Saudi Cultural Missions Theses & Dissertations
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Item Restricted COPD-Aware Modelling of Heart Failure Hospital Admissions Using Routinely Collected Primary Care Prescription Data(Saudi Digital Library, 2025) Alghamdi, Taghreed Safar; AishwaryaprajnaHeart failure (HF) is a leading cause of unplanned hospital admissions in the United Kingdom (UK), consuming 1–2% of the National Health Service (NHS) annual budget, with most costs from inpatient care. Many predictive models oversimplify medication histories, relying on static indicators instead of time-aware prescribing patterns. This study improves HF admission prediction using UK primary care data, focusing on monthly dosage trends of three therapeutic classes angiotensin converting en- zyme inhibitors (ACEIs), beta-blockers, and angiotensin receptor blockers (ARBs) and the influence of Chronic Obstructive Pulmonary Disease (COPD). Three linked datasets patient demographics and comorbidities (patientinfo), prescription records (prescriptions), and chronic condition diagnoses (indexdates) were merged after cleaning and validation. Static attributes and temporal medication features were used to train Long Short-Term Memory (LSTM) networks, Random Forest, and Logistic Regression. Due to poor performance of the LSTM and Random Forest in a multi-class setting (ad- mission count categories), the task was reframed as binary classification (admission vs. no admission), with class imbalance addressed using the Synthetic Minority Oversampling Technique (SMOTE). The final dataset included 963 patients and over 109521 monthly prescription records. The best perfor- mance was from standard Random Forest (without SMOTE), which retained clinical interpretability, identifying COPD status, total monthly medication dosage, and age at HF diagnosis as top predic- tors. COPD patients had a 12% higher admission rate (59.1% vs. 41.8%). These findings show that granular, dosage-aware prescribing data can enhance HF admission prediction. Future work will ex- plore hybrid classification regression models, incorporate laboratory and lifestyle data, and validate externally to improve generalisability and support NHS decision-making.9 0Item Restricted Novel Pharmacological Strategies to Treat Cigarette Smoking-induced Atherogenesis in Chronic Obstructive Pulmonary Disease(Saudi Digital Library, 2025) Almerdasi, Suleman; Vlahos, Ross; Chan, Stanly; Selemidis, StavrosChronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterised by persistent airflow limitation and chronic lung inflammation, primarily driven by exposure to noxious particles and gases such as cigarette smoke (CS). Repeated CS exposure induces oxidative stress and disrupts pulmonary barrier integrity, leading to the “spill-over” of inflammatory mediators into the systemic circulation. This systemic inflammation contributes to vascular dysfunction and platelet activation, which are key drivers of cardiovascular disease (CVD) - a major comorbidity in COPD. This thesis investigated the mechanistic links between CS-induced oxidative stress, systemic inflammation, and vascular pathology using a validated preclinical model of COPD. It further evaluated the therapeutic potential of antioxidant and lifestyle-based interventions, including apocynin, carnosine supplementation, and exercise intervention, with a focus on sex-specific responses. In Chapter 3, apocynin - a NADPH oxidase inhibitor - was shown to attenuate CS-induced airway inflammation, preserve endothelial-dependent vasodilation, and reduce platelet activation, highlighting oxidative stress as a modifiable trait in COPD. Chapter 4 demonstrated that carnosine supplementation or exercise alone reduced airway inflammation and partially restored vascular function, while Chapter 5 revealed that their combination produced synergistic benefits. The combined intervention significantly preserved body weight, improved endothelial function, and prevented platelet activation, outperforming either treatment alone. Chapter 6 explored sex-specific responses to CS and intervention. Males exhibited heightened neutrophilic inflammation, vascular dysfunction, and platelet adhesion, whereas females showed greater lymphocytosis and epithelial thickening. The combined therapy mitigated these effects in both sexes, though the magnitude and mechanisms of response varied, underscoring the importance of sex as a biological variable in COPD research. In conclusion, this thesis provides mechanistic evidence that CS-induced oxidative stress and systemic inflammation drive vascular dysfunction and platelet activation in COPD. It establishes that combining carnosine supplementation with exercise offers a promising strategy to protect vascular integrity and reduce systemic inflammation. The observed sex differences further support the need for personalised therapeutic approaches in COPD management.20 0Item Restricted Individual Respiratory Symptoms and Clinical Outcomes in COPD: Associations with FEV1% and Exacerbation Frequency(Saudi Digital Library., 2025) Almarkhan, Hussam; Jordan, RachelBackground: Chronic obstructive pulmonary disease (COPD) is a progressive and heterogeneous condition characterised by restricted airflow and chronic respiratory symptoms. While