Lesson 16, Volume 16—Harm Reduction in a Persistent Smoker

By David J. Riley, MD, FCCP

Objectives

  1. Describe the concept of harm reduction and how it may be applied to persistent smokers.
  2. Inform readers about the newly introduced tobacco products with claims of being "safer cigarettes."
  3. Discuss the evidence for tobacco harm reduction.
  4. Describe the issues related to use of nicotine replacement products and antidepressants to reduce cigarette smoking.
  5. Describe the public health issues involved in instituting a tobacco harm-reduction program.

Key words

COPD; lung cancer; harm reduction; nicotine replacement products; smoking; tobacco control

Abbreviations

CO = carbon monoxide; FDA = Food and Drug Administration; IOM = Institute of Medicine; SR = sustained release

Cigarette smoking continues to be the single leading cause of preventable death in the United States. Because of the addictive property of nicotine, only about 2.5% of smokers are able to quit for a year. Because of this low quit rate, more attention has been given to making cigarettes less risky. This policy, called harm reduction, aims at minimizing harms without completely eliminating tobacco or nicotine use. A harm reduction strategy is designed to complement the primary goals of smoking cessation, preventing initiation, and eliminating environmental tobacco smoke. It is designed to help the persistent smoker who cannot stop smoking by reducing exposure and thereby reducing risk of disease.

A recent development has prompted a closer look at harm reduction. Tobacco products with claims of being "less hazardous" than conventional cigarettes have been introduced in several US cities. These products are reminiscent of the filtered and low-tar brands promoted in the 1950s and 1960s by tobacco companies as being "safer." In reality, there was no evidence that these products were more safe than conventional cigarettes. Those claims of "less hazardous" went unchallenged by independent scientific evidence because traditional tobacco products in the US were unregulated.

This time, the introduction of new products with health claims has drawn a response from the Food and Drug Administration (FDA), which has authority to regulate products with health claims. If the tobacco companies make health claims that new tobacco products are "less hazardous" than conventional products, the FDA may have the authority to demand proof of the claim before the product can be marketed. In anticipation of this, the FDA requested that the Institute of Medicine (IOM) review the science base of harm reduction. The IOM issued its report, Clearing the Smoke: Assessing the Science Base of Tobacco Harm Reduction, in 2001.1 As a member of the IOM Committee, I thought it appropriate to review the report and offer my opinions on the management of the persistent smoker. Note that my opinions may not necessarily reflect those of the IOM.

The IOM Report

The Committee's charge was not to recommend whether or not tobacco harm reduction should be pursued, but to formulate scientific methods and standards by which potentially harm-reducing products could be assessed. Potentially harm-reducing products are tobacco products or pharmaceuticals developed for their harm-reducing potential. The major conclusions of the IOM Report are shown in Table 1. A key conclusion was that it is "feasible" that reducing exposure to tobacco toxicants may reduce the risk of diseases attributable to tobacco use. Little is known about the health effects of using these products, however, and it will take many years to collect and analyze data on their effects. Until adequate data are available, the Committee called for new regulations of these new products as well as existing products. The report did not discourage cigarette manufacturers from developing potentially harm-reducing tobacco products. A harm-reduction claim was to be permitted, however, with the qualifier that "the 'substantial reduction' in exposure should be sufficiently large that independent scientific experts would anticipate finding a measurable reduction in the morbidity and/or mortality in subsequent clinical or epidemiological studies."1 The report distinguished between harm reduction for a population and risk reduction for an individual. It is possible to have reduced risk in individuals but no reduction in harm in a population. This distinction is important because a health claim would only be permitted for demonstration of reduction in harm, not simply risk reduction in individuals.

Table 1—Institute of Medicine Report*

Purpose

To formulate methods to assess potentially harm-reducing products

Conclusions

  1. No tobacco product is "safe."
  2. Evidence is insufficient to show that the new products are less harmful than conventional cigarettes.
  3. New regulations of all tobacco products are necessary for scientific testing.
  4. The public health impact of these products is unknown.

*From the IOM report.1

The Committee recognized the possibility that aggregate harm from tobacco products might be increased if the public believed "safer" products were available. It is possible that smokers who would otherwise quit might not quit, exsmokers might resume smoking, or nonsmokers might begin to smoke. If these effects outweigh reduced risk to individuals, total harm to the public would be increased. In view of this, the Committee called for future research to include basic, clinical, and epidemiologic studies to establish whether potentially harm-reducing products cause less harm to individuals and populations. To permit valid comparisons with conventional tobacco products, it was recommended that epidemiologic studies be implemented as a part of a comprehensive tobacco-control program. To accomplish tobacco control, regulation of existing products was considered essential. In summary, the IOM Committee concluded that harm reduction is a feasible and justifiable public health policy but to be implemented only if regulation and surveillance are in place to allow risk assessment.

