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Inhaler technique of elderly patients: comparison of metered-dose inhalers and large volume spacer devices.

Large volume spacers (LVSs) reduce systemic absorption of steroid from metered-dose inhalers (MDIs) but there are no data to support the widespread belief that LVSs are easy for older people to use. MDI and LVS technique was examined in 40 inhaler-naive patients [19 men; 70-92 (mean 78.3) years] with chronic airways disease and mental test scores > 7/10. On day 1, technique was taught and errors corrected if possible. Technique was scored and patients asked which device they preferred. They were prescribed the device with which they were most competent. Those competent with both were given a device randomly. Technique was reassessed on day 29 without further tuition. On day 1 only three patients (8%) had inadequate technique for LVS vs. 12 (30%) for MDI (chi 2 = 6.90; p = 0.032). The main problems were inability to trigger the device (two patients with both devices), problems co-ordinating triggering and inhalation (20 patients with MDI), problems inserting the MDI into the LVS (seven patients), and unnecessary repetitive firing of the LVS (three patients); 28 (70%) preferred LVSs. On day 29, 29/30 (97%) with LVSs used them adequately, as did 13/15 (87%) using MDIs (five patients used both). LVSs have advantages over MDIs for elderly patients in terms of patient preference and inhaler technique.

Adrenal Cortex Hormones↗

Clinical use of spacer systems for corticosteroid inhalation therapy: a preliminary analysis.

This is a preliminary report on the first half of a study designed to assess the ability of two different spacer devices to improve the results of aerosol steroid treatment in chronic asthmatic patients given budesonide in low and high dosages. The spacers significantly reduced oropharyngeal candidiasis but did not affect dysphonia - possibly because the incidence of the latter was so low throughout the study. The spacers augmented the airway response to budesonide in these patients without materially increasing systemic absorption of the drug (assessed indirectly in terms of the change in blood eosinophil counts). Pretreatment with inhaled terbutaline did not significantly affect the performance of the spacers, either in terms of the airways responses or the amount of budesonide systemically absorbed. When used properly, these spacers can improve the cost effectiveness of aerosol steroid treatment. Since only adults were studied, it is not known whether these findings apply equally well to children with asthma.

Aerosols↗

Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction.

BACKGROUND: The exact amount of drug deposited in the respiratory and gastrointestinal tract in children with airway obstruction, when delivered from a metered-dose inhaler (MDI) via a spacer with mask, and its distribution in children with airway obstruction, are unknown. METHODS: We studied 15 children, using salbutamol labeled with technetium 99m. Each patient was imaged with a gamma-camera immediately after one puff of labeled salbutamol was administered via a spacer with mask. Drug deposition was then analyzed to measure the distribution of the labeled spray in the oropharynx, the lungs, the stomach, and the spacer with mask (Aerochamber) itself. RESULTS: Fifteen infants and children (mean age, 21 months (range, 3 months to 5 years); mean weight, 9.3 kg (range, 3.2 to 15 kg)) were studied. Mean aerosol deposition was 1.97% +/- 1.4% in the lungs, 1.28% +/- 0.77% in the oropharynx, and 1.11% +/- 2.4% in the stomach. The remainder was trapped in the spacer. Lung imaging after inhalation from an MDI via a spacer showed widespread deposition of the drug in central and peripheral intrapulmonary airways. In two adult volunteers the deposition after one puff of the same radiolabeled drug, inhaled from an MDI via a spacer with a mouthpiece, was 19% in the lungs and 2% in the stomach. CONCLUSIONS: Infants and toddlers with obstructive lung disease can be reliably and safely treated with inhaled medication administered with an MDI via a spacer with mask. The doses of a drug given from an MDI to infants and toddlers when a spacer with mask is used are not yet well defined but should be higher than the currently recommended doses, perhaps as much as an adult dose.

Administration, Inhalation↗

The potential value of a 750-ml spacer for the administration of inhaled corticosteroids to children.

