Elaine MacHale

Objective Assessment of Adherence to Inhalers by COPD Patients.

Rationale: Objective adherence to inhaled therapy by patients with chronic obstructive pulmonary disease (COPD) has not been reported. Objectives: To objectively quantify adherence to preventer Diskus inhaler therapy by patients with COPD with an electronic audio recording device (INCA). Methods: This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCA device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use. Measurements and Main Results: Patients with COPD (n = 244) were recruited. The mean age was 71 years, mean FEV1 was 1.3 L, and 59% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses, and critical technique errors, thus incorporating both intentional and unintentional nonadherence, a measure “actual adherence” was calculated. Mean actual adherence was 22.6% of that expected if the doses were taken correctly and on time. Six percent had an actual adherence greater than 80%. Hierarchical clustering found three equally sized well‐separated clusters corresponding to distinct patterns. Cluster 1 (34%) had low inhaler use and high error rates. Cluster 2 (25%) had high inhaler use and high error rates. Cluster 3 (36%) had overall good adherence. Poor lung function and comorbidities were predictive of poor technique, whereas age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique. Conclusions: These data may inform clinicians in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD.

A Method to Assess Adherence in Inhaler Use through Analysis of Acoustic Recordings of Inhaler Events

Rationale Poor adherence to inhaler use can be due to poor temporal and/or technique adherence. Up until now there has been no way of reliably tracking both these factors in everyday inhaler use. Objectives This paper introduces a device developed to create time stamped acoustic recordings of an individuals inhaler use, in which empirical evidence of temporal and technique adherence in inhaler use can be monitored over time. The correlation between clinical outcomes and adherence, as determined by this device, was compared for temporal adherence alone and combined temporal and technique adherence. Findings The technology was validated by showing that the doses taken matched the number of audio recordings (r2 = 0.94, p<0.01). To demonstrate that audio analysis of inhaler use gives objective information, in vitro studies were performed. These showed that acoustic profiles of inhalations correlated with the peak inspiratory flow rate (r2 = 0.97, p<0.01), and that the acoustic energy of exhalations into the inhaler was related to the amount of drug removed. Despite training, 16% of participants exhaled into the mouthpiece after priming, in >20% of their inhaler events. Repeated training reduced this to 7% of participants (p = 0.03). When time of use was considered, there was no evidence of a relationship between adherence and changes in AQLQ (r2 = 0.2) or PEFR (r2 = 0.2). Combining time and technique the rate of adherence was related to changes in AQLQ (r2 = 0.53, p = 0.01) and PEFR (r2 = 0.29, p = 0.01). Conclusions This study presents a novel method to objectively assess how errors in both time and technique of inhaler use impact on clinical outcomes. Trial Registration EudraCT 2011-004149-42

A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma

In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence. Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis. The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%–17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%). Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy. On a period of monitored adherence only 27% of patients were refractory and adherent and thus need add-on therapy http://ow.ly/ddQr30gTpmb

Predicting asthma exacerbations employing remotely monitored adherence

This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participants inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p < 0.01) higher than remote monitoring adherence. Overall, those with poor adherence had a 1.38 ± 0.34 and 1.42 ± 0.39 (remotely monitored) and 1.25 ± 0.32 and 1.18 ± 0.31 (dose counter) higher relative risk of an exacerbation in model 1 and model 2, respectively. However, this was not found to be statistically significantly different. Remotely monitored adherence holds important clinical information and future research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events.

The Clinical Impact of Different Adherence Behaviours in Patients with Severe COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and is responsible for significant healthcare-associated costs. Clinical trials have shown that currently available inhaled therapies for COPD are effective in reducing exacerbations and improving outcomes (1, 2). However, there is a disconnect between results obtained in these studies and those observed in clinical practice (3), which may be due to “real world” deficiencies in inhaler adherence. Appropriate implementation of inhaled therapy involves both correct timing of intake (regularity) and good technique (4). Using these parameters to define adherence, we previously showed that adherence to inhaled therapy in patients with COPD is poor, with only 6% of patients achieving an optimal adherence of .80% (mean adherence, 22.66 28.9%) (5). However, the impact of variations in adherence on clinical outcomes was not studied (6). In a follow-up study, we assessed the relationship between distinct adherence behaviors and mortality and all-cause healthcare use in these patients over a 1-year time frame. Some of the results of this study have been previously reported in the form of an abstract (7).

In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial.

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.

Personalising adherence-enhancing interventions using a smart inhaler in patients with COPD : An exploratory cost-effectiveness analysis

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.