Commentary on Tobacco Harm Reduction

Managing the persistent smoker is a challenge because almost no data exist to guide the clinician on whether reducing smoking reduces risk. Controlled laboratory studies suggest that potential harm-reducing products might decrease exposure to tobacco toxicants. However, decreased exposure does not necessarily lead to less harm as measured by morbidity and mortality. Clearly, cessation is the only way to confidently assure the patient of risk reduction. If harm reduction is recommended, the practitioner is obligated to inform the patient that no scientific data support this approach. As a practical matter, I prefer that the clinician devote his or her effort to smoking cessation rather than harm reduction. This may require using an aggressive approach combining nicotine replacement products, antidepressants, and counseling. The FDA has approved these pharmacologic products only for smoking cessation to be used for no longer than 3 months. It is intuitively appealing, however, to believe that reducing the amount smoked can lead to less risk from cigarettes. Based on this, some clinicians may choose to recommend reduced smoking as an option for persistent smokers. A general scheme of strategies for tobacco control is outlined in Figure 1. This shows harm reduction for the persistent smoker with continued attempts to move toward cessation. Once smoking ceases, the goal should be to prevent resumption of smoking and to avoid second-hand smoke.

Figure 1. Smoking status and tobacco control.

Reducing Smoking Without Quitting

Evidence suggests that the amount smoked is related to the risk of tobacco-related diseases. This provides supportive evidence for encouraging reduced smoking without actually quitting. Several epidemiologic studies have shown a dose-response relationship between cigarette exposure and the risk of myocardial infarction, COPD, lung cancer, and stroke (reviewed in the IOM report1). Investigators have made estimates of the effect of reducing smoking on lung cancer. One case-control study reported a 20% reduction in risk of lung cancer in a group who decreased daily consumption by > 25% compared with those who continued to smoke, but this was not significant.2 Another study reported that reducing cigarette consumption by 50% reduced the risk of lung cancer by 16%, a barely significant change.3 Other studies showed that smokers who switched to cigars or pipes had a lower risk than those who continued to smoke cigarettes.4 Limitations of these studies include recall bias and lack of independent measurements to validate self-reported smoking.

A large survey conducted by the American Cancer Society5 suggested that a dose-response relationship exists between mortality from COPD and number of cigarettes smoked per day. It was estimated that if smoking 24 cigarettes per day is reduced by half, measurable reductions in morbidity and mortality from COPD may result. It has been shown that an aggressive approach to reduce smoking by combining nicotine replacement products, bupropion sustained release (SR), and counseling can result in a quit rate of 30% over a 2-year period.6 Other studies suggest that most smokers can reduce the number of cigarettes smoked per day to 8 to 10 cigarettes without having major withdrawal symptoms.7 It is conceivable, therefore, that some smokers who smoke 24 cigarettes per day might be able to cut this rate in half with pharmaceutical products and counseling.

Taken together, these dose-response studies appear to justify a harm-reduction strategy if validated by future population studies. However, the assumption of a simple relationship between dose and response is likely oversimplified. The curves relating smoking and death rates are curvilinear, indicating that reduced cigarette consumption may benefit light smokers more than heavy smokers. It should be remembered that there is no evidence of a safe threshold below which the risk of smoking is negligible.

Other observations suggest that reducing the amount smoked leads to less decline in lung function. Three studies have measured the effect of reduced smoking (consumption reduced by at least 25%) over a 1-year period. In one study, tests of small airway function improved 1 year after reduced smoking,8 and a second study showed that FEV1 improved.9 A third study examined the change in FEV1 over a 5-year period in subjects who were able to reduce smoking from > 15 cigarettes per day to < 15 cigarettes per day.10 Regression analysis showed that smoking reduction resulted in a benefit in subjects younger than 55 years of age but not in older subjects. There are important limitations of study design in all three studies, as none were primarily designed to test whether reduced smoking leads to a slower rate of loss of lung function. Prospective studies are needed to extend these studies and examine whether reducing smoking can abate loss of pulmonary function.

Nicotine Replacement Products and Antidepressants

Nicotine replacement products and antidepressants such as bupropion SR may play a role in tobacco harm reduction. These pharmacologic products have demonstrated efficacy as aids for smoking cessation.11 At this time, the FDA has approved these products only as cigarette smoking cessation aids and not solely for reducing cigarette consumption. In theory, nicotine replacements are likely to reduce harm simply by decreasing exposure to pyrolysis products (products that are burned) that are primarily responsible for harm. The FDA has imposed a requirement that ancillary behavioral treatments be provided along with these products because behavioral treatment augments the success rate of medications alone.11 It is likely that behavioral therapy will need to be incorporated into a harm-reduction program.

