Saudi Cultural Missions Theses & Dissertations
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Item Restricted A study to explore how a Physiologist-led home spirometry service (PLHSS) can help identify different asthma phenotypes for an improved patient centred approach.(University College London, 2024-08) Alrashed, Reem; Roy, KayBackground Varying presentations and variability in asthmatics lead to treatment delays and quantitative measurements are to achieve an optimised and personalized management plan. Optimal care relies on an accurate diagnosis. Due to the variable physiology, single tests do not provide enough information about the patient’s condition as peak flows and spirometry can vary between days, seasons and in response to triggers. Asthma can be severe or difficult-to-treat, and many conditions coexist mimicking its symptoms which makes it difficult to determine which aspect is contributing most to the patient’s presentation. A physiology-led home spirometry service (PLHSS) obtaining quality assured spirometry (QAS) ensures spirometry including airflow obstruction is captured with the best patient effort which can help associate patients’ spirometry to their symptoms to objectively evaluate asthma control and determine the most appropriate management. This study will evaluate the value of PLHSS in the management of asthmatics in the outpatient clinic. Methods 20 patients were monitored over 12 weeks in the asthma clinic and onboarded to NuvoAir-PLHSS. Patients were coached by a respiratory physiologist on performing QAS four-times-weekly and when symptomatic. Data are evaluated and reported on a digital platform. Results High (>20%) variability of FEV1 was identified in 11 patients out of 20. 60% of patients had confirmation of a management plan after the first clinic appointment and within a month of initiating the PLHSS as they were referred for biologics or other therapies such as speech-and- language. All patients reported that PLHSS was easy to use and 88% reported it helped their understanding of doing tests with guidance and explanation of what spirometry measured and its importance. Conclusion PLHSS can improve aspects of patient care in an outpatient pathway and clinic utilisation, ensuring treatment plans are formulated sooner, quicker discharges and referrals are made, and severe patients are seen earlier.5 0Item Restricted Delivering a carbon net zero NHS at UCLH through more sustainable inhaler prescribing in the trust(University College London, 2024) Aldosari, Bodour; Roy, KayBackground Climate change, driven by anthropogenic greenhouse gas emissions, significantly impacts global health. The National Health Service (NHS) is committed to achieve net-zero carbon emissions by 2040, targeting reductions in healthcare-related emissions, including those from respiratory inhalers. Short acting beta agonist (SABA) are major contributors to the NHS’s carbon footprint due to their propellant gases. The North Central London has set key performance indicators to increase the use of lower-carbon inhalers. This project aims to primarily optimize asthma care within University College London Hospital (UCLH) by implementing sustainable inhaler prescribing practices in the emergency department (ED) and acute medical unit (AMU), aligning with these environmental goals. Methods Inhaler-sustainability champions delivered a regular education programme with interval performance of prescribing reported, following BTS-asthma 4 and surveys evaluating staff confidence pre- and post-training. Carbon footprint in NCL was calculated at community practice level and department level within UCLH to identify where more attention required. Teaching supported good disease management through prescribing of inhaled steroids and reduction in Salbutamol over-reliance with effective inhaler technique and adherence checks. We collected data pre and post interventions such as teaching to assess the impact of the educational interventions on clinical practice. Results There was an 18% and 40% reduction in SABA prescriptions in the ED and AMU respectively, cutting down carbon emissions by over 1,640 kg. Maintenance and reliever therapy prescriptions increased by 8.6% and 48% in ED and AMU, respectively. The Asthma 4 bundle application improved in the AMU. A staff surveys revealed overall improvement in knowledge and understanding after the educational intervention. Conclusion The implementation of sustainable inhaler prescribing practices in the ED and AMU at UCLH has led to a reduction in carbon emissions and improvements in clinical practice. Additionally, the educational interventions resulted in enhanced staff knowledge and understanding around optimal asthma care. These outcomes highlight the potential for such quality improvement initiatives in achieving both clinical excellence and environmental sustainability within healthcare settings8 0Item Restricted Role of C-reactive protein in airway smooth muscle dysfunction relevant to obstructive lung disease.(University of Leicester, 2024-07-31) Alanazi, Amani; Saunders, RuthC-reactive protein (CRP), is an inflammation marker, often elevated in airways conditions such as asthma and COPD. This research investigated the impact of CRP on airway smooth muscle (ASM) cells, which are crucial in the airway remodelling and hyperresponsiveness which is observed in these conditions. By using primary human ASM cells, this study has shown that purified CRP reduced cell number, increased cell size and intracellular complexity, and maintained cell viability. However, these findings were not replicated with recombinant CRP, which lacks endotoxin, suggesting that endotoxin contamination in the purified CRP may have played a role. Lipopolysaccharide (LPS) treatment, an endotoxin component, resulted in increased intracellular complexity but did not completely replicate the other effects of purified CRP on ASM cells. Moreover, a CRP-neutralizing antibody