Respimat Soft Mist Inhaler Research Articles

Safety of once-daily tiotropium and olodaterol fixed-dose combination via the Respimat in chronic obstructive pulmonary disease in two 1-year studies

Introduction: The fixed-dose combination (FDC) of tiotropium (T), a once-daily long-acting muscarinic antagonist, and olodaterol (O), a once-daily long-acting ß2-agonist, is currently being evaluated in chronic obstructive pulmonary disease (COPD). Two 52-week, Phase III replicate pivotal studies were conducted to assess the efficacy and safety of FDCs of T and O (T+O) delivered via Respimat Soft Mist inhaler in patients (pts) with GOLD Stage 2 – 4 COPD. Pooled safety data from the two studies are presented here.

Once-daily tiotropium and olodaterol fixed-dose combination via the Respimat improves outcomes vs mono-components in COPD in two 1-year studies

Introduction: Tiotropium (T), a once-daily long-acting muscarinic antagonist, is a well-established first-line maintenance treatment in chronic obstructive pulmonary disease (COPD); olodaterol (O) is a once-daily long-acting ß2-agonist that has recently gained approval in several countries. Two Phase III replicate pivotal studies assessed the efficacy and safety of fixed-dose combinations of T and O (T+O) delivered via Respimat Soft Mist inhaler in patients with GOLD Stage 2 – 4 COPD.

Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials.

BackgroundTiotropium is generally well tolerated; however, there has been debate whether antimuscarinics, particularly tiotropium administered via Respimat® Soft Mist™ Inhaler, may induce cardiac arrhythmias in a vulnerable subpopulation with cardiovascular comorbidity. The aim of this study was to provide evidence of the cardiac safety of tiotropium maintenance therapy.MethodsCombined analysis of Holter electrocardiogram (ECG) data from clinical trials of tiotropium in chronic obstructive pulmonary disease (COPD). Trials in the Boehringer Ingelheim clinical trials database conducted between 2003 and 2012, involving tiotropium HandiHaler® 18 μg and/or tiotropium Respimat® (1.25-, 2.5-, 5.0- and 10-μg doses) were reviewed. All trials involving Holter-ECG monitoring during this period were included in the analysis. Men and women aged ≥ 40 years with a smoking history of ≥ 10 pack-years, and a clinical diagnosis of COPD were included. Holter ECGs were evaluated for heart rate (HR), supraventricular premature beats (SVPBs), ventricular premature beats (VPBs) and pauses. Quantitative and categorical end-points were derived for each of the Holter monitoring days.ResultsFour trials (n = 727) were included in the analysis. Respimat® (1.25–10 μg) or HandiHaler® (18 μg) was not associated with changes in HR, SVPBs, VPBs and pauses compared with placebo or the pretreatment baseline period. In terms of cardiac arrhythmia end-points, there was no evidence for an exposure–effect relationship.ConclusionsIn this analysis, tiotropium maintenance therapy administered using Respimat® (1.25–10 μg) or HandiHaler® (18 μg) once daily for periods of up to 48 weeks was well tolerated with no increased risk of cardiac arrhythmia in patients with COPD.

Tiotropium versus placebo for chronic obstructive pulmonary disease.

