Clinical Recommendations for the Management of Biological Treatments in Severe Asthma Patients: A Consensus Statement.

BACKGROUND AND OBJECTIVE: The definition of severe uncontrolled asthma and the best phenotype-driven management are not fully established. Objective: We aimed to reach a consensus on the definition of severe uncontrolled asthma and give recommendations on optimal management with phenotype-targeted biological therapies. METHODS: A modified Delphi technique was used. A scientific committee provided statements addressing the definition of severe uncontrolled asthma and controversial issues about its treatment with biologics. The questionnaire was evaluated in 2 rounds by expert allergists. With the results, the scientific committee developed recommendations and a practical algorithm. RESULTS: A panel of 27 allergists reached agreement on 27 out of the 29 items provided (93.1%). A consensus definition of severe uncontrolled asthma was agreed. Prior to initiation of therapy, it is mandatory to establish the asthma phenotype and assess the presence of clinically important allergic sensitizations. Anti-IgE, anti-IL-5, anti-IL-5 receptor, and anti-IL-13/IL-4 receptor inhibitors are suitable options for patients with allergic asthma and a blood eosinophil level >300/µL (>150/µL in patients receiving oral corticosteroids). IL-5 and anti-IL-5 receptor inhibitors are recommended for patients with an eosinophilic phenotype and can also be used for patients with severe eosinophilic allergic asthma with no or a suboptimal response to omalizumab. Dupilumab is recommended for patients with moderate-severe asthma and a TH2-high phenotype. Only physicians with experience in the treatment of severe uncontrolled asthma should initiate biological treatment. CONCLUSION: We provide consensus clinical recommendations that may be useful in the management of patients with severe uncontrolled asthma.

Allergic sensitization profiles among the foreign-born population in the north of Madrid.

Summary: Background. We assessed differences in allergic sensitization and clinical characteristics in a foreign-born population. Methods. Prospective, observational, descriptive study of patients aged > 12 years who were seen at the Department of Allergy, La Paz Hospital (Madrid, Spain), between January 2017 and December 2018. Patients were classified by geographical origin and ethnicity. Results. We included 150 patients (110 female) with a mean age of 38.38 years. Mean time to onset of respiratory symptoms after immigration was 8.47 years. Significant differences were observed between ethnic groups (p = 0.007). The most frequent sensitization was to grass pollen (75.2%), which was more common in South American patients (p = 0.005). We found that 59% of patients were sensitized to Cupressus and Olea pollen (higher in Asian patients, p = 0.032 and p = 0.049). Conclusions. Allergic sensitization in the foreign-born population was similar to that of the autochthonous population although differences between the groups were identified.

Biologics in the treatment of severe asthma

Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids and with a second controller drug to prevent it from becoming uncontrolled or which remains uncontrolled despite this therapy. Patients with uncontrolled severe asthma require additional treatment options as add-on therapy, including biologics. Biologic therapies in asthma are designed to block key immune regulators, such as IgE, or certain pro-inflammatory cytokines, e.g. interleukin (IL)-5, IL-4, IL-13 or IL-17. Patients with severe asthma and eosinophilic phenotype may benefit from biologic therapies aimed at reducing blood and tissue eosinophils, such as mepolizumab, reslizumab and benralizumab. Patients with Th2-high phenotype may also benefit from therapy with anti-IL-4/anti-IL-13 monoclonal antibodies (dupilumab). The main limitations of asthma treatment with biologic agents are the crossover and overlap of the different pathways in the pathogenesis of asthma which may cause lack of complete success of these therapies, in addition of high costs, which make pharmacoeconomic studies necessary to identify the ideal target patient population to receive these biologic drugs (AU)

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Comparison of two diagnostic techniques, skin-prick test and component resolved diagnosis in the follow-up of a cohort of paediatric patients with pollinosis. Multicentre pilot study in a highly exposed allergenic area.

BACKGROUND: Over the last years, different works have been published about the importance of incorporating new diagnosis techniques in allergic patients such as component-resolved diagnosis (CRD). The objective of this study is to compare the evolution of allergic sensitisation profiles by means of CRD and cutaneous tests (SPT) on pollen-allergic patients. METHODS: A total of 123 patients aged between 2 and 14 years were included in an open, prospective, multicentre study. All the children had symptoms suggestive of seasonal respiratory allergic disease, with the diagnosis confirmed by cutaneous tests. Specific-IgE to major pollen-allergens (CRD) and SPT were performed at basal and after three years of follow-up. RESULTS: Out of 123 patients included, a total of 85 were analysed. The mean age was 8±3 years. Significant changes in the allergic sensitisation profiles were observed for the most prevalent allergens (Olea and grass) but it is in grass, the most relevant allergen in terms of allergen pressure, where changes in both absolute and relative frequencies between SPT and CRD were more evident. CONCLUSION: CRD seems to be an essential tool to carry out an appropriate follow-up of patients with allergic respiratory disease, as well as to decide on the immunotherapy composition that best matches the allergic sensitisation profile of patients.

