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The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days. One hour before each challenge they were pretreated in double-blind fashion using a metered-dose inhaler and Babyhaler spacer. Placebo was given before one challenge, and either 25, 50 or 100 microg of salmeterol before the other. Both the dose and treatment order were random. The provocative concentration of methacholine causing wheeze (PCwheeze) was measured on each occasion. Studies were terminated when wheeze occurred or arterial oxygen saturation (Sa,o2) fell below 91%. Of the 42 children enrolled, 33 completed the study. Two subjects refused the challenge test, two failed to return and five developed upper respiratory tract infections or wheeze between the two tests. The mean (range) age of the population was 27 (8-46) months. Ratios of PCwheeze between treatment and placebo challenges were calculated for each dosage group. The treatment/placebo ratios (95% confidence intervals) were 1.2 (0.6-2.4) for 25 microg, 2.5 (1.4-4.6) for 50 microg (p<0.01), and 4.0 (2.1-7.4) (p<0.001) for 100 microg doses. In recurrently wheezy children aged <4 yrs a single dose of salmeterol between 25 and 100 microg has a dose-dependent effect on methacholine-induced wheeze, and this is significantly different from placebo at 50 and 100 microg. This study suggests that the Babyhaler effectively delivers salmeterol to children <4 yrs of age and that doses between 50-100 microg are efficacious.

Administration, Inhalation↗

Therapeutic response patterns to high and cumulative doses of salbutamol in acute severe asthma.

STUDY OBJECTIVES: To examine the main therapeutic response patterns to high doses of salbutamol and to determine the factors that contribute to outcome in acute severe asthma. SETTING: The emergency department (ED) of a large, urban hospital with primary and referral care responsibilities. PATIENTS AND DESIGN: One hundred sixteen consecutive patients with acute exacerbations of asthma were enrolled in the trial, using a prospective sequential design. INTERVENTIONS: All patients were treated with salbutamol delivered with a metered-dose inhaler into a spacer device in four puffs (400 microg) at 10-min intervals. The protocol involved 3 h of this treatment (1,200 microg each 30 min). MEASURES AND RESULTS: A dose-response increase in pulmonary function was found, but only 70% improved sufficiently to be discharged. Of these, almost 70% required < or =2.4 mg of the drug within 1 h to reach the discharge threshold, whereas the remainder 30% need > or =3.6 mg. In 30% of subjects, salbutamol was ineffective. These patients were characterized by a more severe disease as judged by previous beta2-agonist use, larger duration of attack before ED visit, and a more severe obstruction at presentation. However, the most important predictors of outcome were peak expiratory flow rate (PEFR) as percent of predicted, PEFR as liters per minute, and PEFR variation over baseline value, all at 30 min. CONCLUSIONS: This study described two different therapeutic response patterns to salbutamol. Almost 70% of patients were sensitive to salbutamol (good response pattern), and in this group, 2.4 to 3.6 mg represents optimal treatment. In the remainder 30% of patients (poor response pattern), salbutamol in high doses had little effect. However, the outcome was not determined by the intensity of the initial symptoms or by the value of the presenting PEFR, but rather by the early (30 min) short-term response to treatment.

Acute Disease↗

Duration of protection by inhaled salmeterol in exercise-induced asthma.

Beta-adrenoceptor agonists such as albuterol are very effective in preventing exercise-induced asthma (EIA) when they are given as an aerosol immediately before exercise. However, their duration of protection against EIA is usually less than 2 h. This may be due partly to their rapid clearance from the airways. Salmeterol is a highly lipophylic compound that is thought to bind to an exoreceptor near the beta-receptor. The objective of this study was to compare the protective effect of salmeterol with albuterol against EIA. Exercise was performed 0.5, 2.5, 4.5, and 6.5 hours after administration of the active drugs. Subjects attended the laboratory on four days within six weeks and cycled for 8 min breathing dry compressed air. We studied 17 asthmatic subjects (aged 19 to 49 years) with moderate to severe EIA. Salmeterol (50 micrograms) or albuterol (200 micrograms) was given from a metered dose inhaler via a spacer (Volumatic). On the control day, the mean work load +/- 1 SD was 174 +/- 47 W, ventilation (VE) was 77.9 percent +/- 11.2 percent of the target ventilation (60 percent maximum voluntary ventilation [MVV]), and heart rate was 170 +/- 14 beats per minute. This intensity was maintained for all tests. FEV1 was measured before and after exercise and was expressed as percent predicted and as percentage of the preexercise value (percentage of fall). Thirty minutes after treatment, both drugs were effective in inhibiting EIA--percentage of fall in FEV1, 17 +/- 12 after salmeterol; percentage of fall in FEV1, 15 +/- 15 after albuterol. At 2.5, 4.5, and 6.5 hours, the reduction in FEV1 was significantly less (p less than 0.01) after salmeterol compared with albuterol. At 6.5 hours, the percentage of fall in FEV1 was 20 +/- 10 after salmeterol and 36 +/- 12 after albuterol. Salmeterol also had a more prolonged action as a bronchodilator and values for FEV1 were significantly higher compared with those on albuterol at 4.5 and 6.5 hours. At 6.5 hours, the FEV1 percent predicted was 96 +/- 10 after salmeterol and 84 +/- 12 after albuterol (p less than 0.01). We conclude that the extent of protection against EIA and the bronchodilation induced by both drugs was similar, but that salmeterol has a longer duration of action compared with albuterol. The reason for its superior duration of action may be due to a slower clearance of the drug from the airways.

