Saudi Cultural Missions Theses & Dissertations
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Item Restricted Combination Therapy in Asthma Management: A Systematic Review of Allergen Immunotherapies and Biological Therapies(University of Birmingham, 2024-08) Almajnoni, Akram; Belchamber, KylieAsthma, a prevalent respiratory condition, often requires comprehensive management strategies to control symptoms effectively. This systematic review aims to evaluate the efficacy of combining Allergen Immunotherapy (AIT) with biological therapies in reducing respiratory symptoms and medication use among adult asthmatic patients. A narrative synthesis approach was employed to conduct this systematic review. The literature search, spanning from 2000 to 2024, was conducted using PubMed, MEDLINE, and Embase, yielding 1,220 records. After removing duplicates and screening titles and abstracts, 1,124 studies were evaluated, with five Randomized Controlled Trials (RCTs) meeting the inclusion criteria. Studies were selected based on stringent eligibility criteria, including adult participants and interventions combining AIT and biological therapies. Quality assessment was conducted using the Critical Appraisal Skills Programme (CASP) framework, and data were extracted and synthesised using narrative summary and thematic analysis. The review synthesised data from five RCTs, encompassing a total of 703 participants aged 11 to 65 years. The studies varied in geographic location, including Europe and the United States, and targeted a range of allergens such as house dust mites, grass pollen, and animal dander. The primary outcome, a reduction in respiratory symptoms, was consistently met across all studies. Combination therapies showed significant improvements in symptom control, as measured by tools such as the Asthma Control Questionnaire (ACQ) and Total Asthma Symptom Score (TASS). Additionally, the studies demonstrated a substantial reduction in the use of medications, including inhaled corticosteroids (ICS) and rescue medications, highlighting the effectiveness of the combined treatment approach. This systematic review demonstrates that combining AIT with biological therapies is highly effective in managing asthma and related allergic conditions, such as rhinitis. The findings underscore significant improvements in both symptom control and medication reduction, suggesting that these combination therapies could play a crucial role in advancing asthma treatment strategies. However, the review also highlights challenges such as patient adherence and cost considerations, which need to be addressed to fully integrate these therapies into clinical practice. Future research should focus on standardising protocols, assessing long-term effects, and exploring cost-effective strategies to overcome barriers to implementation, ensuring broader access to these advanced treatments.11 0Item Restricted The Use of Home Carbon Monoxide Monitoring as Part of a Tobacco Dependency Service for Acute Hospital Admissions with COPD and Asthma(University College London, 2024-08-27) Alshammari, Turki Faleh; Roy, KayBackground Tobacco dependency is a significant global public health challenge, affecting the NHS; UK, causing substantial morbidity and mortality, especially in COPD and asthma patients where Tobacco Dependency Services (TDS) have potential to reduce hospital admissions and improve health outcomes. NHS Long-Term Plan prioritizes COPD and smoking-related health inequalities. Although carbon monoxide monitoring (COM) is recommended for smoking cessation, its use in airway diseases has not been studied before. Aim To determine whether the iCOquit has potential value to help quit attempts in respiratory patients (asthmatics and COPD smokers) as part of the TDS in acute trusts and adds to positive experience. Methods COPD and asthma patients admitted to two London hospitals were offered the iCOquit device for home COM and remotely followed for up to 12 weeks, with motivation levels and stages of behavioural change assessed. Pre- and post-intervention surveys were conducted to assess patient experiences. Results 15 COPD and asthma patients were initially reviewed, (mean age 59 years), predominantly male (60%) and White British (80%). Initial motivation to quit smoking was high (73.3% at maximum), with 20% remaining smoke-free after 4 weeks. Patient experience was good but suggested specific technological improvements. Discussion This study introduced a novel approach to enhancing TDS within acute care settings. Initial findings suggest that the iCOquit device may be beneficial for certain patient populations and future research will focus on identifying these groups more precisely and the value of home COM in different settings, alongside a follow-up study incorporating health economic modelling to validate the clinical efficacy, cost-effectiveness, and scalability of iCOquit within the NHS. Collaboration with manufacturers will aim to enhance the device's accessibility and usability, improving data collection and decision-making processes, with the potential for broader