Effectiveness of inhalation technique assessment service for patients with Respimat® inhaler.

OBJECTIVES: The objective of this study was to examine how Inhalation Technique Assessment Service (ITAS) by community pharmacies affect patients' inhalation techniques when using the Respimat® soft mist inhaler. The inhaler was simultaneously updated into a reusable inhaler. The study focused on the Respimat® inhaler because its use is known to be challenging for patients. METHODS: The study was performed as a pre-post design in 33 community pharmacies (CPs) in Finland. Patients' inhalation technique was assessed before ITAS (baseline) and immediately after ITAS (follow-up 1). Follow-up 2 was performed when the patient came to the pharmacy for a refill (1-3 months after the baseline and the follow-up 1). A Respimat specific twenty item checklist was used to assess inhalation technique. The checklist included 1) preparation steps before the first use of the Respimat® inhaler (8 items) and 2) daily use steps of the Respimat® inhaler (12 items). After ITAS, the patients received a brief questionnaire to assess their asthma/COPD history. RESULTS: A total of 228 patients were enrolled at the first visit (mean age 67.8 years, 61.0% female, 85.5% had previous Respimat® use experience) and 42 of them attended the follow-up 2, 1-3 months later (mean age 70.1 years, 69.0% female, 92.9% had previous Respimat® use experience. The median number of the steps performed correctly increased from 17/20 at the baseline to all the 20 steps at the follow-up 1 (p < 0.001). At the baseline, 27.6% of the patients (n = 228) performed all preparation steps correctly, while 87.3% at the follow-up 1 and 71.4% at the follow-up 2. The percentage of the patients with acceptable inhalation technique (all critical daily use steps correct) increased from 69.7% at the baseline to 93.0% at the follow-up 1 (p < 0.001). The corresponding figure at the follow-up 2 was 69.0%. At the baseline, 30.3% of patients had optimal inhalation technique (all daily use steps correct). At the follow-up 1 corresponding figure was 85.1%, and 54.8% at the follow-up 2. CONCLUSIONS: A pharmacist-led intervention significantly improved asthma and COPD patients' inhalation technique with the Respimat® inhaler. Significant improvements were found in the daily use steps and the preparation steps before the first use.

Patient perceptions of the re-usable Respimatt® Soft Mist™ inhaler in current users and those switching to the device: A real-world, non-interventional COPD study.

PLAIN LANGUAGE SUMMARY: Inhalers are often used to treat patients with chronic obstructive pulmonary disease (COPD). However, there are many available, which can lead to confusion and poor inhaler technique. It is important for a patient to be happy with their inhaler. This study looked at how patients liked the re-usable Respimat® Soft Mist™ inhaler vs. their previous inhaler. It also asked whether they would be willing to continue using the device at the end of the study period.After 4-6 weeks of using the re-usable device, patients reported that they were happy with the inhaler and most would be willing to carry on using it.Overall, these results show that doctors can prescribe Respimat re-usable to patients, even if the patient has not used the inhaler before.

Tiotropium in chronic obstructive pulmonary disease - a review of clinical development.

BACKGROUND: Bronchodilators are the mainstay of pharmacological treatment in chronic obstructive pulmonary disease (COPD), and long-acting muscarinic antagonist (LAMA) monotherapy is recommended as initial treatment for Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, and D. MAIN BODY: Tiotropium bromide was the first LAMA available for COPD in clinical practice and, because of its long duration of action, is administered once daily. Tiotropium was initially available as an inhalation powder delivered via a dry-powder inhaler (DPI). Later, tiotropium also became available as an inhalation spray delivered via a soft mist inhaler (SMI). The SMI was designed to overcome or minimize some of the issues associated with other inhaler types (eg, the need for strong inspiratory airflow with DPIs). Results of short- and long-term randomized, controlled clinical trials of tiotropium in patients with COPD indicated tiotropium was safe and significantly improved lung function, health-related quality of life, and exercise endurance, and reduced dyspnea, lung hyperinflation, exacerbations, and use of rescue medication compared with placebo or active comparators. These positive efficacy findings triggered the evaluation of tiotropium in fixed-dose combination with olodaterol (a long-acting ß2-agonist). In this review, we provide an overview of studies of tiotropium for the treatment of COPD, with a focus on pivotal studies. CONCLUSION: Tiotropium is safe and efficacious as a long-term, once-daily LAMA for the maintenance treatment of COPD and for reducing COPD exacerbations. The SMI generates a low-velocity, long-duration aerosol spray with a high fine-particle fraction, which results in marked lung drug deposition. In addition, high inspiratory flow rates are not required.

