Comparison of conventional metered dose inhaler and breath actuated inhaler in elderly patients

Elderly patients frequently fail to achieve or to retain a competent inhaler technique using a conventional metered dose inhaler. In a prospective, randomised, crossover study of 44 subjects aged 64–94 (mean 78) years, we compared a metered dose inhaler (MDI) with a breath actuated inhaler (BAI) in terms of inhaler technique, ease of teaching and patient acceptability. Patients were stratified according to physical, functional or cognitive impairment before randomisation. Structured tuition was provided at the start of treatments, and technique was graded weekly and retaught if deficient. At the start of the treatment periods satisfactory technique was observed in 14 of 35 patients (six impaired, eight unimpaired) using the MDI and in 14 of 35 patients (three impaired, 11 unimpaired) using the BAI (P = 1.0). At the end of the four-week treatment periods satisfactory technique was observed in 19 of 30 patients (seven impaired, 12 unimpaired) using the MDI and in 27 patients (11 impaired, 16 unimpaired) using the BAI (P = 0.01). Mean weekly teaching times (minutes) were similar (MDI 7.0, BAI 6.5, P = 0.41) and there was no difference in terms of patient acceptability (P = 0.38). A breath actuated inhaler may be the preferred device for elderly patients as a greater proportion were able to retain satisfactory inhaler technique.     

Relative lung and total systemic bioavailability following inhalation from a metered dose inhaler compared with a metered dose inhaler attached to a large volume plastic spacer and a jet nebuliser

OBJECTIVE: To compare the lung and systemic delivery of salbutamol following inhalation from a metered dose inhaler (MDI), a MDI attached to a spacer (MDI+SP) and a nebuliser (NEB) using a urinary pharmacokinetic method. METHOD: Twelve healthy subjects each provided urine samples at 0, 30 min and pooled up to 24 h after the start of 5 x 100 microg salbutamol inhaled from MDI and MDI + SP and after 2.5 mg was delivered by NEB. Following nebulisation, the amount of salbutamol trapped on an exhalation filter together with that remaining in the apparatus was determined. The amount left in the spacer and that leaving the MDI mouthpiece was also determined. Thus, for all the methods, the amount available for inhalation from each study dose was determined. RESULTS: The mean (+/- SD) 30-min urinary excretion amounts of salbutamol for MDI, MDI+SP and NEB were 12.6+/-3.5, 27.1+/-6.0 and 16.1+/-4.6 microg, respectively. The mean ratios (90% confidence intervals) for MDI+SP compared with MDI and NEB were 230.2 (186.7, 273.8) and 183.0 (146.4, 219.7) (both P values<0.001), respectively, while that between MDI and NEB was 134 (110.4, 159.1) (P < 0.05). The mean (+/-SD) 24-h urinary excretion values for salbutamol and its metabolite were 287.0+/-46.5, 198.1+/-34.7 and 253.4+/-138.3 microg, respectively. Following inhalation a mean of 202.9+/-51.5 microg was left in the spacer. Similarly, after nebulisation 1387.7+/-88.9 microg was left in the nebuliser chamber, 26.3+/-8.0 microg in the mouthpiece and 553.8+/-68.5 microg exhaled. The mean emitted dose from the MDI was 88.4+/-6.1 microg per actuation. When normalised for the amounts available for inhalation, the mean amounts of salbutamol excreted in the urine during the first 30 min were 2.86+/-0.78, 9.15+/-1.69 and 3.06+/-0.70% following MDI, MDI + SP and NEB, respectively. CONCLUSION: Five 100-microg doses inhaled from a metered dose inhaler attached to a spacer delivered more to the lungs and less to the systemic circulation than either the same doses from a metered dose inhaler used alone or five times the dose given via a jet nebuliser. Spacers should be routinely used instead of nebulisers to manage patients unless they are short of breath.     

Comparability of albuterol delivered by a piezoelectric device versus metered dose inhaler in patients with chronic obstructive airways disease.

