Multidose Inhaler Research Articles

Estimating Tiotropium Wasted Doses After Adding Revefenacin to an Inpatient Formulary: A Single-Center Cross-Sectional Study.

Introduction: Revefenacin is a once-daily nebulized long-acting muscarinic antagonist (LAMA). Revefenacin is supplied as single-use nebulized vials, which may be preferable and less costly for hospital and health-system pharmacies to dispense versus multidose tiotropium inhalers. Estimates of LAMA multidose inhaler wasted doses remains unknown. Methods: This was a single-center descriptive cross-sectional study conducted between January 1 2021 and December 31 2021. Adult patients 18 years and older admitted to a 500-bed academic medical center in the southern United States and were ordered multidose tiotropium packages or single-use revefenacin vials during the study period were included. Results: Among 602 inpatients, there were 705 LAMA orders: 541 tiotropium (76.7%) and 164 revefenacin (23.3%). Four hundred ninety-five tiotropium orders (91.5%) wasted between 20% and 90% of multidose packages. Approximately $24,000 tiotropium doses were wasted versus single-use revefenacin vials. Conclusion: Multidose inhalers of tiotropium dispensed to hospitalized patients contributed to wasted doses compared to nebulized single-use revefenacin vials. Opportunities exist to minimize wasted doses of multidose long-acting inhalers dispensed to hospitalized patients.

Adherence to treatment recommendations of patients with chronic non-communicable respiratory diseases – a narrative review

Despite modern therapeutic solutions, patients with chronic obstructive pulmonary disease (COPD) and asthma do not achieve therapeutic benefits due to emerging obstacles to compliance. This review aimed to present and analyze the results of available studies evaluating the influence of sociodemographic, clinical, and psychosocial factors on the level of adherence of patients with COPD and asthma. This narrative review was based on papers indexed in the following databases: PubMed, MEDLINE, CINAHL, Web of Science, and Scopus. The analyzed studies showed that the adherence level of patients with COPD and asthma is unsatisfactory, ranging from 23.6 to 80%. The main factors increasing the level of adherence of COPD patients mentioned in the analyzed studies were: unemployment, taking LAMA, not smoking cigarettes, belief that medication is necessary, higher education, use of multi-dose DPI and MDI inhalers, a greater sense of self-efficacy, and longer duration of disease. Independent determinants of good adherence of patients with asthma were better quality of life, high level of disease control, treatment with ICS + LABA or FF/UMEC/VI, good knowledge about asthma, and positive attitude towards the disease. According to available studies, determinants lowering adherence among patients with COPD were overweight or obesity, depression, poor quality of life, belief that treatment is harmful, frequent hospitalizations, lack of knowledge about the disease and treatment, sleep disorders, and use of ICS, LABA/ICS. Patients with asthma who received infrequent functional support consumed alcohol and were convinced of the harm and lack of need for treatment were non-adherent. In addition, an association was shown between high levels of adherence and a reduction in ED visits and hospitalizations in asthma and COPD patients.

Determination of a treatment response threshold for the Eosinophilic Esophagitis Endoscopic Reference Score.

Endoscopic features of eosinophilic esophagitis (EoE) are measured using the validated EoE Endoscopic Reference Score (EREFS); however, a threshold for treatment response has not been defined. We aimed to determine a cut-point for endoscopic response as measured by EREFS. We performed a secondary analysis of a randomized clinical trial comparing budesonide slurry with swallowed fluticasone multidose inhaler for initial treatment of EoE. In the parent trial, EREFS was determined before and after treatment (score range 0-9), as were histologic findings and dysphagia symptoms. We performed tabular, flexible trend, and dependent mixture analyses of measures of treatment response to select the best clinical EREFS threshold. In the 111 included patients (mean age 39 years; 67 % male; 96 % white), an EREFS threshold of ≤ 2 was 80 % sensitive (95 % confidence interval [CI] 69 % to 88 %) and 83 % specific (95 %CI 67 % to 94 %) for histologic response (peak of < 15 eosinophils per high-power field). Flexible trend analysis and dependent mixture modeling similarly suggested that a threshold of ≤ 2 best captured the correlation of EREFS with histologic and symptomatic measures. Dependent mixture modeling found near-total membership in the response class at EREFS of 0 or 1 and > 75 % at EREFS of 2 or 3. An EREFS of ≤ 2 was the best clinical threshold for endoscopic response to topical steroid treatment, and was consistent with clinical and histologic response. Therefore, future studies can report a binary outcome of endoscopic response when EREFS is 2 or less.

