Comparison of the efficacy and safety of high doses of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler in steroid-dependent adults with moderate to severe asthma.

Nebulization for the administration of high doses of inhaled corticosteroids can benefit steroid-dependent asthmatics. The objective of this double-blind, double-dummy, multicentre, randomized, parallel-group study was to compare the efficacy and safety of high-dose corticosteroids given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 2-week run-in period, 124 patients, aged 18-70 years, with moderate to severe asthma treated with high-dose inhaled steroids were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 3,000-4,000 microgday(-1) b.i.d. given via a nebulizer (n = 63), or BDP spray 1,500-2000 microgday(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 61). Comparable improvements over baseline, which were statistically significant in most cases, were reported at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, clinical symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was morning pulmonary expiratory flow rate (PEFR). For the intent-to-treat population, in the BDP nebulization group mean morning PEFR increased statistically significantly from 308.7 +/- 107.81 min(-1) to 3 19.2 +/- 104.01 min(-1) while in the BDP MDI group the increase was from 301.5 +/- 94.71 min(-1) to 309.3 +/- 86.71 min(-1). The two treatments were equally well tolerated.A total of 19 patients in each group reported adverse events during the treatment period, and these were generally mild-moderate in severity. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3,000-4,000 microg day(-1) given via a nebulizer and BDP spray 1,500-2,000 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in steroid-dependent adult patients with moderate to severe asthma.

One-year safety study with bambuterol once daily and terbutaline three times daily in 2-12-year-old children with asthma. The Bambuterol Multicentre Study Group.

The aim of this study was to compare bambuterol oral solution (10 mg) administered once daily in the evening with terbutaline oral solution (0.075 mg/kg body weight) administered three times daily in 2-5-year-old children and to compare bambuterol tablets (10 mg or 20 mg) administered once daily in the evening with terbutaline tablets (2.5 mg) administered three times daily in 6-12-year-old children with asthma. The study was of an open, randomized, parallel-group design, and lasted 1 year. The primary objective was to evaluate safety (pulse rate, blood pressure, adverse events, hematology, and clinical chemistry). Plasma terbutaline concentrations were also measured. Evaluation of efficacy (FEV(1)) was a secondary objective. A total of 141 patients (83 boys, 58 girls) were randomized and treated with the study drugs, i.e., 43 patients in the terbutaline group (30 on oral solution and 13 on tablets) and 98 patients in the bambuterol group (62 on oral solution and 36 on tablets). A total of 11 patients discontinued the study: 3 were on terbutaline, and 8 were on bambuterol. There were no clinically important differences between treatment groups regarding pulse rate, or systolic or diastolic blood pressure. There were no clinically important findings in the laboratory tests (hematology and clinical chemistry). Both terbutaline and bambuterol were well-tolerated, and the reported adverse events were mostly mild or moderate. Mean steady state plasma terbutaline concentrations at the visits ranged between 8.0-11.5 nmol/L in the bambuterol tablet group and between 10.6-15.2 nmol/L in the terbutaline tablet group. The corresponding values in children on oral solution were 10.3-11.3 nmol/L in the bambuterol group and 7.5-9.7 nmol/L in the terbutaline group. FEV(1) measured in the 6-12-year-old children increased by more than 0.2 L in both treatment groups during the year in the study. In conclusion, bambuterol tablets or oral solution once daily and terbutaline tablets or oral solution three times daily showed a comparable and favorable safety profile.

Distilled water challenges in asthmatic children. Comparison of different protocols.

Inhalation of ultrasonically nebulized distilled water (UNDW) appears a promising candidate for routine challenge testing in bronchial asthma. We have compared two different methods of application of UNDW in 12 asthmatic children with a positive response to methacholine provocation (MCh), in an attempt to increase UNDW sensitivity and to establish standard testing protocols. In addition, results from UNDW challenges were compared to responses to inhalation of jet-nebulized distilled water (JNDW) and cold air (CACh). Compared to MCh, the sensitivity of continuously or intermittently (iUNDW) inhaled UNDW was 67 percent or 75 percent, respectively, when a positive response was defined by a greater than or equal to 20 percent fall in FEV1, but was higher when definition of a positive response was based on results from flow volume curves. Sensitivity of continuous or intermittent inhalation of JNDW was lower than for UNDW. The UNDW inhalations were better tolerated than CACh. Following stepwise iUNDW challenge, there was a clear reaction plateau for all variables measured. Results indicate that testing protocols with iUNDW inhalations over 6 to 10 min (corresponding to 7 to 11 ml water inhalation) yield the maximum sensitivity attainable with UNDW challenges, and require a minimum of patient and investigator effort.

[Effectiveness and tolerance of aerosol disodium cromoglycate in children with bronchial asthma]. / Wirksamkeit und Verträglichkeit von vernebeltem Dinatrium Cromoglykat bei Kindern mit Asthma bronchiale.

Thirteen centres studied the efficacy and safety of nebulized cromolyn solution in 53 asthmatic children (36 m., 17 f.; mean age 4.8 +/- 1.7 years). During a fiveweek treatment period a significant reduction of asthmatic symptoms was observed by investigators daily symptom scores, as assessed by the parents, also showed a significant improvement during treatment period. In addition, there was also a marked decrease in the use of other anti-asthmatic medication (beta 2-sympathomimetics, theophylline and antihistamines). There were no side effects of nebulized cromolyn solution treatment.

[Sweat collection and osmometry in the diagnosis of cystic fibrosis: a new method]. / Schweissgewinnung und Osmometrie in der Diagnostik der zystischen Fibrose: Eine neue Methode.

Two methods of sweat testing (Gibson and Cooke's vs. sweat osmolality) for the diagnosis of cystic fibrosis were compared in 33 subjects (26 healthy subjects and 7 patients aged 23 days to 28 years). Sweat was collected with a "macroduct"-sweat collection-system, osmolality was measured with the Wescorvapor-pressure osmometry. In a further 18 subjects (13 healthy, 5 patients) electrolytes were determined from filter-paper and the Vescor-macroduct-system. The osmolality in sweat of healthy subjects and patients with CF differed significantly (p less than 0.001). In healthy subjects maximum osmolality was 198 mmol/kg (means 158 +/- 21.3 mmol/kg), in patients with CF 283.9 +/- 10.2 mmol/kg. Assessment of sweat osmolality is a highly reliable procedure for confirming the diagnosis of CF provided borderline-values between 180 and 220 mmol/kg are reevaluated with the conventional filter-paper assay.