composite scores like the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire (SGRQ) are commonly used, the individual impact of respiratory symptoms on clinical outcomes remains unclear. Exploring these relationships is crucial for personalised treatment strategies. Objective: To explore the association between individual respiratory symptoms and clinical outcomes (FEV1% and exacerbation) in a large international COPD cohort. Methods: Retrospective cross-sectional analysis of the pooled Collaborative International Assessment (3CIA) dataset comprising data from 22 COPD studies across seven countries (2008–2014). Variables included respiratory symptoms, FEV1%, and annual exacerbation rates. Two-stage multiple linear regression examined symptom-FEV1% associations, with Stage 1 adjusting for age, sex, and BMI, and Stage 2 including all symptoms and clinical covariates. Poisson regression analysed exacerbation counts with similar adjustments. Results: Women presented higher exacerbation rates despite better lung function than men. Sputum showed the strongest unadjusted association with worse FEV1%, followed by cough and wheeze. However, after covariate adjustment, symptoms lost independent association with FEV1%. For exacerbations, the presence of wheeze (IRR=1.41, p <0.001) and productive symptoms ‘cough and sputum’ (IRR=1.27, p =0.016) remained significant, alongside GOLD severity and mMRC scores. Conclusion: Individual respiratory symptoms associate with poorer outcomes, but relationships are largely explained by global disease severity for FEV1%. Wheeze and productive symptoms independently predict exacerbation frequency. Findings emphasise multidimensional COPD assessment incorporating comprehensive clinical profiling and symptom evaluation for optimal risk stratification.13 0Item Restricted The Influence of Cigarette and Cannabis Smoking on Severity of AATD Related Lung Disease(Saudi Digital Library, 2025) Almutairi, Raad; Anita, PyeAbstract Background: Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder associated with an increased risk of developing chronic obstructive pulmonary disease (COPD), particularly in individuals exposed to environmental risk factors such as smoking behavior. Despite growing awareness, AATD remains underdiagnosed, and many affected individuals may initiate smoking before being aware of their genetic vulnerability. The aim of this project was to explore the relationship between tobacco and cannabis use and lung function in individuals diagnosed with AATD. Methods: This observational cohort study used data from the UK AATD Registry. Variables included smoking status (categorized as current, ex-, or never smokers), cumulative tobacco exposure (pack-years), lung function measured by FEV₁% predicted, and annual exacerbation rates. A total of 1,480 individuals were initially available, 1,115 were enrolled in the analysis after excluding cases with missing key variables such as FEV₁% predicted. Descriptive statistics, non-parametric tests (Kruskal–Wallis), and correlation analyses (Spearman’s rank) were used to assess relationships. Results: Analysis of FEV₁% by smoking history groups revealed significant differences across groups (p < .001). Never-smokers had the highest mean FEV₁%, while ex-smokers had the lowest. A significant overall difference in exacerbation rates was also found between the groups (p = .017). Spearman’s correlation showed a statistically negative correlation between pack-years and FEV₁% (r = –0.278, p < .001). Descriptive statistics showed that among 18 cannabis users, the mean FEV₁% was 58.96%. Conclusion: This study reinforces the harmful effect of smoking on lung function in individuals with AATD. Both current and former smokers exhibited significantly reduced FEV% compared to never-smokers. While primary data on cannabis use suggest potential impairment, further research with larger and more detailed samples is required. These findings support prioritizing early smoking prevention and cessation strategies, particularly in AATD patients.16 0Item Restricted The Association Between Patient-Reported Outcomes and Pulmonary Exacerbation Frequency in Patients with Alpha-1 Antitrypsin Deficiency(University of Birmingham, 2024-08) Almahmoudi, Jameelah Ahmed; Pye, AnitaIntroduction: the negative effect that pulmonary exacerbations have on alpha-1 antitrypsin deficiency patients’ lung function has been explored and proven. Nonetheless, studies addressing the association between patient-reported outcomes (PROs) and exacerbation frequency in patients with AATD are lacking. Study Aim: To analyse the association between pulmonary exacerbations, and patientreported outcomes in alpha-1 antitrypsin deficiency patients. Method: Patients’ data was extracted from The AATD cohort/registry. Information regarding patients’ demographics, genotype, smoking status, smoking rate, COPD diagnosis, and FEV1% were included. The PROs include The St. George's Respiratory Questionnaire (SGRQ), The COPD Assessment Test (CAT), Modified Medical Research Council Dyspnoea Scale (mMRC). The exacerbation frequency in the last 12 months was reported by patients. Statistical association and correlation were reported. Patients with 2 or more exacerbations were labelled as frequent exacerbators (FE), and patients with less than 2 exacerbations were labelled infrequent exacerbators (IE) in the last 12 months. Also, patients were grouped as non-exacerbators with 0 exacerbations or exacerbators with 1 or more exacerbations in the last 12 months. Results: A total of 234 patients were included in this study. The FE group (n=69) reported significantly poorer PROs when compared to the IE group (n=165), even though FEV1% was not significantly different between the two groups (p = 0.055). when comparing exacerbators to non-exacerbators, all PROs and FEV1% were significantly different with poorer results seen in the exacerbators group (p < 0.001 for SGRC and CAT and p = 0.007 for mMRC). Spearman rank correlation supported that lower FEV1% and more exacerbations are significantly correlated with poorer PROs (p ≤ 0.001 in all correlations). The regression model proved that more exacerbations and declined FEV1% are significant predictors of PROs worsening. Conclusion: Frequent exacerbations and declined FEV1% are associated with worse patientreported outcomes in patients with alpha-1 antitrypsin deficiency.31 0Item Restricted A Comparative Analysis of CVD and MSK Comorbidities in Usual COPD and AATD-COPD(University of Birmingham, 2024-08) Mousa, Hatim Hammad; Michael, NewnhamBackground: Chronic obstructive pulmonary disease (COPD) and alpha-1 antitrypsin deficiency-related COPD (AATD-COPD) are complex conditions associated with cardiovascular (CVD) and musculoskeletal (MSK) comorbidities, which exacerbate the severity of the disease and impact patient outcomes. Despite their clinical relevance, the prevalence and impact of these comorbidities in AATD-COPD compared to usual COPD have not been thoroughly investigated. This study aims to address this gap by comparing the prevalence of CVD and MSK comorbidities in these two COPD populations to improve treatment approaches and patient care. Methods: This retrospective cohort analysis utilised data from the INTEGR-COPD trial and the Birmingham Alpha-1 cohort to compare the prevalence of CVD and MSK comorbidities in patients with usual COPD and AATD-COPD. Baseline characteristics, comorbidities, and pulmonary exacerbations were analysed. Non-parametric tests, including chi-square and Mann-Whitney U tests, were employed to compare categorical and continuous variables across the cohorts, respectively. Results: The study analysed 1,663 usual COPD and 754 AATD-COPD patients. CVD comorbidities were more prevalent in usual COPD (52.50%) than AATD-COPD (30.11%) (p < 0.001). Similarly, MSK comorbidities were more prevalent in usual COPD (30.07%) compared to AATD-COPD (11.41%) (p < 0.001). AATD-COPD patients were younger, had better lung function, and reported higher dyspnoea scores. Smoking status varied significantly, with higher current smokers in the usual COPD cohort. Pulmonary exacerbations were significantly more frequent in usual COPD patients with CVD than in AATD-COPD patients (p = 0.0011). Conclusion: This study highlights that usual COPD patients exhibit a higher prevalence of CVD and MSK comorbidities. Additionally, they tend to be older and have worse pulmonary outcomes compared to patients with AATD-COPD, who experience more severe dyspnoea. These findings emphasise the need for tailored clinical management approaches for both populations. Further research should explore the mechanisms and interventions to mitigate these comorbidities and improve patient outcomes.5 0Item Restricted Evaluating FEV1Q as a race-neutral measurement of lung function across three diverse populations in LMICs.(University College London (UCL), 2024-08-28) ALlayadhi, Ayadh; Hurst, JohnIntroduction The adjustment of lung function for ethnicity is controversial and has led to race-neutral approaches, such as forced expired volume in 1st second quotient (FEV1Q), which expresses FEV1 as a multiple of the theoretical lower limit of survival. It is unknown whether this lower limit is similar in diverse populations in different low- and middle-income countries (LMICs) or whether FEV1Q can accurately diagnose chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the FEV1Q as a race-neutral measure of lung function in these regions. Methods This study utilised 10660 participants’ spirometry and anthropometric data, aged ≥40 years, collected from Uganda, Nepal, and Peru, with even sex and site distribution. The assessment included: whether 1st percentiles of absolute FEV1 were similar across these populations, assessing the FEV1Q diagnostic ability for 999 COPD cases, and estimating FEV1Q decline rates under several circumstances. Results The 1st percentiles of absolute FEV1 (L) were similar to the previously reported values of 0.5 L for males and 0.4 L for females in the COPD group, while these percentiles differed in the entire population. FEV1Q had discriminative accuracy in diagnosing COPD (AUC = 0.87). Estimation of FEV1Q decline under normal conditions demonstrated 1 unit/18 years, while it declined every 12.5 years for current smokers and every 17.5 years with biomass exposure. Discussion Although this study addressed the lack of diverse populations in which FEV1Q has been assessed, and presented several strengths, it did not include follow-up measurements of lung function which limit quantifying long-term outcomes; and ethnicity/race