Ipratropium bromide (Atrovent) in childhood asthma: a cumulative dose-response study

Thirteen children with perennial bronchial asthma, with a mean age of 11.2 years, were studied concerning the bronchodilatory effect of ipratropium bromide in cumulative doses. All the children had reduced basal forced expiratory flow (FEV1) and bronchial reversibility of at least 20% after inhalation of salbutamol. The study had a double-blind design with a crossover technique. The inhaled dose of ipratropium bromide solution was increased stepwise from 25 micrograms to 500 micrograms and saline was used as the placebo. FEV1 was recorded 20, 40, and 60 minutes after inhalation of the test solution. At the lower ipratropium bromide dose levels no bronchodilatory effect was seen, but 60 minutes after the inhalation of 500 micrograms ipratropium bromide the increase in the FEV1 was significantly greater than that after placebo. Additional inhalation of salbutamol caused no further rise in FEV1. At the 500-micrograms level a fall in the heart rate was noted. No side effects occurred. We concluded that ipratropium bromide has bronchodilatory properties in childhood asthma when given in sufficiently high doses.     

Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol

Recently, it was suggested that long-term administration of an inhaled beta 2-agonist might increase bronchial hyperresponsiveness (BHR) to histamine, possibly as a consequence of subsensitization to the inhaled beta 2-agonist. To test this hypothesis, we studied two groups of patients with asthma or with chronic obstructive pulmonary disease. An experimental group of 15 patients, inhaling 400 micrograms of salbutamol four times daily during 1 year and subsequently 40 micrograms of ipratropium bromide four times daily for 6 months, and a control group, consisting of 22 patients with the opposite treatment regimen. The BHR, the response in FEV1 to cumulative doses of salbutamol, and the number of beta 2-adrenoceptors and antagonist affinity of these receptors on circulating lymphocytes were assessed at the start of the study and at 6-month intervals for 1 1/2 years. The BHR increased significantly (p = 0.001) during the year salbutamol was inhaled and returned to about the value at the start of the study after inhaling ipratropium bromide for 6 months. No change occurred in the bronchodilating responses to cumulative doses of salbutamol, nor was any change observed in the number and the affinity of beta 2-adrenoceptors on lymphocytes. It was concluded that long-term use of salbutamol caused a small but significant increase in BHR. The increase in BHR was not caused by subsensitization of beta 2-adrenoceptors to salbutamol.     

Comparison of nebulized ipratropium bromide with salbutamol vs salbutamol alone in acute asthma exacerbation in children.

BACKGROUND: Despite multiple doses of beta2-agonists in the treatment of acute asthma exacerbation, significant residual airways obstruction often remains. OBJECTIVE: To determine whether the addition of inhaled ipratropium bromide to salbutamol provides improvement in lung function and clinical asthma symptoms in young children with acute asthma exacerbation. METHODS: This study was a prospective, double-blind randomized control trial of children aged 3 to 15 years who presented with an acute asthma exacerbation at the emergency department or outpatient clinic of Thammasat University Hospital, Pathumthani, Thailand, between September 2001 and February 2003. Subjects were randomized to receive 3 doses of nebulized salbutamol mixed with isotonic sodium chloride solution (control) or ipratropium bromide (treatment) every 20 minutes. Additional doses of salbutamol were given every 30 minutes as needed. Asthma outcome measures were evaluated 40, 70, 100, and 120 minutes after baseline. Primary outcomes were the differences in percent change in asthma clinical score and percent change in peak expiratory flow rate (PEFR) from baseline. Secondary outcomes included change in percent predicted PEFR. RESULTS: Of 74 children randomized and enrolled in the trial, 71 had complete data for analysis. Thirty-three children were in the control group and 38 were in the treatment group. Both the percent change in PEFR and the change in percent predicted PEFR at any time were higher in the treatment group, but these findings were not statistically significantly different. The number of subjects with at least a 100% percent predicted PEFR at any time point was greater in the treatment group. CONCLUSION: Although this study did not demonstrate a significant advantage in clinical score and PEFR, the trend toward additional effect of ipratropium bromide was consistent with previous studies.     