did not reverse the changes induced by purified CRP, indicating the potential involvement of contaminants. The differences between purified and recombinant CRP highlight the challenges in isolating the true effects of CRP from those of other inflammatory agents. Future research will give priority to endotoxin removal or neutralization, using higher concentrations of both CRP and the neutralizing antibody. Additionally, the study will focus on exploring potential synergistic effects between CRP and LPS on ASM cells. Further investigations are needed to fully understand the role of CRP in the ASM dysfunction and the underlying mechanisms, including apoptosis, hypertrophy, and mediator secretion. In conclusion, this study suggests that CRP has the potential to contribute to ASM dysfunction but underscores the importance of strict experimental controls to distinguish its effects from potential contaminants like endotoxin. The research emphasizes the need for further exploration of the complex interplay between CRP, endotoxin, and ASM cells to elucidate their individual or combined contribution to ASM dysfunction in lung diseases.84 0Item Restricted The Effectiveness of Heat and Moisture Exchanger Masks in Controlling Exercise-Induced Bronchoconstriction During Exercise in Asthma Patients: A Systematic Review and Meta-Analysis(Cardiff University, 2024-05-23) Alnajimi, Rana; Edwards, DeborahObjective: This systematic review and meta-analysis aim to evaluate the effectiveness of heat and moisture exchanger (HME) masks in controlling exercise-induced bronchoconstriction (EIB) during exercise in asthma patients. EIB, characterized by airway narrowing triggered by physical activity, affects a significant proportion of individuals with asthma, impeding their ability to engage in physical activities that can otherwise benefit their condition. Methods: A comprehensive search of databases including AMED, PEDro, CINAHL, CENTRAL, MEDLINE, and Embase was conducted to identify relevant randomized controlled trials (RCTs). The studies were screened, and data were extracted and analyzed using the JBI tool. Five studies met the inclusion criteria and were subjected to critical appraisal using the Cochrane Risk of Bias 2 tool. Data were synthesized, and a meta-analysis was performed to determine the effect of HME masks on post-exercise FEV1 decline. Results: The meta-analysis revealed that HME masks significantly reduced the decline in FEV1 post-exercise compared to placebo, with a standardized mean difference (SMD) of -0.775 (95% CI: -1.339 to -0.211, p = 0.007). Sensitivity analyses confirmed the robustness of the results, showing an SMD of -0.626 (95% CI: -1.105 to -0.147, p = 0.01) after excluding a high-bias study. Analyses focusing on sub-zero temperatures further supported the masks' efficacy, indicating a significant benefit with a mean difference of -15.014 (95% CI: -22.887 to -7.140, p < 0.001). Conclusions: The findings suggest that HME masks can effectively mitigate EIB in asthma patients during exercise, particularly in cold environments. However, due to the limited number of studies and moderate-quality evidence, definitive recommendations cannot be made. Further research is required to explore the long-term effectiveness and potential adverse outcomes associated with HME mask use.33 0Item Restricted Systemic Inflammation, Arterial Stiffness, and Vascular Endothelial Dysfunction in Patients with Chronic Lung Disease(University of Dundee, 2024-05-22) Arafah, Abdullah M.; Khan, FaiselChronic lung disease (CLD) is considered a heterogeneous, complex, and multicomponent condition. Types of CLD include bronchiectasis, chronic obstructive pulmonary disease (COPD), and asthma. Cardiovascular events and peripheral vascular disease are highly prevalent among patients who are known to have CLD. It is increasingly acknowledged that cardiovascular comorbidities contribute to the disease’s severity. The underlying mechanisms that link CLD and cardiovascular disease (CVD) are inadequately understood. Systemic inflammation is a key component that could describe the link between CLD and CVD. Changes in vascular endothelial function accompany the increased cardiovascular events in CLD. Atherosclerosis and calcification of macrovascular and microvascular lead to further decrease vascular compliance. These structural changes in the vascular wall contribute to increased arterial stiffness observed in patients with CLD. Endothelial dysfunction and arterial stiffness are early signs of vascular disease and the development of cardiovascular events. Chronic systemic inflammation plays a vital role in linking CLD to the development of endothelial dysfunction and arterial stiffness. Therefore, this study aims to investigate the association between CLD and CVD. To successfully achieve the aims of this project, four work packages were employed, including a systematic review, a retrospective study, a Mendelian randomisation study, and a cross-section study involving the BRIDGE study. The systematic review study related to arterial stiffness in patients with CLD using various pulse wave velocity (PWV) methods, which assessed and summarised the outcomes of all relevant studies regarding the link between CLD and CVD. The retrospective study analysed anonymous data from the SUMMIT study to assess the vascular function in patients with CLD in the presence of CVD and type 2 diabetes mellitus, and shows a significantly greater PWV; p-value = 0.015 and carotid intima-media thickness (CIMT) in the CLD patients; p-value = 0.001. The Mendelian randomisation study investigated potential genetic causal links between CLD and arterial stiffness, which shows a significant association; p-value = 0.021. The cross-section study and BRIDGE study utilised biomarkers to determine if there are shared pathways that contribute to the development and progression of CLD and CVD, and shows significant differences in PWV, and microvascular function; p-value = 0.001, blood biomarkers include adiponectin, VCAM-1, GDF-15, coagulation factor III, syndecan-1, and matrix metalloproteinase (MMP-10); p-value = 0.001. In conclusion, this study revealed a significant association between CLD and CVD. Therefore, monitoring CVD risk, including assessment of endothelial dysfunction and arterial stiffness, in patients with CLD might be helpful for risk stratification and for identifying future CVD pathologies and disease progression. This emphasises the need to identify and manage comorbid CLD and CVD to target new or existing therapeutic approaches to control systemic inflammation and improve overall lung and cardiovascular health.9 0Item Restricted Real-Life Effectiveness of Benralizumab Compared to Other Biological Therapies for Severe Asthma.