Inhaled Corticosteroid Adherence Research Articles

Asthma outcomes, inhaled corticosteroid adherence and socio-economic deprivation in English regions.

Asthma outcomes, inhaled corticosteroid adherence and socio-economic deprivation in English regions.

Assessing Inhaled Corticosteroid Adherence and Responsiveness in Severe Asthma Using Beclometasone Dipropionate/Formoterol NEXThaler Dose-Counting and Nitric Oxide Monitoring

65% of people with severe asthma and a FeNO ≥45 ppb are non-adherent to inhaled corticosteroids (ICS). Digital devices recording both time-of-use and inhaler technique identify non-adherence and ICS responsiveness but are not widely available. As the NEXThaler™ dose counter only activates at an inspiratory flow of 35 L/min, this may provide an alternative to identifying ICS responsiveness. To assess ICS adherence and responsiveness in severe asthma using beclometasone/formoterol (200/6 mcg) NEXThaler™ (BFN) dose-counting. Severe asthmatics with a FeNO ≥45 ppb were invited to use BFN in place of their usual ICS/long-acting β2-agonist (LABA). FeNO, ACQ6, lung function and blood eosinophil count were monitored for 3 months. A log10ΔFeNO ≥0.24 was used to define FeNO suppression as the primary marker of ICS responsiveness at day 28. 27/48 (56%) patients demonstrated significant FeNO suppression at month 1 (median pre-114, post-48 ppb, p<0.001). A small but significant reduction occurred in FeNO non-suppressors. ACQ6 fell a median 1.2 units in FeNO suppressors (p<0.001) and 0.5 units in non-suppressors (p=0.025). These effects were sustained until month 3 in FeNO suppressors with a significant improvement in FEV1 and blood eosinophils. 67% (18/27) of those with baseline ICS/LABA prescription refills of ≥80% were FeNO suppressors suggesting prior non-adherence despite adequate prescription collection. 79% of FeNO suppressors did not require biologics within mean 11.4 months from initial dose counting. BFN dose counting identifies ICS responsiveness in severe asthma with the implication that these patients may not need to progress to biological therapies.

Parents' Beliefs about Medicines and Their Influence on Inhaled Corticosteroid Adherence in Children with Asthma.

The most widespread chronic condition observed amid children globally is asthma. Only half of children with asthma adhere to their prescribed inhaled corticosteroids (ICS) therapy. Parents' emotions and perspectives regarding asthma have an impact on inhalation corticosteroid adherence. The participants in this study were 148 parents of children with asthma, with the aim to redintegrate their beliefs about medicines in general and specifically of ICS and the impact on ICS adherence in children with asthma. Children were mostly male (66.9%), older than five years (58.8%), parents were female, mean age 38, employed, and with a history of consumption of some form of corticosteroids. Parents' answers show that 50% of them disagreed with the statement that medicines are addictive, and 90% agree that medicine helps many to live better. A percentage of 77.7% of parents acknowledge that their child's health relies on inhaled corticosteroids (ICS), and 86.5% of parents agree that these medications safeguard their child from worsening health. Most of the parents (93.2%) adhere to the guidelines and instructions of the doctor. In summary, parents who hold the belief that medicines are neither overused nor harmful tend to exhibit a higher adherence. Furthermore, those with elevated adherence levels express lower levels of concern regarding the use of inhaled corticosteroids (ICS) in their children's asthma therapy.

Development and validation of the BMQ-AIR©: a screening tool for assessing patients' treatment beliefs about switching to anti-inflammatory reliever (AIR) therapy.

