Respectful Insolence

Smoking and Parkinson’s disease

Blogging on Peer-Reviewed ResearchAfter the invasion of the smoking cranks last week into the comments of the three posts I somehow ended up doing on the topic of secondhand smoke (SHS), the health dangers it poses, and some of the deceptive quote mining used in the service of trying to discredit studies demonstrating a moderate but real risk from SHS , I was ready to move on to other topics. I’ll give these guys credit for one thing; they’re almost as persistent as the antivaccinationists. Despite my flooding this blog with fluff unrelated to smoking and the hazards it causes (or even, for that matter, medicine or surgery), both to the smokers and those unfortunate enough to be exposed to SHS, they’re still there. Just like the Energizer Bunny, they keep going and going and going and going. Naturally, they’re not happy that I haven’t answered each and every challenge they have made, but guess what? This is not Usenet. I used to be very active on Usenet; if I were still interested in getting down and dirty with the discussion in a Usenet-style forum, I wouldn’t have started a blog. I would have stayed in Usenet. Basically, this is my blog. It’s my hobby. Sometimes I’ll get heavily involved in the comments section; sometimes I don’t. Personally, I much prefer using that time to produce new material for you, my readers, to mull over, enjoy, attack me for, or whatever.

Besides, I was a bad boy this weekend. I bought the Harry Potter book and got through around 500 pages of it, even to the point of doing very little work on a paper that I need to submit next week. (Bad, bad Orac! I hope my postdoc will forgive me. Don’t worry, though, I’ll be back to my workaholic ways after I finish the book.) I don’t know about you, but I consider finishing the Harry Potter book to be far more important than sparring with smoking apologists. When I finish the book, maybe I’ll get back into it. In the meantime, though, despite my desire to move on to other topics for a while, there was one last smoking-related study that was rather unusual; consequently, I thought I’d look into it a bit before moving on to other topics. Here’s the abstract:

Pooled Analysis of Tobacco Use and Risk of Parkinson Disease. Beate Ritz, MD, PhD; Alberto Ascherio, MD, DrPH; Harvey Checkoway, PhD; Karen S. Marder, MD, MPH; Lorene M. Nelson, PhD; Walter A. Rocca, MD, MPH; G. Webster Ross, MD; Daniel Strickland, PhD; Stephen K. Van Den Eeden, PhD; Jay Gorell, MD

Arch Neurol. 2007;64:990-997.

Context: Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention.

Objective: To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD.

Design, Setting, and Participants: We conducted the first ever pooled analysis of PD combining individual-level data from 8 US case-control and 3 cohort studies (Nurses’ Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age- and sex-matched risk sets.

Main Outcome Measure: Incident PD.

Results: We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (>75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects.

Conclusions: Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.

Basically, this study is a meta-analysis of 8 case-control and 3 cohort studies looking at smoking and its effect on the risk for the development of Parkinson’s disease. Basically, if you boil the meta-analysis down, it reports that there is a protective effect of smoking tobacco when it comes to Parkinson’s disease. If I wanted to be really snarky, I could use the same rationale used by some of the smoking apologists who’ve infested my blog, and declare the study to be a pile of crap because the relative risk is less than 2 (or, more appropriately, between 0.5 and 1.0, meaning the protective effect is less than a 50% reduction). After all, as we have been told by these cranks, any relative risk less than 2 can be discounted. Obviously, by that standard, this study could easily be discounted by us “radical antismokers” (which is what the SHS apologists seem to think I am). What’s good for the goose, as they say.

Fortunately, I’m intellectually honest.

