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.

Association of Toll-like receptor 7, CTLA-4 gene polymorphisms with severe asthma / 公共卫生与预防医学

Objective To explore the association of Toll-like receptor 7, CTLA-4 gene polymorphisms and severe asthma. Methods From February 2018 to March 2020, 175 asthma patients admitted to the respiratory department of our hospital were selected as the research subjects (109 cases of mild disease and 66 cases of severe disease), and 248 cases of healthy people who were included in the outpatient physical examination of our hospital during the same period were selected as the normal control group. Toll-like receptor 7 and CTLA-4 gene polymorphisms in the above groups were determined, and the relationship between Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma was evaluated by calculating the odds ratio (OR) and 95% confidence interval(CI). The relationship between the genotypes of Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma were evaluated by logistic regression analysis. Results The proportion of TLR7 rs3853839 CC genotype, CTLA-4 rs231725 AA genotype, TLR7 rs3853839 C allele frequency and CTLA-4 rs231725 A allele frequency in severe asthma group and mild asthma group were higher than those in normal control group(P<0.05). The proportion of TLR7 rs3853839 CC genotype, the proportion of CTLA-4 rs231725 AA genotype, the frequency of TLR7 rs3853839 C allele, and the frequency of CTLA-4 rs231725 A allele in the severe asthma group were higher than those in the mild asthma group(P<0.05). TLR7 rs3853839 CC genotype (OR=10.32, 95%CI=5.59-23.89), CTLA-4 rs231725 AA genotype (OR=13.21, 95%CI=3.58-20.25), TLR7 rs3853839 C allele frequency (OR=11.32, 95% CI=4.25-21.14) and CTLA-4 rs231725 A allele frequency (OR=13.24, 95% CI=6.59-20.21) could increase the susceptibility to severe asthma(P<0.05). TLR7 rs3853839CC genotype, TLR7 rs3853839C allele frequency, CTLA-4 rs231725AA genotype and CTLA-4 rs231725A allele frequency were risk factors for severe asthma(P<0.05). Conclusion TLR7 rs3853839 CC genotype, TLR7 rs3853839 C allele frequency, CTLA-4 rs231725 AA genotype and CTLA-4 rs231725 A allele frequency are associated with the occurrence of severe asthma.

Anti ige na asma grave 'relato de caso' / Anti ige in severe asthma 'case report / Anti ige en el asma grave 'informe de un caso

A asma grave é uma doença respiratória crônica que afeta as vias aéreas, provocando inflamação e estreitamento dos brônquios. Esse estreitamento pode dificultar a respiração e causar sintomas como tosse, falta de ar, chiado no peito e aperto no peito. Quando a asma não é controlada adequadamente com medicamentos e outras medidas, ela pode evoluir para um quadro de asma grave. O presente artigo científico consiste em uma revisão literária sobre o tratamento da asma grave com elevados níveis de anticorpos IgE por meio do uso do anticorpo monoclonal Omalizumabe, além de apresentar o relato de caso observacional em um paciente pediátrico atendido em um consultório especializado da cidade de Mineiros no estado de Goiás. Os estudos revisados demonstraram que a terapia com Omalizumabe pode melhorar a função pulmonar, reduzir a necessidade de medicação de resgate e melhorar a qualidade de vida em pacientes com asma grave. No entanto, também foi observado que o benefício do Omalizumabe é mais pronunciado em pacientes com níveis mais elevados de IgE e em pacientes que apresentam sintomas asmáticos frequentes. A revisão literária apresentou evidências consistentes de que o Omalizumabe é uma opção terapêutica eficaz e segura para o tratamento de asma grave com elevados níveis de IgE em pacientes pediátricos. Por fim com objetivo de fornecer informações importantes para médicos e profissionais de saúde sobre o uso do Omalizumabe no tratamento da asma grave em crianças, além de destacar a necessidade de mais pesquisas para avaliar a eficácia e segurança do medicamento em populações maiores e com seguimento mais prolongado.

Severe asthma is a chronic respiratory disease that affects the airways, causing inflammation and narrowing of the bronchi. This narrowing can make breathing difficult and cause symptoms such as coughing, shortness of breath, wheezing, and chest tightness. When asthma is not properly controlled with medication and other measures, it can develop into severe asthma. The present scientific article consists of a literature review on the treatment of severe asthma with high IgE antibody levels by the use of the monoclonal antibody Omalizumab, besides presenting the report of an observational case in a pediatric patient seen at a specialized clinic in the city of Mineiros in the state of Goiás. The studies reviewed showed that Omalizumab therapy can improve lung function, reduce the need for rescue medication, and improve quality of life in patients with severe asthma. However, it was also noted that the benefit of Omalizumab is more pronounced in patients with higher IgE levels and in patients who have frequent asthmatic symptoms. The literature review presented consistent evidence that Omalizumab is an effective and safe therapeutic option for the treatment of severe asthma with high IgE levels in pediatric patients. Finally with aim to provide important information for physicians and health care professionals about the use of Omalizumab in the treatment of severe asthma in children, and to highlight the need for further research to evaluate the efficacy and safety of the drug in larger populations and with longer follow-up.