The use of nicotine replacement products for the primary purpose of reducing cigarette consumption has shown significant decreases in the number of cigarettes smoked.12-14 Ten 2-mg pieces of nicotine gum per day reduced cigarette consumption by more than one half and reduced carbon monoxide (CO) levels after 2 months.12 Smokers assigned to use a nicotine replacement product (gum, patch, spray, or tablet) for 2 weeks had reductions in cigarette consumption, CO levels, and withdrawal symptoms compared with baseline.13 Also, smokers assigned to use a nicotine inhaler had reduced smoking and CO levels after 24 months compared with control subjects given placebo.14 No serious adverse effects were observed in any of these studies.

One concern about using nicotine replacement products is potential toxicity when used chronically. Studies have found no major adverse effects with high doses of the nicotine patch or in smokers with cardiovascular disease (reviewed in the IOM report1). Nicotine replacements are contraindicated in pregnancy. Another concern is that the availability of nicotine replacement products may deter individuals from becoming abstinent, but studies have shown this does not occur (reviewed in the IOM report1). When used for 1 year, bupropion SR was found to delay smoking relapse compared with placebo.15 Strategies using a combination of nicotine replacements, antidepressants, and behavior-modification therapies might be more effective in reducing harm than a single agent alone. In summary, evidence suggests that nicotine replacements may be effective in reducing smoking and appear to be safe in concurrent smokers.

New Tobacco Products

Use of the newly introduced tobacco products with claims of reduced harm is not recommended. Little independent research has been done to evaluate these products, and reported results do not show "safer" products compared with conventional cigarettes. Clinicians should be aware of the characteristics of these products, as outlined in Table 2.

Table 2—Tobacco Products
Product Type Company Key Characteristics
Eclipse Cigarette R.J. Reynolds Less combustion than conventional cigarette
Accord Cigarette Phillip Morris Lower operating temperature than conventional cigarette; heat produced by electrical resistance
Advance Cigarette Star Scientific Low-nitrosamine cigarette
Omni Cigarette Vector Tobacco Low-nitrosamine cigarette

Tobacco manufacturers have used two methods that they claim "reduce harm." The first is use of a special tobacco-curing process that leads to reduced levels of tobacco-specific nitrosamines when tested under standard test conditions ("smoking machines"). Advance and Omni are two of the products manufactured using this curing process. Advance is being marketed with the slogan, "All of the taste...less of the toxin"; Omni is advertised as "the first reduced carcinogen cigarette." According to its manufacturer, Advance yields of CO and tar levels are lower than those for three leading brands, but the nicotine content is similar. Omni, according to data collected by its manufacturer, has lower levels of selected carcinogens compared with an unspecified conventional cigarette. This report, however, was limited to only a few of the more than 3,500 known compounds in the cigarette particulate phase, at least 55 of which are known to be potential human carcinogens. No independent yield data have been reported to verify the company's claim, and the levels of other toxins have not been reported.

The second approach involves heating tobacco rather than burning it to reduce release of harmful toxicants. Two products, Eclipse and Accord, use this process, and Eclipse also burns a small amount of tobacco to enhance its "flavor." Company scientists report that under standard smoking test conditions, Eclipse had less tar, nicotine, and CO than conventional cigarettes. However, two independent analyses showed that Eclipse had the same levels of nicotine as conventional brands but higher yields of tar and CO.16,17 Biological effects of Eclipse have been compared with ultra-low-tar reference cigarettes by scientists supported by the manufacturer.18 Significant reductions in lower respiratory tract inflammation in humans and in tumorigenic activity in the skin of animals were reported. However, no differences in other bioassays were found. Company scientists reported that Accord contains reduced tar, nicotine, and CO vs a comparison product. Independent analysis confirmed that under standard test conditions, Accord produced minimal CO and less nicotine than usual brands.19 However, these data are derived from smoking machines that may not reflect true exposure, because smokers can affect cigarette performance to increase yields.

Although some of the newly introduced products could be demonstrated to reduce some tobacco toxicants, these levels likely do not reflect exposures in real life. Carefully conducted clinical and epidemiologic studies are needed to demonstrate an effect on harm reduction. However, it will probably be decades before the impact of these products is demonstrated. Until research on reduced harm is available, none of these tobacco products can be recommended.

Barriers to Harm Reduction

Harm reduction is a policy that aims to reduce the health and societal consequences of undesirable behaviors. It has been used to prevent vehicular injury (seat belts), drug addition (needle exchange, methadone), and the dangers of adolescent sexual activity (sex education). Seat belts are very effective for reducing vehicular injuries, while there is little convincing evidence that sex education reduces unwanted pregnancies. Transferring a harm-reduction strategy to tobacco control may not be simple. The societal costs of tobacco-related disease are hidden, and contemporary American society views smoking, if done privately, as a personal freedom. These issues weaken the urgency of a policy of tobacco harm reduction. A perceived issue with harm reduction is that the strategy might undermine primary prevention and cessation of smoking, the mainstays of tobacco-control policy. The result might be under-financing and/or poorly administered programs. Another issue that may impede a harm-reduction strategy from being implemented is unwillingness of the political process to change the authority to regulate tobacco products. Traditional tobacco products are currently exempt from regulatory oversight. For valid research and surveillance to be conducted, the Congress must empower the regulatory authorities to regulate all tobacco products, whether conventional or modified. The outcome of this legal and political issue is not certain and may take considerable time to resolve.