An open, cross-over trial was conducted on 25 asthmatic children, aged 6-13 years, who required inhaled steroids. They inhaled Budesonide 200 micrograms twice daily, either directly from the metered dose inhaler or via the pear spacer (PS), for 2 months on each, in randomized order. The effects of the treatment were monitored with diary cards recording peak expiratory flow rates twice daily, symptoms and treatment taken, and with monthly clinical assessments including more sensitive lung function studies (flow-volume loops and single breath nitrogen wash-out tests). There was no specifically PS-related improvement in symptoms or in the majority of tests, but the results showed improvement with time when using either method. The improvement was more distinct in some tests reflecting proximal airway calibre (i.e., PEFR) than in tests thought to reflect predominantly peripheral airway calibre (i.e., F50, RV). The bronchodilator responsiveness, as shown by the increase in lung function tests after a beta-agonist was given, was significantly greater for FVC during the periods when the PS was used, although there was no significant improvement in FEV2 or PEFR. The improvement in tests reflecting proximal airways may have been due to optimization of the inhalation technique, greater understanding of asthma, or better compliance with medication associated with regular attendance for the study. The greater bronchodilator response whilst children were inhaling budesonide by the PS may have been due to increased deposition or better distribution of the steroid but was probably related to a difference between the two groups in initial baseline function tests.

Adolescent↗

Artificial neural network prediction of the patterns of deposition of polydisperse aerosols within human lungs.

For optimum therapeutic response from drug administered to the lungs, it is paramount that the aerosolised drug is able to deposit in the lower airways. The filtering characteristics of the respiratory tract, however, make this a particularly challenging task. Computational tools afford a cost-effective means of studying the problem, and here we report on the development of a rapid and reliable method for predicting the pattern of deposition of polydisperse aerosols within human lungs using artificial neural networks (ANNs). Literature (experimental) data on lung deposition of monodisperse aerosols were used to train a single ANN to allow for simultaneous predictions of regional and total aerosol particle deposition patterns in human lungs. When used in modelling the fate of polydisperse aerosols in human lungs, the trained ANN was found to give highly accurate predictions for all lung regions, and all (pharmaceutically relevant) particle sizes and breathing conditions (with errors typically <0.025%). Further testing of the ANN, using 'unseen' in vitro and in vivo data, gave good agreement of lung dosages. It is thus concluded that the ANN produced can be used to provide highly reliable estimates of particle deposition from polydisperse pharmaceutical aerosols generated from breath-actuated dry powder inhalers, nebulizers and metered dose inhalers with spacers.

Aerosols↗

Delivery of therapeutic aerosols to intubated babies.

Delivery of drug aerosols to the lungs of ventilated neonates by metered dose inhaler and spacer (Aerochamber) and ultrasonic nebuliser (Pentasonic) was assessed using sodium cromoglycate. The mean proportion of a known intratracheal dose of sodium cromoglycate excreted in the urine of four intubated infants was 37.5%. After assuming that 38% of the sodium cromoglycate aerosol reaching the neonatal lung will be excreted in the urine, three puffs (15 mg) delivered by metered dose inhaler and spacer resulted in a pulmonary dose of 258 micrograms (1.7%, n = 7). A dose of 20 mg (4 ml) sodium cromoglycate ultrasonically nebulised over five minutes into the inspiratory limb of a standard ventilator circuit produced a pulmonary dose of 257 micrograms (1.3%, n = 7). Of two in vitro lung models assessed, a combination of filter and neonatal test lung was superior to a multistage impactor in estimating the in vivo pulmonary sodium cromoglycate dose delivered by metered dose inhaler and spacer (243 micrograms v 1740 micrograms).

Aerosols↗

Poor inhalation technique, even after inhalation instructions, in children with asthma.

The aim of this study was to evaluate the effect of instructions to children with asthma (given by general practitioners or by pharmacy assistants) on how to inhale from metered dose inhalers with spacers (MDI/s) or dry powder inhalers (DPI). We scored inhalation technique of asthmatic children according to criteria defined by the Netherlands Asthma Foundation, and related the performance to the inhalation instructions given. For each inhaler, a number of steps were considered essential for reliable drug delivery. Patients newly referred for asthma were asked to demonstrate their inhalation technique and to fill out a questionnaire on the inhalation instruction received prior to referral. Children participating in a clinical trial, who had received repeated comprehensive inhalation instructions, served as a control group. Sixty-six newly referred patients (1-14 years of age, median age 5 years; 37 boys) and 29 control patients (5-10 years of age, median age 7 years; 21 boys) completed the study. Sixty patients (91%) had received inhalation instruction prior to referral. Only 29% of these patients, using a dry powder inhaler, performed all essential steps correctly, compared to 67% of children using a metered dose inhaler/spacer combination (P < 0.01). Children who had received comprehensive inhalation instructions with repeated checks of proper inhalation technique at the pharmacy or in the clinical trial setting were more likely to perform all essential steps correctly (79% and 93%, respectively) than children who had received a single instruction by a general practitioner (39%, P < 0.01). Many asthmatic children use their inhalers devices too poorly to result in reliable drug delivery, even after inhalation instruction. Comprehensive inhalation instruction and repeated check-ups are needed to assure reliable inhalation technique.

