Novel Measurements of Cough and Breathing Abnormalities during Sleep in Cystic Fibrosis

This Doctor of Philosophy thesis describes cystic fibrosis (CF), sleep parameters and novel measurement techniques to determine the effect of lung disease on sleep using non-invasive techniques. Cystic Fibrosis (CF) is characterised by lungs that are normal at birth, but as lung disease progresses with age, adults with CF can develop sleep abnormalities including alteration in sleep architecture and sleep disordered breathing. This thesis seeks to investigate simple non-invasive measures which can detect abnormalities of sleep and breathing in CF adults. The identification of respiratory sounds (normal lung sounds, coughs, crackles, wheezes and snores) will be examined using the non-invasive sleep and breathing measurement device, the Sonomat. The characterisation of these respiratory sounds will be based on spectrographic and audio analysis of the Sonomat. Cross-sectional and longitudinal analysis of adults with CF using polysomnography and the Sonomat will further assess objective sleep and breathing abnormalities. Additional to the examination of objective measurements of sleep, subjective evaluation using CF-specific and sleep-specific questionnaires will assess subjective sleep quality and QoL in adults with CF

Domiciliary monitoring to predict exacerbations of COPD

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common, longterm condition that is usually caused by cigarette smoking. In addition to daily symptoms and limitation in activities, patients are prone to chest infections ('exacerbations'). These are a significant problem: unpleasant for patients, and sometimes severe enough to cause hospital admission and death. Reducing the impact of exacerbations is very important. Previous studies have shown that earlier treatment of exacerbations results in faster recovery, and reduced risk of hospital admission. Helping patients to better detect exacerbations early is therefore important. This PhD focuses on measuring overnight heart rate and oxygen saturation, which we hypothesised would provide the best chance of detecting COPD exacerbations earlier than changes in symptoms. // Aim: To evaluate the potential of monitoring physiological variables to provide earlier detection of exacerbations of COPD. // Methods: Firstly, a systematic review was conducted to assess the existing literature on predicting exacerbations of COPD by monitoring physiological variables. Next, two clinical tele-health datasets were accessed, from two different NHS services in London, to report the impact of false alarms on tele-health service, and to examine the feasibility of using downloadable data from home non-invasive ventilation to detect exacerbations resulting in hospitalisation. National and international surveys were conducted to explore the techniques that have been used by healthcare providers on how to customise tele-health alarm limits for each individual, and to explore healthcare providers’ perceptions of tele-health for COPD. These preliminary projects enabled me to formulate my research question and main PhD hypothesis, tested using a prospective randomised controlled trial. Patients were randomised into two groups (one measured physiology only in the morning versus overnight continuous measurement) and patients were monitored for up to six months or the first exacerbation, whichever was sooner. Patients’ acceptance of continuous overnight monitoring was assessed at the end of the study. // Results: Existing studies that used physiological variables were small and heterogeneous using different variables and different protocols. The majority of medical alarms received by tele-health teams are false. Most patients reported a positive acceptance of being monitored overnight. Continuous overnight monitoring identified changes at exacerbation earlier than once-daily monitoring, and earlier than symptoms. Changes in physiological variables were correlated with changes in symptoms during non-stable phases. There is widespread UK national and international use of tele-health monitoring physiological variables in COPD without sufficient evidence base. // Conclusion: Monitoring physiological parameters may be useful in assisting earlier detection of COPD exacerbations but further, robust studies are required to confirm this. A particular challenge is how to set alarm limits for individual patients given the heterogeneity inherent in COPD and COPD exacerbations