implementation of similar digital health tools across healthcare.11 0Item Restricted Assessment of inhomogeneity in gas exchange using a novel methodology(University of Oxford, 2024) Alamoudi, Asma; Robbins, Peter; Petousi, NayiaAccurate measurement of respiratory disease activity within the lung poses a significant challenge, and the inability to achieve it hampers early disease detection, effective disease management and the objective assessment of therapeutic responses. In this thesis, the utility of computed cardiopulmonography (CCP) is explored as a novel, non-invasive way to measure lung inhomogeneity across three distinct cohorts: Healthy (control) study participants, T2-high asthma patients and survivors of severe COVID-19. Standardised normal values for CCP were established by analysis of 98 healthy people, who acted as the control group. Deviations from these baseline values were used to formulate prediction equations for each CCP parameter based on age, height, body mass index and sex. These equations were used to compute Z-scores for the asthma and post-COVID-19 cohorts. The analysis revealed that many patients exhibited abnormal Z-scores for CCP parameters. These findings highlighted deviations from the established normal ranges and demonstrated abnormalities in disease conditions. In the T2-high asthma cohort, the effect of biological treatments on lung inhomogeneity was examined. Ninety-one patients were studied before treatment, and 65 patients were studied before and after they began biological therapies. The study was focused on σlnCL, a metric of lung inhomogeneity, in which it correlated with the level of systemic inflammation as measured by the peripheral blood eosinophil count both at baseline and in relation to treatment effects by biologics. The use of CCP enabled differentiation between responders and non-responders based on changes in σlnCL. Responders in terms of early change in σlnCL were the ones showing improvements in lung function/symptoms and increased change of having remission at one year. This finding indicates that CCP could potentially provide an early treatment response signal that might be useful to guide treatment strategies. The COVID-19 cohort comprised 66 participants recovering from COVID-19 infection of varying clinical severity. The study aimed to assess whether CCP could identify abnormal lung function in recovered patients. Among the most severe cases, significant increases in anatomical dead space and decreases in functional residual capacity were observed. Despite the lack of pre-infection measurements, these findings highlight the potential use of CCP to assess aspects of lung function not easily measured by conventional tests. In conclusion, the work performed for this thesis has demonstrated that CCP offers a valuable tool by which to monitor disease activity in asthma and post-COVID-19 recovery. It underscores the importance of using advanced, non-invasive techniques to enhance our understanding and management of respiratory diseases. Additionally, this thesis represents the first attempt to establish normal values for CCP parameters through the use of Z-scores.12 0Item Restricted A pragmatic cluster randomised controlled trial (cRCT) of an educational intervention to promote asthma prescription uptake in General Practitioner Practices(University of Sheffield, 2024-04-23) Alyami, Rami; Julious, Steven A.; Simpson, Rebecca M.; Oliver, PhillipBackground: Asthma exacerbation rates in school-age children peak following the return to school after the summer break. Studies have shown a decline in prescriptions collection during August, which is followed by an increase in unscheduled visits to healthcare providers. A previous study (the PLEASANT trial) found that sending reminder letters to parents of children with asthma during the summer vacation led to a 30% increase in August prescriptions being prescribed and reduced unscheduled care visits after the return to schools in the period September to December. The intervention also resulted in an estimated cost saving of £36.07 per patient per year. Objective: To determine if informing general practitioner (GP) practices about the PLEASANT trial intervention results leads to its implementation. Design: A pragmatic cluster randomised trial which utilised the Clinical Practice Research Datalink (CPRD) to send the intervention and collect data. Participants: A total of 1,326 GP practices in England, including 90,583 individuals, with 664 practices (44,708 individuals) in the intervention group and 662 practices (45,875 individuals) in the control group. Intervention: In June 2021, the intervention practices received a letter from CPRD about the PLEASANT study findings and recommendations. The letter was sent to the asthma lead and/or practice manager via postal mail and email. Control Arm: Usual care. Randomisation: GP practices were stratified by practice size (decile) and randomly allocated to either the intervention or control group. Main Outcome: The proportion of children with asthma who had a prescription for an asthma preventer medication in