Device use errors with soft mist inhalers: A global systematic literature review and meta-analysis.

Inhaled bronchodilators are the cornerstone of treatment for chronic obstructive pulmonary disease (COPD). Soft mist inhalers (SMIs) are devices that deliver bronchodilators. Although correct device use is paramount to successful medication delivery, patient errors are common. This global systematic literature review and meta-analysis examined device use errors with SMIs among patients with obstructive lung diseases. PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify studies published between 2010 and 2019 that met the following inclusion criteria: (a) English language; (b) a diagnosis of COPD, bronchitis, or emphysema; and (c) reported device use errors among adults receiving long-acting bronchodilator treatment with Respimat® SMI (i.e. Spiriva®, Stiolto®, Spiolto®, and Striverdi®). Descriptive statistics examined sociodemographics, clinical characteristics, and device use errors. Meta-analysis techniques were employed with random-effects models to generate pooled mean effect sizes and 95% confidence intervals (CIs) for overall and step-by-step errors. The I2 statistic measured heterogeneity. Twelve studies (n = 1288 patients) were included in this meta-analysis. Eighty-eight percent of patients had COPD, and most had moderate/very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease spirometric stages II to IV). Aggregate results revealed that 58.9% (95% CI: 42.4-75.5; I2 = 92.8%) of patients made ≥1 device use errors. Among 11 studies with step-by-step data, the most common errors were failure to (1) exhale completely and away from the device (47.8% (95% CI: 33.6-62.0)); (2) hold breath for up to 10 seconds (30.6% (95% CI: 17.5-43.7)); (3) take a slow, deep breath while pressing the dose release button (27.9% (95% CI: 14.5-41.2)); (4) hold the inhaler upright (22.6% (95% CI: 6.2-39.0)); and (5) turn the base toward the arrows until it clicked (17.6% (95% CI: 3.0-32.2)). Device use errors occurred in about 6 of 10 patients who used SMIs. An individualized approach to inhalation device selection and ongoing training and monitoring of device use are important in optimizing bronchodilator treatment.

Comparative Effectiveness of Two Tiotropium Formulations: A Retrospective Cohort Study.

The effectiveness of the tiotropium Respimat® formulation in routine clinical practice is still an open issue due to concern about the generalizability of the Tiotropium Safety and Performance in Respimat® (TIOSPIR) trial findings. Our aim was to compare the incidence of acute respiratory events between new users of tiotropium Respimat® and HandiHaler®. The study population comprised patients aged ≥45 years resident in two Italian regions who received a first tiotropium prescription (HandiHaler® or Respimat®) between 1 July 2011 and 30 November 2013. The cohort was identified within the database of drug prescriptions reimbursed by the Italian National Health Service. Clinical outcomes were obtained from hospital records. The primary outcome was the first hospitalization for respiratory events, including chronic obstructive pulmonary disease (COPD) exacerbation, respiratory failure, hypoxemia/hyperventilation and pneumonia, during the exposure period. The hazard ratios were estimated for the propensity score matched groups with Cox regression. After matching, 31,334 patients with incident tiotropium prescriptions were included. Similar incidence rates of the primary outcome between the Respimat® and HandiHaler® users were identified (adjusted hazard ratio 0.95, 95% CI 0.84-1.07). No differences emerged in the subgroup analyses conducted according to the baseline characteristics of the tiotropium users. This study confirms the findings observed in the TIOSPIR trial in a more heterogeneous population that included patient subgroups with severe respiratory disease and unstable COPD.

A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.

