ICS/formoterol in the management of asthma in the clinical practice of pulmonologists: an international survey on GINA strategy.

BACKGROUND: The treatment with short-acting beta-2 agonists (SABA) alone is no longer recommended due to safety issues. Instead, the current Global Initiative for Asthma (GINA) Report recommends the use of the combination of inhaled corticosteroids (ICS) with the rapid/long-acting beta-2 agonist formoterol, although the use in steps 1 and 2 is still off-label in the EU and in many countries. It is important to understand clinicians' knowledge and opinions on the issue with the ultimate goal to encourage the implementation of the new approach in clinical practice. METHODS: We performed an international survey, directed to pulmonologists interested in the management of patients with asthma. RESULTS: Most participants reported that SABA alone should not be used in GINA Step 1 asthma treatment. As-needed low-dose ICS/formoterol combination to patients in step 1, and as-needed low-dose ICS/formoterol as reliever therapy in any step were found to be of current use prescribed in their real-life settings. SABA alone was still prescribed to a proportion of patients, although the pulmonologists' opinion was that it should no longer be used. CONCLUSIONS: Most specialists are up to date and understand the relevance of the changes in GINA reports from 2019. Nevertheless, dissemination and implementation of GINA novel management strategy is still needed.

[Mexican consensus on fractional exhaled nitric oxide (FeNO) in asthma 2020]. / Consenso mexicano en relación con la fracción exhalada de óxido nítrico (FeNO) en asma 2020.

The fractional exhaled nitric oxide (FeNO) is related to the level of eosinophilic inflammation in the airways and the levels of interleukin-13, as such it could be a diagnostic and monitoring tool in asthma. A working group was convened between pulmonologists, respiratory physiology experts, and allergists to establish criteria for the use of FeNO in asthma in Mexico. Through a simplified Delphi method and group discussion, seven key points regarding the use of FeNO were agreed upon. We agree that the measurement of FeNO serves for the diagnosis of asthma in specialized clinics, both in children and adults, as well as to determine the level of corticosteroid treatment. In severe asthma, we recommend FeNO for endotyping, for detecting poor therapeutic adherence, undertreatment, and the risk of crisis. We suggest FeNO can be used to determine the level of corticosteroid treatment and to identify patients at risk of loss of lung function. We also recommend it in adults to improve the selection of biological therapy and, in this context, we only suggest it in selected cases for children.

La fracción exhalada de óxido nítrico (FeNO) se relaciona con el nivel de inflamación eosinofílica en las vías aéreas y los niveles de interleucina-13, por lo que podría ser una herramienta diagnóstica y de seguimiento en el asma. Se convocó un grupo de trabajo integrado por neumólogos, expertos en fisiología de la respiración y alergólogos, con la finalidad de establecer criterios para el uso de la FeNO en asma en México. Mediante un método Delphi simplificado y discusión grupal, se consensaron varios puntos clave en relación con el uso de la FeNO. Sugerimos que la medición de la FeNO sirve para el diagnóstico de asma en clínicas especializadas, tanto en niños como adultos, así como para determinar el nivel de tratamiento con corticosteroides. En asma grave, recomendamos la FeNO para la endotipificación, detectar la mala adherencia terapéutica, el subtratamiento y el riesgo de crisis. Sugerimos su uso para determinar el nivel de tratamiento con corticosteroides e identificar pacientes con riesgo de tener una pérdida de la función pulmonar. También la recomendamos en el adulto para mejorar la elección de medicamentos biológicos y, en este contexto, solo la sugerimos en casos selectos en niños.

Advantage of inhaled corticosteroids as additional therapy to systemic corticosteroids for pediatric acute asthma exacerbations: a cost-effectiveness analysis.

Objective: Although the efficacy of systemic corticosteroids (SCs) in acute asthma exacerbations is well established, the fact that many children still require admission to hospital and that SCs have a slow onset of action are cause of concern. For this reason, the use of inhaled corticosteroids (ICS) as a therapy added to SCs has been explored, with no clarity about its cost-effectiveness. The aim of the present study was to evaluate the cost-effectiveness of ICS in addition to SCs (ICS + SCs) compared to standard therapy with SCs for treating pediatric asthma exacerbations.Methods: A decision-analysis model was developed to estimate the cost-effectiveness of SCs compared to ICS + SCs for treating pediatric patients with acute asthma exacerbations. Effectiveness parameters were obtained from a systematic review of the literature. Cost data obtained from hospital bills and from the national manual of drug prices. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission.Results: For the base-case analysis, the model showed that compared to SCs, therapy with ICS + SCs was associated with lower total costs (US$88.76 vs.US$97.71 average cost per patient) and a lower probability of hospital admission (0.9060 vs. 0.9000), thus showing dominance.Conclusions: This study shows that compared with standard therapy with SCs, ICS + SCs for treating pediatric patients with acute asthma exacerbations is the preferred strategy because it was associated with a lower probability of hospital admission, at lower total treatment costs.