Despite anti-inflammatory reliever (AIR) therapy now being the preferred treatment choice across all severities of asthma, many patients are still "attached" to their short-acting beta2-agonist (SABA) reliever, believing this to be the best way to control their asthma. To encourage individuals to switch to AIR, it is important to first identify the beliefs that patients hold about AIR. The aim of this paper was to describe the initial development and validation of the BMQ-AIR©, a six-item screening tool which assesses and identifies patients' treatment beliefs about switching to AIR therapy. Statements were identified from the primary literature that assessed patients' perceptions of AIR therapy and adapted from the Beliefs about Medicines Questionnaire (BMQ). Internal reliability was examined using Cronbach's alpha coefficient. Construct validity was evaluated by comparing scores on BMQ-AIR© with a validated measure of medication adherence and SABA beliefs. A total of 446 participants completed the online survey. The BMQ-AIR© contained two subscales with three items each. Both the Necessity and Concerns subscales demonstrated good internal reliability, with Cronbach's α-values of 0.70 and 0.69, respectively. Both subscales were negatively correlated with self-report inhaled corticosteroid adherence (Necessity: r = -0.28, p < 0.0001; Concerns: r = -0.28, p < 0.0001) and positively correlated with SRQ scores (Necessity: r = 0.51, p < 0.0001; Concerns: r = 0.44, p < 0.0001). Preliminary findings indicate that BMQ-AIR© demonstrates satisfactory reliability and validity. BMQ-AIR© is a promising tool that may help tailor interventions to an individual's specific beliefs and barriers to switching to better support individuals in stopping SABA and initiating AIR therapy.

A systematic review of patient-reported adherence measures in asthma: Which questionnaire is most useful in clinical practice?

Suboptimal adherence to inhaled corticosteroid (ICS) in asthma is a worryingly prevalent yet modifiable factor in uncontrolled disease. Several objective measures of adherence exist, but they are time consuming. The use of patient-reported adherence measures (PRAMs) could therefore offer a time-efficient pragmatic approach to adherence assessment in clinical practice and potentially the appropriate interventions to improve it. To identify the PRAMs available for asthma and assess their psychometric quality, accessibility and usefulness in clinical practice. Moreover, to provide recommendations for clinicians based on the aforementioned findings. A systematic review of six databases was conducted. Articles included in this study were: English language full-text original asthma-specific PRAMs or development/validation studies of a generic PRAM that had been administered to adults with asthma; investigated ICS adherence in adults (≥18 years old); and assessed at least one COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) measurement property. 15 PRAM developmental and/or validation studies were included in this systematic review. Studies evaluated a range of COSMIN measurement properties, but none evaluated them all. On the basis of this review, we recommend that if a PRAM is used, that it be the Test of the Adherence to Inhalers (TAI). However, the Adherence Starts with Knowledge-20 (ASK-20), and Adherence Starts with Knowledge-12 (ASK-12) may also be useful. Our results highlight the need for PRAM developers to robustly assess questionnaires and to provide guidance for clinicians on how to act upon PRAM answers by developing materials such as decision support toolkits.

Qualitative study of user perspectives and experiences of digital inhaler technology

Electronic monitoring devices (EMDs) have been trialled in interventions to improve inhaled corticosteroid adherence and clinical outcomes. This study sought to understand the perceptions and experiences of EMD end-users. Participants recruited into a six-month EMD study were invited to a semi-structured interview. Interviews were audio-recorded, transcribed verbatim and analysed using the framework approach. Twenty-eight participants (68% female, median age 47) were interviewed. Individuals described feeling responsible for their asthma control. Recent attacks motivated a desire to maintain control. Study participation led to increased awareness of asthma status and medication use. Several individuals were open to integrating digital monitoring data with other mHealth inputs, perceiving the potential to enhance communication with clinicians and empower self-management. Openness to data sharing was tied to expectations of transparent data use. Data supported integrating beliefs and habit formation to achieve behaviour change. There was a willingness for an integrated, platform-based approach to digital self-management.

