Introduction

The respiratory system extends from the nose and upper airway to the alveolar surface of the lungs, where gas exchange occurs. Inhaled tobacco smoke moves from the mouth through the upper airway, ultimately reaching the alveoli. As the smoke moves more deeply into the respiratory tract, more soluble gases are adsorbed and particles are deposited in the airways and alveoli. The substantial doses of carcinogens and toxins delivered to these sites place smokers at risk for malignant and nonmalignant diseases involving all components of the respiratory tract including the mouth.

Consider, for example, the lungs of a 60-year-old person with a 40-pack-year1smoking history starting at age 20 years. By age 60 years, this person will have inhaled the smoke from approximately 290,000 cigarettes and will bear a substantial risk for chronic obstructive pulmonary disease (COPD) and lung cancer. The dose of inhaled toxic particles and gases received from each of these cigarettes varies depending on the nature of the tobacco, the volume and number of puffs of smoke drawn from the cigarette, the amount of air drawn in through ventilation holes as the smoke is inhaled, and local characteristics within the lung that determine the diffusion of toxic gases and the deposition of particles. Because of this repetitive and sustained injurious stimulus, the repair and remodel process that heals the damaged lung tissue takes place at the same time the lung’s defenses continue to deal with this unrelenting inhalation injury.

This chapter addresses the mechanisms by which tobacco smoke causes diseases other than cancer in the lower respiratory tract: the trachea, bronchi, and lungs. Beginning with the first Surgeon General’s report in 1964 (U.S. Department of Health, Education, and Welfare [USDHEW] 1964), cigarette smoking has been causally linked to multiple diseases and to other adverse effects on the respiratory system (Table 7.1). In addition to causing lung cancer and COPD, smoking increases the risk of death from pneumonia and causes chronic bronchitis (U.S. Department of Health and Human Services [USDHHS] 2004). Typically, the lungs of smokers show evidence of diffuse changes affecting the lining of the airways, the epithelium, and the structure of the bronchioles, which are the smaller air-conducting tubes.

Table 7.1

Causal conclusions on smoking and diseases of the respiratory tract other than lung cancer: the 2004 and 2006 reports of the Surgeon General.

Previous reports of the Surgeon General have also addressed the effects of smoking on the respiratory tract. In discussing the plausibility of associations of cigarette smoke with chronic bronchitis and emphysema, the 1964 report gave full consideration to the nature of tobacco smoke and its effects on the respiratory tract (USDHEW 1964). That report concluded that cigarette smoking “… is the most important of the causes of chronic bronchitis in the United States…” (p. 302) and that “a relationship exists between pulmonary emphysema and cigarette smoking, but it has not been established that the relationship is causal” (p. 302). The 1984 report, which focused on COPD, covered mechanisms by which smoking affects the lung’s structure and function and the deposition and toxicity of cigarette smoke in the lung (USDHHS 1984). The report concluded that “cigarette smoking is the major cause of chronic obstructive lung disease in the United States…” (p. vii). The mechanisms of lung injury were considered further in the 1990, 2004, and 2006 reports (USDHHS 1990,2004,2006).

The principal nonmalignant respiratory diseases caused by cigarette smoking—COPD, emphysema, chronic bronchitis, and asthma—are defined inTable 7.2. The definitions indicate that chronic bronchitis is a specific set of symptoms, whereas emphysema refers to a particular pattern of lung damage. COPD comprises a clinical syndrome characterized by limitation in airflow; persons with COPD often have chronic bronchitis as well, and their lungs typically display emphysema. Other nonmalignant respiratory diseases that have been linked to smoking include asthma and idiopathic pulmonary fibrosis (USDHHS 2004), but the evidence has not reached a level of certainty sufficient to warrant a conclusion of cause and effect.

Table 7.2

Definitions for principal nonmalignant respiratory diseases caused by cigarette smoking.

The nonmalignant respiratory diseases caused by smoking contribute substantially to the burden of morbidity and mortality attributable to smoking in the United States (Table 7.1). In 2005, the Centers for Disease Control and Prevention (CDC) estimated that an average of 123,836 deaths per year could be attributed to lung cancer caused by smoking for the period 1997–2001 (CDC 2005). CDC estimated an additional 90,582 deaths from COPD and 10,872 from pneumonia and influenza annually.

Great advances have been made in our understanding of how smoking causes these diseases. Research has been facilitated by methods that directly assess changes in the lungs. Methods for obtaining biologic material from human lungs include bronchoalveolar lavage (BAL), a technique that allows recovery of cellular and noncellular components of the epithelial surface of the lower respiratory tract (Cantrell et al. 1973;Hunninghake et al. 1979;Reynolds 1987). BAL is of value in the study of immune and inflammatory mechanisms in the lower airways, because most of the cells recovered are believed to be derived from both air spaces and lung interstitium. Lung tissue obtained by biopsy or autopsy procedures can be used for cellular, protein, and nucleic acid assays. Exhaled breath condensate provides information about the composition of epithelial lining fluid (ELF) that can be used to detect inflammation and redox disturbance (Paredi et al. 2002). Blood samples may be used to assess systemic inflammatory responses, and blood cells serve as a source of nucleic acids.

Characteristics of Tobacco Smoke

Tobacco smoke, which comprises an aerosol (a mixture of solid and liquid particles) and gases, has thousands of chemical components, including many well-characterized toxins and carcinogens (International Agency for Research on Cancer [IARC] 2004). Many of these components are in the gas phase, and others are components of the particles. Nicotine, for example, is bound to particles in mainstream smoke. The chemical components in tobacco smoke were covered comprehensively in IARC Monograph 83 (IARC 2004) and described in previous reports of the Surgeon General. Numerous components of the smoke have the potential to injure the airways and alveoli.

Components of tobacco smoke with the potential to injure the lungs through a variety of mechanisms are listed inTable 7.3. Some components adversely affect host defenses; others act through specific or nonspecific mechanisms. Notably, cigarette smoking has very strong oxidant potential in that both the gas and tar phases contain high concentrations of free radicals (Repine et al. 1997). Many of the components of cigarette smoke are the targets of regulations because of their toxic effects: these include nitrogen dioxide, carbon monoxide, and various metals. For information on the toxic effects of components, see reports of the U.S. Environmental Protection Agency (EPA) and other agencies (USEPA 1993,2000;USDHHS 2000) and standard resources in toxicology (Gardner et al. 2000;Klaassen 2001).