Transient expiratory flow interruptions (TEFI) increase expiratory flow in acute asthma exacerbation / Incremento del flujo espiratorio luego de interrupciones transitorias en la exacerbación aguda de asma

We have shown that expiratory flows increase when expirations are rapidly interrupted in stable asthmatic patients. We hypothesized that a similar increase could be obtained in patients with acute exacerbation of bronchial asthma treated in the Emergency Room. A total of 30 asthmatic patients were randomly allocated into two groups, the study and the control groups. Patients in the study group were connected to a device with an inspiratory line designed to administer pressurized aerosols. The expiratory line passed through a valve completely interrupting flow at 4 Hz, with an open/closed time ratio of 10/3. The control group patients were also connected to the device, but with the valve kept open. Mean expiratory flow at tidal volume (MEFTV) was measured under basal conditions and at 4, 8 and 12 minutes after connecting the patients to the device. All patients received standard treatment throughout the procedure. At all time points MEFTV increased more in the study than in the control group (p < 0.003 by two-way ANOVA). There was no residual effect after disconnection from the device. We conclude that TEFI can rapidly improve expiratory flows in patients with acute exacerbations of asthma, while pharmacologic interventions proceed.

Demostramos que el flujo espiratorio máximo, en pacientes asmáticos en estado estable, se incrementaba cuando se generaban rápidas y transitorias interrupciones del flujo. Formulamos la hipótesis de que un incremento similar podría ser observado en pacientes con exacerbación aguda de asma tratados en la sala de emergencias. Un total de 30 pacientes asmáticos fueron distribuidos al azar en dos grupos. Los pacientes del grupo en estudio fueron conectados a un aparato con una vía inspiratoria diseñada para la administración de aerosoles. La vía espiratoria pasaba por una válvula que interrumpía el flujo completamente a 4 hz, con una relación tiempo abierta/tiempo cerrada de 10/3. Los pacientes del grupo control también fueron conectados al aparato pero con la válvula siempre abierta. Se midió el flujo medio de la espiración a volumen circulante en condiciones basales y a los 4, 8 y 12 minutos después de conectado el paciente al equipo. Todos los pacientes recibieron el tratamiento farmacológico estándar a lo largo del ensayo. Se observó un incremento significativamente mayor del flujo espiratorio medio a volumen circulante en el grupo en estudio en comparación al grupo control (p < 0.003 ANOVA de dos vías) durante todo el ensayo. No hubo efecto residual después de la desconexión del equipo. Concluimos que las interrupciones transitorias del flujo espiratorio pueden incrementar rápidamente el flujo espiratorio en pacientes con exacerbaciones agudas de asma dando tiempo a que el tratamiento farmacológico comience a actuar.

Acute severe asthma; salbutamol plus ipratropium bromide nebulization versus salbutamol nebulization alone

To compare the improvement in peak expiratory flow rate [PEFR] of patients presenting to the emergency department with acute severe asthma by using the following two regimens of broncho-dilator therapy. a] Salbutamol nebulization. b] Salbutamol plus Ipratropium bromide nebulization. c] To compare the hospital admission rates in the above mentioned two treatment groups. A comparative study. Military Hospital Rawalpindi, Feb 2002 to Dec 2002. Sixty adult asthmatic patients with peak expiratory flow rate [PEFR] less than 200 liters per minute were randomly assigned to nebulization treatment with salbutamol [5.0 mg initial dose followed by 2 more doses at 30 and 60 minutes] or the same salbutamol regimen plus ipratropium bromide [0.5 mg]. The primary end point was change in PEFR. The PEFR was measured at 30 minutes, 60 minutes and 90 minutes after the onset of study protocol. The proportion of admission in the two groups was examined as secondary end point. The increase in PEFR over time was significantly greater in combined ipratropium plus salbutamol group [p = 0.01] also the proportion of admitted patients was less in combined salbutamol plus ipratropium bromide group 4/30 vs 11/30, p = 0.036. The data suggested that combined iratropium bromide plus salbutamol nebulization was superior to salbutamol nebulization alone and it should be used in the initial management of patients who present with acute severe asthma

Inhaled formoterol versus ipratropium bromide in chronic obstructive pulmonary disease.

