Second-hand smoking study jumps to conclusions....
At work today I was linked to a study that discusses the deleterious effects of second hand smoke. The article is on the web here: Brief secondhand smoke exposure can cause blood vessel and stem cell damage in 30 minutes (_http://healthorbit.ca/NewsDetail.asp?opt=1&nltid=158290408). It's full of scary phrases and innuendo like;
a 30-minute exposure to the level of secondhand smoke that one might normally inhale in an average bar setting was enough to result in blood vessel injury in young and otherwise healthy lifelong nonsmokers. Compounding the injury to the blood vessels themselves, the exposure to smoke impedes the function of the body’s natural repair mechanisms that are activated in the face of the blood vessels’ injury...
That's basically the thesis of the paper. I was a bit skeptical so I went onto science direct and got a pdf copy of the research to check out for myself. There were a few problems that I saw with the logic and argument presented, and to think that this study is used to make such drastic declarations as those above is very disturbing to say the least.
My first problem with the study, is the sample size (n=10). So they based their conclusions off of a extremely small group of the population. The sample was weighed towards males (7 men 3 women) and they were all approximately 30 years old. No discrimination was made for race, and it would have been nice to have racial data, since race has been known to influence how well or not one tolerates substances. Beyond that, of the ten participants, none had been exposed to second hand smoke, nor had every smoked cigarettes before in their life. We're not told if they were recently exposed to a fire, or if they smoked anything besides cigarettes. My guess is they were negative for both accounts, but still, for a scientific paper these things need to be controlled, accounted for, and discussed.
The first line of the study reads, "Exposure to secondhand smoke (SHS) accounts for about 50,000 deaths annually in the United States, mostly from heart disease." That basically sets the tone for the rest of the paper, an idea known as
priming.
Continuing on with the Methods, smokers were categorically excluded from the study. Later, we're told that one of the effects (levels of Epithelial Progenitor Cells, EPCs) is decreased in 'chronic smokers', in contrast to the data here which shows increased EPCs in the sample group. I would have been interested to see a much larger sample set, including smokers.
The cigerattes used in the study were Marlboro Reds, which any smoker can tell you, are not your average cigarette. This brings up another point I often have with the smoking issue.
There is a world of difference between processed, chemical laden cigarettes and those that are additive free with organically grown tobacco. This study makes no distinction, according to them all second-hand smoke is qualitatively equivalent. I won't harp on them too much though, as they were trying to simulate bar-like conditions, and SHS will contain a random sampling from every brand under the sun.
One thing the study pointed out was the concentration of particulate matter vs nicotine (367ug/m3 vs 67ug/m3, respectively). I would have been interested in a chemical analysis of the 'particulate matter', I'm sure it's been done, including as a reference it would have been a nice addition, especially considering some of the other works referenced.
They also measured Endothelium-dependent dilation of the brachial artery (flow-mediated dilation, FMD):
Baseline data for diameter and blood flow velocity of the brachial artery were quantified after 10 min of supine rest in a 21 Degree C room. A forearm blood pressure (BP) cuff was placed distal to the antecubitcal fossa and inflated to 250mm Hg for 5 min. Diameter was measured immediately after cuff deflation, at 20s, 40s, 60s, & 80s. The FMD was expressed as: (DiameterMAX - DiameterBASELINE)/DiameterBASELINE.
This method seemed a bit odd to me, mostly because they don't tell us whether or not the same was repeated to get their data post-exposure to SHS. I would hope that the same methodology was repeated in each instance, as they collected data points at 0h (30min after exposure), 1h, 2.5h & 24h. As the paper stands, we simply do not know.
We're shown their baseline cotinine levels (a metabolite of nicotine), are approximately 0.8ng/ml. This caught my attention because cotinine is a biomarker for second hand smoke, and yet it does occur naturally within the body. This opens up a new line of questioning, such as - What else causes cotinine levels to rise and fall? What is it's natural function within the body?
The way they measured 'vascular damage' was indirect, and I thought this point needed to be emphasized as it was categorically ignored in the article linked above. Their results demonstrated an increased number of EPCs, elevated level of plasma VEGF (vascular endothelial growth factor), increased systolic blood-pressure and increased EMP generation. They cite studies that demonstrate these items to be indicative of vascular damage.
They also performed ex vivo (done outside the body with biological material) experiments to determine EPC motility, and I had a slight issue here as they're drawing conclusions in vivo for processes they measured ex vivo (a small point). This is where their data comes to conclude that the repair mechanisms are 'dysfunctional' or 'impaired', along with the FMD data - which as I mentioned above, were gathered with questionable methodology.
Throughout their discussion I was confronted with phrases like, "our results suggest" "may also affect" "seems to be independent" "may be relevant" "suggest" "potentially" "which may lead to" "has been associated" "our results imply". Those nine alone came from a single paragraph. To give context, this is the type of conjecture associated with the 'discussion' section of a scientific paper, but it seems a bit overabundant. We do have to recall that the sample size was ten nonsmokers and the cigarette used was a marlboro red. These two factors alone discourage this type of conjecture. They also make this admission,
Several controversies exist regarding the nature and potential biological effects of circulating EMPs, and there is no consensus on the method for their identification. The phenotype of circulating microparticles varies depending on the cellular origin and the release mode which may subsequently determine their biological functions.
Yet the authors go on, in the very next sentence to proclaim:
The initial decrease in FMD in our study was paralleled by significantly increased numbers of EMPs in plasma, suggesting that even short exposure to SHS causes acute vascular injury/endothelial and structural damage.
They do go on to correlate their findings with those that demonstrate the same in heart disease patients, those suffering from renal disease & diabetes. However, considering that 'several controversies exist' and 'there is no consensus for their identification' their conclusions seem a bit of a stretch.
Overall the paper was not terribly difficult to read, nor was the terminology unclear - that is one complaint I typically have with proteomics papers. The biggest problem with the paper is the extremely small sample size, even my experiments have tissue coming from 30+ different individuals, and good papers that have human subjects always have at least 20-50 if not 100-1000 different people participating. This gives validity to the data and the conclusions, with such a small sample size we cannot say much for certain, and it seems the authors and those writing about the paper are saying a lot as if it is for certain.
Beyond that my complaints are more superficial, no racial data, some methodology was unclear, and many of their conclusions are drawn from indirect (though supported by parallel research) ways at measuring 'vascular damage'. I do remind the reader that the cigarette used was a marlboro red, and further, that there are hundreds of chemicals added to cigarettes and the paper to yield various affects. What role these chemicals play in the effects seen above we do not know, and this point is completely ignored by the authors of the paper as well as the author of the article. This is disingenuous when drawing conclusions about 'smoking', 'tobacco' and 'nicotine'.
If I were to perform the same study I would use a much larger sample size, n=100, ensure racial diversity and equivalent numbers of men and women within the same age group. I would also perform the experiment once for non-smokers, & once for smokers. Further, I would compare the effects between those inhaling second hand smoke from a mainstream cigarette, (Marlboro, Camel, Newport) and a cigarette containing only 100% natural, organic tobacco with no additives in the tobac or the rolling paper. The conclusions drawn from such a study would much more educational, informative, and valid then those previously presented.
Paper: Brief Secondhand Smoke Exposure Depresses Endothelial Progenitor Cells Activity and Endothelial Function. Christian Heiss, Nicolas Amabile, Andrew Lee, Yerem Yeghiazarians, et al.
UCSF, Journal of the American College of Cardiology, May 2008.