Administration, Inhalation↗

Rapid-onset asthma attack: a prospective cohort study about characteristics and response to emergency department treatment.

STUDY OBJECTIVES: (1) To determine the frequency of rapid-onset asthma attacks (ROAAs) and slow-onset asthma attacks (SOAAs) in adult patients with acute, severe disease (18 to 50 years old), who presented to an emergency department (ED); and (2) to establish whether ROAA patients differ from SOAA patients in terms of clinical and spirometric characteristics; and (3) in terms of the response of treatment. SUBJECTS AND METHODS: Four hundred three patients (with peak expiratory flow [PEF] or FEV(1) of < 50% of predicted value) with acute exacerbations of asthma were enrolled in the trial using a prospective cohort study. Asthma attacks were classified as an ROAA (< 6 h of symptoms) or an SOAA (> or = 6 h). All patients were treated with albuterol, four puffs at 10-min intervals (100 microg per actuation), delivered by metered-dose inhaler with a spacer device during 3 h. RESULTS: On the basis of previously determined criteria, 11.3% of patients were classified as having a ROAA. Male patients comprised 53.6% of the ROAA group (p = 0.03). In ROAA patients, the exacerbation was less likely to be attributed to respiratory tract infection (p = 0.001) and more likely to have no identifiable cause (p = 0.0001). Also, ROAA patients had lower pulmonary function (FEV(1)) at presentation (mean difference, - 0. 13; 95% confidence interval [CI], - 0.22 to - 0.04 L; p = 0.04) than SOAA patients. At the end of treatment, ROAA patients had an overall 48.0 L/min (95% CI, 14.1 to 81.8 L/min) greater improvement in PEF and a 0.31 L (95% CI, 0.08 to 0.54 L) greater improvement in FEV(1) than SOAA patients. Also, ROAA patients presented with less accessory muscle use (p < 0.05) and higher oxygen saturation (p = 0. 005). Finally, SOAA patients showed an increased incidence of hospital admission (relative risk, 3.89; 95% CI, 1.01 to 15.0). CONCLUSIONS: Data from this study support the notion that ROAAs constitute a distinct but uncommon acute asthma ED presentation, with a predominance of male patients. Upper respiratory tract infection was not believed to be a significant trigger factor in these patients, and ROAA patients had rapid deterioration of their conditions followed by a more rapid response to treatment and a lower hospital admission rate than SOAA patients. Thus, we have identified a subgroup of patients who appear to have common characteristics with patients with sudden-onset near-fatal/fatal asthma.

Acute Disease↗

The effect of salbutamol on performance in endurance cyclists.

The effect of salbutamol (S) on cycling performance was examined in 15 highly trained non-asthmatic male cyclists. A double-blind, randomized cross-over design was used with S or placebo (P) administered using a metered-dose inhaler and a spacer device 20 min before each testing session. The S dose was 400 micrograms (four puffs), which is twice the normal therapeutic level. Subjects were habituated to all the laboratory procedures in the week prior to actual data collection. The subjects performed four tests under S and P conditions on separate days over 2 weeks. These included measurement of maximal O2 uptake (VO2max) (cycle ergometry) with assessment of pulmonary function before and after, a submaximal (90% of ventilatory threshold) square-wave work transition from a base of unloaded cycling, a 60-s modified Wingate test, and a simulated 20 km time trial. No significant differences were observed in any of the dependent variables related to aerobic endurance or cycling performance between the S and P conditions. These results support other findings that an acute dose (400 micrograms) of S has no performance-enhancing properties.

