Nivel de adhesión y prevalencia a inhaladores en pacientes ambulatorios con Asma y Enfermedad Pulmonar Obstructiva Crónica / Level of inhaler adhesion and prevalence in outpatients with Asthma and Chronic Obstructive Pulmonary Disease

INTRODUCCIÓN. Para el tratamiento farmacoterapéutico de enfermedades respi-ratorias, el uso de herramientas para abordar la vía inhalatoria es de elección por su mayor eficacia y menos efectos secundarios; registrar su adhesión y prevalencia es importante. OBJETIVO. Determinar el nivel y la prevalencia de adhesión al uso de inhaladores en pacientes con Asma y Enfermedad Pulmonar Obstructiva Cróni-ca. MATERIALES Y MÉTODOS. Estudio analítico transversal. Población de 215 y muestra de 121 Historias Clínicas. Se aplicó el Test de Adhesión a Inhaladores, que consistió en dos cuestionarios complementarios: el de 10 ítems, que valoró el nivel de adhesión, y el de 12 que identificó el tipo de incumplimiento en pacientes de Consulta Externa de la Unidad Técnica de Neumología del Hospital de Especialidades Carlos Andrade Marín, periodo julio 2018 - enero 2019. La tabulación y análisis de datos se realizó con el programa Excel. RESULTADOS. La prevalencia de mala adhesión en asmáticos fue de 83,33% y en Enfermedad Pulmonar Obstructiva Crónica 13,33%. En cuanto al sexo, la prevalencia de mala adhesión fue de 15,28% en hombres y de 40,82% en mujeres, con una p<0,05. No se encontró diferencia significativa respecto a los niveles de instrucción. CONCLUSIÓN. La prevalencia de mala adhesión al uso de inhaladores en pacientes con Asma y Enfermedad Pulmonar Obstructiva Crónica fue alta sobre todo en los asmáticos.

INTRODUCTION. For respiratory diseases and their pharmacotherapeutic treatment, the use of tools to address the inhalation route is chosen due to its greater efficacy and fewer secondary effects; then record the adherence and prevalence is important. OBJECTIVE. To determine both level and prevalence of adherence to the use of inhalers in patients with Asthma and Chronic Obstructive Pulmonary Disease. MATE-RIALS AND METHODS. Cross-sectional analytical study. Population of 215 and sam-ple of 121 patients. The Inhaler Adherence Test was applied, which consisted of two complementary questionnaires: a 10-item questionnaire, which assessed the level of adherence, and a 12-item questionnaire that identified the type of non-compliance in patients of the Pneumology Technical Unit of the Hospital de Especialidades Carlos Andrade Marín, period July 2018 - January 2019. The tabulation and data analysis was performed with Microsoft Excel program. RESULTS. The prevalence of poor ad-herence in asthmatics was 83.33% and in Chronic Obstructive Pulmonary Disease was 13.3%. Regarding gender, the prevalence of poor adherence was 15.28% in men and 40.82% in women, with a p <0.05. No significant differences were found regarding the levels of instruction. CONCLUSION. The prevalence of poor adherence to the use of inhalers in patients with Asthma and Chronic Obstructive Pulmonary Disease was high, especially in asthmatics

Peak inspiratory flow in children and adolescents with asthma using dry powder inhalers: a cross-sectional study / Pico de fluxo inspiratório de crianças e adolescentes com asma que utilizam inaladores de pó: um estudo transversal

ABSTRACT Objective: To measure peak inspiratory flow (PIF) and assess dynamic lung function in children and adolescents with asthma, as well as to determine the association of PIF with dynamic lung function and clinical variables. Methods: This was a cross-sectional study of children and adolescents with asthma using dry powder inhalers (DPIs) regularly. The control group included sex-, age-, weight-, and height-matched individuals without lung disease. Socioeconomic and clinical variables were collected. PIF and dynamic lung function variables were obtained with a specific device. Between-group comparisons were made with the Student's t-test and ANOVA. Multiple linear regression analysis was performed, and Pearson's correlation coefficients were calculated to assess associations between PIF and the other variables. Results: A total of 88 individuals (44 asthma patients and 44 controls) participated in the study. PIF and respiratory muscle strength (S-index) values were lower in the asthma patients than in the controls. PIF correlated positively with age, weight, height, and S-index in the asthma group. After controlling for height, we found an increase of 0.05 units in PIF associated with an increase of 1 unit in the S-index in the asthma group. Conclusions: PIF appears to be lower in children and adolescents with asthma than in those without asthma, correlating positively with age, height, weight, and respiratory muscle strength.