The short-term bronchodilator effects of fenoterol and ipratropium in asthma

We studied the bronchodilator effects of inhaled fenoterol, a relatively selective beta-2 adrenergic agent, and ipratropium an anticholinergic drug, singly and in combination in 10 patients with asthma. The period of observation was 6 hr after aerosol administration. The six drug regimens used were fenoterol 100 micrograms, fenoterol 200 micrograms fenoterol 50 micrograms combined with 20 micrograms of ipratropium, fenoterol 100 micrograms combined with 40 micrograms of ipratropium, 40 micrograms of ipratropium, and placebo. Measurements consisted of spirometry with determination of forced expiratory volume in one second (FEV1), maximal expiratory flow at 50% of vital capacity (V50), specific airway conductance, lung volumes, and heart rate. Bronchodilation with regimens containing fenoterol was rapid, with 75% of the maximum response achieved by 5 min, while the peak effect of ipratropium was delayed for 1 to 2 hr. Fenoterol 100 micrograms produced approximately half the degree of improvement in FEV1 and V50 compared with 200 micrograms of fenoterol. The addition of 40 micrograms of ipratropium to 100 micrograms of fenoterol resulted in bronchodilation equivalent to 200 micrograms fenoterol and was associated with a more prolonged effect than fenoterol 100 micrograms. Tremor was observed in two-subjects inhaling fenoterol 200 micrograms but was not observed with any other regimen. It is concluded that the combination of inhaled ipratropium and fenoterol is an effective bronchodilator in asthma, achieving efficacy similar to that of fenoterol alone but with fewer side effects.     

The effect of inhaled salmeterol on methacholine responsiveness in subjects with asthma up to 12 hours.

The duration of the protective effect of 50 and 100 micrograms of inhaled salmeterol against methacholine-induced bronchoconstriction was compared with that of 200 micrograms of inhaled salbutamol in 12 patients with asthma with a baseline FEV1 of at least 70% and a provocative concentration of inhaled methacholine causing a 20% fall in FEV1 (PC20) greater than or equal to 8 mg/ml. The study was placebo controlled, double blind, randomized, and crossover. The bronchodilating effect was no longer significant 4 hours after inhalation of salbutamol, whereas the effect was still present 12 hours after administration of 50 and 100 micrograms of salmeterol. All active treatments caused PC20 to increase at 1 hour (p less than 0.05). PC20 (milligrams per milliliter) thus reached 3.7 +/- 0.8 after placebo, 13.8 +/- 3.0 after 50 micrograms of salmeterol, 23.2 +/- 4.7 after 100 micrograms of salmeterol, and 13.9 +/- 3.4 after 200 micrograms of salbutamol. The protective effect of 200 micrograms of salbutamol was no longer significant at 4 hours, whereas both doses of salmeterol protected against methacholine challenge up to 12 hours after inhalation (p less than 0.01). An increased incidence of tremor (2/12) and palpitations (2/12) was recorded after inhalation of 100 micrograms of salmeterol. We conclude that inhalation of 50 or 100 micrograms of salmeterol causes a long-lasting bronchodilatation and protects against methacholine-induced bronchoconstriction for at least 12 hours.     

Salbutamol and ipratropium bromide solution in the treatment of bronchospasm in asthmatic children

The effects of the beta 2-adrenergic agonist salbutamol (0.02 mL/kg of a 0.5% solution) and the cholinergic antagonist ipratropium bromide (2 mL of a 0.025% solution), administered alone or in combination at different doses, were evaluated in 48 asthmatic children using a single-dose, double-blind, crossover design. Spirometric measurements were taken before and 10, 30, 60, 120, 180, 240, 300, and 360 minutes after administration of the drugs. All regimens produced significant bronchodilatation 10 to 30 minutes after administration. The improvement began to decline three to four hours after inhalation, particularly when ipratropium bromide was administered alone. The administration of the salbutamol plus ipratropium combination did not significantly improve pulmonary function values as compared to salbutamol alone. The effects of salbutamol and ipratropium bromide in half-dose or full-dose combinations were indistinguishable. No significant adverse effects on blood pressure or heart rate were observed.     

Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5'-monophosphate-induced bronchoconstriction in patients with COPD

BACKGROUND: Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP. OBJECTIVE: To investigate the mechanism of AMP-induced bronchoconstriction in COPD. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60+/-7 years, FEV1 61+/-12% of predicted and FEV1/VC 51+/-8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 microg of inhaled ipratropium bromide, or placebo. RESULTS: GM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P<0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P<0.0001). CONCLUSION: These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.     

