Smoking still exerts a deadly grip on Americans
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Smoking ups mortality threefold

Both men and women who smoke are three times as likely to die as those who don’t.

Two large population-based studies have come to the same conclusion: Smokers are almost certainly going to die years and years sooner than nonsmokers.

    Dr. Michael Thun

"This analysis showed that a person who had never smoked was about twice as likely as a current smoker to reach 80 years of age," Dr. Prabhat Jha and his associates reported in the Jan. 24 issue of the New England Journal of Medicine (N. Engl. J. Med. 2013:368:341-50). "Among current smokers, survival was shorter by about 11 years for women and by about 12 years for men, as compared with participants who had never smoked."

The report wasn’t all bad news, however. Kicking the habit at any time added years of life, said Dr. Jha of the Center for Global Health Research, Toronto, and his coauthors.

The investigators examined smoking and smoking cessation among 113,752 women and 88,496 men who participated in the U.S. National Health Interview Survey from 1997 to 2004. These data were then correlated to information in the National Death Index up until the end of 2006.

The investigators then calculated the probability of survival in each group from 25 to 79 years of age. The mean follow-up was 7 years, with 10,743 deaths occurring in that age range.

After adjusting for education, alcohol use, and adiposity, men and women who smoked were three times more likely to have died than nonsmokers. The estimated probability of survival to the age of 80 years was 38% among women smokers but 70% for those who had never smoked. For male smokers, the probability of survival to age 80 was 26%, compared with 61% for those who had never smoked.

Both women and men who smoked were significantly more likely than nonsmokers to die in all of the smoking-related conditions examined:

• Lung cancer (hazard ratios of 18 and 15 for women and men, respectively).

• Other cancers (HR, 2 and 2).

• All cancers (HR, 3 and 4).

• Ischemic heart disease (HR, 3.5 and 3).

• Stroke (HR, 3 and 2).

• Other vascular disease (HR, 3 and 2).

• Respiratory disease (HR, 8.5 and 9).

• Other unspecified causes (HR, 2 and 2).

• All medical disorders (HR, 3 and 3).

• Accidents (HR, 4 and 2).

"At 25-79 years of age, about 62% of all deaths among female smokers and 60% of all deaths among male smokers would have been avoided if the rates of death from diseases among smokers had been the same as the rates among those who had never smoked," the authors noted.

Quitting smoking, on the other hand, conferred significant survival benefits, no matter when it occurred. Smokers who quit at age 25-34 years had similar survival to that of never-smokers. "Those who quit smoking gained about 10 years of life, as compared with those who continued to smoke."

Quitting at 35-44 years added 9 years of life, the authors found – not quite as good as those who quit earlier, but still a significant gain. "Smokers who had quit by about 39 years of age still had a 20% excess risk as compared with those who had never smoked. Although this hazard is substantial, it is much smaller than the 200% excess risk among those who continued to smoke."

Smokers who stopped at age 45-54 years gained 6 years of life, and those who quit at age 55-64 years about 4 more years of life. "Even cessation at the age of 45 to 54 years reduced the excess risk of death by about two-thirds," according to Dr. Jha and his coauthors.

While the study concluded that quitting at any age is a good idea, it shouldn’t be construed as a license to smoke longer. "That is not to say, however, that it is safe to smoke until 40 years of age and then stop, for the remaining excess risk of about 20% is substantial; it means that about one in six of these former smokers who dies before the age of 80 years would not have died."

The results are consistent with those of other studies around the world, the investigators said. The implications are staggering, especially for lower-income countries where smoking is more common and quitting less common.

"On the basis of current rates of smoking initiation and cessation, smoking, which killed about 100 million people in the 20th century, will kill about 1 billion in the 21st century."

 

 

A second study, also published in the Jan. 24 issue of the New England Journal of Medicine, found, for the first time, that women smokers are dying just as quickly – and from the same conditions – as men who smoke.

