Multiple Sclerosis is an immune mediated disease of the central nervous system associated with a wide range of mainly irreversible psychological and physical disabilities in young adults. Despite the invaluable knowledge gained from the research into the disease, its aetiology and mechanism of progression are poorly understood. The natural history of multiple sclerosis is complex and there are still many unanswered questions in respect to the risk factors associated with its development and the way that the disease evolves with age. Over the years numerous theories about the disease aetiology have been postulated, but the one that best describe the disease, on the basis of our current understanding, both in terms of susceptibility and progression is the gene-environment hypothesis. According to this hypothesis, multiple sclerosis occurs as the result of an exposure(s) to some unknown environmental factor(s) in genetically susceptible individuals. In multiple sclerosis, it has been hypothesised that tobacco smoking is associated with an increased risk of the disease occurrence and adverse effects on the progression of disabilities. Despite the relatively large amount of data on the adverse effect of smoking on multiple sclerosis risk and clinical course, data from a large population based cohort was lacking. The aim of the current work was to investigate the influence of tobacco smoking on the natural history of the disease from the risk of occurrence to mortality. In the first part of the investigation, our age- and sex-matched case-control study showed that tobacco smoking is associated with higher risk of disease occurrence. However, we did not observe any association between parental smoking during patients’ childhood and the risk of multiple sclerosis. When investigating the impact of tobacco smoking on the clinical course and prognosis of the disease, our cohort study failed to show any evidence of the influence of tobacco smoking on the risk of progressive onset multiple sclerosis. However, tobacco smoking was associated with more severe disease and significantly higher levels of psychological and physical disability in current smokers. Moreover, tobacco smoking in current smokers was associated with faster disability progression and shorter time to the progressive stage of the disease in patients with relapse onset multiple sclerosis. A significant impact of tobacco smoking on the risk of premature death and patients’ life expectancy was also evident in our data where tobacco smoking in our cohort was associated with more than 2.5-fold increase in the risk of premature death and almost 10 years reduction in the patients’ life expectancy. Our data also showed that tobacco smoking can account for some of the excess mortality seen in multiple sclerosis patients. A novel finding of our research was that smoking cessation significantly reduced patients’ risk of disease progression and premature death. Although the benefits of smoking cessation were greater for patients who stopped at earlier ages, cessation was found to be beneficial at all ages. To our knowledge, this is the first study that showed smoking cessation could potentially be beneficial in reducing the risk of disability progression and premature mortality in patients with multiple sclerosis. Overall, our findings point toward adverse health impact of tobacco smoking on the clinical course of multiple sclerosis from the occurrence to mortality.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:632463 |
| Date | January 2014 |
| Creators | Manouchehrinia, Ali |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/14150/ |
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