A proof of concept study of respiratory physiology in preterm neonates during high flow nasal cannula therapy

PhD ThesisIntroduction and rationale: High flow nasal cannula therapy is being increasingly used as a form of respiratory support across the world. Its adoption and popularity have been rapid but little is known regarding its key mechanism of action even after more than a decade of its use. I conducted a proof of concept study of respiratory physiology during high flow therapy in preterm neonates. Methods: The study protocol involved measurement of nasopharyngeal airway pressures and gas concentrations as well as measurement of tidal breathing indices. A detailed descriptive review of clinical efficacy of high flow nasal cannula in preterm infants was performed. In order to identify the optimum measuring techniques, in this proof of concept study, three types of pressure measuring techniques, a gas analyser device and a non-invasive tidal breathing indices device were studied and the results are presented in this thesis. In addition, a detailed protocol for a larger randomised crossover study of respiratory physiology during continuous positive airway pressure of 6 cm H2O and high flow nasal cannula therapy ranging from 2-8 litres per minute flow was designed.. Results: In this thesis, the results of a proof of concept physiological study have been presented. The results of the measurements performed in six babies of varying gestational age (less than 37 weeks of gestation) and birth weight are presented. Valid tidal volumes were measured in all babies, nasopharyngeal gas concentrations and pressure measurements in five and two babies respectively. There were no adverse events. Conclusions: It is feasible to measure nasopharyngeal air way pressures and gas concentrations as well as non-invasive tidal breathing indices in babies on high flow nasal cannula therapy safely. This study was successfully followed up by a larger randomised cross over study involving 45 infants with the same protocol.Special Trustees at Newcastle Hospital

Putting medical devices in context: a systematic review of evidence on design targeting low-resource settings

Most medical devices are inaccessible to healthcare facilities in low-resource settings (LRSs), severely limiting medical care for a vast proportion of the world's population. This article characterises the process used for designing medical devices for LRSs and investigate how the context-of-use is integrated into the process. A systematic review of 64 papers was conducted to identify peer-reviewed studies of devices intended for LRSs. Using the biodesign process as an analytic framework, a qualitative meta-analysis was conducted. Findings show the studies predominantly describe the later stages of medical device design, whilst largely neglecting how knowledge of the context is considered. To support engineers and improve outcomes, it is imperative that an understanding of the context is integrated throughout the design and product development process. This article highlights this gap and hopes to stimulate research into how context can be better incorporated into the design process for medical devices targeting those populations most in need.This is the author accepted manuscript. The final version is available from Inderscience Publishers via http://dx.doi.org/10.1504/IJDE.2015.07637

Gender Differences in Obstructive Sleep Apnea

The overall aim of this thesis was to understand gender differences in obstructive sleep apnea (OSA) and use this information to develop a tailored therapy for female patients. Specific aims were to determine whether gender differences commonly reported in the literature are present in mild OSA and upper airway resistance syndrome (UARS) patient groups, and whether symptoms could be linked to respiratory parameters in these groups. The final aim was to develop, test and validate a new AutoSet treatment for female OSA patients. CHAPTER 1 of this thesis provides a detailed review of gender differences in the prevalence, symptoms, clinical experience, and health outcomes of OSA and UARS patients, with a focus on the implications of different scoring rules. CHAPTER 2 reviews of quality of life questionnaires from 259 untreated patients with mild OSA. Females reported statistically significantly higher levels of sleepiness, fatigue, insomnia, and anxiety/depression compared to males. CHAPTER 3 of this thesis reviews polygraphy data from patients with mild OSA. Male patients were found to have significantly more breathing disturbances than females, however many of these difference disappeared when updated scoring criteria were used. Some weak correlations were found between respiratory parameters and symptoms; however, no clear conclusions could be drawn. CHAPTER 4 outlines the development of a new AutoSet device designed for female- specific breathing patterns. The remaining chapters (CHAPTER 5, and CHAPTER 6) of this thesis describe the testing and validation activities undertaken on the AutoSet F, including a clinical trial to test efficacy; a bench test to compare performance against other commercially available devices; a controlled product launch to validate the features of the algorithm; and finally a clinical trial which demonstrated improvements in sleep efficacy and quality of life over a three-month usage period. In summary, this thesis has shown that at the mild end of the OSA spectrum females are more symptomatic than males, even though respiratory differences in the genders are less pronounced than those described in moderate-to-severe patients. An AutoSet designed specifically for female OSA patients was successful in demonstrating efficacy and clinical effectiveness