Beliefs about medicines and adherence to asthma medications during pregnancy

Objective Discontinuation of, and non-adherence to, inhaled corticosteroids (ICS) for asthma treatment is a significant issue in pregnancy. This study characterized beliefs about medicines in pregnant women with asthma and investigated associations with ICS adherence. Methods Pregnant women with relatively mild asthma (n = 302) were grouped according to ICS use and self-reported adherence (≥80% doses taken). They completed questions about dislike of asthma medications and the validated Beliefs about Medicines Questionnaire (BMQ), which consists of ten questions about asthma medicines (“necessity” questions about maintaining health, or “concern” questions about adverse effects), and eight general medicine questions, scored on five-point Likert scales. The Necessity Concerns differential (N-C) was calculated, with positive scores indicating that the patient perceives the benefits of medicines to outweigh the risks. Results ICS was used by 87 (29%) women, with 49 (56%) self-reporting adherence. Of the 22% who disliked taking asthma medications during pregnancy, 20% had the belief that the medication was unsafe. ICS users had a significantly higher BMQ necessity score and higher necessity-concern differential score than nonusers; when adjusted for covariates, ICS non-adherence was associated with a lower necessity score (p = 0.015). Women adherent to ICS were more likely to agree to “my health at present depends on my asthma medication” compared to non-adherent ICS users. Conclusions ICS non-adherence was not associated with having relatively more concerns about asthma medicines; however, ICS users were more likely to perceive that the benefits of medication use outweighed any risks. Interventions to improve asthma medication adherence in pregnancy are needed.

Adherence to inhaled corticosteroids in relation to quality of life and symptoms of anxiety and depression in asthma

ABSTRACT Background Poor asthma control, often caused by non-adherence with controller medication, is a well-known risk factor for impaired quality of life (QoL) and major mood disorders (MMD). Previous studies have shown a relationship between non-adherence, lower QoL, and MMD across chronic diseases, but the relationship remains uncertain in asthma. Methods All asthma patients followed at the respiratory outpatient clinic at Copenhagen University Hospital – Hvidovre were invited to fill-in the Hospital Anxiety and Depression Scale (HADS) and the Mini Asthma Quality of Life Questionnaire (miniAQLQ). Medication Possession Ratio (MPR) was calculated using pharmacy redemption data. Relationships between questionnaire scores, inhaled corticosteroid MPR and use of rescue medication were investigated using Pearson correlation and multivariable linear regression adjusted for age, sex, FEV1, and GINA Step. Data from scheduled visits were collected from patients’ medical records. Results A total of 308 patients (73% females, median age 51 years (interquartile range (IQR) 37, 62)) completed the questionnaires and had 1-year medication data available. Median adherence to inhaled corticosteroids (ICS) was 57% (35%, 75%) with 18% of patients having adherence above 80%. Of the participating patients, 14% and 27% reported depressive and anxiety-related symptoms, respectively, and 72% reported impaired QoL. In correlation analyses, ICS adherence was not significantly associated with either prevalence of MMD symptoms or impaired QoL in asthma patients. However, a strong correlation was found between ACQ-6 and both MMD symptoms and impaired QoL, as well as between rescue medication use and impaired QoL. In adjusted analysis, however, the latter correlation was no longer statistically significant. Conclusion Our results suggest that ICS adherence is not directly correlated with either impaired quality of life or major mood disorder symptoms in asthma patients. Self-reported asthma control, on the other hand, is strongly correlated with both QoL and MMD.

Speech recognition can help evaluate shared decision making and predict medication adherence in primary care setting.

ObjectiveAsthma is a common chronic illness affecting 19 million US adults. Inhaled corticosteroids are a safe and effective treatment for asthma, yet, medication adherence among patients remains poor. Shared decision-making, a patient activation strategy, can improve patient adherence to inhaled corticosteroids. This study aimed to explore whether audio-recorded patient-primary care provider encounters can be used to: 1. Evaluate the level of patient-perceived shared decision-making during the encounter, and 2. Predict levels of patient’s inhaled corticosteroid adherence.Materials and methodsShared decision-making and inhaled corticosteroid adherence were assessed using the SDM Questionnaire-9 and the Medication Adherence Report Scale for Asthma (MARS-A). Speech-to-text algorithms were used to automatically transcribe 80 audio-recorded encounters between primary care providers and asthmatic patients. Machine learning algorithms (Naive Bayes, Support Vector Machines, Decision Tree) were applied to achieve the study’s predictive goals.ResultsThe accuracy of automated speech-to-text transcription was relatively high (ROUGE F-score = .9). Machine learning algorithms achieved good predictive performance for shared decision-making (the highest F-score = .88 for the Naive Bayes) and inhaled corticosteroid adherence (the highest F-score = .87 for the Support Vector Machines).DiscussionThis was the first study that trained machine learning algorithms on a dataset of audio-recorded patient-primary care provider encounters to successfully evaluate the quality of SDM and predict patient inhaled corticosteroid adherence.ConclusionMachine learning approaches can help primary care providers identify patients at risk for poor medication adherence and evaluate the quality of care by measuring levels of shared decision-making. Further work should explore the replicability of our results in larger samples and additional health domains.