BACKGROUND: Short-acting anticholinergic bronchodilator, ipratropium bromide has been recommended as first-line drug in chronic obstructive pulmonary disease (COPD). More recently, long acting beta2-agonist (LABA) bronchodilators such as formoterol have been shown to be useful in COPD. Limited information is available on the relative efficacy of these two drugs in COPD. METHODOLOGY: A randomised, double-blind, cross-over, placebo-controlled study was carried out. Forty-four stable patients with COPD received single doses of formoterol (12 microg), ipratropium bromide (40 microg) or placebo, administered through a metered-dose inhaler on three consecutive days in a random order. Spirometry, static lung volumes, pulse rate and blood pressure, and assessment of sensation of dyspnoea at rest using a visual analog scale (Borg Scale) were recorded at baseline. Subsequently, these were repeated for assessment of response: spirometry at 5, 30 and 60 minutes and static lung volumes, pulse rate, blood pressure and dyspnoea measurement at 60 minute. RESULTS: Formoterol resulted in greater immediate improvement in lung function, with the change in FEV1 at 5 min being greater than that observed with ipratropium. The changes in static lung volumes were similar between the two but superior to placebo. Both the drugs reduced dyspnoea. Formoterol produced a significantly greater increase in heart rate and systolic blood pressure as compared to ipratropium, although the magnitude of these changes was small and clinically unimportant. CONCLUSIONS: Single therapeutic doses of formoterol and ipratropium bromide are equally effective in improving lung function and reducing dyspnoea. However, formoterol appears to be a better bronchodilator producing a faster improvement in lung function.

Avaliação prognóstica precoce da asma aguda na sala de emergência / Early prognosis of acute asthma in the emergency room

OBJETIVO: Estudar medidas clínicas e funcionais pulmonares utilizadas nos primeiros quinze minutos de manejo da asma aguda em um serviço de emergência, para predição prognóstica. MÉTODOS: Estudo de coorte, prospectivo, que incluiu pacientes consecutivos com asma aguda, com idades entre doze e 55 anos e medida do pico de fluxo expiratório menor ou igual a 50 por cento do previsto. Realizaram-se avaliações na admissão, aos quinze minutos e em quatro horas após o início do tratamento. O tratamento incluiu salbutamol e ipratrópio, administrados por aerossol dosimetrado com espaçador, e 100 mg de hidrocortisona intravenosa. O desfecho favorável foi definido pelo pico de fluxo expiratório maior ou igual a 50 por cento do previsto após a quarta hora de tratamento, e o desfecho desfavorável pelo pico de fluxo expiratório menor que 50 por cento do previsto. RESULTADOS: Tiveram desfecho favorável 27 pacientes e desfavorável 24. A análise multivariada identificou o pico de fluxo expiratório em porcentagem do previsto aos quinze minutos como variável mais preditiva. O pico de fluxo expiratório maior ou igual a 40 por cento aos quinze minutos mostrou significativa contribuição em predizer desfecho favorável (sensibilidade = 0,74, especificidade = 1,00 e valor preditivo positivo = 1,00). O pico de fluxo expiratório menor que 30 por cento aos quinze minutos contribuiu para predizer desfecho desfavorável (sensibilidade = 0,54, especificidade = 0,93 e valor preditivo positivo = 0,87). CONCLUSÃO: O estudo sugeriu que a medida do pico de fluxo expiratório aos quinze minutos do manejo da asma aguda em um serviço de emergência é um instrumento útil para avaliação prognóstica.

Beneficios clínicos y funcionales de agregar teofilina a la terapia inhalatoria con broncodilatadores de acción corta en pacientes con enfermedad pulmonar obstructiva crónica / Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD

Background: Although theophylline is considered a third line bronchodilator drug for the treatment of chronic obstructive pulmonary disease (COPD), it is widely used in Chile, because it is administered orally and has a moderate cost. Aim: To evaluate if theophylline adds clinical and/or functional benefits when associated to standard recommended inhaled bronchodilator therapy. Subjects and methods: Thirty-eight stable COPD patients who accepted to participate in the study approved by the Ethics Committee of our institution were studied. Using a randomized double-blind placebo-controlled study, theophylline (250 mg) or placebo was administered twice a day for 15 days in addition to inhaled salbutamol and ipratropium bromide. Prior to and at the end of the study, patients underwent: a) a spirometry to evaluate changes in dynamic pulmonary hyperinflation using slow vital capacity (SVC) and inspiratory capacity (IC), b) the 6 min walking distance (6 MWD); and c) measurement of maximal inspiratory and expiratory pressures. Dyspnea and quality of life (QoL) were evaluated using appropriate questionnaires. Results: Compared to placebo, patients on theophylline showed significant increases in SVC (p=0.014), IC (p=0.002), and 6 MWD (p=0.005). They also experienced an improvement in dyspnea (p=0.042) and QoL (p=0.011). All patients improved at least one of these parameters with 53% of the patients showing an improvement in 3 or more. Conclusions: Our results indicate that adding theophylline to standard treatment with inhaled bronchodilators provides additional benefits in stable COPD patients by reducing dynamic pulmonary hyperinflation, improving exercise tolerance, dyspnea and QoL.

