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Introduction: Asthma is a common disease with a global burden of 358 million patients. Despite improvements in pharmacological and non-pharmacological treatments, many patients still do not achieve complete asthma control. Therefore, innovative pharmacotherapy is important. Areas covered: Following a semi-structured search in Pubmed, an overview of advances in inhaled asthma therapy is provided, looking at innovations in digital inhalers, eco-friendly inhalers and novel inhaled biologic therapies, antibiotics and vaccines, as well as other potential novel asthma therapy targets. Expert opinion: Digital inhalers, sending reminders and monitoring inhalation technique electronically, can support medication adherence and improve asthma control. To reduce the global warming potential of traditional aerosols used in pressurized metered-dose inhalers (HFA-134a, HFA-227ea), greener alternatives are under development (HFA-152a, HFO-1234ze) that are expected to be available by 2025. Current pharmacological advances in asthma therapy are mainly achieved by novel biologicals (anti-IgE, anti-IL5, anti-IL4/13, and anti-TSLP) targeting specific severe asthma phenotypes. While injection is the usual administration route for biologics and vaccines used in asthma, inhalation is an option being explored, although several (mainly formulation) challenges need to be overcome. Other potential novel future inhaled asthma therapies include anti-IL-33/ST2 biologicals and JAK inhibitors, all still requiring more clinical evidence. [ABSTRACT FROM AUTHOR]

Objective adherence data, to motivate people with asthma to adhere to their medication regimen.Methods: A participatory user-centered design approach was employed, involving end-users and other stakeholders throughout the study. The approach consisted of four phases. Semi-structured interviews and a survey were conducted to understand user needs and reasons for poor adherence (Phase 1: define). Key themes were identified, leading to the formulation of behavior change strategies and design and game requirements. Several design directions were ideated, resulting in a concept for a serious game (Phase 2: ideate). Two rounds of user-tests were performed to evaluate a prototype of the serious game in terms of usability, perceived impact on medication adherence and motivation (Phase 3: prototype and Phase 4: evaluate).Results: Findings from semi-structured interviews (n = 6) and the online survey (n = 20) revealed that people's non-adherence was often attributed to the perception of asthma as an episodic condition, the delayed experienced effect of maintenance inhalers, and lack of knowledge regarding difference of effect between maintenance and reliever inhalers. The study used behavior change strategies to translate these insights into design requirements for the development of the narrative-based persuasive game Ademgenoot. This six-week challenge-based game combines various behavior change strategies, including personal goal setting and continuous visual feedback, as well as persuasive game design elements, such as a narrative and rewards, with the aim of enhancing motivation to adhere to their medication regimen. User-testing (n = 8; round 1 and 2) showed that Ademgenoot is feasible in clinical practice and has the potential to support people with mild asthma in adherence to their maintenance medication.Discussion: Future efforts should be directed towards a larger evaluation to assess the impact on motivation and inhaler use behaviour.Plain Language Summary: The goal of this study was to create a serious game that encourages people with asthma to take their medication regularly. During the study, we worked closely with individuals who have asthma and other stakeholders throughout the study. We conducted interviews and surveys to understand why people have difficulties using their maintenance inhaler as prescribed by their doctor. Based on the feedback we received, we developed a serious game called "Ademgenoot". The game uses information on inhaler use automatically collected with a device attached to the inhaler. The game includes features like personal goals and visual feedback on inhaler use to motivate users to take their medication consistently. We tested a prototype of the game with users to see if it was easy to use and if it motivated them to use their maintenance inhaler. The results showed that Ademgenoot is a viable option for helping individuals with mild asthma stay on track with their medication.Key words: medication adherence, serious game design, behavior change, adherence monitoring, participatory design [ABSTRACT FROM AUTHOR]

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 number NL7854., Competing Interests: Competing interests: JWK reports grants, personal fees and non-financial support outside the submitted work from AstraZeneca; grants, personal fees and non-financial support from Boehringer Ingelheim and GSK; grants and personal fees from Chiesi Pharmaceuticals and TEVA; grants from Mundi Pharma; and personal fees from MSD and COVIS Pharma. JWK also holds 72.5% of shares in the General Practitioners Research Institute. JFMvB received grants and/or consultancy fees from AstraZeneca, Chiesi, European Commission COST (COST Action 19132), GSK, Novartis, Teva and Trudell Medical, outside the submitted work and all paid to his institution. BFdB was employed by General Practitioners Research Institute (GPRI) at the time of the study. In the past three years (2019–2021), GPRI conducted investigator-initiated and sponsor-initiated research funded by non-commercial organisations, academic institutes and pharmaceutical companies (including AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis and Teva)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Medication adherence and inhaler technique in patients with asthma remain suboptimal. A digital, smart spacer may support personalised adherence and inhaler technique education. The aim of this study is to assess the feasibility of undertaking a definitive randomised controlled trial of personalised, smart spacer data-driven education and explore clinical benefits., Methods and Analysis: We present the design of the multicentre, randomised controlled OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE feasibility trial of 2 months. Patients will be recruited from four Dutch general practices. At t=-1, patients with asthma ≥18 years using inhaled corticosteroids±long-acting beta-agonists±short-acting beta-agonists administered with a pressurised-metered-dose-inhaler and spacer (n=40) will use a smart spacer for 1 month. The rechargeable CE-marked smart spacer (Aerochamber Plus with Flow Vu) includes a sensor that monitors adherence and inhalation technique to prescribed dosing regimen of both maintenance and reliever inhalers. After 1 month (t=0), patients are 1:1 randomised into two groups: control group (usual care) versus intervention group (personalised education). At t=-1, t=0 and t=1 month, the Asthma Control Questionnaire (ACQ), Work Productivity and Activity Impairment (WPAI) questionnaire and Test of Adherence to Inhalers (TAI) are administered and fractional exhaled nitric oxide (FeNO) is assessed. At t=0 and t=1, spirometry is performed. At t=1, usability and satisfaction will be analysed using the System Usability Scale and interviews with patients and healthcare providers. Primary outcome is the overall feasibility of a definitive trial assessed by patient recruitment speed, participation and drop-out rate. Secondary outcomes are patient and healthcare provider satisfaction and exploratory clinical outcomes are adherence, inhaler technique, TAI score, FeNO, lung function, ACQ and WPAI., Ethics and Dissemination: Ethical approval was obtained from the RTPO in Leeuwarden, Netherlands (number: NL78361.099.21). Patients will provide written informed consent. Study findings will be disseminated through conferences and peer-reviewed scientific and professional journals., Trial Registration Number: NL9637., Competing Interests: Competing interests: HAMK reports a fee for a one time consultancy outside the realm of this study, and grants and fees for consultancy or advisory board participation from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis all outside of the submitted work. All were paid to his institution. JK reports grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Boehringer Ingelheim, grants and personal fees from Chiesi Pharmaceuticals, grants, personal fees and non-financial support from GSK, grants from Mundi Pharma, grants and personal fees from TEVA, personal fees from MSD, personal fees from COVIS Pharma, outside the submitted work; and Janwillem Kocks holds 72.5% of shares in the General Practitioners Research Institute. JFMvB received grants and/or consultancy fees from AstraZeneca, Chiesi, European Commission COST (COST Action 19132), GSK, Lung Alliance Netherlands, Novartis, Teva, and Trudell Medical, outside the submitted work and all paid to his institution. Other authors declare no relevant conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Medication non-adherence to asthma and chronic obstructive pulmonary disease therapy poses a significant burden for patients and societies. Non-adherence encompasses poor initiation, implementation (including poor inhalation technique) and non-persistence. Globally, non-adherence is associated with poor clinical outcomes, reduced quality of life and high healthcare and societal costs. Costs are mainly caused by excess hospitalizations and impaired work productivity. Multiple intervention programs to increase adherence in patients with asthma and chronic obstructive pulmonary disease have been conducted. However, these intervention programs are generally not as effective as intended. Additionally, adherence outcomes are mostly examined with non-objective or non-granular measures (e.g., self-report, dose count, pharmacy records). Recently developed smart inhalers could be the key to objectively diagnose and manage non-adherence effectively in patients with asthma and chronic obstructive pulmonary disease. Smart inhalers register usage of the inhaler, record time and date, send reminders, give feedback about adherence and some are able to assess inhaler technique and predict exacerbations. Still, some limitations need to be overcome before smart inhalers can be incorporated in usual care. For example, their cost-effectiveness and budget impact need to be examined. It is likely that smart inhalers are particularly cost-effective in specific asthma and chronic obstructive pulmonary disease subgroups, including patients with asthma eligible for additional GINA-5 therapy (oral corticosteroids or biologics), patients with severe asthma in GINA-5, patients with asthma with short-acting beta2 agonists overuse, patients with asthma and chronic obstructive pulmonary disease with frequent exacerbations and patients with asthma and chronic obstructive pulmonary disease of working-age. While there is high potential and evidence is accumulating, a final push seems needed to cost-effectively integrate smart inhalers in the daily management of patients with asthma and chronic obstructive pulmonary disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2360). Dr. HAMK reports research grants from GSK, Novartis, and Boehringer, and fees for consultancies in advisory boards from Chiesi, GSK, Novartis, and Boehringer, all paid to his institution. Dr. JWHK reports grants and non-financial support from AstraZeneca, grants and non-financial support from Boehringer Ingelheim, grants from Chiesi Pharmaceuticals, grants and non-financial support from GSK, grants from Novartis, grants from MundiPharma, grants from TEVA, from null, outside the submitted work; and Dr. JWHK holds 72.5% of shares in the General Practitioners Research Institute. Dr. JFMvB reports grants from AstraZeneca, grants and personal fees from Chiesi, personal fees from Teva, grants and personal fees from Trudell medical, personal fees from Novartis, personal fees from Boehringer Ingelheim, outside the submitted work and all paid to his institution. Dr. JFMvB receives funding from European Commission COST Action 19132 (European Network to Advance Best practices & technoLogy on medication adherence). The authors have no other conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Competing Interests: Conflict of interest: J.F.M. van Boven has nothing to disclose. Conflict of interest: S.J. van de Hei has nothing to disclose. Conflict of interest: M. Sadatsafavi has nothing to disclose.