Nicholas R. Anthonisen, MD; Melissa A. Skeans, MS; Robert A. Wise, MD; Jure Manfreda, MD; Richard E. Kanner, MD; John E. Connett, PhD; for the Lung Health Study Research Group*
Grant Support: Lung Health Study III was supported by a cooperative agreement with the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI-1U10-HL59275).
Potential Financial Conflicts of Interest: Honoraria: J.E. Connett (National Institutes of Health/National Heart, Lung, and Blood Institute); Grants received: J.E. Connett (National Institutes of Health/National Heart, Lung, and Blood Institute).
Requests for Single Reprints: John E. Connett, PhD, Coordinating Centers for Biometric Research, University of Minnesota, 2221 University Avenue SE, Room 200, Minneapolis, MN 55414-3080; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Anthonisen: University of Manitoba, Respiratory Hospital, 810 Sherbrook Street, Room 319, Winnipeg, Manitoba R3A 1R8, Canada.
Ms. Skeans and Dr. Connett: University of Minnesota, Coordinating Centers for Biometric Research, 2221 University Avenue SE, Room 200, Minneapolis, MN 55414-3080.
Dr. Wise: Johns Hopkins Asthma and Allergy Center, Division of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224.
Dr. Manfreda: University of Manitoba, Respiratory Hospital RS 115, 810 Sherbrook Street, Winnipeg, Manitoba R3A 1R8, Canada.
Dr. Kanner: University of Utah Medical Center, Pulmonary Division, 701 Wintrobe Building, 50 North Medical Drive, Salt Lake City, UT 84132.
Author Contributions: Conception and design: N.R. Anthonisen, R.A. Wise, R.E. Kanner, J.E. Connett.
Analysis and interpretation of the data: N.R. Anthonisen, M.A. Skeans, R.A. Wise, J.E. Connett.
Drafting of the article: N.R. Anthonisen, M.A. Skeans, J. Manfreda, R.E. Kanner.
Critical revision of the article for important intellectual content: N.R. Anthonisen, M.A. Skeans, R.A. Wise, J. Manfreda, R.E. Kanner, J.E. Connett.
Final approval of the article: N.R. Anthonisen, M.A. Skeans, R.A. Wise, J. Manfreda, R.E. Kanner, J.E. Connett.
Provision of study materials or patients: R.A. Wise, R.E. Kanner.
Statistical expertise: M.A. Skeans, J.E. Connett.
Obtaining of funding: R.A. Wise, R.E. Kanner, J.E. Connett.
Collection and assembly of data: R.A. Wise, J.E. Connett.
Randomized clinical trials have not yet demonstrated the mortality benefit of smoking cessation.
To assess the long-term effect on mortality of a randomly applied smoking cessation program.
The Lung Health Study was a randomized clinical trial of smoking cessation. Special intervention participants received the smoking intervention program and were compared with usual care participants. Vital status was followed up to 14.5 years.
10 clinical centers in the United States and Canada.
5887 middle-aged volunteers with asymptomatic airway obstruction.
All-cause mortality and mortality due to cardiovascular disease, lung cancer, and other respiratory disease.
The intervention was a 10-week smoking cessation program that included a strong physician message and 12 group sessions using behavior modification and nicotine gum, plus either ipratropium or a placebo inhaler.
At 5 years, 21.7% of special intervention participants had stopped smoking since study entry compared with 5.4% of usual care participants. After up to 14.5 years of follow-up, 731 patients died: 33% of lung cancer, 22% of cardiovascular disease, 7.8% of respiratory disease other than cancer, and 2.3% of unknown causes. All-cause mortality was significantly lower in the special intervention group than in the usual care group (8.83 per 1000 person-years vs. 10.38 per 1000 person-years; P = 0.03). The hazard ratio for mortality in the usual care group compared with the special intervention group was 1.18 (95% CI, 1.02 to 1.37). Differences in death rates for both lung cancer and cardiovascular disease were greater when death rates were analyzed by smoking habit.
Results apply only to individuals with airway obstruction.
Smoking cessation intervention programs can have a substantial effect on subsequent mortality, even when successful in a minority of participants.
*For a list of members of the Lung Health Study Research Group, see the Appendix.
Although there are many health benefits for smokers who stop smoking, we still lack evidence from randomized, controlled trials that smoking cessation programs reduce mortality.
In this randomized, controlled trial of a 10-week-long smoking cessation intervention in 5887 smokers with asymptomatic airway obstruction, 14-year mortality rates were higher in the usual care group than in the smoking cessation group (hazard ratio, 1.18 [95% CI, 1.02 to 1.37]). The mortality benefit was greatest among the 21.7% of the intervention group who actually managed to quit smoking.
