Class of 2015 Abstract / Objectives: American residents travel to Mexico to purchase medications, like albuterol inhalers, for 1/3 to 1/5 of the US price without prescription requirements. A previous bioequivalence study found clinical differences (P less than 0.05) between Ventolin and Assal, two Mexican manufactured albuterol inhaler brands. What other differences are there among such inhalers when we test more brands and analyze pharmaceutical qualities like respirable mass? This study seeks to provide some reasonable expectations for a medical tourist of Mexico who purchases albuterol metered dose inhalers (MDIs) by comparing the product performance of some of the brands available to the consumers in Mexico. Methods: This study examined the performance of albuterol MDIs obtained from pharmacies in Nogales, Mexico. At least two units were purchased for each of the following brands: Xeneric-S, Victory, Ventolin (GlaxoSmithKline), Assal, and Sacrusyt. At least two lot numbers of each brand were included, with the exception of Sacrusyt, for which a second lot was unavailable at the purchase times. Sample MDIs were compared to US-purchased albuterol inhalers, Proventil and Ventolin. Total dose and respirable mass were determined for each MDI. These parameters were measured by actuating each inhaler into a USP throat, coupled to a cascade impactor, which separates drug particles based on aerodynamic particle size. Particles with an aerodynamic diameter larger than 4.7 micrometers are considered non-respirable, while particles less than 4.7 micrometers are considered respirable and the total of respirable and non-respirable particles is the respirable mass. The total dose delivered is determined by calculating the amount of drug that deposits onto the throat and the impactor. Quantification of albuterol was determined by high performance liquid chromatography (HPLC). In brief, the HPLC assay utilized an Apollo C18 column with a mobile phase of 1 percent phosphoric acid:methanol (77:23) at a flow rate of 0.75mL/min; UV detection was at 225 nm. Results: Every inhaler was sold in a Spanish-labeled box containing a single page instruction insert and every inhaler label had a visible lot number, expiration date, and noted a 100 microgram dose. Listed manufacturing locations included China, Mexico, India, and Spain. All of the MDIs were purchased for about $3 to $5 each except for non-US Ventolin ($10-$20 each). The measurements of total dose and respirable mass among the five Mexican purchased brands of inhalers varied widely. The MDIs’ average total doses ranged from 57 to 75 micrograms per actuation, while the average total dose of the US purchased MDIs was 79 to 82 micrograms. The respirable mass of the non-US MDIs was more similar. Among the study MDIs, respirable mass ranged from 28 to 41 micrograms, which compares to 38 to 42 micrograms for the two US branded albuterol inhalers. To further investigate the variability among the study MDIs, student t-tests were performed to compare the mean respirable mass for each brand to that of the other four brands. All comparisons were significantly different (p less than 0.05) except for two (Sacrusyt vs Assal, p equals 0.89; Xeneric vs Ventolin, p equals 0.98). Conclusions: Since significant pharmaceutical variability was found among the albuterol MDIs evaluated in this study, clinicians and patients should be conscious of possible differences in quality, therapeutic efficacy, and safety for albuterol MDIs obtained in Mexico. Sample MDIs compared to each other were statistically different in total dose and respirable mass. Thus a patient who has used US MDIs before can’t necessarily expect to get the same dose from non-US brands.

Dry powder inhalers (DPIs) are used for delivering drugs to the airways. In addition to the drug, the formulations often contain a coarse carrier, most commonly alpha lactose monohydrate. The presence of fine lactose particles in the formulation is known to improve the formulation performance. The active site, drug-fines agglomeration and increased cohesion theories have been suggested to explain improved DPI performance upon addition of fine excipient particles. This project aimed to investigate the validity of those theories. The viability of the active sites theory in explaining the improved DPI performance was investigated by studying the impact of loaded drug dose on the in vitro performance for formulation series prepared with coarse carriers with different surface characteristics. The formulations prepared with the rougher lactose carrier were seen to outperform the formulations prepared with the smoother carrier at all drug concentrations. These findings were concluded to be non-compatible with the active sites theory. The impact of addition of lactose fines with different size distributions on powder flow and fluidisation properties and in vitro performance was studied. Powder cohesion increased independent of size distribution of the fines, but did not necessarily correspond to improved performance. Therefore, the increased cohesion theory was concluded not to be the sole explanation for the improvement in DPI performance in the presence of lactose fines. Instead, the increase in performance could be preliminarily attributed to the formation of agglomerated systems. The formation and co-deposition of drug-fines agglomerates, and consequential improvement in the DPI performance was proved using morphologically directed Raman spectroscopy. The project also aimed to develop a universal model for predicting DPI performance based on the lactose properties for a wide range of carriers with different properties. No simple linear correlations between any the lactose properties and the final DPI performance were found. Therefore no single parameter can be used as a universal predictor for DPI performance. To establish more complex relationships, artificial neural networks were used for modelling the importance of different lactose properties in determining DPI performance. The proportion of fine lactose particles (<4.5 μm) was identified as the most important parameter. However, this parameter was capable of explaining only approximately half of the variation seen in the formulation performance. The current study showed that to obtain more accurate predictions for the purposes of quality-by-design approach, also other lactose properties need to be characterised.