The Politeoxygen splitter system (PSS) – a frugal LMIC oxygen delivery technology that expands the utility by up to 700%

Background: Oxygen therapy is indispensable in neonatal care requiring prompt commencement when prescribed. This is often hampered by limited availability of oxygen cylinders or concentrators at busy SCBUs in Nigeria. Where available, these two items of oxygen sources overcrowd the SCBU creating movement barriers leading to injuries, neonatal infections from high traffic of dirty cylinders and noise pollution from many concentrators. This presents the urgent need for a low-cost technique that could help to make oxygen easily administered to as many neonates as the need arises simultaneously. Aim: To describe an oxygen splitter system and compare outcomes of oxygen prescription in neonates pre- and post-system installation. Methods: Politeoxygen® Splitter System (PSS), a novel oxygen distribution system was designed to eliminate oxygen concentrator and cylinder adverse effects whilst enabling only one oxygen source to support up to eight neonates, simultaneously. Five sets of the device were installed and applied. Records of newborns who received oxygen therapy, pre-PSS installation and post-PSS were retrieved. Time delays to oxygen commencement following prescription were assessed in both groups. Incidences of cylinder falls and obstructions were noted. Results: PSS supported multiple numbers of neonates using one oxygen-source with patient-independent humidification and variable flowrates, sharing total flow up to 15 LPM amongst needy neonates as individually required. Six of 105 (6%) newborns received oxygen within 10 minutes of prescription pre-PSS installation, whereas 96%(72/75) post-PSS. The median (range) time delay to commencing oxygen therapy post-PSS was 0(0–90) minutes whereas pre-PSS was 74(0–1110). Conclusion: Unlike pre-PSS group, 100% of post-PSS neonates received oxygen as soon as this was prescribed, leading to prompt therapy initiation and many of them survived. PSS is recommended to enhance prompt far-reaching oxygen to neonates in poor settings

Enhancing the Diagnosis and Management of Obstructive Sleep Apnoea in Atrial Fibrillation Patients

Background: Atrial fibrillation (AF), is the most common sustained cardiac arrhythmia, and significantly increases the risk of stroke and cardiovascular mortality. It is strongly associated with obstructive sleep apnoea (OSA). Aims: 1. Examine the epidemiology of OSA in a hospital cohort with AF. 2. Compare the diagnostic accuracy of clinical screening tools for OSA in patients with AF. 3. Compare cardiac autonomic function in AF patients with and without OSA. 4. Conduct a pilot study of mandibular advancement splint (MAS) therapy for OSA in AF patients. Methods: 107 AF patients were recruited. The diagnostic accuracy of screening tools including a level 3 (portable) sleep study device as compared to polysomnography in AF patients was assessed. Cardiac autonomic function as a potential mechanistic link between OSA and AF was assessed using Heart Rate Variability (HRV). A pilot study of OSA treatment in AF patients using MAS therapy was conducted. Results: 62.6% of patients were newly diagnosed with OSA. Patients with moderate to severe OSA showed an increased BMI, neck circumference and Mallampati score, but were not significantly different in terms of daytime somnolence. Oxygen desaturation index (ODI) derived from a Level 3 portable sleep study device performed best for the diagnosis of moderate to severe and severe OSA, with excellent diagnostic accuracy (AUC 0.899, 95% CI 0.838 – 0.960 and AUC 0.925, 95% CI 0.859 – 0.991 respectively). We found a chronic increase in parasympathetic nervous activity in paroxysmal AF patients with OSA. MAS therapy showed high rates of acceptance, compliance and efficacy in AF patients. Conclusions: This thesis contributes to our understanding of the association between AF and OSA across a spectrum o

Children's Oxygen Administration Strategies Trial (COAST): A randomised controlled trial of high flow versus oxygen versus control in African children with severe pneumonia.

Background: In Africa, the clinical syndrome of pneumonia remains the leading cause of morbidity and mortality in children in the post-neonatal period. This represents a significant burden on in-patient services. The targeted use of oxygen and simple, non-invasive methods of respiratory support may be a highly cost-effective means of improving outcome, but the optimal oxygen saturation threshold that results in benefit and the best strategy for delivery are yet to be tested in adequately powered randomised controlled trials. There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that have stimulated a number of trials investigating permissive hypoxia. Methods: In 4200 African children, aged 2 months to 12 years, presenting to 5 hospitals in East Africa with respiratory distress and hypoxia (oxygen saturation or = 80% (permissive hypoxia); andHigh flow using AIrVO 2TM compared with low flow delivery (routine care). Discussion: The overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines. The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of in-hospital mortality, 9-10% (for those with oxygen saturations of 80-92%) and 26-30% case fatality for those with oxygen saturations <80%. Clinical trial registration: ISRCTN15622505 Trial status: Recruiting

Sleep/wake activity and energy expenditure in overweight and obese obstructive sleep apnea patients : a pre- and post-CPAP comparison.

