Is exposure to pollen a risk factor for moderate and severe asthma exacerbations?

Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation, but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations, and an increase in grass pollen concentration in the previous 2-day overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7-day overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age, an exposure to grass pollen lagged up to 3 days may lower lung function. Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces, and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change.

Safety of biological therapy in elderly patients with severe asthma.

OBJECTIVE: To assess the safety of biological therapy for severe T2 asthma (omalizumab, mepolizumab, benralizumab and reslizumab) under real-life conditions in elderly patients older than 70 years. METHODS: Retrospective data collection including clinical characteristics, comorbidities, treatment, disease control and adverse events (AE) of all patients with severe asthma on biological therapy older than 70 years seen in the Severe Asthma Unit of our hospital. RESULTS: Of 147 patients with severe asthma being treated with biologics, 21 patients older than 70 years were included. The median age of these patients was 76.3 years (range 71-86) and the majority were women (n = 18, 85.7%). There were 9 patients (42.9%) who experienced an AE related to biological treatment. Four (44.4%) were in treatment with omalizumab, two (22.2%) with mepolizumab, two patients (22.2%) with reslizumab and one (11.1%) with benralizumab. The median FEV1 (%) was 66%. These patients had a considerably higher body mass index (BMI). No significant differences were found for any other variable. Most of the AE reported were considered mild with the exception of one case of systemic AE (anaphylaxis) associated with omalizumab. CONCLUSION: This study indicates that the prescription of biological therapy in elderly patients with severe asthma seems to be safe. More evidence is needed in this particular population.

Development of a Tool to Measure the Clinical Response to Biologic Therapy in Uncontrolled Severe Asthma: The FEV1, Exacerbations, Oral Corticosteroids, Symptoms Score.

BACKGROUND: There is a lack of tools to quantify the response to monoclonal antibodies (mAbs) holistically in severe uncontrolled asthma patients. OBJECTIVE: To develop a valid score to assist specialists in this clinical context. METHODS: The score was developed in four subsequent phases: (1) elaboration of the theoretical model of the construct intended to be measured (response to mAbs); (2) definition and selection of items and measurement instruments by Delphi survey; (3) weight assignment of the selected items by multicriteria decision analysis using the Potentially All Pairwise RanKings of All Possible Alternatives methodology using the 1000minds software; and (4) face validity assessment of the obtained score. RESULTS: Four core items, with different levels of response for each, were selected: severe exacerbations, oral corticosteroid use, symptoms (evaluated by Asthma Control Test), and bronchial obstruction (assessed by FEV1 percent predicted). Severe exacerbations and oral corticosteroid maintenance dose were weighted most heavily (38% each), followed by symptoms (13%) and FEV1 (11%). Higher scores in the weighted system indicate a better response and the range of responses runs from 0 (worsening) to 100 (best possible response). Face validity was high (intraclass correlation coefficient of 0.86). CONCLUSIONS: The FEV1, exacerbations, oral corticosteroids, symptoms score allows clinicians to quantify response in severe uncontrolled asthma patients who are being treated with mAbs.

Long and winding road: from infant wheeze to adult asthma.

PURPOSE OF REVIEW: This review aims to recognize the multifactorial cause of asthma, from the influence of mother until adulthood, highlight the main characteristics of the disease at different ages and summarize the evidence of potential prevention strategies. RECENT FINDINGS: To date, regarding the prenatal period, the presence of specific genes, maternal asthma, drugs, and tobacco exposure are the most relevant predisposing features for an asthmatic offspring. For newborns, preterm, bronchopulmonary dysplasia, and low birth weight has been associated with low lung function. Among young children, atopic dermatitis, lower respiratory tract infections, and increased levels of total Immunoglobulin E (IgE) and allergen-specific IgE are important determinants.Breastfeeding has been demonstrated being protective for the onset of asthma. Allergen immunotherapy has also been shown to have significant preventive effect decreasing asthma development. Inhaled corticosteroids use in early childhood prevents exacerbations but does not alter the natural history of asthma. Other interventions, such as the use of palivizumab, probiotics, vitamin D supplementation, and fish consumption presented controversial results. SUMMARY: A good knowledge of risk factors for asthma development, from prenatal period to adulthood, may lead to efficacious preventive strategies. Further data of long-term follow-up in population-based studies according to different phenotypes are needed.

[Allergy to vegetables belonging to the Solanaceae family]. / Alergia a vegetales pertenecientes a la familia de las solanáceas.

BACKGROUND: Although cross-reactivity with other plant-based foods and latex has been described, allergies to potatoes and tomatoes are uncommon. OBJECTIVE: To study the different sensitization patterns in patients who are allergic to potatoes and/or tomatoes. METHODS: Skin prick tests were carried out with fresh foods and extracts, specific IgE determination and allergen detection by SDS-PAGE and IgE-Immunoblotting with both raw and heated potato and tomato extracts. RESULTS: In 10 patients, two thermostable allergens to potato extract were detected; the first one with a molecular weight that is compatible with Sola t 1 (43 kDa, patatin) and the second one with a molecular weight of 14-22 kDa, which could correspond to the allergens Sola t 4 (16 kDa) and Sola t 2 and Sola t 3 (21 kDa); in two patients who are allergic to potatoes and two patients who are allergic to tomatoes, a thermostable allergen that is compatible to Sola I 2 (50 kDa) was detected. The patient had presented oral allergy syndrome with some types of potatoes and showed higher IgE reactivity to two thermostable potato allergens. CONCLUSIONS: The allergen sensitization patterns were similar in all the patients that had been studied, regardless of the symptoms. A new allergen involved in the allergy to solanaceae plants has been detected.