Adrenergic beta-Agonists↗

The use of reservoir devices for the simultaneous delivery of two metered-dose aerosols.

Many patients benefit from using metered-dose inhalers (MDIs) with spacer or reservoir devices. Concomitant therapy with separate MDI doses of cromolyn sodium and a beta-agonist is common practice. If two puffs from each drug could be placed into a chamber, the patient could administer both medications at once, enhancing compliance. A multistage liquid impinger (a four-stage inertial impaction device incorporating an inlet bend and an absolute filter, which separates an aerosol cloud into six fractions) was used to investigate such a possibility. Cromolyn sodium and albuterol MDIs were used with an Aerochamber (Monaghan Medical Corp., Plattsburgh, N.Y.) and an Inspirease (Schering Corp., Kenilworth, N.J.). Results are reported by analyzing milligrams of cromolyn sodium per actuation retrieved. With the Aerochamber, two puffs of cromolyn sodium followed by two puffs of albuterol resulted in the total "dose to patient" being reduced by 75% (0.19 versus 0.05 mg) and the effective dose of fine particles (less than 6.5 microns) being reduced by 80% (0.13 versus 0.03 mg) compared to two puffs of cromolyn sodium alone. With the Inspirease, total dose was decreased by 80% (0.32 versus 0.06 mg), whereas the effective dose of fine particles was reduced by 60% (0.19 versus 0.05 mg) compared to one puff of cromolyn sodium alone. The use of cromolyn sodium and albuterol MDIs in a multipuff combination with the Aerochamber or the Inspirease is not recommended because this leads to a loss of the dose delivered compared to a single administration.

Aerosols↗

Early administration of hydrocortisone in the emergency room treatment of acute asthma: a controlled clinical trial.

STUDY OBJECTIVE: To determine whether early administration of a single dose of intravenous hydrocortisone (500 mg) modified the need for hospitalization and duration of treatment, and improve pulmonary function assessed by subjective and objective criteria of acute asthma patients. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: The emergency room (ER) of a large, urban hospital with primary and referral care responsibilities. PATIENTS: Ninety-eight patients from 18 to 50 years of age with acute bronchial asthma, with a PEFR and FEV1 in the first second below 50% of predicted value (FEV1 mean % of predicted = 27.8 +/- 10.0) and without history of chronic cough or other medical disease. INTERVENTIONS: The corticosteroid group received 500 mg of intravenous hydrocortisone whereas the control group received intravenous normal saline immediately after arrival to the ER. Additional treatment included salbutamol delivered with metered-dose inhaler into a spacer device (Volumatic), in four puffs actuated in rapid succession (100 micrograms per actuation), at 10-min intervals. The final mean dose was 5.7 mg for the steroid group and 5.6 mg for the control one (P = 0.86). Hospitalization was mandatory if total treatment time was greater than 6 h. MEASUREMENTS AND RESULTS: Age, sex, PEFR, FEV1, FVC, symptom index, and corticosteroids use were similar in both groups. FEV1 expressed as mean % of predicted was 54.6 +/- 17.3% in the control group and 54.6 +/- 17.4% in the steroid group (P = 0.75). Duration of ER treatment was 2.22 +/- 1.75 h in the corticosteroid group and 2.24 +/- 1.70 h in the control group (P = 0.81). The hospital admission rate was 10.2% for the corticosteroid group and 8.16% for the control group. There were no differences between the groups when patients admitted or discharged were examined separately. CONCLUSIONS: Early administration of corticosteroids does not modify outcome of ER treatment of asthma, and does not improve pulmonary function in the first 6 h of treatment. In accord with this, administration of corticosteroids to these patients could be delayed by several hours without modifying clinical outcome. When an aggressive beta-agonist bronchodilator regimen is used, it obviates the need for steroids in this early stage of treatment.

Acute Disease↗

Efficacy of a consensus protocol therapy in adults with acute, severe asthma.

