Role of adenylyl cyclase in reduced ß-adrenoceptor-mediated vasorelaxation during maturation

Beta-adrenergic receptor (βAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of βAR subtypes (β1AR, β2AR, and β3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of βAR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of βAR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744-dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The β1AR antagonist CGP20712A (10-7 M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The β2AR antagonist ICI-118,551 (10-7 M) inhibited isoproterenol-dependent aortic relaxation in both groups. The β3AR antagonist SR59230A (10-7 M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All βAR subtypes were expressed in both groups, although β3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of β3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group.

Comparative study of protective effects of salbutamol and beclomethasone against insulin induced airway hyper-reactivity on isolated tracheal smooth muscle of guinea pig

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin [10[-7] to 10[-3] M], insulin pretreated with fixed concentration of salbutamol [10[-7] M] and beclomethasone [10[-6] M] were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean +/- SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 +/- 1.13 mm, 14.55 +/- 0.62 mm and 22 +/- 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction

Comparación de la eficacia y seguridad de dos combinaciones nebulizadas; sulfato de magnesio mas salbutamol versus salbutamol mas solucion salina normal, en el tratamiento del sindrome bronquial obstructivo en pediatría / Comparison of efficacy and safety of two nebulised combinations: magnesium sulfate more salbutamol versus salbutamol more normal saline solution in the treatment of obstructive bronchial syndrome In a pediatric populación

Los síndromes bronquiales obstructivos constituyen una patología muy frecuente y recurrente en la población pediátrica. El tratamiento convencional, incluye el uso de beta dos agonistas nebulizados de corta acción y esteroides sistémicos. Sin embargo existe una proporción de pacientes que no responden a ésta terapia por lo que son justificadas la utilización de otras medidas como ser la combinación nebulizada de sulfato de magnesio más salbutamol el cuál será el objetivo a investigar desde el punto de vista de eficacia y seguridad en comparación a la combinación nebulizada de salbutamol más solución salina normal, con el propósito de sugerir - sí resultase útil - una nueva alternativa de tratamient o. Se estudiaron 100 pacientes, 44 recibieron la combinación de magnesio con salbutamol y el resto salbutamol con solución salina; el 93% del grupo inicial presentó resolución total de su cuadro en las primeras 12 horas en comparación al 63% del grupo con la segunda combinación (p=0.003). Ambas combinaciones fueron seguras...(AU)

Pharmacologic bronchodilation response to salbutamol in COPD patients.

Background: Airway hyperresponsiveness (AHR) is the most characteristic feature of asthma, which is reported in COPD patients and smokers. Increased airway responsiveness to ί-agonists is also demonstrated in asthmatics as well as smokers. However, there is no report regarding AHR to ί-agonist drugs in COPD patients. Therefore, in this study pharmacologic bronchodilation response to salbutamol in COPD patients was examined. Materials and Methods: The threshold concentrations of inhaled salbutamol required for a 20% change in forced expiratory flow in 1 sec (FEV 1 ) as PC 20 , or a 35% change in specific airway conductance (sGaw) as PC 35 was measured in 14 COPD patients and 14 normal subjects. Results: Airway responsiveness to salbutamol in COPD patients (PC 20 = 14.14 ± 1.62 and PC 35 = 9.70 ± 1.48 mg/l) was significantly lower than normal subjects (PC 20 = 224.57 ± 16.62 and PC 35 = 81.87 ± 8.16 mg/l, P < 0.001 for both cases). The values of FEV 1 and sGaw in COPD patients (56.43 ± 14.45 and 0.081 ± 0.120 respectively) were significantly lower than those of normal subjects (104.07 ± 5.72 and 0.194 ± 0.041 respectively), (P < 0.001 for FEV 1 and P < 0.005 for sGaw). There was a significant correlation between FEV 1 with PC 20 salbutamol (r = 0.862, P < 0.001). The correlations between PC 20 and PC 35 was also statistically significant (r = 0.862, P < 0.001). Conclusion: These results showed increased airway responsiveness of most COPD patients to salbutamol which was highly correlated to airway caliber.