Treatment guided by fractional exhaled nitric oxide in addition to standard care in 6- to 15-year-olds with asthma: the RAACENO RCT

BackgroundThe role of fractional exhaled nitric oxide in guiding asthma treatment in children is uncertain.ObjectiveTo compare treatment guided by both fractional exhaled nitric oxide and symptoms (intervention) with treatment guided by symptoms alone (standard care) in children with asthma who are at risk of an asthma exacerbation, in terms of the number of asthma exacerbations over 12 months.DesignThis was a pragmatic, multicentre, randomised controlled trial with embedded cost-effectiveness and qualitative process evaluations. Randomisation (1 : 1) was carried out using a remote web-based system and was minimised on recruitment centre, age, sex and British Thoracic Society treatment step. Clinical teams and participants were not blind to treatment allocation.SettingThe trial took place in 35 hospitals and seven primary care practices in the UK.ParticipantsChildren aged 6–15 years with a diagnosis of asthma who were currently prescribed inhaled corticosteroids and who had one or more parent-/patient-reported asthma exacerbation treated with oral corticosteroids in the 12 months prior to recruitment.InterventionsAsthma treatment guided by symptoms alone (standard care) and asthma treatment guided by symptoms plus fractional exhaled nitric oxide (intervention). Treatment recommendations in both groups were protocolised within a web-based algorithm, incorporating inhaled corticosteroid adherence (objectively measured using an electronic logging device) and current treatment.Main outcome measuresThe primary outcome measure was asthma exacerbations treated with oral corticosteroids in the year post randomisation. Secondary outcomes included time to first exacerbation, number of exacerbations, lung function, fractional exhaled nitric oxide, daily dose of inhaled corticosteroid, asthma control and quality of life.ResultsIn total, 509 eligible participants were recruited and the primary outcome was available for 506 participants. The primary outcome occurred in 123 out of 255 (48.2%) participants in the intervention group and 129 out of 251 (51.4%) participants in the standard-care group (adjusted odds ratio 0.88, 95% confidence interval 0.61 to 1.27). There was algorithm non-compliance on 21% of assessments. Per-protocol and complier-average causal effect analysis did not change the interpretation. This non-statistically significant estimate was consistent across predefined subgroups. There were no differences between the groups in secondary outcomes. There were no serious adverse events or deaths. No meaningful differences in health service costs, direct patient costs or indirect costs to society were identified between the groups. The economic evaluation does not provide evidence to support the cost-effectiveness of the intervention. In the qualitative process evaluation, 15 trial staff and six families were interviewed. Overall, their experiences were positive. The intervention was broadly acceptable, with caveats around clinicians using the algorithm recommendation as a guide and wariness around extreme step ups/downs in treatment in the light of contextual factors not being taken into account by the algorithm.LimitationsPotential limitations included the choice of cut-off point to define uncontrolled asthma and the change in fractional exhaled nitric oxide to trigger a change in treatment. Furthermore, the treatment decisions in the two groups may not have been sufficiently different to create a difference in outcomes.ConclusionsThe RAACENO (Reducing Asthma Attacks in Children using Exhaled Nitric Oxide) trial findings do not support the routine use of fractional exhaled nitric oxide measurements as part of asthma management in a secondary care setting. The potential for other objective markers to guide asthma management in children needs to be evaluated.Trial registrationThis trial was registered as ISRCTN67875351.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. This will be published in full inEfficacy and Mechanism Evaluation; Vol. 9, No. 4. See the NIHR Journals Library website for further project information.

