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Background: The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods., Methods: A 32-week prospective, multicentre, single-blinded, parallel, randomly controlled trial was done in ten severe asthma clinics across Ireland, Northern Ireland, and England. Participants were 18 years or older, had uncontrolled asthma, asthma control test (ACT) score of 19 or less, despite treatment with high-dose inhaled corticosteroids, and had at least one severe exacerbation in the past year despite high-dose inhaled corticosteroids. Patients were randomly assigned in a 1:1 ratio to the active group or the control group, by means of a computer-generated randomisation sequence of permuted blocks of varying sizes (2, 4, and 6) stratified by fractional exhaled nitric oxide (FeNO) concentration and recruitment site. In the control group, participants were masked to their adherence and errors in inhaler technique data. A statistician masked to study allocation did the statistical analysis. After a 1-week run-in period, both groups attended three nurse-led education visits over 8 weeks (day 7, week 4, and week 8) and three physician-led treatment adjustment visits at weeks 8, 20, and 32. In the active group, treatment adjustments during the physician visits were informed by digital data on inhaler adherence, twice daily digital peak expiratory flow (ePEF), patient-reported asthma control, and exacerbation history. Treatment was adjusted in the control group on the basis of pharmacy refill rates (a measure of adherence), asthma control by ACT questionnaire, and history of exacerbations and visual management of inhaler technique. Both groups used a digitally enabled Inhaler Compliance Assessment (INCA) and PEF. The primary outcomes were asthma medication burden measured as proportion of patients who required a net increase in treatment at the end of 32 weeks and adherence rate measured in the last 12 weeks by area under the curve in the intention-to-treat population. The safety analyses included all patients who consented for the trial. The trial is registered with ClinicalTrials.gov, NCT02307669 and is complete., Findings: Between Oct 25, 2015, and Jan 26, 2020, of 425 patients assessed for eligibility, 220 consented to participate in the study, 213 were randomly assigned (n=108 in the active group; n=105 in the control group) and 200 completed the study (n=102 in the active group; n=98 in the control group). In the intention-to-treat analysis at week 32, 14 (14%) active and 31 (32%) control patients had a net increase in treatment compared with baseline (odds ratio [OR] 0·31 [95% CI 0·15-0·64], p=0·0015) and 11 (11%) active and 21 (21%) controls required add-on biological therapy (0·42 [0·19-0·95], p=0·038) adjusted for study site, age, sex, and baseline FeNO. Three (16%) of 19 active and 11 (44%) of 25 control patients increased their medication from fluticasone propionate 500 μg daily to 1000 μg daily (500 μg twice a day; adjusted OR 0·23 [0·06-0·87], p=0·026). 26 (31%) of 83 active and 13 (18%) of 73 controls reduced their medication from fluticasone propionate 1000 μg once daily to 500 μg once daily (adjusted OR 2·43 [1·13-5·20], p=0·022. Week 20-32 actual mean adherence was 64·9% (SD 23·5) in the active group and 55·5% (26·8) in the control group (between-group difference 11·1% [95% CI 4·4-17·9], p=0·0012). A total of 29 serious adverse events were recorded (16 [55%] in the active group, and 13 [45%] in the control group), 11 of which were confirmed as respiratory. None of the adverse events reported were causally linked to the study intervention, to the use of salmeterol-fluticasone inhalers, or the use of the digital PEF or INCA., Interpretation: Evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden., Funding: Health Research Board of Ireland, Medical Research Council, INTEREG Europe, and an investigator-initiated project grant from GlaxoSmithKline., Competing Interests: Declaration of interests DJJ reports grants from AstraZeneca and personal fees from Sanofi Regeneron, AstraZeneca, and GlaxoSmithKline. BDK report personal fees from AstraZeneca and GlaxoSmithKline. GG reports patents to quantify adherence and to predict exacerbations. CH reports fees from Alphabet, granted as part of employment by Google. DMM reports personal fees from AstraZeneca, Teva, GlaxoSmithKline, Sanofi, and Novartis. RBR reports a patent for the use of acoustics to assess inhaler adherence. JFMvB reports institutional grants from Aardex, AstraZeneca, Chiesi, European Commission COST Action 19132 ENABLE, Lung Alliance Netherlands, Novartis, Trudell Medical and personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, Teva, Trudell Medical, and Vertex. LGH was academic lead for the UK MRC Consortium for Stratified Medicine in Severe Asthma—Industrial Pharma partners Amgen, AstraZeneca, Medimmune, Janssen, Novartis, Roche–Genentech, GlaxoSmithKline, and Boehringer Ingelheim; grants or contracts from GlaxoSmithKline, Schering Plough, Synairgen, Novartis and Roche–Genentech MedImmune, Novartis UK, Roche–Genentech and GlaxoSmithKline; and lectures supported by AstraZeneca, Novartis, Roche–Genentech, Sanofi, Circassia, GlaxoSmithKline, Chiesi, and Teva. RWC