the underlying cause of death. A plausible explanation for the continuing increase in deaths from COPD among male smokers is that cigarettes marketed since the late 1950s have undergone design changes that promote deeper inhalation of smoke.34 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. 35 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. These and other design changes in cigarettes may also have contributed to the shift, beginning in the 1970s, in the histologic and topographic features of lung cancers in male smokers,36 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.
