Inhaled salbutamol and beclomethasone for preventing broncho-pulmonary dysplasia: a randomised double-blind study. Delivery of salbutamol by metered dose inhaler and valved spacer to wheezy infants: effect on bronchial responsiveness. Bronchodilators for treatment of mild bronchiolitis: a factorial randomised trial. The role of bronchodilators in the management of bronchiolitis: a clinical trial. Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. Salbutamol or mist in acute bronchiolitis. Randomized trial of salbutamol in acute bronchiolitis. Equivalence of salbutamol 200 microg four times daily propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group. Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis.
Early inflammatory lesions and bronchial hyperresponsiveness are characteristics of the respiratory distress in premature neonates and are susceptible to aggravation by assisted ventilation. We hypothesized that treatment with inhaled salbutamol and beclomethasone might be of clinical value in the prevention of bronchopulmonary dysplasia (BPD) in ventilator-dependent premature neonates. The study was double-blinded and placebo controlled. We studied 173 infants of less than 31 weeks of gestational age, who needed ventilatory support at the 10th postnatal day. They were randomised to four groups and received either placebo + placebo, placebo + salbutamol, placebo + beclomethasone or beclomethasone + salbutomol, respectively for 28 days. The major criteria for efficacy were: diagnosis of BPD (with score of severity), mortality, duration of ventilatory support and oxygen therapy. The trial groups were similar with respect to age at entry (9.8-10.1 days), gestational age (27.6-27.8 weeks), birth weight and oxygen dependence. We did not observe any significant effect of treatment on survival, diagnosis and severity of BPD, duration of ventilatory support or oxygen therapy. For instance, the odds-ratio (95% confidence interval) for severe or moderate BPD were 1.04 (0.52-2.06) for inhaled beclomethasone and 1.54 (0.78-3.05) for inhaled salbutamol.
                This randomised prospective trial does not support the use of treatment with inhaled beclomethasone, salbutamol or their combination in the prevention of BPD in premature ventilated neonates. The efficacy of a new valved spacer device, the Babyhaler inhaler (Glaxo) for administering metered dose inhaler treatment via a facemask to infants was assessed. In a double blind, single dose study, salbutamol (800 micrograms) or placebo were given on separate days to 12 sedated, sleeping, wheezy infants during a symptom free interval. Lung function was measured before and after administration and the bronchial response to aerosol challenge with methacholine was then assessed using the squeeze technique. A small increase in heart rate and a drop in arterial oxygen tension followed salbutamol administration. No other change in lung volume or air flow obstruction was detected. Bronchial responsiveness decreased significantly after the administration of salbutamol by Babyhaler, the PC30 (provoking concentration of methacholine causing a 30% fall in maximal flow at functional residual capacity by the squeeze technique) increasing from a median of 3.8 g/l after placebo to 12.5 g/l after salbutamol. The Babyhaler is an effective device for administering bronchodilator to wheezy infants. The small scale of the response may be attributable to the uncertain effect of beta agonists in this population. Furthermore, pulmonary deposition of inhaled aerosols may be reduced in nose breathing, sleeping infants. A randomised double blind trial was conducted to determine the efficacy of inhaled bronchodilators, salbutamol and ipratropium bromide, compared with placebo in the treatment of bronchiolitis. Patients, who were 2 months to 2 years of age and without underlying cardiac or pulmonary disease, received drug 1 (salbutamol or saline placebo) followed one hour later by drug 2 (ipratropium bromide or placebo). Both agents were administered every four hours. The patients were allocated to one of four groups according to a factorial design. The four groups were similar in demographic characteristics, initial oxygenation, and clinical score. The change in oxygen saturation of recipients of both agents was significantly better than that of recipients of salbutamol alone or ipratropium bromide alone. This change, however, was not statistically different from that of the control group. No difference was observed in the clinical score or hospital duration. Inhaled bronchodilators did not improve the condition of hospitalised mild bronchiolitis. A randomized clinical trial was conducted on young children with bronchiolitis admitted to hospital with moderate illness to determine the efficacy of the bronchodilators Salbutamol and ipratropium bromide, either as a single drug or in combination, given as a nebulized solution, compared with a normal saline placebo. Eighty-nine patients, aged from 23 days to 11 months, were randomized into four groups, depending on administered drug or placebo, as follows: group 1--Salbutamol (n = 20); group 2--ipratropium bromide (n = 23); group 3--combined Salbutamol and Ipratropium bromide (n = 24); group 4--normal saline (n = 22). The groups were identical with respect to age, sex, family history of atopy, respiratory syncytial virus (RSV) positivity and enrollment score. They were scored using the clinical parameters of wheezing, retractions and respiratory rate at enrollment, at 30 and 60 minutes after the first nebulization, and after 60 minutes following completion of subsequent nebulization at 6, 12, 24 and 36 hours. We did not find any significant difference in the rate of improvement and the final score (p = 0.49) in the four groups. The same finding was also noted in children aged more than 3 months (p = 0.35) and in those positive for RSV infection (p = 0.18). The lengths of hospitalization in the four groups were also similar (p = 0.79). It is concluded that there is no role for the nebulized bronchodilators Salbutamol and Ipratropium bromide, either as a single agent or in combination, compared with normal saline placebo in treating young children in hospital with bronchiolitis. In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD. The role of bronchodilators in the treatment of bronchiolitis remains controversial.
