Impact of inhalers used in the treatment of respiratory diseases on global warming.

The term "carbon footprint" describes the emission of greenhouse gases into the environment as a result of human activities. The healthcare sector is responsible for 5-8% of the value of global greenhouse gas emissions, of which medical aerosols account for only 0.03% of the total emissions. The reduction of greenhouse gases, including those used for the production and use of medicinal products and medical devices, is part of the responsibilities that Poland and the respective countries should undertake in order to implement the assumptions of international law. At the level of medical law, this obligation correlates with the need to exercise due diligence in the process of providing health services, including the selection of low-emission medical products and devices (inhalers) and providing patients with information on how to handle used products and devices, with particular emphasis on those that imply greenhouse gas emissions. Pressurized metered dose inhalers (pMDI) containing the hydrofluoroalkane 134a demonstrate the largest carbon footprint, followed by a metered dose liquid inhaler and dry powder inhalers (DPI). The carbon footprint of DPI with a given drug is 13-32 times lower than it is in the case of the corresponding pMDI. Replacement of pMDI by DPI is one of the effective methods to reduce the carbon footprint of inhalers, and the replacement should be based on current medical knowledge. A recycling system for all types of inhalers must be urgently implemented.

Particle engineered mannitol for carrier-based inhalation - A serious alternative?

In dry powder inhalation (DPI), larger carrier particles, typically lactose, are blended with micronised active pharmaceutical ingredient (API) particles to improve handling, processability and inhalable fraction. Alternative carrier materials were researched for years, but did not enter the market yet. In this study, a common lactose carrier for DPI formulations and a spray granulated mannitol carrier were compared to evaluate if the particle engineered mannitol can be considered a serious alternative. Blends with five different API concentrations (0.1 to 4%) were prepared with two APIs. Physical carrier and blend characterisation regarding particle size, morphology, density, shear cell testing and dosing behaviour were performed. Aerodynamic assessment was done using two different inhaler devices (one capsule-based inhaler and one reservoir-based inhaler). In addition, the influence of different flow rates was examined. Results indicated that uniform dosing in metered mass and delivered dose over this API concentration range was achieved due to good flowability of the blends. Furthermore, linear dose delivery could be seen over the added API concentrations. Impaction analysis showed that the respirable fractions of mannitol blends were comparable (for salbutamol sulphate blends) or higher (for budesonide blends) than with a standard lactose carrier.

Prospective evAluatIon foR inhalation devices in Greek patients with COPD and asthma: The PAIR study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and asthma remain a major health burden. Adherence to inhaled therapy is critical in order to optimize treatment effectiveness. Properly designed questionnaires can assess patients' satisfaction with their inhaler devices. PATIENTS AND METHODS: A total of 766 patients with COPD, asthma or Asthma-COPD Overlap (ACO) were initially enrolled. During their first visit, patients were classified into three groups (Diskus™, Elpenhaler®, Turbuhaler®). Patients completed the FSI-10 questionnaire on Day 0 and Day 60. Test-retest reliability was evaluated. RESULTS: A total of 705 patients completed the study. FSI-10 questionnaire had good test-retest reliability (Total Intraclass Correlation Coefficient: 0.86). All dry powder inhaler (DPIs) yielded satisfactory results. Median score of FSI-10 questionnaire in first visit (FSI-10-I) was significantly higher for patients receiving Elpenhaler® (45, 95% CI: 44 to 46) than patients receiving Diskus™ (42, 95% CI: 41 to 43) and Turbuhaler® (42, 95% CI: 41 to 43) (p < 0.001). Accordingly, median score of FSI-10 questionnaire in the final visit (FSI-10-II) was significantly higher for patients receiving Elpenhaler® (46, 95% CI: 45 to 47) than patients receiving Diskus™ (42, 95% CI: 41 to 43) and Turbuhaler® (43, 95% CI: 42 to 44) (p < 0.001). CONCLUSION: FSI-10 questionnaire had good test-retest reliability and thus can be used in the follow-up of patients with COPD, asthma and ACO. All DPIs were highly acceptable among all study groups. Elpenhaler® achieved significantly higher ratings than Diskus™ and Turbuhaler® in FSI-10 score and presented higher preference among patients with obstructive lung diseases.

