Use of nebulized bronchodilators in infants under 1 year of age: analysis of four forms of therapy. A randomized, controlled trial of nebulized terbutaline for the first acute bronchiolitis in infants less than 12-months-old. The use of albuterol in hospitalized infants with bronchiolitis. Early nebulized budesonide in the treatment of bronchiolitis and the prevention of postbronchiolitic wheezing. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis. Effect of treatment with dornase alpha on airway inflammation in patients with cystic fibrosis. Nebulised sodium cromoglycate in the treatment of wheezy bronchitis in infants and young children. Dexamethasone inhalations in RSV bronchiolitis: a double-blind, placebo-controlled study.
The main purpose of this study was to evaluate four different forms of treatment in young infants admitted for acute wheezing (AW). Seventy-nine infants less than one year of age were randomly assigned to one of five groups. Group 1 received nebulized fenoterol plus ipratropium bromide, group 2 fenoterol, group 3 fenoterol plus steroids, and group 4 aminophylline, IV, plus steroids and oral fenoterol; the control group, or group 5, received nebulized normal saline solution. Clinical evaluation was done by means of a scoring system. The effectiveness of treatments was estimated by a score decrease in the first 24 hours, by the percentage of patients whose scores did not decrease during the same period, and by the number of days in the hospital. All infants had significantly decreased scores, except those in the control group; the aminophylline group included a greater percentage of patients who did not abate their scores, and they stayed in the hospital for more days than those in the other groups. The fenoterol group had the shortest hospital stay. All four treatments produced objective clinical improvement in bronchial obstruction. However, the nebulized bronchodilator treatments were more effective than aminophylline IV in decreasing scores on the first day, and they resulted in shorter hospitalization. Despite the common clinical practice, the available evidence on the efficacy of bronchodilators therapy for bronchiolitis is conflicting. The aim of this study is to evaluate the efficacy of nebulized terbutaline in bronchiolitis as measured by improvement in clinical score, oxygen saturation or reduction in duration of hospitalization.
                This prospective, double blind, placebo controlled, randomized clinical trial was performed at Children's Hospital of Tunis from December 2004 to April 2006. A total of 35 patients less than 12 months of age with diagnosis of moderately severe bronchiolitis were enrolled and assigned to receive nebulized terbutaline or normal saline placebo at admission (T0), at 30 minutes after admission (T30) and every four hours during a study period. Outcome measurements included: Respiratory Distress Assessment Instrument (RDAI) score, respiratory rate, oxygen saturation, heart rate and the duration of hospitalization.
                There were no significant difference between terbutaline and placebo at baseline, T30 min, T60 min, and T120 min after start study in RDAI score, oxygen saturation in room air, rate respiratory and heart rate. There was no difference in duration of hospitalization.
                Nebulized terbutaline therapy does not appear effective in treating moderately ill infants with the first acute bronchiolitis. To determine whether the use of albuterol by nebulization enhances physiologic or clinical recovery in hospitalized infants with moderate bronchiolitis.
                This prospective, double-blind, placebo-controlled, randomized clinical trial was performed from December 1995 to March 1996. A total of 52 patients <24 months of age with a diagnosis of moderately severe, acute viral bronchiolitis were enrolled and assigned to receive nebulized albuterol or normal saline placebo for 72 hours under a standardized protocol. Primary outcome measures included improvement in oxygen saturation (SaO2) during hospitalization and survival analysis to assess the time required to reach preestablished discharge criteria on three measures: SaO2, accessory muscle use, and wheezing. An additional secondary outcome measure was actual length of hospital stay. Adverse outcomes also were compared between treatment groups.
                There was no significant difference in mean SaO2 between albuterol and placebo at baseline, 24 hours, or maximum SaO2 achieved during hospitalization. Both groups showed significant improvement in oxygen saturation over time, but there was no significant difference in improvement between the two groups. The study had a power of 90% to detect a difference in mean percentage point improvement of 2% SaO2. There was no difference in time to reach discharge criteria as defined by SaO2, accessory muscle use, or wheezing. There was no difference in length of hospital stay or in the frequency of adverse outcomes.
                Nebulized albuterol therapy does not appear to enhance recovery or attenuate severity of illness in infants hospitalized with acute, moderate bronchiolitis, as evidenced by improvement in oxygen saturation, time to meet standardized discharge criteria, or length of hospital stay. To determine the effectiveness of nebulized budesonide in the treatment of acute bronchiolitis and in the prevention of postbronchiolitic wheezing.
                A randomized, double-blind, placebo-controlled trial was performed.
                Forty infants with bronchiolitis (83% RSV), mean age 13.5 weeks (range 4 to 41 weeks), were admitted to the Royal Alexandra Children's Hospital, Brighton, UK.
