Uso de inhaladores para la enfermedad pulmonar obstructiva crónica en un grupo de pacientes colombianos

Introducción: En Colombia son escasos los datos sobre el uso de los inhaladores en pacientes con EPOC. Objetivo: Describir la técnica de uso de inhaladores de dosis medida y polvo seco en pacientes de un hospital colombiano. Materiales y métodos: Estudio descriptivo en pacientes mayores de 40 años con EPOC atendidos en un hospital en La Virginia, Risaralda, Colombia, entre el 1 de septiembre de 2019 al 31 de enero de 2020. La unidad de análisis fueron los pacientes. Se incluyeron variables sociodemográficas, clínicas y lista de chequeo para uso de inhaladores. Se aplicaron frecuencias y proporciones para variables discretas, estadísticas de tendencia central y dispersión para variables continuas. Resultados: Se incluyeron 104 pacientes con edad media de 73,6 ± 10,1 años; 57 eran mujeres (54,8 %). Además, 48 pacientes estaban clasificados como GOLD-D (46,2 %). Igualmente, 89 pacientes manifestaron haber recibido educación sobre el uso de broncodilatadores (85,6 %). Los más frecuentes fueron los inhaladores de dosis medida (DM) en 95 casos (91,3 %), seguido de los de polvo seco unidosis (7,7 %). Así mismo, 37 pacientes que usaron DM sin inhalocámara (35,6 %) no cumplieron los pasos de la lista de chequeo. En el sistema multidosis, el más realizado fue cerrar de manera adecuada el inhalador y el menos ejecutado, expulsar el aire lentamente evitando hacerlo cerca del inhalador (n = 6; 5,7 %). Discusión: Se lograron describir las características de la técnica de uso de los inhaladores en pacientes con EPOC. A pesar de que ningún paciente logró utilizar el inhalador de forma "perfecta", la mayoría han recibido educación por parte de los profesionales de la salud. Conclusión: Un alto porcentaje de pacientes usa inadecuadamente los dispositivos para suministrar los broncodilatadores. Esto puede impactar negativamente en el control de la enfermedad.

Introduction: In Colombia, there is limited data on the use of inhalers in patients with COPD. Objective: The objective was to describe the technique of using metered-dose inhalers and dry powder in patients in a Colombian hospital. Methods: Observational, descriptive study of patients over 40 years of age with COPD, treated in a hospital in La Virginia, Risaralda, Colombia, between September 1st, 2019 and January 31st, 2020. The unit of analysis were patients in consultation. Sociodemographic and clinical variables, and a checklist for use of inhalers were included. Frequencies and proportions were applied for discrete variables, statistics of central tendency and dispersion for continuous variables. Results: A total of 104 patients with an average age of 73.6 ± 10.1 years were included; 57 were women (54.8%). In addition, 48 patients were classified as GOLD-D (46.2%). Similarly, 89 patients reported having received education on the use of bronchodilators (85.6%). The most common were metered-dose (MD) inhalers in 95 cases (91.3%), followed by single-dose dry powder inhalers in eight patients (7.7%). Likewise, 37 patients who used DM without inhalochamber (35.6%) did not comply with the steps of the checklist. In the multidose system, the most performed was to properly close the inhaler and the least performed was to expel the air slowly, avoiding doing so near the inhaler (n=6; 5.7%). Discussion: The characteristics of the technique of using inhalers in patients with COPD were described. Although no patient was able to use the inhaler "perfectly", most have received education from health professionals. Conclusion: A high percentage of patients misuse the devices to deliver bronchodilators. This can negatively impact the control of the disease.

Índices de internações, de mortalidade e de custos associados à doença pulmonar obstrutiva crônica (DPOC) no Distrito Federal após mudança do Protocolo Estadual de 2018 ­ Dados do mundo real / Hospitalization, mortality rates and costs associated with chronic obstructive pulmonary disease (COPD) in Distrito Federal, Brazil, before and after the change in 2018 state COPD protocol version ­ Real-world data