Antecedentes: Aunque se ha descrito reactividad cruzada con alimentos vegetales y látex, la alergia a la papa y al tomate es infrecuente. Objetivo: Estudiar los diferentes patrones de sensibilización en pacientes alérgicos a la patata o tomate. Métodos: Se realizaron pruebas de punción cutánea con extractos y alimentos frescos, determinación de IgE específica y detección de alérgenos mediante SDS-PAGE e IgE-Immunoblotting con extractos de patata y tomate crudos y calientes. Resultados: En 10 pacientes se detectaron alérgenos termoestables a extracto de patata, uno de peso molecular compatible con Sola t 1 (43 kDa, patatina) y otro de 14-22 kDa que podría corresponder a los alérgenos Sola t 4 (16 kDa), Sola t 2 y Sola t 3 (21 kDa); en dos pacientes alérgicos a la patata y dos alérgicos al tomate se detectó un alérgeno termoestable de aproximadamente 42 kDa. En un paciente alérgico al tomate se detectó un alérgeno termoestable compatible con Sola l 2 (50 kDa); había presentado síndrome de alergia oral con algunos tipos de patatas y mostró mayor reactividad IgE a dos alérgenos termoestables de la patata. Conclusiones: Los patrones de sensibilización a los alérgenos fueron similares en los pacientes, independientemente de los síntomas. Se ha detectado un nuevo alérgeno implicado en la alergia a las solanáceas.

Futuras terapias biológicas en el asma / Future Biologic Therapies in Asthma

Un porcentaje elevado de pacientes con asma no está controlado, incluso a pesar de seguir un tratamiento adecuado. Esto indica que son necesarios tratamientos alternativos que sean eficaces, seguros y selectivos para los fenotipos de asma descritos, especialmente en pacientes con asma grave no controlada. De los nuevos tratamientos en desarrollo para el asma, las opciones más prometedoras son las terapias biológicas, en particular los anticuerpos monoclonales frente a dianas selectivas. Es importante tener en cuenta que los diferentes fármacos, pero especialmente los nuevos tratamientos biológicos, actúan sobre vías patogénicas muy específicas, y por lo tanto cada vez va a ser más importante determinar el perfil individual de alteraciones fisiopatológicas predominante en cada paciente para prescribir el tratamiento más adecuado en cada caso. El tratamiento del asma grave alérgica con un anticuerpo monoclonal anti-IgE (omalizumab) ha mostrado ser eficaz en un número elevado de pacientes, y nuevos anticuerpos anti-IgE con mejores propiedades farmacodinámicas están siendo investigados. Entre las terapias en desarrollo, los medicamentos biológicos dirigidos a bloquear ciertas citoquinas proinflamatorias, como IL-5 (mepolizumab) e IL-13 (lebrikizumab), son los que tienen más visos de ser utilizados clínicamente. Tal vez el bloqueo de más de una vía de citoquinas (como IL-4 e IL-13 con dulipumab) pueda ofrecer una mayor eficacia del tratamiento, junto con una seguridad aceptable. La estratificación de asma en función de los mecanismos patogénicos predominantes en cada paciente (fenoendotipos) está abriendo paso, de forma lenta pero probablemente irreversible, a la medicina personalizada para el asma, y se está convirtiendo en un factor clave en el desarrollo de fármacos para este complejo síndrome respiratorio

Despite the administration of appropriate treatment, a high number of patients with asthma remain uncontrolled. This suggests the need for alternative treatments that are effective, safe and selective for the established asthma phenotypes, especially in patients with uncontrolled severe asthma. The most promising options among the new asthma treatments in development are biological therapies, particularly those monoclonal antibodies directed at selective targets. It should be noted that the different drugs, and especially the new biologics, act on very specific pathogenic pathways. Therefore, determination of the individual profile of predominant pathophysiological alterations of each patient will be increasingly important for prescribing the most appropriate treatment in each case. The treatment of severe allergic asthma with anti-IgE monoclonal antibody (omalizumab) has been shown to be effective in a large number of patients, and new anti-IgE antibodies with improved pharmacodynamic properties are being investigated. Among developing therapies, biologics designed to block certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13 (lebrikizumab), have a greater chance of being used in the clinic. Perhaps blocking more than one cytokine pathway (such as IL-4 and IL-13 with dulipumab) might confer increased efficacy of treatment, along with acceptable safety. Stratification of asthma based on the predominant pathogenic mechanisms of each patient (phenoendotypes) is slowly, but probably irreversibly, emerging as a tailored medical approach to asthma, and is becoming a key factor in the development of drugs for this complex respiratory syndrome

Future biologic therapies in asthma.

Despite the administration of appropriate treatment, a high number of patients with asthma remain uncontrolled. This suggests the need for alternative treatments that are effective, safe and selective for the established asthma phenotypes, especially in patients with uncontrolled severe asthma. The most promising options among the new asthma treatments in development are biological therapies, particularly those monoclonal antibodies directed at selective targets. It should be noted that the different drugs, and especially the new biologics, act on very specific pathogenic pathways. Therefore, determination of the individual profile of predominant pathophysiological alterations of each patient will be increasingly important for prescribing the most appropriate treatment in each case. The treatment of severe allergic asthma with anti-IgE monoclonal antibody (omalizumab) has been shown to be effective in a large number of patients, and new anti-IgE antibodies with improved pharmacodynamic properties are being investigated. Among developing therapies, biologics designed to block certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13 (lebrikizumab), have a greater chance of being used in the clinic. Perhaps blocking more than one cytokine pathway (such as IL-4 and IL-13 with dulipumab) might confer increased efficacy of treatment, along with acceptable safety. Stratification of asthma based on the predominant pathogenic mechanisms of each patient (phenoendotypes) is slowly, but probably irreversibly, emerging as a tailored medical approach to asthma, and is becoming a key factor in the development of drugs for this complex respiratory syndrome.