Positioning of Tezepelumab in Severe Asthma.

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.

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)

The Multiple Trajectories of the Allergic March.

The allergic march comprises the sequential appearance of a series of allergic comorbidities. However, variability in the onset and progression of allergic diseases generates a heterogeneous scenario that does not follow a linear and single trajectory. Almost half of the pediatric population presents at least 1 allergy symptom. However, only 4%-6% present multimorbidity, with several allergic diseases co-occurring. It has recently been shown that although they share etiological mechanisms and risk factors, allergic diseases arise independently. In most cases, progression is not consecutive, or at least not the same in all patients. TH2-mediated inflammation, epithelial barrier dysfunction, and genetic predisposition play a fundamental role in the etiology of allergic diseases, on which the interaction with the exposome acts decisively. Therefore, studying diseases from an omics point of view is essential when attempting to describe the various trajectories of allergic progression and to propose effective interventions to prevent multimorbidity. In this narrative review, we provide an overview of the current perception of the allergic march, including clinical observations, omics data, risk factors, and measures aimed at modifying its course or even preventing its onset.

A real life cohort of Mepolizumab treatment in severe eosinophilic asthma.

Summary: Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.

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.