El asma grave es una enfermedad respiratoria crónica que afecta a las vías respiratorias, causando inflamación y estrechamiento de los bronquios. Este estrechamiento puede dificultar la respiración y causar síntomas como tos, falta de aire, sibilancias y opresión torácica. Cuando el asma no se controla adecuadamente con medicación y otras medidas, puede convertirse en asma grave. El presente artículo científico consiste en una revisión bibliográfica sobre el tratamiento del asma grave con niveles elevados de anticuerpos IgE mediante el uso del anticuerpo monoclonal Omalizumab, además de presentar el informe de un caso observacional en un paciente pediátrico atendido en una clínica especializada de la ciudad de Mineiros, en el estado de Goiás. Los estudios revisados demostraron que el tratamiento con omalizumab puede mejorar la función pulmonar, reducir la necesidad de medicación de rescate y mejorar la calidad de vida en pacientes con asma grave. Sin embargo, también se observó que el beneficio del omalizumab es más pronunciado en pacientes con niveles más altos de IgE y en pacientes que presentan síntomas asmáticos frecuentes. La revisión bibliográfica presentó pruebas consistentes de que omalizumab es una opción terapéutica eficaz y segura para el tratamiento del asma grave con niveles elevados de IgE en pacientes pediátricos. Finalmente con el objetivo de proporcionar información importante para los médicos y profesionales de la salud sobre el uso de Omalizumab en el tratamiento del asma grave en niños, así como destacar la necesidad de nuevas investigaciones para evaluar la eficacia y seguridad del fármaco en poblaciones más grandes y con un seguimiento más prolongado.

Difficult-to-Treat and Severe Asthma

Abstract Introduction: The purpose of this article is to describe the characteristics, comorbidities and phenotypes of patients with difficult-to-treat asthma (DTA) and severe asthma (SA). Materials and Methods: Descriptive, cross-sectional study of patients evaluated at the Difficult-to-Treat Asthma Clinic of the Hospital Británico within the period of one year. We registered the age, gender and anthropometric data, age of diagnosis, FEV1 at the beginning of follow-up and previous exacerbations. We evaluated symptom control with the Asthma Control Test and the Asthma Control Questionnaire. We registered the comorbidities and evaluated the inflammatory profile of patients according to blood biomarker measurements and induced sputum sample. Results: Forty patients, 20 DTA and 20 SA. There weren't any significant differences regarding age, BMI, age of onset of symptoms, symptom control or FEV1 at the beginning of follow-up. Crises were more common in SA patients. The most commonly found co morbidities were obesity, OSAHS and gastroesophageal reflux disease. Psychiatric disorders were more common in SA patients. The most commonly found phenotype was allergen-reactive TH2. Discussion and Conclusion: it is not easy to classify both groups, and many times there are overlapping characteristics. Comor bidities are frequent in both groups: obesity, OSAHS and reflux disease are the most common conditions. Being able to identify the asthma phenotype in order to target the treatment.

Asma grave T2 alto: análisis del diseño de los estudios clínicos de los nuevos biológicos / T2-High Severe Asthma: Analysis of the Design of Clinical Studies of New Biologics

Resumen En los últimos años, la aparición de anticuerpos monoclonales (Biológicos) para el tratamiento del asma grave T 2 alto nos permitió palear las pocas herramientas terapéuticas que teníamos para tratar a este grupo de pacientes, que, aunque pequeño, difiere al manejo del resto de los asmáticos. Al momento, existen diversos trabajos publicados que dieron soporte a las normativas como a las guías de manejo de asma grave en el mundo y fueron tomados por las diferentes sociedades científicas en la elaboración de estas. A pesar de ello, la lectura minuciosa de los mismos deja ver que existen diferencias claras en cuanto a metodología, toma de variables e interpretación de resultados. Con esta premisa, este trabajo permite realizar un análisis crítico de los estudios clínicos de desarrollo Fase III de biológicos en asma grave, tomando en cuenta metodología y diversas variables que conllevan a los resultados publicados.

Abstract In the last years, the appearance of new monoclonal antibodies (biologics) for the treatment of T2-high severe asthma allowed us to use the few therapeutic tools we had to treat this group of patients, which is small but differs from the rest of the asthmatics in its management. So far there are various publications supporting certain rules such as the Guidelines for Severe Asthma Management on a worldwide level, which were used by the different scientific societies for the development of those guidelines. But the thorough reading of cited publications reveals clear differences regarding the methodology, use of variables and interpretation of the results. Based on these premises, this work allows us to conduct a critical analysis of the phase III clinical studies of the development of biologics for severe asthma, taking into account the methodology and different variables that entail the published results.

