Is oral theophylline effective in combination with both inhaled anticholinergic agent and inhaled beta 2-agonist in the treatment of stable COPD? Management of acute asthma in children using metered dose inhaler and small volume nebulizer. Oral montelukast treatment of preschool-aged children with acute asthma. A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group. Effect of three different bronchodilators during an exacerbation of chronic obstructive pulmonary disease.
To investigate the additive effect of oral theophylline on combined inhaled anticholinergic agent and beta 2-agonist therapy, 12 patients with stable COPD (64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial of oral theophylline for a 4-week period (400 mg for 2 weeks, followed by 600 mg for 2 weeks). All of the patients continued to inhale both salbutamol, 200 micrograms, and ipratropium bromide, 40 micrograms, using a metered-dose inhaler four times a day. Spirometry was assessed before, and 15 and 60 min after the inhalation of bronchodilators at 2-week intervals. Even after the inhalation of salbutamol and ipratropium, theophylline significantly improved FEV1 and daily peak expiratory flow rate compared with the placebo. No significant improvement in the daily symptom scores for cough, sputum, wheezing, or shortness of breath was observed throughout the different phases of treatment. This study shows that the additive bronchodilating effect of theophylline, when used in combination with salbutamol, 200 micrograms, and ipratropium, 40 micrograms, is significant but small in stable COPD. The addition of theophylline did not significantly improve the patient's symptoms. Oral theophylline, when used in combination with an inhaled anticholinergic agent and an inhaled beta 2-agonist, may be of limited value in the treatment of stable COPD. 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. The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy.
                In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years.
                Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group.
                The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease. This study evaluates the effect of three different bronchodilators (beta 2-adrenergic, anticholinergic and methylxanthine) alone and in randomized sequence, during an exacerbation in thirteen patients with chronic obstructive pulmonary disease. Dose-response curves were obtained for inhaled salbutamol and inhaled ipratropium bromide. The bronchodilator effect of a perfusion of aminophylline was also assessed. When a plateau of bronchodilatation was achieved with one agent, one dose of a second bronchodilator was administered to see whether additional bronchodilation could be achieved. The increments in FEV1 and FVC were similar with the three agents. The addition of a second bronchodilator did not result in significant increments in most of the patients. In at least half of the patients the doses of salbutamol and ipratropium that produced the maximal bronchodilatation were twice that currently employed.
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.