Tiotropium is an anticholinergic agent which has gained widespread acceptance as a once daily maintenance therapy for symptoms and exacerbations of stable chronic obstructive pulmonary disease (COPD). In the past few years there have been several systematic reviews of the efficacy of tiotropium, however, several new trials have compared tiotropium treatment with placebo, including those of a soft mist inhaler, making an update necessary. To evaluate data from randomised controlled trials (RCTs) comparing the efficacy of tiotropium and placebo in patients with COPD, upon clinically important endpoints. We searched the Cochrane Airways Group's Specialised Register of Trials (CAGR) and ClinicalTrials.gov up to February 2012. We included parallel group RCTs of three months or longer comparing treatment with tiotropium against placebo for patients with COPD. Two review authors independently assessed studies for inclusion and then extracted data on study quality and the outcome results. We contacted study authors and trial sponsors for additional information, and collected information on adverse effects from all trials. We analysed the data using Cochrane Review Manager 5, RevMan 5.2. This review included 22 studies of good methodological quality that had enrolled 23,309 participants with COPD. The studies used similar designs, however, the duration varied from three months to four years. In 19 of the studies, 18 mcg tiotropium once daily via the Handihaler dry powder inhaler was evaluated, and in three studies, 5 or 10 mcg tiotropium once daily via the Respimat soft mist inhaler was evaluated. Compared to placebo, tiotropium treatment significantly improved the mean quality of life (mean difference (MD) -2.89; 95% confidence interval (CI) -3.35 to -2.44), increased the number of participants with a clinically significant improvement (odds ratio (OR) 1.52; 95% CI 1.38 to 1.68), and reduced the number of participants with a clinically significant deterioration (OR 0.65; 95% CI 0.59 to 0.72) in quality of life (measured by the St George's Respiratory Questionnaire (SGRQ)). Tiotropium treatment significantly reduced the number of participants suffering from exacerbations (OR 0.78; 95% CI 0.70 to 0.87). This corresponds to a need to treat 16 patients (95% CI 10 to 36) with tiotropium for a year in order to avoid one additional patient suffering exacerbations, based on the average placebo event rate of 44% from one-year studies. Tiotropium treatment led to fewer hospitalisations due to exacerbations (OR 0.85; 95% CI 0.72 to 1.00), but there was no statistically significant difference in all-cause hospitalisations (OR 1.00; 95% CI 0.88 to 1.13) or non-fatal serious adverse events (OR 1.03; 95% CI 0.97 to 1.10). Additionally, there was no statistically significant difference in all-cause mortality between the tiotropium and placebo groups (Peto OR 0.98; 95% CI 0.86 to 1.11). However, subgroup analysis found a significant difference between the studies using a dry powder inhaler and those with a soft mist inhaler (test for subgroup differences: P = 0.01). With the dry powder inhaler there were fewer deaths in the tiotropium group (Peto OR 0.92; 95% CI 0.80 to 1.05) than in the placebo group (yearly rate 2.8%), but with the soft mist inhaler there were significantly more deaths in the tiotropium group (Peto OR 1.47; 95% CI 1.04 to 2.08) than in the placebo group (yearly rate 1.8%). It is noted that the rates of patients discontinuing study treatment were uneven, with significantly fewer participants withdrawing from tiotropium treatment than from placebo treatment (OR 0.66; 95% CI 0.59 to 0.73). Participants on tiotropium had improved lung function at the end of the study compared with those on placebo (trough forced expiratory volume in one second (FEV1) MD 118.92 mL; 95% CI 113.07 to 124.77). This review shows that tiotropium treatment was associated with a significant improvement in patients' quality of life and it reduced the risk of exacerbations, with a number needed to treat to benefit (NNTB) of 16 to prevent one exacerbation. Tiotropium also reduced exacerbations leading to hospitalisation but no significant difference was found for hospitalisation of any cause or mortality. Thus, tiotropium appears to be a reasonable choice for the management of patients with stable COPD, as proposed in guidelines. The trials included in this review showed a difference in the risk of mortality when compared with placebo depending on the type of tiotropium delivery device used. However, these results have not been confirmed in a recent trial when 2.5 mcg or 5 mcg of tiotropium via Respimat was used in a direct comparison to the 18 mcg Handihaler.

Feasibility of aerosol drug delivery to sleeping infants: a prospective observational study

ObjectivesDelivery of inhaled medications to infants is usually very demanding and is often associated with crying and mask rejection. It has been suggested that aerosol administration during sleep may be...

