con diagnóstico de Asma grave. Valores iniciales de eosinófilos de 180 ­ 630 cél/µL, IgE 176 ­ 2500 Ui/ml, FENO 23 -39, ACT a los 2, 4 y 6 meses de uso, mínima de 9 y final máxima de 25. Mejoría considerable en la prueba ACT desde los primeros dos meses de uso, dismi- nucion de esteroide inhalado y 0 a 2 exacerbaciones en 6 meses. Conclusiones: Existen múltiples estudios, no se cuenta con reportes estadísticamente significativos para demostrar superioridad con el uso de algún biológico en específico, aunado a las diferentes limitantes económicas que existen en el país. Es necesario identificar poblaciones objetivo con los fenotipos que responderán a una terapia específica y dirigir el tratamiento. En México hay pocos centros hospitalarios con estas terapias, es necesario continuar con la evaluación constante y aporte de información para poder encontrar el tratamiento idóneo para la población mexicana.

Avances en el trabajo de equipos multidisciplinares para la atención al paciente con asma grave no controlada. Una visión post-COVID (Proyecto TEAM 2.0) / Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project)

El asma es una enfermedad respiratoria crónica con un alto impacto sanitario, social y económico, en particular, en el caso del asma grave no controlada (AGNC). Por ello, son especialmente necesarias nuevas estrategias para mejorar su abordaje, con un enfoque personalizado a cada paciente y desde una perspectiva multidisciplinar, además de integrar las nuevas prácticas de telemedicina y telefarmacia impulsadas a raíz de la pandemia de COVID-19. En este contexto se ha desarrollado el proyecto TEAM 2.0 («Trabajo en Equipos de Asma Multidisciplinares»), continuación del proyecto TEAM llevado a cabo en 2019, con el objetivo de actualizar y priorizar buenas prácticas de trabajo multidisciplinar en AGNC en un contexto post pandemia y analizar los avances conseguidos. Un grupo coordinador, constituido por 8 equipos multidisciplinares de farmacéuticos hospitalarios, neumólogos y alergólogos, llevó a cabo una revisión bibliográfica actualizada, puesta en común de buenas prácticas multidisciplinares y análisis de avances. A través de 5 reuniones regionales con otros expertos con experiencia en AGNC, se compartieron las buenas prácticas identificadas y fueron sometidas a debate, evaluación y priorización. En total, 23 buenas prácticas de trabajo multidisciplinar en AGNC, agrupadas en 5 ámbitos de trabajo: 1) organización del trabajo en equipos multidisciplinares, 2) educación al paciente, autoadministración y adherencia, 3) resultados en salud, seguimiento de datos y persistencia, 4) telefarmacia y experiencias implantadas durante la pandemia de COVID-19 y 5) formación e investigación, fueron evaluadas y priorizadas por 57 profesionales del ámbito de la farmacia hospitalaria, la neumología, la alergología y la enfermería. Este trabajo ha permitido actualizar la hoja de ruta de acciones prioritarias, para seguir avanzando en modelos óptimos de atención al paciente con AGNC en un contexto post-COVID-19. (AU)

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project (“Work in Multidisciplinary Asthma Teams”) has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context. (AU)

[Translated article] Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project). / Avances en el trabajo de equipos multidisciplinares para la atención al paciente con asma grave no controlada. Una visión post-COVID (Proyecto TEAM 2.0).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Consenso multidisciplinar español sobre las características de los pacientes con asma grave en tratamiento con biológicos susceptibles de pasar a tratamiento domiciliario / Spanish multidisciplinary consensus on the characteristics of severe asthma patients on biologic treatment who are candidates for at-home administration

Antecedentes y objetivo Es bien sabido que las terapias biológicas reducen las exacerbaciones y mejoran el tratamiento del asma grave no controlada. La administración domiciliaria de biológicos ha aumentado durante la pandemia de COVID-19, pero aún no se han identificado las características de los pacientes con asma grave no controlada que pueden beneficiarse de la administración domiciliaria de terapia biológica. Materiales y métodos Este proyecto se basa en la metodología Delphi, diseñada para alcanzar un consenso entre expertos a través de un comité científico multidisciplinar que aborda las siguientes cuestiones: características clínicas, adherencia al tratamiento, capacidad de administración del paciente o cuidador, autocuidado del paciente, relación con el profesional sanitario, preferencias del paciente y acceso al hospital. Resultados Ciento treinta y un profesionales sanitarios (neumólogos, alergólogos, enfermeros y farmacéuticos hospitalarios) cumplimentaron las dos rondas de consenso del cuestionario Delphi. Se identificaron 14 ítems como características prioritarias, siendo los cinco primeros: 1. El paciente sigue las indicaciones/recomendaciones del equipo sanitario para controlar su enfermedad. 2. El paciente es capaz de detectar cualquier deterioro de su enfermedad y de identificar los factores desencadenantes de las exacerbaciones. 3. El paciente recibe tratamiento biológico y tiene una enfermedad estable sin riesgo vital. 4. El paciente se responsabiliza de su autocuidado y 5. el paciente tiene obligaciones laborales/educativas que le impiden acudir al hospital con regularidad (AU)

