Usability and feasibility of the Test of Adherence to Inhalers (TAI) Toolkit in daily clinical practice: The BANANA study.

The Test of Adherence to Inhalers (TAI) Toolkit links an adherence measurement instrument (the TAI) to proven effective interventions for different causes of non-adherence to inhaled medication. This study aimed to assess the usability and feasibility of the TAI Toolkit in clinical practice. The TAI Toolkit was piloted in eight primary and secondary care settings. Each study site included 10 patients with asthma and/or COPD and suspected non-adherence. Healthcare professionals (HCPs) recorded clinical data and TAI Toolkit outcomes. Data on usability and feasibility were collected in semi-structured interviews and with the System Usability Score (SUS). Of the included patients, 81% were non-adherent, and sporadic non-adherence was the most common (69%). The TAI Toolkit was valued with a mean SUS-score of 85.9 by the HCPs. They found the toolkit to 'be visually attractive', 'easy-to-use' and 'give insight into patients' adherence', thereby offering good potential for its use in clinical practice.

Implications of Cardiopulmonary Risk for the Management of COPD: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) constitutes a major global health burden and is the third leading cause of death worldwide. A high proportion of patients with COPD have cardiovascular disease, but there is also evidence that COPD is a risk factor for adverse outcomes in cardiovascular disease. Patients with COPD frequently die of respiratory and cardiovascular causes, yet the identification and management of cardiopulmonary risk remain suboptimal owing to limited awareness and clinical intervention. Acute exacerbations punctuate the progression of COPD in many patients, reducing lung function and increasing the risk of subsequent exacerbations and cardiovascular events that may lead to early death. This narrative review defines and summarises the principles of COPD-associated cardiopulmonary risk, and examines respiratory interventions currently available to modify this risk, as well as providing expert opinion on future approaches to addressing cardiopulmonary risk.

Does mixing inhaler devices lead to unchecked inhaler technique errors in patients with COPD? Findings from the cross-sectional observational MISMATCH study.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that it leads to inappropriate inhaler technique. However, empirical evidence is lacking. AIMS: Compare the nature and frequency of dry powder inhaler (DPI) technique errors in patients with COPD using (1) a single DPI or (2) mixed-devices (a DPI and pressurised metered dose inhaler (pMDI)). METHODS: Data from the PIFotal study-a cross-sectional study on Peak Inspiratory Flow in patients with COPD using a DPI as maintenance therapy, capturing data from 1434 patients on demographic characteristics, COPD health status and inhaler technique-were used to select 291 patients using mixed-devices. Frequency matching based on country of residence and DPI device type was used to select 291 patients using a DPI-only for comparison. Predetermined checklists were used for the evaluation of DPI video recordings and complemented with additional errors that were observed in ≥10%. Error proportions were calculated for the (1) individual and total number of errors, (2) number of critical errors and (3) number of pMDI-related errors. RESULTS: The study sample contained 582 patients (mean (SD) age 69.6 (9.4) years, 47.1% female). DPI technique errors were common, but not significantly different between the groups. The majority of patients made at least one critical error (DPI-only: 90.7% vs mixed-devices: 92.8%). Proportions of total, 'pMDI-related' and critical errors did not significantly differ between the groups. CONCLUSION: The nature and frequency of inhaler technique errors did not substantially differ between patients prescribed with a single DPI and mixed-devices. Currently, 'pMDI-related errors' in DPI use are not accounted for in existing checklists. TRIAL REGISTRATION NUMBER: ENCEPP/EUPAS48776.

Overcoming the Digital Divide for Older Patients With Respiratory Disease: Focus Group Study.