Objetivo: Avaliar os índices de hospitalização, mortalidade e custos associados à doença pulmonar obstrutiva crônica (DPOC) após mudança do Protocolo de Atenção à Saúde da Secretaria do Distrito Federal (SES-DF) em 2018 por um medicamento da mesma classe terapêutica, porém em dispositivo inalatório diferente. Métodos: Foi realizado um estudo observacional, transversal, em uma coorte de pacientes adultos internados em dois períodos específicos: gosto/2017 a julho/2018 (MAT 1 ­ vigência do Protocolo antigo) e agosto/2018 a julho/2019 (MAT 2 ­ vigência do novo Protocolo). Foram avaliados pacientes internados com diagnóstico principal de DPOC de acordo com a Classificação Estatística Internacional de Doenças e Problemas Relacionados com a Saúde Versão 10 (CID-10) estabelecida pelo protocolo de atenção à saúde e registrada no Datasus. Os desfechos avaliados foram número de internações, mortalidade e custos totais associados à internação por DPOC. Resultados: Após análise dos dados relacionados à DPOC, a comparação entre MAT 1 (agosto/2017 a julho/2018) e MAT 2 (agosto/2018 a julho/2019) resultou no aumento na ocorrência de importantes desfechos: +131,3% no número de internações com passagens em unidade de terapia intensiva (UTI) (n = 16 no MAT 1 vs. n = 37 no MAT 2, p < 0,01), +101,0% na frequência de internações com passagem em UTI sobre o total de internações (2,4% no MAT 1 vs. 4,8% no MAT 2, p = 0,01), +566,7% nos óbitos de pacientes internados em UTI (n = 3 no MAT 1 vs. n = 20 no MAT 2, p < 0,01) e +52,9% nos custos totais de internação (R$ 828.761 no MAT 1 vs. R$ 1.267.318 no MAT 2, p = 0,03). Conclusão: Durante os períodos analisados, houve aumento no uso de UTI, na mortalidade em UTI e nos custos totais relacionados à DPOC. A atualização do protocolo alterou tanto o dispositivo inalatório (névoa suave para pó seco) quanto a molécula (tiotrópio para glicopirrônio) e poderia ser um dos fatores responsáveis por esses desfechos, no entanto as limitações desta análise observacional não podem determinar um impacto causal da mudança do protocolo, pois outras variáveis também podem ter levado às diferenças descritas.

Objective: Evaluate the rates of hospitalization, mortality and costs associated with chronic obstructive pulmonary disease (COPD) before and after the change in COPD Treatment Protocol of State Health Secretariat of Distrito Federal (SES-DF). Methods: An observational, cross-sectional study was conducted in a cohort of hospitalized adult patients in two specific periods: August/2017 to July/2018 (MAT 1 ­ old version of Protocol in place) and August/2018 to July/2019 (MAT 2 - after the new Protocol version). Hospitalized patients with COPD as primary diagnosis according to International Statistical Classification of Diseases and Related Health Problems Version 10 (ICD-10) established by COPD Treatment Protocol and registered in DATASUS database were evaluated. The outcomes assessed were the number of hospitalizations, mortality and total costs ssociated with COPD hospitalizations. Results: After analyzing the data related to COPD, the comparison between MAT 1 (August/2017 to July/2018) and MAT 2 (August/2018 to July/2019) periods resulted in an increase in the occurrence of relevant outcomes: +131.3% in the number of hospitalizations with intensive care unit (ICU) admissions (n = 16 in MAT 1 vs. n = 37 in MAT 2, p < 0.01), +101.0% in the frequency of hospitalizations with ICU admissions over total number of hospitalizations (2.4% in MAT 1 vs. 4.8% in MAT 2, p = 0.01), +566.7% in deaths of patients admitted in ICU (n = 3 in MAT 1 vs. n = 20 in MAT 2, p < 0.01), +52.9% in total costs associated with COPD hospitalizations (R$ 828,761 in MAT 1 vs. R$ 1,267,318 in MAT 2, p = 0.03). Conclusion: During the analyzed periods, an increase in ICU usage, mortality in ICU and total costs related to COPD was observed. The update in the protocol switched the inhaler device (from soft mist to dry powder) and also the molecule (tiotropium to glycopyrronium) and could be potentially one of the factors responsible for these endpoints, however the limitations of this observational analysis cannot determine a causal impact of the protocol change as other variables could also have led to the differences described.