ARTIFICIAL INTELLIGENCE-ENABLED EDGE-CENTRIC SOLUTION FOR AUTOMATED ASSESSMENT OF SLEEP USING WEARABLES IN SMART HEALTH

ARTIFICIAL INTELLIGENCE-ENABLED EDGE-CENTRIC SOLUTION FOR AUTOMATED ASSESSMENT OF SLEEP USING WEARABLES IN SMART HEALT

Wearable in-ear pulse oximetry: theory and applications

Wearable health technology, most commonly in the form of the smart watch, is employed by millions of users worldwide. These devices generally exploit photoplethysmography (PPG), the non-invasive use of light to measure blood volume, in order to track physiological metrics such as pulse and respiration. Moreover, PPG is commonly used in hospitals in the form of pulse oximetry, which measures light absorbance by the blood at different wavelengths of light to estimate blood oxygen levels (SpO2). This thesis aims to demonstrate that despite its widespread usage over many decades, this sensor still possesses a wealth of untapped value. Through a combination of advanced signal processing and harnessing the ear as a location for wearable sensing, this thesis introduces several novel high impact applications of in-ear pulse oximetry and photoplethysmography. The aims of this thesis are accomplished through a three pronged approach: rapid detection of hypoxia, tracking of cognitive workload and fatigue, and detection of respiratory disease. By means of the simultaneous recording of in-ear and finger pulse oximetry at rest and during breath hold tests, it was found that in-ear SpO2 responds on average 12.4 seconds faster than the finger SpO2. This is likely due in part to the ear being in close proximity to the brain, making it a priority for oxygenation and thus making wearable in-ear SpO2 a good proxy for core blood oxygen. Next, the low latency of in-ear SpO2 was further exploited in the novel application of classifying cognitive workload. It was found that in-ear pulse oximetry was able to robustly detect tiny decreases in blood oxygen during increased cognitive workload, likely caused by increased brain metabolism. This thesis demonstrates that in-ear SpO2 can be used to accurately distinguish between different levels of an N-back memory task, representing different levels of mental effort. This concept was further validated through its application to gaming and then extended to the detection of driver related fatigue. It was found that features derived from SpO2 and PPG were predictive of absolute steering wheel angle, which acts as a proxy for fatigue. The strength of in-ear PPG for the monitoring of respiration was investigated with respect to the finger, with the conclusion that in-ear PPG exhibits far stronger respiration induced intensity variations and pulse amplitude variations than the finger. All three respiratory modes were harnessed through multivariate empirical mode decomposition (MEMD) to produce spirometry-like respiratory waveforms from PPG. It was discovered that these PPG derived respiratory waveforms can be used to detect obstruction to breathing, both through a novel apparatus for the simulation of breathing disorders and through the classification of chronic obstructive pulmonary disease (COPD) in the real world. This thesis establishes in-ear pulse oximetry as a wearable technology with the potential for immense societal impact, with applications from the classification of cognitive workload and the prediction of driver fatigue, through to the detection of chronic obstructive pulmonary disease. The experiments and analysis in this thesis conclusively demonstrate that widely used pulse oximetry and photoplethysmography possess a wealth of untapped value, in essence teaching the old PPG sensor new tricks.Open Acces

Devices and Data Workflow in COPD Wearable Remote Patient Monitoring: A Systematic Review

Background: With global increase in Chronic Obstructive Pulmonary Disease (COPD) prevalence and mortality rates, and socioeconomical burden continuing to rise, current disease management strategies appear inadequate, paving the way for technological solutions, namely remote patient monitoring (RPM), adoption considering its acute disease events management benefit. One RPM’s category stands out, wearable devices, due to its availability and apparent ease of use. Objectives: To assess the current market and interventional solutions regarding wearable devices in the remote monitoring of COPD patients through a systematic review design from a device composition, data workflow, and collected parameters description standpoint. Methods: A systematic review was conducted to identify wearable device trends in this population through the development of a comprehensive search strategy, searching beyond the mainstream databases, and aggregating diverse information found regarding the same device. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and quality appraisal of identified studies was performed using the Critical Appraisal Skills Programme (CASP) quality appraisal checklists. Results: The review resulted on the identification of 1590 references, of which a final 79 were included. 56 wearable devices were analysed, with the slight majority belonging to the wellness devices class. Substantial device heterogeneity was identified regarding device composition type and wearing location, and data workflow regarding 4 considered components. Clinical monitoring devices are starting to gain relevance in the market and slightly over a third, aim to assist COPD patients and healthcare professionals in exacerbation prediction. Compliance with validated recommendations is still lacking, with no devices assessing the totality of recommended vital signs. Conclusions: The identified heterogeneity, despite expected considering the relative novelty of wearable devices, alerts for the need to regulate the development and research of these technologies, specially from a structural and data collection and transmission standpoints.Introdução: Com o aumento global das taxas de prevalência e mortalidade da Doença Pulmonar Obstrutiva Crónica (DPOC) e o seu impacto socioeconómico, as atuais estratégias de gestão da doença parecem inadequadas, abrindo caminho para soluções tecnológicas, nomeadamente para a adoção da monitorização remota, tendo em conta o seu benefício na gestão de exacerbações de doenças crónicas. Dentro destaca-se uma categoria, os dispositivos wearable, pela sua disponibilidade e aparente facilidade de uso. Objetivos: Avaliar as soluções existentes, tanto no mercado, como na área de investigação, relativas a dispositivos wearable utilizados na monitorização remota de pacientes com DPOC através de uma revisão sistemática, do ponto de vista da composição do dispositivo, fluxo de dados e descrição dos parâmetros coletados. Métodos: Uma revisão sistemática foi realizada para identificar tendências destes dispositivos, através do desenvolvimento de uma estratégia de pesquisa abrangente, procurando pesquisar para além das databases convencionais e agregar diversas informações encontradas sobre o mesmo dispositivo. Para tal, foram seguidas as diretrizes PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), e a avaliação da qualidade dos estudos identificados foi realizada utilizando a ferramenta CASP (Critical Appraisal Skills Programme). Resultados: A revisão resultou na identificação de 1590 referências, das quais 79 foram incluídas. Foram analisados 56 dispositivos wearable, com a ligeira maioria a pertencer à classe de dispositivos de wellness. Foi identificada heterogeneidade substancial nos dispositivos em relação à sua composição, local de uso e ao fluxo de dados em relação a 4 componentes considerados. Os dispositivos de monitorização clínica já evidenciam alguma relevância no mercado e, pouco mais de um terço, visam auxiliar pacientes com DPOC e profissionais de saúde na previsão de exacerbações. Ainda assim, é notória a falta do cumprimento das recomendações validadas, não estando disponíveis dispositivos que avaliem a totalidade dos sinais vitais recomendados. Conclusão: A heterogeneidade identificada, apesar de esperada face à relativa novidade dos dispositivos wearable, alerta para a necessidade de regulamentação do desenvolvimento e investigação destas tecnologias, especialmente do ponto de vista estrutural e de recolha e transmissão de dados