categories were assumed based on site. This highlights the need for future longitudinal studies to assess FEV1Q utility, and shed light on other respiratory conditions. Conclusion FEV1Q is a simple and promising race-neutral measure of lung function; however, further studies are required.17 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.26 0Item Restricted The molecular basis of pathological alpha-1-antitrypsin polymerisation(University College London, 2025) Aldobiyan, Ibrahim Fahad I; Lomas, David A; Irving, James A; Orlova, Elena VAlpha-1-antitrypsin deficiency (AATD) is a rare protein misfolding disease, primarily afflicting Northern European and Iberian populations. The deficiency is due to mutations in the gene encoding alpha-1-antitrypsin which promote its misfolding and subsequent aggregation into polymeric chains within hepatocytes. This results in both gain-of- toxicity and loss-of-function phenotypes, with accumulating polymers inducing cellular damage to hepatocytes, causing liver cirrhosis in the long term. The marked reduction in circulating antitrypsin levels leads to early-onset emphysema. AATD has been studied for over half a century and the mechanism defining the polymerisation pathway in molecular detail remains elusive. Several theories have been proposed, with varying degrees of experimental support, on artificially inducedantitrypsin polymers. We propose that understanding the nature of the intermolecular linkage between the monomeric subunits of ex vivo liver-derived antitrypsin polymers is fundamental to developing therapeutics that inhibit or reverse polymerization. Such therapeutics are necessary as currently, liver transplantation is the only means of curing the condition. The principal aim of this study is to use cryo-electron microscopy (cryo-EM) with single- particle reconstruction techniques to establish the structural changes that lead to polymer formation, using material obtained from human explant tissue. Polymers are technically challenging targets due to their flexibility and heterogeneity. Decorating antitrypsin liver polymers with Fab fragments of known epitope restricted their flexibility and provided valuable orientational information, assisting particle alignment. Despite the challenging sample preparation, the structure of the monomeric subunit of alpha-1-antitrypsin has successfully been reconstructed to 4.2 Å resolution. This reconstruction, in the context of other experiments, allows conclusions to be drawn regarding the polymerisation mechanism, and its implications for the polymerisation of other members of the serpin family. It has been established that an early step in polymerisation involves a monomeric activated state, M*, with perturbations in a region known as the breach. A secondary aim of this project is to better understand the role of the breach region of AAT in the polymerisation pathway. Site-directed mutagenesis was performed on numerous sites within and around the breach. A potent small molecule polymerisation inhibitor was used to probe the effect of these mutations on the ability of antitrypsin to transition to the intermediate M* conformation and polymerise.19 0Item Restricted Association Between Chronic Airflow Obstruction and Physical Activity in A Multinational Study(Imperial College London, 2024) Alharbi, Talal; Amaral, AndreBackground Several studies have suggested that poor respiratory health may strongly impact physical activity. The aim of this study was to investigate whether people with chronic airflow obstruction are more or less likely to be physically active and to examine variations in this association across regions, sexes, and smoking statuses. Methods The data used in this study were from the general population-based Burden of Obstruction Lung Disease (BOLD) follow-up, collected from 18 different sites worldwide. A total of 3,372 participants answered the core questionnaire, provided high-quality lung function spirometry and had no missing data on relevant variables. The level of physical activity was classified into moderate, vigorous, and walking activity. We conducted comprehensive analytic modules using meta-analysis and logistic regression across different sites. The analysis assessed the impact of physical activity on the risk of airflow obstruction in both sexes, with further stratification by sexes. Result Overall, people with chronic airflow obstruction are 33% less likely to report moderate physical activity (OR: 0.67, 95% CI: 0.48 to 0.93), as compared to people without obstruction. Remarkably, the association was significant in females (OR: 0.59, 95% CI: 0.37 to 0.95) but not in males (OR: 0.78, 95% CI: 0.48 to 1.27). These results were consistent across all sites. We found no significant association between vigorous physical activity and chronic airflow obstruction. Conclusion Chronic airflow obstruction seems to have a strong effect on physical activity, particularly in females. However, it is not clear from the data whether participants with chronic airflow obstruction were already less active before developing obstruction. Anyway, integrating pulmonary rehabilitation into clinical intervention for people with chronic airflow obstruction may be important as a way to improve their health outcomes and quality of life.24 0