PGI27 Systematic Review and Network Meta-Analysis: Topical Corticosteroids for Inducing Histological Remission in Eosinophilic Oesophagitis

Topical corticosteroids, comprised mainly of fluticasone multi-dose inhaler content swallowed or budesonide viscous solution (BVS), are the foundation of treatment for eosinophilic oesophagitis (EoE). Recently, a budesonide orodispersible tablet (BOT) has been approved for the treatment of EoE. Given the absence of direct comparisons, we evaluated the relative efficacy of BOT with other topical corticosteroid formulations for inducing histological remission in patients with EoE by a network meta-analysis (NMA). A systematic literature review was performed using MEDLINE and Embase up to August 1, 2019. Eligible studies comprised randomised controlled trials (RCTs) which evaluated adult patients with a diagnosis of active EoE treated with a topical corticosteroid in comparison to placebo or another topical corticosteroid. The outcome of interest was the proportion of patients achieving induction of histological remission defined as a peak oesophageal eosinophil count of <5 eosinophils/high-power field. Direct comparisons were made using the Mantel-Haenszel method and an NMA was performed using a fixed effects Bayesian framework with Markov Chain Monte Carlo simulations. A total of 6 trials (n=447 patients) were included in the quantitative summary. The NMA determined that BOT was associated with a higher odds of histological remission compared to BVS (odds ratio [OR]=4.9 [95% credible interval [CrI]=1.4, 19.1]), fluticasone (7.4 [1.7, 34.5]), nebulised swallowed budesonide (NSB) (25.0 [2.9, 247.2]) and placebo (387.6 [97.5, 2,275.6]). Similar findings were observed for direct comparisons. This NMA of RCTs suggest that BOT is significantly more likely to achieve histological remission in adult patients with EoE compared to BVS, fluticasone, and NSB.

Rapid Recurrence of Eosinophilic Esophagitis Activity After Successful Treatment in the Observation Phase of a Randomized, Double-Blind, Double-Dummy Trial

Eosinophilic esophagitis (EoE) is chronic and recurs if treatment is discontinued. We aimed to determine rates of recurrence, and whether initial treatment with oral viscous budesonide (OVB) resulted in less recurrence than fluticasone from a multidose inhaler (MDI). This was the observation phase of a randomized, double-blind, double-dummy trial comparing OVB with MDI for initial EoE treatment. Subjects with a histologic response (<15 eosinophils/high-power field) in the trial entered an observation phase in which treatment was discontinued and symptoms were monitored. Patients underwent an endoscopy or a biopsy when symptoms recurred or at 1 year. We analyzed time to symptom recurrence and assessed endoscopic severity and histologic relapse (≥15 eosinophils/high-power field) at follow-up endoscopy. Thirty-three of the 58 subjects (57%) had symptom recurrence before 1 year. The overall median time to symptom recurrence was 244 days. There was no difference in the rate of symptom recurrence for subjects treated with OVB vs MDI (hazard ratio, 1.04; 95% CI, 0.52-2.08). At symptom recurrence, 78% of patients had histologic relapse. The patients had significant increases in mean Dysphagia Symptom Questionnaire score (3.8 vs 8.7; P < .001), and the EoE Endoscopic Reference Score (1.3 vs 4.6; P < .001) compared with end of treatment. EoE disease activity recurred rapidly after initial histologic response to topical steroids (either OVB or MDI). Because most subjects had recurrent endoscopic and histologic signs not reliably detected by symptoms, maintenance therapy should be recommended in EoE patients achieving histologic response to topical steroids. Clinicaltrials.gov no: NCT02019758.

