Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial.

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.

The Contribution of Oral and Inhaled Glucocorticoids to Adrenal Insufficiency in Asthma.

BACKGROUND: Exposure to any form of glucocorticoid preparation is associated with a risk of adrenal insufficiency (AI). OBJECTIVE: To establish the contribution of oral corticosteroid (OCS) and inhaled corticosteroid (ICS) exposure to the risk of AI in a cohort of patients (n = 80) with severe, uncontrolled asthma. METHODS: We compiled individualized cumulative OCS and ICS exposure data using a combination of health care records and electronic inhaler monitoring using an Inhaler Compliance Assessment device and estimated the risk of AI for each participant using a morning serum cortisol concentration. RESULTS: The predicted prevalence of AI based on morning cortisol concentrations was 25% (20 of 80). Participants on maintenance OCS therapy had the highest risk of AI at 60% (6 of 10) compared with 17% (11 of 65) in those with no recent OCS exposure. Morning serum cortisol correlated negatively with both OCS exposure (mg/kg prednisolone) (r = -0.4; P < .0002) and ICS exposure (mg/kg fluticasone propionate) (r = -0.26; P = .019). Logistic regression of risk of AI against the number of standard treatment courses of OCS demonstrated a positive relationship although this did not reach statistical significance (odds ratio, 1.41; 95% CI, 0.97-2.05; P = .073). Logistic regression analysis, categorizing patients as high-risk AI (cortisol <130 nmol/L) or not (cortisol >130 nmol/L), showed that cumulative ICS exposure remained a significant predictor of AI, even when exposure to OCS was controlled for (odds ratio, 2.17 per 1 mg/kg increase in cumulative fluticasone propionate exposure; 95% CI, 1.06-4.42; P = .033). CONCLUSIONS: Our data suggest that AI is common among patients with asthma and highlights that the risk of AI is associated with both high-dose ICS therapy and intermittent treatment courses of OCS.

The clinical impact of adherence to therapy in airways disease.

For a physician, the final step of a consultation consists of developing a treatment plan and prescription. For the patient, this is the start of a process. First, their role in the treatment plan must be clarified, then they may have to obtain an alternative prescription from their general practitioner. Next, they must have the prescription filled and dispensed from the pharmacy and, finally, they must take the treatment on time and for the required duration. For people with chronic conditions, this requires repeatedly returning to the pharmacy for the prescription to be renewed and dispensed. Given that many patients are on multiple treatment regimens and may have poor health literacy, this becomes a complex process and it is not surprising that this can, and frequently does, go wrong. Research shows that when a patient does not adhere to standard asthma or COPD treatment, they report poor control and overuse of rescue ß-agonists, experience frequent exacerbations and are often prescribed add-on treatments such as biological agents. In short, poor treatment adherence can manifest in the same way as a refractory condition. These clinical features should prompt a clinician to investigate poor adherence as they might investigate a new blood or radiological finding. Examining a patient's prescription refill records or a digitally enabled inhaler can demonstrate a number of patterns of inhaler use. A small minority regularly use their treatment as prescribed but many appear to be "cluster users": a group of patients who use their treatment correctly when they are unwell, but once some level of personal control is attained, they cease or reduce their use. Others may cease using their treatment because they are not perceiving a benefit or because an alternative condition accounts for their symptoms. In other words, clinicians can consider that treatment adherence is like a clinical sign: something to be investigated so that they may understand the patient's condition better. EDUCATIONAL AIMS: To highlight the clinical consequences of poor adherence to standard treatments for airways diseases.To describe how poor treatment adherence manifests as complications of the condition.To highlight that when a patient does not benefit as might be expected from a treatment, poor adherence should be considered and evaluated for, before more treatment is added.

The effectiveness of continuous respiratory rate monitoring in predicting hypoxic and pyrexic events: a retrospective cohort study.

