Raúl Martínez Fernández
Neurologist and clinical researcher at the Movement Disorders Unit of the Hospital de la Santa Creu i Sant Pau (Barcelona) and at HM CINAC – HM Puerta del Sur University Hospital (Madrid)
Is the research of good quality?
"This is a very high-quality piece of research, based on an epidemiological study with a coherent and robust methodological design, a very large sample size and long-term follow-up.
One of the inherent limitations of epidemiological studies is the difficulty in controlling for all the factors that may come into play throughout a person’s life and that could potentially influence the observed associations. Although a large sample size does not completely eliminate this limitation, it does help to minimise it and lends greater robustness to the results.
Overall, I consider this to be a very well-conducted study that provides relevant information for a better understanding of the relationship between smoking and Parkinson’s disease.”
How does it fit in with the existing evidence?
“The study fits in well with previous evidence, as it reproduces an epidemiological association that has been known for decades: smokers have, statistically speaking, a lower risk of developing Parkinson’s disease.
However, for me, one of the main contributions of this work is that it allows us to pinpoint this association to a specific factor: exhaled carbon monoxide (CO). It is particularly interesting that this association is observed even in people who have never smoked. This raises the possibility that the historically described association between smoking and a lower risk of Parkinson’s disease does not necessarily depend on tobacco itself or all its components, but may be mediated, at least partially, by specific factors related to CO.
Historically, another explanation has been put forward for this inverse association. Dopamine plays a key role in reward and addiction mechanisms and, given that Parkinson’s disease is characterised by a progressive loss of dopamine, it has been suggested that people in the very early or prodromal stages of the disease might have a lower predisposition to developing addictive behaviours, including smoking. According to this hypothesis, it is not smoking that reduces the risk of Parkinson’s, but rather that undiagnosed Parkinson’s disease might reduce the likelihood of becoming a smoker. This study provides new insights into how to interpret this relationship.”
Could findings of this kind encourage people to take up smoking or prevent them from giving up?
“They shouldn’t. In fact, I believe the study’s message points precisely in the opposite direction.
The study does not identify smoking as a protective factor, but rather points to a specific element that could help explain the observed epidemiological association. This is important because it would eventually allow us to study that mechanism without having to expose ourselves to the harmful effects of tobacco.
Furthermore, the study itself shows that smoking is associated with a higher incidence of heart attack, stroke and all-cause mortality. Therefore, these results in no way justify taking up smoking or continuing to smoke.
Even in the hypothetical scenario that smoking had some protective effect against Parkinson’s disease, the risk-benefit balance would still be clearly unfavourable. Parkinson’s disease is a treatable condition and, in many patients, has a relatively benign course over many years. It would make no sense to try to reduce the risk of Parkinson’s whilst simultaneously increasing the risk of cardiovascular and cerebrovascular diseases, cancer and mortality. Conclusion: smoking is harmful.”
What are the implications of these findings for clinical practice?
“At present, they are limited, and recommendations should remain unchanged: smoking remains harmful to health and must be discouraged.
The significance of the study is primarily scientific, as it helps to better understand a well-known epidemiological association. In science, it is essential to distinguish between association and causation. The fact that two phenomena are associated does not necessarily mean that one is the cause of the other. We have known for some time that smoking is associated with a lower incidence of Parkinson’s disease, but that does not prove that smoking is the cause of this reduced risk. Identifying the specific biological factors that explain this association and determining whether any of them actually have a causal relationship is the next step.
If future experimental studies were to provide a solid biological basis for the possible role of carbon monoxide (which this study does not demonstrate), a clinical trial might eventually be considered to investigate its effects via a controlled and safe method of administration, without any need to smoke. Only then could we speak of a possible therapeutic application. At present, we are a long way from being able to make such a recommendation.”
Does the study have any significant limitations that need to be taken into account?
“The main limitation stems from its very nature as an epidemiological study. The study allows us to identify associations, but not to establish a causal relationship or, on its own, to demonstrate the biological mechanism that explains them. Epidemiological studies are, moreover, subject to multiple potential confounding factors related to lifestyle, the environment, individual characteristics and cumulative exposures over the years. In this study, the large sample size and the robustness of the design allow these limitations to be considerably minimised, although not completely eliminated.
Therefore, the results should be interpreted as strong evidence of an association and as an interesting hypothesis for further investigation, but not as proof of a cause-and-effect relationship.
Overall, I consider this to be a high-quality study that helps to put the well-known link between smoking and Parkinson’s disease into context and, above all, paves the way for understanding the mechanisms that may actually underlie this association.”