BACKGROUND: The need for and adoption of eHealth programs are growing worldwide. However, access can be limited among patients with low socioeconomic backgrounds, often resulting in a so-called "digital divide" due to a mismatch between eHealth and target populations that can gain benefit. This digital divide can result in unsuccessful eHealth implementations, which is of critical importance to health care. OBJECTIVE: This study evaluated the opinions of elderly patients with asthma and chronic obstructive pulmonary disease (COPD) about an existing pharmacy-based personalized patient web portal that provides medication overview and information on associated diagnoses. The aim was to obtain insights on the common barriers of elderly people when using health-related websites, which can help to improve accessibility. METHODS: This was a cross-sectional qualitative study of a patient panel of the Groningen Research Institute for Asthma and COPD in primary care. Participants were required to be older than 55 years, be Dutch speaking, have no prior experience with the study website, and be diagnosed with a chronic respiratory illness. Two focus groups were created, and they completed a 45-minute session for testing the website and a 120-minute session for semistructured interviews. The focus group sessions were recorded, transcribed verbatim, and analyzed by content analysis. RESULTS: We enrolled 11 patients (9 women) with a mean age of 66 (SD 9) years. Of these, 5 had asthma, 3 had COPD, 2 had asthma-COPD overlap syndrome, and 1 had bronchiectasis. Participants were generally positive about the website, especially the areas providing disease-related information and the medication overview. They appreciated that the website would enable them to share this information with other health care providers. However, some difficulties were reported with navigation, such as opening a new tab, and others reported that the layout of the website was difficult either because of visual impairments or problems with navigation. It was also felt that monitoring would only be relevant if it is also checked by health care professionals as part of a treatment plan. Participants mentioned few privacy or safety concerns. CONCLUSIONS: It is feasible to develop websites for elderly patients; however, developers must take the specific needs and limitations of elderly people into account (eg, navigation problems, poor vision, or poor hand-eye coordination). The provision of information appears to be the most important aspect of the website, and as such, we should endeavor to ensure that the layout and navigation remain basic and accessible. Patients are only motivated to use self-management applications if they are an integrated part of their treatment. The usability of the website can be improved by including older people during development and by implementing design features that can improve accessibility in this group.

The Use of eHealth for Pharmacotherapy Management With Patients With Respiratory Disease, Cardiovascular Disease, or Diabetes: Scoping Review.

BACKGROUND: eHealth is increasingly considered an important tool for supporting pharmacotherapy management. OBJECTIVE: We aimed to assess the (1) use of eHealth in pharmacotherapy management with patients with asthma or chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD); (2) effectiveness of these interventions on pharmacotherapy management and clinical outcomes; and (3) key factors contributing to the success of eHealth interventions for pharmacotherapy management. METHODS: We conducted a scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review) statement. Databases searched included Embase, MEDLINE (PubMed), and Cochrane Library. Screening was conducted by 2 independent researchers. Eligible articles were randomized controlled trials and cohort studies assessing the effect of an eHealth intervention for pharmacotherapy management compared with usual care on pharmacotherapy management or clinical outcomes in patients with asthma or COPD, CVD, or diabetes. The interventions were categorized by the type of device, pharmacotherapy management, mode of delivery, features, and domains described in the conceptual model for eHealth by Shaw at al (Health in our Hands, Interacting for Health, Data Enabling Health). The effectiveness on pharmacotherapy management outcomes and patient- and clinician-reported clinical outcomes was analyzed per type of intervention categorized by number of domains and features to identify trends. RESULTS: Of 63 studies, 16 (25%), 31 (49%), 13 (21%), and 3 (5%) included patients with asthma or COPD, CVD, diabetes, or CVD and diabetes, respectively. Most (38/63, 60%) interventions targeted improving medication adherence, often combined for treatment plan optimization. Of the 16 asthma or COPD interventions, 6 aimed to improve inhaled medication use. The majority (48/63, 76%) of the studies provided an option for patient feedback. Most (20/63, 32%) eHealth interventions combined all 3 domains by Shaw et al, while 25% (16/63) combined Interacting for Health with Data Enabling Health. Two-thirds (42/63, 67%) of the studies showed a positive overall effect. Respectively, 48% (23/48), 57% (28/49), and 39% (12/31) reported a positive effect on pharmacotherapy management and clinician- and patient-reported clinical outcomes. Pharmacotherapy management and patient-reported clinical outcomes, but not clinician-reported clinical outcomes, were more often positive in interventions with ≥3 features. There was a trend toward more studies reporting a positive effect on all 3 outcomes with more domains by Shaw et al. Of the studies with interventions providing patient feedback, more showed a positive clinical outcome, compared with studies with interventions without feedback. This effect was not seen for pharmacotherapy management outcomes. CONCLUSIONS: There is a wide variety of eHealth interventions combining various domains and features to target pharmacotherapy management in asthma or COPD, CVD, and diabetes. Results suggest feedback is key for a positive effect on clinician-reported clinical outcomes. eHealth interventions become more impactful when combining domains.