BACKGROUND: Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma. OBJECTIVE: We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma. METHODS: In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 µg (2 puffs of 2.5 µg) or 2.5 µg (2 puffs of 1.25 µg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. RESULTS: Compared with placebo, tiotropium 5 µg, but not 2.5 µg, add-on therapy improved the primary end point, peak FEV1 within 3 hours after dosing (5 µg, 139 mL [95% CI, 75-203; P < .001]; 2.5 µg, 35 mL [95% CI, -28 to 99; P = .27]), and the key secondary end point, trough FEV1 (5 µg, 87 mL [95% CI, 19-154; P = .01]; 2.5 µg, 18 mL [95% CI, -48 to 85; P = .59]). The safety and tolerability of tiotropium were comparable with those of placebo. CONCLUSIONS: Once-daily tiotropium Respimat 5 µg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.

Pharmacokinetics of tiotropium administered by Respimat® in asthma patients: Analysis of pooled data from Phase II and III clinical trials.

Tiotropium is a long-acting inhaled antimuscarinic bronchodilator that has recently received marketing authorization for the indication of asthma with dose delivery via the Respimat® inhaler, in addition to its widely established role in the management of chronic obstructive pulmonary disease (COPD). This report presents a combined analysis of tiotropium plasma and urine pharmacokinetics at steady state from 8 Phase II/III clinical trials in asthma and delineates the effects of patient characteristics on systemic exposure based on the parameters fe0-24,ss (fraction of dose excreted unchanged in urine over 24 h post-dose at steady-state) and dose-normalized AUCtau,ss and Cmax,ss. Pharmacokinetics were also compared between asthma and COPD, incorporating data from 3 COPD Phase II/III clinical trials. Tiotropium pharmacokinetics in asthma were dose-proportional up to 5 µg dosed once daily. The following factors showed no statistically significant effects on tiotropium systemic exposure in asthma based on analysis of geometric mean ratios and 90% confidence intervals: age, asthma severity, lung function, reversibility testing, allergy status, smoking history, geographical region, and posology (5 µg once daily or 2.5 µg twice daily via Respimat®). Asian patients showed a moderately but significantly higher systemic exposure compared to White or Black patients. However, no differences in safety by race were observed. Total systemic exposure (AUCtau,ss) was similar between asthma and COPD, but Cmax,ss was 52% lower in asthma patients compared to COPD. It is concluded that in asthma, patient characteristics have no relevant effect on tiotropium systemic exposure. Since systemic exposure to inhaled drugs is an indicator of safety, the lower Cmax,ss compared to COPD is not considered a concern for tiotropium therapy of asthma.

Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial.

BACKGROUND: Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled corticosteroid (ICS) maintenance therapy. OBJECTIVE: We sought to assess the efficacy and safety of once-daily tiotropium Respimat added to ICSs with or without a leukotriene receptor antagonist in a phase III trial in adolescent patients with moderate symptomatic asthma. METHODS: In this 48-week, double-blind, placebo-controlled, parallel-group study, 398 patients aged 12 to 17 years were randomized to receive 5 µg (2 puffs of 2.5 µg) or 2.5 µg (2 puffs of 1.25 µg) of once-daily tiotropium or placebo (2 puffs) administered through the Respimat device every evening, each as add-on treatment to ICS background therapy, with or without a leukotriene receptor antagonist; long-acting ß2-agonist therapy was not permitted during the study. RESULTS: Improvement in peak FEV1 within 3 hours after dosing at 24 weeks (primary end point) was statistically significant with both tiotropium doses compared with placebo: 5 µg of tiotropium, 174 mL (95% CI, 76-272 mL); 2.5 µg of tiotropium, 134 mL (95% CI, 34-234 mL). Significant improvements in trough FEV1 at week 24 (a secondary end point) were observed with the 5-µg dose only. Trends for improvement in asthma control and health-related quality of life over the 48-week treatment period were observed. CONCLUSIONS: Once-daily tiotropium significantly improved lung function and was safe and well tolerated when added to at least ICS maintenance therapy in adolescent patients with moderate symptomatic asthma. Larger responses were observed with the 5-µg tiotropium dose.

[Efficacy and safety of tiotropium Respimat in the treatment of chronic obstructive pulmonary disease: systematic review].