The Tiotropium Safety and Performance in Respimat® Trial (TIOSPIR®), a large scale, randomized, controlled, parallel-group trial-design and rationale

BackgroundTiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat® Soft Mist™ inhaler was at least as efficacious as tiotropium HandiHaler®, however, concerns have been raised about tiotropium’s safety when given via Respimat®.MethodsThe TIOSPIR® trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat® 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler® 18 μ once daily (marketed). The hypotheses to be tested are 1). that tiotropium Respimat® 5 μg once daily and Respimat® 2.5 μg once daily are non-inferior to HandiHaler® in terms of all-cause mortality, and 2). that tiotropium Respimat® 5 μg once daily is superior to HandiHaler® in terms of time to first exacerbation. A spirometry substudy evaluates the bronchodilator efficacy. The trial is a randomized, double-blind, double dummy, event-driven, parallel group study. Participants can use any background treatment for COPD except inhaled anticholinergic agents. The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included. Clinical sites are international and include both primary care as well as specialists.ResultsTo date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2–3 years.ConclusionTIOSPIR® will provide precise estimates of the relative safety and efficacy of the Respimat® and HandiHaler® formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort.

Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials

Objective To systematically review the risk of mortality associated with long term use of tiotropium delivered using a mist inhaler for symptomatic improvement in chronic obstructive pulmonary disease.Data sources Medline,...

Pharmacological Characterization of Olodaterol, a Novel Inhaled β2-Adrenoceptor Agonist Exerting a 24-Hour-Long Duration of Action in Preclinical Models

The preclinical pharmacological profile of 6-hydroxy-8-[(1R)-1-hydroxy-2-[[2-(4-methoxyphenyl)-1,1-dimethylethyl]amino]ethyl]-2H-1,4-benzoxazin-3(4H)-one monohydrochloride (olodaterol, previously known as BI 1744 CL), a novel, enantiomeric pure, inhaled human beta(2)-adrenoceptor (hbeta(2)-AR) agonist, was compared with marketed drugs, such as salmeterol and formoterol. In vitro, olodaterol showed a potent, nearly full agonistic response at the hbeta(2)-AR (EC(50) = 0.1 nM; intrinsic activity = 88% compared with isoprenaline) and a significant selectivity profile (241- and 2299-fold [corrected] against the hbeta(1)- and hbeta(3)-ARs, respectively). Likewise, olodaterol was able to potently reverse contraction induced by different stimuli in isolated human bronchi. In vivo, antagonistic effects of single doses of olodaterol and formoterol were measured against acetylcholine challenges in anesthetized guinea pigs and dogs for up to 24 h by using the Respimat Soft Mist inhaler. Heart rate and metabolic parameters (serum potassium, lactate, and glucose) were monitored to evaluate systemic pharmacodynamic effects in the dog model. In both models, olodaterol provided bronchoprotection over 24 h. Formoterol applied at an equally effective dose did not retain efficacy over 24 h. In both models olodaterol showed a rapid onset of action comparable with formoterol. Taken together, the preclinical behavior of olodaterol suggests that this novel beta(2)-AR agonist has the profile for once-daily dosing in humans concomitant with a fast onset of action and a favorable systemic pharmacodynamic profile.

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.

Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat Soft Mist inhaler.

Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations. A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients' adherence to treatment, and thus potentially affect the long-term outcome. The Respimat((R)) Soft Mist Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs). We review clinical studies of inhaler satisfaction and preference comparing Respimat((R)) SMI against other inhalers in COPD patients. Using objective and validated patient satisfaction instruments, Respimat((R)) SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics. In comparative studies with pMDIs, the patient total satisfaction score with Respimat((R)) SMI was statistically and clinically significantly higher than with the pMDI. In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler((R)) DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat((R)) SMI. Whether the observed higher levels of patient satisfaction reported with Respimat((R)) SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven.