August and September 2021. Results: The intervention did not significantly affect the proportion of children with asthma who had a prescription in August and September 2021 compared to the control arm. In the intervention group, 15,716 out of 44,465 children (35.3%) had a prescription issued, compared to 16,001 out of 45,559 children (35.1%) in the control group (OR 1.01; 95% CI: 0.97 to 1.04). There was also no intervention effect on the number of prescriptions uptake in the same period (IRR 1.01; 95% CI: 0.98 to 1.03). Furthermore, the letter did not reduce the number of unscheduled medical contacts after returning to school from September to December 2021 (IRR 0.99; 95% CI: 0.96 to 1.02) and all medical contacts remained unchanged (IRR 1.00; 95% CI: 0.97 to 1.02). Conclusion: The study findings suggest that passive intervention of providing a letter to GPs did not achieve the intended outcomes. To bridge the gap between evidence and practice, alternative, more proactive strategies could be explored to address the identified issues.10 0Item Restricted Investigating asthma aetiology and remedies in Saudi Arabia and the UK: Assessing the impact of indoor air pollution and healthcare expertise on prescription expenses, within the realm of public health(University of Strathclyde, 2024) Saggah, Abdullah; Amanj, IbrahimThe thesis culminates with a set of references and appendices that supplement the research. The references section provides a comprehensive list of all the sources cited throughout the thesis, ensuring that the research is grounded in existing literature and scientific evidence. The appendices section includes supplementary materials that support the research findings, such as data tables, questionnaires, and additional analyses. In summary, this thesis offers a holistic and nuanced examination of asthma, a condition that affects millions worldwide. By analyzing various factors such as indoor air pollution, healthcare practices, and the impact of the COVID-19 pandemic, the research provides valuable insights into the management and treatment of asthma. The comparative analysis between the Kingdom of Saudi Arabia and the United Kingdom offers a unique perspective on the global and regional dimensions of asthma, making this thesis a significant contribution to the field of public health32 0Item Restricted Investigating The Roles of Gasdermin B in Epithelial Cell Inflammation and Repair(Saudi Digital Library, 2023-10-01) Bukannan, Sheema; Zhang, YoumingThe Gasdermins (GSDMs) are a family of proteins consisting of GSDMA, GSDMB, GSDMC, GSDMD, GSDME, and GSDMF. They are mainly expressed in epithelial and immune cells and are involved in an inflammatory form of cell death known as pyroptosis. GSDMB is the least studied of the GSDMs, partially due to its lack of mouse ortholog. Its roles in pyroptosis and inflammation have been controversial. GSDMB polymorphism markers are found to be associated with asthma severity and exacerbations. GSDMB is overexpressed in various breast and gastric cancers, promoting poor prognosis and increasing therapy resistance. However, GSDMB has also shown to be beneficial as it was found to stimulate epithelial cell restitution and repair. In this study, A GSDMB overexpression (OE) model was established using plasmid expressing human GSDMB. A GSDMB knockout (KO) model created using the CRISPR/Cas9 system in the epithelial cell line HBEC3-KT was also investigated. TNFα, lipopolysaccharide (LPS), poly I:C, calcitriol, and CD14 were used to stimulate inflammation in the cell lines. Inflammation markers Interleukin (IL)-6 and IL-8 release were measured with enzyme-linked immunosorbent assay (ELISA) at 0, 4, 10, and 24 hours after treatment. It was found that TNFα, poly I:C, and a combination of LPS, calcitriol, and CD14 are the most effective inflammatory stimulators. IL-8 levels did not show a significant change between wildtype (WT), OE, and KO within the same time point group, but did show a significance 24 hours after treatment. GSDMB KO released more IL-6 following TNFα and poly I:C stimulation (p<0.05 respectively). Expression of inflammasome associated genes NLRP3, AIM2, NOD2, Caspase 5, and GZMB were measured using RT-qPCR 24 hours following treatment with TNFα. AIM2 showed to express significantly higher in the OE group compared to WT group (p<0.01) before treatment. Following TNFα treatment, AIM2 levels significantly 5 decreased in the OE group (p<0.05). NOD2 expression was significantly higher in the KO group comparing to the WT and OE group (p<0.001, p<0.01 respectively). After treatment, NOD2 levels decreased in KO group (p<0.01). Caspase 5 showed a significant decrease across all samples compared with the WT (p<0.001). NLRP3, on the other hand, significantly increased in just KO compared to all other samples (p<0.001). As results are not consistent, further investigation is required to investigate the discrepancies across the different genes. Scratch assay was used to assess for GSDMB’s wound healing properties by imaging the cells over 48 hours following scratching in untreated and TNFα treated cells