Monday, June 16, 2014

Glantz Asserts that Pulmonary Effects of Smoking May Be No Worse than those of Vaping

In a comment submitted to the FDA, Dr. Stan Glantz has asserted that in terms of pulmonary effects, the use of electronic cigarettes may not be any less hazardous than smoking conventional cigarettes.

Of course, this is the same thing as stating that cigarette smoking may be no worse than vaping in terms of its effects on pulmonary function.

Dr. Glantz writes: "Evidence that e-cigarette aerosol has the same effects on an important measure of lung function as cigarette smoke undermines the assumption that e-cigarettes are uniformly less risky than conventional cigarettes."

This assertion is based on a new study which found that electronic cigarette use, like smoking, results in reduced levels of exhaled nitric oxide. As Dr. Glantz writes:

"The paper, "Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide," by Sara Marini, et al, just published in Toxicology and Applied Pharmacology (Volume 278, Issue 1, 1 July 2014, Pages 9–15), reports important data showing that nicotine e-cigarettes, non-nicotine e-cigarettes, and conventional cigarettes all have similar effects of depression of exhaled nitric oxide."

Based on this single study, Dr. Glantz concludes: "the FDA must be extremely careful about assuming that e-cigarettes uniformly pose less risk than conventional cigarettes."

Stated another way, Dr. Glantz is cautioning the FDA against assuming that e-cigarettes are safer than conventional cigarettes in terms of their effects on lung function.

The Rest of the Story

In my opinion, Dr. Glantz's conclusion from this study is unscientific, illogical, and extremely damaging and destructive to the FDA's consideration of this issue as well as to the public's appreciation of the severe hazards of cigarette smoking.

Dr. Glantz is simply wrong. There is abundant evidence which demonstrates that while vaping does cause some degree of respiratory irritation (and probably triggers a bit of inflammation), it is far safer than smoking and has far less of an effect on lung function.

In fact, in a study by Flouris et al., the investigators found that real cigarettes, but not the fake ones, had a significant detrimental effect on pulmonary function, measured by spirometry. This study documents that while active smoking has immediate, clinically meaningful effects in reducing lung function, electronic cigarettes do not.

The study found that: "Neither a brief session of active e-cigarette smoking (indicative: 3% reduction in FEV1/FVC) nor a 1 h passive e-cigarette smoking (indicative: 2.3% reduction in FEV1/FVC) significantly affected the lung function (p > 0.001). In contrast, active (indicative: 7.2% reduction in FEV1/FVC; p < 0.001) but not passive (indicative: 3.4% reduction in FEV1/FVC; p = 0.005) tobacco cigarette smoking undermined lung function."

The main study finding was as follows: "The assessment of lung function demonstrated that neither a brief session of active e-cigarette smoking nor a 1 hour passive e-cigarette smoking session significantly interfered with normal lung function. On the other hand, acute active and passive tobacco cigarette smoking undermined lung function, as repeatedly shown in previous studies."
The study concluded that: "e-cigarettes generate smaller changes in lung function but similar nicotinergic impact to tobacco cigarettes."

In order to draw the conclusion that Dr. Glantz drew in his comment, one would have to completely ignore this study. Obviously, Dr. Glantz has done exactly that. He has based his comment on one narrow study and ignored the rest of the literature.

But it doesn't end there.

The Marini study demonstrates that electronic cigarettes do lead to a reduction in exhaled nitric oxide, which suggests that they have a mild respiratory irritant effect and induce some inflammation in the airways. This is a finding which has been reported previously in a number of studies. It is not surprising because propylene glycol is known to be a mild respiratory irritant.

But what is the clinical meaning of this effect? In order to find that out, one needs to conduct studies with longer-term end points.

Well, Polosa et al. have conducted exactly such a study. They examined the changes in asthma symptoms among smokers who continue to smoke versus those who switch to electronic cigarettes. These investigators reported that in contrast to real cigarettes, the fake ones result in actual harm reversal. Lung function, asthma control, and asthma symptoms were significantly improved among patients who switched from regular cigarettes to electronic cigarettes. These improvements were even observed among patients who became dual users of both real and fake cigarettes.

It is clear from the overall evidence that electronic cigarettes are not as risky as tobacco cigarettes in terms of acute effects on lung function. On this issue, Dr. Glantz's comment is simply wrong.

The very idea that one would extrapolate from a study finding that vaping, like smoking, reduces exhaled nitric oxide levels to the conclusion that smoking may be no more hazardous than vaping in terms of its acute pulmonary effects defies scientific logic. It also shows a misunderstanding, or at least a misinterpretation of the meaning of exhaled nitric oxide findings.

The finding of reduced exhaled nitric oxide is an indication that an exposure is causing some sort of inflammatory effect on cells lining the respiratory tract. It doesn't mean anything more or less than that. You can't take two exposures - each of which causes respiratory tract inflammation - and make the statement that the effects of both exposures are equal. Risk posed by an exposure depends on many other factors, including the degree of inflammation induced, the reversibility of the effect, the nature of the exposure, the chronicity of the exposure, etc.

To understand how ridiculous Dr. Glantz's extrapolation is, consider some of the other exposures that also cause reductions in exhaled nitric oxide:

1. Taking an exam

When students take their final exam in my course, they are all experiencing acute effects on their respiratory tracts. In fact, if you were to measured their exhaled nitric oxide levels, you would find that there is a significant reduction, just as is observed with smoking.

In fact, this is precisely what Trueba et al. demonstrated in a study of changes in exhaled nitric oxide levels in 41 healthy college students. 

Would one therefore conclude that taking an exam is just as risky, in terms of respiratory effects, as smoking a cigarette? Apparently, Dr. Glantz would draw such a conclusion. But it is easy to see why this is an inappropriate conclusion. And we would never disseminate messages to the public that smoking is no more hazardous than taking an exam.

Can you imagine if the tobacco companies used the same logic as Dr. Glantz? They would, according to his scientific reasoning, be perfectly honest in communicating to the public statements like this:

"Smoking is not uniformly more hazardous than simply taking an exam."

"In terms of acute effects on respiratory function, active smoking is exactly equivalent to the effects of taking a math test."

"Smoking is no more hazardous than taking an exam in terms of its acute respiratory effects."

To be completely honest, Trueba et al. actually found that not only did taking an exam affect nitric oxide levels, but it also produced decreases in lung function measured by spirometry. This is something that has not been observed for electronic cigarettes. 

2. Feeling sad

Trueba et al. also found that higher depressive mood was associated with greater reductions in exhaled nitric oxide.

Using Dr. Glantz's reasoning, the cigarette companies would be perfectly honest in putting out headlines stating:

"Smoking no worse on the lungs than feeling a little sad."

"By improving symptoms of depression, smoking may actually enhance respiratory health."

You can see the quality of the scientific reasoning we are dealing with.

Hopefully, the FDA will not be swayed by this nonsense.

It is worth noting that the conclusions which Dr. Glantz is disseminating are destructive because they undermine decades of public education about the severe hazards of smoking. If the public thinks that smoking is only as risky as vaping, then it is likely that many smokers will decide to continue smoking rather than quitting using electronic cigarettes. And many ex-smokers who have quit with electronic cigarettes may return to smoking, thinking that they might as well since they are not getting any definite health benefit from having made the switch.

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