Evaluation of the Respimat Soft Mist Inhaler using a Concurrent CFD and In Vitro Approach

The Respimat Soft Mist Inhaler is reported to generate an aerosol with low spray momentum and a small droplet size. However, the transport characteristics of the Respimat aerosol are not well understood. The objective of this study was to characterize the transport and deposition of an aerosol emitted from the Respimat inhaler using a combination of computational fluid dynamics (CFD) modeling and in vitro experiments. Deposition of the Respimat aerosol was assessed in the inhaler mouthpiece (MP), a standard induction port (IP), and a more realistic mouth-throat (MT) geometry at an inhalation flow rate of 30 L/min. Aerosols were generated using an albuterol sulfate (0.6%) solution, and the drug deposition was quantified using both in vitro experiments and a CFD model of the Respimat inhaler. Laser diffraction experiments were used to determine the initial polydisperse aerosol size distribution. It was found that the aerosol generated from the highly complex process of jet collision and breakup could be approximated in the model using effective spray conditions. Computational predictions of deposition fractions agreed well with in vitro results for both the IP (within 20% error) and MT (within 10% error) geometries. The experimental results indicated that the deposition fraction of drug in the MP ranged from 27 to 29% and accounted for a majority of total drug loss. Based on the CFD solution, high MP deposition was due to a recirculating flow pattern that surrounded the aerosol spray and entrained a significant number of small droplets. In contrast, deposition of the Respimat aerosol in both the IP (4.2%) and MT (7.4%) geometries was relatively low. Results of this study indicate that modifications to the current Respimat MP and control of specific patient variables may significantly reduce deposition in the device and may decrease high oropharyngeal drug loss observed in vivo.

Asthma patients prefer Respimat&amp;reg; Soft Mist&amp;trade; Inhaler to Turbuhaler&amp;reg;

Device satisfaction and preference are important patient-reported outcomes to consider when choosing inhaled therapy. A subset of adults (n = 153) with moderate or severe asthma participating in a randomized parallel-group, double-dummy trial that compared the efficacy and safety of 12 weeks' treatment with budesonide delivered via Respimat Soft Mist Inhaler (SMI) (200 or 400 microg bd) or Turbuhaler dry powder inhaler (400 microg bd), completed a questionnaire on patient device preference and satisfaction (PASAPQ) as part of a psychometric validation. As the study used a double-dummy design to maintain blinding, patients used and assessed both devices, rating their satisfaction with, preference for, and willingness to continue using each device. The mean age of patients was 41 years, 69% were female and the mean duration of disease was 16 years. Total PASAPQ satisfaction scores were 85.5 and 76.9 for Respimat SMI and Turbuhaler respectively (p < 0.0001); 112 patients (74%) preferred Respimat SMI and 26 (17%) preferred Turbuhaler. Fourteen subjects (9%) indicated no preference for either inhaler. Willingness to continue using Respimat SMI was higher than that for Turbuhaler (mean scores: 80/100 and 62/100, respectively). Respimat SMI was preferred to Turbuhaler by adult asthma patients who used both devices in a clinical trial setting.

The efficacy of tiotropium administered via Respimat ® Soft Mist™ Inhaler or HandiHaler ® in COPD patients

Tiotropium, a once daily inhaled anticholinergic delivered via HandiHaler, provides bronchodilation for >24h and improves patient-centred outcomes. The Respimat Soft Mist Inhaler (SMI), a novel, propellant-free inhaler, has been developed and proposed as an alternative delivery device for use with tiotropium. In a pre-specified, pooled analysis of two 30-week, double-blind, double-dummy, crossover studies, 207 patients with Chronic Obstructive Pulmonary Disease (COPD) were randomised to receive once daily tiotropium 5 microg or 10 microg (aqueous solution delivered via Respimat SMI), tiotropium 18 microg (inhalation powder via HandiHaler) or placebo. The primary endpoint was trough forced expiratory volume in 1s (FEV(1)) response. Forced vital capacity (FVC), peak expiratory flow rate (PEFR), rescue medication use, safety and pharmacokinetics (in a subgroup of patients) were also assessed. Both tiotropium doses delivered by Respimat SMI were significantly superior to placebo and non-inferior to tiotropium 18 microg HandiHaler on the primary endpoint (all p<0.0001). All active treatments were significantly superior to placebo (all p<0.0001) and both doses of tiotropium Respimat SMI were non-inferior to tiotropium 18 microg HandiHaler on the secondary spirometry variables and rescue medication use. The systemic exposure was similar between tiotropium 5 microg Respimat SMI and tiotropium 18 microg HandiHaler but was higher for tiotropium 10 microg Respimat SMI. All active treatments were well tolerated. Tiotropium 5 microg Respimat SMI is comparable with tiotropium 18 microg HandiHaler in terms of efficacy, pharmacokinetics and safety. Respimat SMI is an effective alternative, multi-dose delivery device for tiotropium.