"The relative risks of death from lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, any type of stroke, and all causes are now nearly identical for female and male smokers," Dr. Michael Thun and his colleagues wrote (N. Engl. J. Med. 2013:368:351-64). "This finding is new and confirms the prediction that, in relative terms, ‘women who smoke like men die like men.’ "

Dr. Thun, an epidemiologist with the American Cancer Society, and his colleagues drew their three study cohorts from seven national studies and databases. The entire study group comprised 1.32 million women and 899,000 men. Two of the cohorts were considered historical, covering 1959-1988; five were considered contemporary, covering 2000-2010. The participants’ ages by the end of each group’s follow-up period ranged from 50 years to more than 80 years.

For never-smokers, the analysis showed a general overall improvement in mortality between the historical and contemporary cohorts. But smokers did not enjoy this benefit. Between the historical and contemporary cohorts, all-cause mortality was 50% higher in smokers than in nonsmokers.

Again, women were particularly at risk, the investigators noted. "In contrast, there was no temporal decrease in the all-cause death rate among women who were current smokers and there was a 23.6% decrease among men who were current smokers. ... The risk of death from lung cancer among male smokers appears to have stabilized since the 1980s, whereas it continues to increase among female smokers."

Dr. Thun and his associates also found the threefold increase in the risk of death between smokers and never-smokers. Their data determined that at least two-thirds of these deaths were directly associated with smoking, including ischemic heart disease, all other heart disease, stroke, and lung cancer.

A comparison of nonsmokers and smokers within all the time cohorts showed that the highest risks of death for most disorders occurred from 1982 to 1988. Since then, the mortality risks have declined and stabilized but still remain elevated compared with never-smokers. The lung cancer mortality risks were strikingly evident, the authors said: a relative risk of 25 for both men and women.

In contrast to the stabilized rates of other diseases, the mortality risk of chronic obstructive pulmonary disease has continued to increase in smokers. The biggest jump affected smokers older than 55 years and occurred after the 1980s period. The overall COPD mortality risk in the 2000-2010 cohort was more than double that of the 1980s (RR 10 vs. 25.6). The risks were similar for women (RR, 10.3-22.3) and men (RR, 12.5-27.3).

The increase is somewhat of a mystery, the authors said. It can’t be explained by aging, smoking duration, or the improved ability to diagnose COPD. Instead, the finding may be related to changes in the way cigarettes are manufactured.

"For example, the introduction of blended tobacco and genetic selection of tobacco plants lowered the pH of smoke; as a result, inhalation was easier and deeper inhalation was needed for the absorption of protonated nicotine. Other design changes, such as the use of more porous wrapping paper and perforated filters, also diluted the smoke. Deeper inhalation of more dilute smoke increases exposure of the lung parenchyma," they wrote.

Histologic studies have also found a change paralleling these manufacturing differences, the authors noted. The changes "may also have contributed to the shift, beginning in the 1970s, in the histological and topographic features of lung cancers in male smokers, with an increase in the incidence of peripheral adenocarcinomas that largely offset the decrease in squamous-cell and small cell cancers of the central airways. The likely net effect of deeper inhalation on COPD could be wholly detrimental, since COPD results from injury to the lung parenchyma."

Dr. Jha’s study was funded by the Fogarty International Center, the National Institutes of Health, the Canadian Institutes of Health Research, and the Bill and Melinda Gates Foundation. Dr. Thun’s study was funded by the National Institutes of Health and the American Cancer Society. None of the authors of either study had any financial disclosures.

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"Everyone knows cigarette smoking is bad for you. Most people in the United States assume that smoking is on its way out. But the grim reality is that smoking still exerts an enormous toll on the health of Americans," Dr. Steven A. Schoeder wrote.

In fact, the striking results of both studies may actually under-report the scope of smoking’s deadly grip on Americans’ health, Dr. Schroeder said in an accompanying editorial (N. Engl. J. Med. 2013:368:389-90).

"Population surveys accurately portray overall trends but omit nuances. Since frequency of smoking was not measured, we don’t know whether less illness occurs among light smokers (an increasing proportion of the smoking population), as compared with heavy smokers. Overall, smoking prevalence in the study by Thun et al. was only 9.5% – half the 2011 prevalence of 19% – because the samples overrepresented people who were better educated. Population groups with high rates of smoking (e.g., incarcerated persons and those with mental illness or substance-abuse disorders) are probably undersampled. Because both articles compared relative risks between smokers and nonsmokers, this omission would not alter the direction of the results. But because smokers in these populations smoke more cigarettes per day, the findings probably underestimate the overall mortality among smokers," he wrote.