A quantitative evaluation of adherence and inhalation technique among respiratory patients: An observational study using an electronic inhaler assessment device.

BACKGROUND: Problems related to poor adherence and inhaler technique (IT) are historically reported in the literature. Most common methods used for adherence and IT assessment are reported to be either inaccurate or subjective. Few electronic monitoring devices (EMDs) that provide an objective measure of both adherence and IT while patients use inhalers at home now exist. Therefore, this study aimed to examine adherence level and IT among respiratory patients in community care using such an EMD for the first time in England. METHODS: A prospective, multicentre, observational cohort study was conducted. Patients with chronic obstructive pulmonary disease (COPD) or asthma were recruited from independent community pharmacies within West and South London. Patients were provided with a dry-powder inhaler (DPI) mounted with an EMD to use for 1 month. Adherence was also assessed using pharmacy dispensing data, inhaler dose counter and self-reporting. RESULTS: Data were available for 48 patients. Only eight patients used their inhaler in the correct manner at the correct interval as identified by the chosen EMD. The median actual adherence rate, as measured by the EMD, was 42.7%. This was significantly different from the median dose counter adherence (100%), medication refill adherence (MRA) (100%), proportions of days covered (PDC) (97.8%) and self-reported adherence (P < .001, each). Within a 1-month period, there were 2188 files showing attempted use of the DPI, of which 840 had IT errors. The median technique error rate (TER) was 30.1%. Most common errors recorded were as follows: multiple inhalations, drug priming without inhalation and failure to prime the device correctly. CONCLUSION: The current study demonstrates that measures such as dose counter, prescription refill and self-reporting showed a high level of adherence among the observed patients. However, the objective data provided by the EMD showed a significantly lower actual adherence rate, reflecting how adherence remains variable and problematic among patients in the community.

Dry powder inhalers - between the doctor and the patient.

The article briefly presents currently accessible dry powder inhalers (DPI). Basing on the data from the literature, we discussed the most common mistakes related to the utilisation of DPI as well as their clinical and economic consequences. We also extensively analysed all factors that may influence the efficacy and safety of inhaler therapy of asthma and COPD, mostly with the use of DPI. In addition, we indicated the potential to improve the efficacy of inhaler therapy from the doctor and COPD or asthma patient perspective. We also presented a DPI choice algorithm including the patient's preferences and competences.

Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence.

Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be clinically beneficial for inhaler technique training and the remote monitoring of patient adherence.

Budesonide + formoterol delivered via Spiromax® for the management of asthma and COPD: The potential impact on unscheduled healthcare costs of improving inhalation technique compared with Turbuhaler®.

BACKGROUND: Fixed-dose combinations of inhaled corticosteroids and long-acting ß2 agonists are commonly used for the treatment of asthma and COPD. However, the most frequently prescribed dry powder inhaler delivering this medicine - Symbicort® (budesonide and formoterol, BF) Turbuhaler® - is associated with poor inhalation technique, which can lead to poor disease control and high disease management costs. A recent study showed that patients make fewer inhaler errors when using the novel DuoResp® (BF) Spiromax® inhaler, compared with BF Turbuhaler®. Therefore switching patients from BF Turbuhaler® to BF Spiromax® could improve inhalation technique, and potentially lead to better disease control and healthcare cost savings. METHODS: A model was developed to estimate the budget impact of reducing poor inhalation technique by switching asthma and COPD patients from BF Turbuhaler® to BF Spiromax® over three years in Germany, Italy, Sweden and the UK. The model estimated changes to the number, and associated cost, of unscheduled healthcare events. The model considered two scenarios: in Scenario 1, all patients were immediately switched from BF Turbuhaler® to BF Spiromax®; in Scenario 2, 4%, 8% and 12% of patients were switched in years 1, 2 and 3 of the model, respectively. RESULTS: In Scenario 1, per patient cost savings amounted to €60.10, €49.67, €94.14 and €38.20 in Germany, Italy, Sweden and the UK, respectively. Total cost savings in each country were €100.86 million, €19.42 million, €36.65 million and €15.44 million over three years, respectively, with an estimated 597,754, 151,480, 228,986 and 122,368 healthcare events avoided. In Scenario 2, cost savings totalled €8.07 million, €1.55 million, €2.93 million and €1.23 million over three years, respectively, with 47,850, 12,118, 18,319, and 9789 healthcare events avoided. Savings per patient were €4.81, €3.97, €7.53 and €3.06. CONCLUSIONS: We demonstrated that reductions in poor inhalation technique by switching patients from BF Turbuhaler® to BF Spiromax® are likely to improve patients' disease control and generate considerable cost savings through healthcare events avoided.