Identifying critical inhalation technique errors in Dry Powder Inhaler use in patients with COPD based on the association with health status and exacerbations: findings from the multi-country cross-sectional observational PIFotal study.

BACKGROUND: Correct inhaler use depends on a complex interplay of factors, including device preparation and generating sufficient inspiratory flow. It is currently unknown which inhalation technique errors can be considered critical in Chronic Obstructive Pulmonary Disease (COPD) patients on Dry Powder Inhaler (DPI) maintenance therapy. OBJECTIVE: To investigate the association between inhalation technique errors and health status or exacerbations in patients with COPD. Additionally, the association between the number of errors and COPD outcomes was determined. METHODS: The PIFotal study is a cross-sectional multi-country observational study in a primary care setting, including 1434 COPD patients aged ≥ 40 years (50.1% female; mean age 69.2 yrs) using a DPI for their maintenance therapy. Inhalation technique was video recorded and scored by two independent researchers using inhaler-specific checklists. Health status was assessed with two questionnaires; the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT). The number of moderate and severe exacerbations in the past 12 months was recorded. Critical errors were identified based on their association with health status or exacerbations through multi-level prediction models adjusted for identified confounding. RESULTS: Errors in inhalation technique steps 'Breathe in', 'Hold breath', and 'Breathe out calmly after inhalation' were significantly associated with poorer CCQ and CAT outcomes and thus deemed critical. None of the errors were significantly associated with moderate exacerbations. Patients with errors 'Preparation', 'Hold inhaler in correct position during inhalation', and 'Breathe in' had significantly more severe exacerbations, and therefore these errors were also deemed critical. 81.3% of patients with COPD made at least one critical error. Specific combinations of errors were associated with worse outcomes. The more inhalation technique errors identified, the poorer the health status and the higher the exacerbation rate. CONCLUSION: In this study, we identified multiple critical inhalation technique errors in COPD patients using DPIs each associated with poorer outcomes. Explorative analysis revealed that specific combinations of errors may be of clinical relevance, especially those related to the inhalation manoeuvre. COPD outcomes worsened with increasing error count. These results warrant further prospective longitudinal studies to establish the effect of correcting these errors on COPD control. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04532853 (31/08/2020).

Electronic monitoring with a digital smart spacer to support personalized inhaler use education in patients with asthma: The randomized controlled OUTERSPACE trial.

BACKGROUND: Poor adherence to inhaled medication has been associated with poor outcomes. Smart spacers can monitor inhaler use and technique, yet their feasibility in adults with asthma and their potential benefits are unknown. OBJECTIVE: Assessing the feasibility of undertaking a definitive randomized controlled trial (RCT) of smart spacer-based inhaler education and explore potential clinical benefits in adults with asthma. METHODS: Two-month randomized controlled feasibility OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE (OUTERSPACE) trial comparing personalized smart spacer-based inhaler education versus usual care. Patients were recruited in four Dutch primary care centres. Outcomes were feasibility (inclusion speed, patient acceptance), medication adherence, inhaler technique, clinical effects (lung function, ACQ, FeNO) and usability (System Usability Scale [SUS]). RESULTS: 42 patients were randomized and all completed the study. The feasibility of performing a larger trial focusing on asthma patient education using a smart spacer was demonstrated with all patients included in four months and a participation rate of 86%. In the intervention group, inhalation errors per day decreased by 26.2% while in the usual care group inhalation errors increased by 14.6% (p = 0.021). Adherence decreased slightly in the intervention group as opposed to improvement in the control group (difference 12%, p = 0.028). No changes in lung function, ACQ or FeNO were observed. Usability was deemed high (SUS patients 71, nurses 89). CONCLUSION: This RCT showed that smart spacer-driven education in patients with asthma is feasible and in this short-term study reduced inhaler errors. Longer-term and larger studies are required to assess clinical effects.

