Advanced physiological monitoring of the cardiorespiratory system in healthy subjects and patients with sleep-disordered breathing

Abstract

In this thesis, advanced physiological monitoring of the cardiorespiratory system was examined with the aim to improve outcomes for patient care in the management of respiratory conditions. The load:capacity ratio of the respiratory system was introduced as an indicator that reflects respiratory efficiency, the balance between the physiological load on the respiratory system and the capacity of the respiratory muscles. While Neural Respiratory Drive (NRD) represents a crucial component in assessing respiratory efficiency and its fundamental role in maintaining stable breathing, the load;capacity ratio provides insights into the ability to meet physiological demands, modulate symptoms, and maintain quality of sleep. Three integrated research projects examined different aspects of the load: capacity ratio of the respiratory system. The first study investigated levels of NRD, particularly the electromyographic (EMG) activity of the diaphragm, and its association with the perception of breathlessness, aiming to determine the minimally clinically important difference (MCID) in its activation. NRD, as measured by the respiratory muscle pump EMG, is a marker for inspiratory effort and closely correlates with work of breathing and symptoms, such as breathlessness. A systematic review and meta-analysis were undertaken to determine the MCID of NRD measurement using anchor-based and distribution-based methods. The systematic review identified 21 eligible studies involving 483 adult participants. NRD was primarily defined as the maximal root mean square of the diaphragm EMG as a percentage of maximum (EMGdi %max). In healthy individuals, the absolute range of EMGdi at rest was 6.0 to 16.6 %max, and 56.9 to 71.0 %max during exercise, with a mean difference of 53.3 [95% CI: 49.4; 57.1] %max. In COPD patients, the absolute range of EMGdi at rest was between 12 and 18 %max, and 59 to

72 %max during exercise, with a mean difference of 48.5 [95% CI: 44.8; 52.1] %max. The MCID of EMGdi %max, associated with a clinically large effect size, was 2.43% [95% CI: 1.96; 2.91] in normal subjects and 2.76% [95% CI: 1.92; 3.61] for COPD patients. For the Borg score, the MCID was approximately one unit for both healthy subjects and COPD patients. The second project focused on physiological experiments examining the effects of submental electrical stimulation and chemoreceptor stimulation in normal subjects during head-down tilt conditions while breathing different gas mixtures (room air, hypercapnic, and hypoxic). This research highlighted the importance of the load:capacity ratio in understanding the impact of loading the cardiorespiratory system and sensitising the baro- and chemoreceptors. Using an experimental model of baroreceptor loading induced by head-down tilt, the cardiorespiratory responses were measured during 50° head-down tilt combined with submental electrical stimulation and different gas conditions (hypercapnia, hypoxia, normoxia). The study involved 13 healthy subjects. Analysis from a three-way ANOVA indicated that blood pressure decreased significantly with transcutaneous electrical stimulation, and different gas conditions and postures similarly impacted blood pressure control. Additionally, there was increased minute ventilation with electrical stimulation, and an interaction effect between gas condition and posture on minute ventilation. The third project assessed the feasibility of remote monitoring to improve adherence to non-invasive ventilation (NIV) in patients with sleep-disordered breathing and hypercapnic respiratory failure. The study investigated remote monitoring of home mechanical ventilation (HMV) for treating chronic hypercapnic respiratory failure in patients with Obstructive Sleep Apnoea/Obesity Hypoventilation Syndrome (OSA/OHS). The primary aim was to assess whether remote monitoring could improve and optimise NIV adherence, test patients' willingness to use remote monitoring devices, and evaluate the associated healthcare resource usage and symptom improvement. In total, 32 participants were enrolled and randomly assigned to the intervention (remote monitoring) or usual care arm. The groups were similar in age, gender, and body mass index. While NIV usage in the intervention arm showed an initial improvement at the 6-week follow-up, the primary outcome of average nocturnal NIV adherence at 12 weeks was similar in both groups. Quality of life outcomes did not differ significantly between the intervention and usual care groups at the end of the trial. However, one severe adverse event with acute-on-chronic hypercapnic respiratory failure requiring hospitalization due to NIV non-adherence occurred in the control group. In conclusion, this thesis demonstrated various aspects of assessing the load:capacity ratio and the importance and complexities of understanding the underlying physiology in the context of advanced cardiorespiratory monitoring. The MCID associated with the sensation of breathlessness for the diaphragm EMG was described. A sensitization effect of electrical stimulation on the baroreceptors, impacting blood pressure, was proven. Furthermore, while the value of remote monitoring in patients with OSA/OHS requires further assessment, regular review of cardiorespiratory parameters contributes to the provision of safe follow-up surveillance in this cohort. Each project underlined the relevance of a deeper pathophysiological understanding for the management and treatment of cardiorespiratory conditions. These findings could be used to improve respiratory care by focusing on patient-based, clinically relevant outcomes and optimising healthcare delivery for clinical trials and regular clinical services for patients with respiratory conditions and sleep-disordered breathing.