Imran Sulaiman

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

Acute Pulmonary Admissions Following Implementation of a National Workplace Smoking Ban

BACKGROUND The implementation of workplace smoking bans has contributed to a significant reduction in the incidence of acute coronary syndrome admissions, but their influence on adult acute pulmonary disease admissions is unclear. We sought to assess the impact of a national smoking ban on nationwide admissions of individuals of working age with acute pulmonary illness. METHODS Data relating to emergency hospital admissions of subjects aged 20 to 70 years preceding and succeeding the implementation of the Irish smoking ban were obtained from a central registry. Population, weather, pollution, and influenza data were obtained from the relevant authorities. Poisson regression analysis was used to assess adjusted risk of emergency hospital admission following implementation of the smoking ban. RESULTS Overall admissions with pulmonary illness decreased from 439 per 100,000 population per annum to 396 per 100,000 population per annum following the ban (unadjusted relative risk [RR], 0.91; 95% CI, 0.83-0.99; P = .048). This persisted following adjustment for confounding factors (adjusted RR, 0.85; 95% CI, 0.72-0.99; P = .04) and was most marked among younger age groups and in admissions due to asthma (adjusted RR, 0.60; 95% CI, 0.39-0.91; P = .016). Admissions with acute coronary syndromes (adjusted RR, 0.82; 95% CI, 0.70-0.97; P = .02), but not stroke (adjusted RR, 0.93; 95% CI, 0.73-1.20; P = .60), were also reduced. CONCLUSIONS The implementation of a nationwide workplace smoking ban is associated with a decline in admissions with acute pulmonary disease among specific age groups and an overall reduction in asthma admissions. This may result from reduced exposure of vulnerable individuals to environmental tobacco smoke, emphasizing the potential benefit of legislation reducing second-hand smoke exposure.

Investigating the relationship between peak inspiratory flow rate and volume of inhalation from a Diskus™ Inhaler and baseline spirometric parameters: a cross-sectional study

Drug delivery from a Dry Powder Inhaler (DPI) is dependent on the peak inspiratory flow rate (PIFR) generated. Currently available methods for estimating PIFR from most DPIs are limited and mainly rely on subjective assessment. We aim to show that spirometric and Diskus™ PIFR and Inspiratory Vital Capacity (IVC) are related to the underlying respiratory condition and that spirometric PIFR can be used to assess whether Diskus™ PIFR will be adequate when using this DPI. Healthy volunteers and patients with asthma, COPD, neuromuscular disease and non-respiratory disorders were recruited (n = 85). Demographics and baseline lung function by spirometry were recorded. Flow and volume readings were taken while patients used a Diskus™ DPI, housed in an airtight container connected to a spirometer. T-tests were performed to compare mean spirometric and Diskus™ PIFR/ IVC between groups. Stepwise regression analysis of Diskus™ PIFR versus spirometric PIFR, spirometric IVC, age, gender, condition, BMI, FEV1 and FVC was performed.The Diskus™ PIFR for the COPD and Neuromuscular Disease group was more than 10 L/min lower than the Healthy or Asthma groups (p < 0.05). The mean spirometric and Diskus™ IVC of the Healthy group was significantly (>0.75 L) higher than the mean for the other three groups (p < 0.05). Diskus™ PIFR was moderately correlated with spirometric PIFR and age (Adjusted R2 = 0.58, p < 0.0001). PIFR generated using a Diskus™ DPI is dependent on the underlying disease and age. A spirometric PIFR of less than 196 L/min should prompt further investigation into the suitability of a patient for a Diskus™ DPI, with possible consideration of alternate devices.

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

A protocol for a randomised clinical trial of the effect of providing feedback on inhaler technique and adherence from an electronic device in patients with poorly controlled severe asthma