Overweight and obesity is a major contributing factor in an estimated 70% of all obstructive sleep apnea (OSA) cases. Approximately five percent of the adult population has OSA, and the numbers continue to soar with the rising prevalence of obesity. As a primary therapy, continuous positive airway pressure (CPAP) has demonstrated improvement in many comorbidities associated with both OSA and obesity. Although anecdotal and clinical references support increased energy, activity, and weight loss as a potential benefit of CP AP treatment, there remains little evidence to endorse CP AP as a significant weight-reduction measure for overweight and obese OSA patients. The purpose of this study was to examine sleep/wake activity and energy expenditure, pre- and post-CP AP treatment, in adult overweight and obese patients with OSA. A prospective, observational, longitudinal study design was employed to assess 24-hour actigraphic measures of sleep/wake activity and energy expenditure prior and subsequent to CPAP therapy. Analysis of variance (ANOVA) using repeated measures was performed to identify overall differences between pre-CP AP and one week post-CPAP and pre-CPAP and one month and post-CPAP sleep activity, wake activity, and 24-hour energy expenditure. Sixty-nine subjects were consented, with a total of 35 subjects completing the study. Data analyses revealed statistically significant mean differences in sleep activity, wake activity, and energy expenditure from pre-CPAP to post-CPAP at one week and one month. At baseline, and continuing through one week post-CPAP and one month post-CPAP, the CPAP compliant group demonstrated less sleep activity, more wake activity, and expended more energy than the CPAP noncompliant group. This study concluded that CP AP use is a statistically significant factor affecting sleep activity time, wake activity time, and energy expenditure. Regardless of CP AP compliance and length of use, the entire post-CPAP group demonstrated more sleep activity, had less wake activity, and burned fewer calories. From a clinical perspective, the results of this study do not support the use of CP AP as a potential weight loss measure in overweight and obese OSA patients, and emphasize the need for the inclusion of behavioral weight management and weight loss strategies in an at-risk population for comorbid illnesses

Effects of portable non-invasive ventilation on exercise tolerance in patients with COPD