Twelve months, treatment with inhaled salmeterol in asthmatic patients

Salmeterol is a new beta 2-receptor agonist with a prolonged duration of action after inhalation, exceeding 12 h in most patients. We have performed a 12-month open follow-up study on 11 patients with reversible asthma. All patients were given salmeterol inhalations (50 micrograms twice daily). Additional asthma treatment included inhaled corticosteroids in all patients, and oral slow-release theophylline or beta 2-receptor agonists in a minority of patients (3 and 1, respectively). Before salmeterol treatment was initiated and after 3, 6, 9 and 12 months of salmeterol treatment, a cumulative dose-response curve to inhaled salbutamol (100, 300 and 900 micrograms) was performed, and FEV1 measured. We also evaluated the effect of each salbutamol dose on finger tremor, systemic blood pressure and heart rate. Blood tests, including white blood count and electrolytes, were taken at each visit. After salmeterol treatment was initiated, morning FEV1, measured before the morning asthma medication, was significantly improved (p < 0.05). The responsiveness to inhaled salbutamol was not decreased during salmeterol treatment, except in one patient with asthma worsening over the study year. Baseline finger tremor measured before salbutamol dose-response curves, was significantly lower at the 12-month visit than before treatment was initiated (p < 0.05). Effects of salbutamol on systemic blood pressure, heart rate or finger tremor was not significantly changed during salmeterol treatment. We found a successive and significant decrease in blood eosinophils (p < 0.05) during the 12 months of salmeterol treatment, when the patient with asthma worsening was excluded in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversibility of airway obstruction in asthma and chronic bronchitis (author transl)

Our purpose was to determine whether, in patients with airway obstruction, the change in the forced expiratory volume in one second (FEV1) which occurs after a bronchodilator drug, is helpful in differentiating asthma from chronic bronchitis. Two groups of patients (48 with asthma and 42 with chronic bronchitis) having a comparable level of initial airway obstruction were selected according to clinical criteria. After salbutamol (200 microgram inhaled) the number of subjects showing a change in FEV1 of at least 20 percent of its initial value or 10 percent of its predicted value was significantly greater (p less than 0.01) in the asthmatic than in the bronchitic group. Lesser changes in FEV1 did not significantly separate the two groups. When the changes in FEV1 were expressed as percentages of both initial and predicted values, the number of positive responses increased in the asthmatic group. However, there were still 20 asthmatics with little or no change in FEV1 after salbutamol who could not be distinguished from the patients with chronic bronchitis. From these data we conclude that, in patients with airway obstruction, a large bronchodilator-induced change in FEV1 strongly suggests the diagnosis of asthma but that the presence of "irreversible" airway obstruction does not disprove it.     

Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma

In a randomized, double-blind, parallel-group trial, 47 children with acute asthma received a combination of ipratropium bromide solution (250 μg) and fenoterol hydrobromide solution (625 μg), fenoterol solution (625 μg) alone, or ipratropium solution (250 μg) alone, administered by face mask and nebulizer, with the dose repeated 60 minutes later. The groups did not differ significantly with regard to age, pulmonary function at baseline, or any other variable. They were monitored at 30, 60, 90, and 120 minutes by use of a clinical score, oxygen saturation, and pulmonary function tests. At the end of the study, albuterol was administered to assess residual bronchoconstriction. Clinical scores improved significantly after treatment in all groups at all times compared with baseline. The greatest improvement in FEV, was seen in the patients treated with ipratropium/fenoterol, whether considered as absolute change, change in percent predicted, or percent change from baseline. ipratropium/fenoterol was significantly better than fenoterol alone only when considered as percent change from baseline. Improvement inflow at mid and low lung volumes was significantly greater for the ipratropium/fenoterol combination than for ipratropium alone; no significant differences were noted between ipratropium/fenoterol and fenoterol for flow at mid and low lung volumes. Treatment with albuterol did not significantly improve pulmonary function in the groups receiving ipratropium/fenoterol or fenoterol alone, but it did increase flow at all lung volumes in the group receiving ipratropium alone. No patient complained spontaneously of any adverse reactions, and no clinically significant changes in heart rate or systolic or diastolic blood pressures occurred. Ipratropium/fenoterol solution will be a useful addition to the therapeutic armamentarium for the treatment of acute asthma episodes in children. (J ALLERGY OLIN iMMUNOL 1988;82:1012-8.)     

