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Background: Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence and persistence are not yet in regular widespread use. Implementation costs are a potential barrier to uptake of such programs., Objective: We undertook a systematic literature review and narrative synthesis of studies investigating the cost-effectiveness of treatment adherence-promoting programs or that determined their impact on health care budget directly or via health care resource use (HCRU)., Methods: We identified relevant publications using Medline and PreMEDLINE (PubMed), Embase (Embase.com, Elsevier), and EconLit for publications between January 2000 and July 2021. We also searched clinical trial databases and selected conference proceedings., Results: Of 1,910 potentially relevant articles, 26 met prespecified inclusion criteria and underwent data extraction. Eleven reported a direct assessment of adherence, 15 included economic evaluations, and 17 described HCRU. None included an analysis of biologic medication use. When they were studied, interventions were often found to be highly cost-effective, with dominant incremental cost-effectiveness ratios in some cases. Reductions in direct costs and HCRU (health care visits, hospital admissions, and/or the use of medications, including add-on/reliever treatment and antibiotics) were frequently reported. Reported use of maintenance treatments improved in some studies. Counseling and/or digitally informed programs were used in all cases in which favorable outcomes were observed., Conclusions: Adherence-promoting interventions are mostly cost-effective and often result in reduced HCRU and associated costs. Multidisciplinary care involving one-to-one advice and digitally enhanced communications appear to offer the greatest benefit., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs), are widely used to deliver drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Incorrect use of inhalers is one of the main obstacles to achieving better clinical control. Indeed, with pMDIs, patients fail to synchronise actuation with inhalation due to a lack of coordination and with DPIs insufficient inspiratory effort compromises drug deposition in lungs. More than 50% of patients desire to switch their pMDIs and DPIs for a better device. This led to the development of pressurised breath-actuated inhalers (BAIs) with the aim of combining the beneficial features of pMDIs and DPIs and mitigating their problems. BAIs, e.g., Synchrobreathe™, are designed such that they are activated by a low inhalation effort and mechanically actuate the dose in synchrony to inspiration, thereby resolving the need to coordinate actuation with inspiration. BAIs have advantages, including ease of use, high lung deposition of medication, and greater patient preference. We discussed the design features, operating procedure, and clinical evidence of the Synchrobreathe™ device (Cipla Ltd, India), a BAI available with a wide range of drug combinations. Studies have shown that a higher number of patients (68.19%) used the Synchrobreathe™ without any error than the pMDI (56.21%), and that the vast majority of them (92%) found it easy to understand and use. The Synchrobreathe™ is an innovative, easy-to-use inhaler that may overcome many limitations associated with pMDIs and DPIs, thus potentially improving management of obstructive airway diseases and patients' quality of life., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: There has been an active discussion on the sustainability of inhaler therapy in respiratory diseases, and it has cast a shadow on pMDIs which rely on propellant with high global warming potential (GWP). DPIs offer a lower GWP and effective alternative, but there has been concern whether all patients can generate sufficient inspiratory effort to disperse the drug. This review focuses on airflow resistance of DPIs and its clinical relevance., Areas Covered: For this narrative review, we searched the literature for studies comparing flow patterns with different devices. We also included a section on clinical trials comparing reliever administration with DPI, pMDI with spacer, and nebulizer during exacerbation., Expert Opinion: The evidence supports the efficacy of DPIs irrespective of respiratory condition or age of the patient even during acute exacerbations. Air flow resistance does not limit the use of DPIs and the patients were able to generate sufficient inspiratory flow rate with almost any device studied. None of 16 identified clinical trials comparing reliever administration via DPIs to other types of devices during exacerbation or bronchial challenge showed statistically significant difference between the device types in FEV1 recovery. DPIs performed as well as other types of inhaler devices even during asthma or COPD exacerbation.