Background: Evidence on aerosol delivery via tracheostomy is lacking. The purpose of this study was to evaluate the effect of aerosol device and administration technique on drug delivery in a simulated spontaneously breathing pediatric model with tracheostomy. Methods: Delivery efficiencies during spontaneous breathing with assisted and unassisted administration techniques were compared using the jet nebulizer (JN- MicroMist), vibrating mesh nebulizer (VMN- Aeroneb Solo) and pressurized metered-dose inhaler (pMDI- ProAirHFA). The direct administration of aerosols in spontaneously breathing patients (unassisted technique) was compared to administration of aerosol therapy via a manual resuscitation bag (assisted technique) attached to the aerosol delivery device and synchronized with inspiration. An in-vitro lung model consisted of an uncuffed tracheostomy tube (4.5 mmID) was attached to a collecting filter (Respirgard) which was connected to a dual-chamber test lung (TTL) and a ventilator (Hamilton). The breathing parameters of a 2 years-old child were set at an RR of 25 breaths/min, a Vt of 150 mL, a Ti of 0.8 sec and PIF of 20 L/min. Albuterol sulfate was administered with each nebulizer (2.5 mg/3 ml) and pMDI with spacer (4 puffs, 108 µg/puff). Each aerosol device was tested five times with both administration techniques (n=5). Drug collected on the filter was eluted with 0.1 N HCl and analyzed via spectrophotometry. Results: The amount of aerosol deposited in the filter was quantified and expressed as inhaled mass and inhaled mass percent. The pMDI with spacer had the highest inhaled mass percent, while the VMN had the highest inhaled mass. The results of this study also found that JN had the least efficient aerosol device used in this study. The trend of higher deposition with unassisted versus assisted administration of aerosol was not significant (p>0.05). Conclusions: Drug deposited distal to the tracheostomy tube with JN was lesser than either VMN or pMDI. Delivery efficiency was similar with unassisted and assisted aerosol administration technique in this in vitro pediatric model.

The influence of the size and morphology of carrier particles on drug dispersion performance from passive dry powder inhalers has been extensively studied topic, and a consensus has been reached regarding the adverse effect that larger carrier particle diameters impart to aerosol performance. However, previous studies have generally employed only a few carrier particle size fractions, generally possessing similar surface characteristics. Accordingly, theories developed to explain the influence of the physical characteristics of carrier particles on performance relied heavily on both extrapolation and interpolation. To fill in the gaps from the literature and simultaneously evaluate the influence of carrier particle size and morphology, a comprehensive study was undertaken using 4 lactose grades, each sieved into 13 contiguous sizes, to prepare 52 formulations incorporating a unique lactose grade-size population. The aerosol performance results indicated that large carrier particles possessing extensive surface roughness can improve drug dispersion, in contrast to what has been previously reported. It is proposed that this may be attributed to mechanical detachment forces arising from collisions between the carrier particle and inhaler during actuation. Based on these observations, a novel dry powder inhaler platform was developed, employing carrier particles much larger (> 1 mm) than previously explored in both the scientific and patent literature. Optimization of this technology required the judicious selection of a carrier material, and following an extensive screening process, low-density polystyrene was selected as a model candidate. Given its low mass, diameters in excess of 5-mm could be employed as carriers while still generating high detachment forces. To minimize drug particle aggregation, a novel drug-coating method employing piezo-assisted particle dispersion was developed to compensate for the reduced surface area of the novel carrier particles. In addition, the selection of a suitable inhalation device prototype was instrumental to the overall performance of the technology. In vitro testing of the novel large carrier particles yielded emitted fractions in excess of 85%, and overall drug delivery of up to 69% of the nominal dose. / text