Respiratory rate (RR) is routinely used to monitor patients with infectious, cardiac and respiratory diseases and is a component of early warning scores used to predict patient deterioration. However, it is often measured visually with considerable bias and inaccuracy.Objectives. Firstly, to compare distribution and accuracy of electronically measured RR (EMRR) and visually measured RR (VMRR). Secondly, to determine whether, and how far in advance, continuous electronic RR monitoring can predict oncoming hypoxic and pyrexic episodes in infectious respiratory disease.Approach.A retrospective cohort study analysing the difference between EMRR and VMRR was conducted using patient data from a large tertiary hospital. Cox proportional hazards models were used to determine whether continuous, EMRR measurements could predict oncoming hypoxic (SpO2 < 92%) and pyrexic (temperature >38 °C) episodes.Main results.Data were gathered from 34 COVID-19 patients, from which a total of 3445 observations of VMRR (independent of Hawthorne effect), peripheral oxygen saturation and temperature and 729 117 observations of EMRR were collected. VMRR had peaks in distribution at 18 and 20 breaths per minute. 70.9% of patients would have had a change of treatment during their admission based on the UK's National Early Warning System if EMRR was used in place of VMRR. An elevated EMRR was predictive of hypoxic (hazard ratio: 1.8 (1.05-3.07)) and pyrexic (hazard ratio: 9.7 (3.8-25)) episodes over the following 12 h.Significance.Continuous EMRR values are systematically different to VMRR values, and results suggest it is a better indicator of true RR as it has lower kurtosis, higher variance, a lack of peaks at expected values (18 and 20) and it measures a physiological component of breathing directly (abdominal movement). Results suggest EMRR is a strong marker of oncoming hypoxia and is highly predictive of oncoming pyrexic events in the following 12 h. In many diseases, this could provide an early window to escalate care prior to deterioration, potentially preventing morbidity and mortality.

Patient-Selected Treatment Goals in Severe Asthma.

BACKGROUND: Goal-orientated health care accounts for patient preferences and values, not just physician treatment aims. The Global Initiative for Asthma (GINA) management strategy states that clinicians should elicit patients' own treatment goals as a central part of care. Despite this recommendation, data on patients' treatment goals are sparse among patients with severe asthma. OBJECTIVE: The objective of this study is to investigate the relationship between rates of treatment adherence and goal achievement, and patient-selected goals. METHODS: Thematic analysis was used to characterize patient-selected goals. Previously undescribed goal categories in asthma were identified, quantified, and related to clinical characteristics. Goal achievement was aligned with objectively measured treatment adherence. RESULTS: Three categories of patients-selected goals were identified from 2 randomized control trials: disease-specific (n = 98 [51%] and n = 92 [54%], respectively), function-related (n = 90 [48%] and n = 61 [36%]), and knowledge (n = 1 [1%] and n = 17 [10%]). Only 53% of goals aligned with clinician treatment goals. Patients who chose disease-specific goals were more likely to achieve both control and their specified goal (n = 98 [45%], odds ratio: 1.789, confidence interval: 1.066-3.001). Male participants are more likely to focus on disease-specific goals. Patients who achieved their goals were more likely to be T2-high, have an elevated fractional exhaled nitric oxide (FeNO) at their first visit, and have a lower FeNO value at their final visit. Interestingly, adherence rates decline significantly for those who achieve their goals. CONCLUSION: Almost half of patient-selected goals do not align with GINA clinical asthma management goals. Participants who chose goals that do align with clinicians were more likely to achieve them.

A Clinical Perspective on the Role of Electronic Devices in Monitoring and Promoting Adherence in Airways Disease.

Poor adherence to treatment is a common reason why patients with chronic disease have worse outcomes than might be expected. Poor treatment adherence is of particular concern among people with airways disease because, apart from not taking treatment as prescribed, inhaled medication can also be administered incorrectly. Recently, a number of technological advances that accurately document when an inhaled treatment has been used and, in certain instances, how it was used have been developed. There is good evidence from a number of research groups that these devices, either by patient reminders or physician feedback, promote adherence to inhaled treatments. What is less certain is how, in a real-world setting, these devices change outcomes. In this perspective article, the role of electronic devices in quantifying treatment use and addressing poor treatment adherence and their potential role in clinical practice outside of clinical validation trials are described.