RESUMO Objetivo: Analisar o pico de fluxo inspiratório (PFI) e a função pulmonar dinâmica de crianças e adolescentes asmáticos e verificar sua associação com variáveis clínicas. Métodos: Estudo transversal com crianças e adolescentes asmáticos que faziam uso regular de inaladores de pó. O grupo controle foi composto por participantes sem doença pulmonar, pareados por sexo, idade, peso e altura. Foram coletadas variáveis socioeconômicas e clínicas. O PFI e variáveis de função pulmonar dinâmica foram obtidos através de um dispositivo específico. As associações entre os dois grupos foram estudadas utilizando-se o teste t de Student e ANOVA. Realizou-se um modelo de regressão linear múltipla e foram calculados os coeficientes de correlação de Pearson para estimar associações entre o PFI e as demais variáveis. Resultados: Foram incluídos no estudo 88 participantes (44 em cada grupo). Nos asmáticos, os valores do PFI e de força muscular respiratória (S-índex) foram menores que os dos controles. O PFI nos asmáticos apresentou correlações positivas com as variáveis idade, peso, altura e S-índex. Controlando-se a altura, houve um aumento de 0,05 unidades no PFI associado ao aumento de 1 unidade de S-índex nos asmáticos. Conclusões: O PFI é menor em crianças e adolescentes com asma em comparação àqueles sem asma com características antropométricas semelhantes e apresenta correlações positivas com idade, altura, peso e força dos músculos respiratórios.

Influencia del uso de inhaladores sobre la caries dental en pacientes pediátricos asmáticos: Estudio de casos y controles / Impact of inhaler use on dental caries in asthma pediatrics patients: A case-control study

Introducción. El asma es una enfermedad inflamatoria crónica con alta prevalencia en pacientes pediátricos. Existen resultados contradictorios respecto al efecto de esta enfermedad en los índices de caries dental. El objetivo del estudio fue determinar la prevalencia de caries dental en pacientes pediátricos asmáticos con medicación inhalatoria. Población y métodos. Estudio de casos y controles cuya muestra estuvo conformada por pacientes pediátricos que acudieron al Centro Médico Naval "Cirujano Mayor Santiago Távara" de diciembre de 2014 a marzo de 2015. Se dividieron en dos grupos: el primero (casos), integrado por pacientes asmáticos que utilizaban inhaladores en su tratamiento; el segundo (controles), por pacientes sanos del mismo nosocomio. Se realizó una evaluación médica para determinar tipo, tiempo y frecuencia del tratamiento y un examen oral para determinar la prevalencia de caries dental y el índice de dientes cariados, perdidos y obturados (CPOD). Resultados. Se encontró que la prevalencia de caries dental en el grupo control fue del 34,2 %, mientras, en el grupo casos, fue del 28,3 % (p = 0,094). Con respecto al índice de caries dental, el grupo control presentó CPOD de 4,73 ± 0,32, y el grupo casos, de 3,98 ± 0,31 (p = 0,08). Sin embargo, se evidenció que, a mayor tiempo de tratamiento con los inhaladores, el índice CPOD aumentaba significativamente (p = 0,04).Conclusiones. La medicación inhalatoria no incrementa la prevalencia de caries dental en pacientes pediátricos asmáticos. Sin embargo, existe una relación directa entre la duración del tratamiento y la prevalencia de caries dental

Introduction. Asthma is a chronic inflammatory disease that is highly prevalent among pediatric patients. The results about the effect of asthma on the rate of dental caries are contradictory. The objective of this study was to determine the prevalence of dental caries in asthma pediatric patients using inhaled drugs. Population and methods. Case-control study in a sample made up of pediatric patients who attended Centro Médico Naval "Cirujano Mayor Santiago Távara" between December 2014 and March 2015. Patients were divided into two groups: group A (cases) included asthma patients using inhalers as part of their treatment; group B (controls), healthy subjects who attended the same facility. A medical examination was done to determine the type, time, and frequency of treatment and an oral exam, to establish the prevalence of dental caries and the decayed, missing, and filled teeth (DMFT) index. Results. The prevalence of dental caries was 34.2 % in the control group and 28.3 % in the case group (p = 0.094). In relation to the rate of dental caries, the DMFT index in the control group was 4.73 ± 0.32, and 3.98 ± 0.31 in the case group (p = 0.08). However, it was evidenced that a longer duration of inhaler use led to a significantly higher DMFT index (p = 0.04).Conclusions. Inhaled drugs do not increase the prevalence of dental caries in asthma pediatric patients. However, there is a direct relationship between treatment duration and the prevalence of dental caries.

Efficacy and Safety of a Pressurized Metered-Dose Inhaler in Older Asthmatics: Comparison to a Dry Powder Inhaler in a 12-Week Randomized Trial

PURPOSE: Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.METHODS: We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.RESULTS: A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, P < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, P < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.CONCLUSION: These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.