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.

An online survey detected knowledge gaps and cost-saving opportunities in asthma maintenance treatment among allergists, pulmonologists, ENTs and primary care.

BACKGROUND: In April 2017 the Mexican Asthma Guidelines (GUIMA) were published. Before the launch, physicians' knowledge was explored related to key issues of the guideline. METHODS: A SurveyMonkey® survey was sent out to board-certified physicians of 5 medical specialties treating asthma. Replies were analyzed per specialty against the GUIMA evidence-based recommendations. We present the treatment part here. RESULTS: A total of 364 allergists (ALLERG), 161 pulmonologists (PULM), 34 ENTs, 239 pediatricians (PED) and 62 general practitioners (GPs) replied to the survey and 247-83-14-135-37 respectively finished it. Spirometry is not routinely indicated when asthma is very probable by ALLERG 54%, PULM 47%, ENT 39%, PED 65%, GP 64%. A fictitious case proposed to the physicians with intermittent asthma was erroneously treated with ICS by ALLERG 9%, PULM 11%, ENT 28%, PED 10%, GP 11%. The mild persistent case received mistakenly ICS-LABA by ALLERG 25%, PULM 26%, ENT 33%, PED 27%, GP 23%. The first-line option for moderate persistent asthma was ICS(median dose) instead of ICS(low)+LABA for ALLERG 29%, PULM 25%, ENT 17%, PED 27%, GP 23% and in severe asthma maintenance treatment PULM20%, ALLERG-ENT-PED-GP 22-34% failed to indicate LABA. Concerning the guidelines' recommendation to use one inhaler for maintenance & rescue in moderate-to-severe asthma, PULM45%, ALLERG-ENT-PED-GP 56-80% (p < 0.00001), erroneously indicated ICS-salmeterol could be used, instead of ICS-formoterol. Oral ß2 or theophylline are no longer recommended, but PULM 37% and ALLERG-ENT-PED-GP 42-62% (p < 0.01) still indicate their use. In severe asthma 61-73% of physicians consider adding LTRA to the treatment; only PULM38%, OTHERS12-25% consider adding tiotropium (p < 0.001) and 3-17% consider adding omalizumab, both guideline recommended add-ons. As for asthma in pregnancy, most surveyed are not aware budesonide is the 1st line option ICS. Finally, 81-97% of the group-members recognized allergen immunotherapy, as a viable add-on, in line with GINA/GEMA/GUIMA recommendations. CONCLUSIONS: An online survey could detect knowledge-gaps related to asthma treatment. Interestingly, surveyed physicians tended to over-treat the milder asthma cases, thus clearly leaving room for cost-savings. Caution should be taken in the promotion of the SMART (single-maintenance-and-reliever-treatment) approach, which can only be done with ICS-formoterol. Many physicians opt for other combinations not apt for this approach. Among all surveyed specialties there is ample room for improvement in mild and severe asthma management.

Estudio aleatorizado abierto de niños con exacerbación aguda del asma tratados con esteroides inhalados / Open randomized study of children with acute exacerbation of asthma and treated with inhaled steroids

Introducción: la terapia primaria en la crisis de asma aguda, incluye administración de oxígeno, uso de ß2-agonistas por vía inhalada y la administración de esteroides sistémicos. Las ventajas que se citan sobre el uso de los esteroides inhalados serían, su rápido inicio de acción y su buen perfil de seguridad, en contraposición a los esteroides sistémicos. Objetivo: evaluar la utilidad de los corticoides inhalados en el tratamiento de la crisis de asma aguda en niños mayores de 2 años. Métodos: se realizó un estudio prospectivo, transversal, experimental, aleatorizado, de eficacia clínica; la selección se realizó por medio de una tabla de números aleatorios, y se incluyeron tres grupos: el I recibió terapia estándar, el II la sustitución del esteroide sistémico por el inhalado y el III combinó a la terapia estándar el esteroide inhalado. El análisis estadístico se realizó por medio de ANOVA y chi cuadrado con una p< 0,05 como significativa. Resultados: se estudiaron 165 pacientes, los tres grupos de tratamiento mejoraron la escala de severidad inicial. Los pacientes que recibieron esteroides inhalados adicionados a la terapia estándar, tuvieron 73 por ciento de posibilidades de no ser hospitalizados, 27 por ciento de posibilidades de reducir el riesgo de hospitalizaciones y de cada 100 pacientes tratados con la combinación, se pudieran prevenir 8 hospitalizaciones(AU)

[Mexican Asthma Guidelines: GUIMA 2017]. / Guía Mexicana del Asma: GUIMA 2017.