Background: Switching inhaler regimens can be driven by poor disease control but also by nonclinical factors, such as cost and environmental impact. The consequences of switching for nonclinical reasons are largely unclear., Objective: To systematically review the real-world consequences of switching inhaler regimens for nonclinical reasons in asthma and/or chronic obstructive pulmonary disease patients., Methods: Embase, MEDLINE, EBM Reviews, and EconLit were searched to November 21, 2020. Conference searches and reference checking were also performed. Real-world studies of asthma and/or chronic obstructive pulmonary disease patients undergoing a switch in inhaler regimen for any reason apart from clinical need were included. Two reviewers screened and extracted data. Key outcomes included symptom control, exacerbations, and patient-doctor relationships., Results: A total of 8,958 records were screened and 21 studies included. Higher-quality (matched comparative) studies were prioritized. Five matched studies (6 datasets) reported on symptom control: 5 datasets (n = 7,530) with unclear patient consent reported improved disease control following switching, and 1 dataset (n = 1,648) with non-consented patients reported significantly worsened disease control. Three matched studies (5 datasets, n = 10,084) reported on exacerbation rate ratios; results were heterogeneous depending on the definition used. Two studies (n = 137) reported that switching inhaler regimens could have a negative impact on the doctor-patient relationship, especially when the switches were non-consented. Study quality was generally low., Conclusions: Switching inhaler regimens is a complex issue that can have variable clinical consequences and can harm the patient-doctor relationship. Limited high-quality evidence was identified, and study designs were heterogeneous. A robust framework is needed to guide the personalized switching of inhalers., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences., Methods: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844)., Results and Conclusion: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease., Abbreviations: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Background: Inhaled medications are central to treating asthma and chronic obstructive pulmonary disease (COPD), yet critical inhaler technique errors are made by up to 90% of patients. In the clinical research setting, recruitment of subjects with poor inhaler technique may give a false impression of both the benefits and the necessity of add-on treatments such as biologic therapies., Objective: To assess the frequency with which inhaler technique is assessed and reliably optimized before and during patient enrollment into randomized controlled trials (RCTs) addressing the efficacy of topical therapy, and the escalation of therapy for asthma and COPD., Methods: Systematic searches were conducted of PubMed and Embase for RCTs published in the past 10 years involving patients with a diagnosis of asthma or COPD undergoing escalation of baseline inhaled therapy (stepping up, changing, adding, switching, increasing, etc) or the introduction of biologic agents., Results: Searches highlighted 1,014 studies, 118 of which were eligible after the removal of duplicates as well as screening and full text review. Of these, only 14 (11.9%) included accessible information in the methods section or referred to such information in online supplements or protocols concerning assessment of participants' inhaler technique. We therefore developed the proposed Best Practice Inhaler Technique Assessment and Reporting Checklist., Conclusions: Our study identifies a concerning lack of checking and correcting inhaler technique, or at least reporting that this was undertaken, before enrollment in asthma and COPD RCTs, which may affect the conclusions drawn. Mandating the use of a standardized checklist in RCT protocols and ensuring all published RCTs report checking and correcting inhaler technique before enrollment are important next steps., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The study aimed to determine the associations of Peak Inspiratory Flow (PIF), inhalation technique and adherence with health status and exacerbations in participants with COPD using DPI maintenance therapy. This cross-sectional multi-country observational real-world study included COPD participants aged ≥40 years using a DPI for maintenance therapy. PIF was measured three times with the In-Check DIAL G16: (1) typical PIF at resistance of participant's inhaler, (2) maximal PIF at resistance of participant's inhaler, (3) maximal PIF at low resistance. Suboptimal PIF (sPIF) was defined as PIF lower than required for the device. Participants completed questionnaires on health status (Clinical COPD Questionnaire (CCQ)), adherence (Test of Adherence to Inhalers (TAI)) and exacerbations. Inhalation technique was assessed by standardised evaluation of video recordings. Complete data were available from 1434 participants (50.1% female, mean age 69.2 years). GOLD stage was available for 801 participants: GOLD stage I (23.6%), II (54.9%), III (17.4%) and IV (4.1%)). Of all participants, 29% had a sPIF, and 16% were shown able to generate an optimal PIF but failed to do so. sPIF was significantly associated with worse health status (0.226 (95% CI 0.107-0.346), worse units on CCQ; p = 0.001). The errors 'teeth and lips sealed around mouthpiece', 'breathe in', and 'breathe out calmly after inhalation' were related to health status. Adherence was not associated with health status. After correcting for multiple testing, no significant association was found with moderate or severe exacerbations in the last 12 months. To conclude, sPIF is associated with poorer health status. This study demonstrates the importance of PIF assessment in DPI inhalation therapy. Healthcare professionals should consider selecting appropriate inhalers in cases of sPIF., (© 2022. The Author(s).)

Introduction : Inhaled therapies are likely to continue to dominate asthma and chronic obstructive pulmonary disease treatment. Dry powder inhalers (DPIs) have several advantages over pressurized metered-dose inhaler (pMDIs), that are most frequently marketed world-wide, but often difficult to use. This literature search focus on DPI features, with respect to Easyhaler, that may affect their use and patients' clinical benefit. Areas covered : DPIs are breath-actuated, easy to use, convenient to use, and more environmentally friendly. During inhalation, the formulation in a DPI is disaggregated by a turbulent airflow energy to generate particles with the greatest likelihood of deposition into the airways. The resistance among DPIs varies from low to high and those with high resistance are wrongly considered as difficult to use. Multidose reservoir-type DPIs have been developed to efficiently deliver a wide range of medications, including the fixed-dose combination of budesonide and formoterol. Easyhaler® shares a similar shape with pMDIs and, as other DPIs, its performance is unaffected by environmental and storage conditions. Due to Easyhaler internal design, dose emission is consistent irrespective of the inhalation flow used by each patient. Expert opinion : Easyhaler® may be considered one of the most convenient inhalers, for daily use, in patients with asthma or COPD.