Currently available dry powder inhalers (DPIs) for drug delivery to the lungs require turbulent energy to generate and disperse aerosol particles in the respirable range ≤5μm during inhalation. The patient's inspiratory effort together with the resistance inside the device creates this energy. Different inhalers provide varying degrees of resistance to inhalation flow and require different inhalation techniques for the generation and delivery of drug fine particles in respirable size range to the lungs. The aim of this research programme was to identify the influence of inhalation flow, inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of the salbutamol Accuhaler®, Easyhaler®, and Clickhaler® and the terbutaline Turbuhaler® DPIs. A high-performance liquid chromatography method for the assay of salbutamol sulphate and terbutaline sulphate in aqueous samples was modified and accordingly validated. In-vitro dose emission of the four different DPIs was measured using the pharmacopoeia method with modifications to simulate varying inhalation flows within patient and between patients. The ranges of the total emitted dose (% nominal dose) at the inhalation flow range of 10 - 60 Lmin-1, following one and two inhalations per metered dose for 2L and 4L inhaled volumes were as follows: the Accuhaler (52.64- 85.11; 61.88-85.11 and 59.23-85.11; 62.81-85.11); the Easyhaler (68.35-91.99; 79.94-91.99 and 73.83-92.51; 80.40-92.51); the Clickhaler (46.55-96.49; 51.12-96.49 and 51.18-101.39; 59.71-101.39) as well as the Turbuhaler (46.08-88.13; 51.95-88.13 and 48.05-89.22; 48.64-89.22). The results highlight that the four inhalers have flow-dependent dose emission property to a varying degree using 2L and 4 L inhaled volumes. There was no significant difference in the total emitted dose between a 2L inhaled volume and a 4L inhaled volume at each inhalation flow. Furthermore, the total emitted dose from the Easyhaler®, Clickhaler®, and Turbuhaler® was significantly (p≤0.001) greater with two inhalations than one inhalation per metered dose across the range of inhalation flow (10-60) Lmin-1. This effect was only observed at inhalation flow less than 30 Lmin-1 with the Accuhaler®. Overall there is a significant difference in the total emitted dose. The ex-vivo dose emission of the four different DPIs has been determined using the In- Check Dial device to train twelve non-smoking healthy adult volunteers to inhale at slow (30 Lmin-1) and fast (60 L min-1) inhalation flows through the device with its dial set corresponding to each inhaler. Subsequently each volunteer inhaled at the trained inhalation flows through each active inhaler. The local ethics committee approval was obtained prior to the study and all volunteers gave signed informed consent. The results obtained demonstrate that the studied inhalers have flow-dependent dose emission, thereby enhancing confidence in the use of the In-Check Dial® to identify a patient's inhalation flows through a variety of DPIs. Also the total emitted dose determined by ex-vivo methodology was significantly (p≤0.05) greater with two inhalations than one inhalation per metered dose. The results of the in-vitro aerodynamic dose emission characteristics highlight that the fine particle dose (FPD) from the four studied inhalers is flow dependent. Also the minimum inhalation flow to generate the (FPD) with the appropriate characteristics for lung deposition has been identified to be 20 L min⁻¹ for the Accuhaler®, Easyhaler® and Clickhaler®, while that for the Turbuhaler® is about 30 L min⁻¹. Also the inhalation volume above 2L and the number of inhalations for each dose have respectively no significant (p≤0.05) influence on the FPD emitted from the four studied inhalers. The results support the present instructions to patients using these inhalers to inhale once for each dose as fast as they can.

Lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major health burdens on the global population. To treat diseases of the lung, topical therapies using dry powder inhalers (DPIs) have been employed. However, a relatively small amount of dose (5.5 - 28 %) reaches the lung during DPI therapy leading to high inter-patient variability in therapy response and oropharyngeal deposition. Strategies were assessed to take patient variability in inhalation performance into account when developing devices to reduce throat deposition and to mitigate flow rate dependency of the emitted aerosol. A cyclone-spacer was manufactured and evaluated with marketed and in-house manufactured formulations. An in vivo study showed that a high resistance inhaler would produce longer inhalation times in lung disease patients and that a spacer with high resistance may prove a suitable approach to address inter-patient variability. Two spacer prototypes were evaluated with cohesively- and adhesively-balanced particle blends. The data suggested that the throat deposition dramatically decreased for the emitted particles when the spacers were used with the inhalers (e.g. 18.44 ± 2.79% for salbutamol sulphate, SS 4 kPa) due to high retention of the formulation within the spacer (87.61 ± 2.96%). Moreover, variation in fine particle fraction and dose was mitigated when increasing the flow rate (82.75 ± 7.34 %, 92.2 ± 7.7 % % and 77.0 ± 10.1 % at 30, 45 and 60 Lmin-1, respectively). The latter was an improvement over previous proposed DPI spacers, where variability in emitted dose due to airflow rate was a major issue. Due to the different physicochemical properties of the active pharmaceutical ingredients used in the formulation, throat deposition and respirable fraction for adhesively-balanced particles (e.g. SS) were double that of the cohesively- balanced particles (salmeterol xinafoate, SX) (e.g. 65.83 ± 8.99 % vs. 45.83 ± 5.04 % for SS:Coarse Lactose (CL) and SX:CL, respectively). Scanning electron microscopy revealed that surface-bound agglomerates were more freely removed from the carrier, but subject to decreased impaction-type deagglomeration forces in the spacer than for carrier-bound drug. An ex vivo study using breath profiles from healthy volunteers identified the minimization of differences between adhesively- and cohesively-balanced blends when full breath profiles were studied compared to square-wave airflow. Therefore the use of constant flow for in vitro testing should not be the sole flow regime to study aerosolization when developing new inhalation devices and formulations.

<p>Dry Powder inhalers (DPIs) have been one of the most promising developments in pulmonary drug delivery systems. In general, DPIs are more effective than systemic administrations and convenient to use. However, delivering high-dose antibiotics through a DPI is still a challenge because high powder load may need a very large inhaler or increase the incidence of local adverse effects. Spray drying has been increasingly applied to produce DPI formulations for high-dose antibiotics; nevertheless, many spray-dried particles are amorphous and physically unstable during storage, particularly under the humid environment. </p> <p> </p> <p>My research focuses on addressing critical challenges in physical stability of DPIs for spray-dried high-dose antibiotics. The effects of moisture-induced crystallization on physical stability and aerosol performance of spray-dried amorphous Ciprofloxacin DPI formulations stored at different humidity conditions were studied. Our study not only provided a mechanistic understanding in the impact of crystallization on aerosol performance but also developed novel approaches for improving stability of spray-dried formulations used in DPI.</p> <p> </p> <p>Our work has shown that recrystallization of amorphous spray-dried Ciprofloxacin led to significant changes in aerosol performance of DPIs upon storage, which cause critical quality and safety concerns. These challenges have been solved through co-spray-drying Ciprofloxacin with either excipient such as leucine or synergistic antibiotic like Colistin. Co-spray-drying Ciprofloxacin with Colistin not only improved physical and aerosol stability but also enhanced antibacterial activity which is a great advantage for treating ‘difficult to cure’ respiratory infections caused by multidrug resistant bacteria.</p> <p> </p> <p>My research work is a sincere effort to maximize the utility and efficacy of high-dose DPI, an effective delivery tool for treating severe resistant bacterial respiratory infections.</p>

No description available.

