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.

Translation and cultural adaptation of a specific instrument for measuring asthma control and asthma status: the Asthma Control and Communication Instrument / Tradução e adaptação cultural de um instrumento específico para medir o controle e estado da asma: Asthma Control and Communication Instrument

ABSTRACT Objective: To translate the Asthma Control and Communication Instrument (ACCI) to Portuguese and adapt it for use in Brazil. Methods: The ACCI was translated to Portuguese and adapted for use in Brazil in accordance with internationally accepted guidelines. The protocol included the following steps: permission and rights of use granted by the original author; translation of the ACCI from English to Portuguese; reconciliation; back-translation; review and harmonization of the back-translation; approval from the original author; review of the Portuguese version of the ACCI by an expert panel; cognitive debriefing (the clarity, understandability, and acceptability of the translated version being tested in a sample of the target population); and reconciliation and preparation of the final version. Results: During the cognitive debriefing process, 41 asthma patients meeting the inclusion criteria completed the ACCI and evaluated the clarity of the questions/statements. The clarity index for all ACCI items was > 0.9, meaning that all items were considered to be clear. Conclusions: The ACCI was successfully translated to Portuguese and culturally adapted for use in Brazil, the translated version maintaining the psychometric properties of the original version. The ACCI can be used in clinical practice because it is easy to understand and easily applied.

RESUMO Objetivo: Traduzir e adaptar culturalmente para a língua portuguesa falada no Brasil um instrumento que avalia a comunicação e o controle da asma, denominado Asthma Control and Communication Instrument (ACCI). Métodos: O ACCI foi traduzido e adaptado culturalmente com um protocolo que incluiu etapas internacionalmente aceitas: autorização e cessão de direitos de uso do ACCI de seu idealizador; tradução do ACCI da língua inglesa para a língua portuguesa; reconciliação; retradução; revisão e harmonização da retradução; aprovação do idealizador do ACCI; revisão da versão em português do ACCI por especialistas; desdobramento cognitivo (teste da clareza, compreensibilidade e aceitabilidade da versão traduzida em uma amostra da população-alvo) e reconciliação para a elaboração da versão final. Resultados: Na etapa do desdobramento cognitivo, foram entrevistados 41 indivíduos com asma que preencheram os critérios de inclusão. Todos responderam ao ACCI e avaliaram a clareza dos enunciados/questões e, para todos os itens, obteve-se um índice de clareza superior a 0,9, ou seja, todas as questões foram consideradas claras. Conclusões: A tradução e a adaptação cultural do ACCI para a língua portuguesa falada no Brasil foram bem-sucedidas e mantiveram as propriedades psicométricas do instrumento original. O ACCI pode ser utilizado na prática clínica por ser simples e de fácil compreensão e aplicação.

Phenotypes of asthma in low-income children and adolescents: cluster analysis / Fenótipos de asma em crianças e adolescentes de baixa renda: análise de agrupamentos

ABSTRACT Objective: Studies characterizing asthma phenotypes have predominantly included adults or have involved children and adolescents in developed countries. Therefore, their applicability in other populations, such as those of developing countries, remains indeterminate. Our objective was to determine how low-income children and adolescents with asthma in Brazil are distributed across a cluster analysis. Methods: We included 306 children and adolescents (6-18 years of age) with a clinical diagnosis of asthma and under medical treatment for at least one year of follow-up. At enrollment, all the patients were clinically stable. For the cluster analysis, we selected 20 variables commonly measured in clinical practice and considered important in defining asthma phenotypes. Variables with high multicollinearity were excluded. A cluster analysis was applied using a twostep agglomerative test and log-likelihood distance measure. Results: Three clusters were defined for our population. Cluster 1 (n = 94) included subjects with normal pulmonary function, mild eosinophil inflammation, few exacerbations, later age at asthma onset, and mild atopy. Cluster 2 (n = 87) included those with normal pulmonary function, a moderate number of exacerbations, early age at asthma onset, more severe eosinophil inflammation, and moderate atopy. Cluster 3 (n = 108) included those with poor pulmonary function, frequent exacerbations, severe eosinophil inflammation, and severe atopy. Conclusions: Asthma was characterized by the presence of atopy, number of exacerbations, and lung function in low-income children and adolescents in Brazil. The many similarities with previous cluster analyses of phenotypes indicate that this approach shows good generalizability.

RESUMO Objetivo: Estudos que caracterizam fenótipos de asma predominantemente incluem adultos ou foram realizados em crianças e adolescentes de países desenvolvidos; portanto, sua aplicabilidade em outras populações, tais como as de países em desenvolvimento, permanece indeterminada. Nosso objetivo foi determinar como crianças e adolescentes asmáticas de baixa renda no Brasil são distribuídos através de uma análise de clusters. Métodos: Foram incluídos 306 crianças e adolescentes (6-18 anos de idade) com diagnóstico clínico de asma e sob tratamento médico por pelo menos um ano de acompanhamento. No momento da inclusão, todos os pacientes estavam clinicamente estáveis. Vinte variáveis comumente determinadas na prática clínica e consideradas importantes na definição dos fenótipos de asma foram selecionadas para a análise de clusters. As variáveis com alta multicolinearidade foram excluídas. Uma análise de clusters foi realizada utilizando-se um teste aglomerativo em duas etapas e log-likelihood distance measure. Resultados: Três clusters foram definidos para nossa população. O cluster 1 (n = 94) incluiu indivíduos com função pulmonar normal, inflamação eosinofílica leve, poucas exacerbações, início mais tardio da asma e atopia leve. O cluster 2 (n = 87) incluiu pacientes com função pulmonar normal, número moderado de exacerbações, início precoce da asma, inflamação eosinofílica mais grave e atopia moderada. O cluster 3 (n = 108) incluiu pacientes com função pulmonar ruim, exacerbações frequentes, inflamação eosinofílica e atopia graves. Conclusões: A asma foi caracterizada por presença de atopia, número de exacerbações e função pulmonar em crianças e adolescentes de baixa renda no Brasil. As muitas semelhanças entre esta e outras análises de clusters de fenótipos indicam que essa abordagem apresenta boa generalização.

Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1α in obese patients with different severity of asthma

Asthma studies suggest that alteration in the inflammation pattern may be associated with the severity of asthma. The aim of this study was to compare in vitro the expression of chemokines, chemokine receptors and cytokine production from CD4+ T human lymphocytes of asthmatic, both obese and non-obese patients with different severity levels of asthma. Lymphocytes were labeled with monoclonal anti-human CXCR3/IP-10, MIP-1a/CCR5 antibodies and were analyzed by flow cytometry. Cell culture supernatants were used to measure production of interleukin IL-6 and resistin by ELISA. CXCR3/IP-10 expression increased in non-obese patients with mild persistent asthma (2.2%, p<0.05), moderate persistent asthma (3%, p<0.003) and severe persistent asthma (4%, p<0.004); this effect was stronger in obese patients with severe persistent asthma (35%, p<0.004). MIP-1 α / CCR5 increased in non-obese patients with intermittent asthma (0.65%, p<0.05) and severe asthma (1.4%, p<0.03); in obese patients, this expression was greater in intermittent asthma (8%, p<0.05) and severe persistent asthma (12%, p<0.04). Resistin production strongly increased in obese patients with intermittent (976 ng/ml) and severe persistent asthma (795 ng/ml). IL-6 increased in both lean and obese persons; however, the highest value was registered in the group of severe persistent obese asthmatics (992 pg/ml). Obesity per se increased the inflammatory profile of chemokines / cytokines secreted by cells of the blood, increasing the inflammatory status in asthmatic patients. Resistin showed characteristics of a pro-inflammatory cytokine mainly in severely obese asthmatics.

Características de pacientes asmáticos mexicanos atendidos en consulta externa / Characteristics of Mexican asthmatic subjects attending an outpatient service

Background. Despite the high prevalence of asthma in Mexico, studies describing general characteristics of these patients are scarce. Objective.To analyze the sociodemographic, clinical and respiratory functional profile of asthmatic patients attending for the first time the outpatient service of a tertiary-level hospital, as well as to investigate treatments already received and the abandonment rate. Methods.Adolescent and adult asthmatic subjects seen from February 2000 to November 2002 in the outpatient service of the National Institute of Respiratory Diseases, in Mexico City, were prospectively studied. Sociodemographic information was gathered and clinical and spirometric evaluations were carried out. The severity of the disease was classified according to international criteria. Results. A total of 1403 patients between 12 and 82 years of age, with predominance of the female gender, were included in the analysis. An 88.7% of patients had the mildest forms of the disease, 10% had moderate asthma, and 1.3% had severe asthma. While 21.4% had never received anti-asthma treatment, about one third of the remaining patients had received corticosteroids, independently of the asthma severity, indicating an over-treatment of the intermittent form of the disease and an under-treatment of persistent forms. A high abandonment rate (65.7%) was observed. A positive bronchodilator test was observed in 30.3% of patients with intermittent asthma, though this proportion increased to about 67% in those with moderate and severe asthma. Conclusion.Mildest forms of the disease predominate among asthmatic patients attending for the first time an outpatient service, with a still very high frequency of inadequate use of corticosteroids.

Antecedentes. A pesar de que en México existe una alta prevalencia de asma, hay pocos estudios que describan las características generales de estos pacientes. Objetivo. Conocer el perfil sociodemográfico, clínico y funcional respiratorio de pacientes asmáticos que acuden por primera vez a consulta externa de un hospital de tercer nivel de atención, así como los tratamientos recibidos y su tasa de abandono. Métodos. Se estudiaron, prospectivamente, sujetos asmáticos adolescentes y adultos, atendidos de febrero del 2000 a noviembre del 2002 en el servicio de consulta externa del Instituto Nacional de Enfermedades Respiratorias, de la ciudad de México. Se recabó información sociodemográfica y se realizó evaluación clínica y por espirometría. La gravedad del asma se clasificó de acuerdo con criterios internacionales. Resultados. Se incluyeron 1,403 pacientes de 12 a 82 años de edad, con predominio del sexo femenino. El 88.7% de los pacientes tenían formas leves de la enfermedad, 10% asma moderada, y 1.3% asma grave. El 21.4% no había recibido tratamiento antiasmático. Entre los demás, cerca de una tercera parte recibió corticosteroides, independientemente de la gravedad del asma, indicando sobretratamiento del asma intermitente y subtratamiento de las formas persistentes. Encontramos una alta tasa de deserción (65.7%). Una respuesta positiva a la prueba con broncodilatador se observó en 30.3% de los pacientes con asma intermitente, cifra que se elevó a cerca de 67% en las formas moderada y grave. Conclusión. Entre los pacientes asmáticos que acuden a consulta externa, predominan las formas leves, detectándose que todavía existe una alta frecuencia del uso inadecuado de los corticosteroides.