Administration, Inhalation↗

Current approaches in adult asthma: assessment, education and emergency management.

Asthma is a chronic respiratory disease characterized by smooth-muscle constriction of the airway, bronchial hyperresponsiveness, and an ongoing inflammatory process. Although more common in children, asthma in adults also requires careful management to decrease morbidity and mortality. The majority of chronic asthma cases have an allergic component; therefore, efforts to identify and eliminate environmental triggers may decrease the symptoms of most asthmatics. Asthma-education programs based on patient self-management have been shown to decrease asthma morbidity. Mastery of the following topics is necessary for patient self-management: identifying and avoiding exposure to symptom precipitators, using prescribed medications correctly, managing medication side effects, and recognizing and responding to exacerbations. Advances in diagnostic and treatment modalities include the home use of peak-flow meters to monitor respiratory function, and the use of metered-dose inhalers and spacers for the delivery of inhaled medication. Inhaled beta-adrenergic agonists, administered in higher than usual doses, have become the bronchodilators of choice in the treatment of acute asthma. Studies have demonstrated that metered-dose inhalers can be used for this purpose, even with severe asthma attacks that require hospitalization. Systemic corticosteroids are also important in the management of acute attacks. Care providers who teach patients about common symptom triggers and encourage avoidance techniques, who employ current strategies to enhance patients' medication use and patients' recognition of exacerbations, and who incorporate up-to-date treatment plans for acute asthma attacks may help reverse distressing trends in asthma morbidity and mortality.

Asthma↗

Effects of high-dose inhaled fluticasone propionate via spacer on cell-mediated immunity in healthy volunteers.

BACKGROUND: Systemic corticosteroids are known to alter cell-mediated immunity (CMI). However, the effects of inhaled steroids on CMI are unclear. We therefore sought to assess CMI following high-dose inhaled steroids in healthy subjects. METHODS: Ten healthy nonasthmatic subjects self-administered fluticasone propionate (FP), 440 microg bid, with a spacer device. CMI was assessed by delayed hypersensitivity skin testing to multiple antigens and in vitro by phytohemagglutinin (PHA) stimulation of peripheral blood T lymphocytes. Percentages of CD3(+), CD4(+), and CD3(+)CD8(+) cells expressing CD69(+) were determined by three-color flow cytometry. Studies were conducted before and after 4 weeks of FP treatment. RESULTS: After 4 weeks of FP treatment, two of nine subjects became anergic, whereas six of nine subjects had reduced skin responses (one subject was excluded). Mean total skin test score fell from 18.4+/-10.9 to 9.1 +/-7.2 mm (p = 0.02). There was a decline in tuberculin responses in all four subjects who were positive prior to FP treatment. Following FP treatment, the percentage of unstimulated (from control subjects receiving saline solution) CD3(+)CD4(+)CD69(+) cells declined from 14.8+/-4.2% to 8. 5+/-4.6% (p = 0.02) and the CD3(+)CD8(+)CD69(+) cells decreased from 29.7+/-12.7% to 17.1 +/-5.0% (p = 0.007). PHA stimulation produced significant increases in the percentage of CD3(+)CD4(+)CD69(+) cells before and after FP treatment (67.0+/-9.1%, p<0.02 before FP; 55.4+/-17.0%, p<0.02 after FP), and in the percentage of CD3(+)CD8(+)CD69(+) cells before and after treatment (79.7+/-9.3%, p<0.03 before FP; 71.2+/-11.4%, p = 0. 008 after FP). CONCLUSIONS: High doses of FP suppress the proportion of activated circulating T cells but do not affect the ability of T cells to respond to direct stimulation with PHA. However, depression of skin test responses to antigens following treatment with FP suggests an impairment of in vivo clinical manifestations of T-cell activation by a mechanism that requires further investigation.

Administration, Inhalation↗

beta(2)-Agonist delivery via a resuscitator bag (Ambu MediBag): a comparison with a metered-dose inhaler using the Volumatic-Spacer.