Long-Term Cost-Effectiveness of Digital Inhaler Adherence Technologies in Difficult-to-Treat Asthma.

BACKGROUND: Digital inhalers can monitor inhaler usage, support difficult-to-treat asthma management, and inform step-up treatment decisions yet their economic value is unknown, hampering wide-scale implementation. OBJECTIVE: We aimed to assess the long-term cost-effectiveness of digital inhaler-based medication adherence management in difficult-to-treat asthma. METHODS: A model-based cost-utility analysis was performed. The Markov model structure was determined by biological and clinical understanding of asthma and was further informed by guideline-based assessment of model development. Internal and external validation was performed using the Assessment of the Validation Status of Health-Economic (AdViSHE) tool. The INCA (Inhaler Compliance Assessment) Sun randomized clinical trial data were incorporated into the model to evaluate the cost-effectiveness of digital inhalers. Several long-term clinical case scenarios were assessed (reduced number of exacerbations, increased asthma control, introduction of biosimilars [25% price-cut on biologics]). RESULTS: The long-term modelled cost-effectiveness based on a societal perspective indicated 1-year per-patient costs for digital inhalers and usual care (ie, regular inhalers) of €7,546 ($7,946) and €10,752 ($11,322), respectively, reflecting cost savings of €3,207 ($3,377) for digital inhalers. Using a 10-year intervention duration and time horizon resulted in cost savings of €26,309 ($27,703) for digital inhalers. In the first year, add-on biologic therapies accounted for 69% of the total costs in the usual care group and for 49% in the digital inhaler group. Scenario analyses indicated consistent cost savings ranging from €2,287 ($2,408) (introduction biosimilars) to €4,581 ($4,824) (increased control, decreased exacerbations). CONCLUSIONS: In patients with difficult-to-treat asthma, digital inhaler-based interventions can be cost-saving in the long-term by optimizing medication adherence and inhaler technique and reducing add-on biologic prescriptions.

Anticipated barriers and facilitators for implementing smart inhalers in asthma medication adherence management.

Smart inhalers are electronic monitoring devices which are promising in increasing medication adherence and maintaining asthma control. A multi-stakeholder capacity and needs assessment is recommended prior to implementation in healthcare systems. This study aimed to explore perceptions of stakeholders and to identify anticipated facilitators and barriers associated with the implementation of smart digital inhalers in the Dutch healthcare system. Data were collected through focus group discussions with female patients with asthma (n = 9) and healthcare professionals (n = 7) and through individual semi-structured interviews with policy makers (n = 4) and smart inhaler developers (n = 4). Data were analysed using the Framework method. Five themes were identified: (i) perceived benefits, (ii) usability, (iii) feasibility, (iv) payment and reimbursement, and (v) data safety and ownership. In total, 14 barriers and 32 facilitators were found among all stakeholders. The results of this study could contribute to the design of a tailored implementation strategy for smart inhalers in daily practice.

Investigating the rationale for COPD maintenance therapy prescription across Europe, findings from a multi-country study.