Two important messages emerge from these articles, he said.

"First, in terms of health benefits, it is never too late to quit. Clinicians in general, and especially those who care for patients with smoking-related illnesses (e.g., oncologists, cardiologists, pulmonologists, emergency physicians, psychiatrists, and primary care physicians), should do more to stimulate quit attempts. Second, the importance of smoking as a health hazard needs to be elevated."

The public push for more cancer funding in certain diseases is laudable but misses some of the big picture. And smoking runs the risk of social marginalization, which could make it even more invisible to those who set research and policy priorities.

"Because smoking has become a stigmatized behavior concentrated among persons of low social status, it risks becoming invisible to those who set health policies and research priorities. Yet, the need for greater attention to the policies known to reduce the prevalence of smoking remains urgent. As former Australian Health Minister Nicola Roxon has said, ‘We are killing people by not acting,’ " according to Dr. Schroeder.

Dr. Steven Schroeder is director of the Smoking Cessation Leadership Center at the University of California, San Francisco. He had no financial disclosures.

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"Everyone knows cigarette smoking is bad for you. Most people in the United States assume that smoking is on its way out. But the grim reality is that smoking still exerts an enormous toll on the health of Americans," Dr. Steven A. Schoeder wrote.

In fact, the striking results of both studies may actually under-report the scope of smoking’s deadly grip on Americans’ health, Dr. Schroeder said in an accompanying editorial (N. Engl. J. Med. 2013:368:389-90).

"Population surveys accurately portray overall trends but omit nuances. Since frequency of smoking was not measured, we don’t know whether less illness occurs among light smokers (an increasing proportion of the smoking population), as compared with heavy smokers. Overall, smoking prevalence in the study by Thun et al. was only 9.5% – half the 2011 prevalence of 19% – because the samples overrepresented people who were better educated. Population groups with high rates of smoking (e.g., incarcerated persons and those with mental illness or substance-abuse disorders) are probably undersampled. Because both articles compared relative risks between smokers and nonsmokers, this omission would not alter the direction of the results. But because smokers in these populations smoke more cigarettes per day, the findings probably underestimate the overall mortality among smokers," he wrote.

Two important messages emerge from these articles, he said.

"First, in terms of health benefits, it is never too late to quit. Clinicians in general, and especially those who care for patients with smoking-related illnesses (e.g., oncologists, cardiologists, pulmonologists, emergency physicians, psychiatrists, and primary care physicians), should do more to stimulate quit attempts. Second, the importance of smoking as a health hazard needs to be elevated."

The public push for more cancer funding in certain diseases is laudable but misses some of the big picture. And smoking runs the risk of social marginalization, which could make it even more invisible to those who set research and policy priorities.

"Because smoking has become a stigmatized behavior concentrated among persons of low social status, it risks becoming invisible to those who set health policies and research priorities. Yet, the need for greater attention to the policies known to reduce the prevalence of smoking remains urgent. As former Australian Health Minister Nicola Roxon has said, ‘We are killing people by not acting,’ " according to Dr. Schroeder.

Dr. Steven Schroeder is director of the Smoking Cessation Leadership Center at the University of California, San Francisco. He had no financial disclosures.

Body

"Everyone knows cigarette smoking is bad for you. Most people in the United States assume that smoking is on its way out. But the grim reality is that smoking still exerts an enormous toll on the health of Americans," Dr. Steven A. Schoeder wrote.

In fact, the striking results of both studies may actually under-report the scope of smoking’s deadly grip on Americans’ health, Dr. Schroeder said in an accompanying editorial (N. Engl. J. Med. 2013:368:389-90).