Objective: To evaluate the efficacy and safety of tiotropium Respimat in the treatment of chronic obstructive pulmonary disease (COPD) according to the Cochrane systematic evaluation. Methods: The Cochrane Library, PubMed, EMbase, CNKI, VIP and CBM, Wanfang Data were searched(from the foundation date to Jan. 2016) for the randomized controlled trials (RCTs) of tiotropium Respimat in the treatment of patients with COPD. Two reviewers independently retrieved the RCTs according to the inclusion and exclusion criteria, assessed the methodological quality of the included trials.and performed statistical analysis on the data using RevMan 5.3 software. Results: Totally 11 RCTs on efficacy were finally included.The results of the combined analysis showed that FEV(1) was significantly improved in the tiotropium Respimat group than that in the placebo group[MD=0.12, 95%CI(0.10-0.14), P<0.000 01], while FEV(1) was similar between the tiotropium Respimat group and the tiotropium HandiHaler group[5 µg: MD=0.00, 95%CI(-0.04-0.04), P=0.94; 2.5 µg: MD=-0.04, 95%CI(-0.10-0.01), P=0.12; 10 µg: MD=0.02, 95%CI(-0.06-0.09), P=0.66]. FVC was significantly improved in the tiotropium Respimat group than that in the placebo group[MD=0.18, 95%CI(0.09-0.28), P=0.0002], while FVC was similar between the tiotropium Respimat group and the HandiHaler group[2.5 µg: MD=-0.06, 95%CI(-0.16-0.04), P=0.24; 5 µg: MD=-0.00, 95%CI(-0.08-0.08), P=1.00; 10 µg: MD=0.02, 95%CI(-0.14-0.19), P=0.78]. The risk of acute exacerbations was lower in the tiotropium Respimat group (5 µg / kg) than in the placebo group [OR=0.72, 95%CI(0.60-0.86), P=0.000 3]. It was similar in the tiotropium Respimat group (5 µg) and the HandiHaler group[OR=1.01, 95%CI(0.94-1.09), P=0.71]. The SGRQ total score of the tiotropium Respimat group (5 µg) was significantly different from that of the placebo group[MD=-3.6, 95%CI(-3.88--3.32), P<0.000 01]. C(max, ss) and AUC(0-6 h, ss) were also similar between the tiotropium Respimat group and the HandiHaler group[MD=0.2, 95%CI(-5.1-5.5), P=0.94]; MD=-1.01, 95%CI(-11.78-9.77), P=0.85]. Nine RCTs were included in the evaluation of the incident rates of adverse drug reactions(ADR). There was no significant difference between the tiotropium Respimat group HandiHaler group and the placebo group[RR=0.95, 95%CI(0.89-1.00), P=0.05], [OR=1.07, 95%CI(1.00-1.16), P=0.06]. Conclusions: The efficacy and safety of tiotropium Respimat was similar to tiotropium HandiHaler in the treatment of COPD. They can effectively improve the pulmonary function and clinical symptoms of patients. But the long-term efficacy and safety of tiotropium Respimat still need to be confirmed by higher quality and larger RCTs with long-term follow-up.

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

BACKGROUND: In 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. METHODS: To 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. RESULTS: Published evidence from comparative studies suggests that tiotropium Respimat® 5 µg and tiotropium HandiHaler® 18 µg provide similar clinical outcomes in patients with COPD. CONCLUSIONS: The 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.

Tiotropium Bromide/Olodaterol (Stiolto Respimat): Once-Daily Combination Therapy for the Maintenance of COPD.

Tiotropium bromide/olodaterol (Stiolto Respimat): once-daily combination therapy for the maintenance of COPD.

Pooled analysis of tiotropium Respimat(®) pharmacokinetics in cystic fibrosis.

Tiotropium is the first bronchodilator to be studied systematically in cystic fibrosis (CF). We investigated whether any intrinsic or extrinsic factors affected pharmacokinetic (PK) parameters of inhaled tiotropium delivered by Respimat(®) in adults and children with CF. Tiotropium PK in patients with CF was compared with that of healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). This pooled analysis summarizes the PK parameters of inhaled tiotropium Respimat(®) across 9 early- and late-phase trials involving 27 healthy volunteers (1 trial), 409 patients with CF (3 trials), and 281 patients with COPD (5 trials). Patients with CF aged 5 to 11, 12 to 17, and ≥ 18 years had similar tiotropium plasma concentrations (geometric mean C(0.083,ss,norm): 2.22 pg/mL/µg; not determined for patients aged <5 years). The fraction excreted unchanged in the urine was 3.4-fold lower for patients aged 0.4 to <5 years than for those aged 5 to 11 years (fe(0-4,ss): 1.19% vs 4.09%). Tiotropium PK parameters were similar between CF patients and COPD patients.