Existem evidências na literatura de que a administração de medicações, como corticosteróides inalatórios e broncodilatadores, utilizando inaladores pressurizados dosimetrados, é mais eficaz e segura do que com os nebulizadores convencionais. Entretanto, há evidências de que não só pacientes, mas também profissionais de saúde têm dificuldade no manejo dos inaladores pressurizados dosimetrados. A hipótese do presente estudo é que o conhecimento da técnica inalatória entre os profissionais da nossa Instituição é heterogêneo, sendo que não há informações sobre o nível deste conhecimento entre as diversas categorias profissionais. OBJETIVOS: Avaliar o conhecimento prático e teórico de profissionais da área médica, de enfermagem e fisioterapia sobre a utilização do inalador dosimetrado através de testes padronizados. MÉTODOS: Avaliações teóricas e práticas sobre o conhecimento do uso de inaladores pressurizados dosimetrados foram realizadas com médicos, fisioterapeutas, enfermeiras e auxiliares de enfermagem, atribuindo-se uma nota de 0 a 10 para cada avaliação. Calcularam-se as medianas das notas obtidas pelos profissionais de cada categoria, as questões com maiores e menores índices de erros e feita a comparação descritiva do desempenho das diversas categorias profissionais. Após as avaliações, instrução verbal e escrita sobre a utilização correta dos dispositivos foi fornecida a todos os participantes. A análise estatística foi feita através do método de Kruskal-Wallis de comparação de medianas. Também foi realizada a análise através de regressão logística múltipla seqüencial. RESULTADOS: foram avaliados 30 médicos residentes ou estagiários da pediatria, 23 médicos assistentes, 29 fisioterapeutas, 33 enfermeiras e 31 auxiliares de enfermagem, em um total de146 profissionais. Não foram entrevistados residentes ou assistentes do grupo de Pneumologia. Os médicos residentes, fisioterapeutas e os médicos assistentes obtiveram desempenho significativamente superior que os enfermeiros e auxiliares de enfermagem. Apenas os médicos residentes obtiveram mediana superior a seis. As questões práticas com maiores índices de erros foram as relativas à limpeza do espaçador. Questões relativas à agitação do inalador antes do uso e à limpeza da cavidade oral após a sua utilização também obtiveram alto índice de erros. A questão teórica mais errada foi a respeito do tempo necessário entre dois jatos em aplicações sucessivas do inalador pressurizado dosimetrado. CONCLUSÕES: O conhecimento teórico-prático dos profissionais de saúde da Instituição a respeito do uso de inaladores pressurizados dosimetrados é heterogêneo. Os médicos residentes, fisioterapeutas e médicos assistentes obtiveram desempenho significativamente melhor que os enfermeiros e auxiliares de enfermagem sendo que estes últimos estão diretamente envolvidos na aplicação prática destes dispositivos na rotina hospitalar. / There are data in the literature indicating that the administration of medications such as inhaled corticosteroids and bronchodilators, using metered-dose inhalers, is more effective and safer than its dispensation by conventional nebulizers. However, there is evidence that not only patients but also health care professionals have difficulty in dealing with pressurized dose inhalers. The hypothesis of the present study is that the knowledge of inhalation techniques among health professionals of our Institution is heterogeneous, and there is no information about this knowledge among the diverse categories of professionals. OBJECTIVE: To assess the practical and theoretical knowledge of medical professionals, nursing and physiotherapy on the use of metereddose inhalers by standardized testing. METHODS: Practical and written tests on the use of metered-dose inhalers were applied to physicians, physical therapists, nurses and nursing assistants. A score from 0 to 10 was assigned to each evaluation. Median scores were calculated for each professional category. Questions with higher and lower correct values were identified, and a descriptive comparison was made regarding the performance of the diverse professional categories. Following the examination, oral and written instructions on the correct use of the devices were provided for all participants. Statistical analysis was performed using the Kruskal-Wallis method for comparison of medians. A sequential logistic multiple regression analysis was also performed. RESULTS: A total of 146 professionals were assessed, including 30 fellows in pediatrics, 23 attending physicians, 29 physical therapists, 33 nurses and 31 nursing assistants. Fellows or attending physicians of the Pediatric Pulmonology Unit were not included in the study. Fellows, physical therapists and attending physicians performed significantly better than did nurses and nursing assistants. Only fellows had a median score greater than six. On the practical tests for infants and toddlers, the step most often missed was that related to cleaning the spacer. On practical tests, the steps related to shaking the inhaler and cleaning the mouth also presented high error indices. On the written tests, the question most often answered incorrectly was that related to the waiting time between puffs. CONCLUSIONS: The theoretical and practical knowledge of health professionals of our Institution on the use of metered-dose inhalers is heterogeneous. The performance of fellows, physical therapists and attending physicians was significantly better than that of nurses and nursing assistants who are directly involved in the practical application of these devices in the hospital routine.