Background and objective Biologic therapies are known to reduce exacerbations and improve severe uncontrolled asthma management. The at-home administration of biologics has increased during the COVID-19 pandemic, but the characteristics of severe uncontrolled asthma patients who may benefit from at-home administration of biologic therapy have yet to be identified. Materials and methods This project is based on the Delphi method, designed to reach an expert consensus through a multidisciplinary scientific committee addressing the following questions: clinical characteristics, treatment adherence, patient or caregiver administration ability, patient self-care, relationship with the healthcare professional, patient preference, and access to the hospital. Results One hundred and thirty-one healthcare professionals (pulmonologists, allergists, nurses, and hospital pharmacists) completed two Delphi consensus questionnaires. Fourteen items were identified as priority characteristics, the first five being: 1. The patient follows the healthcare team's indications/recommendations to control their disease, 2. The patient is capable of detecting any deterioration in their disease and of identifying exacerbation triggers, 3. The patient receives biologic therapy and has stable disease with no vital risk, 4. The patient takes responsibility for their self-care, 5. The patient has occupational/educational obligations that prevent them from going to the hospital regularly. Conclusions Disease stability and control plus the ability to identify exacerbation triggers are the most important characteristics when opting for at-home administration for a patient with severe uncontrolled asthma on biologic therapy. These recommendations could be applicable in clinical practice (AU)

Caracterización del asma grave no controlada en adultos mayores de 60 años

Introducción: Los pacientes mayores de 60 años suelen tener un asma más grave, menos controlada y peor función pulmonar que los jóvenes. Objetivo: Caracterizar a los pacientes mayores de 60 años con asma grave no controlada. Métodos: Se realizó un estudio observacional descriptivo, prospectivo y transversal en el Hospital Neumológico Benéfico Jurídico en el período comprendido entre enero del 2020 y enero del 2021. Resultados: Edad predominante 60-69 años (76,5 %). Mujeres (61,8 %). Antecedentes familiares de asma o alergia (64,7 %). Asma de larga evolución (85,3 %). Asma asociada a obesidad y mal control (55,9 %). Reversibilidad del VEF1 (volumen espiratorio forzado en el primer segundo) después de la aplicación del broncodilatador (26,5 %). Adherencia al tratamiento (61,8 %). El riesgo futuro de resultados adversos fue bajo en el 58,8 %, es el principal factor, el mal control actual en el 100 %. Conclusiones: El asma grave no controlada en mayores de 60 años es más frecuente en el sexo femenino, los pacientes suelen tener antecedentes familiares de asma o alergia, presentar asma de larga evolución, obesidad asociada al mal control, disminución de la reversibilidad del VEF1 con la aplicación del broncodilatador, mala adherencia al tratamiento y el mal control actual como riesgo futuro de la enfermedad.

Introduction: Patients older than 60 years tend to have more severe, less controlled asthma and worse lung function than younger people. Objective: To characterize patients older than 60 years with severe uncontrolled asthma. Methods: A descriptive, prospective and cross-sectional observational study was carried out at Benéfico Jurídico Pneumological Hospital from January 2020 to January 2021. Results: The age group 60-69 years (76.5%) predominated. Women also predominated (61.8%), as well as family history of asthma or allergy (64.7%), and long-standing asthma (85.3%). Asthma associated with obesity and poor control was 55.9%. The reversibility of the forced expiratory volume in the first second (FEV1) after the application of the bronchodilator was 26.5%. The adherence to treatment was 61.8%. The future risk of adverse results was low (58.8%), which is the main factor, the current poor control in 100%. Conclusions: Severe uncontrolled asthma in people over 60 years of age is more frequent in women, patients usually have family history of asthma or allergy, there is long-term asthma. It was observed that obesity is associated with poor control, the decreased FEV1 reversibility with the application of the bronchodilator, poor adherence to treatment and poor current control as a future risk of the disease.