Vitiligo induced by specific immunotherapy with grass pollen: the Koebner phenomenon

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Anticholinergics for treatment of Asthma

Asthma management guidelines emphasize the importance of effective treatment to achieve and maintain control of asthma. However, despite widely available and effective treatments, achieving control of asthma is still an unmet need for many patients. Adding a second bronchodilator with a different mechanism of action for the treatment of uncontrolled asthma can be a suitable therapeutic approach. This review focuses on the role of long-acting muscarinic antagonists, particularly tiotropium, in the treatment of asthma. A number of studies have evaluated the efficacy and safety of tiotropium in asthma patients whose disease is poorly controlled with inhaled corticosteroids (ICSs) with or without long-acting β2 -agonists (LABAs). The effect on several clinical and lung function variables of adding tiotropium to an ICS is greater than doubling the dose of the latter and is not inferior to the addition of a LABA (salmeterol). Studies assessing the role of tiotropium as add-on therapy to ICS combined with a LABA have shown modest but clinically significant and dose-dependent improvements in forced expiratory volume in 1 second, as well as a decrease in the risk of exacerbations. In addition, time to the next episode is longer, particularly in patients who experience severe exacerbations. In conclusion, tiotropium proved noninferior to salmeterol and superior to placebo in patients with moderate-severe asthma who were not adequately controlled using ICSs or ICSs combined with a LABA. The major benefits are the increase in lung function and, in the case of severe asthma, the reduction in the frequency of exacerbations. In patients with asthma, tiotropium is usually well tolerated, and no potential safety signals have been observed (AU)

Las guías de manejo del asma destacan la importancia de un tratamiento efectivo del asma para lograr y mantener el control. Sin embargo, a pesar de disponer de tratamientos eficaces, alcanzar el control del asma sigue siendo un reto en muchos pacientes. La adición de un segundo broncodilatador con un mecanismo de acción diferente en el tratamiento de asma no controlada puede representar una aproximación terapéutica apropiada. Esta revisión va enfocada al papel de los antagonistas muscarínicos de acción prolongada (LAMA), especialmente el tiotropio, en el tratamiento del asma. Diversos estudios han evaluado la eficacia y al seguridad del tiotropio en pacientes con asma no controlada en tratamiento con corticosteroides inhalados (CSI) con o sin agonistas β2 de acción prolongada (LABA). El efecto de añadir tiotropio a CSI es superior a doblar la dosis de estos, y no es inferior a la adición de un LABA (salmeterol) en diversas variables clínicas y de función pulmonar. Los estudios que analizan el efecto de tiotropio como terapia adicional a la combinación de CSI y LABA han mostrado mejorías modestas pero clínicamente significativas y dependientes de la dosis en el FEV1, así como una disminución del riesgo de exacerbaciones, con una prolongación del tiempo hasta el siguiente episodio, especialmente en pacientes con exacerbaciones graves. En conclusión, tiotropio ha resultado no ser inferior a salmeterol y es superior al placebo en pacientes con asma moderada a grave no controlada a pesar del tratamiento con CSI o CSI/LABA. Los principales beneficios se observan sobre la función pulmonar, y en el caso de pacientes con asma grave, en la reducción de las exacerbaciones. En los pacientes con asma el tiotropio es por lo general bien tolerado y no se han observado potenciales problemas de seguridad (AU)

Diagnostic and therapeutic approaches in respiratory allergy are different depending on the profile of aeroallergen sensitisation.

BACKGROUND: There are few studies which analyse the characteristics of allergic respiratory disease according to profiles of sensitisation to different allergens. This study describes the clinical features and therapeutic approaches, according to the sensitisation profile to relevant aeroallergens, in a sample of adult patients with a first-time diagnosis of respiratory allergy (rhinitis and/or asthma). METHODS: 1287 patients, enrolled consecutively in the spring of 2010 by 200 allergy specialists, were classified into four groups according to sensitisation to significant allergens in each geographical area (grass pollen, olive pollen, grass and olive pollen, house dust mites). Information was obtained on demographics, diagnostic procedures used, treatments prescribed, clinical characteristics of the rhinitis, and severity and control of asthma. RESULTS: Of the patients, 58.6% had rhinitis only and 38.7% had both rhinitis and asthma. Patients with more severe rhinitis had more severe and poorer controlled asthma. Sensitisation to different allergens was not associated with significant differences in severity and control of asthma, but patients with house dust mite allergy presented persistent rhinitis more frequently. Allergy to grass pollen was significantly associated with food allergies. Differences were observed in the frequency of prescription of immunotherapy and antileukotrienes in patients allergic to house dust mites and of topical corticosteroids in patients with pollen allergy. CONCLUSIONS: It was observed in this study that in respiratory allergy disease, there are clinical differences as well as differences in diagnostic procedure and therapeutic attitudes, depending on the clinically relevant allergen.