A randomized study of tiotropium Respimat ® Soft Mist TM Inhaler vs. ipratropium pMDI in COPD

The aim of these studies was to compare the efficacy and the safety of tiotropium, delivered via Respimat Soft Mist Inhaler (SMI), a novel multi-dose, propellant-free inhaler, with ipratropium pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients. Two identical, 12-week, multi-national, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled studies were performed. COPD patients were randomized to treatment with either inhaled tiotropium (5 or 10 microg) via Respimat SMI administered once daily, ipratropium (36 microg) pMDI QID or placebo. The primary endpoint was the mean trough forced expiratory volume in 1s (FEV(1)) response after 12 weeks of treatment. Secondary endpoints included other spirometry measures and rescue medication use. A total of 719 patients were randomized; the majority were male (69%) with a mean pre-bronchodilator FEV(1) (% predicted) of 40.7%. The mean treatment differences between tiotropium 5 and 10 microg and placebo for the primary endpoint (mean trough FEV(1) response at week 12) were 0.118 and 0.149L, respectively (both P<0.0001). Treatment differences between tiotropium 5 and 10 microg and ipratropium were 0.064L (P=0.006) and 0.095L (P<0.0001). The increases in peak FEV(1), FEV(1) AUC((0-6h)) and FVC for both tiotropium doses were statistically superior to placebo (P<0.01) and higher than ipratropium. All active treatments significantly reduced the rescue medication use compared with placebo, but only tiotropium 10 microg was statistically superior to ipratropium (P=0.04). The incidence of adverse events was comparable across groups. In conclusion, tiotropium 5 and 10 microg daily, delivered via Respimat SMI, significantly improved lung function compared with ipratropium pMDI and placebo.

An In Vitro Study to Assess Facial and Ocular Deposition from Respimat® Soft Mist™ Inhaler

Respimat Soft Mist() inhaler (SMI) is a novel multidose propellant-free inhaler device for delivery of inhaled drugs to patients with asthma and chronic obstructive pulmonary disease. In vitro studies have been undertaken to assess facial and ocular deposition from Respimat SMI in several potential misuse situations. A placebo aqueous drug formulation in Respimat SMI was radiolabeled by addition of (99m)Tc. Deposition was quantified by gamma camera on a removable facemask that was fitted over the head of a resuscitation mannequin. The eyes were simulated by adhesive plaster patches. When Respimat SMI was fired in three preselected positions away from the head, total face deposition (% ex-valve dose) averaged 7.3%, 7.8%, and 9.1%, and eye deposition averaged 0.6%, 0.1%, and 0.3%. When the inhaler was fired into a simulated exhalation, upper face deposition (mean 3.8%) and eye deposition (mean 0.1%) were also small. It is concluded that low deposition on the face, and especially in the eyes, is to be expected when Respimat SMI is fired accidentally outside the body, or is fired at the same time as the patient exhales. When Respimat SMI is misused in the ways described in this study, there is likely to be little potential for unwanted side effects resulting from ocular deposition.

Use of Respimat� Soft Mist? Inhaler in COPD patients

Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy. Respimat Soft Mist Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices. The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs. This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy. In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI. In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases. Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD.