The use of metered-dose inhaler versus nebulization for the delivery of salbutamol in pediatric severe asthma exacerbations: A systematic review

BACKGROUND@#Recent guidelines for the management of asthma have advocated the use of a pressurized metered-dose inhaler (MDI) and spacer in the delivery of salbutamol. However, there is a dearth of research in children with severe exacerbation.@*OBJECTIVES@#To compare the effectiveness of MDI with spacers versus nebulizers in drug delivery of salbutamol for the management of pediatric severe asthma exacerbations. @*METHODOLOGY@#A systematic search of the Pubmed, Cochrane library, Herdin, WPRIM, ClinicalTrials and reference review databases was conducted for studies containing “severe asthma” using MDI and spacer as an intervention with nebulization as a comparator.@*RESULTS@#Of 220 articles, 4 met the criteria. In the subgroup analysis, children who received salbutamol through MDI showed no significant difference in hospital admission, pulmonary score, heart and respiratory rate, oxygen saturation, and lung function.@*CONCLUSION@#In severe asthma exacerbations, there is evidence to support that MDI compared with nebulizer is statistically equal in terms of hospital admission, pulmonary scores, clinical improvement, and side effects@*RECOMMENDATIONS@#Further randomized controlled trials are suggested to explore the intricacies of drug delivery in management of severe asthma. A meta-analysis may be made possible in the future with more evidence.

Application of the mandarin Chinese version of the Leicester cough questionnaire in the chronic disease management of adult patients with severe asthma / 中华健康管理学杂志

Objective:To explore the application of the mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC) in the chronic disease management of adult patients with severe asthma.Methods:Thirty patients with severe asthma without a smoking history who received treatment and chronic disease management in the First Affiliated Hospital of Guangxi Medical University from December 2018 to December 2020 and met the inclusion criteria were selected as the research subjects. Their clinical symptoms, LCQ-MC, asthma control test (ACT), mini asthma quality of life questionnaire (MiniAQLQ), visual analogue scale (VAS) and lung function test were recorded. The reliability of LCQ-MC and its correlation with ACT, MiniAQLQ, VAS and lung function were analyzed.Results:Among the 30 patients, there were 14 males and 16 females, with an average age of (50.5±10.5) years old and a medical history of (38.3±15.5) years. The main manifestations were cough which was observed in 29 cases (96.7%), wheezing in 25 cases (83.3%), nasal symptoms in 14 cases (46.7%) and chest tightness in 11 cases (36.7%). All lung functions were consistent with the diagnosis of asthma. The total score of LCQ-MC was (16.1±4.2), in which the physiological, psychological and social dimensions were (5.0±1.2), (5.6±1.6), (5.5±1.7), respectively; and ACT (18.9+5.5), MiniAQLQ (4.9±1.4), VAS (33.5±32.4). The Cronbach′s α for the questionnaire was more than 0.70, and the results were positively correlated with ACT and MiniAQLQ ( r=0.553, 0.593, P=0.002, 0.001), negatively correlated with VAS ( r=-0.762, P<0.001). The correlations between LCQ-MC and these scores were consistent with the results after 6 months. Conclusion:Cough is an important symptom of severe asthma, and LCQ-MC can be effectively used for evaluation and chronic disease management of adult patients with severe asthma.

Controversias de la ventilación mecánica no invasiva en el asma grave / Controversies of the non-invasive mechanical ventilation in severe asthma

RESUMEN El asma es una enfermedad obstructiva en la que, las resistencias respiratorias se encuentran aumentadas. Los hechos responsables de este aumento de resistencias son el propio broncoespasmo, la inflamación y el remodelado de la vía aérea con reducción de su diámetro. Todavía falta mucho por conocer y estudiar, pero sabemos que la ventilación mecánica no invasiva, como nueva forma de soporte ventilatorio que ha venido tomando auge en las últimas décadas, tiene numerosos beneficios en la práctica médica. A pesar de que algunas investigaciones plantean la controversialidad del empleo de la ventilación no invasiva en el asma grave, queremos realizar con el presente trabajo un acercamiento a varios de los estudios que se han llevado a cabo donde justifican totalmente el empleo de la misma como una medida de éxito en el manejo del asma, con resultados positivos y exitosos. Donde ha probado mejorar la situación funcional y reducir las necesidades de ingreso hospitalario, aliviando el agotamiento muscular y de esta manera mejorando el trabajo respiratorio. Aún queda bastante camino por recorrer con esta variante de ventilación que ha surgido y tomado auge por todos los logros y expectativas que ha venido a cumplir (AU).