Comparative mortality risk of tiotropium administered via handihaler or respimat in COPD patients: are they equivalent?

BACKGROUND: Tiotropium bromide, once daily, long-acting anticholinergic bronchodilator is either administered by handihaler metered dose inhaler or by respimat soft mist inhaler. It has been proved to improve lung function, daily symptoms and quality of life and to decrease the exacerbation and hospitalisation rate of patients with Chronic Obstructive Pulmonary Disease (COPD). Although the efficacy of both formulations is undeniable, concerns have been raised on their effect on cardiovascular and general mortality. METHODS: Two independent authors systematically reviewed Medline, Scopus, Cochrane Library and ClinicalTrials.gov to collect clinical trials, observational studies and meta-analyses studying the safety of tiotropium. The reference list of all the included studies were also reviewed. RESULTS: Limited, early studies suggested a potential increase in cardiovascular and general mortality associated with tiotropium handihaler, but these data were outweighed by following larger trials, real-life studies and meta-analyses which proved the opposite. On the other hand, data on tiotropium respimat (5 µg) have been contradictory, with different studies suggesting increased cardiovascular and general mortality compared to handihaler (18 µg) or placebo, especially in patients with comorbid diseases. TIOSPIR trial suggests comparable safety of the two formulations. However the exclusion of patients with pre-existing unstable cardiovascular disease, moderate or severe kidney disease or any other significantly disease may limit the generizability of these results. CONCLUSION: Although the two tiotropium formulations have similar efficacy, current data cannot prove safety equivalence, since respimat may be associated with increased cardiovascular and general mortality, especially in patients with comorbid diseases.

Use of tiotropium Respimat Soft Mist Inhaler versus HandiHaler and mortality in patients with COPD.

Tiotropium, a long-acting anticholinergic, is delivered via HandiHaler or via Respimat. Randomised controlled trials suggest that use of tiotropium Respimat increases the risk of dying. We compared the risk of mortality between tiotropium Respimat versus HandiHaler. Within the Integrated Primary Care Information database, we defined a source population of patients, aged ≥ 40 years, with ≥ 1 year of follow-up. Based on prescription data, we defined episodes of tiotropium use (Respimat or HandiHaler). The risk of mortality, within these episodes, was calculated using a Cox proportional hazard regression analysis. From the source population, 11 287 patients provided 24 522 episodes of tiotropium use. 496 patients died while being exposed to HandiHaler or Respimat. Use of Respimat was associated with almost 30% increased risk of dying (adjusted HR 1.27, 95% CI 1.03-1.57) with the highest risk for cardiovascular/cerebrovascular death (adjusted HR 1.56, 95% CI 1.08-2.25). The risk was higher in patients with co-existing cardiovascular disease (adjusted HR 1.36, 95% CI 1.07-1.73) than in patients without (adjusted HR 1.02, 95% CI 0.61-1.71). Use of tiotropium Respimat was associated with an almost 30% increase of mortality compared with HandiHaler and the association was the strongest for cardiovascular/cerebrovascular death. It is unclear whether this association is causal or due to residual confounding by chronic obstructive pulmonary disease severity.

COPD Patients' Behaviour When Involved in the Choice of Inhaler Device.