Comparison of the Aerosol Velocity and Spray Duration of Respimat® Soft Mist™ Inhaler and Pressurized Metered Dose Inhalers

Apart from particle size distribution, spray velocity is one of the most important aerosol characteristics that influence lung deposition of inhaled drugs. The time period over which the aerosol is released (spray duration) is also important for coordination of inhalation. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that delivers drug to the lung much more efficiently than pressurised metered dose inhalers (pMDIs). The objective of this study was to compare the velocity and spray duration of aerosol clouds produced by Respimat SMI with those from a variety of chlorofluorocarbon (CFC) and hydrofluoroalkane (HFA) pMDIs. All inhalers contained solutions or suspensions of bronchodilators. A videorecording method was used to determine the aerosol velocity. For spray duration, the time for generation of the Soft Mist by Respimat SMI was initially determined using three different methods (videorecording [techniques A and B], laser light diffraction and rotating disc). Videorecording was then used to compare the spray duration of Respimat SMI with those from the other inhalers. The Soft Mist produced by Respimat SMI moved much more slowly and had a more prolonged duration than aerosol clouds from pMDIs (mean velocity at a 10-cm distance from the nozzle: Respimat SMI, 0.8 m/sec; pMDIs, 2.0-8.4 m/sec; mean duration: Respimat SMI, 1.5 sec; pMDIs, 0.15-0.36 sec). These characteristics should result in improved lung and reduced oropharyngeal deposition, and are likely to simplify coordination of inhaler actuation and inhalation compared with pMDIs.

Aerosol Plumes: Slow and Steady Wins the Race

Journal of Aerosol MedicineVol. 18, No. 3 EditorialAerosol Plumes: Slow and Steady Wins the RaceRajiv DhandRajiv DhandSearch for more papers by this authorPublished Online:23 Sep 2005https://doi.org/10.1089/jam.2005.18.261AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byAnalysis of improved oral drug delivery with different helical stream inhalation modesComputers in Biology and Medicine, Vol. 141Inhaler DevicesIn Vitro Measurements of Spiriva Respimat Dose Delivery in Mechanically Ventilated Tracheostomy Patients Rym Mehri, Abubakar Alatrash, Nicholas Ogrodnik, Edgar A. Matida, and Frank Fiorenza3 August 2021 | Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 34, No. 4Helical fluid-particle flow dynamics for controlling micron-particle deposition in a representative human upper lung-airway modelJournal of Aerosol Science, Vol. 151Clinical implications of the tiotropium/olodaterol inhaler for patients with chronic obstructive pulmonary disease4 July 2018 | Postgraduate Medicine, Vol. 130, No. 6Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography17 February 2016 | Pharmaceutical Research, Vol. 33, No. 5Temporally and Spatially Resolved x-ray Fluorescence Measurements of in-situ Drug Concentration in Metered-Dose Inhaler Sprays12 November 2015 | Pharmaceutical Research, Vol. 33, No. 4Efficiency of Ipratropium Bromide and Albuterol Deposition in the Lung Delivered via a Soft Mist Inhaler or Chlorofluorocarbon Metered‐Dose Inhaler6 March 2016 | Clinical and Translational Science, Vol. 9, No. 2The importance of inhaler devices in the treatment of COPD15 September 2015 | COPD Research and Practice, Vol. 1, No. 1Technological and practical challenges of dry powder inhalers and formulationsAdvanced Drug Delivery Reviews, Vol. 75IMAGING PULMONARY DRUG DELIVERY20 September 2013Respimat®, premier inhalateur « Soft Mist » : intérêt dans la prise en charge de la BPCORevue des Maladies Respiratoires, Vol. 27, No. 10Evaluation of droplet velocity and size from nasal spray devices using phase Doppler anemometry (PDA)International Journal of Pharmaceutics, Vol. 388, No. 1-2Pulmonary Drug Delivery: Medicines for Inhalation19 November 2009Evaluation of the Respimat Soft Mist Inhaler using a Concurrent CFD and In Vitro Approach P. Worth Longest and Michael Hindle7 May 2009 | Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 22, No. 2Current Therapies and Technological Advances in Aqueous Aerosol Drug Delivery20 October 2008 | Drug Development and Industrial Pharmacy, Vol. 34, No. 9Computational Analyses of a Pressurized Metered Dose Inhaler and a New Drug–Aerosol Targeting Methodology Clement Kleinstreuer, Huawei Shi, and Zhe Zhang26 September 2007 | Journal of Aerosol Medicine, Vol. 20, No. 3 Volume 18Issue 3Sep 2005 InformationCopyright 2005, Mary Ann Liebert, Inc.To cite this article:Rajiv Dhand.Aerosol Plumes: Slow and Steady Wins the Race.Journal of Aerosol Medicine.Sep 2005.261-263.http://doi.org/10.1089/jam.2005.18.261Published in Volume: 18 Issue 3: September 23, 2005PDF download

