Breda Cushen

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 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

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.

A novel statistical method for assessing effective adherence to medication and calculating optimal drug dosages.

Objective We derive a novel model-based metric for effective adherence to medication, and validate it using data from the INhaler Compliance Assessment device (INCATM). This technique employs dose timing data to estimate the threshold drug concentration needed to maintain optimal health. Methods The parameters of the model are optimised against patient outcome data using maximum likelihood methods. The model is fitted and validated by secondary analysis of two independent datasets from two remote-monitoring studies of adherence, conducted through clinical research centres of 5 Irish hospitals. Training data came from a cohort of asthma patients (~ 47,000 samples from 218 patients). Validation data is from a cohort of 204 patients with COPD recorded between 2014 and 2016. Results The time above threshold measure is strongly predictive of adverse events (exacerbations) in COPD patients (Odds Ratio of exacerbation = 0.52 per SD increase in adherence, 95% Confidence Interval [0.34–0.79]). This compares well with the best known previous method, the Area Under the dose-time Curve (AUC) (Odds Ratio = 0.69, 95% Confidence Interval [0.48–0.99]). In addition, the fitted value of the dose threshold (0.56 of prescribed dosage) suggests that prescribed doses may be unnecessarily high given good adherence. Conclusions The resulting metric accounts for missed doses, dose-timing errors, and errors in inhaler technique, and provides enhanced predictive validity in comparison to previously used measures. In addition, the method allows us to estimate the correct dosage required to achieve the effect of the medication using the patients’ own adherence data and outcomes. The adherence score does depend not on sex or other demographic factors suggesting that effective adherence is driven by individual behavioural factors.

Targeting patients with asthma for omalizumab therapy: choosing the right patient to get the best value for money

The asthma syndrome has many manifestations, termed phenotypes, that arise by specific cellular and molecular mechanisms, termed endotypes. Understanding an individual’s asthma phenotype helps clinicians make rational therapeutic decisions while the understanding of endotypes has led to the development of specific precision medications. Allergic asthma is an example of an asthma phenotype and omalizumab, a monoclonal antibody that neutralizes serum immunoglobulin (Ig)E, is a specific targeted treatment which was developed as a result of an understanding of the endotype of allergic asthma. Omalizumab has been widely used in clinical practice in Europe for over a decade as an add-on therapy to treat patients who have severe refractory allergic asthma. Over this period, many centres have reported their experience with omalizumab as an add-on therapy in patients with severe asthma. These ‘real world’ clinical effectiveness studies have confirmed the benefits, cost-effectiveness and clinical utility of this medication. Combining the outcomes of both sources of research has yielded important insights that may benefit patients with severe asthma, clinicians who treat them, as well as the funding agencies that reimburse the cost of this medication. The purpose of this review is to describe how to identify and evaluate a patient with asthma for whom treatment with omalizumab may be of clinical and cost-effective benefit. The assessment and investigations used to confirm allergic asthma, the objective assessment of adherence to asthma therapy and the expected benefits of add-on omalizumab treatment are described.

P292 Pilot study to assess bronchodilator response during an acute exacerbation of copd using a vibrating mesh nebuliser versus jet nebuliser for bronchodilator delivery

Introduction Recovery from COPD exacerbation is associated with increases in respirable lung volume. Accelerating these changes through improved bronchodilator delivery could hasten recovery. Hypothesis Vibrating mesh nebuliser (Aerogen® Ultra) results in greater change in lung physiology compared to standard small volume jet nebuliser. Methods Patients with an exacerbation of COPD were randomised to receive combined salbutamol 2.5 mg/ipratropium bromide 0.5mg via vibrating mesh (Active group) or standard hospital jet nebuliser (Control) on one occasion between day 2–7 of hospitalisation. Spirometry, body plethysmography and impulse oscillometry were performed pre-bronchodilator and at 1 hour post. Borg breathlessness score was measured. Results Thirty-one patients have been recruited to date, 16 to the active group and 15 control group. Mean FEV1 was 48 ± 18% predicted. Baseline demographics were comparable between groups. Both groups had significant improvements in FEV1 and Inspiratory Capacity post-bronchodilator, with greater increases in FVC in the active group (0.40 ± 0.39 L vs 0.19 ± 0.19 L, p = 0.06). Significant changes in operating lung volumes and airway impedance were seen in both groups. There was no significant difference in Borg score. Conclusion Bronchodilator administration, during a COPD exacerbation, results in significant improvements in spirometry, lung volume and airway impedance. Drug delivery by vibrating mesh nebuliser results in greater absolute increases in FVC. Further studies will assess whether this translates into accelerated exacerbation recovery.

Pleural effusion arising from a rare pancreatic neoplasm

To the Editors: Pleural effusions are common entities and may complicate a number of disease processes. We present the case of a large pleural effusion associated with a rare pancreatic neoplasm. The patient, a 67-yr-old female, was referred for respiratory opinion by the Breast Cancer Service at St Vincent’s University Hospital (Dublin, Ireland). She had a background of invasive ductal carcinoma of the right breast 4 yrs previously for which she had undergone a wide local excision and was taking hormonal therapy. Other past medical history included a diagnosis of seropositive rheumatoid arthritis requiring only analgesic therapy. She had known tuberculosis (TB) exposure in childhood and was a nonsmoker. She drank alcohol only on occasion. She had initially noticed that she was sinking to the left side while swimming over the previous month. This was followed by progressive dyspnoea on exertion, left-sided chest pain and nocturnal non-productive cough. She denied haemoptysis or weight loss and was systemically well. Physical examination identified stony-dull percussion and reduced breath sounds over the mid-lower left lung. She was comfortable at rest with oxygen saturations of 96% on room air. There was no clubbing or lymphadenopathy. A chest radiograph confirmed a large left-sided pleural effusion (fig. 1a). Pleural …

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.