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Biomedical subjects

K Nikander

Publications and source records attributed to K Nikander.

27 records · Page 2Linked to original sources

Effects of reducing or discontinuing inhaled budesonide in patients with mild asthma.

BACKGROUND: In a previous study, we found that two years of treatment with an inhaled corticosteroid, budesonide, was more effective than treatment with an inhaled beta 2-agonist, terbutaline, in patients with newly diagnosed, generally mild asthma. We continued this study for a third year to investigate whether the steroid dose could be reduced or discontinued and what effect crossover of patients from beta 2-agonist therapy to corticosteroid therapy would have. METHODS: A total of 37 patients treated for two years with inhaled budesonide at a dose of 1200 micrograms per day were randomly assigned to treatment with 400 micrograms of budesonide per day (19 patients) or placebo (18 patients) in a double-blind manner. Another 37 patients, who had received terbutaline during the first two years, were crossed over in an open-label manner to treatment with 1200 micrograms of budesonide per day during the third year. RESULTS: Treatment with the reduced dose of budesonide was sufficiently effective in 74 percent of the patients to maintain bronchial responsiveness at a level similar to that achieved with the higher dose. In contrast, improvement was maintained in only 33 percent of the patients receiving placebo, and the differences in pulmonary function between the steroid and placebo groups were significant (for forced expiratory volume in one second, P = 0.007; for bronchial responsiveness to histamine, P = 0.025; and for peak expiratory flow in the morning, P = 0.040). The condition of patients who were crossed over from terbutaline therapy to treatment with 1200 micrograms of budesonide per day improved. However, the degree of improvement in these patients appeared to be less than in those who were treated with budesonide at the beginning of the three-year study. CONCLUSIONS: Early treatment with inhaled budesonide results in long-lasting control of mild asthma. Maintenance therapy can usually be given at a reduced dose, but discontinuation of treatment is often accompanied by exacerbation of the disease.

Administration, Inhalation↗

Drug delivery systems.

Nebulizers, both jet and ultrasonic, were originally designed to convert a liquid solution into an aerosol. During recent years suspensions for nebulization have been developed and nebulized with the available devices. In-vitro comparisons of drug output from jet and ultrasonic nebulizers have shown significant differences between solutions and suspensions. Ex-vivo comparisons have confirmed the in-vitro results. In an ex-vivo trial with 10 adult healthy volunteers, budesonide suspension was compared with terbutaline solution in terms of inhaled mass of drug, when using either jet or ultrasonic dosimetric nebulizers (Spira). The inhaled mass of drug was defined as the dose of drug on a filter inserted between the nebulizer and the patient. The nebulizers were run to a fixed gravimetrically determined suspension output of 75% of the initial weight. The inhaled mass of drug as a percentage of the nominal dose was close to 50% for the terbutaline solution in both nebulizer systems, while the inhaled mass of drug as a percentage of the nominal dose for the budesonide suspension was about 30% for the jet nebulizer and about 10% for the ultrasonic nebulizer. However, the inhaled mass of drug measured in adults cannot be directly extrapolated to infants and children. In order to study the range of the inhaled mass of budesonide suspension in children an ex-vivo trial in 322 patients with bronchial asthma in the age range 0.6-15.7 years was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Use of budesonide Turbuhaler in young children suspected of asthma.

The question addressed in this study was the ability of young children to use a dry-powder inhaler, Turbuhaler. One hundred and sixty five children suspected of asthma, equally distributed in one year age-groups from 6 months to 8 yrs, inhaled from a Pulmicort Turbuhaler, 200 micrograms budesonide-dose-1, through a filter. The amount of drug trapped by the filter was used as a measure of drug released to the patient. None of the children had prior experience in the use of a Turbuhaler, but they were instructed carefully, together with their parents, in the clinic. The median dose released revealed an age-dependent increase, with a considerable scatter. Accordingly, the dose delivered could not be predicted in these young children. The limitation to effective use in young children appeared to be lack of sufficient co-operation, rather than physical limitations, as even some very young children appeared to obtain a sufficient activation of the device. It is likely that repeated training at home may improve these findings. In conclusion, our results indicate that dry-powder inhalers are not reliable in all circumstances for treatment of young children, and that careful and repeated tuition is required if such devices are to be used.

Asthma↗

Treatment of severe steroid dependent preschool asthma with nebulised budesonide suspension.

The steroid sparing effect of nebulised budesonide suspension was assessed in a double blind placebo controlled parallel group study of 36 preschool children with severe asthma who were dependent on treatment with oral steroids. Nebulised budesonide suspension significantly reduced the requirement for treatment with oral steroids, and produced a marked improvement in overall health as scored on a visual analogue scale during the clinic visits. This study shows a significant step forward in the prophylactic treatment of asthma in children under the age of 3 years, in whom the efficacy of many other nebulised treatments has been questioned.