Perfil de sensibilización alérgica en inmigrantes residentes en la zona centro de España / Allergic sensitization profile in the immigrant population living in the central region of Spain

Introducción. La prevalencia de las enfermedades alérgicas ha aumentado últimamente, especialmente en países industrializados. Puesto que la alergia está influenciada por factores genéticos y ambientales, la población inmigrante constituye un buen modelo epidemiológico para valorar influencia del ambiente. Presentamos las características clínicas de alergia respiratoria en población inmigrante del centro de España. Métodos. Se recogieron datos prospectivamente de 62 pacientes inmigrantes y 33 españoles que acudieron en marzo de 2010 a 7 hospitales de Madrid, Cuenca y Ciudad Real, diagnosticados de alergia respiratoria mediante un estudio alergológico estándar. Resultados. El 63% eran mujeres, edad media 28,4 años. Sus países de origen se distribuyeron en 3 grupos (Norte de África, Latinoamérica, Europa del Este). El 96% presentaban rinitis, aunque sólo el 48% de españoles frente al 76,9% de hispanos sufrían rinitis persistente. La prevalencia de asma fue similar, aunque entre hispanos el porcentaje de asma controlada fue menor. El tiempo de evolución fue menor en pacientes inmigrantes. El polen de gramíneas resultó el alérgeno más relevante salvo en pacientes árabes. La incidencia de sensibilización a polcalcina fue muy baja. Por el contrario, el 44,1% de españoles presentaban sensibilización aprofilina, frente al 4,88 de hispanos, aunque no implicaba sintomatología al tomar vegetales en la mayoría de casos. Conclusiones. Este estudio multicéntrico muestra diferencias significativas en tiempo de evolución y perfiles de sensibilización entre pacientes españoles e inmigrantes con alergia respiratoria. Además, diferencias en la expresión clínica de la rinitis y peor control del asma, pueden condicionar peor evolución clínica en el colectivo inmigrante(AU)

Introduction. The prevalence of allergic diseases has increased worldwide in the last two decades, particularly in developed countries. Respiratory allergy is determined by genetic heredity, influenced by environmental factors. Migration is a good epidemiological model for assessing the influence of the environment. We present the clinical characteristics of respiratory allergy in immigrants in the central region of Spain. Methods. We prospectively collected data on all immigrants referred to the allergy units of 7 different hospitals in Madrid, Cuenca and Ciudad Real in March 2010. Respiratory Allergy was diagnosed using a standard study for allergic diseases. Results in immigrants were compared with data from a similar Spanish population. Results. Sixty-two immigrants and 32 Spanish patients were evaluated (63% female, mean age 28.4 years). Their countries of origin were uniformly distributed among 3 macro areas (North of Africa, Latin America, and Eastern Europe). More than 96% presented rhinitis, although persistent rhinitis was more prevalent amongst Latin Americans (76.9%) than in the Spanish population (48%). No differences were observed in asthma prevalence, although immigrants had higher rates of non-controlled and partially controlled asthma. The meantime of onset of symptoms after immigration was 43 months. Grass pollen was the most relevant allergen with the exception of Arab patients. Sensitization to polcalcin was rare. Otherwise, 44.1% of the Spanish population was sensitized to profilin (only 4.88% among immigrants) although this sensitization did not associate allergy to fruits or other vegetables. Conclusions. In summary, a multicentric study is presented where significant differences have been observed in the sensitization pattern and clinical evolution of respiratory allergy in immigrants and the Spanish population(AU)

Sensibilización al polen de Olea europaea en las diferentes comarcas de la provincia de Zamora / Pollen sensitization to Olea europaea in the different regions of Zamora province

La sensibilización al polen de olivo en la provincia de Zamora debería ser mínima debido a que el olivo, por sus características, no se adapta bien a las condiciones climáticas y a que se ha introducido recientemente en la mayoría de las zonas de la provincia como árbol ornamental. Hemos realizado un estudio retrospectivo descriptivo que ha observado una sensibilización llamativa al polen del olivo, que aumenta en las zonas urbanas

Sensitization to olive pollen should not be important in Zamora city and province because, due to its characteristics, this tree doesn´t adapt to weather conditions in the city and because it has been recently introduced in most of the province’s areas as an ornamental tree. We have performed a retrospective descriptive study observing a significant level of sensitization to olive pollen, which is growing in urban zones

[Analysis of 83 bronchospasm episodes seen at urgent care during one spring night]. / Análisis de 83 episodios de broncoespasmo atendidos una noche de primavera en urgencias.