SUMMARY Asthma is an obstructive disease in which, respiratory resistances are increased. The factors responsible for this increase in resistance are bronchospasm, inflammation and remodeling of the airway with reduction of its diameter. Much remains to be known and studied, but we know that noninvasive ventilation (NIV), as a new form of ventilatory support that has been growing in recent decades, has numerous benefits in medical practice. Although some research raises the controversy about the use of NIV in severe asthma, we want to do with the present work an approach to several of the studies that have been carried out where they totally justify the use of it as a measure of success in managing asthma, with positive and successful results. Where he has tried to improve the functional situation and reduce the need for hospital admission, alleviating muscle exhaustion and thus improving breathing work. There is still enough way to go with this variant of ventilation that has emerged and taken shape for all the achievements and expectations it has come to fulfill (AU).

Frequência de alterações espirométricas, aprisionamento aéreo e hiperinsuflação pulmonar em crianças e adolescentes com asma grave resistente à terapia: um estudo piloto / Frequency of spirometric changes, air trapping, and lung hyperinflation in children and adolescents with therapy-resistant severe asthma: a pilot study

Objetivos: avaliar a frequência de alterações espirométricas e pletismográficas em crianças e adolescentes com asma grave resistente à terapia (AGRT). Além disso, testaram-se possíveis associações entre esses desfechos. Métodos: trata-se de um estudo retrospectivo, no qual foram incluídas crianças e adolescentes (6-18 anos), com diagnóstico de AGRT, e que se encontravam em acompanhamento ambulatorial regular. Todos deveriam possuir informações antropométricas (peso, altura, índice de massa corporal), demográficas (idade, etnia e sexo), clínicas (teste cutâneo, teste de controle da asma, tabagismo familiar e medicações em uso) e de função pulmonar (espirometria e pletismografia corporal) registradas no banco de dados do serviço. Os testes de função pulmonar seguiram as recomendações das diretrizes nacionais e internacionais. Para fins estatísticos, utilizou-se análise descritiva e o teste de qui-quadrado de Pearson. Resultados: de um total de 15 pacientes com AGRT, 12 deles foram incluídos na amostra. A média de idade foi de 12,2 anos, com predomínio do sexo feminino (66,7%). Destes, 50,0% apresentaram a doença controlada, 83,3% foram considerados atópicos e 50,0% tinham histórico de tabagismo familiar. Em relação aos testes de função pulmonar (% do previsto), as médias dos parâmetros espirométricos e de plestismografia corporal encontraram-se dentro dos limites inferiores da normalidade. Apenas 16,7% da amostra apresentou espirometria alterada (130,0%) e 16,7% hiperinsuflação pulmonar (capacidade pulmonar total>120,0%). Houve frequência estatisticamente maior (p=0,045) de aprisionamento aéreo nos participantes com espirometria alterada, em comparação à espirometria normal. Contudo, não se observou diferença (p=0,341) em relação à hiperinsuflação pulmonar. Conclusões: os achados demonstraram pouco comprometimento espirométrico e dos volumes e das capacidades pulmonares em crianças e adolescentes com AGRT. Além disso, aqueles participantes com espirometria alterada obtiveram frequência maior de aprisionamento aéreo no exame de pletismografia corporal

Aims: to assess the frequency of spirometric and plethysmographic changes in children and adolescents with severe therapy-resistant asthma (SRTA). In addition, possible associations between these outcome were tested. Methods: this is a retrospective study. Children and adolescents (6-18 years old), diagnosed with SRTA and who were in regular outpatient follow-up were included. Everyone should have anthropometric (weight, height, body mass index), demographic (age, ethnicity and gender), clinical (skin test, asthma control test, family smoking and medications in use) and pulmonary function (spirometry and body plethysmography) recorded in the service's database. Pulmonary function tests followed the recommendations of national and international guidelines. For statistical purposes, descriptive analysis and Pearson's chi-square test were used. Results: from a total of 15 patients with SRTA, 12 of them were included in the sample. The average age was 12.2 years, with a predominance of females (66.7%). Of these, 50.0% had the disease under control, 83.3% were considered atopic, and 50.0% had a family history of smoking. Regarding the pulmonary function tests (% of predicted), the means of spirometric parameters and body plestismography were within the lower limits of normality. Only 16.7% of the sample had altered spirometry (<5th percentile), 25.0% air trapping (residual volume>130.0%) and 16.7% pulmonary hyperinflation (total lung capacity>120.0%). There was a statistically higher frequency (p=0.045) of air trapping in participants with altered spirometry, compared to normal spirometry. However, there was no difference (p=0.341) in relation to pulmonary hyperinflation. Conclusions: the findings demonstrated little impairment of spirometry and lung volumes and capacities in children and adolescents with AGRT. In addition, those participants with altered spirometry had a higher frequency of air trapping in the body plethysmography exam.