Asthma↗

Delivery of micronized budesonide suspension by metered dose inhaler and jet nebulizer into a neonatal ventilator circuit.

We compared the delivery of a micronized suspension of budesonide by a metered dose inhaler (MDI) with two different spacers (Aerochamber and Aerovent) and by two jet nebulizers (MAD2 and Ultravent) to a ventilated neonatal test-lung using a standard neonatal ventilator circuit. The combination of MDI and Aerochamber was significantly better at delivering budesonide to a filter in front of the test lung (14.2% of aerosolized dose) than were either the MDI and Aerovent (3.6%) or the Ultravent or MAD2 jet nebulizers (0.02% and 0.68% of initial reservoir dose). Of the droplets emerging from the MDI, Aerochamber, and ET tube, 18% of the initial dose was in droplets less than 4.7 microns. Assuming that the test-lung model accurately reflects in vivo deposition, the combination of MDI and Aerochamber appears to be an extremely effective way of delivering budesonide aerosol to ventilated newborn infants.

Aerosols↗

How much nebulised budesonide reaches infants and toddlers?

The amount of budesonide suspension actually delivered to six subjects (aged 4-30 months) by a jet nebuliser and spacer system (System 22) was determined. Two nebulisations were performed in each subject using a filter at the exhalation outlet of the inhalation chamber. An inhalation filter was additionally attached between the facemask and the spacer in the first test. The drug was inhaled during the second test. The nebuliser equipment was washed with ethanol and the amount of drug deposited was determined. The amount of budesonide deposited in the exhalation filter increased when the inhalation filter was omitted. Only 14% of the nominal dose (500 micrograms) of budesonide was found in the inhalation filter, increasing from nine to 19% with increasing age. Approximately 75% of the nominal dose was found in the nebuliser equipment. These findings must be considered when deciding the nominal dose of budesonide suspension to be given to infants and toddlers.

Administration, Inhalation↗

Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma.

BACKGROUND: The presence of airway inflammation even in mild asthma points to the potential value of antiinflammatory therapy. We compared the effect of an inhaled corticosteroid, budesonide, with that of an inhaled beta 2-agonist, terbutaline, in the long-term treatment of newly detected asthma. METHODS: We studied 103 patients (29 male and 74 female patients 15 to 64 years old) in whom asthma had appeared within the previous year. The patients were randomly assigned in blinded fashion to two treatment groups: one to receive 600 micrograms of inhaled budesonide twice a day, and the other to receive 375 micrograms of inhaled terbutaline twice a day. The study period was two years. RESULTS: After six weeks of treatment, the patients treated with budesonide tolerated inhaled histamine better than the patients treated with terbutaline (a difference of one doubling dose step, P less than 0.001), and the difference was sustained. Patients' diaries kept during the first three months of the study and during the last month of the first and second years showed budesonide to be more effective than terbutaline in improving peak expiratory flow in the morning (average increase from the pretreatment value, 32.8 liters per minute for budesonide vs. 4.8 liters per minute for terbutaline; P less than 0.001) and in the evening (P less than 0.01). Budesonide was also more effective in reducing the symptoms of asthma (P less than 0.01) and the use of supplemental beta 2-agonist medication (P less than 0.01). Ten patients were withdrawn from the terbutaline group because treatment was insufficiently effective, whereas only one dropped out of the budesonide group. The adverse reactions to both treatments were few and mild. CONCLUSIONS: Antiinflammatory therapy with inhaled budesonide is an effective first-line treatment for patients with newly detected, mild asthma, and it is superior to the use of terbutaline in such patients.

Adolescent↗

Peak inspiratory flow and inspiratory vital capacity of patients with asthma measured with and without a new dry-powder inhaler device (Turbuhaler).

In 101 asthmatic adults with varying degrees of bronchial obstruction, lung function tests including peak inspiratory flow (PIF), inspiratory vital capacity (IVC), peak expiratory flow (PEF), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) measurements were made. Significant correlations between inspiratory and expiratory volumes were found. In most patients, PIF was less reduced than the expiratory parameters of pulmonary function. When inhalation was performed through the new multi-dose, dry-powder inhalation device, Turbuhaler (PIF-TBH), it was significantly lower than PIF measured without Turbuhaler. In previous studies, PIF-TBH of 30 l.min-1 or more has proven sufficient to produce a therapeutic dose of terbutaline, and to produce significant bronchodilatation. Of 101 asthmatics in the present study, only four had PIF-TBH of less than 30 l.min-1. Although no parameters of spirometry could accurately predict PIF-TBH, there was a tendency for patients with severely impaired ventilatory capacity to produce lower PIF-TBH than patients with normal or near-normal ventilatory capacity. If patients with severely impaired ventilatory capacity are to receive inhalation therapy through Turbuhaler, either PIF or PIF-TBH should be measured, or the effect should be carefully monitored.

Adult↗

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler.

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