BACKGROUND: The need for a national guideline, with a broad basis among specialists and primary care physicians was felt in Mexico, to try unifying asthma management. As several high-quality asthma guidelines exist worldwide, it was decided to select the best three for transculturation. METHODS: Following the internationally recommended methodology for guideline transculturation, ADAPTE, a literature search for asthma guidelines, published 1-1-2007 through 31-12-2015 was conducted. AGREE-II evaluations yielded 3/40 most suitable for transculturation. Their compound evidence was fused with local reality, patient preference, cost and safety considerations to draft the guideline document. Subsequently, this was adjusted by physicians from 12 national medical societies in several rounds of a Delphi process and 3 face-to-face meetings to reach the final version. RESULTS: Evidence was fused from British Thoracic Society Asthma Guideline 2014, Global Initiative on Asthma 2015, and Guía Española del Manejo del Asma 2015 (2016 updates included). After 3 Delphi-rounds we developed an evidence-based document taking into account patient characteristics, including age, treatment costs and safety and best locally available medication. CONCLUSIONS: In cooperation pulmonologists, allergists, ENT physicians, paediatricians and GPs were able to develop an evidence-based document for the prevention, diagnosis and treatment of asthma and its exacerbations in Mexico.

Antecedentes: Con el objetivo de unificar el manejo del asma en México se estructuró una guía clínica que conjunta el conocimiento de diversas especialidades y la atención en el primer nivel de contacto. Se seleccionaron 3 guías publicadas en el ámbito internacional para su transculturación. Métodos: Conforme a la metodología ADAPTE se usó AGREE II después de la búsqueda bibliográfica de guías sobre asma publicadas entre 2007 y 2015. Se fusionó la realidad local con la evidencia de 3/40 mejores guías. El documento inicial fue sometido a la revisión de representantes de 12 sociedades médicas en varias rondas Delphi hasta llegar a la versión final. Resultados: Las guías base fueron la British Thoracic Society Asthma Guideline 2014, la Global Initiative on Asthma 2015 y la Guía Española del Manejo del Asma 2015. Después de 3 rondas Delphi se desarrolló un documento en el que se consideraron las características de los pacientes según edad, costos de los tratamientos y perfiles de seguridad de los fármacos disponibles en México. Conclusión: Con la cooperación de neumólogos, alergólogos, otorrinolaringólogos, pediatras y médicos generales se llegó a un consenso basado en evidencia, en el que se incluyeron recomendaciones sobre prevención, diagnóstico y tratamiento del asma y sus crisis.

Evaluación del uso de corticoides inhalados en altas dosis para el tratamiento de crisis asmática / Evaluation of the Use of High-dose Inhaled Corticosteroids for the Treatment of Acute Asthma

Introducción: El asma es una enfermedad heterogénea caracterizada por la inflamación crónica de la vía aérea. Se caracteriza por síntomas respiratorios como sibilancias, disnea, opresión en el pecho, tos que varía en el tiempo y en la intensidad, además de presentar limitación variable al flujo aéreo. Afecta del 1 al 18% de la población mundial. Existe evidencia que sugiere que los corticoides inhalados pueden mostrar efectos terapéuticos tempranos (< 3 h). Esta rápida respuesta se encontraría vinculada a un efecto tópico (vasoconstricción de la mucosa de la vía aérea), debido a la potenciación del efecto adrenérgico por modificación de los receptores post-sinápticos. Materiales y métodos: Se realizó un estudio prospectivo, aleatorizado, analítico, longitudinal de cohorte y experimental, en pacientes con crisis de asma atendidos en la guardia externa del Hospital de Rehabilitación Respiratoria María Ferrer. Resultados: Se evaluó a un total de 71 pacientes en un período de 10 meses, todos ingresaron por el servicio de guardia del Hospital de Rehabilitación Respiratoria María Ferrer y accedieron a participar del protocolo firmando un consentimiento informado. Ambos grupos presentaron un 63% de respuesta significativa (FEV1 > 60%) a los 30 minutos de iniciado el tratamiento (p: 0.72). Al fnal del protocolo (180 minutos), el grupo control (salbutamol + bromuro de ipratropio) presentó 3 pacientes que no lograron el objetivo del FEV1 > 60% a comparación de 2 pacientes en el grupo tratado con corticoides inhalados a altas dosis (P: 0.97). Conclusión: Actualmente el uso de corticoides inhalados a altas dosis en crisis de asma es una opción terapéutica para pacientes con crisis moderadas a severas. Nuestro estudio no obtuvo valores significativos que apoyen el uso de esta medicación para reducir la incidencia de internaciones o mejorar significativamente la función pulmonar.