Smoking cessation programs substantially reduce mortality even when only a minority of patients stop smoking.
Table 1. Baseline Characteristics of Lung Health Study Participants
Table 2. Causes of Death by Treatment Group
All-cause 14.5-year survival.P
Mortality rates at 14.5 years by cause.
Mortality rates at 14.5 years by cause and smoking status.CHDCVD
Table 3. Hazard Ratios for Death for Usual Care Compared with the Special Intervention, by Subgroup
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A study shows that quitting smoking decreased the death rate in participants by 46 percent.
Gregory J. Bombassei
February 21, 2005
Smoking Cessation and Mortality
I read with interest Anthonisen and colleagues' article on smoking cessation and mortality in a recent issue of the Annals. Because this report dealt with the effectiveness and cost of a smoking cessation strategy, its endpoints were concerned with treatment differences between those patients who were offered the smoking cessation intervention and those who were not.
However, I who counsel patients in practice to quit smoking am even more interested in treatment differences between those patients who actually quit smoking compared to those who continue to smoke, either continuously or intermittently. Knowing these data from a randomized clinical trial would improve my ability to inform my patients of the health benefits of smoking cessation.
It took a close read of the data, for example, to determine that among 5887 patients in this study, 957 were sustained quitters and 4930 were continuous or intermittent smokers. Even Figure 3 in the article, giving rates of death "per 1000 person-years" for each of several causes of death, is not straightforward. That is, the raw data are unknown to the reader, who is instead treated to a "sanitized" version, in which the "rate of death per 1000 person-years" is substituted for a simpler quantity, the proportion of patients who died.
I am interested to know to what extent quitting smoking reduces mortality. I am particularly interested in a Kaplan-Meier curve plotting the proportion of patients surviving versus time for sustained quitters compared to continuous or intermittent smokers.
Can the authors provide this information?
The authors write that "since death rates between special [smoking cessation] intervention and usual care participants with similar smoking habits did not differ, the differences observed in the groups as a whole were almost certainly due to differential cessation rates." Comparing the Kaplan-Meier curve depicted in Figure 1 (All-cause 14.5-year survival in the smoking cessation intervention group and the usual care group) to the Kaplan-Meier curve I suggest (All-cause 14.5-year survival in those who quit smoking and those who did not) would allow the reader to judge that for himself.
Stephen L. Hansen
February 24, 2005
Political Conclusions From An Activist
1)It's an outrage that most health plans still do not cover tobacco cessation services by physician! The Calif.Tobacco Control Alliance has a bill this year to fix that here.
2)The good news is that Medicare will begin cessation coverage in March,and has finally espoused a new preventive medicine ethic.
3)The relative ease and benignity of the abrupt cessation experienced by inmates in prisons (with no tobacco cues)is quite interesting,also. The mileau matters. And quitting is easier in smokefree states,too. California's 32 prisons go tobacco-free (no person may take any form of tobacco inside the gates) on 1 July,2005. Six pilot programs showed very few problems even with psychiatric and violent inmates. Most said:"Thanks,Doc,I couldn't have done this with everyone else still smoking."
4)Cessation reduces disease costs best in those most at risk of serious illness in the near-term.Therefore, teach all clinicians to do cessation,fund clinical efforts,provide support for quitters---including discounted premiums. Or increase premiums for smokers:KY,WV and AL have done this,a la life insurance actuaries (Actuaries ALWAYS knew the results of quitting on life expectancy!) Cheers,SH
Milan C Mathew
Memorial Hospital of Rhode Island/Brown University
March 9, 2005
The Effects of Smoking Cessation Intervention on Mortality: The "Interventions"
I read with great interest the article by Anthonisen et.al., regarding the effects of a smoking cessation intervention on 14.5 year mortality in the Lung Health Study. The authors conclude that 'smoking cessation intervention programs can have a substantial effect on subsequent mortality, even when successful in a minority of participants.' The generalizability of the study results being potentially limited to heavy smokers with pre-existing airway obstruction.
The study provides convincing evidence that smoking cessation lowers all-cause mortality. The mortality experience between the two study groups, the 'usual' care group and 'special' intervention group, did not differ significantly between those with similar smoking habits and hence the decrease in mortality is attributable to differential cessation rates between the two study groups.