Existem evidências na literatura de que a administração de medicações, como corticosteróides inalatórios e broncodilatadores, utilizando inaladores pressurizados dosimetrados, é mais eficaz e segura do que com os nebulizadores convencionais. Entretanto, há evidências de que não só pacientes, mas também profissionais de saúde têm dificuldade no manejo dos inaladores pressurizados dosimetrados. A hipótese do presente estudo é que o conhecimento da técnica inalatória entre os profissionais da nossa Instituição é heterogêneo, sendo que não há informações sobre o nível deste conhecimento entre as diversas categorias profissionais. OBJETIVOS: Avaliar o conhecimento prático e teórico de profissionais da área médica, de enfermagem e fisioterapia sobre a utilização do inalador dosimetrado através de testes padronizados. MÉTODOS: Avaliações teóricas e práticas sobre o conhecimento do uso de inaladores pressurizados dosimetrados foram realizadas com médicos, fisioterapeutas, enfermeiras e auxiliares de enfermagem, atribuindo-se uma nota de 0 a 10 para cada avaliação. Calcularam-se as medianas das notas obtidas pelos profissionais de cada categoria, as questões com maiores e menores índices de erros e feita a comparação descritiva do desempenho das diversas categorias profissionais. Após as avaliações, instrução verbal e escrita sobre a utilização correta dos dispositivos foi fornecida a todos os participantes. A análise estatística foi feita através do método de Kruskal-Wallis de comparação de medianas. Também foi realizada a análise através de regressão logística múltipla seqüencial. RESULTADOS: foram avaliados 30 médicos residentes ou estagiários da pediatria, 23 médicos assistentes, 29 fisioterapeutas, 33 enfermeiras e 31 auxiliares de enfermagem, em um total de146 profissionais. Não foram entrevistados residentes ou assistentes do grupo de Pneumologia. Os médicos residentes, fisioterapeutas e os médicos assistentes obtiveram desempenho significativamente superior que os enfermeiros e auxiliares de enfermagem. Apenas os médicos residentes obtiveram mediana superior a seis. As questões práticas com maiores índices de erros foram as relativas à limpeza do espaçador. Questões relativas à agitação do inalador antes do uso e à limpeza da cavidade oral após a sua utilização também obtiveram alto índice de erros. A questão teórica mais errada foi a respeito do tempo necessário entre dois jatos em aplicações sucessivas do inalador pressurizado dosimetrado. CONCLUSÕES: O conhecimento teórico-prático dos profissionais de saúde da Instituição a respeito do uso de inaladores pressurizados dosimetrados é heterogêneo. Os médicos residentes, fisioterapeutas e médicos assistentes obtiveram desempenho significativamente melhor que os enfermeiros e auxiliares de enfermagem sendo que estes últimos estão diretamente envolvidos na aplicação prática destes dispositivos na rotina hospitalar. / There are data in the literature indicating that the administration of medications such as inhaled corticosteroids and bronchodilators, using metered-dose inhalers, is more effective and safer than its dispensation by conventional nebulizers. However, there is evidence that not only patients but also health care professionals have difficulty in dealing with pressurized dose inhalers. The hypothesis of the present study is that the knowledge of inhalation techniques among health professionals of our Institution is heterogeneous, and there is no information about this knowledge among the diverse categories of professionals. OBJECTIVE: To assess the practical and theoretical knowledge of medical professionals, nursing and physiotherapy on the use of metereddose inhalers by standardized testing. METHODS: Practical and written tests on the use of metered-dose inhalers were applied to physicians, physical therapists, nurses and nursing assistants. A score from 0 to 10 was assigned to each evaluation. Median scores were calculated for each professional category. Questions with higher and lower correct values were identified, and a descriptive comparison was made regarding the performance of the diverse professional categories. Following the examination, oral and written instructions on the correct use of the devices were provided for all participants. Statistical analysis was performed using the Kruskal-Wallis method for comparison of medians. A sequential logistic multiple regression analysis was also performed. RESULTS: A total of 146 professionals were assessed, including 30 fellows in pediatrics, 23 attending physicians, 29 physical therapists, 33 nurses and 31 nursing assistants. Fellows or attending physicians of the Pediatric Pulmonology Unit were not included in the study. Fellows, physical therapists and attending physicians performed significantly better than did nurses and nursing assistants. Only fellows had a median score greater than six. On the practical tests for infants and toddlers, the step most often missed was that related to cleaning the spacer. On practical tests, the steps related to shaking the inhaler and cleaning the mouth also presented high error indices. On the written tests, the question most often answered incorrectly was that related to the waiting time between puffs. CONCLUSIONS: The theoretical and practical knowledge of health professionals of our Institution on the use of metered-dose inhalers is heterogeneous. The performance of fellows, physical therapists and attending physicians was significantly better than that of nurses and nursing assistants who are directly involved in the practical application of these devices in the hospital routine.