Although the administration of beta(2)-agonists by inhalation is recommended in the current guidelines for treatment of patients with acute bronchospasm, the large volume spacer that is necessary often is not available on board an ambulance due to space storage problems. Accordingly, an adapter enabling the application of therapeutic aerosols from a metered-dose inhaler (MDI) via a resuscitator bag (Ambu MediBag) was developed. The aim of this double-blinded, randomised study was to test the clinical efficiency of the Ambu MediBag (volume: approximately 1500 ml) in comparison with the commonly used Volumatic-Spacer (volume: 750 ml). One hundred patients receiving a bronchodilator response test were treated with MDIs of either 200 microg salbutamol via the Volumatic-Spacer or 400 microg salbutamol via the Ambu MediBag. The change of lung function variables was measured by bodyplethysmography before and after drug application. In both groups of 50 patients each, a highly significant reduction of airway resistance was shown after treatment. However, there was no statistically significant difference in lung function variables between the Ambu MediBag and the Volumatic-Spacer. From these results, we conclude that the Ambu MediBag is as effective as Volumatic-Spacer and might improve preclinical and clinical treatment of acute bronchospasm by inhalation with bronchodilators.

Acute Disease↗

Inhalational drug delivery from seven different spacer devices.

BACKGROUND: A study was performed to determine in vitro the difference in drug output of seven currently available spacer devices when used with different inhaled medications. METHODS: A glass multistage liquid impinger (MSLI) was used to determine the amount of disodium cromoglycate (DSCG, 5 mg), salbutamol (100 micrograms), or budesonide (200 micrograms) obtained in various particle size ranges from metered dose inhalers (MDIs) actuated directly into the MSLI or via one of seven different spacer devices; the Fisonair, Nebuhaler, Volumatic, Inspirease, Aerochamber, Aerosol Cloud Enhancer, and Dynahaler. RESULTS: In particles smaller than 5 microns in diameter the dose of DSCG recovered from the Fisonair and Nebuhaler was 118% and 124%, respectively, of that recovered using the MDI alone. The dose recovered from the smaller volume spacers was 90% (Inspirease), 36% (Aerochamber), 33% (Aerosol Cloud Enhancer), and 21% (Dynahaler) of that from the MDI alone. The Volumatic increased the amount of salbutamol in particles smaller than 5 microns to 117% of that from the MDI, and the Inspirease and Aerochamber spacers decreased it by nearly 50%. The amount of budesonide in small particles recovered after use of the Nebuhaler, Inspirease, and the Aerochamber was 92%, 101%, and 78%, respectively, of that from the MDI alone. CONCLUSIONS: Under the test conditions used, large volume spacers such as the Fisonair, Nebuhaler, and Volumatic delivered significantly more DSCG and salbutamol than the smaller spacers tested. The differences between spacers were less for budesonide than the other medications studied. This study shows that there are significant differences in the amount of drug available for inhalation when different spacers are used as inhalational aids with different drugs. Spacer devices need to be fully evaluated for each drug prescribed for them.

Administration, Inhalation↗

Domiciliary comparison of terbutaline treatment by metered dose inhaler with and without conical spacer in severe and moderately severe chronic asthma.

The bronchodilator response to cumulative doses of terbutaline administered by metered dose inhaler with and without a conical spacer device and by Acorn nebuliser has been compared in groups of patients with chronic severe and moderately severe asthma. After laboratory studies the patients undertook a randomised domiciliary crossover comparison of bronchodilator response to terbutaline given by metered dose inhaler with and without a spacer device, during which the severity of asthma was assessed by thrice daily recordings of peak expiratory flow (PEF) and symptom score. Improvement in FEV1 produced in the laboratory by the metered dose inhaler with spacer device was significantly greater than by metered dose inhaler alone (p less than 0.001) and similar to that from the nebuliser in both asthmatic groups throughout a range of terbutaline doses. In the domiciliary comparison mean midday and evening PEF rates were significantly higher with the use of the spacer device both in those with severe (p less than 0.01) and in those with moderately severe (p less than 0.05) asthma, and mean morning PEF was significantly higher in the severe group (p less than 0.05). The spacer device also produced a significant improvement in symptom score in both the severe and the moderately severe groups (p less than 0.05). Regular domiciliary use of the spacer device with the metered dose inhaler improves bronchodilator response, particularly in patients with chronic severe asthma, and may be a useful alternative to nebuliser treatment.

Administration, Inhalation↗

Paper spacers coupled to metered dose inhalers in family practice.