Introduction In clinical practice, it is difficult to distinguish between patients with refractory asthma from those with poorly controlled asthma, where symptoms persist due to poor adherence, inadequate inhaler technique or comorbid diseases. We designed an audio recording device which, when attached to an inhaler, objectively identifies the time and technique of inhaler use, thereby assessing both aspects of adherence. This study will test the hypothesis that feedback on these two aspects of adherence when passed on to patients improves adherence and helps clinicians distinguish refractory from difficult-to-control asthma. Methods This is a single, blind, prospective, randomised, clinical trial performed at 5 research centres. Patients with partially controlled or uncontrolled severe asthma who have also had at least one severe asthma exacerbation in the prior year are eligible to participate. The effect of two types of nurse-delivered education interventions to promote adherence and inhaler technique will be assessed. The active group will receive feedback on their inhaler technique and adherence from the new device over a 3-month period. The control group will also receive training in inhaler technique and strategies to promote adherence, but no feedback from the device. The primary outcome is the difference in actual adherence, a measure that incorporates time and technique of inhaler use between groups at the end of the third month. Secondary outcomes include the number of patients who remain refractory despite good adherence, and differences in the components of adherence after the intervention. Data will be analysed on an intention-to-treat and a per-protocol basis. The sample size is 220 subjects (110 in each group), and loss to follow-up is estimated at 10% which will allow results to show a 10% difference (0.8 power) in adherence between group means with a type I error probability of 0.05. Trial registration number NCT01529697; Pre-results.

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.

The INCATM (Inhaler Compliance AssessmentTM): A comparison with established measures of adherence.

Objective: To compare the Inhaler Compliance AssessmentTM (INCATM), a novel audio-recording device objectively measuring timing and proficiency of inhaler use, against established adherence measures, and explore its discriminant and predictive validity. Design: Prospective observational study; 184 chronic obstructive pulmonary disease (COPD) patients used an INCATM-enabled salmeterol/fluticasone inhaler for one-month post-hospital discharge. Main outcome measures: INCATM (Attempted, Attempted Interval, Actual) adherence correlated with Doses Used Rate, self-reported adherence and prescription refill for concurrent validity. Discriminant validity for reason for admission, cognition and lung function; predictive validity for health status and quality-of-life. Results: Rates of Attempted, Attempted Interval and Actual adherence were 59, 47 and 23%, respectively. Only 7% of participants had Actual adherence >80%. INCATM variables significantly correlated with Doses Used Rate but not with self-report; Attempted and Attempted Interval were weakly associated with prescription refill. Higher cognitive and lung functioning groups had better INCATM adherence. Attempted and Attempted Interval predicted health status, while Doses Used Rate predicted quality-of-life. Conclusion: INCATM did not strongly correlate with self-report or prescription refill data. Discriminant and predictive validity demonstrated by INCATM suggests the potential utility of the INCATM as a method to identify intentional and unintentional adherence to inhaled medication and facilitate targeted intervention.

Characterization of patient inhaler inhalation sounds using non-contact and tracheal microphones

The dose delivery from dry powder inhalers is dependent on user inhalation technique, particularly the peak inspiratory flow rate (PIFR). Non-contact acoustic methods have recently been employed to objectively measure PIFR during inhaler use. This study aimed to further inhaler acoustics research by extracting acoustic features from inhaler inhalation sounds using non-contact and tracheal microphones and correlating these features with PIFR. This study also investigated the repeatability of the position of the peaks and troughs of the inhaler inhalation power spectral density (PSD) profile across patients. The effects of PIFR, inhalation duration, age, gender, body mass index (BMI) and lung function on the PSD profile were also investigated. Fifty three patients (asthma (n = 26), COPD (n = 14) and other respiratory conditions (n = 13), such as obstructive sleep apnea and chronic cough) were recruited for this study. Each patient was asked to inhale at maximal flow rate through a Diskus™ inhaler while non-contact (5 cm from the inhaler mouthpiece) and tracheal microphones recorded the inhalation sounds. A gold standard measurement of PIFR of inhaler inhalations was also measured simultaneously using a spirometer. It was observed that the Shannon entropy (H) of inhalation sounds generated the strongest correlation with PIFR in the non-contact recordings (R 2 = 0.82, p < 0.001). The average power (P ave) of inhalation sounds generated the strongest correlation with PIFR in the tracheal recordings (R 2 = 0.29, p < 0.001). It was found that the position of peaks and troughs in the PSD profile of inhaler inhalations were more repeatable at an intra-patient level (p < 0.001) and that PIFR, inhalation duration and age had weak significant effects on the inhalation PSD profile (p < 0.01). Non-contact acoustic methods show promising opportunities to objectively monitor patient inhalation technique and respiratory health remotely which may greatly benefit both patients and healthcare professionals.

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.