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.

Personalized Biofeedback on Inhaler Adherence and Technique by Community Pharmacists: A Cluster Randomized Clinical Trial.

BACKGROUND: Guidelines recommend that patients treated with inhalers receive adherence counseling and device training. Digital technologies that assess both inhaler adherence and technique have been developed. Using these technologies community pharmacists, who have regular contact with patients, are well placed to deliver personalized inhaler education. OBJECTIVE: To determine the impact of a pharmacist intervention, informed by digital technology, on inhaler technique and adherence of patients with asthma in the community. METHODS: A cluster randomized, parallel-group, multisite pharmacy study was conducted over 6 months. All study groups had an electronic device (inhaler compliance assessment device) attached to their maintenance inhaler. A biofeedback group received personalized inhaler training informed by data recorded by the device. The demonstration group received inhaler training, by physical demonstration with a placebo inhaler. The control group received usual care. The primary outcome was inhaler adherence, which was classified as "actual adherence" and expressed as the proportion of expected drug accumulation if adherence and technique had been perfect. Secondary outcomes were quality-of-life scores as measured by the St George's Respiratory Questionnaire, symptoms, and exacerbations. RESULTS: A total of 152 participants (n = 74 biofeedback, n = 56 demonstration, and n = 22 control) were recruited. Asthma was the predominant condition among participants (n = 83), with chronic obstructive pulmonary disease (n = 55) and asthma/chronic obstructive pulmonary disease overlap also reported (n = 8). In intention-to-treat analysis, adherence in the biofeedback group during month 2 was 62%, 18% higher (95% CI, 6 to 30) than that in the demonstration group (P = .004) and 24% higher (95% CI, 9 to 40) than that in the control group (P = .003). During month 6, adherence was 14% higher (95% CI, -1 to 30; P = .07) in the biofeedback group than in the demonstration group and 31% higher (95% CI, 13 to 48; P = .001) than in the control group. At the end of the study, the biofeedback group had a sustained fall in St George's Respiratory Questionnaire from baseline, -6.1 (95% CI, -9 to -0.4; P = .04) and had significantly improved daily respiratory symptoms. CONCLUSIONS: Community pharmacist-delivered inhaler training informed by a digital technology improved adherence and health status.

Automatic Audio-Based Classification of Patient Inhaler Use: A Pharmacy Based Study.

Chronic respiratory diseases may be controlled through the delivery of medication to the airways and lungs using an inhaler. However, adherence to correct inhaler technique is poor, which impedes patients from receiving maximum clinical benefit from their medication. In this study, the Inhaler Compliance Assessment device was employed to record audio of patients using a Diskus dry powder inhaler. An algorithm that classifies inhaler sounds (blister, inhalation, interference) was developed to automatically assess patient adherence from these inhaler audio recordings. The presented algorithm employed audio-based signal processing methods and statistical modeling in the form of quadratic discriminant analysis (QDA). A total of 350 audio recordings were obtained from 70 patients. The acquired audio dataset was split evenly for training and testing. A total accuracy of 85.35% was obtained (testing dataset) for this 3-class classification system. A sensitivity of 89.22% and 70% was obtained for inhalation and blister detection respectively. This approach may have significant clinical impact by providing healthcare professionals with an efficient, objective method of monitoring patient adherence to inhaler treatment.

Regional infectious disease surveillance networks and their potential to facilitate the implementation of the international health regulations.

The International Health Regulations (IHR) 2005 present a challenge and opportunity for global surveillance and control of infectious diseases. This article examines the opportunity for regional networks to address this challenge. Two regional infectious disease surveillance networks, established in the Mekong Basin and the Middle East, are presented as case studies. The public-private partnerships in the networks have led to an upgrade in infectious disease surveillance systems in capacity building, purchasing technology equipment, sharing of information, and development of preparedness plans in combating avian influenza. These regional networks have become an appropriate infrastructure for the implementation of the IHR 2005.

Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence.

Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be clinically beneficial for inhaler technique training and the remote monitoring of patient adherence.

Advances in Audio-Based Systems to Monitor Patient Adherence and Inhaler Drug Delivery.