                A double-blind, placebo controlled trial was performed to evaluate the clinical response to nebulized salbutamol. One hundred and fifty-six infants aged between 7 weeks and 24 months who had had an episode of wheezing and other signs and symptoms of bronchiolitis were randomized to three groups as follows: (i) nebulized salbutamol was administered to 52 patients in group I at a dose of 0.15 mg/kg in 2 mL saline; (ii) saline was nebulized to 52 patients in group II and (iii) in group III 52 patients received mist in a tent. All three groups were administered oxygen during the procedures. Treatment was repeated with the same agent after 30 min if the respiratory score was 5 or more. Respiratory rate, heart rate, oxygen saturation and presence of cyanosis, wheezing, retractions were recorded before and after each treatment.
                The decrease in the respiratory score was 5.2 +/- 1.8, 0.82 +/- 2.4 and 1.7 +/- 1.3 in group I, II and III, respectively. The decrease in group I was significantly higher than in the other groups. Heart rate was similar between groups. Oxygen saturation decreased in group I without reaching statistical significance.
                Salbutamol was shown to be effective and safe in the treatment of acute bronchiolitis. To test whether nebulized salbutamol (albuterol) is safe and efficacious for the treatment of young children with acute bronchiolitis, we enrolled 83 children (median age 6 months, range 1 to 21 months) in a randomized, double-blind clinical trial. Participants received two treatments at 30-minute intervals of either nebulized salbutamol (0.10 mg/kg in 2 ml 0.9% saline solution) or a similar volume of 0.9% saline solution placebo. Outcome measures were the respiratory rate, pulse oximetry, and a clinical score based on the degree of wheezing and retractions. Patients in the salbutamol arm had significantly greater improvement in clinical scores after the initial treatment (p = 0.04). There was no difference between the groups in oxygen saturation (p = 0.74); patients treated with salbutamol had a small increase in heart rate after two treatments (159 +/- 16 vs 151 +/- 16; p = 0.03). We conclude that salbutamol is safe and effective for the initial treatment of young children with acute bronchiolitis. The phasing out of chlorofluorocarbons (CFCs) requires the development of an alternative non-ozone depleting propellant for use in pressurized metered dose inhalers (pMDIs). The present study assessed the effects on tolerability and efficacy of a switch from the currently available formulation containing the CFC propellants 11 and 12 to an alternative non-CFC formulation using the propellant hydrofluoroalkane (HFA) 134a in patients with mild to moderate asthma. After a 4-week run-in period during which patients received salbutamol 200 microg four times daily from a CFC pMDI, 547 patients were randomized to 12 weeks of treatment with salbutamol 200 microg four times daily administered from either an HFA 134a pMDI (Ventolin CFC-free; 277 patients) or CFC pMDI (Ventolin, 270 patients). At the end of this period, all patients then received a further 4 weeks of treatment with the same dose of salbutamol via a CFC pMDI (run-out period). On the basis that high doses of beta2-agonists are known to increase heart rate, change in heart rate was selected as the primary outcome variable. Small increases in heart rate were observed during the treatment period and these changes were comparable in both groups; the 90% confidence interval for the treatment differences was within the predefined limits for clinical equivalence (+/- 10 beats min(-1)). The incidence of adverse events was similar in both groups and there were no reports of paradoxical bronchospasm. Furthermore, daily PEF measurements showed comparability in terms of lung function. Symptom scores and use of additional bronchodilator were also similar in both groups. These results demonstrate that salbutamol (800 microg day(-1)), formulated with HFA 134a is equivalent to the current CFC formulation in terms of tolerability and efficacy. To test the efficacy of a combined alpha- and beta-receptor agonist in acute bronchiolitis, we compared inhaled racemic epinephrine with salbutamol in a double-blind, crossover, randomized protocol. Twenty-four infants, 4.6 +/- 0.5 (mean +/- SEM) months of age, with their first episode of bronchiolitis were tested. After sedation with chloral hydrate, a clinical score and pulmonary mechanics measurements using simultaneous signals of airflow volume and transpulmonary pressure were recorded. After baseline measurements, infants received either nebulized salbutamol, 0.03 ml/kg, or racemic epinephrine, 0.1 ml/kg. Thirty minutes later, there was a significant decrease in clinical score after treatment with racemic epinephrine compared with the baseline score (p < 0.001); this difference was not present after salbutamol inhalation (p = 0.42). Only 13 patients had a decrease in clinical score after salbutamol therapy, in comparison with 20 infants treated with racemic epinephrine (p < 0.01). Both drug decreased respiratory rate, but the decrease was greater after the use of racemic epinephrine (p < 0.001). There was a significant decrease in inspiratory, expiratory, and total pulmonary resistance after treatment with racemic epinephrine compared with baseline values (p < 0.01) but no significant change after salbutamol inhalation. There was no significant correlation between the clinical score and pulmonary mechanics either at baseline or after drug treatment. We conclude that racemic epinephrine is superior to salbutamol in the treatment of infants with their first episode of acute bronchiolitis.
There are insufficient data to reliably assess the use of salbutamol for the prevention of CLD. Further clinical trials are necessary to assess the role of salbutamol or other bronchodilator agents in prophylaxis or treatment of CLD. Researchers studying the effects of bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes.