Tag: smoking

To smoke or not to smoke that is the question

Barts-MS rose-tinted-odometer  ★ ★ ★ ★ ★

Yawn! I am getting tired of the saying the same-old things on this blog. Is it time to retire and do something new? 

We have done some modelling work and predict that ~20% of new or incident cases of MS could be prevented if we stop the population from smoking. The question is how do we achieve this? Taxation has worked to some extent in that we are seeing a fall in the number of current smokers, but the numbers of teenagers smoking looks as if it is quite resistant to change. The solution must be education, education, education and a war against the tobacco industry. 

Public Health England

If social media is such a powerful tool to hack the brains of voters, why don’t public health departments use this technology to promote their agenda? What we need are companies like Cambridge Analytica to do some good in the world and to promote a ‘Don’t Start Smoking’ campaign. 

We did try and get some insights into why teenage girls start smoking when Amy Sankey, a work experience student, did a survey in her school for us. Despite the almost universal awareness of the harms of smoking in terms of lung cancer, most girls, however, did not know that there is a link between smoking and autoimmunity. I suspect even if they knew about the link it would be unlikely to prevent them from starting to smoke. 

We are interested in smoking as a risk factor for MS as it is telling us something about the cause of the disease. It appears that smoking must be acting via the lungs and is due to tobacco itself. Use of oral, non-smoked, tobacco is in fact associated with a reduced risk of getting MS, hence it is not tobacco exposure. Solvent exposure is also associated with an increased risk of getting MS, which supports the lung hypothesis of developing MS. 

Lung hypothesis #1 argues that damage to the lung from smoking or solvents creates a pro-inflammatory environment that is sufficient to activate pre-existing autoreactive T-cells. In comparison, lung hypothesis #2 argues that smoking damages proteins by a process called post-translational modification and that these proteins stimulate an immune response that then cross-reacts with normal antigens to set-up autoimmunity. The argument for the latter in triggering rheumatoid arthritis, an autoimmune disease of joints, is quite compelling but is less compelling when it comes to MS. We hope to study whether post-translational modification of CNS antigens is relevant in MS via an ECTRIMS fellowship we have supported.  

What is interesting is that smoking interacts with genetic risk factors for developing MS and with EBV infection suggesting that there is a critical gene-environment interaction that causes MS. Wouldn’t it be interesting to study and find out what these interactions are? We have an exceptionally bright and able young researcher, Ben Jacobs, who wants to do a PhD on this exact topic; gene-environment interactions. At the moment we are ruminating about the best approach he should take to address this question. It is not an easy experiment so if you have suggestions please feel free to contact us.

I would also like to remind you that smokers who have MS have a much poorer prognosis, which is why we recommend that you stop smoking if you can.

If you are interested in smoking and MS there is a new review that has just come out. 

Rosso &  Chitnis. Association Between Cigarette Smoking and Multiple Sclerosis: A Review. JAMA Neurol. 2019 Dec 16. doi: 10.1001/jamaneurol.2019.4271

IMPORTANCE: Cigarette smoking is a common environmental exposure and addiction, which has severe health consequences. Smoking is a risk factor for multiple sclerosis (MS); also, smoking has been associated with disease activity and overall prognosis for patients with MS.

OBSERVATIONS: Cigarette smoking is an irritative agent on the lungs, in which a proinflammatory cascade starts that culminates in autoimmunity. Inflammation may increase the risk of MS in some individuals, in a process driven by antigen cross-reactivity between lung antigens and myelin antigens. Genetics plays a central role in the individual predisposition to mounting an autoimmune reaction. Also, free radicals, cyanates, and carbon monoxide in cigarette smoke may be directly toxic to neurons. Patients with MS who smoke have higher rates of disease activity, faster rates of brain atrophy, and a greater disability burden. Some of the outcomes of smoking were found to be reversible, which makes counselling key.

CONCLUSIONS AND RELEVANCE: The pathways involved in cigarette smoking should be further analyzed to understand the mechanisms whereby smoking worsens MS prognosis. The proinflammatory and neurotoxic outcomes of cigarette smoking may be shared by other environmental exposures, such as pollution and organic solvents. From a global perspective, efforts should be made to diminish the prevalence of cigarette smoking in patients with MS.

CoI: multiple

What’s your excuse?

What will it take to get me to stop smoking?

If you are a smoker and continue to smoke you need to think about how you want to manage your own MS. We debate endlessly about the lack of progress in developing effective treatments to slow down the worsening of MS and ignore the obvious. The first study below implies that by simply stopping smoking it will have a major impact on the outcome of your MS. Do you want to stop smoking? If you do please ask your GP or family doctor to refer you to a stop smoking cessation clinic; please note it is very difficult to stop smoking without professional help.

I am going to use this post to blow our own trumpet. In this week’s New England Journal of Medicine is a paper from a group in our University showing that e-cigarettes are superior to nicotine replacement therapies in getting people to stop smoking. This is good news; e-cigarettes give those who are really addicted to nicotine the necessary ‘nicotine hit’, whilst reducing the harm associated with cigarettes. In my opinion, there is now really now no excuse for someone with MS to continue smoking. Or am I wrong?