Hundreds of millions of people worldwide have asthma and COPD. Current medications to control these chronic respiratory diseases can be administered using inhaler devices, such as the pressurized metered dose inhaler and the dry powder inhaler. Provided that they are used as prescribed, inhalers can improve patient clinical outcomes and quality of life. Poor patient inhaler adherence (both time of use and user technique) is, however, a major clinical concern and is associated with poor disease control, increased hospital admissions, and increased mortality rates, particularly in low- and middle-income countries. There are currently limited methods available to health-care professionals to objectively and remotely monitor patient inhaler adherence. This review describes recent sensor-based technologies that use audio-based approaches that show promising opportunities for monitoring inhaler adherence in clinical practice. This review discusses how one form of sensor-based technology, audio-based monitoring systems, can provide clinically pertinent information regarding patient inhaler use over the course of treatment. Audio-based monitoring can provide health-care professionals with quantitative measurements of the drug delivery of inhalers, signifying a clear clinical advantage over other methods of assessment. Furthermore, objective audio-based adherence measures can improve the predictability of patient outcomes to treatment compared with current standard methods of adherence assessment used in clinical practice. Objective feedback on patient inhaler adherence can be used to personalize treatment to the patient, which may enhance precision medicine in the treatment of chronic respiratory diseases.

Objective Assessment of Patient Inhaler User Technique Using an Audio-Based Classification Approach.

Many patients make critical user technique errors when using pressurised metered dose inhalers (pMDIs) which reduce the clinical efficacy of respiratory medication. Such critical errors include poor actuation coordination (poor timing of medication release during inhalation) and inhaling too fast (peak inspiratory flow rate over 90 L/min). Here, we present a novel audio-based method that objectively assesses patient pMDI user technique. The Inhaler Compliance Assessment device was employed to record inhaler audio signals from 62 respiratory patients as they used a pMDI with an In-Check Flo-Tone device attached to the inhaler mouthpiece. Using a quadratic discriminant analysis approach, the audio-based method generated a total frame-by-frame accuracy of 88.2% in classifying sound events (actuation, inhalation and exhalation). The audio-based method estimated the peak inspiratory flow rate and volume of inhalations with an accuracy of 88.2% and 83.94% respectively. It was detected that 89% of patients made at least one critical user technique error even after tuition from an expert clinical reviewer. This method provides a more clinically accurate assessment of patient inhaler user technique than standard checklist methods.

Monitoring Inhaler Inhalations Using an Acoustic Sensor Proximal to Inhaler Devices.

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: All acoustic features were significantly correlated with PIFR (p < 0.001). The mean power of the inhalation sound generated the most consistent correlation across all inhalers [R2 = 0.77 (Diskus™), R2 = 0.7 (Turbuhaler™), R2 = 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.

Changes in inhaler inhalation acoustic features during induced bronchoconstriction: a pilot study.

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 Diskus™ 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.

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 participant's 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 effect of providing feedback on inhaler technique and adherence from an electronic audio recording device, INCA®, in a community pharmacy setting: study protocol for a randomised controlled trial.

BACKGROUND: Poor adherence to inhaled medication may lead to inadequate symptom control in patients with respiratory disease. In practice it can be difficult to identify poor adherence. We designed an acoustic recording device, the INCA® (INhaler Compliance Assessment) device, which, when attached to an inhaler, identifies and records the time and technique of inhaler use, thereby providing objective longitudinal data on an individual's adherence to inhaled medication. This study will test the hypothesis that providing objective, personalised, visual feedback on adherence to patients in combination with a tailored educational intervention in a community pharmacy setting, improves adherence more effectively than education alone. METHODS/DESIGN: The study is a prospective, cluster randomised, parallel-group, multi-site study conducted over 6 months. The study is designed to compare current best practice in care (i.e. routine inhaler technique training) with the use of the INCA® device for respiratory patients in a community pharmacy setting. Pharmacies are the unit of randomisation and on enrolment to the study they will be allocated by the lead researcher to one of the three study groups (intervention, comparator or control groups) using a computer-generated list of random numbers. Given the nature of the intervention neither pharmacists nor participants can be blinded. The intervention group will receive feedback from the acoustic recording device on inhaler technique and adherence three times over a 6-month period along with inhaler technique training at each of these times. The comparator group will also receive training in inhaler use three times over the 6-month study period but no feedback on their habitual performance. The control group will receive usual care (i.e. the safe supply of medicines and advice on their use). The primary outcome is the rate of participant adherence to their inhaled medication, defined as the proportion of correctly taken doses of medication at the correct time relative to the prescribed interval. Secondary outcomes include exacerbation rates and quality of life measures. Differences in the timing and technique of inhaler use as altered by the interventions will also be assessed. Data will be analysed on an intention-to-treat and a per-protocol basis. Sample size has been calculated with reference to comparisons to be made between the intervention and comparator clusters and indicates 75 participants per cluster. With an estimated 10 % loss to follow-up we will be able to show a 20 % difference between the population means of the intervention and comparator groups with a power of 0.8. The Type I error probability associated with the test of the null hypothesis is 0.05. DISCUSSION: This clinical trial will establish whether providing personalised feedback to individuals on their inhaler use improves adherence. It may also be possible to enhance the role of pharmacists in clinical care by identifying patients in whom alteration of either therapy or inhaler device is appropriate. REGISTRATION: ClinicalTrials.gov NCT02203266 .