Assessment of the efficacy and safety of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler versus a multi-dose inhaler in patients with chronic obstructive pulmonary disease

BackgroundThis study tested the clinical non-inferiority of the fluticasone propionate/salmeterol combination 50/250 μg (FSC) Rotacaps®/Rotahaler® system, a single unit dose inhaler, with the multi-dose FSC Diskus® inhaler in adults with chronic obstructive pulmonary disease (COPD). MethodsThis multi-centre, randomised, double-blind, double-dummy, two-way cross-over study compared 12 weeks' treatment of FSC administered twice daily using Rotacaps/Rotahaler or Diskus. The primary endpoint was change from baseline in trough morning forced expiratory volume in 1 s (FEV1) at Day 85, and the pre-defined non-inferiority criteria was: the lower limit of the confidence interval (CI) for the treatment difference (Rotacaps/Rotahaler-Diskus) in least squares (LS) mean change from baseline, being greater than −45 mL. Secondary endpoints included change in breathlessness (as measured by transition dyspnoea index (TDI)) and COPD-specific health status measures. ResultsThe LS mean increase from baseline in trough FEV1 at Day 85 was 116 mL in the Rotacaps/Rotahaler group and 91 mL in the Diskus group (difference in model-adjusted LS mean change: 25 mL (95% CI 2 mL, 47 mL)), the lower limit of the CI for the treatment difference being greater than the protocol-defined criterion for non-inferiority i.e. −45 mL. Data for breathlessness, COPD-specific health status and safety parameters were similar following FSC treatment via either inhaler. ConclusionsThis study demonstrated the clinical non-inferiority of FSC 50/250 μg when administered using Rotacaps/Rotahaler compared with Diskus in patients with COPD. The risk:benefit profile for the two inhalers was comparable.

A systematic review of comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease: does inhaler choice matter?

BackgroundIn many countries worldwide, the long-acting anticholinergic drug tiotropium is available as a dry powder formulation delivered by means of the HandiHaler® inhalation device and as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler. Tiotropium HandiHaler® is a single-dose, dry powder, breath-actuated inhaler that provides delivered doses and lung deposition of tiotropium that are, over a wide range, not influenced by the severity of chronic obstructive pulmonary disease (COPD). Tiotropium Respimat® is a propellant-free, multi-dose inhaler that delivers a metered dose of medication as a fine, slow-moving, long-lasting soft mist, independently of patient inspiratory effort. The high fine-particle fraction of droplets produced by the Respimat® inhaler optimizes the efficiency of drug delivery to the lungs.MethodsTo help inform the choice of tiotropium inhaler for prescribers and patients, this systematic review summarizes the available pharmacokinetic, efficacy and safety data from comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in COPD, focusing on the licensed once-daily doses of 5 and 18 μg, respectively. Data sources reviewed include publications and abstracts identified from database searches.ResultsPublished evidence from comparative studies suggests that tiotropium Respimat® 5 μg and tiotropium HandiHaler® 18 μg provide similar clinical outcomes in patients with COPD.ConclusionsThe findings indicate that physicians can base their decision about an inhaler for tiotropium on factors other than efficacy or safety. These could be patient preference for a particular inhaler, ease of use and the efficiency of drug delivery, with the aim of optimizing adherence and clinical outcomes with long-term tiotropium maintenance therapy. Video (MP4 314368 kb) Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0291-4) contains supplementary material, which is available to authorized users.

Assessment of the efficacy and safety of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler and a multi-dose inhaler in patients with asthma

BackgroundIn developing countries, there is a need for access to affordable inhaled respiratory medicines. This study tested the clinical non-inferiority of fluticasone propionate/salmeterol combination (FSC) 50/250 μg Rotacaps®/Rotahaler® compared with FSC 50/250 μg Diskus®. MethodsA multi-centre, randomised, double-blind, double-dummy study evaluated 12 weeks, twice daily treatment of FSC 50/250 μg administered using Rotacaps/Rotahaler or Diskus inhaler in a crossover design in patients with asthma (pre-bronchodilator forced expiratory volume in 1 s (FEV1) 40%–85% of predicted, FEV1 reversibility ≥12%, prior stable dose with inhaled corticosteroid (ICS) or ICS/long acting beta-agonist). The primary efficacy endpoint, change from baseline in trough morning FEV1 at Day 85, was analysed using a model for repeated measures analysis. The pre-defined criterion for non-inferiority was the lower limit of the CI (0.025, one-sided significance level) for the treatment difference (Rotacaps/Rotahaler-Diskus) in least squares (LS) mean change from baseline, being greater than −125 mL. Secondary endpoints included serial FEV1 measurements, morning peak expiratory flow (PEF), rescue medication use, day- and night-time asthma symptoms, Asthma Control Test (ACT) scores, and serial cortisol measured over 12 h (area under the curve (AUC0-12)). ResultsTreatment with FSC 50/250 μg via Rotacaps/Rotahaler or Diskus resulted in a similar LS mean increase from baseline in trough FEV1 at Day 85 (231 mL and 203 mL respectively). The difference in the model-adjusted LS mean change was 28 mL (95% CI -24 mL, 80 mL), fulfilling the criterion for non-inferiority. Data for all secondary endpoints were similar for the two treatments, supporting the primary endpoint findings. Both treatments were well tolerated and demonstrated similar safety profiles. ConclusionThis study demonstrated the clinical non-inferiority of FSC 50/250 μg when administered using Rotacaps/Rotahaler compared with administration using Diskus in patients with asthma, and suggests there is no difference in the risk:benefit profile between the two FSC inhalers.