reports institutional grants from GlaxoSmithKline, Aerogen, and Enterprise Ireland; personal fees from AstraZeneca, Teva, GlaxoSmithKline, PMD solutions, and Novartis; and a patent for the use of acoustics to assess inhaler adherence, to quantify adherence and to predict exacerbations. EM, CM, MCM, BC, IS, VB, PJK, MB, IC, JF, JH, MK, RC, LL, JW, SP, TAM, and AMNK declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Guidelines recommend that patients treated with inhalers receive adherence counseling and device training. Digital technologies that assess both inhaler adherence and technique have been developed. Using these technologies community pharmacists, who have regular contact with patients, are well placed to deliver personalized inhaler education., Objective: To determine the impact of a pharmacist intervention, informed by digital technology, on inhaler technique and adherence of patients with asthma in the community., Methods: A cluster randomized, parallel-group, multisite pharmacy study was conducted over 6 months. All study groups had an electronic device (inhaler compliance assessment device) attached to their maintenance inhaler. A biofeedback group received personalized inhaler training informed by data recorded by the device. The demonstration group received inhaler training, by physical demonstration with a placebo inhaler. The control group received usual care. The primary outcome was inhaler adherence, which was classified as "actual adherence" and expressed as the proportion of expected drug accumulation if adherence and technique had been perfect. Secondary outcomes were quality-of-life scores as measured by the St George's Respiratory Questionnaire, symptoms, and exacerbations., Results: A total of 152 participants (n = 74 biofeedback, n = 56 demonstration, and n = 22 control) were recruited. Asthma was the predominant condition among participants (n = 83), with chronic obstructive pulmonary disease (n = 55) and asthma/chronic obstructive pulmonary disease overlap also reported (n = 8). In intention-to-treat analysis, adherence in the biofeedback group during month 2 was 62%, 18% higher (95% CI, 6 to 30) than that in the demonstration group (P = .004) and 24% higher (95% CI, 9 to 40) than that in the control group (P = .003). During month 6, adherence was 14% higher (95% CI, -1 to 30; P = .07) in the biofeedback group than in the demonstration group and 31% higher (95% CI, 13 to 48; P = .001) than in the control group. At the end of the study, the biofeedback group had a sustained fall in St George's Respiratory Questionnaire from baseline, -6.1 (95% CI, -9 to -0.4; P = .04) and had significantly improved daily respiratory symptoms., Conclusions: Community pharmacist-delivered inhaler training informed by a digital technology improved adherence and health status., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Adherence to inhaled maintenance therapy in severe asthma is rarely adequately assessed, and its influence on trial outcomes is unknown. We systematically determined how adherence to maintenance therapy is assessed in clinical trials of "add-on" therapy for severe asthma. We model the improvement in trial power that could be achieved by accurately assessing adherence.A systematic search of six major databases identified randomised trials of add-on therapy for severe asthma. The relationship between measuring adherence and study outcomes was assessed. An estimate of potential improvements in statistical power and sample size was derived using digitally recorded adherence trial data.87 randomised controlled trials enrolling 22 173 participants were included. Adherence assessment was not reported in 67 trials (n=13 931, 63%). Studies that reported adherence used a range of self-report and subjective methods. None of the studies employed an objective assessment of adherence. Studies that reported adherence had a significantly reduced pooled variance in forced expiratory volume in 1 s (FEV 1 ) compared to those that did not assess adherence: s 2 =0.144 L 2 versus s 2 =0.168 L 2 , p<0.0001. Power to detect clinically relevant changes in FEV 1 was significantly higher in trials that reported adherence assessment (mean power achieved 59% versus 49%). Modelling suggests that up to 50% of variance in FEV 1 outcomes is attributable to undetected variations in adherence. Controlling for such variations could potentially halve the required sample size.Few trials of add-on therapy monitor adherence to maintenance inhaled therapy, resulting in a greater variance in trial outcomes and inadequate power for determining efficacy., Competing Interests: Conflict of interest: M.C. Mokoka has nothing to disclose. Conflict of interest: M.J. McDonnell has nothing to disclose. Conflict of interest: E. MacHale has nothing to disclose. Conflict of interest: B. Cushen has nothing to disclose. Conflict of interest: F. Boland has nothing to disclose. Conflict of interest: S. Cormican has nothing to disclose. Conflict of interest: C. Doherty has nothing to disclose. Conflict of interest: F. Doyle has nothing to disclose. Conflict of interest: R.W. Costello has nothing to disclose. Conflict of interest: G. Greene has nothing to disclose., (Copyright ©ERS 2019.)