Pharmacokinetics of the Inhaled Selective Glucocorticoid Receptor Modulator AZD5423 Following Inhalation Using Different Devices.

AZD5423 is a non-steroidal glucocorticoid receptor modulator, with low aqueous solubility, developed for treatment of asthma and COPD. In this work, we aim to evaluate and compare the absorption pharmacokinetics (PK) of AZD5423 after inhalation via four devices, (Spira®, I-neb®, Turbuhaler® and a new dry powder inhaler (new DPI)) with two formulations using differently sized primary particles, and to compare the pulmonary bioavailability with the predicted lung deposited dose. Plasma concentration-time data after intravenous, oral and inhaled administration via four devices were available from two clinical studies in healthy and asthmatic subjects. A population PK modelling approach was taken to sequentially incorporate each route of administration, assuming parallel absorption compartments for inhaled AZD5423. A non-compartmental analysis for derivation of PK parameters was performed for comparison. Pulmonary bioavailability varied between devices, with the lowest estimates for I-neb (27%) and Turbuhaler (30%) and the highest for the new DPI (46%) and Spira (35-49%). The pulmonary bioavailability was substantially lower than the predicted lung deposited dose (range 59-90%). Lung absorption was separated into a faster and a slower process in the model. The half-life of the faster absorption appeared formulation-dependent, while the slower absorption (half-life of 0.59-0.78 h) appeared independent of formulation. The large difference in the estimated pulmonary bioavailability and the predicted lung deposited dose for AZD5423 implies an impact of mucociliary clearance. The lung absorption half-life indicates that AZD5423 is retained in the lung for a relatively short time.

Inhaler Errors in the CRITIKAL Study: Type, Frequency, and Association with Asthma Outcomes.

BACKGROUND: Poor inhaler technique has been linked to poor asthma outcomes. Training can reduce the number of inhaler errors, but it is unknown which errors have the greatest impact on asthma outcomes. OBJECTIVE: The CRITical Inhaler mistaKes and Asthma controL study investigated the association between specific inhaler errors and asthma outcomes. METHODS: This analysis used data from the iHARP asthma review service-a multicenter cross-sectional study of adults with asthma. The review took place between 2011 and 2014 and captured data from more than 5000 patients on demographic characteristics, asthma symptoms, and inhaler errors observed by purposefully trained health care professionals. People with asthma receiving a fixed-dose combination treatment with inhaled corticosteroids and long-acting beta agonist were categorized by the controller inhaler device they used-dry-powder inhalers or metered-dose inhalers: inhaler errors were analyzed within device cohorts. Error frequency, asthma symptom control, and exacerbation rate were analyzed to identify critical errors. RESULTS: This report contains data from 3660 patients. Insufficient inspiratory effort was common (made by 32%-38% of dry-powder inhaler users) and was associated with uncontrolled asthma (adjusted odds ratios [95% CI], 1.30 [1.08-1.57] and 1.56 [1.17-2.07] in those using Turbohaler and Diskus devices, respectively) and increased exacerbation rate. In metered-dose inhaler users, actuation before inhalation (24.9% of patients) was associated with uncontrolled asthma (1.55 [1.11-2.16]). Several more generic and device-specific errors were also identified as critical. CONCLUSIONS: Specific inhaler errors have been identified as critical errors, evidenced by frequency and association with asthma outcomes. Asthma management should target inhaler training to reduce key critical errors.

Optimizing drug delivery in COPD: The role of inhaler devices.