Most frequent errors in inhalation technique of patients with asthma treated at a tertiary care hospital / Erros mais frequentes na técnica inalatória de pacientes com asma brônquica em tratamento em hospital terciário

ABSTRACT Objective: To demonstrate the most frequent errors in inhalation technique in patients with asthma undergoing treatment at a tertiary care hospital. Methods: A cross-sectional study with a convenience sample of asthma patients aged 18 years or over, treated at a pulmonology outpatient clinic of a tertiary care hospital. The assessment of inhalation technique of users of the dry powder inhalers Aerolizer®, Aerocaps and Diskus®, or metered-dose inhalers was based on the manufacturer's instructions for use of each inhaler device. Patients demonstrated the inhalation technique with empty inhaler devices, and it was considered correct when all stages were performed properly, or when errors probably did not interfere with the treatment outcome. Results: Among 71 participants, 43 (60.5%) performed inhalation technique incorrectly. Among metered-dose inhalers and dry powder inhalers users, inhalation technique errors were found in 84.2% and 51.9%, respectively (p=0.013). Errors were more frequent at the exhalation stage (67.4%), followed by breathing in (58.1%) and apnea (51.2%). In the group using dry powder inhalers, the most common errors occurred during exhalation and, for those using metered-dose inhalers, the most compromised stage was aspiration. Conclusion: Errors were more frequent among those using metered-dose inhalers compared with dry powder inhalers. Misconceptions are more common at the expiration stage among users of dry powder inhalers and in aspiration among those on metered-dose inhalers.

RESUMO Objetivo: Demonstrar os erros mais frequentes na técnica inalatória de pacientes com asma brônquica em tratamento em hospital terciário. Métodos: Estudo transversal, com amostra de conveniência de pacientes com asma, com 18 anos ou mais, em tratamento em ambulatório de pneumologia de um hospital terciário. A avaliação da técnica inalatória dos usuários dos dispositivos de pó seco Aerolizer ®, Aerocaps® ou Diskus®, ou de aerossóis dosimetrados teve como base as orientações da bula do fabricante de cada dispositivo inalatório. Os pacientes demonstraram a técnica inalatória com dispositivos inalatórios vazios, e ela foi considerada correta quando todas as etapas foram realizadas de forma apropriada, ou quando os equívocos provavelmente não interferiam no resultado do tratamento. Resultados: Entre os 71 participantes, 43 (60,5%) realizaram a técnica inalatória de forma incorreta. Dentre os usuários de aerossóis dosimetrados e dispositivos de pó seco, ocorreram erros de técnica inalatória em 84,2% e 51,9%, respectivamente (p=0,013). Os erros foram mais frequentes na etapa da expiração (67,4%), seguidos da aspiração (58,1%) e da apneia (51,2%). No grupo que usava dispositivos de pó seco, os erros mais comuns aconteceram na expiração e, nos que utilizavam aerossóis dosimetrados, a etapa mais comprometida foi a aspiração. Conclusão: Os erros foram mais frequentes entre os que usavam aerossóis dosimetrados em comparação com dispositivos de pó seco. Os equívocos foram mais comuns na etapa da expiração entre os usuários de dispositivos de pó seco e na aspiração entre os que usavam aerossóis dosimetrados.

Short-term Evaluation of a Comprehensive Education Program Including Inhaler Training and Disease Management on Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

BACKGROUND: Proper education regarding inhaler usage and optimal management of chronic obstructive pulmonary disease (COPD) is essential for effectively treating patients with COPD. This study was conducted to evaluate the effects of a comprehensive education program including inhaler training and COPD management. METHODS: We enlisted 127 patients with COPD on an outpatient basis at 43 private clinics in Korea. The patients were educated on inhaler usage and disease management for three visits across 2 weeks. Physicians and patients were administered a COPD assessment test (CAT) and questionnaires about the correct usage of inhalers and management of COPD before commencement of this program and after their third visit. RESULTS: The outcomes of 127 COPD patients were analyzed. CAT scores (19.6±12.5 vs. 15.1±12.3) improved significantly after this program (p<0.05). Patients with improved CAT scores of 4 points or more had a better understanding of COPD management and the correct technique for using inhalers than those who did not have improved CAT scores (p<0.05). CONCLUSION: A comprehensive education program including inhaler training and COPD management at a primary care setting improved CAT scores and led to patients' better understanding of COPD management.

Repercussões cardiorrespiratórias agudas no uso correto de inaladores aerossóis de pó seco / Acute cardiopulmonary repercussions in the correct use of the dry-powder inhalers

Modelo do estudo: Trata-se de estudo original, transversal, clínico e comparativo. Objetivo do estudo: Avaliar as repercussões cardiorrespiratórias agudas no uso correto de inaladores aerossóis de pó seco (IPS) em pacientes com asma. Metodologia: Foram avaliados, em dois momentos, 17 pacientes adultos asmáticos em uso de IPS (Formoterol e Budesonida). As variáveis avaliadas, pré e pós-uso do IPS, foram: antropométrica, cognitiva, força muscular, sinais vitais, saturação de oxigênio, pressões respiratórias e pico de fluxo. No primeiro momento (M1) foi avaliada e monitorada a execução rotineira antes e imediatamente após uso do IPS e entregue folheto explicativo sobre o uso correto. No segundo momento (M2), 30 dias após M1, houve a mesma avaliação, entretanto, com execução correta do IPS. Resultados: No M2 ocorreram aumentos significativos da pressão inspiratória de 64,2±2,03 para 74,1±31,7 (cmH2O); pressão expiratória de 71,05±33,8 para 80±31,4 (cmH2O); capacidade vital de 3,3±0,9 para 3,9±0,9 (l) e reduções na frequência de pulso de 80,310,7 para 72,2±9,4 (bpm) e do duplo produto de 10001±1693 para 8846±1416 (teste t-Student pareado, p<0,05). Conclusões: O uso correto de IPS traz ao paciente repercussões cardiorrespiratórias positivas, melhorando as condições respiratórias e reduzindo o trabalho cardíaco.

