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.

[Inhalotherapy: Recommendations for Argentina 2021]. / Inhaloterapia: Recomendaciones para Argentina 2021.

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.

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.

Ventas de medicamentos para enfermedades pulmonares obstructivas y mortalidad por asma en Argentina en los últimos 40 años / Sales of Medication for Obstructive Pulmonary Diseases and Asthma Mortality in Argentina for the Last 40 Years

Resumen Introducción: A nivel mundial, la mortalidad por asma sigue siendo un tema no resuelto a pesar de existir tratamientos muy eficaces. Esto mismo ocurre en Argentina, donde también se dispone de tratamientos efectivos, pero se desconoce si existe vinculación entre mortalidad por asma y las ventas de medicación inhalatoria. El objetivo fue analizar las ventas en farmacias de medicación para enfermedades respira torias obstructivas y las muertes por asma, antes y después de la aparición de los corticosteroides inhalados (ICS) y sus combinaciones. Materiales y métodos: Los datos de mortalidad por asma de 1983 a 2018 en Argentina se obtuvieron de un informe oficial. Todos los datos sobre ventas en farmacias fueron brindados por la misma fuente (IQVIA Solutions Argentina), pero no hay datos de ventas desde 1990 a 1999. Resultados: El promedio ± desvío standard del cociente entre el total de ventas de broncodilatadores agonistas β2 adrenérgicos de acción corta (SABA) sobre total de ventas de ICS y sus combinaciones fue 13,68 ± 2,85 entre 1983-1988 y 1,03 ± 0,12 entre 2010 a 2019 (p < 0.0001). Hubo una significativa correlación entre los cocientes SABA/ICS y el número de muertes por asma desde 1983 a 2018 (correlación de Pearson: r = 0,977, p < 0,0001). Durante el período 2010 a 2018 hubo una significativa caída en las muertes comparado con 1980-1989 (145,9 ± 28,58 vs 43,1 ± 5,2; p < 0,0001). Las ventas de SABA mostraron una declinación a partir del 2016 y fueron superados por las combinaciones de ICS/ Broncodilatadores de acción prolongada (LABA) en 2019. Conclusiones: La significativa correlación entre el cociente de ventas SABA/ICS y las muertes por asma haría replantear el estereotipo de tratamiento muy arraigado del uso de SABA en el manejo de asma.

Sales of Medication for Obstructive Pulmonary Diseases and Asthma Mortality in Argentina for the Last 40 Years

Abstract Introduction: Global asthma mortality is still an unresolved issue, despite the existence of highly effective treatments. This occurs in Argentina, where there are also some effective treatments, but there is few information about the relationship between asthma mortality and sales of inhaled medication. The purpose of this study was to analyze sales in pharmacies of medication for obstructive respiratory diseases and asthma deaths, before and after the appearance of inhaled corticosteroids (ICSs) and their combinations. Materials and Methods: An official bulletin was the source document for data about asthma mortality in Argentina between 1983 and 2018. All data on pharmacy sales were provided by the same source (IQVIA Solutions Argentina), but there are no sales data from 1990 to 1999. Results: The mean ± standard deviation of the ratio between total sales of short-acting β2-adrenergic agonist bronchodilators (SABAs) over total sales of ICS and their combinations was 13.68 ± 2.85 between 1983-1988 and 1.03 ± 0.12 between 2010-2019 (p < 0.0001). There was a significant correlation between the SABA/ICS ratios and the number of asthma deaths from 1983 to 2018 (Pearson correla tion: r = 0.977, p < 0.0001). During the period from 2010 to 2018 there was a significant decrease in the number of deaths compared to 1980-1989 (145.9 ± 28.58 vs. 43.1 ± 5.2; p <0.0001). Since 2016, SABA sales started to decrease and were overtaken in 2019 by the combinations of ICS/long-acting b2-agonist bronchodilators (LABAs). Conclusions: The significant correlation between the SABA/ICS sales ratio and asthma deaths would make us rethink the long-established treatment stereotype of SABAs for the management of asthma.

The clinical recovery of tuberculosis patients undergoing specific treatment is associated with changes in the immune and neuroendocrine responses.

Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n = 24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion. At T0, TB patients showed increased plasma levels of interleukin-6 (IL-6), C reactive protein, interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-ß). These mediators decreased during treatment, reaching levels similar to those from healthy controls (n = 26). Specific treatment led to an increased lymphoproliferative response along with clinical improvement. Newly diagnosed patients had low levels of DHEA, with increased cortisol amounts and cortisol/DHEA ratio, which normalized upon specific treatment. As regards glucocorticoid receptors (GR), TB patients at diagnosis presented a reduced mRNA GRα/GRß ratio in their peripheral blood mononuclear cells. Furthermore, multivariate analysis showed that cortisol/DHEA ratio was positively associated with inflammatory mediators for which this ratio may constitute a disease biomarker. Anti-mycobacterial treatment results in a better immune-endocrine scenario for the control of physiopathological processes accompanying disease development and hence implied in clinical recovery.

Recomendaciones prácticas para el manejo de la crisis asmática en pacientes adultos / Practical Recommendations for the Management of Acute Asthma in Adult Patients

Las exacerbaciones de asma pueden ser graves y ponen en riesgo la vida de los pacientes. En estos casos es fundamental reconocer signos y síntomas de riesgo, incluyendo la medición de la obstrucción al flujo aéreo y la oximetría de pulso, con la finalidad de objetivar la gravedad de la crisis. La administración adecuada del tratamiento incluyendo broncodilatadores, corticoesteroides y oxigenoterapia permite revertir la obstrucción bronquial y preservar la vida del paciente. A pesar de estas premisas básicas en el manejo de la crisis asmática, en nuestro medio se ha detectado recurrentemente una atención defciente de estos eventos. El contar con recomendaciones de fácil implementación, adecuadas a las necesidades locales y desarrolladas por médicos especialistas en medicina respiratoria podría mejorar la calidad de atención de estos pacientes. Con este objetivo se realizó una revisión bibliográfica clasificando la información según el grado de evidencia. Los resultados fueron evaluados por un panel de expertos y se desarrolló un algoritmo de manejo del asma aguda. El algoritmo propone una evaluación inicial en base a signos de severidad, datos de medición del flujo aéreo (FEV1 y/o FPE) y oximetría de pulso que permitirán clasificar las exacerbaciones según su grado de severidad e indicar detalladamente los pasos terapéuticos a seguir en cada caso, como así también los criterios de internación y alta. El uso de estas recomendaciones permitirá una mejor distribución de recursos y optimización del tratamiento de los pacientes atendidos por exacerbaciones de asma.

Asthma exacerbations can be severe and life threatening. In order to assess in a correct and objective way the severity of the exacerbation, it is essential to recognize risk signs and symptoms, including the measurement of airflow obstruction and pulse oximetry. Proper treatment including bronchodilators, corticosteroids, and oxygen can reverse bronchial obstruction and preserve patient's life. Despite these basic facts, inappropriate care in the management of acute asthma events is frequent in Argentina. Recommendations developed by specialists in respiratory medicine, which are easy to implement and adapted to local needs, could improve the quality of care of these patients. In order to accomplish these goals, an exhaustive review of the literature was conducted and the information was classified according to the degree of evidence. The results were evaluated by a panel of experts and an algorithm for the management of acute asthma was designed. This algorithm proposes an initial assessment based on asthma severity including measurement of airflow obstruction (FEV1 and/or PF) and pulse oximetry. Thus, it allows classifying exacerbations by degree of severity, leading to appropriate sequential therapeutic options as well as criteria for admission and discharge. The use of these recommendations is intended to allow a correct management of asthma exacerbations in Argentina and an optimized use of medical resources.

Development of a simple binary response questionnaire to identify airflow obstruction in a smoking population in Argentina.