Effect of single inhalation of a salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic obstructive airway disease.

BACKGROUND: Chronic obstructive airway disease (COAD) is associated with hyperplasia and hypertrophy of the mucus producing glands. The beneficial effect of inhaled drug may be due to improved mucociliary function. The present study was done to evaluate the effect of salbutamol, ipratropium bromide and beclomethasone dipropionate inhalation on mucociliary clearance in patients with COAD. METHODS: Ten patients of COAD were taken up, two patients however did not complete the study. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four separate days. Radioaerosol inhalation lung cine-scintigraphy after inhalation of the different drugs was followed up to two hours and than after 24 hours. RESULTS: There was no significant visually noticeable increased mucociliary clearance on any of the days. Two patients showed definite steep slope in the time activity curves with salbutamol as compared to other drugs or placebo. All the quantitative indices analysed at the end of one hour and two hours for the three drugs were comparable to placebo. CONCLUSIONS: A single dose of inhaled salbutamol, ipratropium bromide and beclomethasone dipropionate has no appreciable effect on mucociliary clearance in patients with COAD.

Lower arrythmogenic risk of low dose albuterol plus ipratropium.

OBJECTIVE: Wheezy infants are in need of urgent bronchodilatation owing to their intermittent bronchoconstriction. beta 2 agonists are frequently used in emergencies and have previously shown to increase the QT dispersion (QTd), which may be associate with high risk of cardiac arrhythmia, in asthmatics. However, effect of low dose beta 2 agonist therapy in combination with the anticholinergic agents on QTd in wheezy infants is not known. This study aimed to assess the effect of standard dose of nebulized albuterol (NAB) and low doses of NAB combined with ipratropium-bromide (NIB) on QTd in wheezy infants. METHODS: Twenty-nine children, under 2 years old, with the diagnosis of wheezy infant with acute exacerbation were enrolled in the study. Thirteen were treated by standard dose of NA therapy (0.15 mg/kg) and low doses of NAB (0.075 mg/kg) plus NIB (250 micrograms/dose) therapy was given to the remaining subjects. Respiratory distress score, O2 saturation and side effects were studied and QTd were measured from the standard electrocardiograms at baseline and after treatment. Significant improvement was achieved in clinical score and oxygenation of both groups. RESULT: The evaluation of the corrected QTd (QTcd) showed that there was no significant difference between pretreatment values of both groups (p > 0.05). However, while there was no statistically significant difference in the pre and post-treatment values of QTcd of infants treated with combination therapy, QTcd was found to be significantly increased in NAB group after treatment (p < 0.05). CONCLUSION: Our results suggest that, while clinical improvement is same, the increase of the QT dispersion is more prominent with the use of standard dose of NAB compared to low dose NAB plus NIB therapy. So, low dose of beta 2 agonist in combination with anticholinergic agents may much safer than the use of standard dose of beta 2 agonists alone in regard to preventing the possibility of arrythmogenic effects in wheezy infants with acute exacerbation.

Caracterización de los pacientes portadores de enfermedad pulmonar obstructiva crónica y su respuesta a ipratropio y teofilina / Characterization of chronic obstructive pulmonary disease patients and their response to ipratropium and theophylline