INHALER COUNSELLING, THE REAL DEAL OR JUST FRESH AIR?

AimTo evaluate whether healthcare professionals within the local community are able to counsel paediatric patients on the essential steps required for drug delivery with multi-dose inhalers (MDI), MDIs with a...

Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler

PurposeThe aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances.MethodsThe two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a combination of formoterol fumarate and beclomethasone dipropionate. A breath simulator was used to mimic inhalatory patterns previously determined in vivo. A multivariate approach was adopted to estimate the significance of the effect of the investigated variables in the explored domain.ResultsBreath simulator was a useful tool to mimic in vitro the in vivo inspiratory profiles of asthmatic patients. The type of throat coupled with the impactor did not affect the aerodynamic distribution of the investigated formulation. However, the type of inhaler and inspiratory profiles affected the respirable dose of drugs.ConclusionsThe multivariate statistical approach demonstrated that the multidose inhaler, released efficiently a high fine particle mass independently from the inspiratory profiles adopted. Differently, the single dose capsule inhaler, showed a significant decrease of fine particle mass of both drugs when the device was activated using the minimum inspiratory volume (592 mL).

Dispensing inhalers to patients with chronic obstructive pulmonary disease on hospital discharge: Effects on prescription filling and readmission.

The effects of dispensing inhalers to patients with chronic obstructive pulmonary disease (COPD) on hospital discharge were evaluated. Data were collected in 2011-12 for patients with COPD who had hospital orders for the study inhalers (preintervention group) and after implementation of the multidose medication dispensing on discharge (MMDD) service (2013-14) (postintervention group). The primary objective of this study was to assess inhaler adherence and readmission rates before and after MMDD implementation. Adherence was defined as filling the discharge prescription for the multidose inhaler at a Harris Health pharmacy within three days of discharge or having at least seven days of medication left in an inhaler from a previous prescription that was filled or refilled before hospital admission. All patients in the postintervention group were considered adherent, since every patient was given the remainder of his or her multidose inhaler when discharged. Data from 620 patients (412 in the preintervention group, 208 in the postintervention group) were collected. During the preintervention time period, 88 of 412 patients were readmitted within 30 days compared with 18 of 208 patients during the postintervention period (p < 0.001). The intervention was associated with a significant reduction in 30-day readmissions (p = 0.0016) and 60-day readmissions (p = 0.0056). A targeted pharmacy program to provide COPD patients being discharged from the hospital with the multidose inhalers they had used during hospitalization was associated with improved medication adherence, as measured by prescription filling behavior, and reduced rates of 30- and 60-day hospital readmissions.

Preference, satisfaction and critical errors with Genuair and Breezhaler inhalers in patients with COPD: a randomised, cross-over, multicentre study.

Background:The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD).Aims:To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use.Methods:Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication. The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire). Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device.Results:Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years). Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs. 27.3%; P<0.001). Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs. 5.3, respectively; P<0.001). After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs. 3.3%, respectively).Conclusions:Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler. The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler.

Comparison of the Pharmacokinetics of Salmeterol and Fluticasone Propionate 50/100 µg Delivered in Combination as a Dry Powder Via a Capsule-Based Inhaler and a Multi-Dose Inhaler.