Interpretation of European Academy of Allergy and Clinical Immunology Biologicals Guidelines-Recommendations for severe asthma / 中华实用儿科临床杂志

Severe asthma imposes a significant burden on patients, families, and healthcare systems.Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems.Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals.However, there are still many issues that require further clarification.These include selection of a certain biological, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen.

Hospitalization time and family financial burden of children under 14 years old with severe asthma / 公共卫生与预防医学

Objective To explore the hospitalization time and family financial burden of children under 14 years old with severe asthma in this region. Methods Children under 14 years old with severe asthma who were admitted to our hospital from January 2017 to December 2019 as a result of an acute attack were selected in this study. Questionnaire surveys, hospital charging system, and follow-up methods were used to collect clinical data, length of hospital stay, and direct and indirect costs of the children with asthma. Stepwise regression was applied to analyze the factors influencing the total cost. Results A total of 206 children were enrolled from 2017 to 2019, including 117 males and 89 females, with an average age of (7.24±1.53) years old. The total age distribution mainly consisted of six months to 3 years old (33.01%), >3 to 4 years old (24.27%), and >6-13 years old (20.39%). The onset season was mainly autumn and winter (33.01%). The average length of hospital stay was (8.50±1.42) d. The annual average family cost was (6884.20±957.61) RMB. The length of hospital stay decreased year by year, while the total cost increased year by year (P<0.05). Multiple stepwise regression analysis showed that the length of hospitalization, antibiotic use time, and presence/absence of allergic rhinitis, pulmonary heart disease and GINA standard treatment were the related factors affecting the total cost in children with severe asthma (P<0.05). Conclusion From 2017 to 2019, the hospitalization time of children under 14 years old with severe asthma in this region decreased over time, while the total cost gradually increased. Shortening the hospitalization time, actively preventing and controlling complications, and standardizing treatment can effectively reduce the financial burden of children's families.

Guia prático de abordagem da criança e do adolescente com asma grave: Documento conjunto da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Practical guide to approaching children and adolescents with severe asthma: a joint document of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Asma grave é a asma que requer tratamento com altas doses de corticosteroide inalado associado a um segundo medicamento de controle (e/ou corticosteroide sistêmico) para impedir que se torne "descontrolada" ou permaneça "descontrolada" apesar do tratamento. Asma grave é considerada um subtipo de asma de difícil tratamento. A prevalência em crianças evidenciada pelo International Study of Asthma and Allergies in Childhood variou entre 3,8% e 6,9%. Existem diversos instrumentos para avaliação subjetiva, como diários de sintomas e questionários, bem como para avaliação objetiva com função pulmonar e avaliação da inflamação por escarro induzido, ou óxido nítrico exalado. A abordagem terapêutica varia desde doses altas de corticosteroide inalado e/ou oral, broncodilatadores de longa duração, antaganonistas de receptores muscarínicos, até os mais recentes imunobiológicos que bloqueiam a IgE ou IL-5.

Severe asthma is asthma that requires treatment with high doses of inhaled corticosteroids in combination with a second control drug (and/or a systemic corticosteroid) to prevent it from becoming "uncontrolled" or remaining "uncontrolled" despite treatment. Severe asthma is considered a difficult-to-treat asthma subtype. The prevalence in children found by the International Study of Asthma and Allergies in Childhood ranged from 3.8% to 6.9%. There are several instruments for subjective assessment, such as symptom diaries and questionnaires, as well as for objective assessment, including pulmonary function testing and evaluation of inflammation by induced sputum or exhaled nitric oxide. The therapeutic approach includes high doses of inhaled and/or oral corticosteroids, long-acting bronchodilators, muscarinic receptor antagonists, and the latest biologics that block IgE or IL-5.

Normativa: técnica de esputo inducido en enfermedades inflamatorias broncopulmonares / Technical Guidelines for Induced Sputum in Bronchopulmonary Inflammatory Diseases

Las enfermedades broncopulmonares se asocian a diversos mecanismos inflamatorios de las vías aéreas. Evaluar y comprender el perfil inflamatorio de estos pacientes podría contribuir a conocer la etiología y así optimizar el tratamiento. El esputo inducido es una técnica mínimamente invasiva, por lo que su implementación resulta de interés en la práctica habitual. Aunque el estudio del esputo inducido ha demostrado utilidad y seguridad, los centros que desarrollan esta técnica en la Argentina son escasos. Con el objetivo de estandarizar el procedimiento de recolección y análisis de muestras de esputo inducido en pacientes con enfermedades inflamatorias broncopulmonares, se desarrolló esta guía consensuada por los centros con experiencia en esta técnica en nuestro país. Es nuestra intención difundir esta técnica, mínimamente invasiva, para su aplicación en servicios especializados. Esta guía de procedimientos detalla los materiales que son requeridos, los métodos y los estándares de calidad y seguridad tanto para los pacientes como para los operadores.

