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Review
. 2017 Dec 1;109(12):djx075.
doi: 10.1093/jnci/djx075.

Cigarette Filter Ventilation and Its Relationship to Increasing Rates of Lung Adenocarcinoma

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Review

Cigarette Filter Ventilation and Its Relationship to Increasing Rates of Lung Adenocarcinoma

Min-Ae Song et al. J Natl Cancer Inst. .
Free PMC article

Abstract

The 2014 Surgeon General's Report on smoking and health concluded that changing cigarette designs have caused an increase in lung adenocarcinomas, implicating cigarette filter ventilation that lowers smoking machine tar yields. The Food and Drug Administration (FDA) now has the authority to regulate cigarette design if doing so would improve public health. To support a potential regulatory action, two weight-of-evidence reviews were applied for causally relating filter ventilation to lung adenocarcinoma. Published scientific literature (3284 citations) and internal tobacco company documents contributed to causation analysis evidence blocks and the identification of research gaps. Filter ventilation was adopted in the mid-1960s and was initially equated with making a cigarette safer. Since then, lung adenocarcinoma rates paradoxically increased relative to other lung cancer subtypes. Filter ventilation 1) alters tobacco combustion, increasing smoke toxicants; 2) allows for elasticity of use so that smokers inhale more smoke to maintain their nicotine intake; and 3) causes a false perception of lower health risk from "lighter" smoke. Seemingly not supportive of a causal relationship is that human exposure biomarker studies indicate no reduction in exposure, but these do not measure exposure in the lung or utilize known biomarkers of harm. Altered puffing and inhalation may make smoke available to lung cells prone to adenocarcinomas. The analysis strongly suggests that filter ventilation has contributed to the rise in lung adenocarcinomas among smokers. Thus, the FDA should consider regulating its use, up to and including a ban. Herein, we propose a research agenda to support such an effort.

Figures

Figure 1.
Figure 1.
Trends of incidence of lung cancer among US men and women and from various birth cohorts. Adapted from the 2014 Surgeon General’s Report (1). (A–C) Graphs present trends in age-standardized incidence rates in the United States from 1973 to 2010 for lung cancer for men (A, left) and women (A, right) and histologic type of lung cancers using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Among men, there has been a shift in the histology patterns, with an increase of adenocarcinomas over squamous cell carcinoma (B); similar trends are seen for women (C). Graphs present trends in incidence rates of lung cancer in the United States for 1905 and 1945 from birth cohorts of men (B) and for 1900 and 1945 from birth cohorts of women (C) and histologic type of lung cancers. NSCLC = non–small cell carcinoma.
Figure 2.
Figure 2.
The modern cigarette. An adapted depicted modern cigarette as to elucidate mechanisms in and around the burning cigarette by Richard R. Baker in 1982 (https://industrydocuments.library.ucsf.edu/tobacco/docs/#id=knyy0131) (1).
Figure 3.
Figure 3.
The framework for the relationship of filter ventilation to the increased rate of adenocarcinoma. The placement and increase of filter ventilation lead to higher levels of mutagens and carcinogens, compensation with the greater depth of inhalation, and deposition of smoke that increases exposures to in the peripheral portion of the lungs. Thus, smokers who smoke low-tar cigarettes have developed a greater risk for adenocarcinoma of the lung. TSNAs = tobacco-specific nitrosamines.
Figure 4.
Figure 4.
Sales-weighted average tar and nicotine deliveries, 1954 to 1993, and percentage of filter ventilation of cigarettes based on tar yields using the Federal Trade Commission. A) Tar and nicotine as measured by a smoking machine. Source: Hoffmann D, Djordjevic MV, Hoffman I. The changing cigarette. Prev Med. 1997;26(4):427–434. (19). B) Adapted from: Centers for Disease Control and Prevention. Filter ventilation levels in selected U.S. cigarettes, 1997. MMWR Morb Mortal Wkly Rep., 1997;46(44):1043–1047 (22). Bars represent 95% confidential interval. Percentage of filter ventilation is the percentage of a standard puff (two second duration, 35 mL), that is, air taken into puff through the filter vents. A cigarette with no filter ventilation would produce a puff undiluted by air from filter vents; a cigarette with 80% filter ventilation would produce a puff that is 80% air from vents and 20% smoke undiluted by air from vents. Descriptors are no longer allowed by law because they are misleading and because the classification and nicotine yields vary by definition in the literature. ET = expanded tobacco; F = filter; Nic. = nicotine; RT = reconstituted tobacco.
Figure 5.
Figure 5.
The relationship of filter ventilation to changes in chemical yields and toxicity. With increased filter ventilation, smokers take higher puff volumes and inhale more toxicants and mutagens, tobacco burns longer and at a reduced temperature that increases incomplete combustion with increased toxicants and mutagens, and increased particle size becomes a bigger carrier for toxicants and mutagens.
Figure 6.
Figure 6.
The increase in mutagenicity per % increase in ventilation, which was statistically significant. Source: Mutagenicity of the mainstream smoke condensate of 30 research cigarettes with differences in 6 parameters,” 1993. Philip Morris Records. https://industrydocuments.library.ucsf.edu/docs/#id=thcc0126 (81).
Figure 7.
Figure 7.
Evidence blocks for causation analysis. Grading of evidence showing the confidence in the weighting, from 0 to 45, based on scientific judgment: no relationship (0), limited evidence (+), strongly suggestive evidence ( ++), sufficient evidence ( +++), or inadequate study (IA); the taller the block, the higher the level of evidence. Both IA and no relationship are treated as 0 and do not appear in blocks. Some criteria are weighted more heavily than others, as follows: Consistency and human intervention are adjusted for the greatest weight (factor of 3), dose response and biological plausibility are adjusted for a medium weight (factor of 2) and the others are unadjusted.

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