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Comparison of inhaled terbutaline administered by either the Turbuhaler dry powder inhaler or a metered-dose inhaler with spacer in preschool children with asthma.

We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler, the Turbuhaler, or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age. The bronchodilator response did not differ between the two inhalational devices. The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used.

Administration, Inhalation↗

Pulmonary distribution and kinetics of inhaled [11C]triamcinolone acetonide.

UNLABELLED: Triamcinolone acetonide (TAA) is an anti-inflammatory steroid used for topical treatment of allergic rhinitis and asthma. Drug deposition onto target tissues is an important parameter, so methods for accurate deposition measurement are needed. Lung deposition is especially problematic to measure because of the large field of view and low relative drug penetration. Our main objective was to use PET to measure the deposition and postdeposition kinetics of TAA in the lung after administration from the Azmacort inhaler. The second objective was to evaluate changes in distribution caused by the inhalation spacer that is built into the product. METHODS: 11C-labeled TAA was formulated as the Azmacort product, 5 healthy volunteers inhaled it, and PET scans were obtained of its distribution in the head and chest. Region-of-interest analysis with CT overlay was used to analyze the distribution and kinetics in the airway and lung. RESULTS: From 10% to 15% of the inhaled drug dose was deposited in target airway regions in a distally decreasing pattern. Deposition in the oral cavity was about 30% of the dose. Slow absorption or clearance of drug from target tissues was observed over time. Use of the inhalation spacer caused statistically significant increases in all target tissues (factor of 2-5) and a roughly 40% decrease in oral deposition. Measurable amounts of the drug remained in target regions throughout the scanning period. CONCLUSION: Local pulmonary distribution and kinetics of inhaled drugs can be measured accurately by PET for drug development. The integrated actuator-spacer significantly enhanced deposition of TAA in target tissues and reduced deposition in the oropharyngeal region.

Administration, Inhalation↗

Treatment of acute severe asthma with inhaled albuterol delivered via jet nebulizer, metered dose inhaler with spacer, or dry powder.

Despite the increasing use of dry powder formulations in the ambulatory setting, there is a paucity of information on the efficacy of this therapeutic modality to treat acute severe asthma. In addition, studies that compared wet nebulization vs metered dose inhalers formulated with chlorofluorocarbon (CFCMDI) attached to holding chambers have yielded discrepant results. Thus, it is unclear which of the three delivery systems would elicit a superior bronchodilator response, particularly in patients with life-threatening asthma. In a prospective, randomized open design, we studied the response to inhaled albuterol (salbutamol) in 27 adult asthmatics presenting to the emergency department (ED) with an FEV1 <30% predicted. Subjects were treated with one of the following regimens (nine subjects in each group): group A, mean (SD) baseline FEV1 of 0.7 (0.2) L, received albuterol solution, 5 mg, via a nebulizer (Puritan-Bennett Raindrop; Lawrenceville, Ga) impelled with oxygen (O2) at 8 L/min; group B, baseline FEV1 of 0.6 (0.15) L, received albuterol, 400 microg, via a CFCMDI attached to a 145-mL valved aerosol holding chamber (Aerochamber; Trudell Medical; London, ON); and group C, baseline FEV1 of 0.6 (0.17) L, received albuterol powder, 400 microg, by another means (Rotahaler; Glaxo; Research Triangle Park, NC). All groups received the respective treatments on arrival in the ED, every 30 min during the first 2 h, and then hourly until the sixth hour. Clinical parameters and FEV1 were recorded on ED admission and 15 min after each dose of albuterol. At the time of ED admission, all patients also received continuous O2 and one dose of I.V. steroids (dexamethasone, 8 mg). The total dose of inhaled albuterol administered during the 6-h treatment was 45 mg of nebulized solution in group A and 3,600 microg of albuterol aerosol and dry powder in groups B and C, respectively. No significant differences were found in the population demographics, baseline FEV1, and arterial blood gas values on air. FEV1 improved significantly in all patients after the 6 h of treatment. The 6-h area under the curve FEV1 improved similarly with the three delivery methods despite differences in the total dose administered. No patient was discontinued during the trial or admitted to hospital and no evidence of cardiovascular adverse events was apparent in any of the study groups. These data support the view that the three delivery methods appear adequate to treat subjects with acute severe asthma.

Administration, Inhalation↗

Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis.