BACKGROUND: Inhaled medication is the cornerstone of the pharmacological treatment for patients with asthma and chronic obstructive pulmonary disease (COPD). Several inhaler devices exist, and each device has specific characteristics to achieve the optimal inhalation of drugs. The correct use of inhaler devices is not granted and patients may incur in mistakes when using pressurized metered-dose inhalers (pMDIs) or dry-powder inhaler (DPIs). The incorrect use of inhaler devices can lead to a poorly controlled disease status. Unfortunately, guidelines provide limited guidance regarding the choice of devices. This article presents a review of the literature on different inhaler device requirements. Data from literature (PubMed and Google Scholar) on the commercially available inhaler devices have been evaluated and the history of inhaler medicine described. Furthermore, advantages and disadvantages of each type of device have been analyzed. The evaluation of literature indicated the availability of robust data on the devices characteristics and factors influencing selection of delivery devices. Each type of device has its own pro and cons. The age, cognitive status, visual acuity, manual dexterity, manual strength and ability to coordinate the inhaler actuation with inhalation may be as important as the disease severity in determining the correct approach to delivery of respiratory medication. The administration of effective therapies via a device that is simple to use and accepted by patients may help to improve treatment outcomes in patients with COPD.

Irregular and Ineffective: A Quantitative Observational Study of the Time and Technique of Inhaler Use.

BACKGROUND: Cross-sectional observational studies suggest that between 50% and 60% of patients misuse a dry powder inhaler, whereas studies with electronic monitors indicate that patients sometimes overuse/underuse their inhalers. It is not known what impact errors and erratic use have on inhaler adherence. OBJECTIVES: The purpose of this study was to longitudinally quantify when and how patients adhered to a twice-daily preventer treatment by using a novel acoustic recording device attached to an inhaler (INhaler Compliance Assessment). METHODS: Patients with a history of asthma or chronic obstructive pulmonary disease (n = 123) from primary care and community pharmacies were given an INhaler Compliance Assessment-adapted inhaler for 1 month. Analysis of the audio files provided quantitative information on time and technique of inhaler use. RESULTS: Data were available for 103 patients. Twenty-one patients (20%) used their inhaler in the correct manner at the correct interval. There were 5045 audio files with attempted inhalations, of which 1204 had technique errors (24%). Errors included inadequate flow (27%), drug priming without inhalation (19%), exhalation into the inhaler (18%), and multiple inhalations (25%). On average, participants made errors 20% of the time. Of 60 doses expected to be taken in a month per person, on average 49 doses (82%) were attempted and when errors were accounted for, the average number of actual doses taken was 34 doses (57%; P < .01) comparing attempted to actual doses. DISCUSSION: These data highlight that ineffective and irregular inhaler use is common and when combined in a single calculation indicate that only 20% of participants used their inhaler correctly and on time.

Characteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: an analysis of salbutamol Easyhaler data.

The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma) were included (n=121, age: 57.8±17.3 years). Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12). Forty-six asthmatics served as controls. Reversibility was tested with 400 µg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland). Demographic data and patients' perceptions of Easyhaler compared with ß2-agonist pressurized metered dose inhalers (pMDIs) were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001). Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001). Reversibility was equally often found in smokers as in never-smokers (33% vs 34%). Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced Easy-haler somewhat easier to use than smokers and patients with COPD. In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler. Nonreversible patients with COPD were characterized by higher weight and body mass index, and a higher FEV1/FVC ratio. Most patients preferred Easyhaler compared with a pMDI.

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting.

OBJECTIVE: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). METHODS: This was a historical, multinational, cross-sectional study (2011-2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with ≥1 serious errors. RESULTS: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made ≥1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with ≥1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26-3.40); obesity (OR 1.75; 1.17-2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04-2.36); female sex (OR 1.51; 1.08-2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04-2.02). CONCLUSIONS: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate.

Randomized equivalence trial: A novel multidose dry powder inhaler and originator device in adult and adolescent asthma.

