Faculty Bibliography

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 (INCAâ„¢) 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 Diskusâ„¢. 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.

OBJECTIVES/OBJECTIVE:among patients with chronic obstructive pulmonary disease (COPD) who currently receive the 23-valent pneumococcal polysaccharide vaccine (PPV-23) according to vaccination status, use of antibiotics and steroids. To investigate the prevalence of PPV-23 and 13-valent pneumococcal conjugate vaccine (PCV-13) serotypes within the study cohort. DESIGN/METHODS:A non-interventional, observational, prospective cohort study with a 12 -month follow-up period inclusive of quarterly study visits. SETTING/METHODS:Beaumont Hospital and The Royal College of Surgeons in Ireland Clinical Research Centre, Dublin, Ireland. PARTICIPANTS/METHODS:Patients with an established diagnosis of COPD attending a tertiary medical centre. PRIMARY OUTCOME MEASURE/METHODS:. SECONDARY OUTCOME MEASURE/UNASSIGNED:and its relationship with the incidence of exacerbations of COPD. RESULTS:fluctuated over the four seasons with a peak of 6.6% in spring and the lowest rate of 2.2% occurring during winter. Antibiotic use was highest during periods of low colonisation. CONCLUSIONS:colonisation among patients with COPD which may reflect antibiotic use in autumn and winter. The predominance of non-vaccine types suggests that PCV-13 may have limited impact among patients with COPD in Ireland who currently receive PPV-23. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT02535546; post-results.

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.

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: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.

RATIONALE:Currently, studies on adherence to inhaled medications report average adherence over time. This measure does not account for variations in the interval between doses, nor for errors in inhaler use. OBJECTIVES:To investigate whether adherence calculated as a single area under the (concentration-time) curve (AUC) measure, incorporating the interval between doses and inhaler technique, was more reflective of patient outcomes than were current methods of assessing adherence. METHODS:We attached a digital audio device (INhaler Compliance Assessment) to a dry powder inhaler. This recorded when the inhaler was used, and analysis of the audio data indicated if the inhaler had been used correctly. These aspects of inhaler use were combined to calculate adherence over time, as an AUC measure. Over a 3-month period, a cohort of patients with asthma was studied. Adherence to a twice-daily inhaler preventer therapy using this device and clinical measures were assessed. MEASUREMENTS AND MAIN RESULTS:Recordings from 239 patients with severe asthma were analyzed. Average adherence that was based on the dose counter was 84.4%, whereas the ratio of expected to observed accumulated AUC, actual adherence, was 61.8% (P < 0.01). Of all the adherence measures, only adherence calculated as AUC reflected changes in asthma quality of life, β-agonist reliever use, and peak expiratory flow over the 3 months (P < 0.05 compared with other measures of adherence). CONCLUSIONS:Adherence that incorporates the interval between doses and inhaler technique, and calculated as AUC, is more reflective of changes in quality of life and lung function than are the currently used measures of adherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01529697).

BACKGROUND:The efficacy of drug delivery from inhalers is very much dependent on the user's peak inspiratory flow rate (PIFR). Current methods to measure PIFR in inhalers are based on subjective checklists. There is a lack of methods currently available to objectively remotely monitor PIFR in pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). In this study, for the first time, non-contact acoustic methods were employed to estimate PIFR through three commonly used inhalers (Diskus™ DPI, Turbuhaler™ DPI, and Evohaler™ pMDI) with the aim of applying these methods to remotely monitor inhaler inhalation technique in future clinical applications. METHODS:Each inhaler was placed inside an airtight container connected to a spirometer to measure PIFR. A high quality microphone was placed 5 cm from the mouthpiece of the inhalers to record inhalation sounds. Over 2000 inhaler inhalation sounds were recorded from 11 healthy participants. A range of temporal and spectral acoustic features from the inhalation sounds were correlated with PIFR. The variation of acoustic features and the repeatability of the inhalation acoustic spectral profile were investigated to further characterize inhaler inhalation sounds and to determine the reliability of acoustics to estimate PIFR. RESULTS: = 0.75 (Evohaler™)]. Acoustic features generated low variation and the spectral profile of inhalation sounds was repeatable regardless of flow rate, suggesting that acoustic methods are a reliable method of estimating PIFR. CONCLUSIONS:The methods presented in this study may be employed in a wearable monitoring device in future applications to measure inhaler PIFR. Objective monitoring of PIFR in inhalers may help patients improve their inhaler inhalation technique and therefore may be of significant clinical benefit to both patients and clinicians.

