PRINCIPLES OF TOXICOLOGY

180 PULMONOTOXICITY: TOXIC EFFECTS IN THE LUNG
Air-Pollutant Gases
Many of the air pollutants are inhaled as gases, such as carbon monoxide, sulfur dioxide, and the
various oxides of nitrogen. By far, the number one killer as far as toxic gases are concerned is carbon
monoxide. The incomplete burning of various fuels results in the emission of carbon monoxide, and
every year there are many deaths and injuries from individuals who breathe this gas in an enclosed
space. While some of these are suicides, there are also many industrial exposures to carbon monoxide
and other combustion pollutants. A number of air pollutant gases are produced by a complex interaction
of sunlight, humidity, temperature, hydrocarbons, and the oxides of nitrogen. These interactions
generate smog, as well as other gases such as ozone and the aldehydes.
Tobacco Smoke
Toxicity resulting from the intentional and unintentional inhalation of tobacco smoke is an important
consideration given its enormous magnitude of incidence, its interaction with the toxicity of other
inhaled industrial pollutants, and its representation of the toxicity of both particulates and gases. The
number of people who die and are significantly injured each year in the United States due to inhalation
exposures to industrial chemicals cannot be stated with certainty; however, it is definitely much smaller
than the number of people who die and are experiencing diminished health status as a result of tobacco
smoke inhalation. The smoking of tobacco products causes pulmonary emphysema, chronic bronchitis,
and lung cancer in many thousands of Americans each year.
Interference with Pulmonary Defense Tobacco smoke inhalation results in the derangement of the
pulmonary defense mechanisms necessary to protect against the inhalation of industrial toxins. It has
been shown that, following chronic cigarette smoking, the cilia in the mucociliary escalator become
increasingly paralyzed. The decrease in ciliary activity slows or prevents the removal of deposited
toxins from the nasopharyngeal and tracheobronchial regions, as the gel layer becomes more sedentary.
Many of the more than 2000 components of tobacco smoke are known to be respiratory irritants, and
these irritating properties lead to an increased production of mucous in the respiratory system.
Therefore, there is a decreased movement (and removal) of mucous simultaneously with an increase
in mucous production. Eventually, some of the airways can become impeded and even blocked,
severely limiting the respiratory volume of the affected individual. Sometimes the overworked mucous
glands will increase in size sufficiently to block the airways themselves, further impeding airflow and
increasing resistance.
It has been shown that the cellular defense mechanisms of the lung, particularly the alveolar
macrophages and the alveolar polymorphonuclear leukocytes, are significantly impacted by tobacco
smoke inhalation. In many cases, these cells may be killed, causing the release of proteolytic enzymes,
which come in contact with the respiratory membrane surfaces. Pulmonary emphysema can result, if
this process is extensive, from the severe rupturing of the septa walls. Even short of cell death, these
cells become less efficient in the removal of particulates and other toxins. Therefore, the inhalation of
toxic agents in industrial environments has the potential to exert greater toxicity in smokers than in
equally exposed nonsmokers. This has been shown repeatedly for many exposures to toxic chemicals
in occupational studies, such as with asbestos. For this reason, occupational epidemiologists and
physicians will often look for correlations between toxicity in an industrial worker population and
tobacco use.
Lung Cancer and Tobacco Smoke Bronchogenic carcinoma data from the 1980s estimated that
approximately 90 percent of the more than 100,000 lung cancer cases each year in the United States
are due to tobacco smoke inhalation. A very distressing aspect of this unpleasant data is that the
incidence of lung cancer, previously occurring more often in men, is growing rapidly in the female
population. The increasing incidence of tobacco smoke inhalation by women has been followed in an
appropriate timeframe by an explosion in lung cancer cases in women. Whereas breast cancer was