Inhaloterapia: recomendaciones para Argentina 2021 / Inhalotherapy: recommendations for Argentina 2021

Resumen En las últimas décadas ha habido un importante desarrollo de dispositivos inhalados (DI) que permiten aumentar la eficacia de las drogas y disminuir los eventos adversos. Su correcto uso es de fundamental importancia para el control de las enfermedades respiratorias obstructivas. En la Argentina no existen recomendaciones locales sobre el uso de los DI. Se revisó la base biofísica, indicación, ventajas y limitaciones, técnica de correcto uso, errores frecuentes, mantenimiento y limpieza de cada DI. El uso de nebulizaciones ha quedado restringido a la administración de drogas que no están disponibles en otros DI (ejemplo: tratamiento de fibrosis quística), o ante la falla de los otros DI. No deben ser usados durante la pandemia de SARS-CoV2. Los inhaladores de dosis medida (aerosol) deben ser indicados siempre con aerocámaras (AC), las que reducen la incidencia de eventos adversos y aumentan el depósito de la droga en el pulmón. Son los dispositivos de elección junto a los inhaladores de polvo seco. Los aerosoles se deben usar en pacientes que no generan flujos inspiratorios altos. Los inhaladores de polvo seco deben recomendarse en aquellos que pueden realizar flujos inspiratorios enérgicos. Se revisaron los diferentes DI en fibrosis quística y en pacientes con asistencia respiratoria mecánica. La elección del DI dependerá de varios factores: situación clínica, edad, experiencia previa, preferencia del paciente, disponibilidad de la droga y entrenamiento alcanzado con el correcto uso.

Abstract Last decades, a broad spectrum of inhaled devices (ID) had been developed to enhance efficacy and reduce adverse events. The correct use of IDs is a critical issue for controlling obstructive respiratory diseases. There is no recommendation on inhalation therapy in Argentina. This document aims to issue local recommendations about the prescription of IDs. Each device was reviewed regarding biophysical laws, indication, strength, limitations, correct technique of use, frequent mistakes, and device cleaning and maintenance. Nebulization should be restricted to drugs that are not available in other IDs (for example, for treatment of cystic fibrosis) or where other devices fail. Nebulization is not recommended during the SARS-CoV2 pandemic. A metered-dose inhaler must always be used with an aerochamber. Aerochambers reduce the incidence of adverse events and improve lung deposition. Metered-dose inhalers must be prescribed to patients who cannot generate a high inspiratory flow and dry powders to those who can generate an energetic inspiratory flow. We reviewed the use of different IDs in patients with cystic fibrosis and under mechanical ventilation. The individual choice of an ID will be based on several variables like clinical status, age, previous experience, patient preference, drug availability, and correct use of the device.

Avaliação da técnica inalatória em atendimentos de primeira consulta em ambulatório de asma de hospital terciário / Evaluation of the inhalation technique in first care visits in an asthma outpatient clinic at a tertiary hospital

Introdução: Técnica inalatória (TI) correta é fundamental para o controle da asma. Objetivo: Avaliar TI de pacientes em atendimento de primeira consulta em um ambulatório de asma. Métodos: Estudo observacional transversal com amostra de conveniência de asmáticos com idade ≥ 18 anos, em primeira consulta no ambulatório de asma do Hospital Universitário Antonio Pedro (HUAP) da Universidade Federal Fluminense e em uso de medicamentos disponíveis para uso em aerossol dosimetrado (AD), Aerocaps, Aerolizer ou Diskus. Participantes preencheram questionário com dados sociodemográficos, avaliação de controle da doença segundo o documento GINA, existência de orientações médicas para uso dos dispostivos inalatórios (DI), tempo de uso de DI e especialidade do médico encaminhador. A TI era considerada apropriada quando todas as etapas foram realizadas corretamente baseando-se nas bulas das medicações e foram demonstradas com os DI vazios. Resultados: Entre os 51 pacientes incluídos, 43 (84,3%) tinham TI incorretas e 4 (7,8%) apresentavam asma controlada. Trinta e cinco (70%) referiram orientação prévia quanto ao uso do DI. A TI correta associou-se com tempo de uso maior que 2 anos (p=0,006) e uso de DI de pó seco em detrimento de AD (p=0,019). Conclusão: Somente 16% dos pacientes encaminhados ao ambulatório da pneumologia específico de asma, de um hospital terciário, tinham a TI correta em sua primeira consulta e a quase totalidade não tinha a asma controlada. Atenção deve ser dada sempre a supervisão da qualidade da TI, principalmente dos usuários de AD e dos que usam seus DI há menos de 2 anos.