BACKGROUND:One-third of patients with an exacerbation of Chronic Obstructive Pulmonary Disease(COPD) are re-hospitalised at 90 days. Exacerbation recovery is associated with reductions in lung hyperinflation and improvements in symptoms and physical activity. We assessed the feasibility of monitoring these clinical parameters in the home. We hypothesised that the degree of change in spirometry and lung volumes differs between those who had an uneventful recovery and those who experienced a further exacerbation. METHODS:Hospitalised patients with an acute exacerbation of COPD referred for a supported discharge program participated in the study. Spirometry and Inspiratory Vital Capacity(IVC) were measured in the home at Days 1, 14 and 42 post-discharge. Patients also completed Medical Research Council(MRC), Borg and COPD Assessment Test(CAT) scores and were provided with a tri-axial accelerometer. Any new exacerbation events were recorded. RESULTS:≥100 ml(AUROC 0.6613) and mean daily step count ≥396 steps(AUROC 0.6381) predictive of recovery. CONCLUSION:Monitoring the pattern of improvement in spirometry, lung volumes, symptoms and step count following a COPD exacerbation may help to identify patients at risk of re-exacerbation. It is feasible to carry out these assessments in the home as part of a supported discharge programme.

Asthma is a chronic respiratory disease affecting millions of people worldwide, and is consequently a major issue for global health. Exacerbations are acute events involving the worsening of asthma's primary respiratory symptoms and are a major cause of morbidity in asthma patients, largely due to the unpredictability of their onset. This study aimed to investigate the relationship between changes in acoustic features of inhaler inhalations and changes in forced expiratory volume in one second (FEV1) that occur during a simulated exacerbation, a bronchial challenge test (BCT). This is a clinical test that simulates an asthma exacerbation through the administration of a bronchoconstrictor agent. Eight patients indicated for a BCT were recruited for this study. Non-contact and tracheal microphones were employed to record Diskusâ„¢ inhaler inhalations throughout the course of a BCT. A spirometer was employed to measure inhaler peak inspiratory flow rate (PIFR). In patients responsive to the BCT (n=4), significant correlations between changes in FEV1 and acoustic features on both microphones existed, with fractal increment of Katz fractal dimension yielding the strongest correlation (R=0.58), and between FEV1 and PIFR (R=0.62). These findings suggest that inhaler inhalation acoustic features may assist in the early detection of exacerbations. Future research will determine whether this is the case in a larger cohort of patients with non-simulated exacerbations.

BACKGROUND:Cross-sectional observational studies suggest that between 50% and 60% of patients misuse a dry powder inhaler, whereas studies with electronic monitors indicate that patients sometimes overuse/underuse their inhalers. It is not known what impact errors and erratic use have on inhaler adherence. OBJECTIVES:The purpose of this study was to longitudinally quantify when and how patients adhered to a twice-daily preventer treatment by using a novel acoustic recording device attached to an inhaler (INhaler Compliance Assessment). METHODS:Patients with a history of asthma or chronic obstructive pulmonary disease (n = 123) from primary care and community pharmacies were given an INhaler Compliance Assessment-adapted inhaler for 1 month. Analysis of the audio files provided quantitative information on time and technique of inhaler use. RESULTS:Data were available for 103 patients. Twenty-one patients (20%) used their inhaler in the correct manner at the correct interval. There were 5045 audio files with attempted inhalations, of which 1204 had technique errors (24%). Errors included inadequate flow (27%), drug priming without inhalation (19%), exhalation into the inhaler (18%), and multiple inhalations (25%). On average, participants made errors 20% of the time. Of 60 doses expected to be taken in a month per person, on average 49 doses (82%) were attempted and when errors were accounted for, the average number of actual doses taken was 34 doses (57%; P < .01) comparing attempted to actual doses. DISCUSSION:These data highlight that ineffective and irregular inhaler use is common and when combined in a single calculation indicate that only 20% of participants used their inhaler correctly and on time.

BACKGROUND:Mortality rates within the Irish farming community are increasing, whilst that of the general population falls. The aim of this cross-sectional study was to determine the prevalence of respiratory disease amongst Irish farmers. METHODS:All study participants were farming volunteers attending an agricultural exhibition. Data collected by questionnaire included baseline demographics, respiratory history, presence of respiratory symptoms and occupational exposures. Spirometry was performed on all participants. RESULTS:Data from 372 farmers was analysed. The majority were male (76%) with median age of 55 years. 61% were never smokers. 13% were previously diagnosed with airway disease (Chronic Obstructive Pulmonary Disease(COPD)/Asthma/Inhaler use) with 14% reporting hayfever/allergies. Almost two-thirds reported one or more chronic respiratory symptom. Forty-four (12%) had obstructive spirometry using fixed FEV1/FVC < 0.70 criterion and 29 (7.8%) using FEV1/FVC < 5% lower limit of normal. The majority, two-thirds, were never smokers. Amongst never smokers with obstruction (13%), there was a significantly higher proportion with a prior diagnosis of airway disease and hayfever/allergies. There was no significant association between specific occupational exposures and obstruction. CONCLUSION:The majority of Irish farmers are never smokers. They have a high prevalence of respiratory symptoms. 13% of never smokers have airflow obstruction (FEV1/FVC < 0.70). The presence of airflow obstruction is significantly associated with self-reported allergy history and prior airway disease. Further studies are needed to identify the workplace factors accounting for these findings.