Bronchopulmonary diseases are associated with different inflammatory mechanisms of the airways. Assessing and understanding the inflammatory profile of these patients could contribute to the understanding of the etiology and thus optimize the treatment. Induced sputum is a minimally invasive technique, so its implementation is of interest in the usual practice. Although the studies of induced sputum have shown usefulness and safety, the centers that develop this technique in Argentina are scarce. With the aim of standardizing the procedure that includes the collection and analysis of induced sputum samples in patients with bronchopulmonary inflammatory diseases, some centers in our country with experience in this technique achieved a consensus on the development of this Guide. It is our intention to disseminate this minimally invasive technique for its application in specialized services. This procedure guide details the necessary materials and methods and quality and safety standards for both patients and operators.

Valoración de la calidad de vida en pacientes con asma severa posterior al tratamiento con biológicos en el marco de la medicina personalizada

RESUMEN El asma severa incluye un pequeño porcentaje de pacientes que varía de acuerdo a los diferentes países, aun así, los pacientes con asma grave no controlada tienen una morbilidad desproporcionadamente alta junto a una utilización de la asistencia sanitaria. Objetivos: Evaluar la respuesta al tratamiento con biológicos en pacientes asmáticos severos y la importancia de realizar la clasificación de fenotipo y endotipo, en una muestra de pacientes asmáticos severos entre 18 y 60 años de ambos sexos que concurrieron al servicio de Alergia e Inmunología del Hospital Nuevo San Roque, Córdoba, Argentina en el periodo marzo 2016 y marzo 2019. Material y métodos: Se realizó análisis de historia clínica, determinación de IgE, eosinófilos, clasificación de asma según GINA, espirometría, pruebas cutáneas, Test de control de Asma (Asthma control Test) (ACT) y respuesta según Evaluación Global Efectividad Tratamiento por el médico (Global evaluation of treatment effectiveness) (GETE). Resultados: Un total de 12 pacientes asmáticos severos, con test cutáneos positivos (Prick test), valores de IgE y eosinófilos elevados. En los valores espirometricos de pos BD, se observaron diferencias en las tres etapas de seguimiento, los valores iniciales fueron de 50,1 ± 4,4, aumentando a 83,5 ± 4,4 a los 6 meses, y con resultados medios de 88,5 ± 4,15 a los 12 meses. Los valores de ACT fueron al inicio 10,17 ± 1,44, a los 6 meses 22,33 ± 0,68 y al año de 24,67 ± 0,14. Puntaje GETE a los 6 meses, la mayoría de los pacientes refirió tener GETE control completo del asma (42%) o mejor control del asma (33%), mientras que el profesional que los asistió no refirió haber observado ningún paciente con nivel excelente mientras que el 75% fueron clasificados como mejor control del asma. Conclusión: La evaluación inicial correcta del paciente asmático y el tratamiento de precisión adecuado son las herramientas que deben aplicarse para obtener no solamente la remisión de las manifestaciones clínicas si no también una amplia mejoría en su calidad de vida.

ABSTRACT BACKGROUND Severe asthma includes a small percentage of patients that varies across different countries, yet patients with uncontrolled severe asthma have disproportionately high morbidity and healthcare utilization. Objectives: To assess the response to treatment with biologics in severe asthmatic patients and the importance of performing the phenotype and endotype classification in a sample of severe asthmatic patients between 18 and 60 years of age of both sexes who attended the Allergy and Immunology service of the Nuevo Hospital San Roque, Córdoba, Argentina from March 2016 to March 2019. Material and methods :Analysis of: medical history, measurement of laboratory parameters: IgE, eosinophils, asthma classification according to GINA, spirometry, skin tests, Asthma control Test (ACT) and response according to Global evaluation of treatment effectiveness (Global Evaluation Effectiveness Treatment by the doctor). Results: A total of 12 severe asthmatic patients, with positive Prick tests, elevated IgE and eosinophil values. Regarding spirometry: in the post BD values, differences were observed in the three stages of follow-up: the initial spirometry values were 50.1 ± 4.4, increasing to 83.5 ± 4.4 at 6 months, and with mean results of 88.5 ± 4.15 at 12 months. The ACT values were at baseline 10.17 ± 1.44, at 6 months 22.33 ± 0.68 and at one year: 24.67 ± 0.14. GETE score At 6 months, most of the GETE patients reported having complete asthma control (42%) or better asthma control (33%), while the professional who assisted them did not report having observed any patient with an excellent level; and 75% were classified as better asthma control. Conclusion: The correct initial evaluation of the asthmatic patient and the appropriate precision treatment are the tools that must be applied to obtain not only the remission of the clinical manifestations but also a broad improvement in their quality of life.