Introduction: Correct inhalation technique (IT) is essential for asthma control. Objective: To evaluate the IT of patients making their first visit to the asthma outpatient clinic. Methods: Cross-sectional observational study with a convenience sample of asthmatics aged ≥ 18 years, in their first visit to the asthma outpatient clinic of the Hospital Universitário Antonio Pedro (HUAP) of the Universidade Federal Fluminense and using medications available in metered-dose aerosol (DA) , Aerocaps, Aerolizer or Diskus. Participants completed a questionnaire with sociodemographic data, assessment of disease control according to the GINA document, existence of medical guidelines for the use of inhalation devices (IDs), length of ID use, and specialty of the refer-ring clinician. IT was considered appropriate when all steps were performed correctly based on medication package inserts and were demonstrated with empty IDs. Results: Among the 51 patients included, 43 (84.3%) had incorrect IT and 4 (7.8%) had controlled asthma. Thirty-five (70%) reported previous guidance regarding the use of ID. Correct IT was associated with time of use greater than 2 years (p=0.006) and use of dry powder ID rather than DA (p=0.019). Conclusion: Only 16% of the patients referred to the asthma-specific pulmonology outpatient clinic of a tertiary hospital had the correct IT at their first appointment and almost all of them did not have controlled asthma. Attention should always be given to the supervision of IT quality, especially for DA users and those who have been using their ID for less than 2 years.

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.

Preparation and in vitro Release Property Study of Curcumin Dry Powder Inhalation Loaded by Nanoporous Flower-shaped Lactose / 中国药房

OBJECTIVE：To preparea novel Curcumin （Cur）dry powder inhalation （DPI）loaded by nanoporous flower-shaped lactose（FL），and to provide a safe and effective intrapulmonary drug delivery method for the therapy of chronic obstructive pulmonary disease with insoluble drugs. METHODS ：FL-loaded Cur （Cur-FL） compound powder was prepared by solution adsorption method. Using drug-loading amount and adsorption rate as indicators ，single-factor experiment was used to optimize Cur concentration，Cur-FL ratio （m/m）and adsorption time so as to determine the optimal preparation technology for Cur-FL compound powder. Fourier transform infrared spectroscopy ，scanning electron microscope and differential scanning calorimetry were used to characterize the physical and chemical properties of Cur-FL compound powder prepared with optimal technology. The water content and aerodynamic properties were determined ；in vitro drug release behavior was investigated by simulating the environment of artificial lung fluid. RESULTS ：The optimal preparation technology of Cur-FL compound powder was Cur concentration of 5 mg/mL，Cur-FL ratio of 1 ∶ 4，adsorption time of 1 h. The drug-loading amount of compound powder was （23.37±0.43）％，the encapsulation rate was （91.64±0.44）％，and the adsorption rate was （30.50±0.72）％. Cur-FL particles were flower shaped ；Cur was physically adsorbed in the pores of FL without chemical changes. The bulk density of Cur-FL compound was （0.21±0.02） g/cm3，tap density was （0.33±0.01）g/cm3，angle of repose was（24.07±0.31）°，average particle size was （3.96±0.80） μm，aerodynamic particle size was （3.33±0.99）μm，water content was （5.63 ±0.24）％，emptying rate was （92.53± 0.87）％，and deposition rate of effective parts in vitro was son- （45.93 ± 1.77）％ . Its 24 h solubility in artificial lung gwen.tan@csu.edu.cn fluid [（358.93±1.67）μg/mL] were 3.28 times of Cur ，48 h cumulative release ratesin in vitro （90.21％）were 1.63 times of Cur ，but Cur+FL physical mixture could not improve the solubility and release of Cur in artificial lung fluid. CONCLUSIONS ：Cur-FL compound powder has good in vitro release property ，and its powder properties ，solubility，water content ，fluidity and aerodynamic properties meet the requirements of DPI in Chinese Pharmacopoeia.