BACKGROUND: Inhaler therapy plays a crucial role in controlling respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD). Incorrect or partially correct use of inhaler devices causes many chronic obstructive pulmonary disease (COPD) patients to continue to have respiratory symptoms due to poor drug deposition in the airways as a result of poor inhaler technique, leading to increased healthcare costs due to exacerbations and multiple emergency room presentations. Choosing the right inhaler device for each individual patient is a bigger challenge for doctors and chronic obstructive pulmonary disease (COPD) patients. The type of inhaler device and the correct inhaler technique depends on the control of symptoms in chronic obstructive pulmonary disease (COPD). Physicians treating patients with chronic obstructive pulmonary disease (COPD) play a central role in educating patients about the correct use of inhalation devices. The steps for the correct use of inhalation devices should be taught to patients by doctors in the presence of the family so that if the patient has difficulties handling the device correctly, the family can support them. METHODS: Our analysis included 200 subjects divided into two groups-recommended group (RG) and chosen group (CG)-and aimed primarily to identify the behaviour of chronic obstructive pulmonary disease (COPD) patients when faced with deciding which type of inhaler device is most suitable for them. The two groups were monitored three times during the 12-month follow-up period. Monitoring required the physical presence of the patient at the investigating physician's office. The study included patients who were smokers, ex-smokers, and/or with significant exposure to occupational pollutants, aged over 40 years diagnosed with chronic obstructive pulmonary disease (COPD), risk group B and C according to the GOLD guideline staging, and on inhaled ICS+LABA treatment, although they had an indication for LAMA+LABA dual bronchodilation treatment. Patients presented for consultation on their own initiative for residual respiratory symptoms under background treatment with ICS+LABA. The investigating pulmonologist who offered consultations to all scheduled patients, on the occasion of the consultation, also checked the inclusion and exclusion criteria. If the patient did not meet the study entry criteria, they were assessed and received the appropriate treatment, and if the study entry criteria were met, the patient signed the consent and followed the steps recommended by the investigating pulmonologist. As a result, patient entry into the study was randomised 1:1, meaning that the first patient was recommended the inhaler device by the doctor and the next patient entered into the study was left to decide for themselves which type of device was most suitable for them. In both groups, the percentage of patients who had a different choice of inhaler device from that of their doctor was statistically significant. RESULTS: Compliance to treatment at T12 was found to be low, but compared to results previously published on compliance, in our analysis, compliance was higher and the only reasons identified as responsible for the better results were related to the selection of the target groups and the regular assessments, where, in addition to reviewing the inhaler technique, patients were encouraged to continue treatment, thus creating a strong bond between patient and doctor. CONCLUSIONS: Our analysis revealed that empowering patients by involving them in the inhaler selection process increases adherence to inhaler treatment, reduces the number of mistakes in inhaler use of the inhaler device, and implicitly the number of exacerbations.

Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines.

Tuberculosis (TB) remains one of the most lethal infectious diseases globally. The only TB vaccine approved by the World Health Organization, Bacille Calmette-Guérin (BCG), protects children against severe and disseminated TB but provides limited protection against pulmonary TB in adults. Although several vaccine candidates have been developed to prevent TB and are undergoing preclinical and clinical testing, BCG remains the gold standard. Currently, BCG is administered as an intradermal injection, particularly in TB endemic countries. However, mounting evidence from experimental animal and human studies indicates that delivering BCG directly into the lungs provides enhanced immune responses and greater protection against TB. Inhalation therapy using handheld delivery devices is used for some diseases and allows the delivery of drugs or vaccines directly into the human respiratory tract. Whether this mode of delivery could also be applicable for live attenuated bacterial vaccines such as BCG or other TB vaccine candidates remains unknown. Here we discuss how two existing inhalation devices, the mucosal atomization device (MAD) syringe, used for influenza vaccines, and the Respimat® Soft Mist™ inhaler, used for chronic obstructive pulmonary disease (COPD) therapy, could be repurposed for mucosal delivery of live attenuated TB vaccines. We also outline the challenges and outstanding research questions that will require further investigations to ensure usefulness of respiratory delivery devices that are cost-effective and accessible to lower- and middle-income TB endemic countries.

YouTube as a Guide for Respimat® Soft Mist™ Inhaler Technique.