The aim of this study was to examine the dose-response relationship of inhaled budesonide in adolescents and adults with asthma. A meta-analysis was carried out on placebo-controlled, randomised clinical trials, presenting data on at least one outcome measure of asthma and using at least two doses of budesonide, delivered by turbuhaler or metered-dose inhaler + spacer twice daily. A total of six studies of 1,435 adolescents and adults, with mild to moderately severe asthma, met the inclusion criteria for the meta-analysis. A negative exponential model indicated that 80% of the benefit at 1,600 micrograms.day-1 was achieved at doses of approximately 200-400 micrograms.day-1 and 90% by 300-600 micrograms.day-1. Meta-regression with a quadratic term in dose showed that the maximum effect was obtained with doses of approximately 1,000 micrograms.day-1. In conclusion, the available published data indicate that, in adolescents and adults with mild to moderate asthma, most of the therapeutic benefit of budesonide delivered by turbuhaler or metered-dose inhaler + spacer is achieved with a dose of approximately 400 micrograms.day-1 and the maximum effect is achieved at approximately 1,000 micrograms.day-1. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids and that the subjects included in this meta-analysis had predominantly mild to moderate asthma.

Administration, Inhalation↗

[Comparison of treatment of acute asthma attacks in children with salbutamol dispensed by the Volumatic dispenser or by a nebulizer].

Eighteen children with acute asthma were administered equal doses of Salbutamol either through a nebulizer and face mask or a dose-metered inhaler, spacer (Volumatic) and tidal breathing mechanism. Consecutive doses at twenty minute intervals were administered until either no significant improvement in pulmonary function was observed or until a cumulative dose of 0.15 mg/Kg (maximum of 5 mgs) had been given. All subjects finally received a dose of 0.15 mg/Kg (maximum of 5 mgs) of nebulized Salbutamol at the end of the study. No difference in bronchodilation was obvious between the methods of treatment. No significant side-effect was observed in any patient. Treatment of acute asthma in children with Salbutamol via a pressurized inhaler, spacer and tidal breathing mechanism may be an efficacious, safe and readily available method, but further work is needed before it can be recommended for routine home management of asthma attacks.

Acute Disease↗

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing.

BACKGROUND: Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM: To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis. METHODS: Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 microg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months. RESULTS: Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group. CONCLUSION: Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.

Acute Disease↗

Experience with a metered-dose inhaler with a spacer in the pediatric emergency department.

Studies of adults suggest that metered-dose inhalers with spacers are as effective as hand-held nebulizers for bronchodilator delivery. We studied 13 children with acute asthma. They received two puffs every 2 minutes from metered-dose inhalers with spacers (range, 4 to 14 puffs) titrated until improvement stopped. Peak expiratory flow increased 34% for metered-dose inhalers with spacers after the first 2 puffs and increased 87% for metered-dose inhalers with spacers after dose titration. After titration, respiratory rate decreased by 12%, heart rate increased by 2%, and breath sounds improved in 92% of the patients. We concluded that the metered-dose inhalers with spacers are an effective device for the treatment of asthma in the pediatric emergency department and that the use of metered-dose inhalers with spacers with titration can achieve significant bronchodilation in the treatment of patients with acute asthma.

Acute Disease↗

[Pharmacologic therapy of bronchial asthma].

The main feature in asthma is bronchial eosinophilic inflammation, induced, in genetically predisposed subjects, by known (aeroallergens, viral infection, occupational agents) and unknown agents. Inflammation critically increases bronchial responsiveness so that even rather mild stimuli (exercise, cold air, mist, allergens) are able to induce obstructive reactions. When preventive measures (specific immunotherapy, avoidance of inflammatory and precipitating factors) are inadequate, a pharmacological treatment is necessary. This should, in addition relieve bronchospasm, neutralize precipitating factors and reduce inflammation. In the first case bronchospasmolytic antireactive agents (beta 2-stimulants, antimuscarinic agents, theophyllines) should be used, whereas, in the second case, the first choice drugs are corticosteroids. Chromon derivatives can also be considered for both their antireactive and antiflogistic effects. It is impossible to elaborate rigid therapeutic schemes. Therapy must be individualized on the basis of symptoms, objective physical signs and functional data. Drugs, except theophylline (for which slow release oral formulations are preferred), should be preferably administered by inhalation. For patients who cannot properly master the use of metered dose inhalers, spacer devices or dry powder inhalers are indicated. Whereas mild asthmatic forms can be treated without corticosteroids, these are absolutely necessary when bronchospasmolytics and chromon derivatives, although appropriately used, do not provide a satisfactory control of the asthmatic syndrome. Many other drugs are now under study (antileukotrienes, anti-PAF, anti-5-lipoxygenase, anti-phospholipase A2), but the results published so far do not seem very promising. Anti-histamines, calcium antagonists, alpha-blocking drugs are justified only in some circumstances. The antireactive activity of loop diuretics is interesting, but its real therapeutic value is still to be assessed. Antibiotics are only needed in the (rare) cases of worsening of asthmatic symptoms due to infective sensitive agents.

Adrenal Cortex Hormones↗