Breathlessness is the dominant symptom that limits exercise tolerance in patients with COPD. Several ergogenic approaches have been employed to improve exercise tolerance in this population including bronchodilators, oxygen and heliox supplementation, intermittent exercise and non-invasive ventilation (NIV). Although application of NIV during exercise is beneficial for increasing exercise capacity in patients with COPD, there are several disadvantages that limit its wider application during exercise, including lack of compliance with the equipment, and the time required to set up and supervise the equipment in the setting of pulmonary rehabilitation. Recent advances in technology have facilitated the development of portable non-invasive ventilation (pNIV) devices aiming to alleviate breathlessness during activities of daily living. The VitaBreath (Philips, Respironics) was developed in 2016 as a portable, handheld, battery powered, bi-level, NIV device, providing fixed positive inspiratory and expiratory airway pressure support (IPAP:18 and EPAP: 8 cmH2O, respectively). Accordingly, this dissertation aimed to investigate the physiological effects of pNIV application during controlled laboratory exercise conditions and activities of daily living, in patients with advanced COPD. As the VitaBreath device is no longer commercially available, but similar devices may come to market, the present dissertation provides proof of concept on how pNIV can be applied intermittently during exercise in patients with COPD, and how to select patients most likely to respond to pNIV. This in turn may encourage the development of more suitable devices. Intermittent exercise was chosen to evaluate the effects of pNIV in comparison to the commonly adopted pursed lip breathing (PLB) technique, as this type of exercise allowed regular application of the pNIV device or the PLB technique during recovery periods. Patients retained the device for 3 months to investigate the acceptability, comfort and usability of the device during activities of daily living. Twenty-four COPD patients were randomised to perform two intermittent exercise protocols sustained at different work intensities (60% WRpeak for 6-min and 80% WRpeak for 2-min) alternated with 2-min rest periods. Within each intermittent exercise modality, patients performed two identical exercise tests using either pNIV or the PLB technique in a balanced order sequence, during the recovery phases of intermittent exercise. The findings of this study showed that with both intermittent protocols average endurance time was greater when pNIV was applied compared to PLB. Improvements in exercise tolerance were due to lower degrees of dynamic hyperinflation (DH) and breathlessness with pNIV compared to PLB. An important finding of the aforementioned study was that a subgroup of patients (8/24) failed to show a clinical important improvement in DH with pNIV compared to PLB and did not improve exercise tolerance. Analysis identified that these 8 patients experienced greater resting lung hyperinflation, greater exercise-induced DH and breathlessness, secondary to the adoption of a tachypnoeic breathing pattern with pNIV compared to PLB. Interestingly, these patients also reported less benefit from using the device at home, in terms of anxiety around breathlessness and recovery time from breathlessness. Considering the variation of response reported in the present thesis it is important that clinicians assess the response to pNIV on an individual basis. As with any new method, it was important to appreciate the physiological consequences of the acute application of pNIV on thoracoabdominal volume regulation and respiratory muscle recruitment (assessed by optoelectronic plethysmography), and central hemodynamic responses. Compared to PLB, acute application of pNIV was associated, in the majority of patients, with increased end-inspiratory and end-expiratory rib cage volumes and greater rib cage muscle recruitment, as well as decreased end-expiratory abdominal volumes reflecting reduced expiratory abdominal recruitment. Measurement of cardiac output revealed no adverse circulatory responses with the application of positive airway pressures provided by pNIV during the recovery periods. However, the pattern of thoracoabdominal volume regulation and respiratory muscle kinematics confirmed the findings of the original studies, thereby identifying responders and non-responders to pNIV. Interestingly, responders to pNIV exhibited greater recruitment of the expiratory abdominal muscles compared to non-responders, thereby facilitating them to combat end-expiratory rib cage dynamic hyperinflation effectively. When patients used the VitaBreath device during their daily physical activities, the majority of patients felt less anxious about becoming breathless and felt that their breathlessness recovered faster when using the device at home for 3 months. Moreover, almost all patients used the device at least weekly and all patients rated the ease of VitaBreath use to be between good and excellent. Additionally, most patients felt that using the device had benefited them and that they would recommend the device to other patients. The main disadvantage of the device was reported to be the high cost and its portability. The pNIV method provided fixed IPAP and EPAP. This represents a very important disadvantage of this particular pNIV device, which clearly mitigated the beneficial impact it had on some patients. Future research into pNIV devices should examine how best to identify patients who benefit from a pNIV method in everyday life. On-going development of auto-adjusted ventilators would facilitate a larger fraction of COPD patients to be physically active and experience a better quality of life

Use of bubble continuous positive airway pressure (bCPAP) in the management of critically ill children in a Malawian paediatric unit: An observational study

INTRODUCTION: In low-resource countries, respiratory failure is associated with a high mortality risk among critically ill children. We evaluated the role of bubble continuous positive airway pressure (bCPAP) in the routine care of critically ill children in Lilongwe, Malawi. // METHODS: We conducted an observational study between 26 February and 15 April 2014, in an urban paediatric unit with approximately 20 000 admissions/year (in-hospital mortality <5% approximately during this time period). Modified oxygen concentrators or oxygen cylinders provided humidified bCPAP air/oxygen flow. Children up to the age of 59 months with signs of severe respiratory dysfunction were recruited. Survival was defined as survival during the bCPAP-treatment and during a period of 48 hours following the end of the bCPAP-weaning process. // RESULTS: 117 children with signs of respiratory failure were included in this study and treated with bCPAP. Median age: 7 months. Malaria rapid diagnostic tests were positive in 25 (21%) cases, 15 (13%) had severe anaemia (Hb < 7.0 g/dL); 55 (47%) children had multiorgan failure (MOF); 22 (19%) children were HIV-infected/exposed. 28 (24%) were severely malnourished. Overall survival was 79/117 (68%); survival was 54/62 (87%) in children with very severe pneumonia (VSPNA) but without MOF. Among the 19 children with VSPNA (single-organ failure (SOF)) and negative HIV tests, all children survived. Survival rates were lower in children with MOF (including shock) (45%) as well as in children with severe malnutrition (36%) and proven HIV infection or exposure (45%). // CONCLUSIONS: Despite the limitations of this study, the good outcome of children with signs of severe respiratory dysfunction (SOF) suggests that it is feasible to use bCPAP in the hospital management of critically ill children in resource-limited settings. The role of bCPAP and other forms of non-invasive ventilatory support as a part of an improved care package for critically ill children with MOF at tertiary and district hospital level in low-resource countries needs further evaluation. Critically ill children with nutritional deficiencies and/or HIV infection/exposure need further study to determine bCPAP efficacy