OBJECTIVES: 1. To assess the clinical efficacy of drug delivery using paper spacer devices coupled to metered dose inhalers (MDI). 2. To compare the effectiveness of paper spacers with the standard volumatic spacer. DESIGN: Randomised double-blind placebo controlled clinical trial. SETTING: Asthma clinic of a family practice at Kalutara. PATIENTS: 134 patients over 12 years of age, who attended the clinic with an acute episode of wheezing. METHOD: All patients over 12 years of age with an acute episode of wheezing who could speak a sentence of over 5 words were randomly allocated into 4 groups and administered salbutamol inhalations through a MDI coupled to a spacer. The first group used a 6-inch paper spacer, second group an 8-inch paper spacer, the third group a 10-inch paper spacer and the fourth group used a standard 750 ml volumatic spacer. MEASUREMENTS: In each subject, the peak expiratory flow rate (PFR) was recorded at the start, after placebo inhalation and after salbutamol inhalation. An increase of PFR of over 20% from the basal value was assessed as a good response. RESULTS: The number of patients who showed a good response after salbutamol inhalations in all four groups were very significant compared with the responses after placebo inhalations (p < 0.001). No significant differences were found in the effectiveness of salbutamol among the four other groups (p > 0.1). CONCLUSIONS: 1. All devices show equal efficacy. Metered dose inhalers and all 3 paper devices are as effective as the standard volumatic spacer. 2. The cost of a paper spacer device is negligible compared to that of the volumatic spacer. 3. The use of paper spacers in Sri Lankan family practices makes inhaled MDI therapy much cheaper without decreasing the effectiveness of drug delivery.

Administration, Inhalation↗

Aerosol delivery to non-ventilated infants by metered dose inhaler: should a valved spacer be used?

In a randomized double-blind cross-over study on 20 spontaneously breathing, oxygen-dependent preterm infants who had received positive pressure ventilation for respiratory distress syndrome, we tested the hypothesis that the one-way non-rebreathing valves of aerosol spacer devices might impair rather than enhance the delivery of aerosols to small infants by metered dose inhalers (MDI). Ten infants were given 2 doses (200 micrograms/dose) of MDI albuterol through a neonatal Aerochamber 4 h apart. At random sequence, one dose was delivered with the non-rebreathing valve of the Aerochamber in place; for the other dose, the valve had been removed. The experiment was repeated on another ten infants using a different spacer device (Babyhaler) with or without its one-way inspiratory valve removed. During the first hour following aerosol administration, use of the non-valved spacers was associated with a significantly greater degree of tachycardia in both groups, and also lower transcutaneous carbon dioxide tension in the Aerochamber group. All infants showed a reduction in respiratory system resistance and an improvement in functional residual capacity following albuterol treatment. In both groups, maximum reduction in respiratory system resistance, recorded 30 min after aerosol delivery, was significantly greater following the use of the non-valved spacers (Aerochamber: 51.2 +/- 3.1% vs. 35.0 +/- 2.8%, P < 0.0001; Babyhaler: 38.8 +/- 2.3% vs. 19.2 +/- 1.4%, P < 0.0001) than following the use of the spacers with a valve. The findings provide indirect evidence supporting our hypothesis and suggest that when the MDI is used to deliver therapeutic aerosols to non-ventilated newborns or small infants, a spacer device without a non-rebreathing valve should be used.

Aerosols↗

Effect of multiple actuations, delayed inhalation and antistatic treatment on the lung bioavailability of salbutamol via a spacer device.

BACKGROUND: The aim of this study was to extend previous in vitro observations regarding the effects of multiple actuations of aerosols into spacer devices, delayed inhalation, and antistatic treatment of spacer devices on the amount of drug delivered for inhalation. An in vivo study of lung bioavailability of salbutamol from a large volume (Volumatic) spacer was conducted. METHODS: Ten healthy volunteers of mean age 20.5 years with a mean forced expiratory volume in one second of 112.1% predicted were studied in a randomised single blind (investigator blind) crossover study. 1200 micrograms of salbutamol was given with mouth rinsing (100 micrograms/puff) on four study days: single puffs via spacer, multiple puffs via spacer (3 x 4 puffs), single puffs with 20 second delay before inhalation via spacer, and single puffs via an antistatic treated spacer. All spacers, including those treated with antistatic, were prewashed prior to each study day. Measurements of lung bioavailability were made at five, 10, and 20 minutes after inhalation to determine peak (Cmax) and average (Cav) plasma salbutamol levels. Systemic beta 2 responses including finger tremor, heart rate, and plasma potassium levels were also evaluated. RESULTS: Single puffs from the spacer produced higher plasma salbutamol levels and greater systemic beta 2 responses than either multiple puffs or single puffs with delayed inhalation for a 1200 micrograms dose. For Cmax this amounted to a 1.93-fold (95% CI 1.68 to 2.19) greater lung bioavailability for single puffs than for multiple puffs and a 1.80-fold (95% CI 1.59 to 2.00) greater lung bioavailability for single puffs than for single puffs with a 20 second delay. Comparison of the normal and antistatic treated spacers (both prewashed) revealed differences for Cmax with levels 1.23-fold (95% CI 1.04 to 1.41) greater for the normal spacer. CONCLUSIONS: Delayed inhalation from a Volumatic spacer and the use of multiple puffs results in a considerable decrease in the delivery of salbutamol to the lungs with an approximate twofold reduction in lung bioavailability. Washing a Volumatic spacer is as effective as an antistatic lining in reducing the effects of static charge on salbutamol delivery in vivo.

