ABSTRACT
The lungs of a 60-year-old person with a 40-pack-year smoking history starting at age
20 will have inhaled the smoke generated from approximately 290,000 cigarettes. The
dose of inhaled toxic particles and gases received from each of these cigarettes varies
with the nature of the tobacco, the size, and number of puffs of smoke drawn from the
cigarette. The amount of air added as the smoke is inhaled and local conditions within
the lung that determine the diffusion of toxic gases and deposition of particles.
Tobacco smoking interferes with the innate defenses of the lung, which includes
mucus production and clearance, epithelial barrier, and infiltrating inflammatory
immune cells (1,2). This interference increases the opportunity for infection by both
increasing the production of mucus and decreasing its clearance from the airways
lumen (2,3); disruption of the tight junctions that form the epithelial barrier allows
foreign material to enter the sub-epithelium (4,5). This stimulates the infiltration of
the damaged tissue by polymorphonuclear and mononuclear phagocytes as well as
natural killer (NK) cells, CD-4, CD-8, and B-cell lymphocytes (6-17). The
organization of the lymphocytes into follicles with germinal centers can be
demonstrated in about 5% of the smaller airways of smokers with the normal lung
function (15) and this rises to 20% to 30% of airways in the later stages of chronic
obstructive pulmonary disease (COPD) (15-17). The formation of these follicles
provides anatomic evidence for the presence of an adaptive immune response to
foreign antigen, but the source of antigen that drives this sharp increase in the
adaptive immune response in GOLD-3 and GOLD-4 COPD is unknown. It could be
related to either the colonization or infection of the lower airways by a variety of
microbes in the later stages of the disease or to auto-antigens that develop in the
damaged tissue. Interestingly this inflammatory immune process persists following
smoking cessation (18,19), even though discontinuing the habit slows the rate of
decline in the lung function and delays death in those who successfully quit (20,21).
Most importantly the repetitive tissue injury caused in the lung tissues by smoking is
associated with a repair and remodeling process that attempts to restore damaged
tissue. The primary objective of this chapter is to briefly review the nature of the
inflammatory immune process in relation to concurrent repair and remodeling of the
lung tissue damaged by tobacco smoke and to discuss the contribution of these
processes to the pathogenesis of the lesions that define COPD.