Spanish multidisciplinary consensus on the characteristics of severe asthma patients on biologic treatment who are candidates for at-home administration.

BACKGROUND AND OBJECTIVE: Biologic therapies are known to reduce exacerbations and improve severe uncontrolled asthma management. The at-home administration of biologics has increased during the COVID-19 pandemic, but the characteristics of severe uncontrolled asthma patients who may benefit from at-home administration of biologic therapy have yet to be identified. MATERIALS AND METHODS: This project is based on the Delphi method, designed to reach an expert consensus through a multidisciplinary scientific committee addressing the following questions: clinical characteristics, treatment adherence, patient or caregiver administration ability, patient self-care, relationship with the healthcare professional, patient preference, and access to the hospital. RESULTS: One hundred and thirty-one healthcare professionals (pulmonologists, allergists, nurses, and hospital pharmacists) completed two Delphi consensus questionnaires. Fourteen items were identified as priority characteristics, the first five being: 1. The patient follows the healthcare team's indications/recommendations to control their disease, 2. The patient is capable of detecting any deterioration in their disease and of identifying exacerbation triggers, 3. The patient receives biologic therapy and has stable disease with no vital risk, 4. The patient takes responsibility for their self-care, 5. The patient has occupational/educational obligations that prevent them from going to the hospital regularly. CONCLUSION: Disease stability and control plus the ability to identify exacerbation triggers are the most important characteristics when opting for at-home administration for a patient with severe uncontrolled asthma on biologic therapy. These recommendations could be applicable in clinical practice.

Bronchodilator Reversibility in the GAN Severe Asthma Cohort

Background: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit a negative BDR response. Aim: To describe the frequency of positive and negative BDR response in patients with severe asthma and study associations with phenotypic characteristics. Methods: A positive BDR response was defined as an increase in FEV1 >200 mL and >12% upon testing with a short-acting ß-agonist. Results: BDR data were available for 793 of the 2013 patients included in the German Asthma Net (GAN) severe asthma registry. Of these, 250 (31.5%) had a positive BDR response and 543 (68.5%) a negative BDR response. Comorbidities significantly associated with a negative response were gastroesophageal reflux disease (GERD) (28.0% vs 40.0%, P<.01) and eosinophilic granulomatosis with polyangiitis (0.4% vs 3.0%; P<.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and comorbid chronic obstructive pulmonary disease (COPD) (5.2% vs 7.2%) were similar in both groups. Patients with a positive BDR response had worse asthma control (median Asthma Control Questionnaire 5 score, 3.4 vs 3.0, P<.05), more frequently reported dyspnea at rest (26.8% vs 16.4%, P<.001) and chest tightness (36.4% vs 26.2%, P<.001), and had more severe airway obstruction at baseline (FEV1% predicted, 56 vs 64, P<.001) and higher fractional exhaled nitric oxide (FeNO) levels (41 vs 33 ppb, P<0.05). There were no differences in diffusion capacity of the lung for carbon monoxide, single breath (% pred, 70% vs 71%). Multivariate linear regression analysis identified an association between positive BDR response and lower baseline FEV1% (P<.001) and chest tightness (P<.05) and a negative association between BDR and GERD (P<.05). Conclusion: In this real-life setting, most patients with severe asthma had a negative BDR response. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD. (AU)