This study aims to understand healthcare professionals' thoughts and motivations about optimal management and treatment of patients with chronic obstructive pulmonary disease (COPD). We conducted a DELPHI survey through an online questionnaire distributed to 220 panellists from six European countries and a discrete choice experiment to describe the relationship between selected clinical criteria and the initial COPD treatment of choice. One hundred twenty-seven panellists (general practitioners [GPs] and pulmonologists) completed the survey. Despite the familiarity and use (89.8%) of the GOLD classification for initial treatment selection, a frequent use of LAMA/LABA/ICS was noted. In fact, panellists agreed that inhaled corticosteroids (ICS) are over-prescribed in the primary care setting. Our study showed that GPs felt less confident than pulmonologists with ICS withdrawal. This mismatch observed between best practice and behaviour indicates the need to increase awareness and efforts to improve the adherence to guidelines in clinical practice.

Recognizing and Tackling Inhaler Technique Decay in Asthma and Chronic Obstructive Pulmonary Disesase (COPD) Clinical Practice.

A poor inhaler technique continues to represent a substantial barrier to effective asthma and chronic obstructive pulmonary disease management. It can result in perceived lack of treatment effectiveness even with apparent adherence to a prescribed regimen of inhaled maintenance therapies, potentially resulting in an unnecessary change or escalation of treatment. Many patients are not trained to inhaler mastery in real-world practice; furthermore, even where mastery is initially achieved, an ongoing assessment and education are seldom maintained. In this review, we present an overview of the evidence for deterioration of the inhaler technique over time after training, investigate the factors that contribute to this deterioration, and explore innovative approaches to addressing the problem. We also propose steps forward drawn from the literature and our clinical insights.

A Charter to Fundamentally Change the Role of Oral Corticosteroids in the Management of Asthma.

Asthma affects 339 million people worldwide, with an estimated 5-10% experiencing severe asthma. In emergency settings, oral corticosteroids (OCS) can be lifesaving, but acute and long-term treatment can produce clinically important adverse outcomes and increase the risk of mortality. Therefore, global guidelines recommend limiting the use of OCS. Despite the risks, research indicates that 40-60% of people with severe asthma are receiving or have received long-term OCS treatment. Although often perceived as a low-cost option, long-term OCS use can result in significant health impairments and costs owing to adverse outcomes and increased utilization of healthcare resources. Alternative treatment methods, such as biologics, may produce cost-saving benefits with a better safety profile. A comprehensive and concerted effort is necessary to tackle the continued reliance on OCS. Accordingly, a threshold for OCS use should be established to help identify patients at risk of OCS-related adverse outcomes. Receiving a total dose of more than 500 mg per year should trigger a review and specialist referral. Changes to national and local policies, following examples from other chronic diseases, will be crucial to achieving this goal. Globally, multiple barriers to change still exist, but specific steps have been identified to help clinicians reduce reliance on OCS. Implementing these changes will result in positive health outcomes for patients and social and economic benefits for societies.

Budesonide/formoterol maintenance and reliever therapy versus fluticasone/salmeterol fixed-dose treatment in patients with COPD.

BACKGROUND: Maintenance and reliever therapy (MART) with inhaled corticosteroid (ICS)/formoterol effectively reduces exacerbations in asthma. We aimed to investigate its efficacy compared with fixed-dose fluticasone/salmeterol in chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD and ≥1 exacerbation in the previous 2 years were randomly assigned to open-label MART (Spiromax budesonide/formoterol 160/4.5 µg 2 inhalations twice daily+1 prn) or fixed-dose therapy (Diskus fluticasone propionate/salmeterol combination (FSC) 500/50 µg 1 inhalation twice daily+salbutamol 100 µg prn) for 1 year. The primary outcome was rate of moderate/severe exacerbations, defined by treatment with oral prednisolone and/or antibiotics. RESULTS: In total, 195 patients were randomised (MART Bud/Form n=103; fixed-dose FSC n=92). No significant difference was seen between MART and FSC therapy in exacerbation rates (1.32 vs 1.32 /year, respectively, rate ratio 1.05 (95% CI 0.79 to 1.39); p=0.741). No differences in lung function parameters or health status were observed. Total ICS dose was significantly lower with MART than FSC therapy (budesonide-equivalent 928 µg/day vs 1747 µg/day, respectively, p<0.05). Similar proportions of patients reported adverse events (MART Bud/Form: 73% vs fixed-dose FSC: 68%, p=0.408) and pneumonias (MART: 5% vs FSC: 1%, p=0.216). CONCLUSIONS: This first study of MART in COPD found that budesonide/formoterol MART might be similarly effective to fluticasone/salmeterol fixed-dose therapy in moderate to severe patients with COPD, at a lower daily ICS dosage. Further evidence is needed about long-term safety.