In recent years, there has been increased interest in developing propellant-free inhalers for the treatment of patients with chronic obstructive airways disease. Various powder inhalators have been developed. A recent alternative to the dose-metered aerosols has been produced using the piezoelectric effect. This double-blind, double-dummy, randomized, dual-dose, four-period crossover study was designed to compare the effect of albuterol inhaled from the piezoelectric device (PED) and albuterol inhaled from the metered dose inhaler (MDI). The primary efficacy variables were forced expiratory volume in one second (FEV1) and area under the curve (AUC). Although we found a statistically significant device effect for the primary efficacy variables, the two treatments (PED [test] and MDI [reference]) are comparable. The only variable for which comparability was not found was time of onset. We found no dose differences. In conclusion, we found a similar effect of albuterol inhaled by a PED versus an MDI in patients with chronic obstructive airways disease.     

影响慢性阻塞性肺疾病患者正确使用定量型气雾剂的因素分析及对策

目的 探讨慢性阻塞性肺疾病（COPD）患者正确使用定量型气雾剂的必要性和可行性. 方法 对120例COPD患者使用定量型气雾剂,按使用的7个步骤进行初试记录.出院前复试,出院后2周再次复试.比较患者在初、复试中的正确使用率. 结果 初始时,120例COPD患者中能正确使用定量型气雾剂者18例（15%）,常见的错误为：先按压后吸气（90例次）、连喷几次后再吸气（30例次）、吸气后无屏气（28例次）、吸人激素后无漱口（20例次）、使用前无摇匀（18例次）、先吸入糖皮质激素后再吸入β2受体激动剂（80例次）.出院前复试时总的正确使用率增至88例（73%）.出院2周第二次复试时总的正确使用率降至56%（68例）. 结论 定量型气雾剂在COPD患者中使用的正确率低影响疗效.建立规范化的指导和定期培训才能保证使用的正确性和有效性.     

Characterization of a microprocessor-controlled tubular multiple metered dose inhaler aerosol generator for inhalation exposures of pharmaceuticals.

A microprocessor-controlled tubular multiple metered dose inhaler (MDI) aerosol generator was constructed for the delivery of pharmaceutical aerosols to inhalation chambers. The MDIs were mounted in four cassettes containing one to four MDIs on a stepped end plate. The MDIs in each cassette were pneumatically activated at intervals that were controlled by the microprocessor. The cassettes permitted easy replacement of each set of MDIs with a fresh set of MDIs whenever necessary. Aerosol concentration was controlled by varying the number of active MDIs in each cassette and the frequency of activations per minute of each row. Aerosol from the MDIs flowed along the long axis of the tube, which provided a path length sufficient to diminish impaction losses. Using a light-scattering device to monitor the aerosol concentration, the pulsatile output from the MDIs in the cassettes was demonstrated to be adequately damped out provided that the dilution/mixing/aging chamber exceeded 3 ft in length. The tube diameter selected was the minimum compatible with mounting the required number of MDIs so that the linear velocity of the aerosol was adequate to efficiently transport the aerosol out of the dilution chamber. Aerosol concentration and particle size data were recorded for a nose-only rodent exposure chamber. Reproducible aerosol concentrations ranging from 0.03 to 0.6 mg/L were generated. Particle sizes ranged from 2- to 3-microm mass median aerodynamic diameter. Thus, the aerosol generated was within the size range suitable for inhalation exposures.     

A critical comparison of the dose delivery characteristics of four alternative inhalation devices delivering salbutamol: pressurized metered dose inhaler, Diskus inhaler, Diskhaler inhaler, and Turbuhaler inhaler.

Salbutamol is a short-acting beta 2 agonist which is effective as a rescue therapy in the treatment of asthma. This study uses in vitro test methods to compare the capability of four alternative devices to deliver an accurate and precise dose of salbutamol. It is demonstrated that the conventional metered dose inhaler (MDI) achieves excellent accuracy and precision in dose delivery. Additionally, it is the most efficient inhaler in terms of generating in-vitro a fine particle fraction from the dose. A spacer device has been shown to further enhance the dosing characteristics. When tested over a wide range of inspiratory air flow rates, the Diskus (GlaxoWellcome, Hertfordshire, UK) has comparable accuracy and precision to the MDI tested at 60 L/min, and it offers an advantage over two alternative dry powder inhalers (DPIs), delivering a more consistent dose across the range of flow rates tested and being more efficient at generating a fine particle fraction than either Turbuhaler (Astra, Lund, Sweden) or Diskhaler (GlaxoWellcome) at both 28 and 60 L/min inspiratory flow rates. Diskus, Diskhaler, Ventolin, Volumatic, and Rotadisk are trademarks of the GlaxoWellcome Group of companies. The Accuhaler is the alternative to the Diskus in those countries where the Diskus trademark is not available. Inspiryl and Turbuhaler are trademarks of the Astra Group of companies.     

Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler

Aims The number of dry powder inhaler (DPI) devices could increase because they are easier to use than a metered dose inhaler (MDI). Using urinary excretion, the relative bioavailability of salbutamol to the lungs and the body for a prototype DPI has been compared with an MDI.
Methods A randomized, double-blind, two way crossover study compared the amount of salbutamol in the urine 30  min following inhalation of 2×100  μg salbutamol from a prototype DPI (Innovata Biomed Ltd, UK) and a Ventolin^® (Allen and Hanburys Ltd, UK) MDI in 10 volunteers. The amount of salbutamol and its metabolite, the ester sulphate conjugate, renally excreted up to 24  h post inhalation was also determined to evaluate the relative bioavailability of salbutamol to the body.
Results The mean (s.d.) 30  min post-treatment urinary excretion for the prototype DPI and MDI was 8.4 (2.6) and 5.0 (1.9)  μg, respectively ( P <0.001). The total amount of salbutamol and its ester metabolite excreted in the urine over the 24  h period after inhalation was 187.9 (77.6) and 137.6 (40.0)  μg ( P <0.05).
Conclusions The prototype DPI delivered more salbutamol to the body and the lungs than a conventional MDI. This finding supports further development of the prototype DPI. The urinary salbutamol method is able to discriminate between two different inhalation systems.     

Breathlessness and exercise tolerance in chronic airflow obstruction: 2-hourly versus 4-hourly salbutamol by inhalation

Breathlessness, exercise tolerance, and spirometry were measured in 12 patients whose major symptom was breathlessness, secondary to severe chronic airflow limitation, during a double-blind crossover comparison of inhaled salbutamol in two dosages (200 micrograms 4-hourly and 200 micrograms 2-hourly) with placebo. Daily visual analogue scores of breathlessness, exercise tolerance and spirometry were all significantly improved with salbutamol in both dosages compared to placebo. The 2-hourly regimen was superior to the 4-hourly regimen only in terms of exercise tolerance. Walking distance had deteriorated significantly 2 hours after salbutamol on the 4-hourly regimen and was usefully increased by an extra dose of salbutamol on the 2-hourly regimen at the equivalent time, without side-effects. Salbutamol provided considerable symptomatic relief in addition to spirometric improvement in patients with chronic airflow limitation.     

Local versus total systemic bioavailability of beclomethasone dipropionate CFC and HFA metered dose inhaler formulations.

For inhaled formulations, the balance between desired local effects and undesired systemic activity can be expressed by L/T, where L represents bioavailability of drug from the lungs and T represents total systemic bioavailability. L/T is most useful when comparing formulations of the same inhaled substance. A high L/T is desirable as this implies efficient drug delivery to the target site, and minimization of unwanted activity from non-targeted drug delivery. The objective of this publication is to compare L/T for CFC and HFA inhaler formulations of beclomethasone dipropionate (BDP). Predictions of the L/T comparison were tested with clinical trials. From five deposition and pharmacokinetic studies, L/T ratios for CFC-BDP and HFA-BDP were calculated as 0.21 and 0.92, respectively. These ratios predicted two differences for the therapeutic use of these products: (1) a smaller dose of HFA-BDP than CFC-BDP may be required for efficacy; and (2) a smaller number of adverse events may be observed for the HFA-BDP product, when delivered at the equivalent dose, compared to the CFC comparitor. A dose-response study confirmed that less than half the dose of HFA-BDP is needed to give the same efficacy as CFC-BDP. Two safety studies that measured adrenal suppression demonstrated less suppression with HFA-BDP than with a comparable efficacious dose of CFC-BDP. It is concluded that L/T is a useful parameter that incorporates the systemic contributions of lung deposition and pharmacokinetics. It is recommended that this parameter be considered whenever deposition and pharmacokinetic data for two formulations of the same inhaled substance are compared.     

Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system.