Low incidence of paradoxical bronchoconstriction in asthma and COPD patients during chronic use of Respimat ® soft mist™ inhaler

Respimat Soft Mist Inhaler (SMI) is a new-generation inhaler that offers improved lung deposition compared with chlorofluorocarbon metered dose inhalers (CFC-MDIs). Bronchodilators administered via Respimat SMI are preserved and stabilised with low concentrations of benzalkonium chloride and ethylene diamine tetra-acetic acid, both of which have been reported to cause dose-related paradoxical bronchoconstriction. The aim of this analysis was to compare the incidence of paradoxical bronchoconstriction after chronic use of bronchodilators via Respimat SMI and CFC-MDI. Data from three clinical trials, in which patients with asthma or chronic obstructive pulmonary disease (COPD) received ipratropium bromide alone or in combination with fenoterol hydrobromide, or placebo via Respimat SMI or CFC-MDI for 12 weeks, were included in the analysis. In order to evaluate the risk of paradoxical bronchoconstriction, we identified four respiratory events that might have occurred within 30 min of inhalation on four test days; these were: 'bronchospasm', 'other respiratory adverse events', 'rescue medication use' and 'asymptomatic drop in FEV(1) 15% from baseline'. In total, 631 asthma and 1538 COPD patients participated in the three studies. No occurrences of bronchospasm were reported with Respimat SMI on any test day. Overall, the incidence of respiratory events possibly indicative of paradoxical bronchoconstriction was low and similar for both devices. There was no increase in the incidence of events during 12 weeks' treatment. Delivery of bronchodilators by Respimat SMI is safe with regard to paradoxical bronchoconstriction during chronic use in patients with asthma or COPD.

Respimat?? Soft Mist??? Inhaler versus Hydrofluoroalkane Metered Dose Inhaler

In addition to offering favorable pharmaceutical performance, an ideal inhaler should be well accepted by patients, as this may facilitate compliance. We report a study that specifically assessed inhaler preference in patients with obstructive lung disease after treatment with ipratropium bromide/fenoterol hydrobromide (Berodual delivered via either Respimat Soft Mist Inhaler (SMI) or hydrofluoroalkane metered dose inhaler (HFA-MDI). Patients with COPD, asthma or mixed disease were randomized to receive ipratropium bromide/fenoterol hydrobromide 20/50 microg via Respimat SMI or 40/100 microg via HFA-MDI for 7 weeks each, in a crossover design. Patients were trained in inhaler use and given < or =5 attempts to demonstrate satisfactory technique. At the end of each treatment period, patients completed a 15-item satisfaction questionnaire, and inhaler technique was re-tested. On study completion, patients were asked which inhaler they preferred and they rated their willingness to continue using each inhaler. Clinical efficacy outcomes were measured by diary card to check whether switching inhaler affected efficacy. In total, 245 patients were randomized and 224 used both inhalers within their respective treatment periods. Of 201 patients expressing a preference, 162 (81%) preferred Respimat SMI and 39 (19%) preferred HFA-MDI (p < 0.001). Patients would rather continue using Respimat SMI than HFA-MDI (p < 0.001). Mean scores for 13 of the 15 satisfaction questions were significantly higher for Respimat SMI than HFA-MDI (p < 0.05); in addition, the total score was also significantly higher for Respimat SMI (p < 0.001). Most patients (217/224; 97%) were judged to have good technique with Respimat SMI after 7 weeks' use. Differences in efficacy measures between the devices were not significant. These data indicated that a large majority of patients preferred Respimat SMI to HFA-MDI.