Chest
Volume 131, Issue 5, May 2007, Pages 1557-1566
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Special Feature
Systemic Effects of Smoking

https://doi.org/10.1378/chest.06-2179Get rights and content

Smoking is one of the major lifestyle factors influencing the health of human beings. Life-long cigarette smokers have a higher prevalence of common diseases such as atherosclerosis and COPD with significant systemic impact. The present review evaluates current knowledge concerning possible pathways through which cigarette smoking can affect human health, with special focus on extrapulmonary effects. Long-term smoke exposure can result in systemic oxidants-antioxidants imbalance as reflected by increased products of lipid peroxidation and depleted levels of antioxidants like vitamins A and C in plasma of smokers. A low-grade systemic inflammatory response is evident in smokers as confirmed by numerous population-based studies: elevated levels of C-reactive protein (CRP), fibrinogen, and interleukin-6, as well as increased counts of WBC have been reported. Furthermore, rheologic, coagulation and endothelial function markers like hematocrit, blood and/or plasma viscosity, fibrin d-dimer, circulating adhesion molecules (intracellular adhesion molecule-1, selectins), tissue plasminogen activator antigen, and plasminogen activator inhibitor type I are altered in chronic cigarette smokers. Although most of smoking-induced changes are reversible after quitting, some inflammatory mediators like CRP are still significantly raised in ex-smokers up to 10 to 20 years after quitting, suggesting ongoing low-grade inflammatory response persisting in former smokers. New longitudinal epidemiologic and genetic studies are required to evaluate the role of smoking itself and possible gene/environment interplay in initiation and development of smoking-induced common diseases affecting humans.

Section snippets

Systemic Oxidative Stress in Smokers

Cigarette smoke contains approximately 1017 oxidant molecules per puff.7 This oxidative stress can be registered in several different ways, either by direct measurements of the oxidative burden (reactive oxygen species [ROS] production by peripheral blood cells) or by the effects of oxidative stress on target molecules (lipid peroxidation products and oxidized proteins), or as the responses to the oxidative stress (antioxidant capacity of plasma)8 [Table 1].

Only a few studies9, 1011 have used

Systemic Inflammation in Smokers

Activation and release of inflammatory cells into the circulation, and an increase in circulating inflammatory mediators such as acute phase proteins and proinflammatory cytokines, characterize the systemic inflammation.

Circulating Inflammatory Cells

The systemic inflammatory response is characterized by the stimulation of the hematopoietic system, specifically the bone marrow resulting in the release of leukocytes and platelets into the circulation. Numerous studies32, 3334 have shown that long-term cigarette smoking increases total WBC counts, mainly due to an increase in polymorphonuclear neutrophil (PMN) counts in the circulation of smokers. A large population-based study35 of 6,902 men and 8,405 women performed in Great Britain

Inflammatory Mediators in Peripheral Blood of Smokers

Activated inflammatory cells produce a great variety of inflammatory mediators in response to cigarette smoke, first of all, acute-phase proteins (APPs) and cytokines. Conditions that commonly lead to substantial changes in the plasma concentrations of APPs and cytokines include infection, trauma, surgery, burns, tissue infarction, various immunologically mediated inflammatory conditions, and cancer. In recent years, these inflammatory mediators have been studied as potential markers of subtle

Smoking and Markers of Endothelial Dysfunction, Coagulation, and Hemostasis

The biological mechanism linking smoking and atherogenesis, the process leading to cardiovascular diseases, is complex and not fully understood. Besides inflammation, proposed potential mechanisms by which smoking increases the risk of cardiovascular pathology include several other pathways: vascular endothelial dysfunction, systemic hemostatic and coagulation disturbances, and lipid abnormalities. Many of these indexes including fibrinogen (marker of coagulation), fibrin d-dimer (a marker of

Vascular Endothelial Dysfunction

Endothelial dysfunction is mainly caused by diminished production or availability of NO.61 It has been demonstrated that the serum concentration of nitrate and nitrite, metabolic end-products of NO, is significantly decreased in smokers relative to that in nonsmokers.74 In cigarette smokers, low-density lipoprotein (LDL) is more prone to oxidation due to higher level of ROS and reactive nitrogen species.75 Oxidatively modified LDL limits the bioactivity of endothelium-derived NO; and, in turn,

Hemostatic and Coagulation Markers

There is increasing evidence that blood levels of rheologic variables are associated with subsequent cardiovascular events.70 These indexes include whole-blood viscosity and its main determinants: hematocrit and plasma viscosity, principally composed by plasma fibrinogen and lipoproteins.67 Several studies33, 67 revealed that current smokers have increased blood viscosity, associated with increased hematocrit or/and plasma viscosity resulting in a procoagulant condition. Increased plasma

Conclusion

The possible biological mechanisms responsible for the observed association of smoking with various diseases and global mortality are numerous and, in spite of a many attempts to find causative relationships, are still unclear. It is a great scientific task to unravel exact pathways through which smoking affects human health. Although the effects of smoking on inflammatory markers may persist for many years, a majority of the adverse health effects of smoking are reversible. Therefore, quitting

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    Funding was provided by the European Respiratory Society (fellowship No. 161).

    The authors have no conflicts of interest to disclose.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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