Técnica de oscilações forçadas na análise da resposta broncodilatadora em voluntários sadios e indivíduos portadores de asma brônquica com resposta positiva / Using the forced oscillation technique to evaluate bronchodilator response in healthy volunteers and in asthma patients presenting a verified positive response

OBJETIVO: Analisar, através da técnica de oscilações forçadas, pacientes asmáticos com resposta broncodilatadora positiva pelo laudo espirométrico e comparar esses resultados com os obtidos em indivíduos sadios. MÉTODOS: Foram analisados 53 indivíduos não tabagistas, sendo 24 sadios sem história de doença pulmonar e 29 asmáticos com resposta broncodilatadora positiva segundo o laudo espirométrico. Todos foram submetidos à técnica de oscilações forçadas e a espirometria antes e após vinte minutos da administração de salbutamol spray (300 g). Os parâmetros derivados da técnica de oscilações forçadas foram: resistência total, reatância total, resistência extrapolada para o eixo y, coeficiente angular da reta de resistência e complacência dinâmica. Na espirometria, os parâmetros utilizados foram o volume expiratório forçado no primeiro segundo e a capacidade vital forçada. RESULTADOS: No grupo controle, a utilização do broncodilatador produziu alteração significativa na resistência extrapolada para o eixo y (p < 0,001), embora o coeficiente angular da reta de resistência e a complacência dinâmica não tenham apresentado diferenças estatisticamente significativas. A análise dos asmáticos mostrou que a diferença entre as medidas pré e pós-broncodilatador foi significativa, tanto para os parâmetros espirométricos quanto para os de técnica de oscilações forçadas. Valores de p < 0,001 foram obtidos em todas as comparações relacionadas aos asmáticos. CONCLUSÃO: As alterações nos parâmetros obtidos a partir da técnica de oscilações forçadas mostraram-se em estreita concordância com a fisiopatologia da resposta broncodilatadora em asmáticos, indicando que a técnica de oscilações forçadas pode ser útil como análise complementar à espirometria nesses pacientes.

Effect of salbutamol on innervated and denervated rat soleus muscle

The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a ß2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10), treated with salbutamol (N = 30), denervated (N = 30), and treated with salbutamol after denervation (N = 30). Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21 percent) in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2 percent compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other ß2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.

Evaluation of tocolytic efficacy of selective beta2 adrenoceptor agonists on buffalo uterus.

Present study was conducted on prostaglandin F2alpha (PGF2alpha), oxytocin, (OT), potassium chloride (KCI) and barium chloride (BaCl2) pre-contracted perimetrial uterine strips of dioestrus and pregnant buffaloes to evaluate the tocolytic efficacy of selective beta2 adrenoceptor agonists-albuterol (salbutamol) and terbutaline. Cumulative concentration-response curves of both the beta2 adrenoceptor agonists were constructed and the mean effective concentration (EC50) values determined and compared statistically. Based on the comparative EC50 values in relaxing the pre-contracted uterine strips with different spasmogens, the rank order potency of albuterol was found to be--PGF2alpha > BaCl2 > OT > KCl on uterine strips from dioestrus animals, while OT> BaCl2> PGF2alpha >KCl on the uterine strips of pregnant buffaloes. The rank order potency of terbutaline on uterine strips from dioestrus stage animals was- BaCl2 > OT > KCl > PGF2alpha, while BaCl2 > PGF2alpha > KCl > OT on uterine tissues of pregnant animals. Thus, irrespective of the state of uterus, whether gravid or non-gravid, KCl-depolarized uterine tissues required comparatively higher concentrations of albuterol or terbutaline to produce tocolytic effect. High concentrations of K+ in biophase may have interfered with the beta2 adrenoceptor agonists-induced outward K+ current and hyperpolarization. From the results of present study, it was evident that selective beta2 adrenergic agonists had good tocolytic efficacy on the uterus of buffaloes. Further, indirectly the possibility of existence and activation of K(Ca) channels by selective beta2 adrenoceptor agonists in mediating tocolysis of buffalo myometrium can not be ruled out, however, detailed studies using specific K(Ca) channel blockers are required for characterizing the nature of such channels in buffalo uterus.