BACKGROUND: International guidelines recommend multiple doses of inhaled beta2-agonists and anticholinergics plus early administration of systemic corticosteroids for acute, severe asthma. This study examined the efficacy of this protocol in adults and analyzed those factors associated with unresponsiveness to the protocol therapy. OBJECTIVE: Ninety-three consecutive patients 18 to 55 years old presenting for treatment of acute asthma with a peak expiratory flow rate (PEFR) < or = 50% of the predicted value were analyzed. METHODS: All subjects received 400 microg of salbutamol every 20 minutes for three doses and 400 microg of oxitropium bromide with each of the three salbutamol doses by means of a metered-dose inhaler with a spacer device, plus intravenously 8 mg betamethasone. PEFR was measured at baseline and at 20, 40, 60, and 120 minutes. RESULTS: Sixty-nine percent of subjects improved sufficiently to be discharged. In 31% of subjects, the protocol therapy failed. There were no significant differences in age, sex, smoking status, or beta-agonist use within 6 hours between the two groups. Logistic regression analysis demonstrated that a PEFR < 35% of the predicted value at presentation (odds ratio [OR]; 16.3, 95% confidence interval [CI] 4.5 to 59.9), viral respiratory tract infection symptoms > or = 2 days (OR, 4.8, 95% CI 1.3 to 17.1), and asthma hospitalization in the past year (OR, 4.6, 95% CI 1.1 to 19.9) were significantly associated with unresponsiveness to the protocol. CONCLUSIONS: Unresponsiveness to protocol therapy occurs in nearly one-third of individuals presenting with acute, severe asthma. Our findings underscore the need to explore more effective strategies for improving lung function and reducing hospital admission rates.

Acute Disease↗

Overcoming the adverse effect of humidity in aerosol delivery via pressurized metered-dose inhalers during mechanical ventilation.

The well-known problem of reduced drug delivery that occurs when heated, humid air is used with pressurized metered-dose inhalers (pMDIs) and spacers in intubated settings is carefully studied with Airomir using an in vitro model under controlled conditions of temperature and humidity. A better understanding of the physical processes leading to the aforementioned drop in performance is obtained, and a method is devised to circumvent the problem without having to reduce the temperature or humidity of the ventilator circuit. The present study shows that the mole fraction of water vapor in the ventilation air (and not the temperature) is the major factor behind the sharp drop in the amount of drug delivered to the lung. However, the presence of water vapor does not affect performance because of hygroscopic growth. Instead, it influences the initial atomization process and the early stages of aerosol generation. Removal of these negative effects can be achieved by using a larger spacer that allows longer times for the aerosol to evaporate, as is demonstrated in the present study.

Aerosols↗

Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children.

We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5 mg/d for 2 d on the bronchoconstriction induced by hyperventilation of cold, dry air in 13 asthmatic children 3 to 5 yr old. The bronchoconstriction was measured as the specific airway resistance (sRaw) in a whole-body plethysmograph before and 4 min after challenge with cold, dry air. The repeatability of the bronchoprotection was examined by repeating the placebo-controlled study in six of the 13 children. sRaw increased by an average of 46% (95% confidence interval [CI]: 30 to 63%) after placebo treatment and 17% (95% CI: 3 to 31%) after montelukast (p < 0.01). Eight of the children were receiving regular treatment with budesonide delivered by an inhaler with a spacer in a mean daily dose of 350 microg, but the bronchoprotection provided by montelukast was independent of concurrent steroid treatment. There was no convincing evidence of failure to respond, and the protective effect of montelukast was consistent upon repeated testing (p = 0. 02). We conclude that the LTRA montelukast provided clinically significant bronchoprotection against the effect of hyperventilation of cold dry air in asthmatic children 3 to 5 yr old. The bronchoprotection appeared to be homogeneous among the children, and seemed independent of steroid treatment. This suggests that LTRAs may be of therapeutic use in limiting clinical symptoms of asthma in young children.

Acetates↗

Bronchodilator response to salbutamol after spontaneous recovery from nonspecific bronchial provocation tests in asthma.

Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion. However, it is not known whether this can be done accurately. Therefore, this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second (FEV1) in a group of asthmatic subjects. On two separate occasions at the same time of day, concentration-response studies with inhaled histamine or methacholine, or a sham challenge with normal saline were carried out in a blinded, randomized manner. Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer. The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init). Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9% (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge day respectively. It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second. Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients.

Adolescent↗

Bronchodilator reversal of bronchospasm and symptoms incurred during methacholine bronchoprovocation challenge. Documentation of safety and time course.

We undertook a prospective study of bronchoprovocation challenge (BPC) to look at issues of safety and reversibility of bronchospasm and symptoms induced by BPC. Over a 14-month interval, we documented 62 consecutive cases of bronchial hyperresponsiveness. During BPC, there was a statistically significant but clinically modest increase in both cough and dyspnea. Both bronchospasm and symptoms were readily reversed with a simple protocol of inhaled albuterol using a metered-dose inhaler with a spacer. Routine protocol was effective in every case; there was never a need for individualized physician intervention. Our prospective data document the safety of BPC; we could find no reason why BPC would need to be confined to the hospital. We conclude that BPC is a valuable clinical test which merits wider dissemination and use.