Factors related to the discrepancy between patient-perceived and actual disease control remain unclear. Identifying patients at risk of overestimation of asthma control remains elusive. This study aimed to (i) investigate the relationship between patient-reported and actual level of asthma control (ii), compare the characteristics between patients who believe their asthma is well controlled that accurately report 'well-controlled' asthma with those that do not, and (iii) identify factors associated with inaccurately reported 'well-controlled' asthma. A historical, multinational, cross-sectional study using data from the iHARP (initiative Helping Asthma in Real-life Patients) review service for adults with asthma prescribed fixed-dose combination therapy. Data from 4274 patients were analysed. A major discrepancy between patient-reported and Global Initiative for Asthma defined asthma control was detected; 71.1% of patients who reported 'well-controlled' asthma were inaccurate in their perception despite receiving regular maintenance therapy. Significant differences were noted in age, gender, body mass index, education level, medication use, side effects, attitudes to preventer inhaler use, inhaler technique review and respiratory specialist review between patients who accurately reported 'well-controlled' asthma and those who did not. Independent risk factors associated with inaccurately reported 'well-controlled' asthma were: having taken a maximum of 5-12 puffs or more of reliever inhaler on at least one day within the previous 4 weeks; being female; having seen a respiratory specialist more than a year ago (rather than in the previous year); and having required oral corticosteroids for worsening asthma in the previous year. The study highlighted the significant hidden burden associated with under-recognition of poor asthma control, on the part of the patient and the need for targeted interventions designed to address the continuing discrepancy between perceived and actual disease control.

Inhalable medications for patients with asthma and chronic obstructive pulmonary disease (COPD) can be confusing even for health care professionals because of the multitude of available devices each with different operating principles. Dry powder inhalers (DPI) are a valuable option for almost all of the patients with asthma or COPD. Based on recorded patient inspiratory profiles, the peak inspiratory flow requirement of 30 L min -1 of high-resistance devices does not usually pose any practical limitations for the patients. Suboptimal adherence and errors in device handling are common and require continuous checking and patient education in order to avoid these pitfalls of all inhalation therapy. The aim of this opinion paper is to describe the working principles of DPIs and to summarise their key properties in order to help prescribing the correct inhaler for each patient.Funding: Orion Pharma.

Background: Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists., Methods: In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices. Patients initially demonstrating ≥1 error with their current device, and then achieving mastery with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]-observed errors), were eligible for the longitudinal phase. In the longitudinal phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary endpoints were the proportions of patients achieving device mastery after three training steps and maintaining device mastery (defined as the absence of HCP-observed errors after 12 weeks of use). Secondary endpoints included device preference, handling error frequency, asthma control, and safety. Exploratory endpoints included assessment of device mastery by an independent external expert reviewing video recordings of a subset of patients., Results: Four hundred ninety-three patients participated in the cross-sectional phase, and 395 patients in the longitudinal phase. In the cross-sectional phase, more patients achieved device mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%) (odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05-6.95], p < 0.001). Longitudinal phase data indicated that the odds of maintaining inhaler mastery at 12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80-1.98], p = 0.316). Asthma control improved in both groups with no significant difference between groups (OR 0.11 [95% CI -0.09-0.30]). An exploratory analysis indicated that the odds of maintaining independent expert-verified device mastery were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11 [95% CI 1.25-3.54])., Conclusions: In the cross-sectional phase, a significantly greater proportion of patients using Spiromax versus Turbuhaler achieved device mastery; in the longitudinal phase, the proportion of patients maintaining device mastery with Spiromax versus Turbuhaler was similar. An exploratory independent expert-verified analysis found Spiromax was associated with higher levels of device mastery after 12 weeks. Asthma control was improved by treatment with both BF Spiromax and BF Turbuhaler., Trial Registration: EudraCT 2013-004630-14 (registration date 23 January 2014); NCT02570425 .

Nonadherence to treatment, and its associated health and economic burden, is particularly problematic in asthma and chronic obstructive pulmonary disease management because of heterogeneous patient populations and the need for an inhaled route of drug administration. Symptom variability, comorbidities, and device switching further add to suboptimal adherence rates. As opposed to controlled clinical trials, real-life studies show consistently low inhaler adherence in daily practice, yet exact adherence rates have long been affected by disagreement on standardized definitions. The recently developed Ascertaining Barriers to Compliance taxonomy helps to address adherence research disparities by identifying 3 phases of adherence (initiation, implementation [including correct inhaler technique], and discontinuation). This review considers the reasons for and impact of suboptimal adherence, together with summaries of key studies that demonstrate how improving adherence can reduce exacerbations, inhaled corticosteroid use (in cases of better inhaler technique), hospitalizations, and treatment costs. Strategies to help ensure optimal adherence are discussed, including the choice of a patient-tailored inhaler, patient empowerment, education and training, and the potential of electronic monitoring and digital technology. It is concluded that a combined effort from payers, health care professionals, and manufacturers could make a real difference to asthma and chronic obstructive pulmonary disease control, as well as to health care budgets., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Proceedings of the European Seminars in Respiratory Medicine course, Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD, held in Taormina, Italy, on 3-4 March, 2017.

Background: Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD). However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment., Methods: A systematic review was conducted to define 'critical' errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2)., Results: Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total). Search-2 identified 9 studies. We observed 299 descriptions of critical error. Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency. A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden., Conclusions: We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes. Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.