Reversibilidad espirométrica en la enfermedad pulmonar obstructiva crónica: efecto diferencial del salbutamol sobre el volumen espiratorio forzado del primer segundo y el volumen pulmonar / Spirometric reversibility to Salbutamol in chronic obstructive pulmonary disease (COPD): differential effects on FEV1 and on lung volumes

Background: In recent years it has been suggested that in COPD, lung volumes can be modified more than expiratory flows, with bronchodilators. Aim: To study the acute effects of salbutamol on FEV1 and lung volumes at rest. Subjects and Methods: Forty stable COPD patients were studied using a single dose of salbutamol (200 µg). Forced expiratory volumen in 1 second (FEV1), slow vital capacity (SVC), forced vital capacity (FVC), and inspiratory capacity (IC) were measured at baseline and after salbutamol administration. Results: After salbutamol, 39/40 patients exhibited a clinically significant increase in volumes (SVC, FVC or IC ×10 percent predicted). A significant increase in FEV1 (×10 percent predicted) was observed in only 13 patients. Conclusions: Our results demonstrate that changes in lung volumes, and consequently in dynamic lung hyperinflation, take place more frequently than changes in maximal expiratory flows during the spirometric test in patients with COPD. Assessment of spirometric reversibility based only on changes in FEV1 underestimates the effect of bronchodilator drugs in these patients.

Effect of inhalation of salbutamol, beclomethasone dipropionate & ipratropium bromide on mucociliary clearance in some patients with chronic stable bronchial asthma.

BACKGROUND & OBJECTIVES: Asthma is now regarded as an inflammatory disease and bronchial inflammation may disrupt mucociliary function. Inhaled drugs may act by improving mucociliary function. The aim of the study was to investigate the effect of salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic stable asthma and to compare the efficacy of these drugs on mucociliary clearance. METHODS: Ten patients with chronic stable asthma were enrolled in the study, but two patients did not complete the study. Patients with bronchial asthma were chosen on clinical grounds. (99m)Tc phytate radioaerosol generated through a nebulizer, was given to each patient on four days. After each administration the radioactivity over the thorax was constantly measured in sequential frame mode for 120 min. Radioactivity in the thorax was also measured after 24 h. A base-line pulmonary function test with reversibility was obtained. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four days. RESULTS: The mean age of patients (n = 8) was 36 +/- 9.3 yr and mean duration of symptoms was 5 +/- 6.6 yr. There was no visual impression that mucociliary clearance was enhanced with any of the drugs. The time activity curves did not show any visually recognisable change in slope. In only one patient the curve tended to show a steeper slope with ipratropium inhalation. In the rest of the patients the curves showed no difference at all with medication when compared with placebo. All the quantitative indices analyzed by two-way ANOVA at the end of one and two hours were comparable for the three test drugs and placebo. None of the three test drugs demonstrated statistically significant mucociliary clearance effect compared with placebo. However, the temporal difference in airways clearance efficiency (ACE) was significant with beclomethasone and ipratropium bromide. INTERPRETATION & CONCLUSION: Inhalation of any of the three drugs tested did not produce any immediate improvement in mucociliary clearance as compared to placebo in patients with stable bronchial asthma suggesting the need for further studies using higher doses of drugs for longer duration in a large sample.

Airway Reactivity to Bronchoconstrictor and Bronchodilator: Assessment Using Thin-Section and Volumetric Three-Dimensional CT

OBJECTIVE: To determine the extent to which thin-section and volumetric three-dimensional CT can depict airway reactivity to bronchostimulator, and to assess the effect of different airway sizes on the degree of reactivity. MATERIALS AND METHODS: In eight dogs, thin-section CT scans were obtained before and after the administration of methacholine and ventolin. Cross-sectional areas of bronchi at multiple levels, as shown by axial CT, proximal airway volume as revealed by three-dimensional imaging, and peak airway pressure were mea-sured. The significance of airway change induced by methacholine and ventolin, expressed by percentage changes in cross-sectional area, proximal airway volume, and peak airway pressure was statistically evaluated, as was correlation between the degree of airway reactivity and the area of airways. RESULTS: Cross-sectional areas of the bronchi decreased significantly after the administration of methacholine, and scans obtained after a delay of 5 minutes showed that normalization was insufficient. Ventolin induced a significant increase in cross-sectional areas and an increase in proximal airway volume, while the effect of methacholine on the latter was the opposite. Peak airway pres-sure increased after the administration of methacholine, and after a 5-minute delay its level was near that of the control state. Ventolin, however, induced no significant decrease. The degree of airway reactivity did not correlate with airway size. CONCLUSION: Thin-section and volumetric spiral CT with three-dimensional reconstruction can demonstrate airway reactivity to bronchostimulator. The degree of reactivity did not correlate with airway size.