Introduction: Asthma is a heterogeneous disease characterized by chronic inflammation of the airways. Its more common respiratory symptoms such as wheezing, breathlessness, chest tightness and cough vary in time and intensity, in addition to displaying variable airflow limitation. Asthma affects 1 to 18% of the world population. Evidence suggests that inhaled corticosteroids may show early therapeutic effects (<3 hours). This quick response would be linked to a local effect (vessel constriction of the airway mucosa) due to the potentiation of the adrenergic effect that modifies the postsynaptic receptors. Materials and methods: A prospective, randomized, analytical and experimental longitudinal cohort study in patients with acute asthma treated at the emergency services of the Respiratory Rehabilitation Hospital Maria Ferrer, Buenos Aires. Results: A total of 71 patients were evaluated over a period of 10 months who had agreed to participate in the study by signing an informed consent. Both the study and the control groups had a 63% significant response (FEV1> 60%) within 30 minutes of starting treatment (p = 0.72). At the end of the observation (180 minutes), three patients of the control group (Salbutamol + ipratropium bromide) did not achieve the objective of FEV1> 60% compared to 2 patients in the study group treated with high-dose inhaled corticosteroids (P group: 0.97). Conclusion: Currently the use of high-dose inhaled corticosteroids in asthma attack is a therapeutic option for patients with moderate to severe crisis. The results of our study do not provide significant evidence in support of the use of this medication to reduce the incidence of hospitalizations or improve the lung function.

Periodontal disease and high doses of inhaled corticosteroids alter NTPDase activity in the blood serum of rats.

BACKGROUND: Certain drugs such as glucocorticoids may interfere with the modulation of periodontal disease. In contrast, corticosteroid treatment has been associated with a protective effect with regard to periodontal breakdown, depending on the dose, pathway, and exposure time. Considering the potential relevance of nucleotidases in coordinating the cardiovascular system and inflammation processes, the aim of this study was to investigate the nucleotidase activities in the blood serum of rats with periodontal disease exposed chronically to inhaled corticosteroids. METHODS: Adult male Wistar rats (n=26) were randomly assigned to one of the following four study groups: a control group that received no intervention; a periodontal disease group that received saline solution; a 'low dose' group that received 30 µg of budesonide daily; and a corresponding 'high dose' group that received 100 µg daily over a 15-day time course. The hydrolysis of ATP, ADP, and AMP were analysed in blood serum. RESULTS: Periodontal disease diminished the hydrolysis of ATP and enhanced the hydrolysis of ADP. Repeated administration of either a low or high dose in the periodontal disease model of inhaled corticosteroids reversed the observed increase in ADP hydrolysis, and only the repeated administration of low doses of inhaled corticosteroids was able to reverse the decrease in the hydrolysis of ATP induced by periodontal disease. CONCLUSION: The variables investigated in this study may be involved in the pathophysiology of periodontal disease and may participate in the mechanisms that mediate the development of some of the side effects of inhaled corticosteroids.

Crescimento em asmáticos pré-púberes em uso de corticosteróide inalatório / Linear growth in pre-pubertal asthmatics and inhaled corticosteroid use