Objective: Healthcare professionals (HCPs) are required to assess and train patients in the correct use of inhalers but are often unable to demonstrate correct technique themselves. We sought to assess the level of training required for HCPs to master and maintain device mastery when using two different dry powder inhalers (DPIs)., Methods: We conducted a randomized, un-blinded, crossover study in undergraduate HCPs who undertook a six-step training procedure (intuitive use, patient information leaflet, instructional video, individual tuition from expert, then two repeats of individual tuition) for the use of Turbuhaler® (an established device) and Spiromax® (a newer device, reportedly easier to use). Device mastery (absence of errors) was evaluated by expert assessors at each training step. Maintenance of mastery was assessed 4 ± 1 week (visit 2) and 8 ± 2 weeks (visit 3) after initial training (visit 1)., Results: Of 516 eligible participants, 113 (22%) demonstrated device mastery prior to training on Spiromax® compared with 20 (4%) on Turbuhaler® (p < 0.001). The median number of training steps required to achieve mastery was 2 (interquartile range [IQR] 2-4) for Spiromax® and 3 (IQR 2-4) for Turbuhaler® (p < 0.001). A higher number of participants maintained mastery with Spiromax® compared with Turbuhaler®, at visits 2 and 3 (64% vs 41% and 79% vs 65%, respectively; p < 0.001)., Conclusions: There are significant differences in the nature and extent of training required to achieve and maintain mastery for Spiromax® and Turbuhaler® devices. The implications on clinical practice, device education delivery, and patient outcomes require further evaluation.

Background: Poor inhaler technique has been linked to poor asthma outcomes. Training can reduce the number of inhaler errors, but it is unknown which errors have the greatest impact on asthma outcomes., Objective: The CRITical Inhaler mistaKes and Asthma controL study investigated the association between specific inhaler errors and asthma outcomes., Methods: This analysis used data from the iHARP asthma review service-a multicenter cross-sectional study of adults with asthma. The review took place between 2011 and 2014 and captured data from more than 5000 patients on demographic characteristics, asthma symptoms, and inhaler errors observed by purposefully trained health care professionals. People with asthma receiving a fixed-dose combination treatment with inhaled corticosteroids and long-acting beta agonist were categorized by the controller inhaler device they used-dry-powder inhalers or metered-dose inhalers: inhaler errors were analyzed within device cohorts. Error frequency, asthma symptom control, and exacerbation rate were analyzed to identify critical errors., Results: This report contains data from 3660 patients. Insufficient inspiratory effort was common (made by 32%-38% of dry-powder inhaler users) and was associated with uncontrolled asthma (adjusted odds ratios [95% CI], 1.30 [1.08-1.57] and 1.56 [1.17-2.07] in those using Turbohaler and Diskus devices, respectively) and increased exacerbation rate. In metered-dose inhaler users, actuation before inhalation (24.9% of patients) was associated with uncontrolled asthma (1.55 [1.11-2.16]). Several more generic and device-specific errors were also identified as critical., Conclusions: Specific inhaler errors have been identified as critical errors, evidenced by frequency and association with asthma outcomes. Asthma management should target inhaler training to reduce key critical errors., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and adverse effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery. The availability of small-particle aerosols of corticosteroids, bronchodilators, or their combination enables a higher total lung deposition and better peripheral lung penetration and provides added clinical benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Asthma has been demonstrated to be as common in the elderly as in younger age groups. Although no specific recommendations exist to manage the disease differently in older individuals, functional features and clinical presentations may be affected by age per se, and by age-related conditions, such as comorbidities and polypharmacy. In this review article, we aimed to explore the efficacy and safety in elderly asthmatic patients of one of the most currently used inhaled treatments for asthma, that is, the fixed-dose combination of budesonide/formoterol. We attempted to address some practical questions that are relevant to the daily practice of clinicians. We focused on the efficacy and real-world effectiveness of inhaled corticosteroids and long-acting β-adrenergic bronchodilators (ICS/LABA) as treatment in the elderly population, since data are extrapolated from younger populations. We investigated whether a maintenance and reliever therapy approach is more effective in the elderly as opposed to maintenance regimens, from both the general practitioner's and the pulmonologist's perspective. To address these questions, we scanned electronic databases (PubMed, MEDLINE, Embase, Scopus and Google Scholar) from the date of inception up to October 2016 with a cross-search using the following keywords: 'asthma', 'elderly', 'SMART therapy', 'MART therapy', 'Turbuhaler', and 'budesonide/formoterol'. The available literature on the topic confirms that when the age-associated changes are properly managed in clinical practice, asthma in older populations can be optimally controlled with inhaled treatment including ICS/LABA. This also applies for the budesonide/formoterol fixed combination, thus allowing for the maintenance and reliever therapy approach.