"Population surveys accurately portray overall trends but omit nuances. Since frequency of smoking was not measured, we don’t know whether less illness occurs among light smokers (an increasing proportion of the smoking population), as compared with heavy smokers. Overall, smoking prevalence in the study by Thun et al. was only 9.5% – half the 2011 prevalence of 19% – because the samples overrepresented people who were better educated. Population groups with high rates of smoking (e.g., incarcerated persons and those with mental illness or substance-abuse disorders) are probably undersampled. Because both articles compared relative risks between smokers and nonsmokers, this omission would not alter the direction of the results. But because smokers in these populations smoke more cigarettes per day, the findings probably underestimate the overall mortality among smokers," he wrote.

Two important messages emerge from these articles, he said.

"First, in terms of health benefits, it is never too late to quit. Clinicians in general, and especially those who care for patients with smoking-related illnesses (e.g., oncologists, cardiologists, pulmonologists, emergency physicians, psychiatrists, and primary care physicians), should do more to stimulate quit attempts. Second, the importance of smoking as a health hazard needs to be elevated."

The public push for more cancer funding in certain diseases is laudable but misses some of the big picture. And smoking runs the risk of social marginalization, which could make it even more invisible to those who set research and policy priorities.

"Because smoking has become a stigmatized behavior concentrated among persons of low social status, it risks becoming invisible to those who set health policies and research priorities. Yet, the need for greater attention to the policies known to reduce the prevalence of smoking remains urgent. As former Australian Health Minister Nicola Roxon has said, ‘We are killing people by not acting,’ " according to Dr. Schroeder.

Dr. Steven Schroeder is director of the Smoking Cessation Leadership Center at the University of California, San Francisco. He had no financial disclosures.

Title
Smoking still exerts a deadly grip on Americans
Smoking still exerts a deadly grip on Americans

Both men and women who smoke are three times as likely to die as those who don’t.

Two large population-based studies have come to the same conclusion: Smokers are almost certainly going to die years and years sooner than nonsmokers.

    Dr. Michael Thun

"This analysis showed that a person who had never smoked was about twice as likely as a current smoker to reach 80 years of age," Dr. Prabhat Jha and his associates reported in the Jan. 24 issue of the New England Journal of Medicine (N. Engl. J. Med. 2013:368:341-50). "Among current smokers, survival was shorter by about 11 years for women and by about 12 years for men, as compared with participants who had never smoked."

The report wasn’t all bad news, however. Kicking the habit at any time added years of life, said Dr. Jha of the Center for Global Health Research, Toronto, and his coauthors.

The investigators examined smoking and smoking cessation among 113,752 women and 88,496 men who participated in the U.S. National Health Interview Survey from 1997 to 2004. These data were then correlated to information in the National Death Index up until the end of 2006.

The investigators then calculated the probability of survival in each group from 25 to 79 years of age. The mean follow-up was 7 years, with 10,743 deaths occurring in that age range.

After adjusting for education, alcohol use, and adiposity, men and women who smoked were three times more likely to have died than nonsmokers. The estimated probability of survival to the age of 80 years was 38% among women smokers but 70% for those who had never smoked. For male smokers, the probability of survival to age 80 was 26%, compared with 61% for those who had never smoked.

Both women and men who smoked were significantly more likely than nonsmokers to die in all of the smoking-related conditions examined:

• Lung cancer (hazard ratios of 18 and 15 for women and men, respectively).

• Other cancers (HR, 2 and 2).

• All cancers (HR, 3 and 4).

• Ischemic heart disease (HR, 3.5 and 3).

• Stroke (HR, 3 and 2).

• Other vascular disease (HR, 3 and 2).

• Respiratory disease (HR, 8.5 and 9).

• Other unspecified causes (HR, 2 and 2).

• All medical disorders (HR, 3 and 3).

• Accidents (HR, 4 and 2).

"At 25-79 years of age, about 62% of all deaths among female smokers and 60% of all deaths among male smokers would have been avoided if the rates of death from diseases among smokers had been the same as the rates among those who had never smoked," the authors noted.

Quitting smoking, on the other hand, conferred significant survival benefits, no matter when it occurred. Smokers who quit at age 25-34 years had similar survival to that of never-smokers. "Those who quit smoking gained about 10 years of life, as compared with those who continued to smoke."