Study model: It is a cross-over, clinical and comparative study. Objective: To evaluate the acute respiratory and cardiac respercussions in correct use of the dry powder inhalers (DPI) in patients with asthma. Methodology: Seventeen adult patients with asthma using DPI (Formoterol and Budesonide)were evaluated in two moments. The mensuared variables, before and after use of DPI, were: anthropometric, cognitive, muscle strength, vital signs, periferic oxygen saturation, respiratory pressures and peak expiratory flow. In the first moment (M1) was evaluated and monitored the usual performance before and immediately after using DPI and delivered an explicative leaflet about the correct use. In the second moment (M2), 30 days after M1, there was the same evaluation, however, with correct use ofthe DPI. Results: In the M2 there were increases to inspiratory pressure of 64,2±2,03 to 74,1±31,7(cmH2O); expiratory pressure of 71,05±33,8 to 80±31,4 (cmH2O); vital capacity of 3,3±0,9 to 3,9±0,9(l) and reductions in the pulse frequence of 80,3±10,7 to 72,2±9,4 (bm) and double product of 10001±1693 to 8846±1416 (paired t test, p<0,05). Conclusions: The correct use of the DPI promoves the positive respiratory and cardiac repercussions, improving respiratory conditions and reducing cardiac work.

Validation of scores of use of inhalation devices: valoration of errors / Validação de escores de uso de dispositivos para inalação: valoração dos erros cometidos

AbstractObjective: To validate two scores quantifying the ability of patients to use metered dose inhalers (MDIs) or dry powder inhalers (DPIs); to identify the most common errors made during their use; and to identify the patients in need of an educational program for the use of these devices.Methods: This study was conducted in three phases: validation of the reliability of the inhaler technique scores; validation of the contents of the two scores using a convenience sample; and testing for criterion validation and discriminant validation of these instruments in patients who met the inclusion criteria.Results: The convenience sample comprised 16 patients. Interobserver disagreement was found in 19% and 25% of the DPI and MDI scores, respectively. After expert analysis on the subject, the scores were modified and were applied in 72 patients. The most relevant difficulty encountered during the use of both types of devices was the maintenance of total lung capacity after a deep inhalation. The degree of correlation of the scores by observer was 0.97 (p < 0.0001). There was good interobserver agreement in the classification of patients as able/not able to use a DPI (50%/50% and 52%/58%; p < 0.01) and an MDI (49%/51% and 54%/46%; p < 0.05).Conclusions: The validated scores allow the identification and correction of inhaler technique errors during consultations and, as a result, improvement in the management of inhalation devices.

ResumoObjetivo: Validar dois escores para medir a habilidade de pacientes em utilizar inaladores pressurizados (IPs) ou inaladores de pó (IPos), verificar os erros mais comuns na sua utilização e identificar os pacientes que necessitam de um programa educacional para o uso desses dispositivos.Métodos: Este estudo foi realizado em três etapas: validação da confiabilidade dos escores de uso dos dispositivos inalatórios; validação do conteúdo dos escores utilizando-se uma amostra de conveniência; e realização de testes para a validação de critério e a validação discriminante desses instrumentos em pacientes que preenchiam os critérios de inclusão do estudo.Resultados: A amostra de conveniência foi composta por 16 pacientes, e houve discordância interobservador em 19% e 25% para os escores de IPo e IP, respectivamente. Após a análise de expertos no assunto, os escores sofreram modificações e foram aplicados em 72 pacientes. A dificuldade mais relevante no uso de ambos os dispositivos foi a manutenção da capacidade pulmonar total após inspiração profunda. O grau de correlação dos escores por observador foi de 0,97 (p < 0,0001). Houve boa concordância interobservador na classificação dos pacientes como aptos/não aptos para uso de IPo (50%/50% e 52%/58%; p < 0,01) e de IP (49%/51% e 54%/46%; p < 0,05).Conclusões: Os escores validados permitem identificar e corrigir os erros da técnica inalatória ao longo das consultas e, em consequência, melhorar o manejo dos dispositivos para inalação.

Recent progress of dry powder inhalation of proteins and peptides / 药学学报

To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder.