Background: Serious inhaler technique errors can impair drug delivery to the lungs. This randomised, crossover, open-label study evaluated the proportion of patients making predefined serious errors with Pulmojet compared with Diskus and Turbohaler dry powder inhalers., Methods: Patients ≥18 years old with asthma and/or COPD who were current users of an inhaler but naïve to the study devices were assigned to inhaler technique assessment on Pulmojet and either Diskus or Turbohaler in a randomised order. Patients inhaled through empty devices after reading the patient information leaflet. If serious errors potentially affecting dose delivery were recorded, they repeated the inhalations after watching a training video. Inhaler technique was assessed by a trained nurse observer and an electronic inhalation profile recorder., Results: Baseline patient characteristics were similar between randomisation arms for the Pulmojet-Diskus (n = 277) and Pulmojet-Turbohaler (n = 144) comparisons. Non-inferiority in the proportions of patients recording no nurse-observed serious errors was demonstrated for both Pulmojet versus Diskus, and Pulmojet versus Turbohaler; therefore, superiority was tested. Patients were significantly less likely to make ≥1 nurse-observed serious errors using Pulmojet compared with Diskus (odds ratio, 0.31; 95 % CI, 0.19-0.51) or Pulmojet compared with Turbohaler (0.23; 0.12-0.44) after reading the patient information leaflet with additional video instruction, if required., Conclusions: These results suggest Pulmojet is easier to learn to use correctly than the Turbohaler or Diskus for current inhaler users switching to a new dry powder inhaler., Trial Registration: ClinicalTrials.gov Identifier: NCT01794390 (February 14, 2013).

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

Prescription cost-containment measures are increasing in many European countries and, as more inhaler devices become available, there may be pressure to switch patients from reference inhaled medication to cheaper generic inhaled drugs. Indeed, in some countries, such a substitution is mandated by current regulations, and patients who do not accept the substitution have to pay the difference in cost. Generic inhaled drugs are therapeutically equivalent to original branded options but may differ in their formulation and inhalation device. This new situation raises questions about the potential impact of switching from branded to generic inhaled medications in patients with asthma or chronic obstructive pulmonary disease (COPD), with or without their consent, in countries where this is permitted. Acquisition cost savings from a substitution could be offset by costs related to deterioration in asthma control or worsening in COPD outcomes if the patient is unable or unwilling to use the inhaler device properly. Non-adherence to therapy and incorrect inhaler usage are recognised as major factors in uncontrolled asthma and worsening of COPD outcomes. Switching patients to a different inhaler device may exacerbate these problems, particularly in patients who disagree to switch. Where switching is permitted or mandatory, it is crucial that the reason for switching has been properly explained to the patient and adequate instruction for operating correctly the inhaler have clearly been provided., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Asthma and chronic obstructive pulmonary disease (COPD) are both diseases with an increasing prevalence worldwide. Inhaled therapy for these conditions has a number of advantages over systemic therapy, but requires the patients to use, and to master the use of, an inhaler device. However, many patients cannot use inhalers correctly, and over 50% of patients struggle to use a metered-dose inhaler properly. Poor inhaler technique is associated with a reduced asthma control, worst COPD outcomes, and wastage of economic resources. Of perhaps more concern is the fact that many health professionals also do not know how to use inhalers correctly and are therefore not in a position to coach patients effectively. Training patients and caregivers in the correct inhaler preparation and use is an essential component in the process toward achieving reliable and repeatable medication delivery. Instructions should be inhaler-specific, and they include instruction on how to load or prime the device. Providing only the leaflet that comes with the medicines does not lead to adequate inhalation technique, not even immediately after the patient has read the instructions and practiced with the inhaler. One-on-one sessions with health-care professionals probably represent the most effective educational method. However, it appears that, by itself, even repeated instruction could be insufficient to achieve improved adherence in the long term, as there is a tendency for patients or caregivers to forget what they have learned as time elapses since the training event. Thus, despite the development of several new and improved types of inhaler device, the evidence currently available points to little or no progress having been made with patients' ability to use their inhalers. As the range of drugs delivered by inhalation increases, inhaler technique checks and training need to be an integral part of the routine management of any patient with either asthma or COPD.