Diagnostic Performance of a Machine Learning Algorithm (Asthma/Chronic Obstructive Pulmonary Disease [COPD] Differentiation Classification) Tool Versus Primary Care Physicians and Pulmonologists in Asthma, COPD, and Asthma/COPD Overlap.

BACKGROUND: The differential diagnosis of asthma and chronic obstructive pulmonary disease (COPD) poses a challenge in clinical practice and its misdiagnosis results in inappropriate treatment, increased exacerbations, and potentially death. OBJECTIVE: To investigate the diagnostic accuracy of the Asthma/COPD Differentiation Classification (AC/DC) tool compared with primary care physicians and pulmonologists in asthma, COPD, and asthma-COPD overlap. METHODS: The AC/DC machine learning-based diagnostic tool was developed using 12 parameters from electronic health records of more than 400,000 patients aged 35 years and older. An expert panel of three pulmonologists and four general practitioners from five countries evaluated 119 patient cases from a prospective observational study and provided a confirmed diagnosis (n = 116) of asthma (n = 53), COPD (n = 43), asthma-COPD overlap (n = 7), or other (n = 13). Cases were then reviewed by 180 primary care physicians and 180 pulmonologists from nine countries and by the AC/DC tool, and diagnostic accuracies were compared with reference to the expert panel diagnoses. RESULTS: Average diagnostic accuracy of the AC/DC tool was superior to that of primary care physicians (median difference, 24%; 95% posterior credible interval: 17% to 29%; P < .0001) and was noninferior and superior (median difference, 12%; 95% posterior credible interval: 6% to 17%; P < .0001 for noninferiority and P = .0006 for superiority) to that of pulmonologists. Average diagnostic accuracies were 73%, 50%, and 61% by AC/DC tool, primary care physicians, and pulmonologists versus expert panel diagnosis, respectively. CONCLUSION: The AC/DC tool demonstrated superior diagnostic accuracy compared with primary care physicians and pulmonologists in the diagnosis of asthma and COPD in patients aged 35 years and greater and has the potential to support physicians in the diagnosis of these conditions in clinical practice.

Development of a tool to detect small airways dysfunction in asthma clinical practice.

BACKGROUND: Small airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of the Small Airways Dysfunction Tool (SADT) questionnaire, basic patient characteristics and respiratory tests available depending on the clinical setting to predict SAD in asthma. METHODS: This study was based on the data of the multinational ATLANTIS (Assessment of Small Airways Involvement in Asthma) study including the earlier developed SADT questionnaire. Key SADT items together with clinical information were now used to build logistic regression models to predict SAD group (less likely or more likely to have SAD). Diagnostic ability of the models was expressed as area under the receiver operating characteristic curve (AUC) and positive likelihood ratio (LR+). RESULTS: SADT item 8, "I sometimes wheeze when I am sitting or lying quietly", and the patient characteristics age, age at asthma diagnosis and body mass index could reasonably well detect SAD (AUC 0.74, LR+ 2.3). The diagnostic ability increased by adding spirometry (percentage predicted forced expiratory volume in 1 s: AUC 0.87, LR+ 5.0) and oscillometry (resistance difference between 5 and 20 Hz and reactance area: AUC 0.96, LR+ 12.8). CONCLUSIONS: If access to respiratory tests is limited (e.g. primary care in many countries), patients with SAD could reasonably well be identified by asking about wheezing at rest and a few patient characteristics. In (advanced) hospital settings patients with SAD could be identified with considerably higher accuracy using spirometry and oscillometry.