How smoking speeds up the onset and rate of progressive MS is unknown. Smoking may simply unregulate proinflammatory mechanisms, reduce recovery mechanisms in the brain and spinal cord or speed up the development of comorbidities in particular vascular disease, which in turn speeds up the rate of worsening in progressive MS.

The effect of smoking on progressive MS may be independent of it being a risk factor for developing MS in the first place. We need more research in this area to see what it is about smoking that triggers MS. Based on other Swedish data it appears that it is something that is in smoked tobacco that is to blame. In Sweden use of snuff or non-smoked tobacco, does not increase your risk of getting MS; in fact, the risk of getting MS in snuff users is actually lower than that of the general population.

With my #PreventMS hat on is that if we get the population not to start smoking in the first place we can prevent 1 in 5 future people from developing MS. This is why it upsets me so much when my own children smoke. Even more worrying is that if you are loaded with the correct genetic factors that predispose you to develop MS your odds of getting MS are increased dramatically if you smoke. The latter is more reason to make sure your brothers and sisters, children, nephews and nieces don’t smoke. Tragically this is easier said than done.

Study 1

Ramanujam et al. Effect of Smoking Cessation on Multiple Sclerosis Prognosis. JAMA Neurol. 2015 Oct 1;72(10):1117-1123.

IMPORTANCE: Smoking tobacco is a well-established risk factor for multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system usually characterized by bouts and remissions and typically followed by a secondary progressive (SP) course. However, it is not clear whether smoking after diagnosis is detrimental.

OBJECTIVE: To determine whether smoking after MS diagnosis is associated with a change in time to SP disease.

DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients with prevalent MS who smoked at diagnosis (n = 728) taken from the Genes and Environment in Multiple Sclerosis Study, which consists of patients from the Swedish National MS Registry. The study entrance date was at time of first-year smoking. The study was conducted between November 2008 and December 2011, with patient environmental data collected from November 2009 to March 2011 via questionnaire. Study participants were from all counties in Sweden diagnosed as having MS at the time of the Genes and Environment in Multiple Sclerosis Study and registered in the Swedish National MS Registry. Patients with MS with relapsing-remitting disease course or SP were included. These patients’ conditions were diagnosed according to the McDonald criteria and the patients responded to recruitment letters with detailed questionnaires.

EXPOSURE: Smoking, considered yearly after diagnosis and combined into a time-invariant covariate before diagnosis.

MAIN OUTCOMES AND MEASURES: Time to SPMS, measured using an accelerated failure time model, with smoking as a time-varying covariate. Other covariates included sex, age at diagnosis, snuff use, and smoking before diagnosis.

RESULTS: The optimized model illustrated that each additional year of smoking after diagnosis accelerated the time to conversion to SPMS by 4.7% (acceleration factor, 1.047; 95% CI, 1.023-1.072; P < .001). Kaplan-Meier plots demonstrated that those who continued to smoke continuously each year after diagnosis converted to SPMS faster than those who quit smoking, reaching SP disease at 48 and 56 years of age, respectively.

CONCLUSIONS AND RELEVANCE: This study provides evidence that continued smoking is associated with an acceleration in time to SPMS and that those who quit fare better. Therefore, we propose that patients with MS should be advised to stop smoking once a diagnosis has been made, not only to lessen risks for comorbidities, but also to avoid aggravating MS-related disability.

Study 2

Hajeck et al. A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. N Engl J Med. 2019 Jan 30.

BACKGROUND:  E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments.

METHODS: We randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. Participants who were lost to follow-up or did not provide biochemical validation were considered to not be abstinent. Secondary outcomes included participant-reported treatment usage and respiratory symptoms.

RESULTS: A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath.

CONCLUSIONS: E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. (Funded by the National Institute for Health Research and Cancer Research UK; Current Controlled Trials number, ISRCTN60477608 .).

Study 3

Hedström et al. Smoking is a major preventable risk factor for multiple sclerosis.Mult Scler. 2015 Oct 12. pii: 1352458515609794.

BACKGROUND: Both smoking and exposure to passive smoking have repeatedly been associated with increased multiple sclerosis (MS) risk, but have never before been studied together. We assessed the public health impact of these factors.

METHODS: In a Swedish population-based case-control study (2455 cases, 5336 controls), we calculated odds ratios of developing MS associated with different categories of tobacco smoke exposure, together with 95% confidence intervals, by using logistic regression. The excess proportion of cases attributable to smoking and passive smoking was calculated as a percentage.

RESULTS: Both smoking and exposure to passive smoking contribute to MS risk in a dose-dependent manner. At the population level, 20.4% of all cases were attributable to smoke exposure. Among subjects carrying the genetic risk factor HLA-DRB1*15 but lacking HLA-A*02, 41% of the MS cases were attributable to smoking.

CONCLUSIONS: From a public health perspective, the impact of smoking and passive smoking on MS risk is considerable. Preventive measures in order to reduce tobacco smoke exposure are, therefore, essential. In particular, individuals with a history of MS in the family should be informed regarding the impact of smoking on the risk of MS, and the importance of preventing their children from being exposed to passive smoke.