The Rotacaps(®)/Rotahaler(®) system is a single unit dose inhaler being developed to deliver inhaled salmeterol/fluticasone propionate combination (SFC) as an alternative treatment option to the metered dose inhaler and the multi-dose dry powder inhaler, Diskus(®). The aim of this study was to compare the systemic exposure of SFC 50/100 µg following delivery via the Rotacaps(®)/Rotahaler(®) and the Diskus(®). This was an open-label, randomized, cross-over, repeat-dose (3.5 days of twice-daily dosing) study comparing salmeterol and fluticasone propionate systemic exposure following inhaled SFC 50/100 µg delivered via the Rotacaps(®)/Rotahaler(®) and Diskus(®), in healthy subjects. Pharmacokinetic sampling was conducted over 12 h post-dose on the last day of each treatment. Pharmacokinetic samples were analysed using solid phase extraction followed by high performance liquid chromatography/tandem mass spectrometry. Co-primary endpoints were fluticasone propionate area under the concentration-time curve over the dosing interval (AUC0-τ ) and salmeterol maximum plasma concentration (C max) on the last day of treatment. Following SFC 50/100 µg Rotacaps(®)/Rotahaler(®), fluticasone propionate and salmeterol systemic exposures were comparable with Diskus(®) in terms of both AUC0-τ [geometric mean ratio (GMR) with 90 % confidence interval (CI) of Rotahaler(®)/Diskus(®) for fluticasone propionate: 0.98 (0.91, 1.06) and salmeterol: 1.04 (0.99, 1.10)] and C max [GMR (90 % CI) for fluticasone propionate: 1.04 (0.94, 1.15) and salmeterol: 0.97 (0.87, 1.08)], meeting the pre-defined criteria for comparability (upper limit of the 90 % CI for the GMRs (Rotahaler(®)/Diskus(®)) ≤1.25]. SFC delivered from both inhalers was well tolerated. SFC 50/100 µg Rotacaps(®)/Rotahaler(®) showed comparable fluticasone propionate and salmeterol systemic exposure to Diskus(®) for all pharmacokinetic endpoints with GMR and both upper and lower limits of 90 % CIs within conventional acceptance criteria for bioequivalence (0.8, 1.25), sufficient for considering progression of the Rotacaps(®)/Rotahaler(®) product for further clinical development.

Pharmacokinetics of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler and a multi-dose inhaler

AimTo compare salmeterol (SALM) and fluticasone propionate (FP) systemic exposure following inhaled salmeterol/fluticasone propionate combination (SFC) from a unit-dose capsule-based inhaler (Rotacaps®/Rotahaler®) and a multi-dose dry powder inhaler (Diskus®) in healthy volunteers. MethodsAn open-label, randomised, repeat-dose, cross-over, adaptive design study (n = 36 in each part) evaluated SFC 50/250 μg and SFC 50/100 μg in Rotacaps used with two types of Rotahaler inhalers (airflow resistance similar to (S) and lower than (L) Diskus) versus the Diskus. Primary endpoints were area under the concentration-time curve over the dosing interval [AUC0–τ] and maximum plasma concentration [Cmax]. ResultsSFC 50/250 μg Rotacaps/Rotahaler (S) showed 1.2–1.9-fold greater FP and SALM systemic exposure compared with Diskus. FP and SALM systemic exposure were comparable to DISKUS following SFC 50/250 μg Rotacaps/Rotahaler (L) (90% CI of ratio of Rotahaler to DISKUS within 0.8–1.25) for salmeterol (AUC0–τ and Cmax) and FP (AUC0–τ). Following SFC 50/100 μg Rotacaps/Rotahaler (L), FP and SALM systemic exposures were 1.2–1.4 fold higher in terms of FP (AUC0–τ and Cmax) and salmeterol (Cmax) compared with Diskus. SFC at both doses and via both inhalers was well tolerated. ConclusionsSFC 50/250 μg Rotacaps/Rotahaler (L) showed comparable systemic exposure to Diskus in terms of FP AUC and SALM AUC and Cmax. These results merit further progression of SFC 50/250 μg Rotacaps/Rotahaler (L) to phase 3 clinical evaluation in asthma and COPD patients. The lack of pharmacokinetic comparability between the inhalers for SFC 50/100 μg requires further evaluation.