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

Effects of trypan blue on the action of adrenergic agonists in the guinea-pig isolated atrium.

It has been reported that trypan blue, a diazo dye with polyamphipathic structure, can inhibit the coupling of receptors to G-proteins. The present study was carried out to investigate the effect of trypan blue on the actions of adrenoceptor agonists in the guinea-pig atrium. Trypan blue (10 and 100 microM) antagonized the positive inotropic effects of isoprenaline and dobutamine by shifting their concentration-response curves to the right. With the selective beta 2-adrenoceptor agonist, salbutamol, there was a reduction of response in the presence of trypan blue. Therefore, we concluded that trypan blue diminish the response to beta-adrenoceptor agonists possibly via decoupling receptors from Gs. Trypan blue and similar agents, due to their unique mode of action, can be used as tools for the investigation of the mechanism of receptor-G protein coupling in the whole tissue preparation.

Saturación arterial de oxígeno contra flujo espiratorio máxima como valores predictivos en la evolución de la crisis asmática en niños / The value of arterial oxygen saturation versus peak expiratory flow rate measurements as predictors of the outcome of the asthmatic crisis in children

Estudio prospectivo, longitudinal, observacional, comparativo, en 50 niños de uno y otro sexo (30 masculino y 20 femeninos), con edades entre 6 y 18 años, con crisis asmática moderada. Se determinó la saturación arterial de oxigeno (SaO2) y el flujo espiratorio máximo (FFM) al momento de su llegada a urgencias y a los 30 minutos, 2, 4 y 24 horas después de la administración de salbutamol en aerosol (100 mcg/dosis), con el propósito de relacionar el valor de ambas mediciones con el pronóstico de dichos pacientes. De los 50 pacientes evaluados 48 se trataron en forma ambulatoria y dos requirieron hospitalización. Se observaron diferencias estadisticamente significativas en la SaO2, basal y los registros tomados a las 2, 4 y 24 horas postratamiento (p < 0.01), y sólo se observaron diferencias estadisticamente significativas entre el FEM basal y el registro tomado a las 24 horas postratamiento. En conclusión la SaO2 tiene un mejor valor predictivo que el FEM en la evolución de la crisis asmática en niños

Resposta broncodilatadora de doses cumulativas de salbutamol aerossol em asmáticos / Bronchodilator agents response to cumulative dose of salbutamol aerosol in asthmatic patients

Avaliamos a eficácia e segurança de doses crescentes de salbutamol em aerossol dosificador de 0,1 mg a 1,5 mg, e comparadas com placebo, em crianças asmáticas. Iniciamos com 1 "puff" e a cada 15 minutos era adicionado mais 1 "puff" totalizando 5 "puffs" ou 15 "puffs" acumulados. Em relaçäo aos valores basais houve aumento do VEF1 e FEF 25-75 por cento com 0,1 mg (1 "puff"). Comparando com o efeito do placebo, o salbutamol provocou aumento significativo do VEF1 a partir de 2 "puffs". A freqüência cardíaca e pressäo arterial näo variaram durante o estudo. Tremor de mäos näo foi observado até a dose de 0,3 mg de salbutamol; com a dose máxima de 1,5 mg, 6/10 pacientes referiam tremor. A dose broncodilatadora ótima nesse grupo de crianças foi entre 3 a 6 doses do aerossol, provavelmente entre 0,3 e 0,6 mg de salbutamol. Administrado por aerossol dosificador, o salbutamol mostra-se, além de eficaz, seguro para crianças com asma, e alternativa para alívio do broncoespasmo nos que têm habilidade para uso do aerossol.