Associations Between Sleep Quality, Household Income and Medication Adherence in Adolescents With Asthma

Adolescents with asthma are at-risk for poor sleep quality. Little research has examined the relationship between sleep quality and inhaled corticosteroids (ICS) adherence. Individuals from lower-income backgrounds experience disparities that may alsocontribute to sleep quality. This study sought to 1) examine associations between household income and sleep quality and 2) analyze the relationship between sleep quality and ICS adherence among adolescents with asthma.Forty-one adolescents with persistent asthma (Mage = 14.83, SD = 1.28) completed the Adolescent Sleep Wake Scale (ASWS) to measure sleep quality across five subscales. Caregivers provided their estimated household income per year and completed a free response question measuring ICS adherence. Spearman’s rank-order correlations were used to examine associations between sleep quality,household income and ICS adherence. Sleep quality and household income were not significantly related (r = .262, p = .098). Sleep quality was not associated with ICS adherence (r = -.028, p = .867). Sleep quality was not significantly related to household income or ICS adherence in adolescents with asthma. Limitations include limited power given a small sample size and less reliable measures of household income and adherence therefore, future directions should focus on using more precise measures. Additional research with larger sample sizes may help better understand potential relationships between sleep quality, ICS adherence, and household income within youth with asthma.

Managing Exacerbations in Thunderstorm Asthma: Current Insights.

Epidemic thunderstorm asthma (ETSA) occurs following a thunderstorm due to the interaction of environmental and immunologic factors. Whilst first reported in the 1980s, the world’s largest event in Melbourne, Australia, on November 21, 2016 has led to a wealth of clinical literature seeking to identify its mechanisms, susceptibility risk factors, and management approaches. Thunderstorm asthma (TA) typically presents during an aeroallergen season in individuals sensitized to perennial rye grass pollen (RGP) in Australia, or fungus in the United Kingdom, in combination with meteorological factors such as thunderstorms and lightning activity. It is now well recognized that large pollen grains, which usually lodge in the upper airway causing seasonal allergic rhinitis (SAR), are ruptured during these events, leading to sub-pollen particles respirable to the lower respiratory tract causing acute asthma. The identified risk factors of aeroallergen sensitization, specifically to RGP in Australians with a history of SAR, and individuals born in Australia of South-East Asian descent as a risk factor for TA has been key in selecting appropriate patients for preventative management. Moreover, severity-determining risk factors for ETSA-related asthma admission or mortality, including pre-existing asthma or prior hospitalization, poor inhaled corticosteroid adherence, and outdoor location at the time of the storm are important in identifying those who may require more aggressive treatment approaches. Basic treatments include optimizing asthma control and adherence to inhaled corticosteroid therapy, treatment of SAR, and education regarding TA to increase recognition of at-risk days. Precision treatment approaches may be more beneficial in select individuals, including the use of allergen immunotherapy and even biologic treatment to mitigate asthma severity. Finally, we discuss the importance of environmental health literacy in the context of concerns surrounding the increased frequency of ETSA due to climate change and its implications for the frequency and severity of future events.

Pictorial versus written asthma action plans for youth: initial impact on regimen knowledge, medication adherence, symptom control, and family satisfaction

Objective Asthma action plans (AAP) are recommended to guide asthma management. Written AAPs (WAAPs) are under-utilized and can be difficult to understand. Our study designed and tested a simplified pictorial AAP (PAAP). We hypothesized that better outcomes would be obtained for youth with the PAAP. Methods One hundred and sixty-nine (169) youth (aged 8–17; AAP-naïve) were screened for this pilot, 2-arm randomized controlled trial. Feasibility, usability and preliminary efficacy of PAAP compared to a WAAP, for improving outcomes (inhaled corticosteroid (ICS) adherence, symptom control, AAP knowledge, AAP satisfaction) were assessed quantitatively. Youth received an AAP from their physician after completing baseline measures and completed measures at three additional time points (1-, 3-, and 6-month). Results Forty-five youth were recruited (PAAP = 22; WAAP = 23). Youth AAP knowledge was higher for the PAAP group compared to the WAAP group (p = .017). ICS adherence did not differ between groups, over time, or based on prescribed dosing; however, for WAAP participants, adherence was lower with a higher daily prescription (4 puffs) relative to a lower dose (p = .006). Symptom control improved with both AAPs, but the change was not statistically significant. Lung function did not change significantly by AAP type or time, and literacy variables were not related significantly to outcomes. Youth satisfaction with AAP improved significantly for the PAAP group compared to the WAAP group (p = .03). Conclusions Higher AAP knowledge and satisfaction among youth in the PAAP group suggests that structured education from a physician using a PAAP is beneficial. Intervention and study design insights gained will guide future research.