Efficacy and safety of the single-capsule combination of fluticasone/formoterol in patients with persistent asthma: a non-inferiority trial / Eficácia e segurança da associação fluticasona/formoterol em cápsula única em pacientes com asma persistente: estudo de não inferioridade

OBJECTIVE: Fluticasone and formoterol are effective in the treatment of asthma. When a corticosteroid alone fails to control asthma, combination therapy is the treatment of choice. The objective of this study was to compare the efficacy and safety of formulations containing budesonide/formoterol (BUD/FOR), fluticasone alone (FLU), and the single-capsule combination of fluticasone/formoterol (FLU/FOR) on lung function in patients with mild-to-moderate persistent asthma. METHODS: This was a randomized, multicenter, open phase III trial conducted in Brazil. The primary efficacy analysis was the assessment of non-inferiority between FLU/FOR and BUD/FOR combinations regarding FEV1 (in L) at the final visit. The secondary analyses were PEF, level of asthma control, serum cortisol levels, frequency of adverse events, adherence to treatment, and appropriate inhaler use. RESULTS: We randomized 243 patients to three groups: FLU/FOR (n = 79), BUD/FOR (n = 83), and FLU (n = 81). In terms of the mean FEV1 after 12 weeks of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L (95% CI: −0.06 to 0.49), whereas the difference between the FLU/FOR and FLU groups was 0.26 L (95% CI: −0.002 to 0.52). Non-inferiority was demonstrated by the difference between the lower limits of the two 95% CIs (−0.06 vs. −0.002). The level of asthma control and PEF were significantly greater in the FLU/FOR and BUD/FOR groups than in the FLU group. There were no significant differences among the groups regarding patient adherence, patient inhaler use, or safety profile of the formulations. CONCLUSIONS: The single-capsule combination of FLU/FOR showed non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and ...

OBJETIVO: A fluticasona e o formoterol são efetivos no tratamento da asma. A terapia combinada é o tratamento de escolha quando o corticosteroide isolado não controla a asma. O objetivo deste estudo foi comparar a eficácia e segurança de formulações contendo budesonida/formoterol (BUD/FOR), fluticasona (FLU) e fluticasona/formoterol (FLU/FOR) em cápsula única sobre a função pulmonar em pacientes com asma persistente leve e moderada. MÉTODOS: Estudo de fase III multicêntrico brasileiro, aleatorizado e aberto. A análise primária de eficácia foi a avaliação de não inferioridade da combinação FLU/FOR perante a combinação BUD/FOR em relação ao VEF1 (em L) na visita final. As análises secundárias foram PFE, nível de controle da asma, nível de cortisol sérico, frequência de eventos adversos, aderência ao tratamento e uso adequado do inalador. RESULTADOS: Foram randomizados 243 pacientes nos grupos FLU/FOR (n = 79), BUD/FOR (n = 83) e FLU (n = 81). Após 12 semanas de tratamento, a média da diferença do VEF1 foi de 0,22 L (IC95%: −0,06 a 0,49) entre os grupos FLU/FOR e BUD/FOR e de 0,26 L (IC95%: −0,002 a 0,52) entre os grupos FLU/FOR e FLU. A não inferioridade ficou demonstrada pela diferença de limite inferior do IC95% (−0,06 vs. −0,002). O nível de controle da asma e o PFE foram significativamente maiores nos grupos FLU/FOR e BUD/FOR em comparação com o grupo FLU. Não houve diferenças significativas em relação a adesão, uso do inalador e perfil de segurança entre os grupos. CONCLUSÕES: ...

Assessment of inhaler techniques employed by patients with respiratory diseases in southern Brazil: a population-based study / Avaliação da técnica de utilização de dispositivos inalatórios no tratamento de doenças respiratórias no sul do Brasil: estudo de base populacional

OBJECTIVE: To identify incorrect inhaler techniques employed by patients with respiratory diseases in southern Brazil and to profile the individuals who make such errors. METHODS: This was a population-based, cross-sectional study involving subjects ≥ 10 years of age using metered dose inhalers (MDIs) or dry powder inhalers (DPIs) in 1,722 households in the city of Pelotas, Brazil. RESULTS: We included 110 subjects, who collectively used 94 MDIs and 49 DPIs. The most common errors in the use of MDIs and DPIs were not exhaling prior to inhalation (66% and 47%, respectively), not performing a breath-hold after inhalation (29% and 25%), and not shaking the MDI prior to use (21%). Individuals ≥ 60 years of age more often made such errors. Among the demonstrations of the use of MDIs and DPIs, at least one error was made in 72% and 51%, respectively. Overall, there were errors made in all steps in 11% of the demonstrations, whereas there were no errors made in 13%.Among the individuals who made at least one error, the proportion of those with a low level of education was significantly greater than was that of those with a higher level of education, for MDIs (85% vs. 60%; p = 0.018) and for DPIs (81% vs. 35%; p = 0.010). CONCLUSIONS: In this sample, the most common errors in the use of inhalers were not exhaling prior to inhalation, not performing a breath-hold after inhalation, and not shaking the MDI prior to use. Special attention should be given to education regarding inhaler techniques for patients of lower socioeconomic status and with less formal education, as well as for those of advanced age, because those populations are at a greater risk of committing errors in their use of inhalers. .