                Twenty-one infants received nebulized budesonide 1 mg every 12 hours for 5 days, then 500 micrograms every 12 hours continuing to a total of 6 weeks. Nineteen received nebulized placebo (0.9% saline) for 6 weeks. A clinical scoring system was used to rate acute symptoms, and diary cards were used to assess persistent respiratory symptoms over a 6-month follow-up period.
                No significant differences were found between the budesonide and placebo groups in change in clinical score 48 hours after trial entry, mean oxygen requirements, or length of hospital stay during the acute illness. At 6-month follow-up, the two groups did not differ significantly in prevalence of wheeze, respiratory symptom scores, or proportion requiring bronchodilators or steroids.
                This study did not demonstrate that a 6-week course of nebulized budesonide reduced the symptoms of acute bronchiolitis or prevented postbronchiolitic wheezing. To investigate the use of nebulized 3% hypertonic saline (HS) for treating viral bronchiolitis in moderately ill hospitalized infants by a prospective, randomized, double-blinded, controlled, multicenter trial.
                A total of 96 infants (mean age, 4.7 months; range, 0.3 to 18 months) admitted to the hospital for treatment of viral bronchiolitis were recruited from 3 regional pediatric centers over 3 bronchiolitis seasons (December 2003 to May 2006). Patients were randomized to receive, in a double-blind fashion, repeated doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group), in addition to routine therapy ordered by the attending physician. The principal outcome measure was hospital length of stay (LOS).
                On an intention-to-treat basis, the infants in the HS group had a clinically relevant 26% reduction in LOS to 2.6 +/- 1.9 days, compared with 3.5 +/- 2.9 days in the NS group (P = .05). The treatment was well tolerated, with no adverse effects attributable to the use of HS.
                The use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis. To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis.
                A multicentre randomised double blind placebo controlled trial.
                Infants admitted to hospital with their first episode of RSV positive bronchiolitis.
                Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months.
                Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up.
                161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8).
                There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis. Recombinant human deoxyribonuclease (rhDNase) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis (CF), but its long-term effect on airway inflammation remains unknown. In this study, we used bronchoalveolar lavage (BAL) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease. A total of 105 patients with CF (> or =5 years of age) having normal lung function were randomized to receive rhDNase (2.5 mg/day) or no rhDNase. Patients with a normal percentage of neutrophils in BAL fluid at baseline were not randomized and served as the control group. The percentage of neutrophils in the pooled BAL sample was similar in both randomized groups at baseline. A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects, whereas neutrophils remained unchanged in patients treated with rhDNase. Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase. We conclude that in patients with CF, an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment. 44 children under 2 years of age suffering from recurrent or persistent wheezy bronchitis, completed a double-blind crossover trial comparing nebulised sodium cromoglycate and matching placebo. Analysis showed that treatment response was age-related. Sodium cromoglycate proved significantly superior to placebo in reducing night cough, sleep disturbance, wheeze and activity limitation in the 24 patients aged 12 months and above (mean 17.3) on entry to the study. Whereas no significant differences were observed in the 20 children below 12 months of age (mean 8.3). These findings were confirmed by weekly clinical assessment. Both age groups spent fewer days in hospital during the active treatment period. Final subjective assessments showed that the older age group, parents favoured cromoglycate treatment, whereas in the younger age group, parents favoured placebo, although neither reached statistical significance. Both age groups showed marked placebo response to nebulised water. To evaluate the effect of inhaled dexamethasone on hospitalization for respiratory syncytial virus (RSV) bronchiolitis.
                A double-blind, placebo-controlled study compared nebulization of dexamethasone versus nebulization of 0.9% saline. Both groups were treated with epinephrine nebulizations. Follow-up continued for 3 mo.
                Sixty-one infants with bronchiolitis aged 3 to 12 mo were included. They were randomly allocated to nebulizations with 0.25 mg dexamethasone every 6 h (group 1) or an equivalent amount of normal saline (group 2).
                No statistically significant differences with respect to clinical score, oxygen saturation, or IV fluid requirement between the groups were noted. Using Kaplan-Meyer's method, the cumulative proportion of in-hospital stay was significantly lower in group 1 compared with group 2, mainly in days 5 and 6 post-hospitalization (p<0.038). A subgroup of prematurely born children in group 1 had a shorter hospitalization period (6.5+/-1.7 d) compared with group 2 children (9.1+/-1.9) (p<0.018). Follow-up revealed similar wheeze and hospitalization rates in the two groups.
                Inhaled dexamethasone may reduce the length of hospitalization among infants with acute viral bronchiolitis, especially among those born prematurely.
The results based on the three included studies in this review did not support the use of nebulised rhDNase in children under 24 months of age hospitalised with acute bronchiolitis. In these patients, treatment did not shorten the length of hospitalisation or improve clinical outcomes. It might have a role in severe bronchiolitis complicated by atelectasis, but further clinical studies would need to be performed.