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.

Assessment of Errors during Inhaler Usage among Asthma and COPD Patients.

BACKGROUND The cornerstone therapy for respiratory diseases is drugs for inhalation. Effectiveness of inhalers can be influenced by factors such as gender, age, educational status, and type of inhaler used and correct inhalation technique. The aim of this study is to provide information about common errors in technique that occur during inhalation.METHODSMale and female patients who met the inclusion criteria (age 18 - 80) years, using inhalers particularly MDI and DPI were included in the study. The study patients were asked to perform inhalation technique and the errors in technique that occur during inhalation were recorded. The sample size was 150 and duration of study was 6 months.RESULTSThe common errors during the use of inhalers included, no exhalation before inhalation, no breath hold, and absence of proper washing of mouth after inhalation. Among the 86 MDI users, no exhalation before inhalation (n=50), no breath hold (n=35) and absence of proper washing of mouth after inhalation (n=21). For the 64 patients using DPI, no exhalation before inhalation (n=68), no breath hold (n=51) and absence of proper washing of mouth after inhalation (n=35).

Preparation of berberine hydrochloride dry powder inhalation and its effect on Staphylococcus aureus pneumonia / 中草药

Objective: To prepare berberine hydrochloride dry powder inhalation, and investigate its pharmacological effect on Staphylococcus aureus pneumonia after pulmonary administration. Methods: Berberine hydrochloride dry powder by spray drying and the experimental conditions was optimized by orthogonal experiment. The lung deposition, fluidity and appearance were characterized. The pharmacodynamic effects of the preparations on S. aureus pneumonia were performed with SD rats. Results: A berberine hydrochloride dry powder was prepared at an inlet temperature of 130 ℃ with a gas volume flow of 610 L/h and a feed volume flow of 3 mL/min. The berberine hydrochloride dry powder had a lung deposition rate (FPF) of 76.4% and an aerodynamic diameter of 4.61 μm. The stability index (SI) ≈ 1, the aeration energy ratio (AR) = 1.76 > 1, and the inflation energy (AE10) = 2.1 mJ < 10 mJ. Through the pharmacodynamic evaluation of S. aureus, we can know that the berberine hydrochloride dry powder inhalation effectively improved the pathological state of pneumonia rats, and significantly reduced (P < 0.05) the number of WBC, neutrophils, and the expression of inflammatory factors (TNF-α, IL-1β, and IL-6) in pneumonia rats. Conclusion: Berberine hydrochloride dry powder inhalation can directly reach the lesion site through pulmonary administration, so it has significant therapeutic effect on S. aureus pneumonia.

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.

Patients’ sensory perception and satisfaction with use of metered dose inhalers and dry powder inhalers in moderate persistent asthma

Background: Inhalers containing corticosteroid and a long acting ?2 agonist (LABA) are widely used in asthma treatment. This study assessed the patient sensory perception and satisfaction of budesonide/formoterol fixed dose combination by pressurized metered dose inhalers (pMDI) with spacer and dry powder inhalers (DPI) in patients of moderate persistent asthma.Methods: This was a 6 week prospective, randomized, open label, comparative, parallel group clinical study. All patients had a forced expiratory volume in 1 second (FEV1) of 60-80% predicted normal. The patients were assessed for sensory perception and satisfaction in group I (pMDIs with spacers) and group II (DPIs) using patient evaluation questionnaire (PEQ) and patient satisfaction and preference questionnaire (PASAPQ) at the end of 6th week.Results: In PEQ, statistical analysis of the mean attribute ratings showed that both the devices were easy to use by patients. More medication was felt reaching throat using DPIs. Patients on DPI liked the taste and felt it to be less strong than patients on pMDIs. The overall liking was statistically comparable in two groups. In PASAPQ, the patients on DPI group were very satisfied with the treatment than pMDI (p<0.05).Conclusion: Overall liking of both DPIs and pMDIs was comparable and patients on DPI were satisfied more with the treatment device. Patient sensory perception and satisfaction may be taken into account in selecting device to improve compliance to treatment.

Formula Optimization of Rifampicin Dry Powder Inhalation with Chitosan-Xanthan Carrier Using Response Surface Methodology

This study was aimed to obtain an optimum formula of rifampicin dry powder inhalation (DPI) with chitosan-xanthan(CX) as a carrier by spray drying method using response surface methodology (RSM). Fourteen experimental formulaswere designed statistically by Box Behnken method by varying three parameters namely concentration of CX solution,rifampicin/CX ratio, and inlet temperature of the spray dryer. The entrapment efficiency (EE), particle size, and drugrelease in pH 7.4 (pulmonary condition) and pH 4.5 (pulmonary macrophages condition) of the rifampicin DPI werecharacterized. The optimum formula of rifampicin DPI was obtained using Design Expert software. The obtained DPIfrom those 14 formulas possessed EE of 112.00–149.08% and average particle sizes of 0.599–5.506 µm. Rifampicinrelease in phosphate buffer medium pH 7.4 was 6.54%–22.95% and in pH 4.5 was 12.02–48.60%. The DesignExpert predicted that the optimum formula would be obtained with a concentration of CX solution of 0.5%, a ratio ofrifampicin to CX 1:1, and inlet temperature of the spray dryer at 143°C. The optimized formula produced a rifampicinDPI with EE of 108.9%, the particle size of 1.177 µm, and the rifampicin release of 14.49% (at pH 7.4) and of 37.97%(at pH 4.5).

Drug Release in vitro and Acute Toxicity in vivo of Curcumin Solid Lipid Nanoparticles Dry Powder Inhaler and Its Effects on Inflammatory Response in Asthmatic Model Mice / 中国药房

OBJECTIVE： To study in vitro drug release and acute toxicity in vivo of Curcumin （Cur） solid lipid nanoparticles （SLN） dry powder inhaler （DPI） and its effects of inflammatory response in asthmatic model mice. METHODS： Cur-SLN-DPI was obtained with spray-drying method by micronizing the Cur-SLN suspension prepared by the microemulsion method and thoroughly mixing with lactose （200 mesh） etc. The drug release in vitro was investigated by dynamic membrane dialysis. Accumulative release rates （Q） of Cur raw material， Cur-SLN and Cur-SLN-DPI in 3 kinds of release mediums [phosphate buffer solution （PBS， pH 7.4） containing 1.0％ sodium dodecyl sulfate （SDS）， PBS （pH 7.4） containing 0.2％ tween 80， normal saline-20％ ethanol solution] were compared 5， 15， 30 min and 1， 1.5， 3， 6， 8， 12， 18， 24， 36， 48 h after releasing. Drug release model was fitted. The effects of intravenous injection of maximal dose 2 000 mg/kg Cur-SLN-DPI via tail vein on KM mice were investigated by acute toxicity test. KM mice were randomly divided into normal control group， model group， positive drug group （budesonide 3 mg）， Cur-SLN-DPI high-dose and low-dose groups （100， 50 mg/kg）， with 7 mice in each group. The ovalbumin （OVA） was used as sensitizer to induce asthma model； the model mice were given relevant medicine with aerosol administration 30 min before aerosol administration of OVA inducing asthma on Monday， Wednesday and Friday per week， for consecutive 3 weeks. Within 24 h after last induction， total number of leukocyte， the number of lymphocyte， neutrophil and eosinophil were counted in broncho alveolar lavage fluid （BALF）； the pathological changes of bronchus and lung tissue were observed. RESULTS： Compared with Cur raw material， Cur-SLN and Cur-SLN-DPI showed good sustained-release effect， and Cur-SLN-DPI had more stable sustained release in 3 kinds of release mediums. The characteristics of drug release conformed to the Weibull model. Intravenous injection of 2 000 mg/kg Cur-SLN-DPI via tail vein had no significant acute toxicity in mice. Compared with normal control group， total number of leukocyte， the number of lymphocyte， neutrophil and eosinophil were increased significantly （P＜0.01）； bronchial mucosal epithelium was covered with pseudostratified ciliated columnar cells， with severe infiltration of inflammatory cells， pulmonary congestion and moderate interstitial pneumonia. Compared with model group， the number of above cells in BALF of mice were decreased significantly in administration group （P＜0.01）； tracheal lesions of mice were improved in Cur-SLN-DPI low-dose and high-dose groups； pulmonary congestion of them were alleviated， and that of high-dose group was alleviated more significantly. CONCLUSIONS： Cur-SLN-DPI shows sustained-release effect in vitro and has no obvious acute toxicity to mice. Cur-SLN-DPI can improve the inflammatory response of the airway and the degree of pulmonary congestion in asthmatic model mice.

Incorrect use of inhalation devices among patients with bronchial asthma. A hospital-based cross-sectional study in Rio de Janeiro, Brazil

ABSTRACT CONTEXT AND OBJECTIVE: Treatment of asthma implies inhalation of specific drugs to reach high concentrations in the respiratory tree and ensure low drug bioavailability and few adverse effects. This study aimed to evaluate the effectiveness of the inhalation technique among outpatients with asthma. DESIGN AND SETTING: Tertiary-care hospital-based cross-sectional study in Rio de Janeiro. METHODS: We evaluated inhalation practices in a convenience sample. A questionnaire was used to investigate sociodemographic data and assess disease control level, duration of use of the inhalation device, length of treatment and previous instructions provided by the prescribing physician. Patients demonstrated their inhalation technique using empty devices, and their technique was considered correct when all steps were appropriately performed or when errors did not interfere with the treatment outcome. RESULTS: Among the 71 participants, 53 (74.7%) had been using the same inhaler device for at least two years and 41 (57.8%) had been under treatment for two years or more. Twelve (17.1%) said that they had been taught once and 57 (81.4%) at least twice, while one (1.4%) reported not having received any guidance regarding use of inhaler devices. Eighteen patients (25.3%) presented controlled asthma and 28 (39.5%) performed the inhalation technique correctly. Incorrect technique was associated with fewer evaluations of the inhalation technique (P =0.04) and uncontrolled asthma (P = 0.01). CONCLUSIONS: Less than half of the sample performed the inhalation technique correctly. Incorrect inhalation technique was related to lower number of evaluations of the use of the inhalation device and uncontrolled asthma.

Prescription pattern among patients having mild to moderate bronchial asthma using metered dose inhaler and dry powder inhaler in tertiary hospital in western india

Background: Bronchial asthma is a syndrome characterized by airflow obstruction that manifests as shortness of breath, wheezing and cough. The treatment is tailored according to the severity of the disease. The drugs used for treatment of bronchial asthma include inhaled corticosteroids, beta-2 agonists, methylxanthines, leukotriene antagonists and mast cell stabilizers. Despite the availability of all these drugs, which are recommended for the treatment, not every patient achieves complete control of the disease. The reason behind this could be irrational prescribing of drugs for the treatment and errors in the technique of using inhaler devices. Though rational prescribing of drugs and correct technique for the use of inhaler can be improved by proper training of target population, but there is paucity of such data in our country.Methods: This study was planned to monitor prescription pattern and errors in use of inhalation devices, in patients diagnosed as cases of mild to moderate bronchial asthma, attending Out Patient Department (OPD) of respiratory medicine of a tertiary hospital. A total of 207 patients were recruited and their prescription pattern and inhalation technique were assessed.Results: The study showed that inhaled short acting ?2-agonists and inhaled corticosteroids were the most commonly used drug groups, which were prescribed to all the patients in the study, followed by long acting ?2-agonists, leukotriene antagonists and methylxanthines in decreasing order.Conclusions: As a conclusion, the treating physicians were prescribing according to the laid down guidelines. It is concluded that such studies should be periodically done to ensure the adherence to the treatment guidelines.

Formula Optimization of Bromhexine Hydrochloride Dry Powder Inhalations by Central Composite Design-response Surface Methodology / 中国药师

Objective: To optimize the formula of bromhexine hydrochloride dry powder inhalations (BH DPIs). Methods: BH DPIs were prepared by freezing-drying combined with an air-jet milling method. Three factors, including the weights of mannitol (X1), leucine (X2) and poloxamer 188 (X3) in the formula were known to be associated with the quality of BH DPIs. A central composite design was used to investigate the effects of the three factors on the response angle (Y1), fine particle fraction (FPF, Y3) and aerody-namic diameter (Y4). Response surface and overlay contour plot were delineated according to the best-fit mathematic models. Opti-mum formula was selected by overlay contour plot. Results: The quantitative relationships between the three factors and the three re-sponses were obtained. The optimal formula was mannitol﹕leucine﹕poloxamer 188 (2. 4: 2. 22: 0. 05) in the excipients. The pre-dicted and observed values of the optimum formula were similar. Conclusion: The multi-objective simultaneous optimization of the for-mula of BH DPIs is achieved by central composite design-response surface methodology.