The impending phaseout of chlorofluorocarbon (CFC)-containing metered dose inhalers (MDIs) has challenged the pharmaceutical industry to rethink and redesign many components of the technology involved in delivering asthma medication to the lungs. Along with the emergence of the first formulation using the nonozone-depleting propellant, hydrofluoroalkane (HFA) 134a to replace CFC propellants, advances in drug delivery technology have improved the performance characteristics of the MDI itself. Although MDIs have remained the mainstay of asthma therapy for 40 years, MDI technology still presents challenges. Some of the shortcomings of existing CFC MDIs affect the reliability of dosing. These challenges have been addressed in the development of the first CFC-free beta-agonist for the treatment of asthma. Airomir CFC-free (salbutamol sulfate; 3M Pharmaceuticals, St. Paul, MN), which is currently available in over 30 countries and was recently approved in the United States (Proventil HFA; Schering-Plough, Madison, NJ), incorporates numerous design and technological improvements which together with the introduction of CFC-free propellants mark the beginning of the next generation of asthma therapy. Although the new generation of CFC-free MDIs incorporates several improvements in dose reproducibility, these changes should be virtually transparent to the patient switching from a CFC MDI to a CFC-free MDI. What may be noticeable is a "softer puff," which is the result of valve and actuator redesign. The taste of the new CFC-free product may also be a little different yet totally acceptable to users.     

Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology.

The popular pressurized metered dose inhaler (pMDI), especially for asthma treatment, has undergone various changes in terms of propellant use and valve design. Most significant are the choice of hydrofluoroalkane-134a (HFA-134a) as a new propellant (rather than chlorofluorocarbon, CFC), a smaller exit nozzle diameter and attachment of a spacer in order to reduce ultimately droplet size and spray inhalation speed, both contributing to higher deposition efficiencies and hence better asthma therapy. Although asthma medicine is rather inexpensive, the specter of systemic side effects triggered by inefficient pMDI performance and the increasing use of such devices as well as new targeted drug-aerosol delivery for various lung and other diseases make detailed performance analyses imperative. For the first time, experimentally validated computational fluid-particle dynamics technique has been applied to simulate airflow, droplet spray transport and aerosol deposition in a pMDI attached to a human upper airway model, considering different device propellants, nozzle diameters, and spacer use. The results indicate that the use of HFA (replacing CFC), smaller valve orifices (0.25 mm instead of 0.5 mm) and spacers (ID = 4.2 cm) leads to best performance mainly because of smaller droplets generated, which penetrate more readily into the bronchial airways. Experimentally validated computer simulations predict that 46.6% of the inhaled droplets may reach the lung for an HFA-pMDI and 23.2% for a CFC-pMDI, both with a nozzle-exit diameter of 0.25 mm. Commonly used inhalers are nondirectional, and at best only regional drug-aerosol deposition can be achieved. However, when inhaling expensive and aggressive medicine, or critical lung areas have to be reached, locally targeted drug-aerosol delivery is imperative. For that reason the underlying principle of a future line of "smart inhalers" is introduced. Specifically, by generating a controlled air-particle stream, most of the inhaled drug aerosols reach predetermined lung sites, which are associated with specific diseases and/or treatments. Using the same human upper airway model, experimentally confirmed computer predictions of controlled particle transport from mouth to generation 3 are provided.     

驱动器的规格与吸入辅助装置对气雾剂体外沉积性质的影响

目的 考察驱动器的规格——孔径、孔长以及吸入辅助装置的使用对气雾剂体外沉积性质的影响.方法 以自制丙酸氟替卡松混悬型气雾剂为模型药物,装配不同规格的驱动器,使用Andersen多级撞击器(Andersen cascade impactor,ACI)测定体外沉积率;将丙酸氟替卡松气雾剂装配筛选好的特定规格的驱动器,分别在不使用吸入辅助装置与使用吸入辅助装置的情况下,对体外沉积性质进行对比研究.结果 在孔径固定的情况下,随着孔长的延长,驱动器的残留量降低,Andersen多级撞击器装置的L型连接管沉积量增加,微细粒子剂量降低.在孔长固定的情况下,随着孔径的增加,驱动器的残留量降低,Andersen多级撞击器装置的L型连接管沉积量增加,微细粒子剂量降低.根据试验结果、混悬型气雾剂本身的剂型特点以及驱动器的实际使用情况,最终,将0.42 mm孔径、0.70 mm孔长的驱动器作为优选驱动器;在使用吸入辅助装置的情况下,Andersen多级撞击器装置L型连接管的沉积量极大地降低,微细粒子剂量增加,原来沉积在L型连接管的大粒子很大一部分被截留在吸入辅助装置当中.结论 驱动器的规格会对吸入气雾剂的体外沉积产生一定的影响,在药品研发的过程中,可根据气雾剂产品的具体特点(溶液型或混悬型,原料药的粒径大小等)进行驱动器的筛选;吸入辅助装置的使用可以提高气雾剂的药物利用率,推荐患者用药时使用.     