The CODE questionnaire (COPD detection questionnaire), a simple, binary response scale (yes/no), screening questionnaire, was developed for the identification of patients with chronic obstructive pulmonary disease (COPD). We conducted a survey of 468 subjects with a smoking history in 10 public hospitals in Argentina. Patients with a previous diagnosis of COPD, asthma and other respiratory illness were excluded. Items that measured conceptual domains in terms of characteristics of symptoms, smoking history and demographics data were considered. 96 (20.5%) subjects had a diagnosis of COPD according to the 2010 Global Initiative for Chronic Obstructive Lung Disease strategy document. The variables selected for the final questionnaire were based on univariate and multivariate analyses and clinical criteria. Finally, we selected the presence or absence of six variables (age ≥50 years, smoking history ≥30 pack-years, male sex, chronic cough, chronic phlegm and dyspnoea). Of patients without any of these six variables (0 points), none had COPD. The ability of the CODE questionnaire to discriminate between subjects with and without COPD was good (the area under the receiver operating characteristic curve was 0.75). Higher scores were associated with a greater probability of COPD. The CODE questionnaire is a brief, accurate questionnaire that can identify smoking individuals likely to have COPD.

Changes in the immune and endocrine responses of patients with pulmonary tuberculosis undergoing specific treatment.

We evaluated immune and endocrine status following antituberculosis treatment in HIV-negative patients with newly diagnosed tuberculosis (TB). Treatment led to a decrease in IL-6, IL-1ß, and C-reactive protein levels. Cortisol levels decreased throughout the anti-TB treatment, particularly after 4 months, but changes were less pronounced than those seen in proinflammatory mediators. Specific therapy resulted in increased dehydroepiandrosterone (DHEA) levels, which peaked after 4 months and started to decline after 6 months of treatment, reaching levels below those detected at inclusion. In contrast, in most patients, dehydroepiandrosterone sulfate (DHEAS) levels remained unchanged, although a trend toward increased concentrations was observed in a few cases 3 months after the treatment was finished. Specific therapy also resulted in more balanced cortisol/DHEA and cortisol/DHEAS ratios. Etiologic treatment involves favorable immune and endocrine changes, which may account for its beneficial effects.

Tiotropium and risk for fatal and nonfatal cardiovascular events in patients with chronic obstructive pulmonary disease: systematic review with meta-analysis.

BACKGROUND: There are safety concerns regarding the use of anticholinergics in the COPD patient population. The purpose of this review was to evaluate the cardiovascular risk of regular use of inhaled tiotropium bromide in patients with COPD of any severity. METHODS: Systematic searches were conducted in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, manufactures' trial register, and FDA databases, without language restriction. Primary outcomes were a composite of major adverse cardiovascular events, cardiovascular mortality, and nonfatal myocardial infarction (MI) or stroke during the treatment period. Relative risks (RR) were estimated using fixed-effects models and statistical heterogeneity was estimated with the I2 statistic. RESULTS: Nineteen randomized controlled trials (18,111 participants) were selected. There was no difference in the incidence of adverse cardiovascular events (RR=0.96; 95% CI, 0.82-1.12, I2=6%). Among individual components of the composite outcome, tiotropium did not significantly increase the risk of cardiovascular death (RR=0.93; 95% CI, 0.73-1.20, I2=1%), nonfatal MI (RR=0.84; 95% CI, 0.64-1.09, I2=0%), and nonfatal stroke (RR=1.04; 95% CI, 0.78-1.39, I2=0%). A smoking history of > or = 55 pack-years presented a trend to a higher rate of cardiovascular adverse events in patients receiving tiotropium. CONCLUSIONS: Compared with control (placebo or salmeterol), tiotropium did not significantly increase the risk of adverse major cardiovascular events among COPD patients. Subgroup analysis suggested that smoking history can modify the risk of cardiovascular adverse events.

Hospitalizaciones por asma aguda durante el período 1994-2004 en Argentina y Uruguay: el estudio EAGLE / Hospitalizations for acute asthma during the period 1994-2004 in Argentina and Uruguay: the EAGLE study