Bronchodilator and bronchoprotective effects of salmeterol in young patients with asthma.

BACKGROUND: In adults with asthma, the selective beta 2-adrenergic agonist salmeterol has a prolonged bronchodilator and bronchoprotective effect. To date, there are few published studies of salmeterol in children. METHODS: We compared the bronchodilator and bronchoprotective effects of salmeterol, 25 and 50 micrograms, with salbutamol, 200 micrograms, and with placebo, administered via metered-dose inhaler, in a randomized, double-blind, within-patient, four-way crossover, single-dose study in 20 children. RESULTS: Mean baseline forced expiratory volume in 1 second (FEV1) and PC20 methacholine were not significantly different (p > 0.05) on the 4 study days, and did not change significantly after placebo. FEV1 increased significantly from 5 to 30 minutes after salbutamol, and from 5 minutes to 12 hours after 25 micrograms or 50 micrograms salmeterol, compared with placebo. After 25 micrograms or 50 micrograms salmeterol, FEV1 was significantly lower than after salbutamol at 5 and 10 minutes, did not differ from salbutamol at 30 minutes, and was significantly greater than after salbutamol from 3 to 12 hours. No significant difference occurred between the effect of 25 micrograms salmeterol and the effect of 50 micrograms salmeterol on FEV1. After salbutamol, there was a significant increase in PC20 only at 30 minutes. After 25 micrograms or 50 micrograms salmeterol, PC20 increased significantly from 30 minutes to 12 hours. Salmeterol, 25 micrograms and 50 micrograms provided significantly greater bronchoprotection than salbutamol from 3 to 12 hours and from 30 minutes to 12 hours, respectively. Salmeterol, 50 micrograms, provided significantly better bronchoprotection than 25 micrograms salmeterol from 30 minutes to 12 hours. The amount of change in PC20 accounted for by change in FEV1 varied from 14% to 28%, indicating that protection against bronchoconstriction was not entirely dependent on bronchodilation. CONCLUSIONS: Salmeterol is a potent, long-acting bronchodilator, with a slower onset of bronchodilation than salbutamol. It provides significantly greater and longer-lasting protection against bronchoconstriction than salbutamol.     

Separate and combined effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness in asthma.

We have investigated separate and interactive effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness. Twelve allergic subjects with asthma were treated in a double-blind, crossover, randomized study with budesonide, 1.6 mg daily for 3 weeks, prednisone, 40 mg daily, for 8 days, and placebo. After each period, dose-response curves were measured on 4 study days with doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo until a plateau in FEV1 was reached. A histamine challenge was then performed, and the provocation concentration causing a 20% fall in FEV1 (PC20) was calculated. The budesonide and prednisone regimens were equipotent. FEV1 was 81.2% of predicted after budesonide, 81.0% predicted after prednisone, and 67.5% predicted after placebo, bronchodilatation thus being 13.7% predicted (budesonide) and 13.5% predicted (prednisone). PC20 improved with 2.17 doubling concentrations (DCs) after budesonide, and 1.86 DCs after prednisone, compared with that of placebo. Salbutamol caused stronger bronchodilatation than ipratropium (26.2% versus 14.7% predicted) and a better protection against histamine challenge (3.95 versus 1.12 DC). The effects of corticosteroids and bronchodilators on FEV1 and PC20 were, in general, additive. This study emphasizes different modes of action on both airflow obstruction and airway hyperresponsiveness by corticosteroids and bronchodilators, and it demonstrates no enhancement of bronchodilator action by corticosteroids.     

Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma.