Adult↗

Dexamethasone aerosol use in an asthmatic nursing-home patient with Parkinson's disease and dementia.

Management of asthmatic or emphysematous elderly patients who cannot use metered-dose inhalers with spacers because of severe physical and mental disabilities is difficult. We report a case of a nursing-home patient with dementia and Parkinson's disease who required aerosolized corticosteroids to avoid repeated systemic corticosteroid courses for asthmatic exacerbations. The patient was unable to use a triamcinolone metered-dose inhaler with spacer devices because of his impairments. Therefore, nebulized dexamethasone solution was prepared and administered. Since initiation of nebulized dexamethasone, the patient has not required systemic corticosteroids. In addition, his hypopituitary adrenal axis has remained intact as evidenced by provocative cosyntropin testing. Therefore, nebulized dexamethasone solution may be an alternative to the aerosol corticosteroid metered-dose inhaler when patients are too impaired to use inhalers, even with spacers.

Aerosols↗

Cough after inhalation of corticosteroids delivered from spacer devices in children with asthma.

Children using a spacer device rather than another device for delivering inhaled corticosteroids (ICS) has been identified as a risk factor for cough immediately after inhalation. The aim of this study was to point out the different factors influencing the occurrence of such lateral side-effects. We studied this local side-effect in 402 asthmatic children (55.6 +/- 34.9 months; 65.6% boys) treated for at least 1 month with beclomethasone dipropionate (n = 331), budesonide (n = 47) or fluticasone propionate (n = 24) delivered from pressurized metered-dose inhalers and small (75.1%) or large volume (24.8%) spacer devices mainly used with face mask (90.7%). A total of 219 patients (54.5%), treated with either high doses of ICS or ICS and long-acting beta2-agonist, were considered as having severe asthma. Cough was reported after each inhalation of corticosteroids in 216 patients (53.7%). Among them, about 30% also complained of cough with beta2-agonists. Despite different propellants and dispersants, all corticosteroids induced cough similarly. Cough was not linked with asthma severity, but was significantly related to therapy duration and use of long-acting beta2-agonist. Type and volume of the spacer device, use of a face mask or mouthpiece were not influencing factors. Cough after inhalation of corticosteroids delivered from spacer devices is a frequent local side-effect in children with asthma. This side effect can greatly alter compliance. A practitioner must be sought at each visit.

Administration, Inhalation↗

Comparison of the antiasthmatic, oropharyngeal, and systemic glucocorticoid effects of budesonide administered through a pressurized aerosol plus spacer or the Turbuhaler dry powder inhaler.

To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device (Astra Pharma Production AB, Södertälje, Sweden) or pressurized metered-dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB), we compared these devices in a randomized, open, parallel-group trial. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8, 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Turbuhaler (n = 30) or pMDI + Nebuhaler (n = 28). Dose-dependent effects were demonstrated on asthma symptoms (p = 0.0001), daily peak expiratory flow (p = 0.02), blood eosinophils (p = 0.0001), urinary cortisol output per day (p = 0.0001), serum cortisol (p = 0.006), serum osteocalcin (p = 0.0001), and the oropharyngeal Candida colony count (p = 0.0007. analysis of covariance). The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found (p > or = 0.29). However, the 95% confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48. Thus in adults who use inhalation devices efficiently and have optimally controlled asthma, conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide, then down-titrated to minimize possible systemic effects. Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler.

Administration, Inhalation↗