Introducción: El objetivo de este estudio consistió en un análisis de la base de datos del proyecto EAGLE (características de los pacientes hospitalizados por asma) limitado a la Argentina y el Uruguay. Pacientes y métodos: Para evaluar los cambios producidos en los asmáticos hospitalizados en Argentina y Uruguay, fueron revisadas las historias clínicas de 215 pacientes (15-69 años de edad) hospitalizados en 4 centros médicos durante los años 1994, 1999 y 2004. Resultados: Si bien se verificó una reducción significativa en el uso de teofilinas, la utilización de corticoides inhalados fue baja (16% de todos los pacientes) y se mantuvo incambiada. Se verificó una tendencia a una disminución en el tiempo de hospitalización (10.5 días en 1994 a 8.2 días en 2004, p = 0.2). La tasa global de mortalidad para todos los pacientes estudiados durante los tres años fue 1.4% correspondiendo a un total de 3 fallecimientos. Por el contrario el uso de espirometría o flujo espiratorio máximo en urgencias se mantuvo por debajo del 60% de los pacientes hospitalizados. Globalmente, un 29% de todos los pacientes hospitalizados fueron ingresados a una unidad de cuidados intensivos. Conclusiones: Aunque este estudio sugiere algunas mejoras en el manejo del asma tanto durante el período intercrisis como durante las exacerbaciones, todavía subsisten importantes carencias tanto en Argentina como en Uruguay.

Introduction: The objective of this study was to assess the data base of project EAGLE (characteristics of the patients hospitalized because of asthma) in Argentina and Uruguay. Patients and Methods: In order to evaluate the changes produced in asthma hospitalizations in Argentina and Uruguay, the records of 215 patients (15-69 years old) admitted for acute asthma at third level hospitals during the years of 1994, 1999, and 2004 were reviewed. Results: Although a the use of theophylline was significantly decreased, the utilization of inhaled corticosteroids was low (16% of all patients) and remained unchanged during the study period. There was a trend towards a reduction in the length of hospital stay (from 10.5 days in 1994, to 8.2 days in 2004, p = 0.2). The overall case fatality rate for all patients admitted during the study period was 1.4% (3 deaths). The use of spirometry or peak expiratory flow measurements in the emergency room was registered in less of 60% of hospitalized patients. Overall, 29% of hospitalized patients required admission into an intensive care unit. Conclusions: Although this study suggests some improvements in the management of asthma in the period between severe exacerbations and during hospitalization, suboptimal case management is still common in Argentina and Uruguay.

The adrenal steroid response during tuberculosis and its effects on the mycobacterial-driven IFN-gamma production of patients and their household contacts.

Earlier studies revealed that patients with tuberculosis (TB) have imbalanced immunoendocrine responses and that adrenal steroids [cortisol and dehydroepiandrosterone (DHEA)] can modify their specific cell-mediated immune response. Because most household contacts (HHCs) of contagious TB patients develop a subclinical and self-controlled process (latent TB), we studied some features of their immune and endocrine responses, particularly those related to the hypothalamic-pituitary-adrenal axis. Nineteen HHCs, 24 untreated TB patients (15 moderate, 9 advanced), and 18 healthy controls of similar age were studied. Patients had increased and reduced levels of cortisol and DHEA, respectively. DHEA levels were also reduced in HHCs. Stimulation of peripheral blood mononuclear cells (PBMC) with Mycobacterium tuberculosis sonicate resulted in increased in vitro lymphoproliferation in HHCs, while advanced patients showed the lowest response. Significantly higher amounts of interferon (IFN)-gamma were detected in supernatants from stimulated PBMC of HHCs when compared to controls and TB patients. Addition of cortisol to the cultures inhibited mycobacterial antigen-driven IFN-gamma production in all groups, although HHC supernatant contained significantly higher concentrations. In contrast, addition of DHEA to cultures of cells from HHCs resulted in increased IFN-gamma levels. These results suggest the existence of a particular immunoendocrine relation assuring a preserved IFN-gamma production in healthy housemates of TB patients.