So, let’s look at the study. Here’s what is perhaps the meat of the study, a table that shows the decrease in relative risk as a function of pack-years smoked in case control studies:

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Basically, the relative risk falls from 1.00 for nonsmokers to 0.52 for women and 0.64 for men who’ve smoked more than 60 pack-years. (So close to the magical decrease in relative risk by 2, but so far…) This study also looked at some subgroup analyses (although this was somewhat limited by the fact that the overwhelming majority of the subjects of the studies used in the meta-analysis were white). There was no difference in the inverse association between smoking and Parkinson’s disease based on sex or educational status. More interesting, there was even a modest reduction in relative risk (13%-32%) noted even in those who had quit smoking up to 25 years prior to a diagnosis of Parkinson’s disase. Quoth the authors: “This later observation suggests that the risk reduction is unlikely to be attributable to recent changes in smoking habits resulting from behavior modifications related to incipient disease onset.”

Given the number of studies suggesting a protective effect of smoking on Parkinson’s disease, I tend to accept the results of this meta-analysis as probably vaild. So the question is: Should you smoke up in order to avoid Parkinson’s disease?

Don’t be silly!

Given the massively increased risk of lung cancer and heart disease due to smoking, it would be foolish to take up the habit to avoid Parkinson’s disease. In any sort of risk-benefit analysis, it would be obvious that smoking causes far more harm than good. Still, this result is interesting for a number of reasons. First, it is, as we say in the biz, “hypothesis generating.” Assuming that the result is valid and smoking really does have a modest protective effect against Parkinson’s disease, then there are a number of hypotheses that can be tested that could help us understand the etiology of Parkinson’s disease better than we do now. For example, one very obvious hypothesis that comes out of this research is that perhaps nicotine (or some other substance in tobacco smoke) somehow has a protective effect on the dopamine-producing neurons whose dying off results in Parkinson’s disease, whether the mechanism is due to alterations in enzyme activity or other causes. Another hypothesis to test is based on the observation from this study that there was an inverse association between smoking and Parkinson’s disease in whites and Asians, but this association was not observed in Hispanics or or African American subjects. This sort of observation screams that there is likely a genetic component involved in any protective effect of smoking on Parkinson’s disease. Finally, as with all epidemiological research, it is not possible to rule out confounding factors, as the authors point out:

Alternatively, behavioral characteristics or personality traits of patients with PD may be confounding the observed smoking association in that the same genetic or constitutional traits that increase susceptibility to PD may also prevent subjects from smoking. Thus, these traits would be the common cause for both smoking behavior and PD. Observations that smoking and personality are associated with dopaminergic functions lend support to this argument.

Of course, the most useful aspect of this sort of work is not so much smoking itself, but rather identifying what, specifically, it is in smoking that might be causing the protective effect. If there is a compound in cigarette smoke that protects against Parkinson’s disease, it’s possible that the same coumpound, whatever it might be, could be used to reverse the disease or slow its progression. Alternatively, if it is a genetic component that leads to something in cigarette smoke having a protective effect, then that could lead to a better understanding of genetic alterations that predispose people to developing Parkinson’s disease.

Of course, if one followed the strict, dogmatic line that relative risks of less than 2 are crap, as so many of the people claiming that SHS is not harmful seem to do, this potential line of research would have to be rejected out of hand. After all, if you look at the quote that were mined out of context, you’ll see that it’s epidemiologists who are supposedly saying that relative risks of less than 2 (or of greater than 0.5 for protective effects) should be rejected out of hand in epidemiological studies like this.

Comments

  1. #1 Greg P
    July 23, 2007

    We live in an age when it seems we have created many epidemiologists who need to publish to keep their jobs, thus things like this. We also have some recent data suggesting a direct relationship between excessive weight and degenerative diseases. But, as you say, what’s the mechanism?

    In the end, this is not the proper way to assess this risk. This was done by starting with a population of PD patients from studies, pooling data, then creating “matched” controls. Not the best science.
    One of the things at the outset is that you have to see what the criteria were for inclusion in or exclusion from these studies. Is this really a representative sample of PD patients? It’s probably not random.