OBJETIVO: Conhecer os erros na técnica de uso de dispositivos inalatórios empregada por pacientes com doenças respiratórias no sul do Brasil e o perfil daqueles que possuem dificuldades em realizá-la. MÉTODOS: Estudo transversal, de base populacional, com indivíduos com idade ≥ 10 anos e em uso de inaladores pressurizados (IPrs) ou inaladores de pó (IP) em 1.722 domicílios de Pelotas (RS). RESULTADOS: Foram incluídos 110 indivíduos que utilizavam 94 IPrs e 49 IP. Os principais erros no uso dos IPrs e IP foram não expirar antes da inalação (66% e 47%, respectivamente), não fazer uma pausa inspiratória após a inalação (29% e 25%) e não agitar o IPr antes do uso (21%). Os indivíduos com idade ≥ 60 anos mais frequentemente cometeram erros. Das demonstrações de uso do IPr e IP, respectivamente, 72% e 51% apresentaram ao menos um erro, enquanto 13% das demonstrações foram plenamente corretas e 11% apresentaram erros em todas as fases. A proporção de indivíduos com menor nível de escolaridade que cometeram ao menos um erro foi significativamente maior do que a daqueles com maior nível de escolaridade tanto no uso de IPrs (85% vs. 60%; p = 0,018) quanto no de IPs (81% vs. 35%; p = 0,010). CONCLUSÕES: Nesta amostra, os principais erros cometidos no uso dos inaladores foram não realizar a expiração antes da inalação, não fazer a pausa inspiratória após a inalação e não agitar o IPr. Pacientes com menor nível socioeconômico e educacional, assim como aqueles com idade avançada, merecem especial atenção na educação sobre a realização da técnica inalatória, pois apresentam um maior risco de cometer erros durante o uso dos inaladores. .

Preparation and characterization of tetrandrine-loaded PLGA nanocomposite particles by premix membrane emulsification coupled with spray-drying method / 药学学报

For effective inhalable dry-powder drug delivery, tetrandrine-PLGA (polylactic-co-glycolic acid) nanocomposite particles have been developed to overcome the disadvantages of nanoparticles and microparticles. The primary nanoparticles were prepared by using premix membrane emulsification method. To prepare second particles, they were spray dried. The final particles were characterized by scanning electron microscopy (SEM), dry laser particle size analysis, high performance liquid chromatography (HPLC), X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared analysis (IR) and confocal laser scanning microscope (CLSM). The average size of the primary particles was (337.5 ± 6.2) nm, while that second particles was (3.675 ± 0.16) μm which can be decomposed into primary nanoparticles in water. And the second particles were solid sphere-like with the drug dispersed as armorphous form in them. It is a reference for components delivery to lung in a new form.

Evaluation of Inhaler Techniques among Asthma Patients Seen in Nigeria: An Observational Cross Sectional Study

Background: An Adequate and an effective dose of inhalation drugs can be administered only if the correct inhaler-specific technique is followed by asthma patients. There is paucity of data on this subject among Nigerians and Africans. Aims: This observational study was to assess the inhaler techniques among asthma patients in Nigeria and also to identify the factors related to an inaccurate or poor inhaler use. Subjects and Methods: Consenting asthma patients on inhalers; who attended medical out-patients clinic; of two university hospitals in Nigeria were asked to use their inhalers while an inhaler-administration checklist was used to assess each patients inhaler technique. Information on demographics; asthma symptoms history and history of technique education were obtained. Data was analyzed using standard statistical methods. Results: A total of 140 asthma patients participated out of which 75 were females. All the patients used pressurized metered dose inhalers (pMDI) type; 51 of them used dry powder inhalers (DPI) in addition. For pMDI; 22.1 (31/140) completed all required steps while 37.3 (19/51) did so for DPI (P = 0.04). Patients with higher educational qualification (P 0.01) and those with less frequent asthma symptoms (P 0.01) are more likely to use the pMDI inhalers more accurately while patients who have been taught previously by a Doctor were more likely to use the DPI better. Conclusion: Majority of asthma patients use their inhalers inaccurately. Patient-dependent factors were identified as the cause of incorrect technique of inhaler use. Asthma patients on inhalation medications should have routine assessment of their inhaler technique at every visit and corrected if found to be poor

Preparation, in vitro evaluation of excipient-free dry powder inhalation of extraction of Trollius chinensis / 中国中药杂志

To prepare and evaluate dry powder inhalation (DPI) of extraction of Trollius chinensis Bunge (TCB). Orthodox design was employed to optimize the parameters of spray drying to prepare micronized TCB powder, the DPI was prepared by mixing micronized TCB powder and lactose. The results showed that the fine particle fraction (FPF) and emitted dose (ED) of micronized TCB powder was (21.07 +/- 1.74)%, (75.31 +/- 21.05)%, respectively, and for DPI was (56.4 +/- 2.2)%, (95.9 +/- 3.0)%, respectively. Therefore, the prepared DPI meeted requirements in the Chinese Pharmacopeia, indicating a good application prospect.

Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI) for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI) with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

Desenvolveram-se formulações por inalação de dipropionato de beclometasona, livres de CFC, com o objetivo de tratar a asma profilaticamente. Prepararam-se inaladores de pó seco (DPI) para o dipropionato de beclometasona com diferentes gradações de lactose monoidratada. Estudou-se a influência do transportador e dos excessos de fármaco em relação ao rotulado no desempenho do DPI. Inaladores de dose calibrada (MDI) com propelentes à base de hidrofluoralcanos (HFA) foram formulados com várias doses, excessos de fármaco em relação ao rotulado e diferentes concentrações de álcool. Avaliaram-se as DPI e MDI formuladas por vários métodos oficiais e não oficiais de controle de qualidade. Estudaram-se a influência da superdosagem na liberação da válvula, o efeito dos excessos na dose emitida e a influência do álcool no padrão do spray do MDI. Obtiveram-se a melhor partícula fina e a dose emitida do DPI formulado com proporção de 10:90 de lactose fina:lactose grossa e 20% p/p de excesso. Os estudos em MDI revelaram que 15% de sobredose são requeridos para a liberação efetiva da válvula e 20% de excessos, para a liberação de 100% dos fármacos. Álcool a 5-10% v/v permitiu alcançar ótima dose emitida e fração de partícula fina.

The influence of spray drying process conditions on physical, chemical properties and lung inhaling performance of Panax notoginseng saponins - tanshinone II A composite particles / 药学学报

This study is to report the influence of conditions in spray drying process on physical and chemical properties and lung inhaling performance of Panax notoginseng Saponins - Tanshinone II A composite particles. According to the physical and chemical properties of the two types of components within the composite particles, three solvent systems were selected including ethanol, ethanol : acetone (9 : 1, v/v) and ethanol : acetone (4 : 1, v/v), and three inlet temperature: 110 degrees C, 120 degrees C, 130 degrees C to prepare seven different composite particle samples; each sample was characterized using laser diffraction, scanning electron microscopy (SEM), dynamic vapour sorption (DVS) and atomic force microscope (AFM), and their aerodynamic behavior was evaluated by a Next Generation Impactor (NGI). The results indicate that under the conditions of using the mixed solvent system of ethanol--acetone volume ratio of 9 : 1, and the inlet temperature of 110 degrees C, the resulting composite particles showed rough surface, with more tanshinone II A distributing in the outer layer, such composite particles have the best lung inhaling performance and the fine particle fraction (FPF) close to 60%. Finally it is concluded that by adjusting the conditions in co-spray drying process, the distribution amount and existence form of tanshinone II A in the outer layer of the particles can be changed so that to enhance lung inhaling performance of the drug composite particles.

Equivalência farmacêutica da formulação combinada de budesonida e formoterol em cápsula única com dispositivo inalador de pó / Pharmaceutical equivalence of the combination formulation of budesonide and formoterol in a single capsule with a dry powder inhaler

OBJETIVO: Avaliar a equivalência farmacêutica da formulação teste (associação fixa de budesonida e fumarato de formoterol em cápsula única dispensada com o dispositivo Aerocaps®) em relação a uma formulação referência (budesonida e fumarato de formoterol em duas cápsulas distintas dispensadas com o dispositivo Aerolizer®). MÉTODOS: Estudo in vitro no qual foram realizadas identificação/quantificação dos ingredientes ativos por HPCL e determinação da uniformidade da dose liberada e da distribuição aerodinâmica das partículas das formulações teste e referência. RESULTADOS: Na formulação teste, o teor de budesonida e de formoterol foi de 111,0% e 103,8%, respectivamente, enquanto esse foi de 110,5% e 104,5% na formulação referência. Na formulação teste, a uniformidade das doses de budesonida e de formoterol foi de 293,2 µg e 10,2 µg, respectivamente, enquanto essa foi de 353,0 µg e 11,1 µg na formulação referência. Esses resultados estão dentro da faixa recomendada para esse tipo de formulação (75-125% da dose rotulada). A fração de partículas finas (< 5 µm) para budesonida e formoterol foi de, respectivamente, 45% e 56% na formulação teste e de 54% e 52% na formulação referência. CONCLUSÕES: As formulações teste e referência apresentaram níveis de ingredientes ativos, uniformidade de doses e diâmetros aerodinâmicos apropriados ao uso com seus respectivos dispositivos inalatórios de pó.

OBJECTIVE: To evaluate the pharmaceutical equivalence of a test formulation (fixed-dose combination of budesonide and formoterol fumarate in a single capsule dispensed in an Aerocaps® inhaler) in relation to a reference formulation (budesonide and formoterol fumarate in two separate capsules dispensed in an Aerolizer® inhaler). METHODS: This was an in vitro study in which we performed the identification/quantification of the active ingredients by HPLC and determined dose uniformity and aerodynamic particle size distribution in the test and reference formulations. RESULTS: In the test formulation, the content of budesonide and formoterol was 111.0% and 103.8%, respectively, compared with 110.5% and 104.5%, respectively, in the reference formulation. In the test formulation, dose uniformity regarding budesonide and formoterol was 293.2 µg and 10.2 µg, respectively, whereas it was 353.0 µg and 11.1 µg in the reference formulation. These values are within the recommended range for this type of formulation (75-125% of the labeled dose). The fine particle fraction (< 5 µm) for budesonide and formoterol was 45% and 56%, respectively, in the test formulation and 54% and 52%, respectively, in the reference formulation. CONCLUSIONS: For both of the formulations tested, the levels of active ingredients, dose uniformity, and aerodynamic diameters were suitable for use with the respective dry powder inhalers.