Valoración espirométrica del salbutamol en pacientes asmáticos mediante el uso de dos espaciadores: asmacámara y volumatic / Spinal metric valuacion of the salbutanol in asthmatic patients by means of the use of two: asthmacara and volumatic

Los espaciadores son comúnmente utilizados en la terapia aerosol. Sin embargo los existentes en el mercado son costosos. En la región se diseño un espaciador llamado Asmacámara y el objeto del presente estudio fue comparar la eficacia de la Asmacámara versus un espaciador convencional, el Volumatic, mediante la respuesta espirométrica del Salbutamol en pacientes asmáticos. Se estudiaron 27 pacientes (F: 18; M:9; edad media; 15.8) con asma estable, ellos asistían al laboratorio de la Unidad de Farmacología Clínica donde se evaluaron los siguientes parámetros: VEF-1; CVF; PEFR; frecuencia cardíaca y presión arterial basal. Se administraban dos inhalaciones del Salbutamol (200 µg) a través de uno de los dos espaciadores, seleccionados al azar. Los mismos parámetros fueron medidos 10 y 30 minutos después. El otro espaciador fue evaluado 48 horas después, utilizando el mismo procedimiento. Los resultados encontrados demuestran que los incrementos de las pruebas espirométricas, fueron ligeramente superiores cuando la Asmacámara fue utilizada. Sin embargo, ello no alcanzó a ser estadísticamente significativa, con la sóla excepción de la CVF a los 30 minutos (p<0,05). La frecuencia cardíaca y presión arterial no sufrieron cambios significativos en ninguna de las pruebas. En conclusión, la administración del salbutamol a través de la Asmacámara, fue tan efectiva como la obtención a través del Volumatic. La Asmacámara representaría una alternativa confiable en el uso de los espaciadores en el tratamiento del asma mediante inhaladores

Effect of thyroxine on experimental bronchospasm in guinea pigs.

Effect of Thyroxine was studied in histamine induced bronchospasm in guinea pigs. Chronic treatment with the drug significantly protected against experimental bronchospasm. Thyroxine also potentiated salbutamol evoked bronchodilation in this experimental model. Up-regulation of beta-2 adrenoceptors in bronchial smooth muscle may be the probable mechanism of action of thyroxine.

Broncodilatadores en síndrome bronquial obstructivo del lactante / Bronchodilator agents in obstructive bronchial syndrome in infants

Se evalúa la respuesta clínica a diferentes broncodilatadores en 100 lactantes con síndrome bronquial obstructivo que, por la intensidad de éste requerían hospitalización, mediante un estudio prospectivo doble ciego, en el que se asignaron 25 niños menores de lactantes por grupo. Los niños del grupo I recibieron ipratropio (I), los del grupo II cloruro de sodio 9 por ciento (NaCI), en el grupo III se empleó fenoterol-ipratropio (FI) y en el grupo IV salbutamol (S), en todos los casos por nebulización. La calificación de Tal era similar al ingreso en los 4 grupos (día 0). Al día 1 del tratamiento era significativamente menor (p<0,05) en FI, como también el día 2 (p<0,01): (promedios día 1: 4,6 (I); 4,5 (NaCI); 3,8 (FI); 4,6 (S); día 2: 3,8 (I) 4,1 (NaCI); 2,1 (FI); 3,9 (S); día 3: 3,0 (I); 3,4 (NaCI); 1,6 (FI); 3,2 (S). El promedio de días estada fue I: 4,64 ñ 1,29; NaCI: 5,44 ñ 1,61; FI: 3,08 ñ 1,28; S: 5,28 ñ 1,69; p<0,001 a favor de FI. Los niños tratados con NaCI requirieron con mayor frecuencia terapia adicional con broncodilatadores (p<0,05) en claro contraste con los manejados con FI, que requirieron menos broncodilatadores adicionales que el resto (p<0,01) desde el día 1 del ingreso. No se registraron efectos secundarios indeseables con los diferentes regímenes aplicados