Autism spectrum disorders and sleep disturbances in a pediatric patient

INTRODUCTION Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that often presents before the child enters the educational system and is characterized by developmental deficits with impairments in three main areas [1] personal, [2] social, and [3] academic or occupational functioning. The neurodevelopmental disorders represent a group of conditions with an onset early in the developmental period. Sleep disorders are commonly reported by parents of children with an ASD diagnosis with between 50% to 80% of parents reporting sleep problems with their children. Problems can be categorized into dyssomnias (problems falling and/or remaining asleep) and parasomnias (abnormal and/or unnatural movements, behaviors, emotions, perceptions, and dreams).

Pharmacokinetics and Pharmacodynamics of Fluticasone Propionate and Salmeterol Delivered as a Combination Dry Powder from a Capsule-Based Inhaler and a Multidose Inhaler in Asthma and COPD Patients

The object of this study was to assess whether a capsule-based and multidose dry powder inhaler containing salmeterol (as xinafoate salt) 50 μg plus fluticasone propionate (FP) 250 μg [combination (SFC 50/250)] could be equivalent in terms of in vivo drug delivery and systemic exposure. This was a randomized, double-blind, double-dummy, replicate treatment design comparative bioavailability study of SFC 50/250 delivered in a capsule-based inhaler (Rotahaler®) and a multidose dry powder inhaler (Diskus®). Subjects with asthma or chronic obstructive pulmonary (COPD) disease (n=60) were randomized to receive twice-daily SFC 50/250 via a Rotahaler and via Diskus each for two 10-day treatment periods (GlaxoSmithKline Protocol ASR114334). For FP and salmeterol, the in vitro aerodynamic particle size profiles were within±15% of Diskus for the fine particle mass (FPM) and emitted dose (ED) using the Andersen Cascade Impactor, and ED, mass median aerodynamic diameter, and geometric standard deviation using the New Generation Impactor (NGI). This was also the case for FP but not salmeterol for FPM and fine particle dose using the NGI. For the combined asthma and COPD subjects, the plasma AUC and Cmax for FP and salmeterol were higher for Rotahaler:Rotahaler/Diskus geometric mean ratios (90% confidence intervals) for FP AUC0-τ of 1.52 (1.37-1.67) and Cmax of 1.94 (1.75-2.10) and salmeterol AUC0-τ of 1.15 (1.09-1.21) and Cmax of 1.56 (1.42-1.67). Corresponding values for the primary pharmacodynamic endpoint, weighted mean (0-12 hr) serum cortisol, were 0.928 (0.886-0.971). Inhaled FP/salmeterol via both inhalers was well-tolerated. One serious adverse event, considered possibly related to study medication, resulted in subject withdrawal from the study. The in vitro tests and systemic pharmacodynamic endpoints revealed no major differences between the two inhalers, but lacked predictive power and sensitivity to guide in vivo drug delivery performance and systemic exposure. Based on pharmacokinetic endpoints, the inhalers were not considered bioequivalent in terms of systemic exposure. Further studies to refine the Rotahaler performance are ongoing.

Tiotropium 5 μg via Respimat and 18 μg via HandiHaler; efficacy and safety in Japanese COPD patients

To compare the efficacy and safety of tiotropium inhaled via Respimat Soft Mist Inhaler, a multidose propellant-free inhaler and HandiHaler, a single-dose dry powder inhaler, in a phase 2 study of Japanese COPD patients. Patients with FEV(1)<or=70% predicted, FEV(1)/FVC<or=70% and a smoking history of >10 pack-years received tiotropium once daily via Respimat (5microg) and HandiHaler (18microg) for 4 weeks each in a randomised, double-blind, double-dummy, two-way crossover study. Lung function, adverse events, pharmacokinetics and safety were assessed. Of 184 patients screened, 134 were evaluable. The trough FEV(1) response on Day 29 showed Respimat to be non-inferior to HandiHaler (mean treatment difference, 0.008L; 95% CI, -0.009 to +0.024L; p<0.001). Peak and average FEV(1) and FVC responses on Day 1 and Day 29 were very similar for the two treatments. Tiotropium plasma levels and excretion kinetics showed a similar profile of systemic exposure for the two formulations of tiotropium. Adverse events were reported by similar numbers of patients on each treatment, i.e. 27.9 and 30.6% in the Respimat and HandiHaler groups, respectively. In Japanese patients with COPD, tiotropium Respimat 5microg and tiotropium HandiHaler 18microg showed a similar profile of efficacy, safety and pharmacokinetics.