Antecedentes: La reversibilidad broncodilatadora (RB) positiva es un criterio diagnóstico para el asma. Sin embargo, los pacientes con asma pueden presentar una prueba RB negativa. Objetivos: Describir la frecuencia de RB positivas y negativas en pacientes con asma grave y sus asociaciones con características fenotípicas. Métodos: La RB positiva se definió como un aumento del FEV1 > 200 ml y > 12% tras la inhalación de un agonista beta de acción corta (SABA). Resultados: De 2013 pacientes incluidos en el registro de asma grave del German Asthma Net (GAN), 793 tenían datos sobre RB. De estos, 250 (31,5%) tuvieron una prueba RB positiva y 543 (68,5%) negativa. Las comorbilidades significativamente asociadas con RB negativa fueron el reflujo gastroesofágico (ERGE) (28,0% frente a 40,0%, p<0,01) y EGPA (0,4% frente a 3,0%; p<0,05), mientras que el antecedente de tabaquismo (activo: 2,8% frente a 2,2%; exfumador: 40,0% vs. 41,7%) y la comorbilidad de la EPOC (5,2% vs. 7,2%) fueron similares en ambos grupos. Los pacientes con RB positiva tenían peor control del asma (mediana ACQ-5 3,4 vs. 3,0, p<0,05), más disnea en reposo (26,8% vs. 16,4%, p<0,001) y mayor opresión torácica (36,4% vs. 26,2%, p<0,001), además presentaban una obstrucción de las vías respiratorias más grave al inicio del estudio (FEV1% pred: 56 frente a 64, p<0,001) y niveles más altos de FeNO (41 frente a 33 ppb, p<0,05), mientras que la capacidad de difusión fue similar (DLCO-SB% pred. 70% vs. 71%). El análisis de regresión lineal multivariable identificó una asociación de FEV1% basal inferior (p<0,001) y opresión torácica (p<0,05) con RB positiva y ERGE (p<0,05) con RB negativa. Conclusión: En este entorno en vida real, la mayoría de los pacientes con asma grave tuvieron una RB negativa. Curiosamente, esto no se asoció con antecedentes de tabaquismo o EPOC, sino con FeNO más bajo y presencia de ERGE. (AU)

Response to Monoclonal Antibodies in Asthma: Definitions, Potential Reasons for Failure, and Therapeutic Options for Suboptimal Response

Real-life data reveal that more than half of severe asthma patients treated with monoclonal antibodies (mAbs) do not achieve a complete response. Response to mAbs must be assessed holistically, considering all the clinically meaningful therapeutic goals, not only reduction of exacerbations and oral corticosteroids. There are 2 different ways of measuring the response to mAbs. One, qualitative, classifies patients according to the degree of disease control they have achieved, without explaining how much a given patient improves relative to the baseline (pre-mAb) clinical situation; the other, quantitative, scores the changes occurring after treatment. Both methods are complementary and essential to making clinical decisions on whether to continue treatment. The various potential causes of suboptimal response to mAbs include incorrect identification of the specific T2 pathways, comorbidities that reduce the room for improvement, insufficient dose, autoimmune phenomena, infections, change in the initial inflammatory endotype, and adverse events. Once a suboptimal response has been confirmed, a well-structured and multifaceted assessment of the potential causes of failure should be performed, with emphasis on the resulting inflammatory process of the airway after mAb therapy and the presence of chronic or recurrent infection. This investigation should guide the decision on the best therapeutic approach. The present review aims to help clinicians gain insights into how to measure response to mAbs and proceed in cases of suboptimal response (AU)

Los estudios clínicos en vida real revelan que más de la mitad de los pacientes con asma grave, tratados con anticuerpos monoclonales (mAb), no logran una respuesta completa. La respuesta a los mAbs debe evaluarse de manera integral, considerando todos los objetivos terapéuticos clínicamente significativos y no solo las exacerbaciones o la reducción de corticosteroides orales. Existen dos formas diferentes de medir la respuesta a los mAbs: una, cualitativa, que clasifica a los pacientes según el grado de control de la enfermedad que han logrado, sin explicar cuánto mejora un determinado paciente con respecto a su situación clínica basal (pre-mAb); y la otra, cuantitativa, la cual puntúa los cambios ocurridos después del tratamiento. Ambos métodos son complementarios y claramente esenciales a la hora de tomar decisiones clínicas sobre la continuación del tratamiento con estos fármacos biológicos. Se han descrito varias causas posibles de respuesta subóptima a los mAbs que son: la identificación incorrecta de las vías T2 específicas, las comorbilidades que reducen el margen de mejora, una dosis insuficiente, fenómenos autoinmunes, infecciones, cambio del endotipo inflamatorio inicial y la aparición de efectos adversos. na vez que se ha confirmado una respuesta subóptima, se debe realizar una evaluación bien estructurada y polifacética de estas posibles causas del fracaso, considerando, en particular, el proceso inflamatorio residual de las vías respiratorias tras la terapia con mAb y la presencia de infecciones crónicas o recurrentes. Esta evaluación es la que debe guiar las decisiones sobre el mejor enfoque terapéutico. Esta revisión tiene como objetivo ayudar a los clínicos a obtener un conocimiento más profundo sobre cómo medir la respuesta a los mAbs y cómo proceder con los pacientes que presenten una respuesta subóptima (AU)

