Perspectives on Pulmonary Inflammation and Lung Cancer Risk in Cigarette Smokers

Cigarette mainstream smoke (MSS) inhaled by smokers is a complex aerosol composed of minute liquid droplets suspended within a mixture of combustion gases (CO, CO₂, NO_x, etc.) and semivolatile compounds. The minute liquid droplets represent the particulate or “tar” phase, while the combustion gases and semivolatiles comprise the vapor phase. For historical and technical reasons, the vast majority of studies on the carcinogenicity of MSS have focused on the particulate phase. The particulate phase is mutagenic and cytotoxic in vitro, proinflammatory, and promotes tumor formation in animal models. In addition to cytotoxic compounds found in the particulate phase, the vapor phase of MSS contains a number of cytotoxic constituents including reactive aldehydes and carbonyls capable of damaging cells and inducing pulmonary inflammation. A large body of evidence suggests that smoking-induced pulmonary inflammation may play an important role in increasing lung cancer risk in smokers. Use of aspirin and nonsteroidal anti-inflammatory drugs is associated with reduced cancer development in animal models and lower lung cancer rates in smokers. A number of benign nonpulmonary and pulmonary diseases characterized by chronic inflammation increase the risk of cancer at the affected site in the absence of chemical exposure. Animal models displaying tumorigenic responses following exposure to either whole smoke or smoke fractions show elevated rates of cellular proliferation. A relationship between pulmonary inflammation and lung cancer is mechanistically plausible because inflammatory cells secrete activated oxygen species, inflammatory mediators, and proteolytic enzymes that can both damage DNA and lead to increases in reparative cell proliferation rates.