Continuous remote monitoring of COPD patients—justification and explanation of the requirements and a survey of the available technologies

Remote patient monitoring should reduce mortality rates, improve care, and reduce costs. We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers. Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field. We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain. Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO2) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients. We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise. We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters. The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems

Cardiorespiratory Function in Young Adults With a History of Covid-19 Infection

Objective. Respiratory complications may persist several months into the recovery period following COVID-19 infection. This study evaluated respiratory function and oxygen saturation variability between young adults with a history of COVID-19 infection and controls. Associations between cardiorespiratory function with potential biobehavioral correlates of COVID-19 infection were also explored.Methods. 57 adults ages 18 to 65 participated in this study (24 COVID+, 33 Control). Spirometry was used to assess pulmonary function volumes of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC and peak expiratory flow (PEF). Exhaled nitric oxide (FeNO) was measured using the NiOX VERO, a handheld electrochemical nitric oxide analyzer and taken as a proxy of airway inflammation. Systemic inflammation levels were assessed using salivary concentrations of inflammatory biomarkers. Oxygen saturation variability was quantified via extended continuous oxygen saturation (SpO2) monitoring using linear and nonlinear analyses. Network physiology analysis was conducted to evaluate cardiorespiratory control between SpO2, heart rate (HR), respiratory rate and skin temperature signals measured by continuous ambulatory monitoring with an Equivital EQO2 LifeMonitor. Physical activity levels and sedentary time were assessed using 9-day accelerometry. COVID-19 symptom severity was assessed by participant self-report via questionnaires. Results. No group differences were observed for pulmonary function of FVC (COVID+: 4.22±1.01, C: 4.43±1.06 L, p=.663), FEV1 (COVID+: 3.45±0.72, C: 3.57±0.92 L, p=.865), PEF (COVID+: 349.63±105.54, C: 373.73±140.61 L/min, p=.370), or FeNO (COVID+: 16.61±13.04, C: 20.03±20.11 ppb, p=.285). Linear and nonlinear oxygen saturation variability did not differ between adults with a history of COVID-19 infection and controls with no history of infection (p\u3e0.05). Cardiorespiratory function measured using network analysis of did not differ between recovering COVID-19 individuals and controls (p\u3e0.05). Sedentary time was inversely associated with FEV1 (r=-.392, p=.040), PEF (r=-.579, p=.003), and IL-6 concentrations (r=- .370, p=.049). COVID-19 disease severity was inversely associated with FVC (r=-.461, p=.012) and FEV1 (r=-.365, p=.040). Number of symptoms was inversely associated with FVC (r=-.404, p=.025). Conclusions. Pulmonary function, inflammation levels and oxygen saturation variability were similar between individuals with a history of COVID-19 infection and controls without a history of COVID-19 infection. Network interactions between regulatory components of the cardiorespiratory system were also similar between recovering COVID-19 individuals and controls. Findings suggest that cardiorespiratory function and dynamic control of SpO2 may not be impaired following COVID-19 infection in young adults. Moreover, increased sedentary time and disease severity may have negative effects on pulmonary function in individuals recovering from COVID-19

Remote patient monitoring strategies and wearable technology in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is highly prevalent and is associated with a heavy burden on patients and health systems alike. Exacerbations of COPD (ECOPDs) are a leading cause of acute hospitalization among all adult chronic diseases. There is currently a paradigm shift in the way that ECOPDs are conceptualized. For the first time, objective physiological parameters are being used to define/classify what an ECOPD is (including heart rate, respiratory rate, and oxygen saturation criteria) and therefore a mechanism to monitor and measure their changes, particularly in an outpatient ambulatory setting, are now of great value. In addition to pre-existing challenges on traditional ‘in-person’ health models such as geography and seasonal (ex. winter) impacts on the ability to deliver in-person visit-based care, the COVID-19 pandemic imposed additional stressors including lockdowns, social distancing, and the closure of pulmonary function labs. These health system stressors, combined with the new conceptualization of ECOPDs, rapid advances in sophistication of hardware and software, and a general openness by stakeholders to embrace this technology, have all influenced the propulsion of remote patient monitoring (RPM) and wearable technology in the modern care of COPD. The present article reviews the use of RPM and wearable technology in COPD. Context on the influences, factors and forces which have helped shape this health system innovation is provided. A focused summary of the literature of RPM in COPD is presented. Finally, the practical and ethical principles which must guide the transition of RPM in COPD into real-world clinical use are reviewed