BACKGROUND: Guideline-defined asthma control can be achieved and maintained in patients by treatment with fluticasone propionate-salmeterol (FP-Sal). OBJECTIVE: To compare the efficacy and safety of FP-Sal delivered via a novel multidose dry powder inhaler (mDPI) versus an originator device in adolescent and adult patients with moderate-to-severe persistent asthma. METHODS: Patients ages 12-65 years (N = 555) were randomized to treatment with FP-Sal novel mDPI 100 µg-50 µg or 500 µg-50 µg, or originator device 100 µg-50 µg or 500 µg-50 µg in a double-blind, double-dummy, parallel-group, multicenter study. Primary efficacy measures were absolute change in forced expiratory volume in 1 second (FEV1) from baseline and the area under the 12-hour serial FEV1 curve at the end of 12 weeks of treatment. Secondary end points included mean changes in FEV1; FEV1 % predicted; morning predose peak expiratory flow; daytime, nighttime, total asthma symptom scores; rescue medication use; percentage of patients with guideline-defined controlled asthma; global efficacy evaluation; patients' device preference; and safety. RESULTS: FP-Sal mDPI and originator device-mediated increases in FEV1 from baseline to the end of treatment were not significantly different, difference in least squares mean, -0.065 L (95% confidence interval, -0.154 to 0.024 L) at 100 µg-50 µg, and -0.032 L (95% confidence interval, -0.121 to 0.057 L) at 500 µg-50 µg). Both doses of FP-Sal mDPI improved FEV1 area under the 12-hour serial FEV1 curve from baseline and all secondary efficacy measures with no significant differences from the originator device at equivalent doses, with similar safety profiles. CONCLUSIONS: FP-Sal mDPI demonstrated equivalent efficacy and safety profile to the originator device and is an alternative in this patient group.

Evaluation of inhaler technique, adherence to therapy and their effect on disease control among children with asthma using metered dose or dry powder inhalers.

OBJECTIVE: To address the problems about correct use of inhaler devices, adherence to inhaler corticosteroid treatment and the effects of these problems on the control of asthma. METHODS: Children with asthma were evaluated for the correct use of inhaler devices and adherence to therapy using a questionnaire. Effect of these on control of asthma was defined. RESULTS: A hundred and seventy-one patients and/or their families were interviewed. The mean age was 8.29 ± 4.65 years (1-19) and 62.6% were male. Metered dose inhaler (MDI) with spacer was used by 119 (69.5%) patients and 52 (30.5%) used dry powder inhalers (DPIs). The devices were used correctly by 68.1% of patients using MDI and 34.6% of patients using DPI (p < 0.001). The most common improper step was "breathe in from the spacer 5-6 times or 10 s" for MDI (24.4%) and "exhale to residual volume" for DPI (51.9%). Frequency of correct use was higher in patients trained 3 times (p < 0.001). Asthma was controlled more frequently among correct users (p < 0.001). Partial or poor adherence was showed 22.8% of patients. Patients with mothers who had lower educational status had higher frequency of incorrect use of inhaler device (p = 0.007). CONCLUSION: It was found that asthma control was better among correct users. Repetitive training about using devices may contribute improving inhaler technique. Especially children whose mothers had low education level and patients using DPI should be evaluated more carefully.

[The choice of inhalation device: A medical act]. / Le choix du dispositif d'inhalation (hors nébulisation) : un acte médical.

Inhaled treatments are essential for respiratory diseases management, including COPD and asthma. Optimal control of the disease largely depends on patient's compliance and proper use of these treatments. Different types of ready-to-use inhaler devices are available: metered dose inhaler, dry powder inhaler or soft mist inhaler. Each of these devices presents specific characteristics and constraints that have to be evaluated and taken into account before prescription. In order to optimize adherence and treatment efficacy, the choice of inhaler device should depend on the specific needs, abilities and preferences of each patient and a specific education to treatment should be provided. Inhaled treatments, even containing the same drug, have different technical constraints and are thus not easily interchangeable. Their substitution without prior medical consent and without proper training can lead to errors in taking treatment, treatment failures and increased health care consumption. In France, substitution by the pharmacist is not authorized. While patient education must be carried out in collaboration with all health professionals, it is preferable that the choice of inhaler device remains the responsibility of the physician.