Efectividad de reslizumab en asma grave no controlada (AGNC) eosinofílica con poliposis nasal asociada / Effectiveness of reslizumab in severe uncontrolled asthma (AGNC) eosinophilic with associated nasal polyposis

In order to better characterize the profile of asthmatic patients who could benefit from monoclonal antibody treatments, the present study evaluated the effectiveness of reslizumab after one year of treatment in patients with severe uncontrolled eosinophilic asthma, distinguishing those with chronic rhinosinusitis. with associated nasal polyposis (RSCcNP). Reslizumab proved to be effective in this series of patients by reducing asthma exacerbations, improving lung function and asthma control, in addition to reducing the size and symptoms caused by nasal polyposis. (AU)

Con el fin de caracterizar mejor el perfil de pacientes asmáticos que podrían beneficiarse de tratamientos con anticuerpos monoclonales, en el presente estudio se evaluó la efectividad de reslizumab tras un año de tratamiento en pacientes con asma grave no controlada eosinofílica, distinguiendo aquellos que presentaban rinosinusitis crónica con poliposis nasal (RSCcPN) asociada. Reslizumab demostró ser efectivo en esta serie de pacientes al reducir las agudizaciones asmáticas, mejorar la función pulmonar y el control del asma, además de lograr disminuir el tamaño y sintomatología ocasionada por la poliposis nasal. (AU)

Autoadministración domiciliaria de biológicos. Una encuesta de satisfacción en una unidad de asma grave en tiempo de pandemia por COVID-19 / Home self-administration of biologics. A satisfaction survey in a severe asthma unit during a COVID-19 pandemic

Objetivo: Evaluar las preferencias y satisfacción de los pacientes con asma grave, relacionadas con el lugar de administración de fármacos biológicos subcutáneos: hospital, centro de salud y domicilio, durante la pandemia COVID-19. Métodos: Estudio observacional, descriptivo y transversal que analizó, mediante una encuesta telefónica realizada del 23 al 27 de noviembre de 2020, las preferencias y el grado de satisfacción con la administración de fármacos biológicos subcutáneos en pacientes asmáticos atendidos en la consulta de Alergología de un Hospital General. Resultados: Respondieron la encuesta 33 pacientes, edad media 51,5 años, 57,6% mujeres. Un 57,6% de los pacientes se administraron los fármacos (omalizumab, mepolizumab y benralizumab) en su domicilio, 21,2% en el Hospital de Día y en el Centro de Salud, respectivamente. Los motivos para la administración fuera del hospital fueron la comodidad y evitar el contagio por virus SARS-CoV-2 (30,7%).Tras la pandemia, los pacientes preferían continuar con la dispensación y autoadministración domiciliaria del biológico y tener consultas médicas presenciales. El grado de satisfacción fue 9,7 (escala 0 a 10). Conclusiones: Los pacientes prefieren autoadministrarse en su domicilio los fármacos biológicos para el AG con el apoyo de la dispensación domiciliaria de éstos, mostrando un alto grado de satisfacción por la comodidad que les aporta. Finalizada la pandemia, demandan que las visitas médicas sean presenciales pero desean continuar autoadministrándose el fármaco tras su dispensación domiciliaria por el Servicio de Farmacia. (AU)

Objective: To assess preferences and satisfaction of patients with severe asthma about the place of administration of subcutaneous biological drugs: hospital, health center and home, during the COVID-19 pandemic. Methods: Observational, descriptive and cross-sectional study that analyzed, from November 23 to 27, 2020, through a telephone survey, the preferences and degree of satisfaction with the administration of subcutaneous biological drugs in asthmatic patients treated in the Allergology consultation of a General Hospital. Results: A total of 33 patients responded to the survey, the mean age was 51.5 years, 57.6% were women. The patients that received subcutaneous biological drugs (omalizumab, mepolizumab and benralizumab) at home were 57,6%, at the Day Hospital and at the Health Center 21,2 %, in both cases. The reasons for the administration outside the hospital were comfort and to avoid the spread of the SAR-CoV-2 virus (30.7%). After the pandemic, patients prefer home deliveries, self-administration and face-to-face medical consultations. The degree of satisfaction with the treatment was very high. Conclusions: Patients prefer to self-administer biological drugs for GA at home with the support of their home dispensing, showing a high degree of satisfaction with the comfort it provides. Once the pandemic is over, they demand that medical visits be face-to-face but they want to continue self-administering the drug after it is dispensed at home by the Pharmacy Service. (AU)