Daily adherence variability and psychosocial differences in adolescents with asthma: a pilot study.

Adolescents with asthma endorse psychosocial difficulties as barriers to inhaled corticosteroid adherence. This study examined patterns of variability in adherence and within-person associations of psychosocial variables with adherence across days. Participants included twenty-five adolescents (Mage = 14.7, SD = 1.68; 48% male) with persistent asthma. We measured adherence via electronic monitoring. Adolescents completed daily surveys measuring asthma symptoms, stress, mood, and affect. We examined within-person differences in the effect of symptoms and psychosocial variables on adherence. Adherence decreased over time. The addition of a random slope improved model fit (- 2ΔLL(1) = 9.36, p < .01). Greater asthma symptoms were significantly associated with higher adherence at the within-person level and with lower adherence between persons. We observed evidence of individual differences in the associations of stress and affect with adherence. Within-person, day-level fluctuations in adherence occur. Symptoms and psychosocial variables may influence adherence. Individually tailored interventions may effectively address nonadherence.

Reducing Asthma Attacks in Children Using Exhaled Nitric Oxide as a Biomarker to Inform Treatment Strategy – A Randomised Trial

Background: The benefit of Fractional Exhaled Nitric Oxide (FeNO) in guiding asthma treatment is uncertain. Our hypothesis was that FeNO plus symptom-guided treatment reduces exacerbations in children with asthma compared to symptom-guided treatment alone. Methods: A multicentre randomised controlled trial recruited 6-15 year olds with asthma treated with inhaled corticosteroids (ICS) with an exacerbation in the previous year. Randomisation was to asthma treatment guided by FeNO plus symptoms (intervention) or by symptoms only (standard care). A web-based algorithm using symptom control, ICS adherence, current treatment and (within the intervention group) FeNO gave treatment recommendations. Participants attended assessments 3, 6, 9 and 12-months post-randomisation. The primary outcome was exacerbation requiring oral corticosteroid over the 12 months post-randomisation. Findings: There were 509 children recruited. At randomisation, the mean (SD) age was 10∙1y (2.6), median (IQR) FeNO 21 ppb (10, 48), mean (SD) %FEV 1 90% (18), 56% received ≤400 microg budesonide equivalent ICS and 50% had controlled symptoms. The primary outcome occurred in 123/255 (48%) of the intervention group and 129/251 (51%) of the standard care group. The adjusted difference in percentage of participants who received the intervention where the primary outcome occurred exacerbation compared to those receiving standard care was -3∙13% (95% CI: -11∙9% to 5∙6%). In adjusted intention-to-treat analysis, the odds ratio (OR) for primary outcome was 0 ∙88 [95%CI 0∙61 to 1∙27]. In 377 of 1771 assessments, the algorithm recommendation was not followed. In complier average causal effect analysis, adjusting for algorithm adherence, the OR for those fully adherent was 0∙82 [95% CI 0∙48 to 1∙41]. There were no differences in secondary outcomes between groups. Interpretation: In this exacerbation-prone population, adding FeNO to symptom-guided treatment did not reduce exacerbations. Trial Registration: ISRCTN number #67875351. Funding: This study was funded by the Efficacy and Mechanisms Evaluation programme of the National Institute for Health Research (reference 15-18-14). Declaration of Interest: David Price has board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Thermofisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Theravance and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. Ethical Approval: The study was approved by the North of Scotland Research Ethics Committee (16/NS/0106).

Assessment of adherence to corticosteroids in asthma by drug monitoring or fractional exhaled nitric oxide: A literature review.