in WT and KO cells. GSDMB was found to induce wound healing in epithelial cells, with WT cells showing more efficient wound healing when treated with TNFα compared to KO, indicating both GSDMB and TNFα to be involved in the wound healing process. The results of this study warrant further investigations of GSDMB roles in pyroptosis and inflammation in the epithelium. Further investigation will provide new insights into inflammatory diseases and cancers, potentially allowing for the development of novel therapeutic GSDMB targets for the diseases.9 0Item Restricted EFFECTIVENESS OF INSPIRATORY MUSCLE TRAINING IN IMPROVING INSPIRATORY MUSCLE STRENGTH, EXERCISE CAPACITY, AND MANAGING ASTHMA SYMPTOMS IN ADULTSV(Saudi Digital library, 2023-07-28) Shawani, Mothaqab; Visser, KarenThis systematic review is aim to examine the efficacy of Inspiratory Muscle Training in enhancing inspiratory muscle strength and exercise endurance among adults diagnosed with asthma. Furthermore, secondary objectives involve evaluating the impact of IMT on various aspects such as asthma symptoms and control, lung function, use of rescue medication, and health-related quality of life . A thorough search was conducted across various electronic databases such as CINAHL (via EBSCO), Medline (via OVID), Scopus, Web of Science, EMBASE, and Cochrane Library, resulting in the identification of 7 RCTs deemed relevant for inclusion. Following critical appraisal by two independent reviewers, the 7 RCTs were selected for data extraction. Owing to the clinical variability among the studies included, a narrative synthesis was performed. The RCTs included in this review revealed that IMT programme led to a substantial increase in inspiratory muscle strength across all studies (p < 0.005) and exercise capacity (p < 0.001). Additionally, IMT was found to have a positive impact on asthma symptoms, resulting in a significant reduction in medication use (p < 0.001) and perceived dyspnea. No significant changes in lung function were observed. Furthermore, IMT exhibited the potential to enhance inspiratory muscle endurance and improve QoL in the long term.18 0Item Restricted THE RELEVANCE OF PHYSIOLOGICAL SMALL AIRWAYS FUNCTION IN DIAGNOSING ASTHMA AND ASSESSING BRONCHODILATOR RESPONSE(2024) Almeshari, Mohammed Ahmed M; Sapey, ElizabethAsthma is a common, chronic and heterogenous disease that is characterised by variable flow rate. Objectively assessing and diagnosing asthma can be difficult due to disease variability. Testing bronchodilator response (BDR) is one of the objective assessments for asthma, however, BDR can be found in other diseases such as chronic obstructive pulmonary disease (COPD) patients. Small airways dysfunction (SAD) is common in asthma and COPD, however the utility or standards of small airways function is new well described in asthma guidelines. The aim of this thesis was to evaluate the current evidence for the use of physiological small airways function in the diagnosis of asthma. Furthermore, the thesis aimed to evaluate the current evidence for small airways BDR compared to larger airways. It also aimed to understand the relationship between large and small airways indices using spirometry and the prevalence and risk factors of SAD. Firstly, a systematic review was conducted to review the current evidence for using physiological small airways tests in diagnosing asthma which includes spirometry (MMEF and FEF50) and Oscillometry (R5, R5-20, Ax, and X5). Ten studies were included in the review. Overall, studies were small, heterogeneous and were not standardised, however, differences were found in small airways measurements compared to healthy controls. Secondly, a retrospective analysis of real-world data assessed the physiological measurements of SAD, its prevalence in asthma and in those with airflow obstruction (AO), and risk factors for SAD. SAD was prevalent in asthma and although a strong relation was found between small and large airways indices, some patients had evidence of SAD without AO. This highlighted the potential importance of assessing the small airways, especially in smokers, which was found to be associated with SAD in asthma. Thirdly, a systematic review was conducted to assess the BDR in the small airways compared to large airways (forced expiratory volume in the 1st second (FEV1)) in asthmatics patients. The studies were small, with diverse methodologies used to conduct the BDR assessment. However, greater BDR was reported for small airways indices compared to FEV1 and approximately 25% of patients demonstrated BDR in the small airways tests but not in FEV1. Finally, a retrospective analysis of real-world data was conducted to assess the BDR for the large and the small airways and their relation to SAD. A greater improvement was found in small airways indices and SAD at baseline was found to be a predictor for a positive BDR for both FEV1 and MMEF, whereas AO was not. Overall, this thesis suggests there might be utility in assessing the small airways in asthma, but that standardisation is needed in order to enable definitive research studies.47 0