Quitting at 35-44 years added 9 years of life, the authors found – not quite as good as those who quit earlier, but still a significant gain. "Smokers who had quit by about 39 years of age still had a 20% excess risk as compared with those who had never smoked. Although this hazard is substantial, it is much smaller than the 200% excess risk among those who continued to smoke."

Smokers who stopped at age 45-54 years gained 6 years of life, and those who quit at age 55-64 years about 4 more years of life. "Even cessation at the age of 45 to 54 years reduced the excess risk of death by about two-thirds," according to Dr. Jha and his coauthors.

While the study concluded that quitting at any age is a good idea, it shouldn’t be construed as a license to smoke longer. "That is not to say, however, that it is safe to smoke until 40 years of age and then stop, for the remaining excess risk of about 20% is substantial; it means that about one in six of these former smokers who dies before the age of 80 years would not have died."

The results are consistent with those of other studies around the world, the investigators said. The implications are staggering, especially for lower-income countries where smoking is more common and quitting less common.

"On the basis of current rates of smoking initiation and cessation, smoking, which killed about 100 million people in the 20th century, will kill about 1 billion in the 21st century."

 

 

A second study, also published in the Jan. 24 issue of the New England Journal of Medicine, found, for the first time, that women smokers are dying just as quickly – and from the same conditions – as men who smoke.

"The relative risks of death from lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, any type of stroke, and all causes are now nearly identical for female and male smokers," Dr. Michael Thun and his colleagues wrote (N. Engl. J. Med. 2013:368:351-64). "This finding is new and confirms the prediction that, in relative terms, ‘women who smoke like men die like men.’ "

Dr. Thun, an epidemiologist with the American Cancer Society, and his colleagues drew their three study cohorts from seven national studies and databases. The entire study group comprised 1.32 million women and 899,000 men. Two of the cohorts were considered historical, covering 1959-1988; five were considered contemporary, covering 2000-2010. The participants’ ages by the end of each group’s follow-up period ranged from 50 years to more than 80 years.

For never-smokers, the analysis showed a general overall improvement in mortality between the historical and contemporary cohorts. But smokers did not enjoy this benefit. Between the historical and contemporary cohorts, all-cause mortality was 50% higher in smokers than in nonsmokers.

Again, women were particularly at risk, the investigators noted. "In contrast, there was no temporal decrease in the all-cause death rate among women who were current smokers and there was a 23.6% decrease among men who were current smokers. ... The risk of death from lung cancer among male smokers appears to have stabilized since the 1980s, whereas it continues to increase among female smokers."

Dr. Thun and his associates also found the threefold increase in the risk of death between smokers and never-smokers. Their data determined that at least two-thirds of these deaths were directly associated with smoking, including ischemic heart disease, all other heart disease, stroke, and lung cancer.

A comparison of nonsmokers and smokers within all the time cohorts showed that the highest risks of death for most disorders occurred from 1982 to 1988. Since then, the mortality risks have declined and stabilized but still remain elevated compared with never-smokers. The lung cancer mortality risks were strikingly evident, the authors said: a relative risk of 25 for both men and women.

In contrast to the stabilized rates of other diseases, the mortality risk of chronic obstructive pulmonary disease has continued to increase in smokers. The biggest jump affected smokers older than 55 years and occurred after the 1980s period. The overall COPD mortality risk in the 2000-2010 cohort was more than double that of the 1980s (RR 10 vs. 25.6). The risks were similar for women (RR, 10.3-22.3) and men (RR, 12.5-27.3).

The increase is somewhat of a mystery, the authors said. It can’t be explained by aging, smoking duration, or the improved ability to diagnose COPD. Instead, the finding may be related to changes in the way cigarettes are manufactured.

"For example, the introduction of blended tobacco and genetic selection of tobacco plants lowered the pH of smoke; as a result, inhalation was easier and deeper inhalation was needed for the absorption of protonated nicotine. Other design changes, such as the use of more porous wrapping paper and perforated filters, also diluted the smoke. Deeper inhalation of more dilute smoke increases exposure of the lung parenchyma," they wrote.