    What would need to be done is the difficult task that the originating researchers might have to hand off to another group, that of starting with a single very large group of matched smokers and nonsmokers at a young age, then following them for 60 or more pack years. Aside from anything else, you need to see how many smokers don’t even live 60 pack years. There is no reason to believe that those who survive 60 pack years are the same population as those who survive only 20, and the difference isn’t just that they didn’t get PD.

  2. #2 Andrew
    July 23, 2007

    What kind of unit is a “pack-year”? I can’t figure out how that’s a useful measure. I mean, if I smoked ten packs over ten years does that make me a 100-pack-year smoker and therefore relatively safe from Parkinson’s? Because that would seem to me more like one cigarette every three weeks. If I smoked two packs over fifty years is that exactly as good? Only that’s about a cigarette every year, and I’d expect that would be pretty harmless even if you do it for centuries.

    Total cigarettes smoked would seem like the best unit to me: or, in annual terms, the number of cigarettes a year, integrated over the years of your life. But that’s not pack-years: that’s just packs.

  3. #3 angry doc
    July 23, 2007

    “This later observation suggests that the risk reduction is unlikely to be attributable to recent changes in smoking habits resulting from behavior modifications related to incipient disease onset.”

    So they don’t think it’s the tremors that made them stop smoking, eh?

  4. #4 BZimmerman
    July 23, 2007

    Andrew said: “What kind of unit is a “pack-year”? ”

    It’s a standard unit used to quantify smoking history. It’s “number of packs per day” times “Years smoked.” If you smoke 1 ppd for 20 years, that’s 20 pack-years. If you smoke 1/2 ppd for 20 years, that’s 10 pack-years. And so forth. It’s commonly used in discussions of the effects of smoking.

  5. #5 Bob O'H
    July 23, 2007

    I’m too lazy to look at the actual paper, so do they rule out the possibility that smokers don’t get Parkinson’s Disease simply because they’ve already keeled over from lung cancer?

    Bob

  6. #6 Coin
    July 23, 2007

    I’m too lazy to look at the actual paper, so do they rule out the possibility that smokers don’t get Parkinson’s Disease simply because they’ve already keeled over from lung cancer?

    It seems this is an important question, since my understanding is that both smokers and ex-smokers are less likely to live longer, and Parkinson’s is a late-onset disease…

  7. #7 Joseph
    July 23, 2007

    Coffee consumption also has an inverse correlation with PD.

    All correlation studies are iffy, unfortunately. You cannot definitely conclude there’s causation from a correlation. And there could always be confounds no one has thought of.

    I guess the common sense of “plausibility” always plays an important role in deciding if a correlation holds.

  8. #8 trrll
    July 24, 2007

    I’m too lazy to look at the actual paper, so do they rule out the possibility that smokers don’t get Parkinson’s Disease simply because they’ve already keeled over from lung cancer?

    If they are independent events, that should not affect the frequency of Parkinson’s Disease in smokers who are lucky enough to survive to a ripe old age.

    The inverse association of Parkinson’s Disease with smoking has been a relatively consistent finding, and has been common knowledge in the field for years (although it is still nice to see somebody do a formal meta-analysis). Of course, if one really wanted to protect oneself against PD, and was not just seeking a rationalization to keep smoking, one would probably choose something like nicotine gum or nicotine patch rather than smoking.

    Of course, we don’t know that nicotine is the causative agent, but it’s everybody’s first guess. It’s biologically plausible, since nicotine affects receptors in the brain. And we don’t know that long-term use of pure nicotine is benign. It is certainly biologically plausible that the cardiovascular risk of smoking is nicotinic. But there is a long list of known carcinogens in tobacco smoke, so it only makes sense to avoid them as possible, particularly since the risk of lung cancer in a smoker is much greater than the risk of PD in a nonsmoker (except maybe if you’re from Guam).

  9. #9 Eamon Knight
    July 24, 2007

    Well, my mother never smoked, and she had Parkinson from about age 70 on. Since personal anecdote is the only kind of data that counts, that just proves what this study says. I’ll be taking up the Filthy Habit as soon as I can get to the store to by a pack…..