BACKGROUND: Flovent Diskus is a powder formulation of the inhaled corticosteroid fluticasone propionate (FP) delivered via a breath-actuated, multidose inhaler. OBJECTIVE: To determine the efficacy and safety of dry powder FP administered once or twice daily (200 microg per day) to children with persistent asthma. METHODS: Twelve-week, randomized, double-blind, placebo-controlled, multicenter trial with a 52-week, open-label extension. Children aged 4 to 11 were required to have pulmonary function 50% to 85% of predicted values. The population was stratified for baseline therapy (inhaled corticosteroid/cromolyn or bronchodilators only). After a 2-week placebo run-in, 242 patients received dry powder FP 200 microg each morning, dry powder FP 100 microg BID, or placebo for 12 weeks; 192 were rerandomized to the QD or BID regimen for an additional 52 weeks of open-label treatment. Primary endpoints were mean changes in FEV1 and morning PEF recorded at clinic visits. RESULTS: Both dry powder FP regimens significantly improved FEV1, evening PEF, and asthma symptoms at the double-blind phase endpoint (P < or = .017 compared with placebo). The BID regimen also significantly improved morning PEF and nighttime awakenings due to asthma (P < or = .005). Among patients previously treated with inhaled corticosteroids/cromolyn, improvements observed with the QD and BID regimens were similar. Patients switched from BID to open-label QD treatment showed additional improvements at week 52 generally comparable to patients who received the BID regimen during both phases. Fluticasone propionate was well tolerated for up to 64 weeks with few reports of drug-related adverse events or morning plasma cortisol abnormalities. CONCLUSIONS: Once daily dosing of dry powder FP 200 microg is an effective and convenient alternative for children whose asthma is controlled with a more frequent dosing regimen of inhaled corticosteroids.     

The superiority of combination beclomethasone and salbutamol over standard dosing of salbutamol in the treatment of chronic asthma

We studied the clinical effect of a combination aerosol containing salbutamol and beclomethasone dipropionate in comparison to doubling the standard dose of salbutamol from an inhaler. Fifty-seven patients completed the double-blind, crossover study. They were treated with either an aerosol of 100 micrograms beclomethasone dipropionate and 200 micrograms salbutamol or 400 micrograms salbutamol alone. Both regimens were administered four times a day for 4 weeks. The patients showed significant improvement in FEV1, PEFR, and symptom scores after treatment with beclomethasone dipropionate and salbutamol compared with pre-trial values and with treatment with double the dose of salbutamol. The patients demonstrated a clear preference for treatment with the combination of beclomethasone dipropionate and salbutamol. Regular treatment with beclomethasone dipropionate in addition to salbutamol as a combination inhaler provides much better control of asthma than merely increasing the dose of salbutamol in those patients poorly controlled on standard doses of inhaled bronchodilators.     

Effect of vasoactive intestinal peptide (VIP) on propranolol-induced bronchoconstriction

There is now considerable evidence in favor of vasoactive intestinal peptide (VIP) as a neurotransmitter of nonadrenergic noncholinergic nerves in the airways. The purpose of our study was to evaluate the influence of inhaled VIP on bronchomotor tone after a beta-adrenergic- and cholinergic-receptor blockage. The study was performed in six patients with asthma in 4 days. On the first day, a propranolol provocative dose producing a 20% change in FEV1 (PD20) was determined from the individual semilogarithmic dose-response curve. On the other days, the propranolol challenge was performed after inhalation of ipratropium bromide (40 micrograms), VIP (70 micrograms), and both drugs in randomized double-blind order. Statistical analysis was performed by two-way analysis of variance. The results demonstrated that mean propranolol PD20 was 0.14 mg (geometric mean + SD = 1.22). Ipratropium bromide administration, like VIP administration, significantly raised the PD20 value. The administration of both drugs elicited a further remarkable increase of mean propranolol PD20. The results demonstrated that inhaled VIP influences bronchomotor tone and that this effect is independent of the cholinergic blockage.     

Which patients benefit from adding theophylline to beta 2-agonist treatment in severe acute asthma?

The aim of this investigation was to study whether certain patients benefit from adding theophylline to the beta 2-agonist treatment of acute asthma. The study group comprised 101 patients who were taking oral theophylline. The patients received inhaled salbutamol (albuterol) (0.15 mg/kg x 2) (n = 53) or IV salbutamol (5 micrograms/kg) (n = 48). Aminophylline (3 mg/kg) was infused intravenously 60 minutes after the start of the salbutamol treatment. The mean increase in peak flow (PEF) after the aminophylline infusion was 22 +/- 33 L/min or 4% +/- 6% of the predicted value (mean +/- SD). A change in PEF correlated negatively to plasma theophylline before treatment (P less than .01) and positively to a change in plasma-theophylline after treatment (P less than .05). All patients with an increase in PEF of more than 10% of the predicted value (n = 14) after the theophylline infusion had plasma-theophylline levels before treatment of below 7.5 mg/L (41 mumol/L). No significant difference in the change in PEF after the theophylline infusion was found between patients who had received inhaled or intravenous salbutamol. This investigation could indicate that IV theophylline as an additive to beta 2-agonist treatment should be reserved for patients who are either not taking theophylline or who have only taken a low dose before arriving for the emergency treatment of acute asthma.     