A pharmacoepidemiological study of prescription patterns of ?2 sympathomimetic bronchodilators in exacerbation of non-severe asthma in tertiary care hospitals, not needing hospitalization

Background: Arformoterol, the (R, R) enantiomer of the racemic (R, R / S, S) diastereomer, formoterol, is a short and long acting ?2 agonist bronchodilator. Levosalbutamol, the (R, R) enantiomer of racemic diastereomer (R, R / S, S) salbutamol, has a greater affinity for the ?2 receptor. Occupation of ?2 receptors by agonists result in the activation of the Gs-adenylyl cyclase-cAMP-PKA pathway, followed by phosphorylative events leading to bronchial smooth muscle relaxation. The aim of this pharmacoepidemiological study was to analyse the prescription patterns, and prescription content analysis, of arformoterol, levosalbutamol, formoterol or salbutamol, in non-severe asthma exacerbation in tertiary care hospitals, not needing hospitalization.Methods: It was a multi-centre, retrospective, observational and analytical study of 100 asthmatic patients’ hospital medical records, treated with 3 doses of arformoterol, levosalbutamol, formoterol or salbutamol nebulization, followed by peak expiratory flow rates (PEFR) measurement at the baseline and 6 minutes, after each dose; along with adverse effects recording. The number of prescriptions of 100 patients was recorded, the percentage of prescriptions was calculated, and the prescription content analysis was done.Results: PEFR of the patients showed significant increase after the first, second and third doses of bronchodilator nebulisation, with negligible adverse effects. Salbutamol was most commonly prescribed (45 prescriptions, 45%), followed by levosalbutamol (35 prescriptions, 35%), formoterol (15 prescriptions, 15%) and arformoterol (5 prescriptions, 5%). All aspects of prescription content analysis showed 100% completeness.Conclusions: Arformoterol was more effective, but equally safe, as compared to levosalbutamol, formoterol and salbutamol. Prescription frequency of salbutamol was followed by levosalbutamol, formoterol and arformoterol. Prescription content analyses showed 100% completeness.

Guia para o manejo da asma grave 2019 ­ Associação Brasileira de Alergia e Imunologia / Guide to the management of severe asthma 2019 ­ Brazilian Association of Allergy and Immunology

Antes de rotular um paciente como tendo asma grave, é crucial confirmar o diagnóstico da doença e de sua gravidade, além de excluir diagnósticos diferenciais de condições que podem se assemelhar ou se confundir com a asma, tais como: tuberculose, doença pulmonar obstrutiva crônica, disfunção de corda vocal, apneia do sono, bronquiectasia, entre outras. Neste guia são abordados, além dos diagnósticos diferenciais, dados de história clínica e exames laboratoriais que permitem classificar o paciente com relação à evolução da doença (controlado ou não controlado) e, assim, possibilitar a instituição do esquema terapêutico mais apropriado. São apresentadas alternativas terapêuticas disponíveis para a abordagem clínica desses pacientes, incluindo os imunobiológicos.

Prior to labeling a patient as having severe asthma, a crucial step is to confirm the diagnosis and severity as well as to exclude conditions that may resemble or be mistaken for asthma such as tuberculosis, chronic obstructive pulmonary disease, vocal cord dysfunction, sleep apnea, bronchiectasis, among others. In addition to differential diagnoses, this guide addresses clinical history data and laboratory tests that classify the patient regarding disease progression (controlled or uncontrolled asthma), allowing the establishment of an adequate therapeutic plan. Therapeutic options available for the treatment of these patients are detailed, including biologics.

Prevalence of allergic bronchopulmonary aspergillosis among patients with severe bronchial asthma in a tertiary care hospital in Northern India

Introduction: The link between fungi and asthma has been known for centuries. About one-third to one-half of severe asthmatics has history of atopic sensitization to filamentous fungi, most predominantly to Aspergillus fumigatus. Allergic bronchopulmonary aspergillosis (ABPA) is the one of the most documented fungal presentations among patients with asthma. This study was done on 50 patients with severe asthma who were consecutively enrolled from January 2016 to June 2017 to look for prevalence of ABPA. Materials and Methods: Blood samples were collected from 50 patients with severe asthma, and serum was separated to test for absolute eosinophil count, total IgE, and Aspergillus fumigates–specific IgE. Results: The prevalence of ABPA was found to be 70% (35/50). Of these, ABPA-B (ABPA with bronchiectasis) was less 31.4% (11/35) when compared with 68.5% (24/35) of patients with serological ABPA. Out of these 35 patients, there were 18 females and 17 were males. The mean age of the patients was 41.3 years. Conclusion: ABPA prevalence is high in patients with severe asthma, and there is a need to look for and evaluate this association further.