Adolescent↗

Early prediction of poor response in acute asthma patients in the emergency department.

STUDY OBJECTIVES: The aim of this study was to develop an acute asthma index for utilization in the early differentiation between patients with poor and good therapeutic response in the emergency department (ED) setting. SETTING: The ED of a large tertiary-care hospital in Montevideo, Uruguay. PATIENTS AND DESIGN: The study included 145 consecutive adult patients (mean age [+/- SEM], 33.4+/-0.97) who presented to an ED (analysis sample). The inclusion criteria were: (1) age between 18 and 50 years; (2) a peak expiratory flow rate (PEFR) or FEV1 below 35% of predicted; and (3) no history of chronic cough or cardiac, hepatic, renal, or other medical disease. INTERVENTIONS: All patients were treated with salbutamol delivered by metered-dose inhaler into a spacer device in four puffs actuated at 10-min intervals. The protocol involved 3 h of this treatment. After that time, patients with poor response received hydrocortisone, 500 mg IV. The outcome was defined as the FEV1 after 3 h of treatment in a dichotomized form: < or =45% of predicted = poor response, and >45% of predicted = good response. RESULTS: Biserial correlations between different variables and the outcome showed that PEFR as percent of predicted and PEFR variation over baseline, both measured at 30 min, were the most important predictors of a good or poor response after 3 h of treatment. Next, we developed an acute asthma index using these predictive measures. A comparison of index sensitivity, specificity, predictive values, and the area under the receiver operating characteristic (ROC) curve across different cutoff scores indicates that a score of 4 results in the least error of classification (sensitivity = 0.79; specificity = 0.96; area under the ROC curve = 0.87; positive predictive value = 0.94; and negative predictive value = 0.86). To validate the developed index, we prospectively studied a second sample of 77 consecutive patients (mean age 32.6+/-1.22 years) who presented for treatment of acute asthma (validation sample). The area under the ROC for the analysis sample was not greater than the validation sample area (p = 0.24). Thus, the validation sample showed similar levels of sensitivity and specificity, positive and negative predictive values, and area under the ROC curve (0.80, 0.88, 0.85, 0.84, and 0.89, respectively), indicating the stability of the model. CONCLUSIONS: The study suggested the predictive accuracy of a two-item bedside index. This acute asthma index provides a tool for assessing acute asthma severity using objective criteria easily accessible to the ED physician.

Acute Disease↗

Withdrawal from treatment as an outcome in the ISOLDE study of COPD.

OBJECTIVES: To investigate the determinants of patient withdrawal from our study, and the effect of these withdrawals on the outcome of treatment with inhaled corticosteroids in patients with COPD. DESIGN: A double-blind, placebo-controlled, randomized trial. SETTING: Eighteen outpatient centers in the United Kingdom. PARTICIPANTS: Seven hundred fifty-one patients with stable COPD defined clinically and as baseline postbronchodilator FEV(1) > or = 0.8 L and < 85% predicted, FEV(1)/FVC ratio < 70%, and FEV(1) change after albuterol < 10% of predicted. INTERVENTION: Random assignment of either 500 microg bid of inhaled fluticasone propionate (FP) using a spacer device or an identical placebo inhaler. Treatment was continued for 3 years or until patients withdrew from follow-up. MEASUREMENTS AND RESULTS: Postbronchodilator FEV(1) was measured on three occasions before randomization and every 3 months thereafter. Health status was assessed by the disease-specific St. George Respiratory Questionnaire (SGRQ) and the modified short-form 36 questionnaire (SF-36) at baseline and every 6 months. Three hundred thirty-nine patients withdrew, of whom 156 patients received FP. Prescription of frequent courses of oral prednisolone was the most common reason for withdrawing as specified in the protocol (69 patients in the FP group withdrew due to respiratory symptoms, compared with 93 patients in the placebo group). This explained the significantly greater dropout of placebo-treated patients that was most evident when FEV(1) was < 50% predicted. Patients withdrawing had a significantly more rapid decline in health status, measured by both the SGRQ and the SF-36 (p < 0.001). Those withdrawing from the placebo group had a more rapid decline in FEV(1) and more exacerbations than the FP-treated groups. Baseline FEV(1) was lower in dropouts than in patients completing the study receiving placebo, but there was no difference between the respective groups receiving FP. CONCLUSIONS: Patients who withdrew from follow-up were those with the most rapidly deteriorating health status and lung function. Losing these patients from the final analysis can reduce the power of a study to achieve its primary end point.