Additive effect of albuterol and ipratropium bromide in the treatment of bronchospasm in children

Inhaled albuterol (A) (salbutamol) alone and albuterol plus ipratropium bromide (IB) were administered to 12 asthmatic children. Following administration of A alone or in combination with IB, there was a significant increase in FEV1 and FEF. Significant statistical difference in favor of the association A plus IB was observed at 120 and 240 minutes for FEV1 and in the period 120, 180, and 240 minutes for FEF. The additive effect was present both in the large and small airways. The short-lived additive effect of A plus IB suggests the opportunity to increase the frequency of drug administration in patients with severe bronchial obstruction.     

A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group.

BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.     

Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma

Ulrik CS, Backer V, Bach-Mortensen N. Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma. The purpose of this study was to compare the bronchodilating effect of ipratropium bromide (IB) administered by a conventional Ingelheim powder device system (IPI) and by a metered dose inhaler (MDI) in children and adolescents with stable bronchial asthma. Seventy patients, aged 7 to 16 years, with stable bronchial asthma from our outpatient clinic were tested for bronchial responsiveness to inhaled IB. Fifteen (21%) of the 70 subjects were found to have a substantial bronchial response to inhalation of 40 γg IB, i.e. at least 15% increase in FEV₁ 30 min after inhalation; the remaining 55 subjects had <15% increase in FEV₁. No relationship between severity of asthma, age or sex and bronchial responsiveness to inhaled IB was found. Among the 15 subjects who had substantial bronchial response to IB, the increase in FEV₁ after inhalation of fenoterol tended to be greater than the response to inhaled IB, although this did not reach statistical significance. Responders, i.e. subjects who had at least 15% increase in FEV₁ after inhalation of IB, took part in a double-blind, cross-over study of the bronchodilating effect of 40 γg IB delivered by IPI and MDI. We found no significant differences in the bronchodilating effect during a 6-h follow-up. Maximum bronchodilating effect of IB was reached after 30 min and the maximum response lasted for 90 min. No side or adverse effects were observed following inhalation of IB. We conclude that before starting treatment with ipratropium bromide for bronchial asthma in children and adolescents, the patients should be tested for bronchial responsiveness to inhaled IB to find out whether they are responders or nonresponders; and further that, among responders, inhalation of powder is as effective as inhalation from a dosis-aerosol.     

Epinephrine improves expiratory flow rates in patients with asthma who do not respond to inhaled metaproterenol sulfate

One hundred patients with acute asthma and peak expiratory flow rates (PEFR) less than 150 L/min were randomized and treated in a double-blind treatment protocol with either metaproterenol sulfate aerosol (MPA) inhalation and placebo injection or epinephrine injection (EPI) and inhaled placebo at entry and at 30 and 60 minutes, and then were treated with the crossover comparison regimen at 120, 150, and 180 minutes. The two groups had similar entry PEFRs and FEV1 (MPA, 112 L/min; 0.94 L, respectively; EPI, 111 L/min; 0.85 L, respectively) and similar plasma theophylline levels (MPA, 12.2 micrograms/ml; EPI, 13.8 micrograms/ml). PEFR and FEV1 were measured every 30 minutes for 4 hours. Mean expiratory flow rates among both groups were similar at entry and at 120 and 240 minutes. At 120 minutes, flow rates had improved in 28/46 MPA-treated patients (61%) and 48/54 EPI-treated patients (89%). Among these improved patients, flow rates were significantly higher in the MPA-treated group. At 120 minutes, 18/46 MPA-treated patients (39%) and 6/54 EPI-treated patients (11%) had PEFRs less than 120 L/min and PEFR and FEV1 less than 120% of baseline values (p less than 0.01). In 13 of these 18 MPA-treated patients who did not improve compared to 1/6 EPI-treated patients who did not improve, PEFRs were greater than 120 L/min, and PEFR and FEV1 had increased 20% or more above baseline values after treatment with the crossover comparison regimen (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)