  10. #10 marion
    July 25, 2007

    I seem to remember that smoking has also been shown to ameliorate the effects of Crohn’s disease (and that very definitely was not a case where lung cancer might have killed off the patient group in question before they were old enough to get the disease). Just proves to me that nicotine, like many other substances, may not be 100% bad. That doesn’t mean that inhaling it through your lungs with a nice bouquet of tobacco is a good idea. Smoking-related deaths tend to be nasty ways to go. At least people who have skydiving accidents tend to die quickly.

  11. #11 trrll
    July 25, 2007

    I seem to remember that smoking has also been shown to ameliorate the effects of Crohn’s disease (and that very definitely was not a case where lung cancer might have killed off the patient group in question before they were old enough to get the disease).

    Actually, it’s the other way around. Before development of some of the newer drugs, most people with Crohn’s disease didn’t live long enough to get lung cancer. I know one who did, who was a smoker. These days, there are some pretty decent drugs for Crohn’s disease (albeit palliative rather than curative) that don’t have lung cancer as a side effect.

  12. #12 Tim Slagle
    July 25, 2007

    At the risk of starting another avalanche:

    Perhaps I’m just putting my scientific illiteracy back on parade, but I need to know if am I reading this right:

    “In multivariable analysis adjusting for age, sex, physical activity, smoking, and intake of fat, total calories and other dietary factors, metabolic syndrome prevalence findings were: 48% higher among participants who reported drinking at least one diet or regular soft drink daily compared with those who did not report drinking soda on the physician-administered questionnaire (odds ratio 1.48, 95% CI 1.30 to 1.69).”

    http://www.medpagetoday.com/Endocrinology/MetabolicSyndrome/tb/6225

    It would seem that the risk of heart disease, presented by SHS, is roughly the same, as drinking a Coke every day.

    Perhaps in the interest of health, we should ban soda guns from bars and restaurants.

  13. #13 DuWayne
    July 25, 2007

    Tim -

    Huge difference here, nobody drinking soda, is inflicting the results on others. That said, I’m not a supporter of smoking bans in bars. On the MAX platforms (Portland’s light rail public trans) I’m all for the bans, in bars, not so much.

    I would add that as a handyman, I have on a few occasions used Coke for paint removal and flooring adhesive removal. It is great for situations where residents may have sensitivities to the rather nasty fumes that result from using keytone based solvents that are common for that application. The thought of drinking something that is an adequate substitute for keytone based solvents is rather nauseating.

  14. #14 trrll
    July 26, 2007

    It would seem that the risk of heart disease, presented by SHS, is roughly the same, as drinking a Coke every day.

    Perhaps in the interest of health, we should ban soda guns from bars and restaurants.

    Or to make the parallel more accurate, make it illegal to force somebody to drink a soda against their will.

  15. #15 tim Slagle
    July 26, 2007

    I agree.

    Nobody should be dragged into a bar against their will.

  16. #16 Orac
    July 26, 2007

    One is tempted to note that Tim seems to have accepted that science shows that secondhand smoke is indeed harmful and that his previous contention that the evidence doesn’t show it to cause adverse health effects was incorrect.

    Of course, the workers don’t necessarily have a choice but to be subjected to it for periods of time far longer than all but the most degenerate barflies. No doubt Tim will claim that no one has to work in a bar or restaurant with smoking, but that is, of course, a naively touching bit of Libertarian fantasy that has little relationship to the real world.

  17. #17 trrll
    July 26, 2007

    I agree.

    Nobody should be dragged into a bar against their will.

    Or obliged to expose themselves to a hazardous pollutant (or drink sodas) as a condition of employment.

  18. #18 Tim Slagle
    July 27, 2007

    Orac writes: “that is, of course, a naively touching bit of Libertarian fantasy that has little relationship to the real world.”