Influences of gender and anthropometric features on inspiratory inhaler acoustics and peak inspiratory flow rate.

Inhalers are hand-held devices used to treat chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Medication is delivered from an inhaler to the user through an inhalation maneuver. It is unclear whether gender and anthropometric features such as age, height, weight and body mass index (BMI) influence the acoustic properties of inspiratory inhaler sounds and peak inspiratory flow rate (PIFR) in inhalers. In this study, healthy male (n=9) and female (n=7) participants were asked to inhale at an inspiratory flow rate (IFR) of 60 L/min in four commonly used inhalers (Turbuhaler(™), Diskus(™), Ellipta(™) and Evohaler(™)). Ambient inspiratory sounds were recorded from the mouthpiece of each inhaler and over the trachea of each participant. Each participant's PIFR was also recorded for each of the four inhalers. Results showed that gender and anthropometric features have the potential to influence the spectral properties of ambient and tracheal inspiratory inhaler sounds. It was also observed that males achieved statistically significantly higher PIFRs in each inhaler in comparison to females (p<;0.05). Acoustic features were found to be significantly different across inhalers suggesting that acoustic features are modulated by the inhaler design and its internal resistance to airflow.

An acoustic method to automatically detect pressurized metered dose inhaler actuations.

Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) affect over 400 million people and are incurable. The pressurized metered dose inhaler (pMDI) has been the most popular inhaler device in inhaled therapy in recent times. However the pMDIs require good coordination between inhaling and actuating the inhaler to deliver the aerosolized drug most effectively. Poor coordination can greatly reduce the amount of drug delivered to a patient and therefore reducing the control of respiratory disease symptoms. Acoustic methods have been recently employed to monitor inhaler technique quite effectively. This study employs a noninvasive acoustic method to detect actuation sounds in a portable monitoring device. A total of 158 actuation sounds were obtained from a group of healthy subjects (n=5) and subjects suffering from respiratory diseases (n=15). The developed algorithm generated an overall accuracy of 99.7% demonstrating that this method may have clinical potential to monitor pMDI actuation coordination. The informative feedback from this method may also be employed in clinical training to highlight patient actuation technique.

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 individual's 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.

Trust across borders: responding to 2009 H1N1 influenza in the Middle East.

Disease surveillance networks in the Middle East, Southeast Asia, and Africa are models for the kind of transnational cooperation that can mount the needed flexible and coordinated response to the spread of 2009 H1N1 influenza and future pandemic threats. For example, members of the Middle East Consortium on Infectious Disease Surveillance (MECIDS), a regional disease surveillance network of public health experts and ministry of health officials from Israel, the Palestinian Authority, and Jordan, have coordinated the screening, laboratory testing, and risk communication strategies to detect and control 2009 H1N1 influenza. This coordination is made possible by trust and by well-exercised national and regional pandemic preparedness policies. The consortium illustrates the value of regional disease surveillance networks in shaping and managing cohesive policies on current and future threats. The MECIDS alliance partnership also exemplifies to other parts of the world that are experiencing conflict-like South Asia-that finding common ground is imperative to promoting health security and cooperation where it is most lacking and needed and that developing cohesive infectious disease control policies can build trust across the most difficult boundaries in the world. This article provides an overview of the history of MECIDS and similar networks and of the MECIDS response to 2009 H1N1 influenza.