Conclusion

First, the medical and scientific community should keep an open mind about the feasibility of tobacco harm reduction. It might be that reducing exposure to tobacco toxicants leads to less harm to the population. It will be a long and difficult road to answer this question, but our community should support this effort by promoting a change in public policy and supporting research in this area. Second, there is little to guide the practitioner about how to reduce the risk of tobacco exposure in the persistent smoker. Intuitively, it makes sense that reducing the amount smoked should reduce individual risk, but history has taught us there is no safe cigarette. My recommendation is to get patients to smoke less, but this should not dilute efforts toward the primary goals of smoking cessation and preventing initiation of smoking.

References

  1. Stratton K, Shetty P, Wallace R, et al, eds. Clearing the smoke: assessing the science base for tobacco harm reduction. Washington, DC: National Academy Press, 2001
  2. Benhamou E, Benhamou S, Auquier A, et al. Changes in patterns of cigarette smoking and lung cancer risk: results of a case-control study. Br J Cancer 1989; 60:601–604
  3. Lubin JH, Blot WJ, Berrino F, et al. Modifying risk of developing lung cancer by changing habits of cigarette smoking. BMJ (Clin Res Ed) 1984; 288:1953–1956
  4. Wald NJ, Watt HC. Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases. BMJ 1997; 314:1860–1863
  5. Burns DM, Shanks TG, Choi W, et al. The American Cancer Society Cancer Prevention Study: 12-year follow-up of one million men and women. In: Changes in cigarette-related diseases risks and their implications for prevention and control. Smoking and Tobacco Control Monograph 8. Washington, DC: National Cancer Institute, 1997; Publication No. 97-4213; 113–304
  6. Anthonisen NR, Connett JE, Kiley JP, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline in FEV1: the Lung Health Study. JAMA 1994; 272:1497–1505
  7. Hughes J. Reduced smoking: an introduction and review of the evidence. Addiction 2000; 95(suppl 1):S3–S7
  8. Buist AS, Sexton GJ, Nagy JM, et al. The effect of smoking cessation and modification on lung function. Am Rev Respir Dis 1976; 114:115–122
  9. McCarthy DS, Craig DB, Cherniack RM. Effect of modification of the smoking habit on lung function. Am Rev Respir Dis 1976; 114:103–113
  10. Lange P, Groth S, Nyboe J, et al. Effects of smoking and changes in smoking habits on the decline of FEV1. Eur Respir J 1989; 2:811–816
  11. Fiore M, Bailey W, Cohen S, et al. Treating tobacco use and dependence. Clinical Practice Guideline series. Rockville, MD: US Department of Health and Human Services, Public Health Service, 2000
  12. Rennard SI, Daughton D, Fujita J, et al. Short-term smoking reduction is associated with reduction in measures of lower respiratory tract inflammation in heavy smokers. Eur Respir J 1990; 3:752–759
  13. Fagerström KO, Tejding R, Westin A, et al. Aiding reduction of smoking with nicotine replacement medications: hope for the recalcitrant smoker? Tob Control 1997; 6:311–316
  14. Bolliger CT, Zellweger J-P, Danielsson T, et al. Smoking reduction with oral nicotine inhalers: double blind, randomized clinical trial of efficacy and safety. BMJ 2000; 321:329–333
  15. Hays JT, Hurt RD, Rigotti NA, et al. Sustained-release bupropion for pharmacologic relapse prevention of smoking cessation. Ann Intern Med 2001; 135:423–433
  16. Fagerström KO, Hughes JR, Rasmussen T, et al. Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behavior, nicotine and carbon monoxide exposure, and motivation to quit. Tob Control 2000; 9:327–333
  17. Labstat International Inc. Test report: Project Identifier GC7. September 6, 2000. Available at http://www.tobaccofreekids.org/reports/eclipse. Accessed January 24, 2002
  18. Eclipse Expert Panel. A safer cigarette? A comparative study: a consensus report. Inhal Toxicol 2000; 12(suppl 5):1–48
  19. Buchhalter AR, Eissenberg T. Preliminary evaluation of a novel smoking system: effects on subjective and physiological measurements and on smoking behavior. Nicotine Tob Res 2000; 2:39–43

Copyright ©2002 American College of Chest Physicians