    Coal mines exist in the “real world.” Even with modern OSHA regulations, 3% of all coal miners will still contract Black Lung Disease by the time they are 50. And I would suggest, there are far more employment opportunities in Chicago for a non-smoker, then there are in a coal mining town in West Virginia.

    Should we stop mining coal? (Is it even a possibility?)

    There are risks inherent in every profession. A world where all the risks are removed from the workplace, is an unattainable “fantasy,” only visited by the truly delusional.

  19. #19 Orac
    July 27, 2007

    Tim’s failure to answer my question about whether or not he now accepts that he was mistaken when he claimed that the scientific evidence doesn’t show that secondhand smoke does not cause adverse health effects is duly noted.

    As for his comment, Tim makes two mistakes, a logical fallacy and a bad analogy. First, the logical fallacy: Tim uses a strawman argument when he implies that I (or other supporters of indoor smoking bans) are arguing that we should try to remove “all the risks” from the workplace. I never said anything of the sort, nor do those in favor of indoor smoking bans. (But it’s a nice strawman that’s much easier to attack.) What we do say is that risks that can reasonably and practically be eliminated should be. We can argue about whether the cost of eliminating exposure of workers in the food and beverage industry to SHS is too high compared to the expected benefits, but no one said anything about eliminating “all risk.” Indeed, implying or suggesting that the argument about SHS is about eliminating “all risk” strikes me as the more “delusional” statement.

    This brings us to Tim’s bizarre analogy about coal mines. Tim seems to be arguing that exposure to SHS is an inherent risk of working in bars and restaurants that workers must simply accept or find work elsewhere. That is, of course, ridiculous. There’s nothing inherent in the work required in bars or restaurants that demands exposure to SHS, other than tradition. In contrast, exposure to coal dust is a risk inherent to working in coal mines that can’t be completely eliminated. You can’t change the properties or location of coal to prevent worker exposure to coal dust. Even so, guess what? We do try to decrease that risk as much as possible. In fact, assuming that Tim’s figures are correct, they are an excellent argument that OSHA should do more to decrease the unavoidable risks inherent in coal mining, not that we as a society should do less to minimize risks to workers not inherent to the job that can be fairly easily decreased in other areas.

    But, hey, it was a nice try.

  20. #20 Tim Slagle
    July 28, 2007

    Orac writes:Tim’s failure to answer my question about whether or not he now accepts that he was mistaken when he claimed that the scientific evidence doesn’t show that secondhand smoke does not cause adverse health effects is duly noted.

    Answer here.

    And I never said you wanted to remove every risk from the workplace, I said that anyone who attempted it, is delusional. Just like you find Libertarian fantasy “naively touching;” I feel people who believe they can run a business, they know nothing about, “remarkably dellusional.”

    you write: ” There’s nothing inherent in the work required in bars or restaurants that demands exposure to SHS, other than tradition.”

    It’s beyond tradition, it’s why many people go into a bar in the first place. A place to smoke and drink. What you are saying is almost like: “There is no reason to add Tequilla to a Margarita, other than tradition.” or “I just don’t see why exotic dancers need to take their clothes off.”

    You might think that a bar should be able to survive, just providing a place to drink, but statistics prove otherwise. In the Twin Cities, over a hundred bars have closed since the smoking bans went into effect there. That’s at least a hundred families who have lost their life investment, and at least a thousand more people out looking for work.

    Do you find that acceptable in the interest of health? I certainly don’t.

  21. #22 marcus aurelius
    July 29, 2007

    Speaking of science, here are some air quality test results which measured secondhand smoke levels in bars and restaurants (the places affected by smoking bans)…….not in theoretical epidemiological petrie dishes:

    http://cleanairquality.blogspot.com/2007/04/bmj-published-air-quality-test-results.html

    http://cleanairquality.blogspot.com/2007/07/case-against-smoking-bans-part-2.html

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