Al Zahrani, Yousef
(2019)
Defining the relationship between clinical and immunological features of asthma.
MSc(Res) thesis, University of Nottingham.
Abstract
Background: Asthma is a chronic inflammatory disease in children and adults that is caused by many factors. The most common respiratory symptoms associated with asthma are wheezing, shortness of breath, chest tightness, and coughing, which alter with the duration and severity of the disease. Furthermore, other comorbidities are associated with severe asthmatics patients, such as allergic rhinitis, hay fever, and non-allergic rhinitis. Asthma is increasingly prevalent and affects around 300 million people worldwide. Approximately 5-10% of the asthma population suffers from a more severe form of the disease and has frequent exacerbations. There is a need for better understanding of how asthma presents in different patients, which will allow for stratified medicine approaches.
Objective: To define the relationship between the clinical and immunological features of asthma, I establish and perform a quality control (QC) on a well-characterized asthma cohort from multiple centres. In this cohort, I examine the relationship between blood eosinophils and clinical features of asthma, the impact of smoking on asthma presentation, and clinical and immunological features of asthma subjects that are prone to exacerbation.
Method: In this thesis, the Genetics of Asthma Severity and Phenotypes (GASP) recruited 8534 subjects. The GASP has four different cohorts, which are classified as control (n=1913), asthma (n=5713), chronic obstructive pulmonary disease (COPD) (n=678), and asthma-COPD overlap (n=230). Statistical analysis was performed on the GASP using the software package SPSS and graphs presented with the use of GraphPad Prism software.
Findings: This study included 3804 non-related asthma subjects, Majority are females (66%) with mean age of 40.48 years old. I identified a relationship between blood eosinophils and IgE utilizing data from 635 patients presented with r= 0.232 and p=value of <0.0001. Moderate-severe asthma population identified a relationship between blood eosinophil counts and atopy with p-value of 0.004. On the other hand, a total of 307 subjects reported with current smoking, and they are significantly associated with a lower lung function. I identified a relationship between lung function and ever vs never smoking groups, it has been showed that FEV1 % predicted presented with median value of 76.56% in ever group. While a reduction in median (72.72%) among never group has been showed. Females were over-represented in those patients that were prone to exacerbation, and a higher symptoms score in subjects experienced exacerbation as reported with p value 0.007
Conclusion: I developed a comprehensive database of clinical and immunological features of asthma. Using this database identified that blood eosinophil counts associated with atopic subjects. Also, it has been identified that smoking were more likely associated with reduction of lung function. In addition, females were more associated with recurrent exacerbation and presented with higher asthma symptoms. Future work will include examined the role of genetics in driving these phenotypes/characteristics.
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