La respuesta clínica y funcional a dos broncodilatadores, bromuro de ipratropio y teofilina en enfermedad pulmonar obstructiva crónica fue evaluada en 62 pacientes, procedentes del programa de enfermedades bronquiales obstructivas del Instituto Nacional del Tórax. Conjuntamente se describen las características clínicas, radiológicas y de laboratorio de los 62 pacientes. El estudio duró 6 meses y los pacientes recibieron bromuro de ipratropio 40 mg 4 veces al día por vía inhalatoria o teofilina oral 200 mg 2 veces al día. Por distribución aleatoria se dividieron en dos series : ipratropio (n=30) y teofilina (n=32) realizándose cambio de terapia a los 3 meses. Los pacientes fueron sometidos mensualmente a un seguimiento clínico y funcional durante el tiempo de duración del estudio. Al final del período de tratamiento, la disnea mejoró solo durante el período con ipratropio (p<0,01), aunque no se apreció cambios significativos en la función pulmonar con ninguno de los dos medicamentos. Durante el período con ipratropio se presentó una menor frecuencia de reacciones adversas severas (p < 0,05)

Efecto broncodilatador de salbutamol más bromuro de ipratropio en niños asmáticos: relación dosis respuesta / Bronchodilator effect of ipratropium bromide plus salbutamol in asthmatic children: dose response relationship

El bromuro de ipratropio (BI) asociado con un agente beta 2 agonista en aerosol producido por inhalador de dosis medida (IDM) es frecuentemente empleado en lactantes y niños con obstrucción bronquial. En este estudio se evaluó el efecto broncodilatador de dos dosis diferentes (2 y 4 puffs) de una mezcla de BI más salbutamol (S) en IDM (Combivent) en 28 niños con asma leve a moderada. El estudio fue aleatorio, cruzado, controlado con placebo y simple ciego. La CVF, VEF1 y FEF25-75 se midieron en condiciones basales, antes y después de placebo y de cada una de las dosis empleadas. El análisis estadístico se realizó mediante pruebas no paramétricas para muestras pareadas. No hubo diferencias significativas en ninguno de los índices espirométricos descritos al usar 2 o 4 "puffs" de BI+S. Sin embargo, en los pacientes que tuvieron un aumento del VEF1 > o igual 15 por ciento con cualquiera de las 2 dosis de BI+S, el aumento del FEF25-75 fue significativamente mayor al usar 4 "puffs". Lo anterior sugiere que 2 "puffs" de BI+S serían igualmente efectivos para producir broncodilatación en niños asmáticos. Sin embargo, en aquellos pacientes que presentan un mayor grado de obstrucción bronquial, o como en este estudio, una reversibilidad bronquial más alta al broncodilatador, el empleo de 4 "puffs" de BI+S podría ser más eficiente para obtener una mejor broncodilatación

Teofinila e fenoterol isolados ou combinados com brometo de ipratrópio em DPOC: efeitos a longo prazo medidos por funçäo pulmonar seriada, qualidade de vida e uso adicional de broncodilatador / Theophylline and fenoterol isolated or combined with ipratropium bromide in COPD: long-term effects measured by serial peack expiratory flow rate, quality of life and extra-use of bronchodilator

OBJETIVO: Comparar o efeito do fenoterol e brometo de ipratróprio em doses acima das usuais e teofilina, isolados ou combinados em DPOC. MÉTODOS: foram incluídos pacientes com VEF1 abaixo de 60 por cento do previsto e VEF1/CVF menor do que 70 por cento após broncodilatador (Bd). Tolerância à teofilina foi necessária para inclusäo. Após período basal de três semanas, em que apenas fenoterol em spray usado se necessário era permitido, os pacientes foram alocados de maneira aberta e randomizada para cinco períodos de tratamento de três semanas com: fenoterol (F) 600mcg quatro vezes ao dia; teofilina de liberaçÝo lenta (T) duas vezes ao dia; F 300 mcg e brometo de ipratrópio (BI) 120mcg quatro vezes ao dia ; F 600mcg e T; F300 mcg, BI 120mcg quatro vezes ao dia e T. A resposta foi avaliada por medida seriada do pico de fluxo expiratório (PFE), qualidade de vida, espirometria, teste de caminhada de seis minutos e uso adicional de Bd para controle sintomático. RESULTADOS: Trinta pacientes completaram o estudo. O VEF1 foi de 1,15 mais ou menos 0,37 L. A mediana da resposta ao Bd agudamente foi de 16 por cento. O nível sérico da T foi de 13,8 mais ou menos 2,8 mg/l. Näo ocorreram mudanças significativas na CVF1, VEF1 e distância caminhada. Cada um dos esquemas aumentou o PFE em relaçäo ao período basal (F=5,25-p menor que 0,01), mais nos respondedores ao Bd no laboratório. Os valores do PFE foram menores que o tratamento F. A dispnéia caiu de modo semelhante em todos os grupos, mas sua variaçäo näo se correlacionou com as variaçöes do PFE. Todos os tratamentos resultaram em reduçäo significativa do número de doses extras de Bd (x2=28,06-p menor que 0,05) mais com F+T e F+t+BI e em melhora na qualidade de vida (x2 =19,5-p menor que 0,001), mas sem diferenças entre os tratamentos. CONCLUSÖES: A resposta a broncodilatadores avaliada por medidas de qualidade de vida e dispnéia näo se correlaciona com a resposta funcional avaliada por espirometria e medidas seriadas do PFE. A resposta ao uso regular de betagonista é menor do que a encontrada com teofilina ou a combinaçäo de betagonista e ipratrópio, estes últimos sendo equivalentes. Quando betagonista é combinado com teofilina ou com teofilina e ipratrópio, é vista maior reduçäo no uso de Bd adicional, porém os efeitos colaterais aumentaras; PFE, dispnéia e qualidade de vida permaneceram inalterados.