BACKGROUND: Consumers are involved more than ever in their health care, with many utilizing the Internet for health information. YouTube is a convenient and vast source of health education videos. Pharmaceutical companies, health organizations, providers, and others post instructional videos for the use of the Respimat® Soft Mist™ Inhaler device on sites like YouTube. Therefore, review of content and quality is important to ensure consumers are directed to the best information available. OBJECTIVE: Assess content and quality of YouTube videos demonstrating Respimat Soft Mist inhaler technique. METHODS: YouTube was queried May 16, 2018 using the term "Respimat inhaler." The first 35 unique videos in English with instructions for use were assessed. Technical quality of each video was evaluated using a validated scale and content assessed using manufacturer/package insert. RESULTS: Of 35 videos reviewed, median duration was 2 minutes 50 seconds (interquartile range [IQR]: 1 minute 23 seconds-4 minutes 22 seconds). Target audience was laypeople for 97% (n = 34) of videos. The source was a professional organization for 70% (n = 24). Most (74%, n = 24) received the maximum quality score of 5. Commonly omitted steps included documentation of the discard date (74%), repetitive dose activation until spray is visible (49%), and pointing inhaler to the back of the throat (43%). CONCLUSIONS: Proper technique is crucial for patients to achieve optimal results from inhaled medications. While many videos are available through YouTube for demonstration of Respimat Soft Mist inhaler technique, some omitted key steps. Thorough and repetitive patient education should be provided, and augmented with reputable online sources.

Switching COPD patients from the disposable to the new reusable Respimat soft mist inhaler: a real-world study from Switzerland.

OBJECTIVE: The aims of the survey were to assess first experiences of Swiss COPD patients switching from the disposable to the new reusable Respimat inhaler, and to evaluate physicians´ and patients´ views of the new training material. METHODS: Patients with a confirmed diagnosis of COPD using a disposable Respimat inhaler for at least three months were included. Patients´ demographics, COPD stage, current treatment, and comorbidities relevant for the handling of the device were assessed. Further, patients were trained on the reusable Respimat by placebo inhaler, patient brochure, video cards/demo films and SMS reminder service. After at least one cartridge change, patients gave comprehensive feedback on their satisfaction with the reusable Respimat and physicians evaluated the need for re-training. RESULTS: 235 patients participated in the survey. Of these, 37% suffered from comorbidities restricting the handling of the Respimat. 216 (92%) patients had a better overall satisfaction with the reusable than with the disposable Respimat. Dose counter (86%), monthly preparation (81%) and daily handling (77%) were also assessed as better by most of the patients. In 80% of cases, the user ability was stated as better than for the disposable Respimat. Less than 15% of the patients required further training. Placebo inhaler was the mostly preferred training material by both, physicians (in 86% of the patients) and patients (75%). In patients with comorbidities affecting inhaler handling, overall satisfaction was also better in 86% of the patients. CONCLUSION: The majority of patients were satisfied with the new reusable Respimat device and proper handling could be attained using the provided training material, even in patients with restricting comorbidities.

Impact of long-acting muscarinic antagonists on small airways in asthma and COPD: A systematic review.

Small airway disease is recognized as a cardinal pathological process of chronic obstructive pulmonary disease (COPD), and recently small airways have been recognized as a major site of airflow obstruction also in asthmatic patients. The transversal involvement of small airways in COPD and asthma has warranted research efforts to identify therapeutic strategies able to unlock the small airway compartment. The mainstay of COPD treatment is represented by long-acting ß2-adrenoceptor agonists (LABAs) and long-acting muscarinic antagonists (LAMAs). In asthma, the efficacy of LAMAs administered add-on to inhaled corticosteroids (ICSs) or ICS/LABA combinations has been investigated only in recent years. The aim of this systematic review was to examine the current literature concerning the impact of LAMAs on small airways and their lung deposition in both COPD and asthma. LAMAs administered either alone or in combination induced an effective bronchorelaxant effect of small airways, however the effectiveness of respiratory medications not only relies on the selected drug, but also on the employed inhalation device and patient's adherence. Tiotropium delivered via Respimat® SMI achieved a superior drug deposition in the peripheral lung compared to HandiHaler® dry powder inhaler and metered-dose inhalers (MDIs). The use of co-suspension™ delivery technology for MDIs and the introduction of the eFlow® nebulizer to deliver glycopyrronium improved aerosol drug delivery to the peripheral lung, by achieving uniform distribution of drug particles. This systematic review provides a synthesis of current literature concerning the impact of LAMAs on small airways and an insight on LAMAs distribution within the lung.