Effect of inhalation flow rate on the dosing characteristics of dry powder inhaler (DPI) and metered dose inhaler (MDI) products.

Both the dose delivered from the device and the particle size of the medication are important parameters for inhalation products because they influence the amount of drug that is delivered to the patient's lung. The inspiratory flow rate may vary from dose to dose in a given patient and between patients. The Marple-Miller Cascade Impactor, a new multistage inertial impactor that operates at two flow rates (30 and 60 liters/min) with comparable particle size cut-offs, provides a means to study the effect of inhalation flow rate on the particle size distributions of inhalation products. The medication delivery, mass median aerodynamic diameter (MMAD), and fine particle mass were determined, in a randomized fashion, for albuterol, beclomethasone, budesonide, and terbutaline in both metered dose inhaler (MDI) and dry powder inhaler (DPI) products as a function of flow rate. In all cases, independent of drug or device used, the MDI products had a more reproducible respirable dose than the breath-actuated DPI products tested as a function of inhalation flow rate.     

Evaluation of levalbuterol metered dose inhaler in pediatric patients with asthma: a double-blind,randomized, placebo- and active-controlled trial

ABSTRACT

Objective: To evaluate the efficacy and safety of levalbuterol metered dose inhaler (MDI) in children aged 4-11 years (n = 173).

Research design and methods: Multicenter, randomized, double-blind 28‐day study of QID levalbuterol 90?µg, racemic albuterol 180?µg, and placebo (2:1:1 ratio). Serial spirometry was performed on Days 0, 14, and 28. The primary endpoint was the double-blind average peak percent (%) change in FEV₁ from visit pre-dose; the primary comparison was with placebo. Secondary endpoints included the area under the FEV₁ percent change from pre-dose curve and peak % predicted FEV₁. Safety endpoints included adverse events, laboratory tests, rescue medication use, and electrocardiograms.

Results: Levalbuterol significantly improved the least square mean peak percent change in FEV₁ compared with placebo (levalbuterol 25.6% ± 1.3% [p < 0.001]; racemic albuterol 21.8% ± 1.8% [p = ns]; placebo 16.8% ± 1.9%). Results for levalbuterol were similar for the other spirometry endpoints (?p < 0.05 vs. placebo). No levalbuterol-treated patients had a peak percent change in FEV₁ < 10% (compared with 15.8% of racemic albuterol-treated patients and 30.3% of placebo-treated patients). The incidence of adverse events was 43.4% for levalbuterol, 56.4% for racemic albuterol, and 51.4% for placebo. The rate of discontinuation was 1.3% for levalbuterol, 2.6% for racemic albuterol, and 8.6% for placebo. The rate of asthma attacks (10.5%, 12.8%, 14.3%, respectively) was similar among treatments. Levalbuterol and racemic albuterol both reduced rescue medication use (?p < 0.01 vs. placebo) and produced changes in ventricular heart rate and QT_c‐F that were similar to placebo.

Conclusions: In this study, levalbuterol administered via MDI significantly improved airway function in comparison with placebo in asthmatic children aged 4–11 years with a safety profile that was similar to placebo.     