Adult↗

[Controversies in the pharmacological management of acute asthma in children].

OBJECTIVE: To present a review of controversial issues related to the pharmacological management of the treatment of acute asthma in children. SOURCES: Articles published in national and international scientific journals. Data were selected from Lilacs and Medline databases. SUMMARY OF THE FINDINGS: The article was organized into topics, presenting aspects on which there is consensus regarding the pharmacological treatment of asthma in children. Issues related to the use of metered dose inhaler versus nebulizers, the role of beta2-adrenergic drugs administered intravenously as well as the role of methylxanthine and magnesium sulfate are approached critically. CONCLUSIONS: Inhaled beta2-agonist drugs combined with corticosteroids remain the treatment of choice for acute episodes of asthma in children. Either nebulizers or metered dose inhalers connected to spacers are efficient for the relief of acute symptoms. Patients who are refractory to conventional treatment and develop severe acute asthma should receive beta2-agonist drugs intravenously, provided they are properly monitored. Methylxanthine and magnesium sulfate should be considered a second choice for selected patients.

English Abstract↗

Efficacy and safety of a novel beclomethasone dipropionate dry powder inhaler (Clickhaler) for the treatment of adult asthma. Amsterdam Clinical Study Group.

A randomized, double-blind, double-dummy protocol was used to compare the safety and efficacy of beclomethasone dipropionate (BDP) delivered by a novel dry powder inhaler (DPI, Clickhaler) or by a pressurized metered-dose inhaler (MDI) plus spacer. There was a four-week run-in period, completed by 240 adult patients, who received BDP via an MDI. Patients with stable asthma were then randomized into a 12-week treatment period and received BDP (< or =2 mg/day via DPI or MDI). There were no significant differences in morning peak expiratory flow (PEF) (primary endpoint), evening PEF, overall daytime or nighttime symptom scores, or lung function parameters (forced expiratory volume in 1 sec, forced vital capacity) between DPI and MDI. The safety profiles were similar and patient acceptability for Clickhaler was high. In conclusion, BDP administered via Clickhaler was found to be clinically equivalent to an optimally used MDI. Patients with stable asthma currently receiving BDP via MDI may be effectively switched to treatment via Clickhaler DPI.

Anti-Asthmatic Agents↗

[Bronchodilation induced by fenoterol in asthmatic patients: comparison of jet nebulization and spacer device].

OBJECTIVE: To compare bronchodilation attained by fenoterol administered through a jet nebulizer and through a spacer device. TYPE OF STUDY: Open, randomized. PATIENTS: 44 adults with asthma, peak-flow rate varying between 120 and 200 l/min. Patients were divided into two groups. TREATMENT [corrected]: Group A was treated with fenoterol (2.5 mg) with saline to complete 3 ml given through a jet nebulizer; 30 minutes later, an additional dose (1 mg) was given through a 500 ml spacer. Group B was treated with the same dosage, but the spacer [corrected] was used first. EVALUATION: Peak-flow meter in zero, 30 and 60 minutes. RESULTS: No significant difference in bronchodilation was seen between groups A and B. CONCLUSION: Fenoterol through a spacer can replace inhalation in adult asthma patients with non-severe obstruction. Lower cost and home treatment are the main advantages.

Adult↗

[A comparison of two delivery devices on the bronchodilatory effects of procaterol from a metered dose inhaler].

The bronchodilatory response to procaterol delivery by a metered dose inhaler with a spacer device (Volumatic) and a corniced extension tube was studied in a double blind manner in 18 asthmatic children, who were brought to our emergency room with acute attacks. The mean percent increase in forced expiratory volume in 1 second (FEV1) with the Volumatic was 55.6 +/- 39.3%, and 46.2 +/- 37.4% with the extension tube. There were no significant differences in the mean percent increase in FEV1, forced vital capacity (FVC), maximal flow rate at 50% of vital capacity (V50), maximal flow rate at 25% of vital capacity (V25) and peak expiratory flow rate (PEFR) between the two devices. It is concluded that there is no difference in the bronchodilatory effects of the two devices. The corniced extension tube has the advantage of being less expensive and more convenient to carry around.

Acute Disease↗