Effect of Stepping Up to High-Dose Inhaled Corticosteroids in Patients With Asthma: UK Database Study.

BACKGROUND: It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICSs). OBJECTIVE: To determine the effectiveness of stepping up to high-dose ICSs. METHODS: A historic cohort study of patients with asthma (≥13 years old), identified from 2 large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICSs were compared with those who stepped up from medium- to high-dose ICSs, whereas patients who stepped up from low- to medium-dose ICSs were compared with those who stepped up from low- to high-dose ICSs. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and the number of exacerbations and antibiotics courses was analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding. RESULTS: The mean follow-up time to first exacerbation was 2.7 ± 2.7 years for those who remained on stable medium-dose ICSs and 2.0 ± 2.2 years for those who stepped up from medium- to high-dose ICSs. A similar pattern was noted for those who stepped up from low- to medium-dose ICSs (2.6 ± 2.5 years) and from low- to high-dose ICSs (2.3 ± 2.5 years). Patients who stepped up from medium- to high-dose ICSs (n = 6879) had a higher risk of exacerbations during follow-up compared with those who remained on medium-dose ICSs (n = 51,737; hazard ratio, 1.17; 95% CI, 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n = 3232) compared with low- to medium-dose (n = 12,659) ICSs (hazard ratio, 1.10; 95% CI, 1.04-1.17). A step-up to high-dose ICSs was also associated with a higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts. CONCLUSIONS: We found no evidence that a step-up to high-dose ICSs is effective in preventing future asthma exacerbations.

Effectiveness, usability and acceptability of a smart inhaler programme in patients with asthma: protocol of the multicentre, pragmatic, open-label, cluster randomised controlled ACCEPTANCE trial.

INTRODUCTION: Suboptimal asthma control is associated with incorrect inhaler use and poor medication adherence, which could lead to unfavourable clinical and economic outcomes. Smart inhaler programmes using electronic monitoring devices (EMDs) could support self-management and increase medication adherence and asthma control. However, evidence on long-term benefits and acceptability is scarce. This study aims to investigate the effectiveness of a smart inhaler asthma self-management programme on medication adherence and clinical outcomes in adults with uncontrolled asthma, to evaluate its acceptability and to identify subgroups who would benefit most based on patient characteristics. METHODS AND ANALYSIS: This open-label cluster randomised controlled trial of 12 months will be conducted in primary care in the Netherlands. General practices will be randomly assigned to either intervention or control group. We aim to include 242 patients. The intervention consists of (1) an EMD attached to the patient's inhaler that measures medication use; (2) a smartphone application to set medication reminders, receive motivational messages and track asthma symptoms; and (3) a portal for healthcare professionals to view data on medication use. The control group is passively monitored by the EMD but cannot view their inhaler data or receive feedback. Eligible patients are adults with suboptimal controlled asthma (Asthma Control Questionnaire score ≥0.75) with evidence of non-adherence established by the EMD during a 6-week run-in period. Primary outcome is the difference in mean medication adherence between intervention and control group. Secondary outcomes include asthma control, asthma-related quality of life, exacerbations, acceptance, cost-effectiveness and whether the effect of the intervention on medication adherence and asthma control is modified by patient characteristics (eg, self-efficacy, medication beliefs and eHealth literacy).Trial registration numberNL7854.

Clinical recommendations for dry powder inhaler use in the management of COPD in primary care.