Encuesta en 8 regiones de Argentina sobre manejo pre-hospitalario de la crisis de asma / Survey of eight regions of Argentina regarding the pre-hospital management of acute asthma

El manejo correcto pre-hospitalario de la crisis asmática sería la medida más provechosa para reducir las muertes por asma. En él influyen el nivel de conocimientos y la aplicación de las guías por parte de los médicos a cargo. Con el objetivo de evaluar la aplicación de guías y su conocimiento, se distribuyó una encuesta anónima a médicos en las reuniones con tele conferencia satelital organizadas por un laboratorio en 2005. La encuesta permitía obtener un puntaje de 0 a 10 para calificar a los participantes. De las 8 regiones del país se obtuvieron 243 encuestas para analizar. El rango del año de graduación fue de 1965 a2005. Los encuestados refirieron atender en total 1523 pacientes en las últimas 4 semanas. El puntaje promedio de toda la muestra fue 7.13 ± 1.83. El promedio más alto fue alcanzado por los neumonólogos (9% del total de encuestados), con una diferencia significativa según el test de Tukey-Kramer de comparación múltiple, entre neumonólogos versus médicos generalistas (6%) y médicos sin especialidad (37%; p<0.05). El 82% manifestó tomar decisiones en base a guías. Aunque, llamativamente, el 50% no usaba medidor de flujo pico; el 45% no administraba anticolinérgicos inhalatorios; el 41% modificaba totalmente sus decisiones ante una crisis asmática en el primer trimestre del embarazo y un 29.5% no indicaba agonistas beta2 inhalados cuando la crisis presentaba un pulso mayorde 120/min. Un 14.9% usaba ansiolíticos sublinguales. La ciudad con mayor puntaje fue Bariloche. Se concluye que exceptuando a los neumonólogos, los resultados de esta encuesta muestran un puntaje no aceptable de calidad de atención pre-hospitalaria.

Asthma mortality could be reduced by improving acute asthma management inpre-hospital setting. Generally, it is difficult to carry out the recommendations of guidelines.In order to assess this issue and the physicians’ knowledge of acute asthma treatment, we designed a score between cero and ten points in a written survey to be distributed during a satellital conference in 8 regions of Argentina in 2005. We collected a total of 243 samples for analysis. Participants assisted a total of 1523 patients in the last 4 weeks. They had been graduated as MD, between 1965 and 2005. The designed score showed a mean 7.13± 1.83. Strikingly, 82% of the inquired participants answered that they follow the guidelines; while 50% did not use Peak Flow Meters. Furthermore, 45% did not administer inhaled anticholinergic bronchodilators. In case of acute asthma and pregnancy 41% absolutely modified their management. When the pulse was greater than 120/min, 29.5% of theparticipants did not indicate inhaled beta2 agonists and 14.9% used sublingua sedatives.Pulmonologists (9% of all participants) achieved a significant higher mean score in comparison with general practitioners. Bariloche city obtained the highest score. We concluded that with the exception of pulmonologists, these results showed an unacceptablequality of the pre-hospital management of acute asthma.

Encuesta en 8 regiones de Argentina sobre manejo pre-hospitalario de la crisis de asma / Survey in 8 regions of Argentina on pre-hospitable handling of the asthma crisis

El manejo correcto pre-hospitalario de la crisis asmática sería la medida más provechosa para reducir las muertes por asma. En él influyen el nivel de conocimientos y la aplicación de las guías por parte de los médicos a cargo. Con el objetivo de evaluar la aplicación de las guías y su conocimiento, se distribuyó una encuesta anónima a médicos en las reuniones con tele conferencia satelital organizadas por un laboratorio en 2005. La encuesta permitía obtener un puntaje de 0 a 10 para calificar a los participantes. De las 8 regiones del país se obutvieron 243 encuestas para analizar. el rango del año de graduación fue de 1965 a 2005. Los encuestadores refirieron atender en total 1523 pacientes en las últimas 4 semanas. El puntaje promedio de toda la muestra fue 7.13+-1.83. El promedio más alto fue alcanzado por los neumonólogos(%) del total de encuestados), con una diferencia significativa según el test de Tukey-Kramer de comparación múltiple, entre neumonólogos versus médicos generalistas (6%) y médicos sin especialidad( 37%; p<0.05). El 82% manifestó tomar decisiones en base a guias. Aunque llamativamente, el 50% no usaba medidor de flujo pico; el 45% no administraba anticolinérgicos inhalatorios; el 41% modificaba totalmente sus decisiones ante una crisis asmática en el primer trimestre del embarazo y un 29,5% no indicaba agonistas beta inhalados cuando la crisis presentaba un pulso mayor de 120/min. Un 14,9% usaba ansióliticos sublinguales. La ciudad con mayor puntaje fue Bariloche. Se concluye que exceptuando a los neumonólogos, los resultados de esta encuesta muestran un puntaje no aceptable de calidad de atención pre-hospitalaria.