Evaluation of levalbuterol metered dose inhaler in pediatric patients with asthma: a double-blind, randomized, placebo- and active-controlled trial

OBJECTIVE: To evaluate the efficacy and safety of levalbuterol metered dose inhaler (MDI) in children aged 4-11 years (n = 173). RESEARCH DESIGN AND METHODS: Multicenter, randomized, double-blind 28-day study of QID levalbuterol 90 microg, racemic albuterol 180 mug, and placebo (2:1:1 ratio). Serial spirometry was performed on Days 0, 14, and 28. The primary endpoint was the double-blind average peak percent (%) change in FEV(1) from visit pre-dose; the primary comparison was with placebo. Secondary endpoints included the area under the FEV(1) percent change from pre-dose curve and peak % predicted FEV(1). Safety endpoints included adverse events, laboratory tests, rescue medication use, and electrocardiograms. RESULTS: Levalbuterol significantly improved the least square mean peak percent change in FEV(1) compared with placebo (levalbuterol 25.6% +/- 1.3% [p < 0.001]; racemic albuterol 21.8% +/- 1.8% [p = ns]; placebo 16.8% +/- 1.9%). Results for levalbuterol were similar for the other spirometry endpoints (p < 0.05 vs. placebo). No levalbuterol-treated patients had a peak percent change in FEV(1) < 10% (compared with 15.8% of racemic albuterol-treated patients and 30.3% of placebo-treated patients). The incidence of adverse events was 43.4% for levalbuterol, 56.4% for racemic albuterol, and 51.4% for placebo. The rate of discontinuation was 1.3% for levalbuterol, 2.6% for racemic albuterol, and 8.6% for placebo. The rate of asthma attacks (10.5%, 12.8%, 14.3%, respectively) was similar among treatments. Levalbuterol and racemic albuterol both reduced rescue medication use (p < 0.01 vs. placebo) and produced changes in ventricular heart rate and QT(c-F) that were similar to placebo. CONCLUSIONS: In this study, levalbuterol administered via MDI significantly improved airway function in comparison with placebo in asthmatic children aged 4-11 years with a safety profile that was similar to placebo.     

Comparison of the lung absorption of FK224 inhaled from a pressurized metered dose inhaler and a dry powder inhaler by healthy volunteers.

FK224 is a cyclopeptide drug with poor oral absorption due to proteolysis in the gastrointestinal tract. The objectives of this study were to investigate the absorption of FK224 from the lung in healthy volunteers, and compare the pharmacokinetic profiles of FK224 after inhalation from a pressurized metered dose inhaler (pMDI) and dry powder inhaler (DPI). The pMDI (Suspension type, 1 mg as FK224/puff) and DPI (4 mg and 10 mg as FK224/capsule, using Spinhaler as the device) were developed by formulating the same micronized particles of FK224 which were premixed with beta-cyclodextrin (beta-CyD) to improve the solubility of FK224. In the case of pMDI, 1, 4 or 8 mg was inhaled by the corresponding number of puffs with the pMDI. In addition, the in vitro drug delivery characteristics of the inhalers were evaluated using a multistage liquid impinger. In both inhalers, it was observed that FK224 could be absorbed into the systemic circulation from the lungs of the healthy volunteers, and the AUC and C(max) were proportionally increased depending on the emitted dose after inhalation. However, the pharmacokinetic (PK) parameters for DPI were significantly higher than that of pMDI, in spite of usage of the same fine particles for the formulations in both inhalers. Based on the distribution from the in vitro examination, the fine particle dose, which is defined as the dose region delivered as particles <3.8 microm, was calculated from the emitted dose inhaled by the healthy volunteers. It was found that the PK parameters for both inhalers were proportionally increased depending on the predicted fine particle dose regardless of the type of inhaler. This suggests that the absorption from the lung is influenced by the fine particle dose. We concluded that DPI is a suitable inhaler for FK224, and the alveolus, which is generally known as the site of action of the fine particles, is a possible absorptive site for FK224.     

Comparison of a fenoterol/ipratropium combination with salbutamol from metered dose inhalers in subjects with chronic partially reversible airways obstruction

We have compared the acute bronchodilator response following salbutamol 200 micrograms and fenoterol 200 micrograms with ipratropium 80 micrograms, from metered dose inhalers in ten subjects with severe partially reversible airflow obstruction. Treatment with the combination resulted in a similar degree of bronchodilation but with a significantly longer duration of action.     

Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler.