However, the article fails to adequately recognize and/or address the role of the 'other' intervention received by those in the special intervention group. In addition to the smoking cessation program that included a strong physician message and 12 two-hour group sessions, using behavior modification and nicotine gum and followed by 5-years of reinforcement, they received either an 'iptratopium' or a 'placebo' inhaler. It is noteworthy that mortality did not differ significantly between those assigned to iptratropium or placebo groups. The presence of an additional intervention raises the question of what led to the differential smoking cessation rates between the special intervention and usual care groups: Was it the cessation program, the inhaler, or was it a combination of both. It can be argued that use of inhalers, irrespective of the ingredient, by heavy smokers in the special intervention group encouraged them to quit when compared to the usual care group. Furthermore, it can be argued that the role played by the inhalers in promoting cessation in this study is as significant or even more significant than the smoking cessation intervention itself. Of note is that smoking status established at 5 years in the study, changed relatively little over the next six years, especially among sustained quitters.
In summary, it would have been more appropriate to conclude that smoking cessation intervention programs in conjunction with use of inhalers lead to increased smoking cessation and decreased all-cause mortality among heavy smokers with pre-existing air-way disease. By not recognizing the role played by the co-intervention, the 'inhalers,' the article inordinately focuses the readers attention on only one of the interventions.
Weill Medical College of Cornell University
March 18, 2005
Letter to Editor
In reference to the article by Anthonisen et al (1) on the effects of a smoking cessation intervention on 14.5-year mortality among chronic obstructive pulmonary disease subjects, we would like to submit the following comments.
In this randomized controlled trial, a subgroup analysis shows significant increase in mortality among younger subjects and those who smoked more than 40 cigarettes per day (p < 0.05). However, United States population data(2) suggests that the prevalence of smoking is higher among the age groups 45 and 64 years. As study subjects between 35 and 44 years of age at baseline would have aged during the course of the study, one may conclude that the number of cigarettes smoked per day may reflect age related increase in smoking behavior. Therefore, cigarette smoking or age alone may not have an independent effect on the mortality as described in the study. The readers will certainly be interested to learn whether there is an interaction between age and number of cigarettes smoked. In addition, the relatively high prevalence of smoking among the study groups (31 cigarettes per day) compared to the general population (2) (11 "“ 18 cigarettes per day) may limit this study finding to heavy cigarette smokers.
References: 1.Anthonisen NR et al. for the Lung Health Study Research Group. The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality: A Randomized Clinical Trial. Ann Intern Med 2005; 142: 233-239 2.Schoenborn CA, Adams PF, Barnes PM, Vickerie JL, Schiller JS. Health Behaviors of Adults: United States, 1999"“2001. National Center for Health Statistics. Vital Health Stat 10(219). 2004.
Nicholas R Anthonisen
University of Manitoba
April 13, 2005
Dr. Mathew rightly points out that the Lung Health Study smoking cessation program was accompanied by the prescription of inhalers, and believes that we may not have considered the latter adequately. He agrees that the content of the inhalers [placebo or bronchodilator] didn't make any difference, and appears to accept that it was differences in smoking habits that determined the improved survival in the special intervention group. It therefore follows that if the inhalers were important, it was because they made the smoking cessation program more effective. Maybe so, but we are unapologetic about attributing smoking cessation largely to the program we designed to induce it. Inhalers per se probably have little to no effect on smoking habits, as evidenced by the fact that smoking rates are about as high in asthmatics as they are in the general population [1,2].
Dr. Bombassi is interested in Kaplan-Meier survival curves in Lung health Study participants who quit smoking as compared to those who did not. In the paper we indicated that mortality was 6.04 per 1000 person- years in sustained quitters, 7.77 per 1000 person years in intermittent quitters, and 11.09 per 1000 person-years in continuing smokers. We have sent a figure that will be published in the Annals.
N.R. Anthonisen, MD
Nicholas R. Anthonisen, MD email@example.com University of Manitoba, Winnipeg, Manitoba, Canada
References 1. Higenbottam TW, Feyeraband C, Clark TJ. Cigarette smoking in asthma. Br J Dis Chest 1980; 49: 881-884. 2. Silverman RA, Boudreaux ED, Woodruff PG, Clark S, Camargo CA. Cigarette smoking among asthmatic adults presenting to 64 emergency departments. Chest 2003; 123: 1472-1479.
Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE, et al. The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality: A Randomized Clinical Trial. Ann Intern Med. 2005;142:233–239. doi: 10.7326/0003-4819-142-4-200502150-00005
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Published: Ann Intern Med. 2005;142(4):233-239.
Cardiology, Coronary Risk Factors, Pulmonary/Critical Care, Smoking, Tobacco, Alcohol, and Other Substance Abuse.
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