Development of a Dry Powder Multi-dose Inhaler using Computational Modeling

This paper is based on developing a new reusable multi-dose dry powder inhaler at low cost since available multi-dose inhalers are not affordable to poor. Low cost is achieved by making the inhaler reusable. Layer separation method of the blister strip was used in the new model. It is capable of holding a blister strip, having a maximum of 60 doses. Therefore the patient is able to use it at least a month before reloading. Initial geometry of the inhalation air chamber was modeled by considering the simplicity of construction. Commercially available 3D software tool named Pro/E was used to create the virtual geometrical model. Computational fluid dynamic software tool named Star/CD was used for the numerical analysis. Analyses were carried out for varying inlet diameters and outlet diameters for the inhalation air chamber at volume flow rate (60L/min). Velocity, pressure and particle track distributions were studied. Optimum values for each dimension were obtained. Other dimensions were kept constant while changing one parameter. Device resistance to the air flow through the inhaler was considered as a key factor for the inhaler model.

A Whooping Cough of a Time: An Employee with Pertussis in an Adult Hospital

ISSUE: Infection Control (IC) was notified when a Respiratory Care employee was diagnosed with pertussis. Patients (pts) & employees on the Bone Marrow Transplant (BMT) Unit & an intensive care unit (ICU) were exposed. PROJECT: The Respiratory Care manager was contacted & a list of pts for whom the employee provided care was generated. Occupational Health (OH) contacted the employee for more detailed information on the disease course. The period of communicability was determined after the information was obtained from the employee. The Hospital Epidemiologist was consulted to determine short-term versus prolonged exposure based on CDC recommendations. Prolonged exposure included if a pt received ventilator care, nebulizer treatments, multi-dose inhaler (MDI) treatment or MDI instruction. Exposed pt's Physicians were notified by fax & mail. Follow-up phone calls were made to the physician offices the day after faxes were sent. An E-Mail was sent to nurse managers explaining the exposure & providing a pertussis fact sheet. All Respiratory Care employees were queried for symptoms of pertussis. RESULTS: The employee had contact with 62 pts during the period of communicability before exposure was reported. Twenty-three pts received oxygen per nasal cannula (indicating short-term exposure), 28 pts had prolonged exposure, & 11 pts expired with diagnosis not related to the exposure. Two of the 4 exposed pts still in the hospital presented with new respiratory symptoms. These pts were isolated. Two of the 24 discharged pts developed new respiratory symptoms. Three pts were available for nasopharyngeal swabs & were negative for B. pertussis by PCR testing. No sick hospital employees were identified. Infection Control spent approximately 40 hours identifying, notifying & performing surveillance on this one pertussis exposure. LESSONS LEARNED: One ill employee can expose many pts & staff to communicable disease in a hospital setting. It is critical to have more than one method to notify a physicians' office when faced with an exposure to ensure proper notification. IC & OH must collaborate with many disciplines to promptly identify, define & communicate an exposure.

Bronchodilating effects of cumulative doses of formoterol from a novel multi-dose inhaler (Airmax®)

The bronchodilating properties of formoterol from a novel multi-dose inhaler, Airmax® 6μg and from a single-dose dry powder inhaler Foradil® Aeroliser® 12μg were investigated in 31 adult asthmatics with FEV 1≥60% predicted and a reversibility ≥12%. Patients received on a single day four doses of formoterol: cumulative dose 6, 12, 24 and 48μg from Airmax, or 12, 24, 48 and 96μg from Aeroliser®. The mean FEV 1 ( SD) from baseline to 1h after the final cumulative dose increased by 0.81l from 2.62 (0.58) to 3.43l (0.70) with Airmax® and by 0.85l from 2.65 (0.60) to 3.5l (0.68) with Aeroliser®. All 90% CIs for all four dose comparisons were within the equivalence range ±0.1l. There was a higher incidence of hypokalaemia and hyperglycaemia at highest doses during treatment with the Aeroliser® than with Airmax®. In conclusion, formoterol delivered from Airmax® provides a dose-dependent bronchodilating effect which is similar to that obtained by Aeroliser® at double the dose.