Predicting short term response to anti-inflammatory therapy in young children with asthma. Management of acute asthma in children using metered dose inhaler and small volume nebulizer. Oral montelukast treatment of preschool-aged children with acute asthma. Controlled trial of nebulized albuterol in children younger than 2 years of age with acute asthma. Reduction of nocturnal asthma by an inhaled anticholinergic drug.
Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.
                To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.
                A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.
                Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.
                Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma. To determine whether the administration of beta2-agonist by Metered Dose inhaler (MDI) with accessory device (AD) is a as effective as the administration of beta2-agonist by small volume nebulizers (SVN) for the treatment of acute asthma.
                A cross sectional study was conducted at Emergency Room (ER) of National Institute of Child Health (NICH), Karachi, between October 2000 to March 2001. This study included 150 children, 6 months and older with a history of wheeze and presenting with an acute asthma exacerbation. Children were categorized into mild, moderate and severe asthma according to medical scoring system. Children were assigned randomly into group A and B to receive standard dose of beta2-agonist (salbutamol) by MDI/AD (group A) or SVN (group B). Baseline characteristics and asthma severity were recorded. All variables (dyspnoea, use of accessory muscles, cyanosis, respiratory rate, heart rate, blood pressure, oxygen saturation, pulsus paradoxus, and wheeze) and Peak Expiratory Flow Rate (PEFR) in children 5 years and older, were determined at pre and post inhalation therapy.
                Both groups did not differ in demographic characteristics. There were no significant differences in outcome measures. In children treated with MDI/ADs and SVNs. PEFR increased significantly in both the groups after completion of treatment, but PEFR was not statistically significant when compared in between groups.
                The data suggested that MDI/AD is an effective alternative to nebulizer for the treatment of children with acute asthma exacerbation in the ER. Increased amounts of cysteinyl leukotrienes have been demonstrated in urine samples from asthmatic patients, particularly during exacerbations of asthma. Although the use of leukotriene receptor antagonists has been recommended in the treatment of chronic asthma, no guidelines are available regarding their use in the treatment of acute asthma.
                To investigate the safety and effectiveness of a 4-mg tablet of oral montelukast in addition to short-acting beta2-agonist bronchodilator as the initial treatment in mild to moderate asthma exacerbations in children between 2 and 5 years old.
                Fifty-one patients who were experiencing mild to moderate asthma exacerbation were included in a randomized, double-blind, placebo-controlled, parallel-group study. Each patient received either a 4-mg tablet of montelukast or placebo in addition to inhaled salbutamol and were followed up for 4 hours. The pulmonary index score, respiratory rate, and pulse were determined at baseline and throughout 4 hours after administration.
                Compared with placebo, the pulmonary index scores and respiratory rates were significantly lower in the montelukast group starting at 90 minutes (P = .01). This difference persisted at 120, 180, and 240 minutes of the study (P = .008, P = .02, and P = .048, respectively). At the end of the first hour of treatment, oral steroid need was 20.8% and 38.5% in patients randomized to the montelukast and placebo groups, respectively (P = .22). Hospitalization rates were not different between the 2 treatment groups.
                A single 4-mg tablet of montelukast had the potential to provide additive clinical benefit in mild to moderate acute asthma in preschool-aged children when administered concomitantly with short-acting beta2-agonist bronchodilators as the initial treatment. To determine the response to nebulized beta 2 agonist, 28 children younger than 2 years of age who visited the emergency department during an episode of acute asthma were studied. Each subject had a previous history of recurrent wheezing episodes. They were randomly assigned to receive two administrations of either nebulized albuterol (0.15 mg/kg per dose) or placebo (normal saline) with oxygen, 1 hour apart. After two nebulizations, the albuterol-treated patients had a greater improvement in clinical status (respiratory rate, degree of wheezing and accessory muscle use, total clinical score, and arterial oxygen saturation) than the placebo group. None of the patients in the albuterol group experienced a decrease of arterial oxygen saturation of greater than or equal to 2%. It is concluded that a trial of nebulized beta 2 agonists is warranted in the treatment of acute asthma in infants and young children. Although the mechanisms of nocturnal asthma are still uncertain, increased vagal cholinergic tone may be contributory factor. To examine this hypothesis, we have studied the effect of an anticholinergic drug, oxitropium bromide, on the early morning fall in peak expiratory flow (PEF) in patients with nocturnal asthma. Eighteen patients (aged 18 to 76 years; seven men) with documented nocturnal asthma were studied in a double-blind randomized cross-over study in which they received either oxitropium bromide (200 micrograms or 400 micrograms) or placebo in a single dose at night for two-week periods. With placebo the mean (+/- SE) fall in PEF (expressed as percentage of evening PEF) was 17.3 +/- 2.0 percent, which was significantly reduced to 10.3 +/- 3.3 percent after oxitropium (400 micrograms) (p less than 0.05; ANOVA). Closer analysis revealed that nine of the 18 patients had responded in a dose-dependent manner, with the mean percentage decreases with placebo, 200 micrograms, and 400 micrograms of oxitropium being 19.1 +/- 3.2, 11.5 +/- 4.4, and 5.0 +/- 4.5 percent, respectively (p less than 0.01 between each treatment). The remaining patients were unaffected by therapy. There were no differences between "responders" and "non-responders" in terms of age, atopic status, duration of asthma, severity of asthma, or bronchodilator response to albuterol (salbutamol). There were no differences in nocturnal symptoms between periods of treatment, and no side effects were recorded. We conclude that anticholinergic drugs may protect against nocturnal asthma in some patients, indicating the involvement of vagal cholinergic mechanisms.
In children over the age of two years with acute asthma exacerbations, inhaled anticholinergics as single agent bronchodilators were less efficacious than beta2-agonists. Inhaled anticholinergics were also less efficacious than inhaled anticholinergics combined with beta2-agonists. Inhaled anticholinergic drugs alone are not appropriate for use as a single agent in children with acute asthma exacerbations.