Background: Inhaled therapy is the cornerstone of pharmacotherapy in patients with asthma and chronic obstructive pulmonary disease (COPD). Appropriate inhalation device selection is as important as drug choice but device-specific guidance appears to be lacking., Methods: To quantify the level of inhalation-device recommendations in clinical guidelines, a review was conducted by hand-searching national and international asthma and COPD guidelines (Global Initiative for Asthma [GINA] and Global initiative for chronic Obstructive Lung Disease [GOLD] guidelines) and an international guideline on device selection (the American College of Chest Physicians/American College of Asthma, Allergy, and Immunology [ACCP/ACAAI]). For each guideline, the number of pages, tables/figures and references relating to inhalation devices was identified., Results: GINA and GOLD guidelines contain very little inhalation device-specific guidance beyond recommendations for demonstrating and testing correct inhalation technique: <2% of pages or references and <3% of tables/figures are dedicated to devices. Device-related content in the ACCP/ACAAI device selection guideline was considerably higher with 54% of pages, 88% of tables/figures and 82% of references, respectively. Results in national guidelines reflect those on international guidelines., Conclusions: These results indicate that there is a considerable lack of clear and specific guidance regarding inhalation devices in current asthma/COPD guidelines. More robust studies on the impact of inhalation devices are needed to increase the number of evidence statements and recommendations regarding inhalation devices., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Efficacy trials suggest that extra-fine particle beclometasone dipropionate-formoterol (efBDP-FOR) is comparable to fluticasone propionate-salmeterol (FP-SAL) in preventing asthma exacerbations at a clinically equivalent dosage. However, switching from FP-SAL to efBDP-FOR has not been evaluated in real-world asthma patients., Aims: The REACH (Real-world Effectiveness in Asthma therapy of Combination inHalers) study investigated the clinical and cost effectiveness of switching typical asthma patients from FP-SAL to efBDP-FOR., Methods: A retrospective matched (1:3) observational study of 1,528 asthma patients aged 18-80 years from clinical practice databases was performed. Patients remaining on FP-SAL (n=1,146) were compared with those switched to efBDP-FOR at an equivalent or lower inhaled corticosteroid (ICS) dosage (n=382). Clinical and economic outcomes were compared between groups for the year before and after the switch. Non-inferiority (at least equivalence) of efBDP-FOR was tested against FP-SAL by comparing exacerbation rates during the outcome year., Results: efBDP-FOR was non-inferior to FP-SAL (adjusted exacerbation rate ratio 1.01 (95% CI 0.74 to 1.37)). Switching to efBDP-FOR resulted in significantly better (p<0.05) odds of achieving overall asthma control (no asthma-related hospitalisations, bronchial infections, or acute oral steroids; salbutamol ≤200μg/day) and lower daily short-acting β2-agonist usage at a lower daily ICS dosage (mean -130μg/day FP equivalents; p<0.001). It also reduced mean asthma-related healthcare costs by £93.63/patient/year (p<0.001)., Conclusions: Asthma patients may be switched from FP-SAL to efBDP-FOR at an equivalent or lower ICS dosage with no reduction in clinical effectiveness but a significant reduction in cost.

Respiratory responses to bronchoconstriction in asthma have been partially assessed and their significance is unclear. In 44 mild asthma patients we investigated respiratory responses during increasing levels of methacholine-induced bronchoconstriction. Inspiratory muscle activity, tidal volume, inspiratory and expiratory times were continuously monitored; breathing discomfort was rated. Mean inspiratory flow, respiratory frequency and ventilation were calculated. Lung function was assessed prior to and at maximum bronchoconstriction. Bronchoconstriction "dose-dependently" increased inspiratory muscle activity and breathing discomfort (P<0.01). In 37 patients (84.1%), the increase in inspiratory muscle activity was associated with increases in mean inspiratory flow and ventilation (P<0.01) because of selective rises in breathing depth (volume responders), or rate (frequency responders) or both (dual responders). In seven patients (15.9%) ventilation was unchanged. Individual respiratory responses were reproducible. With bronchoconstriction, frequency responders displayed greater hyperinflation and stronger breathing discomfort than volume responders (P<0.01). Analysis of the responses to induced bronchoconstriction disclosed distinctive and reproducible respiratory adjustments that may identify functionally different asthma subpopulations., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Incorrect usage of inhaler devices might have a major influence on the clinical effectiveness of the delivered drug. This issue is poorly addressed in management guidelines., Methods: This article presents the results of a systematic literature review of studies evaluating incorrect use of established dry powder inhalers (DPIs) by patients with asthma or chronic obstructive pulmonary disease (COPD)., Results: Overall, we found that between 4% and 94% of patients, depending on the type of inhaler and method of assessment, do not use their inhalers correctly. The most common errors made included failure to exhale before actuation, failure to breath-hold after inhalation, incorrect positioning of the inhaler, incorrect rotation sequence, and failure to execute a forceful and deep inhalation. Inefficient DPI technique may lead to insufficient drug delivery and hence to insufficient lung deposition. As many as 25% of patients have never received verbal inhaler technique instruction, and for those that do, the quality and duration of instruction is not adequate and not reinforced by follow-up checks., Conclusions: This review demonstrates that incorrect DPI technique with established DPIs is common among patients with asthma and COPD, and suggests that poor inhalation technique has detrimental consequences for clinical efficacy. Regular assessment and reinforcement of correct inhalation technique are considered by health professionals and caregivers to be an essential component of successful asthma management. Improvement of asthma and COPD management could be achieved by new DPIs that are easy to use correctly and are forgiving of poor inhalation technique, thus ensuring more successful drug delivery.

Aims: To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction., Methods: Eighteen patients inhaled methacholine (MCh) until FEV(1) decreased by 35% of control. Following administration of placebo, 200 microg salbutamol or 400 microg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV(1) and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method., Results: For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV(1) and volume-adjusted mid-expiratory flow similar to those obtained with 200 microg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) microg, 395 (95% CI 388, 404) microg and 404 (95% CI 393, 415) microg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07)., Conclusions: Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus.