Bronchodilator effect of zafirlukast in subjects with chronic obstructive pulmonary disease.

Cysteinyl leukotrienes (LT) are involved in airway inflammation and mucus hypersecretion, characteristically present in asthma and chronic obstructive pulmonary disease (COPD). Zafirlukast is an LT receptor antagonist that improves airway function within 1-3 h after oral administration in subjects with chronic persistent asthma. Through a randomised, double-blind, crossover and placebo-controlled study, we assessed the short-term effects of zafirlukast in patients with severe COPD. We enrolled 23 subjects (seven women) aged 59.4 (1.67) yr [mean (SEM)] with a smoking history of 60.7 (5.2) pack-yr. At screening day the mean FEV(1)was 0.876 (0.72) l; FEV(1) % predicted=35 (3)% and 107 (14) ml increment post-salbutamol. They came two different days, apart from each other at least 72 h. After baseline spirometry, a single oral dose of 40 mg zafirlukast or the corresponding placebo was administered. FVC and FEV(1) was measured every 30 min until 2 hrs. On zafirlukast day, the mean FEV(1) at 90 min [0.813 (0.64) l] and the mean FVC at 90 min [1.76 (0.1) l] were significantly higher than the respective means at placebo day (mean FEV(1)=0.747 (0.55) l; mean FVC=1.63 (0.1) l; p<0.05 Tukey Kramer multiple comparisons test). The maximum mean increase in FEV(1) was 75 (19) ml. A positive correlation was found between absolute response to salbutamol in FEV(1) and the response to zafirlukast (r=0.41; p<0.04). In conclusion, these findings suggest that zafirlukast has a bronchodilator or antibronchoconstrictor effect in COPD patients with severe airflow limitation.

Efecto del Bromuro de ipratropio sobre la broncoconstriccion por histamina en sujetos con obstruccion cronica al flujo aereo / Effect of ipratropium bromide on histamine-induced bronchoconstriction in subjects with chronic airway obstruction

El bromuro de ipratropio (B I) es un agente anticolinérgico muy recomendado para el tratamiento de la obstrucción crónica al flujo aéreo (EPOC). No obstante, no hay definición respecto a la existencia de efectos preventivos (no broncodilatadores) del BI. Con el fin de evaluar la acción del BI (80 µg en aerosol) ante una prueba de histamina se estudiaron 9 sujetos (hombres) con EPOC moderada, mediante un diseño doble ciego, aleatorio, controlado y cruzado entre placebo y BI. Tenían una edad promedio (ñ error standard de media) = 57,9 ñ 2,4 años con antecedentes de tabaquismo de 54,6 ñ 5,1 paquete-años y un FEV1 basal = 1,36 ñ 0,08 litros (47,2 ñ 3,8 percent del teórico).La hiperreactividad bronquial a la histamina en el día control fue logPC20 =-0,54 ñ 0,24 mg/ml (media geométrica: 0,27 mg/ml). El BI produjo un aumento significativo en el FEV1 basal; aunque no hubo correlación entre la obstrucción basal (FEV1, FEV1/FVC percent) y la broncodilatación con la hiperreactividad (logPC20). El BI redujo la broncoconstricción por histamina (logPC20 BI = -0,15 ñ 0,17 mg/ml; media geométrica [MG] = 0,70 mg/ml) en comparación con placebo (logPC20 post placebo = -0,76 ñ 0,22 mg/ml [MG = 0,17 mg/ml]; P = 0,018) y la dosis doble fue para BI = 2,02 ñ 0,68 vs placebo = -0,62 ñ 0,79; p: 0,024. Tanto el fenoterol como el BI revirtieron totalmente la caída del FEV1 al final de la prueba de histamina. Se concluye que el BI mostró un efecto protector ante la histamina en estos sujetos con diagnóstico de EPOC moderada