Avaliação de custo-efetividade e impacto orçamentário do tratamento adicional de omalizumabe em pacientes com asma alérgica grave não controlada / Cost-effectiveness and budget impact analysis of additional treatment of omalizumab in patients with severe uncontrolled allergic asthma

Objetivo: Avaliar a custo-efetividade e o impacto orçamentário da adição do omalizumabe (Oma) ao tratamento padrão [corticosteroide inalatório [CI] em dose média/alta e agente beta 2-agonista de longa ação (LABA)] no tratamento da asma alérgica grave não controlada, sob a perspectiva do sistema privado de saúde no Brasil. Método: Na análise econômica, utilizou-se o modelo de Markov baseado na evolução da asma, considerando os seguintes desfechos clínicos: exacerbações graves clinicamente significantes (EGCS) e exacerbações não graves clinicamente significantes (ECS), além de taxa de mortalidade por asma e uso de recursos e custos com o tratamento. Calculou-se razões de custo-efetividade incremental (RCEI) e o impacto orçamentário, com base em dados da saúde suplementar sobre população elegível e horizonte de 5 anos. Resultados: A análise de custoefetividade realizada mostrou que o tratamento com Oma teve maior benefício, se comparado ao tratamento padrão, e gerou uma RCEI de R$ 60.293,00 por ano de vida salvo, que é três vezes inferior ao produto interno bruto (PIB) per capita no Brasil. A análise de sensibilidade, para avaliar o impacto da incerteza dos parâmetros sobre o resultado encontrado, demonstrou que os resultados permanecem estáveis a favor do Oma. A análise do impacto orçamentário apontou um custo por beneficiário de R$ 0,40 no primeiro ano, chegando a R$ 1,80 no quinto ano. Conclusão: A análise econômica demonstrou que a combinação do tratamento com Oma com o padrão para asma alérgica grave não controlada é custo-efetivo no cenário nacional, e a sua incorporação na saúde suplementar é viável.

Objective: To evaluate the cost-effectiveness and budgetary impact of adding omalizumab (Oma) to standard treatment (medium/highdose inhaled corticosteroid [ICS] and long-acting beta 2-agonist [LABA]) in the treatment of severe uncontrolled allergic asthma, from the perspective of the Brazilian private health system (PHS). Method: In economic analysis, the Markov model was used based on the progression of asthma considering the following clinical outcomes: clinically significant severe exacerbations (CSSE) and clinically significant non-severe exacerbations (CSNSE), as well as asthma mortality rate and use of resources and costs of treatment. Incremental cost-effectiveness ratios (ICER) and budgetary impact were calculated based on PHS data regarding eligible population and 5-year horizon scanning. Results: The cost-effectiveness analysis showed that treatment with Oma provided greater benefit compared to the standard treatment and generated an ICER of BRL 60,293 per life-years saved, corresponding to less than three times the gross domestic product (GDP) per capita in Brazil. A sensitivity analysis to evaluate the impact of parameter uncertainty showed that results still favor Oma. The budget impact analysis showed a cost of BRL 0.40 per recipient in the first year, reaching BRL 1.80 in the fifth year. Conclusion: The economic analysis demonstrated that combined Oma treatment and standard treatment of uncontrolled severe allergic asthma is cost-effective in the national setting and its incorporation into PHS is feasible.

Characteristics of Adult Severe Refractory Asthma in Korea Analyzed From the Severe Asthma Registry

PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.

The clinical characteristics and airway inflammatory phenotypes in 35 patients with severe asthma / 中华内科杂志

Objective@#To analyze the clinical features and airway inflammatory phenotypes in patients with severe asthma.@*Methods@#Patients with severe asthma were recruited in this cross-sectional study in our center. History of asthma, blood and sputum samples, and respiratory function were tested and recorded. The phenotypes of inflammation in airway were evaluated.@*Results@#A total of 35 asthmatic patients with the mean age 41.4 years were involved in this study from January 2013 to December 2013. The disease duration were (14.3±13.6) years with mostly male in China-Japan Friendship Hospital. Thirteen patients reported the history of smoking. Twenty-one patients had the complications such as allergic rhinitis, followed by chronic rhinosinusitis of 11 cases, nasal polyp of 7 cases, gastroesophageal reflux disease of 5. The forced expiratory volume in one second/predicted value ratio (FEV1%pred) in 29 patients was lower than 80%.Twenty-one participants did not react in bronchial reversibility test. Sixteen patients were administrated with oral cortical steroids (OCS). The average annual cost per patient was 22 thousand RMB. Sixteenrefractory asthmatics were diagnosed as eosinophilic asthma.@*Conclusions@#The clinical features associated with severe asthma include male gender, smoking, persistent airway limitation. Systemic use of corticosteroids is common and treatment costs are high. The eosinophilic asthma is the main inflammatory phenotype in patients with severe asthma.