A randomised cross-over trial investigating the ease of use and preference of two dry powder inhalers in patients with asthma or chronic obstructive pulmonary disease.

OBJECTIVES: The objective of this randomised, cross-over study was to compare a new single-dose dry powder inhaler (Elpenhaler (EH)), with a widely used, multi-dose dry powder inhaler (Diskus (DK)) on critical errors, patient preference, and satisfaction with the inhalers. METHODS: First, patients read the instructions of one device, followed by a first inhalation attempt. Inhalation errors were assessed and if mistakes were made, correct inhaler use was demonstrated. Then patients had to demonstrate again and mistakes were registered. This was repeated up to four times. After completing the first device, the same procedure was started with the second inhaler. Primary outcome was the percentage of patients making at least one critical error after reading the insert. Secondary outcomes were inhaler preference and satisfaction with the inhalers. RESULTS: After reading the insert, 19 of 113 patients (17%) made at least one critical error with DK and 40 (35%) with EH (p = 0.001); 73% preferred the DK and 27% the EH (p < 0.001). The mean overall satisfaction score (1 = very satisfied; 5 = very dissatisfied) for DK was 1.59 and for EH 2.48 (p < 0.001). CONCLUSION: With DK fewer errors were made, more patients preferred DK over EH and patients were more satisfied with DK. This may enable DK to improve treatment outcomes more than EH.

Minimal inspiratory flow from dry powder inhalers according to a biphasic model of pressure vs. flow relationship.

Inhalation therapy using the dry powder inhaler (DPI) is now the first choice for obstructive pulmonary diseases. We previously measured relationships between inspiratory pressure (PI) and flow rate of almost all of the DPIs available in Japan, and described an importance of inspiratory efforts. In the present study, we further analyzed the data obtained in the previous study. Although there were linear relationships between PI and flow2, the slope became steeper when PI was less than a certain value (critical PI, existed between 15-20 cmH2O). When PI was less than critical PI, linear rather than parabolic regression between PI and flow yielded better fits (r > 0.90, p < 0.001). Inspiratory flows at the critical PI were 53.9 (Diskus), 65.8 (Diskhaler), 45.9 (Turbuhaler for Pulmincort), 48.6 (Turbuhaler for Symbicort) and 38.0 l/min (Twisthaler). These findings suggested that flow through the DPI becomes laminar rather than turbulent flow in the range below critical PIs. We suggest that patients should inhale from the DPIs with inspiratory pressure higher than critical PI.

A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler.

Short-term knemometry is a highly sensitive and accurate method for non-invasive assessment of systemic activity of inhaled corticosteroids in children with asthma. However, there are no randomized data available to elucidate the relation between inhaled corticosteroid suppressed short-term lower leg and height growth. The aim of the present study was to assess the relation between short-term lower leg and 1-yr height growth in children with asthma treated with inhaled budesonide from the new Pulairmax inhaler 200 µg once daily in the morning or montelukast 5 mg once daily. A total of 52 pre-pubertal children with asthma were included in a randomized open-label parallel group study. Length of the lower leg and height were measured by knemometry and stadiometry, respectively, at study entry and after 2, 4, 12, 20, 28, 36, 44 and 52 wks. Lower leg and height growth rates were significantly lower in the budesonide than in the montelukast group (p < 0.0001). Mean 2-wks lower leg growth rate was 0.17 mm/wk in the budesonide and 0.39 mm/wk in the montelukast treated children (p = 0.02). Mean 1-yr height growth rate was 5.51 cm/yr in the budesonide and 6.51 cm/yr in the montelukast group [95% CI: (0.20; 1.79)]. There was a strong linear correlation between lower leg and height growth in both groups, rho = 0.96 (budesonide) and 0.98 (montelukast). In conclusion, 1-yr height growth suppression of budesonide 200 µg administered via the Pulairmax inhaler once daily in the morning was indicated from suppressed short-term lower leg growth providing evidence that short-term knemometry is able to predict 1-yr height growth suppression of inhaled corticosteroids. Short-term knemometry should be performed as part of the safety assessments of new inhaled corticosteroids and inhalation devices in children with asthma before long-term height growth evaluations are initiated.