Introdução: O objetivo deste estudo retrospectivo foi identificar a relação entre o uso de corticosteróide inalatório e o crescimento linear de asmáticos pré-púberes. Métodos: Análise retrospectiva de uma amostra selecionada por conveniência, constituída por pacientes pré-púberes ( dez anos de idade) com diagnóstico de asma e tratados com corticosteróide inalatório. As medidas da estatura foram avaliadas pelo escore de desvio-padrão da estatura (H505) em três ocasiões diferentes. Para análise estatística utilizaram-se os testes de ANOVA. Resultados: A média de idade dos 22 pacientes (14 do sexo masculino) foi de 7,7 anos na primeira consulta. A maior parte dos pacientes apresentava asma leve (dez casos) e mode-rada (dez) e apenas dois pacientes tinham asma de intensidade grave. O tempo médio decorrido entre as três ocasiões em que os pacientes foram avaliados foi de doze meses. Dezessete pacientes (77,2%) utilizavam corticosteróide inalatório em doses baixas (até 500 mcg/dia de beclometasona ou doses equivalentes de outros corticosteróides inalatórios). A mediana do escore H5D5 obtido na primeira, segunda e terceira consultas foi respectivamente de 0,35; 0,25 e 0,20 respectivamente (p =0, 284). Conclusões: Neste grupo de asmáticos pré-púberes a média de H505 mostrou que, independente da dose de corticosteróide inalatório utilizada, os pacientes mantiveram seu canal de crescimento.

Introduction: The aim of this study was to verify the rE tion between pre-pubertal asthmatics linear growth and use of inhaled corticosteroids. Methods: Pre-pubertal asthmatic patients (~ 10 years c under inhaled corticosteroids were included. The height mea re was determined by height standard deviation score (H5[ in three d ifferent occasions. Data were analysed by ANC tests. Results: The mean age of the 22 subjects (14 males) inc ded was 7,7 years at first visito The majority of the patie had mild asthma (10 cases) and moderate (10), and only ~ them had severe asthma. The mean time between the th occasions when the subjects were analyzed was 12 mont 5eventeen subjects (77,2%) were under low doses of inha corticosteroid (~500 mcg/day beclomethasone or equival dose of different inhaled steroid). The median H505 at fi second and third visits was respectively 0,35; 0,25 and O (p=0,284). Conclusions: ln this group of asthmatics the H5D5 rru showed that, regardless the inhaled corticosteroid dose, th was no influence on linear growth.

Adesão ao uso de corticóide inalatório na asma: taxas relatadas pelos responsáveis e mensuradas pela farmácia / Compliance with inhaled corticosteroid treatment: rates reported by guardians and measured by the pharmacy

OBJETIVO: A morbidade associada à asma é elevada, principalmente nos países em desenvolvimento, e as falhas na adesão ao uso de corticóide inalatório contribuem para esta elevação. Este estudo objetiva comparar as taxas de adesão ao uso de beclometasona relatadas pelos responsáveis e as mensuradas pelos registros de dispensação farmacêutica do medicamento. MÉTODOS: Foi realizado um estudo de coorte concorrente com duração de 12 meses, do qual participaram 106 crianças e adolescentes asmáticos, selecionados aleatoriamente. Através da regressão linear, as taxas de adesão relatadas pelos responsáveis e pelos registros de dispensação da farmácia do serviço foram correlacionadas, quadrimestralmente, a partir da admissão no estudo. RESULTADOS: As taxas de adesão relatadas pelos pais e/ou responsáveis foram sempre superiores (p < 0,001) e apresentaram fraca correlação com aquelas mensuradas pelos registros de farmácia nos períodos estudados, quarto (r = 0,37) e 12º (r = 0,31) mês do seguimento.CONCLUSÃO: As taxas de adesão relatadas pelos pais foram superestimadas em todos os períodos do estudo. Crianças com asma deveriam ter suas taxas de adesão também monitoradas por outros métodos e, neste caso, os registros de farmácia foram efetivos em revelar as falhas na adesão. Dado ao seu baixo custo, esse método está indicado para a verificação dessas taxas.

OBJECTIVE: There is elevated morbidity associated with asthma, particularly in developing countries, and failure to comply with inhaled corticosteroid treatment contributes to this morbidity. The objective of this study is to compare rates of compliance with beclomethasone treatment reported by parents or guardians with those measured by pharmacy dispensing records. METHODS: A concurrent cohort study of 12 months' duration was carried out, enrolling 106 asthmatic children and adolescents, selected at random. Linear regression was used to compare rates of compliance reported by parents or guardians with the pharmacy dispensing records at the service, every 4 months after enrollment on the study. RESULTS: Compliance rates reported by parents and/or guardians were always higher (p < 0.001) and exhibited a weak correlation with pharmacy records during the period studied; fourth (r = 0.37) and twelfth (r = 0.31) months of follow-up. CONCLUSIONS: The rates of compliance reported by parents were overestimated during all study periods. The compliance rates of children with asthma should also be monitored by other methods and, in this case, pharmacy records effectively revealed compliance failures. Given its low cost, this method is indicated for verification of these compliance rates.