Four inhaler adherence clusters have been identified using the INCA audio device in COPD patients: (1) regular use/good technique, (2) regular use/frequent technique errors, (3) irregular use/good technique, and (4) irregular use/frequent technique errors. Their relationship with healthcare utilization and mortality was established, but the cost-effectiveness of adherence-enhancing interventions is unknown. In this exploratory study, we aimed to estimate the potential cost-effectiveness of reaching optimal adherence in the three suboptimal adherence clusters, i.e., a theoretical shift of clusters 2, 3, and 4 to cluster 1. Cost-effectiveness was estimated over a 5-year time horizon using the Irish healthcare payer perspective. We used a previously developed COPD health-economic model that was updated with INCA trial data and Irish national economic and epidemiological data. For each cluster, interventions would result in additional quality-adjusted life years gained at reasonable investment. Cost-effectiveness was most favorable in cluster 3, with possible cost savings of €845/annum/person.

Background: Researchers, using checklists, have identified that 30%-90% of patients make errors in inhaler use. It is not certain whether these errors affect the delivery of medication. We have developed an electronic monitor (INCA™) that records audio each time an inhaler is used, providing objective information on inhaler technique. The aim of this study was to assess the effect that correctly identified inhaler errors, with the INCA device, have on drug delivery., Methods: This was a prospective study of healthy volunteers using a salbutamol Diskus™. The inclusion criteria allowed for the recruitment of healthy participants who were nonfrequent users of Salbutamol. Each participant was assigned to one control "phase" first and two/three subsequent error "phases." Each phase consisted of six doses of the drug taken 6 hours apart, and the participants' blood was drawn before and 25 minutes after doses one and six. This allowed us to sample their trough and peak serum salbutamol levels., Results: Fourteen healthy volunteers were studied. The inhaler technique errors simulated in this study included exhaling into the device after drug priming but before inhalation, low inspiratory flow, multiple inhalations, low breath hold, missed doses, and wrong inhaler position. Only the exhalation error, low inspiratory flow, and missed doses led to a significant reduction in serum salbutamol levels. After six doses of the exhalation error, there was a 62% reduction in peak salbutamol levels. Low inspiratory flow led to a 52% reduction in peak salbutamol levels and a 78% reduction in trough levels. Missed doses led to a 37% reduction in trough salbutamol levels., Conclusions: These findings confirm that technique errors affect drug delivery. Furthermore, we were able to identify that the most critical technique errors with the Diskus inhaler are exhalation into the device before inhalation, poor inspiratory flow, and missing doses.

Introduction: Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes., Methods and Analysis: This prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated., Ethics and Dissemination: The results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals., Trial Registration: NCT02307669; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Stress urinary incontinence (SUI) is frequently under-reported in patients with chronic lung disease and may have negative psychosocial consequences. We conducted a prospective study to determine the prevalence, severity and treatment outcomes of SUI in female bronchiectasis patients referred for airway clearance techniques. Nineteen out of 40 (48%) patients reported SUI symptoms. Of these, 14 (74%) reported a reduced quality of life secondary to SUI. Following personalised intervention, symptom improvement was observed in 13/19 (68%). Five out of 19 (26%) required specialist referral for further continence care. No associations with lung disease severity and SUI were noted. SUI is common in adult female bronchiectasis patients and should be routinely screened for to improve patients' overall quality of life.

Upper airway obstruction can present with stridor or expiratory or inspiratory wheeze and is commonly misdiagnosed as asthma. As asthma is common, such cases can remain hidden among patients with lower airway obstruction who attend primary care or respiratory clinics. We describe four causes of upper airway obstruction (paradoxical vocal cord movement, subglottic stenosis, retrosternal goitre and double aortic arch) which were misdiagnosed as 'poorly controlled asthma'.