Histologic studies have also found a change paralleling these manufacturing differences, the authors noted. The changes "may also have contributed to the shift, beginning in the 1970s, in the histological and topographic features of lung cancers in male smokers, with an increase in the incidence of peripheral adenocarcinomas that largely offset the decrease in squamous-cell and small cell cancers of the central airways. The likely net effect of deeper inhalation on COPD could be wholly detrimental, since COPD results from injury to the lung parenchyma."

Dr. Jha’s study was funded by the Fogarty International Center, the National Institutes of Health, the Canadian Institutes of Health Research, and the Bill and Melinda Gates Foundation. Dr. Thun’s study was funded by the National Institutes of Health and the American Cancer Society. None of the authors of either study had any financial disclosures.

Both men and women who smoke are three times as likely to die as those who don’t.

Two large population-based studies have come to the same conclusion: Smokers are almost certainly going to die years and years sooner than nonsmokers.

    Dr. Michael Thun

"This analysis showed that a person who had never smoked was about twice as likely as a current smoker to reach 80 years of age," Dr. Prabhat Jha and his associates reported in the Jan. 24 issue of the New England Journal of Medicine (N. Engl. J. Med. 2013:368:341-50). "Among current smokers, survival was shorter by about 11 years for women and by about 12 years for men, as compared with participants who had never smoked."

The report wasn’t all bad news, however. Kicking the habit at any time added years of life, said Dr. Jha of the Center for Global Health Research, Toronto, and his coauthors.

The investigators examined smoking and smoking cessation among 113,752 women and 88,496 men who participated in the U.S. National Health Interview Survey from 1997 to 2004. These data were then correlated to information in the National Death Index up until the end of 2006.

The investigators then calculated the probability of survival in each group from 25 to 79 years of age. The mean follow-up was 7 years, with 10,743 deaths occurring in that age range.

After adjusting for education, alcohol use, and adiposity, men and women who smoked were three times more likely to have died than nonsmokers. The estimated probability of survival to the age of 80 years was 38% among women smokers but 70% for those who had never smoked. For male smokers, the probability of survival to age 80 was 26%, compared with 61% for those who had never smoked.

Both women and men who smoked were significantly more likely than nonsmokers to die in all of the smoking-related conditions examined:

• Lung cancer (hazard ratios of 18 and 15 for women and men, respectively).

• Other cancers (HR, 2 and 2).

• All cancers (HR, 3 and 4).

• Ischemic heart disease (HR, 3.5 and 3).

• Stroke (HR, 3 and 2).

• Other vascular disease (HR, 3 and 2).

• Respiratory disease (HR, 8.5 and 9).

• Other unspecified causes (HR, 2 and 2).

• All medical disorders (HR, 3 and 3).

• Accidents (HR, 4 and 2).

"At 25-79 years of age, about 62% of all deaths among female smokers and 60% of all deaths among male smokers would have been avoided if the rates of death from diseases among smokers had been the same as the rates among those who had never smoked," the authors noted.

Quitting smoking, on the other hand, conferred significant survival benefits, no matter when it occurred. Smokers who quit at age 25-34 years had similar survival to that of never-smokers. "Those who quit smoking gained about 10 years of life, as compared with those who continued to smoke."

Quitting at 35-44 years added 9 years of life, the authors found – not quite as good as those who quit earlier, but still a significant gain. "Smokers who had quit by about 39 years of age still had a 20% excess risk as compared with those who had never smoked. Although this hazard is substantial, it is much smaller than the 200% excess risk among those who continued to smoke."

Smokers who stopped at age 45-54 years gained 6 years of life, and those who quit at age 55-64 years about 4 more years of life. "Even cessation at the age of 45 to 54 years reduced the excess risk of death by about two-thirds," according to Dr. Jha and his coauthors.

While the study concluded that quitting at any age is a good idea, it shouldn’t be construed as a license to smoke longer. "That is not to say, however, that it is safe to smoke until 40 years of age and then stop, for the remaining excess risk of about 20% is substantial; it means that about one in six of these former smokers who dies before the age of 80 years would not have died."

The results are consistent with those of other studies around the world, the investigators said. The implications are staggering, especially for lower-income countries where smoking is more common and quitting less common.

"On the basis of current rates of smoking initiation and cessation, smoking, which killed about 100 million people in the 20th century, will kill about 1 billion in the 21st century."