Over 1400 patients using dry powder inhalers (DPIs) to deliver COPD maintenance therapies were recruited across Europe and Australia. Their peak inspiratory flow (PIF) was measured, inhaler technique was observed, and adherence to treatment assessed. From relating the findings with patient health status, and thereby identifying critical errors, key clinical recommendations for primary care clinicians were determined, namely - measure PIF before prescribing a DPI to ensure inhalation manoeuvre ability is well-matched with the device. Some patients could benefit from inhalation training whereas others should have their DPI changed for one better suited to their inspiratory ability or alternatively be prescribed an active device (such as a soft mist inhaler or pressurized metered dose inhaler). Observing the inhalation technique was valuable however this misses suboptimal PIF (approaching one fourth of patients with a satisfactory observed manoeuvre had a suboptimal PIF for their DPI). Assess adherence as deliberate non-adherence can point to a mismatch between a patient and their inhaler (deliberate non-adherence was significantly associated with PIFs below the minimum for the DPI). In-person observation of inhalation technique was found to be inferior to video rating based on device-specific checklists. Where video assessments are not possible, observation training for healthcare professionals would therefore be valuable particularly to improve the ability to identify the critical errors associated with health status namely 'teeth and lips sealed around mouthpiece', 'breathe in' and 'breathing out calmly after inhalation'. However, it is recommended that observation alone should not replace PIF measurement in the DPI selection process.Trial registration: https://clinicaltrials.gov/ct2/show/NCT04532853 .

Digital Coaching Using Smart Inhaler Technology to Improve Asthma Management in Patients With Asthma in Italy: Community-Based Study.

BACKGROUND: Reliance on short-acting ß-2 agonists and nonadherence to maintenance medication are associated with poor clinical outcomes in asthma. Digital health solutions could support optimal medication use and therefore disease control in patients with asthma; however, their use in community settings has not been determined. OBJECTIVE: The primary objective of this study is to investigate community implementation of the Turbu+ program designed to support asthma self-management, including adherence to budesonide and formoterol (Symbicort) Turbuhaler, a combination inhaler for both maintenance therapy or maintenance and reliever therapy. The secondary objective is to provide health care professionals with insights into how patients were using their medication in real life. METHODS: Patients with physician-diagnosed asthma were prescribed budesonide and formoterol as maintenance therapy, at a dose of either 1 inhalation twice daily (1-BID) or 2 inhalations twice daily (2-BID), or as maintenance and reliever therapy (1-BID and reliever or 2-BID and reliever in a single inhaler), and they received training on Turbu+ in secondary care centers across Italy. An electronic device attached to the patients' inhaler for ≥90 days (data cutoff) securely uploaded medication use data to a smartphone app and provided reminders, visualized medication use, and motivational nudge messages. Average medication adherence was defined as the proportion of daily maintenance inhalations taken as prescribed (number of recorded maintenance actuations per day or maintenance inhalations prescribed per day) averaged over the monitoring period. The proportion of adherent days was defined as the proportion of days when all prescribed maintenance inhalations were taken on a given day. The Wilcoxon test was used to compare the proportion of adherent days between patients in the maintenance regimen and patients in the maintenance and reliever regimen of a given dose. RESULTS: In 661 patients, the mean (SD) number of days monitored was 217.2 (SD 109.0) days. The average medication adherence (maintenance doses taken/doses prescribed) was 70.2% (108,040/153,820) overall and was similar across the groups (1-BID: 6332/9520, 66.5%; 1­BID and reliever: 43,578/61,360, 71.0%; 2-BID: 10,088/14,960, 67.4%; 2-BID and reliever: 48,042/67,980, 70.7%). The proportion of adherent days (prescribed maintenance doses/doses taken in a given day) was 56.6% (31,812/56,175) overall and was higher with maintenance and reliever therapy (1-BID and reliever vs 1-BID: 18,413/30,680, 60.0% vs 2510/4760, 52.7%; P<.001; 2-BID and reliever vs 2-BID: 8995/16,995, 52.9% vs 1894/3740, 50.6%; P=.02). Rates of discontinuation from the Turbu+ program were significantly lower with maintenance and reliever therapy compared with maintenance therapy alone (P=.01). CONCLUSIONS: Overall, the high medication adherence observed during the study might be attributed to the electronic monitoring and feedback mechanism provided by the Turbu+ program.