Eficácia e segurança de dois inaladores de pó seco usados para a aplicação de furoato de mometasona em pacientes com asma / Efficacy and safety of two dry-powder inhalers for the administration of mometasone furoate in asthma patients

OBJETIVO: O furoato de mometasona (FM) é um novo corticosteroide inalatório sintético potente. Internacionalmente, o FM é fornecido em um inalador de pó seco que permite sua administração em múltiplas doses. Para se obter uma preparação com melhor relação custo-eficácia, foram desenvolvidas no Brasil formulações de FM em cápsulas de pó seco para serem administradas em dose única. O presente estudo teve como objetivo avaliar a eficácia e a segurança dos dois inaladores usados para a administração de FM em pacientes asmáticos. MÉTODOS: Estudo clínico, aberto, comparativo, paralelo e multicêntrico com 74 adultos portadores de asma persistente e moderada, randomizados em dois grupos para receber FM em uma dose de aproximadamente 400 µg, fornecida por um inalador de dose múltipla ou pelo novo inalador de dose única, uma vez ao dia durante 60 dias. RESULTADOS: Não foram observadas diferenças significantes entre os dois grupos estudados nos desfechos primários (VEF1 e frequência do uso de medicação de resgate) ou nos desfechos secundários (PFE matinal, tolerabilidade e segurança, essa última avaliada pelo estudo do eixo hipotálamo-hipófise-adrenal). CONCLUSÕES: A administração de FM com o novo inalador de dose única desenvolvido no Brasil tem eficácia e segurança comparáveis à administração com o inalador de dose múltipla no tratamento de pacientes asmáticos.

OBJECTIVE: Mometasone furoate (MF) is a new, potent synthetic inhaled corticosteroid. Worldwide, MF is administered via a dry-powder inhaler that contains multiple doses. As a preparation that would be more cost-effective, single-dose MF capsules were developed in Brazil. The objective of the present study was to evaluate the efficacy and safety of the two inhalers for MF administration in patients with asthma. METHODS: A randomized, multicenter, open-label, parallel-group clinical trial involving 74 adult patients with moderate, persistent asthma who were randomized into two groups to receive approximately 400 µg of MF once a day for 60 days, either via the multiple-dose inhaler or via the newly developed single-dose inhaler. RESULTS: No significant differences were observed between the two groups regarding the primary endpoints (FEV1 and rescue medication use) or the secondary endpoints (morning PEF, tolerability, and safety, the last as assessed on the basis of hypothalamic-pituitary-adrenal axis function). CONCLUSIONS: The use of the single-dose inhaler developed in Brazil for MF administration is as effective and safe as is that of a standard inhaler in the treatment of patients with asthma.

A novel pulmonary delivery system--dry powder inhalers / 药学学报

Dry powder inhalers (DPIs) have received considerable attention because of their propellant-free composition and stability. DPIs include the DPI devices and inhalation powders. The purpose of this review is to address the development of the DPIs, including the mechanisms of absorption, the products, the devices, the preparation technology, and the characteristics.

Evaluation of the inhalation performance in patients with asthma / 천식및알레르기

BACKGROUND: The proper use of inhaler drugs is critical in the management of chronic asthma. In this study, we investigated the inhalation performance of asthmatic patients and effectiveness of the regular education of inhalation technique. METHODS: The 145 asthmatic patients who had been educated the inhaler technique for more than 3 times were enrolled. The inhalation performance of each patient was scored using a checklist form (9 items for metered dose inhaler [MDI], 4 items for dry powder inhaler [DPI]) whenever they visited the clinic. Clinical characteristics affecting inhalation performance were evaluated in the groups using each type of inhaler. RESULT: In MDI, the mean initial performance score was significantly low when the patients were female sex, aged patients (>65 years old), or had lower educational backgrounds. Some items of the checklist, which include tilting head back, placing the mouthpiece with a distance from lips, continuing deep inspiration, and holding breath after inhalation for 10 seconds, were improperly performed in about 25% of the MDI users. No significant change was observed in the final performance scores assessed after intensive repeated education for proper inhalation technique of MDI. In DPI, the mean initial performance score was significantly low in the patients with old age (>65 years old) or lower educational backgrounds. The final performance scores were significantly improved after the repeated education for proper use of DPI inhalation in contrast to MDI. CONCLUSION: For the effective management of asthma, it may be important to choose proper type of inhaler with consideration of individual characteristics of the patients. The evaluation of inhalation performance and regular education of inhalation technique could be useful to maintain and improve the effective use of inhaler, especially in DPI.