NOT PEER REVIEWED We wish to comment on the findings of Smerecnik et al.1 with respect to significant advances in genetic testing , which are highly relevant to their review. Unlike the early single genetic marker tests analysed by Smerecnik et al.,1 where subjects are dichotomised to positive or negative results, genetic susceptibility tests for lung cancer are now multivariate risk tests.2 These new risk tests incorporate clinical and genetic data to derive a composite gene-based risk score. In doing so they recognise that (1) environmental factors, like how much you smoked, are important and (2) genetic data alone is not sufficiently accurate to assess a person's risk. These distinguishing features of the recently developed lung cancer susceptibility tests are very important in assessing how patients respond for two reasons. First, this approach acknowledges that environment is important and that regardless of level of risk, all smokers can significantly mitigate that risk by quitting smoking (a unique feature of smoking-related lung diseases). This means there is no concern about genetic determinism (or nihilism), risk reduction is always possible. Second, in contrast to these early single marker tests, there are no "positive" and "negative" tests, all smokers tested have some level of risk and importantly, only lifelong non-smokers are "low risk" (more accurately reflecting the real-world situation). We have developed a gene-based lung cancer risk score based on a persons smoking, age, COPD, family history and genetic markers, where these previously validated variables are combined to derive a composite score.2 This score has been prospectively verified and assigns smokers to elevated, high and very high risk according to their total risk profile.3 We have assessed the potential clinical utility of this lung cancer risk score in a feasibility study where randomly selected smokers underwent brief counselling and were offered smoking cessation treatment. We found 84% of the smokers offered the test took the test, of which 52% took NRT and 28% had quit smoking 6 months after testing (2 fold and 5 fold greater than controls respectively).4 We conclude that our lung cancer susceptibility test improved the outcome of brief intervention, by facilitating the use of smoking cessation products (NRT) and subsequent quit rate. Such a finding concurs with the tension-trigger-treatment model proposed by Robert West where our gene-based test increased motivational tension, undermined optimistic bias and, for 30-50% of smokers, triggered a favourable outcome (NRT uptake and/or quitting smoking).

References 1. Smerecnik C, Grispen JE, Quaak M. Effectiveness of testing for genetic susceptibility to smoking-related diseases on smoking cessation outcomes: a systematic review and meta-analysis. Tob Control 2012; 21: 347-354. 2. Young RP, Hopkins RJ, Whittington CF, et al. Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub -phenotyping for COPD. Plos One 2011; 6: e16467. 3. Young RP, Hopkins RJ, Hay B, Gamble GD. GWAS and candidate SNPs for COPD and lung cancer combine to identify lung cancer susceptibility: validation in a prospective study. Am J Respir Crit Care Med 2010; 181: A3738. 4. Hopkins RJ, Young RP, Hay B, et al. Lung cancer risk testing enhances NRT uptake and quit rates in randomly recruited smokers offered a gene- based risk test. Am J Respir Crit Med 2012; 185: A2590.

Conflict of Interest:

Dr Young has helped to develop a gene-based risk test for lung cancer susceptibility. Patents related to this test are held by Synergenz Bioscience Ltd who helped fund the research underlying the develeopment of this test.

NOT PEER REVIEWED This study violates basic ethical principles of research conduct because it exposes children to unreasonable and unnecessary risks, intentionally encourages parents to put their children at risk, and fails to incorporate alternative methods that would reduce these risks.

The Helsinki declaration states that:

"The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances:

1. The use of placebo, or no treatment, is acceptable in studies where no current proven intervention exists; or

2. Where for compelling and scientifically sound methodological reasons the use of placebo is necessary to determine the efficacy or safety of an intervention and the patients who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care must be taken to avoid abuse of this option."

In the present study, children in group 1 were provided with an intervention to reduce their exposure to secondhand smoke: parents were asked not to smoke in the presence of their children. Children in group 2 were not provided with any treatment. According to the Helsinki declaration, this would have been acceptable only if: (1) there was no treatment available; or (2) children receiving no treatment would not be subject to any risk of serious harm. Neither of these conditions are met.

Furthermore, this study goes beyond simply providing no treatment to the children in group 2. Instead of simply observing these children over time, the study protocol called for "asking" the parents not to change their smoking habits.

In other words, the investigators knowingly and intentionally placed the children in group 2 at significant risk of health damage.

In the United States, the federal regulations on the protection of human subjects (section 46.406a) would have allowed this research to be conducted on minors only if: "The risk represents a minor increase over minimal risk." This condition is clearly not met, as the risks of pneumonia, bronchitis, respiratory illness, and cardiovascular damage are a major increase over minimal risk.

Moreover, there was an alternative procedure available that would have provided the same scientific knowledge without putting children at substantially more than minimal risk. The investigators could have encouraged all parents not to smoke around their children and then followed all the children over time as a single group. Then, they could have assessed changes in secondhand smoke exposure and related those changes (or lack of changes) to the persistence or disappearance of sleep bruxism.

There is no justification for the investigators asking parents to continue to smoke in the presence of their children.