P65 Quality of inpatient care for copd exacerbations and it’s impact on clinical outcomes

High rates of rehospitalisation in the 90 days following COPD exacerbation are a concern internationally due to their unpredictable nature, the impact on patient’s health and the pressures they pose on healthcare systems. Strategies to reduce rehospitalisation have looked to improve inpatient management at the time of the index admission. We assessed the rate of adherence to international acute COPD management guidelines and examined which components of these guidelines have the greatest impact on clinical outcomes. Data from 208 patients hospitalised with an acute exacerbation of COPD was retrospectively collected from the medical chart. Adherence to five key components of COPD management was assessed. These included 1) Arterial blood gas measurement, 2) Administration of Controlled Oxygen therapy, 3) Regular short-acting bronchodilator therapy, 4) Prescription of systemic steroids (oral if suitable) and 5) Prescription of appropriate antibiotics, where applicable. Hospital length of stay(LOS) and readmissions up to 90 days following discharge were recorded. The mean age was 71 years and the majority were female. The mean FEV1 was 48% predicted and the median DECAF score was 1 (2) suggesting a low risk exacerbation. Almost 50% had a co-existent consolidation on chest radiograph. The median LOS was 8 days; 80% were discharged directly to home. In the majority of cases only 3 of the 5 acute management components were completed. More than 90% of patients received antibiotics but only one-third were prescribed guideline-directed therapy. Intravenous steroids were used in the majority of cases, 67%, in preference to oral steroids. On multivariate linear regression analysis adjusting for exacerbation severity, age, FEV1 and discharge destination, appropriate prescription of oral steroid therapy reduced LOS by 1.3 days, p=0.023. By day 90, 38% of patients had been readmitted to hospital. The probability of readmission was decreased in those who had received guideline-directed antibiotic therapy, OR 0.35 (95% CI 0.15–0.79) p=0.012. Adherence to acute COPD management guidelines is suboptimal. The greatest improvements in clinical outcomes were associated with prescription of oral steroids, where applicable, and guideline-directed selection of antibiotic therapy. These components should, therefore, be a focus of strategies to improve quality of inpatient care in COPD.

Relationship of inhaler adherence behaviour to clinical outcomes in copd: an observational study

COPD remains a leading cause of healthcare use despite the availability of effective inhaled therapies. We examined adherence to maintenance therapy by assessing the key components of good inhaler use: habit of use and inhaler technique. The relationship between adherence patterns, specific patient characteristics and clinical outcomes at one year was examined. We recruited 226 hospitalised patients with a diagnosis of COPD to this prospective observational study. Inhaler adherence was remotely monitored for 90 days after hospital discharge using an INCATM audio recording device. Cluster analysis grouped patients by their adherence behaviour based on the mean rate of attempted use and critical technique errors. The clinical and psychosocial characteristics of each cluster were examined. The rate of all–cause mortality and healthcare use at 12 months was recorded. Survival analysis was used to evaluate the time to first event across adherence groups. Adherence data was available for 195 patients. We identified four patterns of Adherence behaviour: (1) Regular habit of use and good technique (28%); (2) Regular habit of use and poor technique (21%); (3) Poor habit of use and good technique (33%); (4) Poor habit of use and poor technique (19%). The overall event rate was lowest in Cluster 1, 5.46/person/year. Cluster 2 had the lowest annual rate of hospital presentation, but accounted for the majority of community prescriptions for antibiotics and steroids, mean 4.6/person/year. In an adjusted Cox regression model, Cluster 3 had an increased risk of any adverse outcome compared to Cluster 1, Hazard Ratio 1.8 (1.1–2.9), p=0.02. This group were notable for high anxiety scores and mild cognitive impairment. There was a stepwise increase in mortality across groups, from 11% in Cluster 1% to 33% in Cluster 4, p<0.001. Cluster 4 was older, female, with higher co-morbidity and cognitive impairment. We have identified four clusters of adherence behaviour. There is an association between adherence patterns and clinical outcomes. Each cluster also exhibits distinct clinical and psychosocial traits which may act as drivers of their behaviour. Personalised interventions targeting these specific adherence behaviour patterns may prove a cost-effective strategy to curtail COPD-related healthcare costs.

Reduction in exhaled nitric oxide tracks improved patient inhaler compliance in difficult asthma–a case study

ABSTRACT Introduction: Exhaled nitric oxide is believed be a useful surrogate for airways inflammation while non-adherence with therapy is known to be associated with worsening of asthma control. Case: We present the case of a 49-year-old female with steroid-dependent asthma and an exacerbation rate of >20/year. She was enrolled in a 3-month-long prospective study using a validated diagnostic inhaler device that provided objective evidence of inhaler compliance. Fractional exhaled nitric oxide (FeNO), peak expiratory flow rates, asthma control questionnaires were measured throughout the study period. Peripheral eosinophil count was obtained prior to the study, during the study, and immediately afterwards. Results: Improvement in compliance at the end of the study led to significant improvements in lung function peak expiratory flow rate (PEFR), and objective scores of asthma. There was an observed improvement in PEFR after 4 weeks, with an associated decrease in FeNO from 92 to 9 ppb that plateaued over the remainder of the study. Her eosinophil count was 0.79 × 109/litre prior to starting in the study, 0.37 × 109/litre after 2 months, and 0.1 × 109/litre at the end of the study. Conclusion: We believe that this is the first case study to objectively prove that improvements in compliance can lead to dramatic reductions in the overall inflammatory airway response and in particular that improvements in patient compliance are mirrored by marked reduction in FeNO levels. These changes occurred in tandem with an observed clinical improvement in our patient.