BackgroundAlthough the efficacy of corticosteroid treatment in controlling asthma is widely accepted, its effectiveness is undermined by poor adherence. However, the optimal method for measuring adherence to asthma therapy remains unclear.ObjectiveTo perform a review of the literature reporting biological, objective methods for assessing adherence to inhaled or oral corticosteroids in asthma; we included studies reporting direct measurement of exogenous corticosteroids in blood, or the effect of adherence on exhaled nitric oxide.DesignWe searched three databases MEDLINE (using both PubMed and Ovid), the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Web of Science for articles published between January 1975 and July 2020. Quality of the studies was assessed using the National Institute of Health checklist.ResultsFrom 2850 screened articles, 26 fulfilled the inclusion criteria. Measurement of blood prednisolone with or without cortisol was used in eight studies as a measure of oral corticosteroid adherence, and fractional exhaled nitric oxide (FeNO) in 17 studies for inhaled corticosteroid adherence. Inhaled corticosteroids were measured directly in the blood in one study. By direct measurement of drug levels in the blood, adherence rates to oral corticosteroids ranged from 47% to 92%, although the performance and timing of the test were often not known, making interpretation of findings and serum prednisolone concentrations difficult. FeNO is generally lower in adherent than non‐adherent patients, but no absolute cut‐off can be proposed based on the available data. However, a fall in FeNO following supervised inhaled corticosteroid dosing could indicate previous poor adherence.Conclusions and Clinical RelevanceDespite prednisolone and cortisol levels commonly being used as adherence markers in clinical practice, further work is required to assess the influence of the dose and timing on blood levels. The promising findings of FeNO suppression testing should be explored in further prospective studies.

Diagnosis and Management of Problematic Severe Asthma.

This review will outline an evidence-based approach for diagnosing and managing children with problematic severe asthma (PSA). Children with PSA have uncontrolled asthma symptoms, despite maximal prescribed asthma treatment. These children have high morbidity and mortality and should be referred for specialist respiratory assessment and management. The first step in the assessment of a child with PSA is confirming the diagnosis of asthma using objective evidence. Following this, an assessment of inhaled corticosteroid adherence and a multi-disciplinary team approach is essential for separating difficult asthma (DA) from severe therapy resistant asthma (STRA). The majority of children have DA which entails uncontrolled asthma symptoms due to underlying modifiable factors including poor treatment adherence, poor inhaler technique, exposure to environmental allergens, co-morbid conditions and psycho-social factors. Approximately 20% of children with PSA have STRA, and have persistent asthma symptoms despite good treatment adherence and correction of modifiable factors. Children with STRA typically have multiple and severe aeroallergen sensitization, eosinophilic airway inflammation and high fraction exhaled nitric oxide (FeNO). Further investigation of children with STRA includes an assessment of systemic steroid responsiveness, this is important for confirming the diagnosis of STRA and guiding the choice of additional treatment. Biologics are an add on (immune targeted) therapy for STRA. The current biologics used in children target the T2 helper (Th2) pathway mediating eosinophilic, allergic asthma. CONCLUSION: Future clinical trials of biologics in children will be essential to help identify childhood specific biomarkers and to decide which biologic is best for which individual child.

Tailored Medication Adherence Incentives Using mHealth for Children With High-Risk Asthma (TAICAM): Protocol for a Randomized Controlled Trial.

BackgroundPoor adherence to inhaled corticosteroid medications for children with high-risk asthma is both well documented and poorly understood. It has a disproportionate prevalence and impact on children of minority demographics in urban settings. Financial incentives have been shown to be a compelling method to engage those in a high-risk asthma population, but whether adherence can be maintained by offering financial incentives and how these incentives can be used to sustain high adherence are unknown.ObjectiveThe aim of this study is to determine the marginal effects of a financial incentive–based intervention on inhaled corticosteroid adherence, health care system use, and costs.MethodsParticipants include children aged 5 to 12 years who have had either at least two hospitalizations or one hospitalization and one emergency department visit for asthma in the year prior to their enrollment (and their caregivers). Participants are given an electronic inhaler sensor in order to track their medication use over a period of 7 months. After a 1-month period of observation, participants are randomized to 1 of 3 arms for a 3-month period. Participants in arm 1 receive daily text message reminders, feedback, and gain–framed, nominal financial incentives; participants in arm 2 receive daily text message reminders and feedback only, and participants in arm 3 receive no reminders, feedback, or incentives. All participants are subsequently observed for an additional 3-month period with no reminders, feedback, or incentives to assess whether any sustained effects are apparent.ResultsStudy enrollment began in September 2019 with a target sample size of N=125 children. As of June 2020, 61 children have been enrolled. Data collection is estimated to be completed in June 2022, and analyses will be completed by June 2023.ConclusionsThis study will provide data that will help to determine whether a financial incentive–based mobile health intervention for promoting inhaled corticosteroid use can be effective in patients with high-risk asthma over longer periods.Trial RegistrationClinicaltrial.gov NCT03907410; https://clinicaltrials.gov/ct2/show/NCT03907410International Registered Report Identifier (IRRID)DERR1-10.2196/16711