Rather than acknowledge that they made a mistake, the instead defend the study. But in defending the study, they deliver a definitive knock-out blow to their argument that the study was ethical. They point out that after being randomized to group 2, a number of the families dropped out of the study, refusing to participate because: "aware of the risks of SHS, [they] decided to reduce it and therefore did not participate."

If the subjects themselves realized that they were being put at undue risk by agreeing to participate in the study, then it is quite clear that this research was unethical. In fact, after a number of families refused to participate because of the risks to which they were being asked to be exposed, the IRB should have been informed and the study should have been halted.

The authors go on to justify their research by noting that "all of the parents of group 2 remaining in the trial were those who reported not being able to reduce children's exposure to SHS." This is an unacceptable argument. A feeling that one is not able to take a particular action is no justification for investigators putting the children of those subjects at risk and failing to deliver any intervention to encourage those parents to quit, reduce their smoking, or not smoke in the presence of their children.

Conflict of Interest:

None declared

Omid Fotuhi,1 Geoffrey T Fong,1,2 Mark P Zanna,1 Ron Borland,3 Hua- Hie Yong,3 K Michael Cummings4

1. Department of Psychology, University of Waterloo, Waterloo, Ontario, Canada 2. Ontario Institute for Cancer Research, Toronto, Ontario, Canada 3. The Cancer Council Victoria, Melbourne, Victoria, Australia 4. Department of Health Behavior, Roswell Park Cancer Institute, Buffalo, New York, USA

Email for lead author, Omid Fotuhi: ofotuhi@uwaterloo.ca

NOT PEER REVIEWED Response to letter:

In our recent study--using a large set of nationally representative samples of smokers from Canada, the US, the UK, and Australia--we reported on the longitudinal patterns of smoking-related beliefs and how these beliefs vary with changes in smoking status. We found a consistent pattern of attitude-behaviour congruence: smokers highly endorsed risk-minimizing beliefs (e.g., "I have the genetic make-up that allows me to smoke without any health problems") and functional beliefs (e.g., "Smoking helps me concentrate"). But the most interesting finding was the longitudinal pattern of how these justifications for smoking changed over time as their smoking status changed: smokers endorsed these beliefs the least when they had quit; and again endorsed these beliefs to their pre-quit levels if they relapsed back to smoking, whereas the levels of endorsement of these beliefs stayed low among those smokers who had quit smoking and were able to stay quit in the long-term. We proposed that the waxing and waning of these smoking-related beliefs as a function of smoking status were driven by motivations to reduce cognitive dissonance (Festinger, 1957)--a fundamental human motivation to maintain consistency between one's attitudes and one's behaviours.

In response to these findings, Gould, Clough, and McEwen have offered a thoughtful commentary. In addition to writing about the importance for public health measures to target smokers' erroneous beliefs that smoking reduces stress, they agreed with our view that smokers are driven to modify their risk-minimizing beliefs because of their motivation to reduce dissonance.

However, Gould et al. suggest that an alternate mechanism is responsible for the longitudinal pattern of functional beliefs that we report in our study. Rather than being driven by dissonance-reducing motivations, they suggest that higher endorsements of functional beliefs among smokers are "representations of smokers' genuine experiences of nicotine withdrawal 'in between' cigarettes or on quitting."

We, on the other hand, do not see a contradiction between their interpretation and ours. Rather, we suggest that the physiological reactions to withdrawal and dependence are the starting point for the cognitive dissonance process. This is a view that has long been shared by dissonance researchers (e.g., Zanna, Cooper, & Taves, 1978; Croyle & Cooper, 1983).

So the Gould et al. account does not, at the core, differ from our account. They are pointing out the nature of the reasons for the justifications, which is the whole point of our argument: the fact that smokers are addicted and that they suffer withdrawal symptoms leads to the search for justifications for their smoking (rather than saying that "I am addicted"). The physiological symptoms of dependence and withdrawal can, therefore, lead to effects far outside the realm of the physiology of the smoker.

Thus, their account is not an alternative explanation--it may well be the starting point for what then become biases in cognitions to justify smoking.

In addition, when looking at the data from our study, we note that non-quitters endorsed both risk-minimising and functional beliefs more, compared to successful and failed quitters, at all three waves--even at times when all three groups were smoking (wave 1). Because it is unlikely that the pattern of risk-minimizing beliefs (e.g., "You've got to die someday, so why not enjoy yourself and smoke") is driven primarily by withdrawal symptoms--and given the strikingly similar pattern for both functional and risk-minimizing beliefs--we suggest that, at least in part, similar dissonance-reducing processes may also be responsible for the shifting of functional beliefs as smokers vacillate between smoking and having quit.

Furthermore, let us be clear that we do not claim that all smokers' smoking-related beliefs are distortions that serve only to reduce dissonance. We fully acknowledge that there may, in fact, be unique and genuine physiological experiences of nicotine consumption and withdrawal. We propose, however, that these experiences can more effectively be captured by specific measures that tap into the visceral aspects of nicotine addiction. For instance, the Hughes (1992) article cited by Gould and colleagues nicely captures these physiological experiences among quitters at various time points (e.g., increased irritability, hunger, restlessness, and cravings to smoke). These items are more directly representative of physiological responses to nicotine consumption and withdrawal than some of our functional beliefs measure (e.g., "Smoking is an important part of your life" or "Smoking makes it easier to socialize").