(Saudi Digital Library, 2023-08-25) Almarhabi, Mohammed; Mansur, Adel; Ellis, PaulBackground: Severe asthma affects a small proportion of patients, remaining uncontrolled despite high-dose medications. It encompasses phenotypes including allergic, non-allergic, eosinophilic, and neutrophilic severe asthma. Biologic therapies such as anti-IgE, anti-IL5, and anti-IL4 may be used for severe asthma. The aim of this research is to evaluate and compare the efficacy of benralizumab in the treatment of severe asthma and eosinophilic asthma to that of other biological therapies, including dupilumab, reslizumab, mepolizumab, and omalizumab. Methods: In a cross-sectional study utilising the Birmingham Regional Severe Asthma Registry data, outcomes of benralizumab versus other biologic treatments were compared in terms of oral corticosteroid use, FeNO levels, blood eosinophils count, lung function, quality of life indices, emergency visits, and hospital admissions. Parametric (t-test) or non-parametric (Kruskal-Wallis) analyses were undertaken to compare continuous variables depending on data distribution, whilst cross-tabulation was performed to compare categorical data underwent evaluation via cross-tabulation (Chi-square tests). Results: The study included 516 patients using biological treatments, distributed across the following groups, benralizumab (n=97), omalizumab (n=196), dupilumab (n=16), and mepolizumab (n=207). Medians, accompanied by p-values were utilised to compare outcomes across the biologics. Just around 29.9% of benralizumab remained on oral steroids, similar to other biologics (25-31%). Benralizumab, dupilumab, and omalizumab showed an FEV1% improvement ranging from 77% to 102.5% compared to pre-biological treatment database 71.2%. While all biologics demonstrated clinically meaningful improvements in quality-of-life scores greater than 55 compared to the pre-biological treatments database, the differences in pre-bronchodilator FEV1 and quality-of-life scores among biologics were not statistically significant. Unique to benralizumab was an elevated FeNO level with a median of 48 ppb (IQR 9, 239) and a reduced blood eosinophil count to a median of 0 x109 /L (IQR 0, 2), aligning with its anti-IL5 mechanism and distinguishing it from anti-IL4 and anti-IgE medications. Furthermore, emergency visits decreased across biologics, with benralizumab, dupilumab and mepolizumab reducing median visits to 0 and omalizumab lowering to 1 visit, compared to 5 median visits pre-biologics database. Furthermore, all biologics, on average, reduced hospital admissions to a median of 0 hospital admission, down from a median of 1 in the pre-biological treatment database. Conclusion: Real-world data suggest that benralizumab may demonstrate differences in FeNO levels and blood eosinophils. However, other clinical outcomes appeared consistent when compared with other biologics in patients with severe asthma. In general, all biologics including benralizumab showed improvements in clinical outcomes when compared to the pre-biologics database.55 0Item Restricted Does Physical Activity Lower the Risk of Developing Asthma for Children?(Saudi Digital Library, 2016) Aldaadi, Abdullah; Russell, Melissa; Cassim, Raisa; Lowe, AdrianBackground: Asthma is the leading cause of chronic diseases in children, and its prevalence has been increasing in many countries especially for children. It is the one of the leading factors contributing to school absenteeism and has a sizable impact on health care expenditure. Physical activity was suggested as a protective factor against asthma incidence, with a recent review finding a marginally significant odds ratio supporting this claim for adults. However, there is only one study of this association for children that did not find a significant association. We aim to perform our own analysis of this association on Australian children. Methods: We used two waves of data from the longitudinal study of Australian children, a study that is representative of all Australian children with some exceptions. This study used a double staged clustered design, choosing postcodes before choosing children from those postcodes and they collected data in a cross sectional manner every two years. Children with asthma at baseline were excluded since we are looking at incidence, with the remaining children with complete data entering a multivariable logistic regression. Results: The unadjusted and adjusted analyses found no effect of physical activity on asthma incidence in this study sample of Australian children with an odds ratio of about one and a 95% confidence interval that crosses the null value. There is a possibility that the remaining sample size did not have enough power to detect an effect size of this association, and that there was a misclassification of exposure and outcome. Conclusion: The results of this study do not provide us with enough evidence to support the hypothesis that physical activity is protective against asthma incidence. Further research specific to this association is needed preferably with a larger sample size and objective measures of physical activity and asthma.15 0