 

 

A second study, also published in the Jan. 24 issue of the New England Journal of Medicine, found, for the first time, that women smokers are dying just as quickly – and from the same conditions – as men who smoke.

"The relative risks of death from lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, any type of stroke, and all causes are now nearly identical for female and male smokers," Dr. Michael Thun and his colleagues wrote (N. Engl. J. Med. 2013:368:351-64). "This finding is new and confirms the prediction that, in relative terms, ‘women who smoke like men die like men.’ "

Dr. Thun, an epidemiologist with the American Cancer Society, and his colleagues drew their three study cohorts from seven national studies and databases. The entire study group comprised 1.32 million women and 899,000 men. Two of the cohorts were considered historical, covering 1959-1988; five were considered contemporary, covering 2000-2010. The participants’ ages by the end of each group’s follow-up period ranged from 50 years to more than 80 years.

For never-smokers, the analysis showed a general overall improvement in mortality between the historical and contemporary cohorts. But smokers did not enjoy this benefit. Between the historical and contemporary cohorts, all-cause mortality was 50% higher in smokers than in nonsmokers.

Again, women were particularly at risk, the investigators noted. "In contrast, there was no temporal decrease in the all-cause death rate among women who were current smokers and there was a 23.6% decrease among men who were current smokers. ... The risk of death from lung cancer among male smokers appears to have stabilized since the 1980s, whereas it continues to increase among female smokers."

Dr. Thun and his associates also found the threefold increase in the risk of death between smokers and never-smokers. Their data determined that at least two-thirds of these deaths were directly associated with smoking, including ischemic heart disease, all other heart disease, stroke, and lung cancer.

A comparison of nonsmokers and smokers within all the time cohorts showed that the highest risks of death for most disorders occurred from 1982 to 1988. Since then, the mortality risks have declined and stabilized but still remain elevated compared with never-smokers. The lung cancer mortality risks were strikingly evident, the authors said: a relative risk of 25 for both men and women.

In contrast to the stabilized rates of other diseases, the mortality risk of chronic obstructive pulmonary disease has continued to increase in smokers. The biggest jump affected smokers older than 55 years and occurred after the 1980s period. The overall COPD mortality risk in the 2000-2010 cohort was more than double that of the 1980s (RR 10 vs. 25.6). The risks were similar for women (RR, 10.3-22.3) and men (RR, 12.5-27.3).

The increase is somewhat of a mystery, the authors said. It can’t be explained by aging, smoking duration, or the improved ability to diagnose COPD. Instead, the finding may be related to changes in the way cigarettes are manufactured.

"For example, the introduction of blended tobacco and genetic selection of tobacco plants lowered the pH of smoke; as a result, inhalation was easier and deeper inhalation was needed for the absorption of protonated nicotine. Other design changes, such as the use of more porous wrapping paper and perforated filters, also diluted the smoke. Deeper inhalation of more dilute smoke increases exposure of the lung parenchyma," they wrote.

Histologic studies have also found a change paralleling these manufacturing differences, the authors noted. The changes "may also have contributed to the shift, beginning in the 1970s, in the histological and topographic features of lung cancers in male smokers, with an increase in the incidence of peripheral adenocarcinomas that largely offset the decrease in squamous-cell and small cell cancers of the central airways. The likely net effect of deeper inhalation on COPD could be wholly detrimental, since COPD results from injury to the lung parenchyma."

Dr. Jha’s study was funded by the Fogarty International Center, the National Institutes of Health, the Canadian Institutes of Health Research, and the Bill and Melinda Gates Foundation. Dr. Thun’s study was funded by the National Institutes of Health and the American Cancer Society. None of the authors of either study had any financial disclosures.

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Major Finding: Smokers are three times more likely to die than nonsmokers, with nearly all of the excess deaths directly attributable to smoking.

Data Source: Two studies comprising nearly 2.5 million people.

Disclosures: The studies were sponsored by the National Institutes of Health, American Cancer Society, Bill and Melinda Gates Foundation, Fogarty International Center, and the Canadian Institutes of Health Research. None of the authors had any financial disclosures.