The objective of this study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP) from a breath-activated inhaler (QVAR Autohaler) compared with proper and improper press and breathe (QVAR P&B) metered dose inhaler (MDI) technique. The hypothesis was that that the smaller particles of BDP from HFA-BDP would stay suspended longer in the inspiratory air of patients and thus reduce the deleterious effects of inhaler discoordination. The study was an open label, four period, cross-over design. Asthmatic patients (n = 7) with a history of asthma symptoms, an FEV-1 of >70% of predicted normal, and a history of reversibility to a beta-agonist of >or=12% were utilized. BDP was radiolabeled with technetium-99m and delivered from the QVAR Autohaler or QVAR P&B device in patients trained to reproducibly utilize coordinated and discoordinated P&B MDI technique. Patients using Autohaler MDI exhibited 60% lung deposition of BDP. Patients using coordinated technique with the P&B MDI exhibited 59% lung deposition. Patients trained to consistently actuate the P&B MDI before inhaling exhibited 37% lung deposition. Patients trained to consistently actuate the P&B MDI late in the inspiration (i.e., 1.5 sec into a 3-sec inspiration) exhibited 50% lung deposition. In conclusion, the breath-activated Autohaler automatically provided optimal BDP lung deposition of 60%. Patients with good P&B MDI technique also received optimal lung deposition of 59%. The degree of lung deposition was decreased as patients demonstrated poor inhaler technique. However patients with poor technique still received a large lung dose of BDP (i.e., >or=37%) compared with lung deposition values of 4-7% for CFC-BDP MDIs previously published and confirmed in this study.     

A comparative study of the efficacy of beclomethasone dipropionate delivered from a breath activated and conventional metered dose inhaler in asthmatic patients

Summary

In order to overcome the problem of poor co-ordination with the use of the conventional press and breathe metered dose inhaler, a breath-activated inhaler (‘Autohaler’ inhalation device) has been developed. The clinical response to equal doses of beclomethasone dipropionate administered from the ‘Autohaler’ device and the conventional metered dose inhaler was compared in 36 stable asthmatic patients receiving regular inhaled beclomethasone dipropionate. The study was performed using a double-blind, double-dummy crossover design. Each treatment was given for 4 weeks. Objective and subjective measures of asthma severity were compared in the second 14 days of each treatment period, with clinical equivalence defined as a difference of 20% or less in the adjusted mean values for the 30 patients with data from both treatment periods. Equivalence at the ± 5% level was found in the objective measures of pre-bronchodilator FEV₁, (p≤0.001); post-bronchodilator FEV₁ (p<0.001); morning and evening peak expiratory flow rate (both p≤0.001). Patient diary cards established there was equivalent usage of inhaled bronchodilator, and equivalent symptom scores for daytime disability and daytime and night-time breathlessness. The results show that, in stable asthmatics, treatment with beclomethasone dipropionate is clinically equivalent when delivered by the ‘Autohaler’ device or the conventional metered dose inhaler used efficiently.     

Drug delivery from the Turbuhaler and Nebuhaler pressurized metered dose inhaler to various age groups of children with asthma.

A total of 198 children aged 3 to 15 years inhaled a single dose of 200 micrograms budesonide from a Nebuhaler pressurized metered dose inhaler (pMDI) and a Turbuhaler dry powder inhaler in a randomized crossover study. The budesonide dose delivered to a patient was assessed by measuring the amount of drug deposited on a filter inserted between the inhaler outlet and the patient's mouth. The dose of budesonide deposited on the filter and the estimated dose of particles with a mass median aerodynamic diameter (MMAD) of 5 microns or less after inhalation from the Turbuhaler were both approximately twice the values inhaled from the pMDI Nebuhaler in children less than 5 years of age (P < 0.01). The variation in the dose delivered to the patient was similar for the two inhalers in children over 5 years old. In 3- to 4-year-old children, dose delivery to the patient was higher and/or more consistent from the pMDI Nebuhaler than from the Turbuhaler. Filter dose after Turbuhaler treatment varied significantly from peak inspiratory flow rate through the Turbuhaler (PIFTbh) (P < 0.01). The percentage of children producing a PIFTbh greater than 50 L/min decreased with age (89%, 45%, and 14% in 5-, 4-, and 3-year-old children, respectively). It is concluded that drug delivery to a child with asthma varies with age and inhalation device. Further studies are needed to assess the clinical importance of this finding.