Aims: This study aimed at evaluating changes in airway patency, lung volumes and perception of breathing discomfort intensity following salbutamol administration via the Diskus dry-powder inhaler (DPI) or a pressurized metered-dose inhaler with the Volumatic valved holding chamber (pMDI + Volumatic) in asthmatic patients with methacholine-induced bronchoconstriction., Methods: On six different study days, 18 patients inhaled methacholine until forced expiratory volume in 1 s (FEV(1)) decreased by approximately 35% of baseline. Following placebo, 200 and 400 microg of salbutamol through the pMDI + Volumatic or the Diskus, changes in FEV(1), volume-adjusted mean forced expiratory flow from 25 to 75% of the forced vital capacity (isoFEF(25-75)), lung volumes and breathing discomfort intensity, assessed by visual analogue scale (VAS) score, were repeatedly measured over a 60-min observation period., Results: Induced bronchoconstriction was accompanied by obvious reductions in lung volumes and increases in VAS score. After salbutamol administration, FEV(1) and VAS score changes were similar in all experimental conditions. However, following 400 microg salbutamol via pMDI + Volumatic, isoFEF(25-75) values increased up to 4.48 l s(-1) (95% confidence interval 4.06, 4.90), a significantly (P < 0.01) higher value than those attained in all other experimental conditions. Independently of the salbutamol dose, lung volumes rose to significantly (P < 0.01) higher levels in pMDI + Volumatic than in Diskus trials. The low salbutamol dose via the pMDI + Volumatic and the high dose via the DPI increased isoFEF(25-75) and lung volumes to similar extents., Conclusions: Salbutamol via the pMDI + Volumatic provides greater isoFEF(25-75) and lung volume increases in asthmatic patients with induced bronchoconstriction; salbutamol-induced changes in VAS scores poorly reflect those in small airway patency. The lack of differences in FEV(1) increases observed after 200 and 400 microg salbutamol may reflect attainment of the flat portion of the dose-response curve using either device.

We investigated the effects of static and rhythmic handgrip on the time course of recovery of airway resistance measured with the interrupter technique (Rint) following bronchoconstriction induced by methacholine (MCh) inhalation in 17 asthmatic patients. On three separate occasions, a 100 +/- 5% increase in baseline Rint was induced by MCh inhalation. Subsequently, patients either rested [control trials (CTs)] or performed 3-min bouts of static or rhythmic handgrip. Respiratory and cardiovascular variables were continuously monitored. Rint changes were assessed at 1-min intervals for 30 min after rest and both types of handgrip. Plasma catecholamine concentrations were also determined at scheduled intervals. Bronchoconstriction increased ventilation (P < 0.01) but did not affect cardiovascular variables and plasma catecholamine concentrations. Handgrip provoked an increase in cardiovascular variables (P < 0.01) and plasma norepinephrine concentrations (P < 0.05) but caused no additional changes in ventilation. Rint only partially recovered within 30 min after CTs, whereas it consistently decreased 1 min after both handgrip paradigms and remained lower than after CTs (P always <0.01) for the whole 30-min observation period. Sympathetic activation and withdrawal of cholinergic input to the airway smooth muscle reflexly induced by activation of skeletal muscle and carotid sinus receptors may be the primary events accounting for the bronchodilator response induced by handgrip. Mediators co-released in response to sympathetic activation may also have contributed.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler® device, a high- or medium–high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases. 5TEfF4YsHYx_1PQHoqCf7D Enhanced feature (slides, video, animation) (MP4 43768 kb) [ABSTRACT FROM AUTHOR]

Purpose: There is a dearth of research regarding the prevalence and nature of patient-reported rhinitis and its relationship with risk of asthma exacerbations. The aim of this study was to (i) determine the prevalence, severity and treatment of self-reported rhinitis symptoms among adults aged ≥ 18 years with asthma treated at Global Initiative for Asthma (GINA) Step 3 and above and (ii) compare the demographics, clinical characteristics, medication use, side-effects and healthcare practitioner review between patients who report rhinitis symptoms and those who do not and (iii) determine whether patient-reported rhinitis is associated with risk of asthma exacerbations in the total patient sample. Patients and Methods: This analysis used data from the iHARP (Initiative Helping Asthma in Real-life Patients) asthma review service – a cross-sectional observational study (2011 and 2014) in seven countries that captured data on patient demographics, rhinitis symptoms, asthma symptoms, indicators of exacerbations, medication use, oropharyngeal effects and side-effects, using practitioner- and patient-reported questionnaires. Comparisons between patients with and without rhinitis were tested. Univariate logistic regression was used to identify variables associated with risk of exacerbations for entry into multivariable logistic regression. Results: This report contains data from 4274 patients: 67.4% (2881/4274) reported rhinitis symptoms and of which 65.7% (1894/2881) had not received a doctor diagnosis; 36.5% (1052/2881) had moderate-severe rhinitis, 12.4% (358/2881) had used intranasal corticosteroids and 19.8% (569/2881) oral antihistamines. Patients with coexisting moderate-severe rhinitis were more likely to have GINA-defined uncontrolled asthma than those with mild rhinitis or no rhinitis. Moderate-severe rhinitis was associated with 40% increased risk of asthma exacerbations (OR=1.40, 95% CI: 1.02– 1.90). Conclusion: This study identified a major gap in the diagnosis and management of rhinitis in a cohort of people with asthma treated at GINA Step 3 and above who are managed in general practice. It highlights the need for practitioners to identify, evaluate and optimally treat rhinitis in adults with asthma, which is a significant factor associated with exacerbation risk. [ABSTRACT FROM AUTHOR]

Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

Pulmonary drug delivery is currently the focus of accelerated research and development because of the potential to produce maximum therapeutic benefit to patients by directly targeting drug to the site of pathology in the lungs. Among the available delivery options, the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. However, because drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is proving to be a great challenge. Development of DPI systems that target the delivery of fine drug particles to the deeper airways in the lungs using a combination of improved drug formulations and enhanced delivery device technologies means that each of these factors contributes to overall performance of the aerosol system. There are a large range of devices that are currently available, or under development, for clinical use, however no individual device shows superior clinical efficacy. A major concern that is very relevant in day-to-day clinical practice is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs from the inhalation devices, where the extent of variability depends on the drug formulation, the device design, and the patient's inhalation profile. This variability may result in under-dosing of drug to the patient and potential loss of pharmacological efficacy. This article reviews recent advances in capsule-based DPI technology and the introduction of the 'disposable' DPI device. [ABSTRACT FROM AUTHOR]

Poor inhaler technique hampers the efficacy of drug therapy in asthma and chronic obstructive pulmonary disease. Not only does this affect individual patient care, but it also impacts on the wider health care economics associated with these conditions. Treatment guidelines recommend a systematic approach to drug class selection; however, standardization of inhaler selection is currently difficult owing to the complexity of the interaction between the inhaler device and the patient. Specifically, individual patient preference can influence how successful a treatment is overall. This article reviews inhaler devices from the patient perspective, with a particular focus on the dry powder inhaler HandiHaler® and Respimat® Soft Mist™ Inhaler. It discusses factors that influence device preference and treatment compliance and reviews tools that can aid health care professionals to better match inhaler devices to individual patients' needs. [ABSTRACT FROM AUTHOR]

Drug delivery to the lungs is an effective way of targeting inhaled therapeutic aerosols and treating obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In the past 10 years, several new drugs for the management of asthma and COPD have been marketed and more are under development. These new therapeutic respiratory drugs have been furthered by innovations in all categories of pulmonary drug delivery systems to ensure optimal aerosolisation performance, consistency in efficacy and satisfactory patient adherence. In this review, we discuss the technological advances and innovations in recent inhaler devices and the evolving roles of pressurised metered-dose inhalers, dry powder inhalers and nebulisers, as well as their impact on patient adherence to treatment. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: For inhaled medications, bioequivalence testing is becoming increasingly important owing to the availability of many inhalation devices. We evaluated agreement between the Finney bioassay and the E max model in the assessment of bioequivalence of salbutamol administered via a metered-dose inhaler with a spacer (pMDI+Volumatic) or via a dry-powder inhaler (Diskus) in asthmatic patients with methacholine-induced bronchoconstriction. Eighteen patients inhaled methacholine until FEV1 decreased by ≈35% of control. Following inhalation of placebo, 200 and 400mcg salbutamol through the pMDI+Volumatic or the Diskus, changes in FEV1 were repeatedly measured over a 60-min observation period. Bioequivalence of salbutamol administered via the two inhalation devices was assessed by calculating the relative potency of each device by using the Finney 2-by-2 parallel regression analysis and the non-linear, E max model. Agreement between these methods in calculating relative potency was evaluated by using the Bland–Altman method. After salbutamol FEV1 values were similar irrespective of the device employed, and greater (P<0.01) than those after placebo. However, assessment of relative potencies obtained with both the Finney (1.97, 90% CI 1.62–2.32) and the E max (2.25, 90% CI 1.90–2.60) methods revealed that twice the salbutamol dose was needed to reverse methacholine-induced bronchoconstriction when the drug was inhaled via the Diskus than via the pMDI+Volumatic. The mean difference in relative potency (−0.28, 90% CI −0.001 to −0.56) calculated with both methods did not significantly differ from zero, and none of the individual differences exceeded the limits of agreement. The Finney and the E max methods provide comparable results in the evaluation of bioequivalence of different salbutamol formulations. The pMDI+Volumatic is twice as efficient as the Diskus in lung delivery of salbutamol in asthma patients. [Copyright &y& Elsevier]

Background: A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/ long acting β2-agonist (ICS/LABA) combinations. Methods: The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/ formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs. Results: The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N=16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N=239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N=257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N=258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N=275/1643), respectively. Conclusions: The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be readily explained by differences in features of the respective studies and may be related to the favorable pharmacological/mechanistic characteristics of the constituent components fluticasone and formoterol compared to other drugs in their respective classes. [ABSTRACT FROM AUTHOR]