Study on the Quality and Stability of Bromhexine Hydrochloride Dry Powder Inhalations / 中国药师

Objective: To study the quality and stability of bromhexine hydrochloride dry powder inhalations (BH DPIs). Meth-ods: BH DPIs were prepared by freeze-drying with an air jetting method. The humidity and critical relative moisture of the inhalations were investigated. The aerodynamic particle size ( Dae) and water content were also analyzed. The powder morphology was observed under a scanning electronic microscope. The fine particle fraction (FPF) and delivered dose uniformity (DDU) of BH DPIs were de-termined. The stability of the inhalations was determined by accelerated testing and long-term testing. Results: The prepared BH DPIs exhibited the following properties: the critical relative humidity was 65% ; Dae was <5 μm; the water content was less than 2% ; FPF was >30% ,and DDU was good according to the requirement of Chinese Pharmacopoeia. The accelerated testing and long-term testing both indicated promising stability of BH DPIs. Conclusion: Bromhexine hydrochloride dry powder inhalations are stable, and suitable for the use in pulmonary delivery system.

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.

Study on matrix sustained release tablets of brucine solid lipid nanoparticles / 中草药

Objective To prepare brucine solid lipid nanoparticles (SLN) and its lyophilized powder, and then hydrogel matrix sustained-release tablets (HMST) of brucine SLN (SLN-HMST) were prepared. The factors that may influence drug release in vitro and release mechanism were also investigated in present study. Methods Based on single factor test, orthogonal test was designed to gain the optimum prescription. Zero-order, First-order and Higuchi models were used for the model fitting of drug release. Ritger-Pappas models were employed to study release mechanism of brucine SLN-HMST. Results Brucine SLN-HMST was better agreed with First-order kinetics model. The equation was ln(1-Mt/M∞) = -0.212 1 t + 0.106 4 (r = 0.992 3). The cumulative release could achieve 91.48% in 12 h. The sustained release features were obviously. The drug release from the tablets was controlled by diffusion and degradation of the matrix. Conclusion The prepared brucine SLN-HMST can deliver drug continually for 12 h with good reproducibility.

Preparation of resveratrol-DPPC liposomal dry powder inhalations and its antibacterial activities / 中草药

Objective To prepare the resveratrol-DPPC liposomal dry powder inhalations (RDLDPIs), and solve the problem of lower bioavailability of resveratrol after oral administration. Methods The RDLDPIs were prepared by film-dispersion and freeze drying. The formulation was optimized by orthogonal design. The particle size, entrapment efficiency, electric potential, in vitro release, and lung deposition were characterized. The broth microdilution method was used to evaluate the antibacterial activity and determine the minimal inhibitory concentration (MIC) in vitro. Results The optimized ratio of DPPC/cholesterol, resveratrol/DPPC, and mannitol/DPPC was 3:1, 1:3, and 2:1 in the prescription of RDLDPIs, respectively; And hydration time was 15 min. The entrapment efficiency of RDLDPIs was (69.8 ± 1.6)%, the drug loading was (2.4 ± 0.9)%, the particle size was (191.5 ± 4.5) nm, and the zeta potential was (12.4 ± 1.5) mV. The aerodynamic particle size of the powder was (3.2 ± 0.2) μm and the in vitro pulmonary deposition ratio was 28.1% in vitro. The antibacterial activity against Staphylococcus aureus, Acinetobacter baumannii, Streptococcus pneumoniae, and Pseudomonas aeruginosa was evaluated in vitro. The crude drug group had no antibacterial activity in four species of bacteria, while RDLDPIs had antibacterial activity of Staphylococcus aureus and Acinetobacter baumannii, and MIC was 4 mg/mL and 2 mg/mL, respectively. Conclusion The prepared RDLDPIs have small size and uniform distribution with good stability and high lung deposition rate and in vitro antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, which is expected to be an substitute for traditional antibiotics for the treatment of bacterial pneumonia.