Validity of the Medication Adherence Rating Scale for Adherence to Inhaled Corticosteroids among Older Adults with Asthma or Chronic Obstructive Pulmonary Disease

Regular use of inhaled corticosteroids (ICS) is the standard of care for patients with persistent asthma and chronic obstructive pulmonary disease (COPD). Adherence to ICS is measured using the 10-item Medication Adherence Report Scale (MARS), a self-reported medication adherence assessment. However, data on the validity of this measure are limited. Data were obtained from two cohort studies that examined the association of health literacy with self-management behaviors among adults ages 65 and older with asthma and adults ages 40 and older with COPD. ICS adherence was objectively measured over a 4-week period using electronic monitoring devices. Adequate adherence by MARS assessment was defined as a score ≥4.5, and by electronic monitoring as ≥80% of doses prescribed. We assessed the criterion validity using correlations between self-reported adherence and electronic adherence. Receiver Operating Characteristic (ROC) curve analysis was performed between the two measures. Among patients with asthma, the continuous values for adherence measured by self-report and electronically were weakly correlated (r = 0.33, p < 0.001); similarly, the agreement between the dichotomized measures was weak (kappa 0.30, p=.49). Findings were similar for COPD patients: r = 0.26, p = 0.003; kappa 0.19, p = .60. Area under curve (AUC) values generated from ROC analysis was 0.69 and 0.61, for asthma and COPD patients, respectively. Commonly used measure for adherence performed weakly compared to electronic monitoring in separate populations of patients with asthma and COPD. Investigators measuring self-reported medication adherence among patients with these pulmonary diseases should consider using alternative instruments or using objective measures exclusively.

Refill Reminder Preference and Inhaled Corticosteroid Adherence Among Patients with Asthma

Refill reminders can help patients improve adherence to inhaled corticosteroid (ICS) therapy. However, little is known about patient preferences for reminder type or whether patients who express a preference differ from patients who do not. To describe patient preferences for ICS prescription refill reminder type and to compare baseline ICS therapy adherence, measured as proportion of days covered (PDC) 1 year before initiating preference-based reminders, between patients who did and did not express a preference. This substudy within a randomized multi-intervention study was conducted at Kaiser Permanente Colorado. Adults with asthma randomized to intervention were offered the opportunity to choose text, telephone, or email reminders. Patients who did and did not provide a preference were compared by baseline characteristics using log-binomial models. The primary outcomes were reminder preference and type. A total of 1497 of 4545 patients (32.9%) expressed a preference; 789 (52.7%) chose text. The adjusted relative risk (aRR) of not providing a preference increased with decreasing PDC (PDC of 0.50 to < 0.80: aRR, 1.14; 95% confidence interval [CI], 1.04-1.25; PDC < 0.5: aRR, 1.76; 95% CI, 1.59-1.95) compared with patients with a PDC of 0.80 or greater. Among patients who expressed a preference, text reminders were preferred. Patients who expressed a preference had higher baseline adherence. Further research is needed to determine whether expressing a preference for a refill reminder type is itself associated with adherence. Given that offering the opportunity to choose a reminder type only engaged a subset of patients, further work is needed to understand how best to leverage technology-enabled communication outreach to help patients optimize adherence.