In fact, we would even argue that in comparison to risk-minimizing beliefs, functional beliefs are more readily employed in the service of dissonance reduction because they are less likely to be countered by reality constraints (Kunda, 1990). Specifically, we think that the functional beliefs in our study [(1) "You enjoy smoking too much to give it up"; (2) "Smoking calms you down when you are stressed or upset"; (3) "Smoking helps you concentrate better"; (4) "Smoking is an important part of your life"; and (5) "Smoking makes it easier for you to socialize"] are exactly the kind of malleable beliefs that smokers commonly employ--more so than the risk-minimizing beliefs which may be countered by rational thought (e.g., "The medical evidence that smoking is harmful is exaggerated")--to rationalize a behaviour that they know is harmful to their health.

Nonetheless, we appreciated the comments by Gould et al. because they encouraged us to take a closer look at our data and, consequently, to further think about our original interpretation of the findings.

We hope that further research continues to explore the role of attitudes in the domain of health behaviour, and specifically addictive behaviours, such as smoking. Experimental studies that more clearly determine causality and studies that examine the taxonomy of rationalizations commonly used by smokers would be especially useful for the advancement of this research topic. These findings would also have the important potential of informing policies to more effectively help save lives.

References

Croyle, R. T., & Cooper, J. Dissonance arousal: Physiological evidence. J Pers Soc Psychol. 1983;45:782-791.

Festinger L. A Theory of Cognitive Dissonance. Evanston, IL: Row, Peterson, 1957.

Hughes JR. Tobacco withdrawal in self-quitters. J Consult Clin Psychol. 1992;60(5):689-97.

Kunda Z. The case for motivated reasoning. Psychol Bull. 1990;108:480e98.

Zanna, M. P., & Cooper, J. Dissonance and the pill: An attribution approach to studying the arousal properties of dissonance. J Pers Soc Psychol 1974;29:703-709.

Conflict of Interest:

None declared

Smith et al provides us with a remarkable review of tobacco industry efforts to influence tobacco tax which deserves several comments.(1)

First, such efforts can be quite successful as in France: From February 2004 to September 2012 there was no increase in tobacco taxes, accordingly cigarette sales remained unchanged and smoking prevalence of the youngest increased during Sarkozy's presidency, an exception among developed countries.(2) The WHO must scrutinize the implementation of Article 5.3 of the Framework Convention on Tobacco Control which requires protecting public health policies from the influence of the tobacco industry. Indeed, the French example of the influence of the tobacco industry on a government is not unique.(3)

Second, the 16th point of industry tactics (Table 2 in 1) which is "trying to undermine tobacco control experts" can be harder and damaging, eg. slapping and sacking.(4) In November 2009, one of us (GD) was sued for libel by the French tobacconists' Union, because he stated on television that cigarettes kill two smokers each year for every tobacconist. In December 2009 as a tenured senior consultant in GD's unit, I (AB) was sacked by the Ministry of Health, even against the advice of the National Statutory Committee. Both of us won in court, the tobacconists' claim was rejected in 2011 by the Appeal Court and the sacking was cancelled in 2012 by the Administrative Court of Paris on the grounds that it was illegal.(5) However, none of us received compensation for the damages.

Third, even low and middle income countries can successfully resist tobacco industry efforts to influence tobacco control. Uruguay's tobacco- control campaign is associated with a substantial, unprecedented decrease in tobacco use of 4*3% per year during 2005-11.(6) We must keep in mind that the little Uruguay (GDP $31 billion) has been even sued in 2009 by the giant Philip Morris ($25 billion in total revenues for a market capitalization of $95 billion) before the World Bank's International Center for Settlement of Investment Disputes.(7)

Integrity, courage and mainly enduring efforts are needed against the tobacco industry.

References

1 Smith KE, Savell E, Gilmore AB. What is known about tobacco industry efforts to influence tobacco tax? A systematic review of empirical studies. Tob Control 2012, Online First August 12. DOI: 10.1136/tobaccocontrol-2011-050098

2 Braillon A, Mereau AS, Dubois G. [Tobacco control in France: effects of public policy on mortality].Presse Med. 2012;41:679-81.

3 Arnott D, Berteletti F, Britton J et al. Can the Dutch Government really be abandoning smokers to their fate? Lancet 2012;379:121-2.

4 Dubois G. Abuse of libel laws and a sacking: The gagging of public health experts in France. Tobacco Control Blog November 8th, 2010. Available at http://blogs.bmj.com/tc/2010/11/08/

5 Witton J and O'Reilly J. Tobacco scientist win against illegal sacking. Addiction 2012;107:1714-5

6 Abascal W, Esteves E, Goja B et al. Tobacco control campaign in Uruguay: a population-based trend analysis. Lancet 2012, Early Online Publication, 14 September. doi:10.1016/S0140-6736(12)60826-5

7 Lencucha R. Philip Morris versus Uruguay: health governance challenged. Lancet. 2010;376:852-3.

Conflict of Interest:

None declared