Helium/oxygen flow volume curves in normal Indian males > 50 year, and the effect of bronchodilator aerosols on airflow variables in this subject group.

Fourteen healthy males (mean age 54.7 yr) described maximal flow volume curves after Air breathing (AB) and after inspiring 10 deep breaths of a mixture of 80% Helium/20% Oxygen (He/O2). Vmax 50% FVC as obtained from the AB curves was 3.11 +/- 1.27 lps, and this increased by 38.1 +/- 17%, with He/O2. The Vmax 50% He-O2/Air ratio was 1.32 +/- 0.17, while the V iso V was 1.1 +/- 0.35 liters (30.9% of the FVC). Inhalation of 80 micrograms (4 puffs) of Ipratropium bromide, a vagolytic aerosol, or salbutamol (200 micrograms; 2 puffs), a beta 2 adrenergic stimulant did not alter the He/O2 curves significantly. As another aspect of the study, airflow variables viz. Vmax 50% of the FVC, Vmax 25%-75%, and Vmax 25% were measured from the AB curves, and the effect of bronchodilator aerosols was investigated in order to evaluate the degree of control of the bronchomotor tone by either the adrenergic receptors, or the vagus. Only the Vmax 25%-75% increased significantly with Salbutamol administration. While the degree of increase brought about by salbutomol aerosol for all of the variables under investigation was more than that seen with ipratropium br., the difference in this increase between the two bronchodilators used was not significant. The result may indicate that almost an equivocal influence is exerted by the two arms of the autonomic nervous system on bronchomotor tone in middle aged normal males, and that a more sensitive test (viz He-O2 breathing) does not elucidate this any further.

Eficácia do brometo de ipratrópio na rinite alérgica / On the efficacy of ipratropium bromide in allergic rhinitis

O presente estudo avaliou a eficácia do brometo de ipratrópio (BI)2 como coadjuvante no tratamento da rinite alérgica com intenso componenente vasomotor, caracterizada pela rinorréia abundante além dos sintomas clássicos de espirros, prurido e obstruçåo nasal. Foram testados dois grupos de 21 pacientes onde se administrou ao primeiro um anti-H1 (Loratadine 10mg - uma vez por dia, via oral) + BI spray nasal (Boehringer Ingelheim 80mg - três vezes por dia), e apenas o anti-H1 (Loratadine 10mg - uma vez por dia via oral) ao segundo grupo por um período de 30 dias (Fig. 1). Observamos uma significante reduçåo da rinorréia nos grupos de pacientes que fizeram uso do brometo de ipratrópio associado ao anti-histamínico. A tolerabilidade foi boa e eventuais queixas locais foram superadas com a diminuiçåo da dosagem. Nåo foi relatado nenhum efeito colateral siostêmico de natureza anticolinérgica durante o período de administraçåo do BI

Study of ipratropium bromide inhalation in stable asthma.

An open two weeks short term trial of Ipratropium Bromide (IB) inhalation (0.02 mg per dose) was carried out in 20 stable asthamatics to study its efficacy and safety. Early significant rise in PEFR (P < 0.001) and FEV1 (P < 0.05) was observed after 15 min of IB inhalation and reached significant peak (P < 0.01) after 1 hour which was persistent beyond three hours after IB inhalation. No side effects were observed. It was concluded that Ipratropium Bromide Imhalation is safe and has efficient bronchodilatory effect on short term basis in stable asthmatics.