BACKGROUND: The new treatments for the bronchial inflammation in asthma, have contributed to decrease the mortality rate. However, there is still a group of population with no diagnosis fo asthma, who requires urgent medical attention in situations such as air pollution or risen pollen levels. On 2nd June 2000, 83 subjects with an acute crisis of asthma, came to the Emergency Room in our Hospital in just 6 hours, coinciding with the highest annual pollen measurement and a strong storm. METHODS AND RESULTS: Personal data from those 83 patients, medical behaviour at the Casualty and post-attention recommendations were considered for analysis. 21 % never had previous diagnosis of asthma and 93 % followed no regular medical control. 61.45 % did no treatment. A chest radiography was taken in 53.76 % of the patients. Salbutamol was administrated in most of them (92.18 %) and parentally administration of steroids in 23.47 %. 21 % were referred to an specialist. CONCLUSIONS: A significant rate of asthmatics is under-diagnosed, under-controlled and under-treated. Public Health authorities should consider the creation of new Allergy Units, a fluid communication between general practitioners and specialists, and the monitorization of pollen recounts with special plans of emergency situations to contribute to solve this problem.

Análisis de 83 episodios de broncoespasmo atendidos una noche de primavera en Urgencias / Analysis of 83 episodes of bronchospasm attended a spring night in the emergency department

Objetivos: el tratamiento de la inflamación bronquial en el asma ha contribuido a una menor mortalidad. Sin embargo, existe un grupo importante de población infradiagnosticado, pudiendo requerir atención médica urgente en situaciones como el aumento de los recuentos polínicos o los niveles de contaminación. El 2 de junio de 2000 en Madrid, 83 pacientes acudieron, en sólo 6 horas, al Servicio de Urgencias del Hospital Clínico aquejados de un broncoespasmo, coincidiendo con el pico anual de polen de gramíneas y una fuerte tormenta.Método y resultados: se recogieron datos de esos 83 pacientes, analizando factores personales, actuación médica en Urgencias e indicaciones al Alta. Un 21 por ciento de los pacientes nunca habían sido diagnosticados de asma. El 93 por ciento no seguía control médico regularmente y un 61,45 por ciento no hacía tratamiento. Se realizó una radiografía de tórax al 53,76 por ciento, pautándose salbutamol (92,18 por ciento) y corticoides parenterales (23,43 por ciento). Un 21 por ciento fue remitido directamente al especialista.Conclusiones: un porcentaje importante de asmáticos está infradiagnosticado, lleva un control médico insuficiente y realiza un tratamiento inadecuado. Las autoridades sanitarias deben considerar que esta situación puede saturar, en determinadas circunstancias, los Servicios de Urgencias. Un refuerzo de las unidades de Alergia, una mejor comunicación entre la Atención Primaria y la Especializada, y el seguimiento de los recuentos polínicos en las Urgencias, con la instauración de planes de alerta y protocolos ágiles de derivación al especialista, pueden mejorar este problema (AU)

Background: The new treatments for the bronchial inflammation in asthma, have contributed to decrease the mortality rate. However, there is still a group of population with no diagnosis for asthma, who requires urgen medical attention in situations such as air pollution or risen pollen levels. On 2nd June 2000, 83 subjects with an acute crisis of asthma, came to the Emergency Room in our Hospital in just 6 hours, coinciding with the highest annual pollen measurement and a strong storm. Methods and results: Personal data from those 83 patients, medical behaviour at the Casualty and post-attention recommendations were considered for analysis. 21 % never had previous diagnosis of asthma and 93 % followed no regular medical control. 61.45 % did no treatment. A chest radiography was taken in 53.76 % of the patients. Salbutamol was administrated in most of them (92.18 %) and parentally administration of steroids in 23.47 %. 21 % were referred to an specialist. Conclusions: A significant rate of asthmatics is under-diagnosed, under-controlled and under-treated. Public Health authorities should consider the creation of new Allergy Units, a fluid communication between general practitioners and specialists, and the monitorization of pollen recounts with special plans of emergency situations to contribute to solve this problem (AU)