tracheobronchial tree is comprised of an average of 23 generations of 
dichotomous branching tubes, ending in the alveoli (see Weibel, 1991 for 
review) (Figures 1.9.1-A, 1.9.1-B). The region from the trachea to about 
the 16th generation is referred to as the "conducting zone" , structures 
that serve to conduct air from the external environment to the gas exchang- 
ing regions. The airways in this region are referred to as "bronchi". By 
the 16th generation, there are approximately 66,000 bronchi. From the 17th 
through the 20th generations are the "bronchioles", the smallest airways. 
From the 17th generation ending in the alveoli is referred to as the "tran- 
sition" and "respiratory" zones, the latter being the actual site of gas 
exchange. By the 20th generation, there are 10 6 airways and by the 23rd 
generation, 3xl0 8 alveoli. 
The walls of bronchi consist of three concentric tubes (Figures 1.9.1-C, 
1.9.1-D): (1) a mucosa comprised of an epithelial cell layer resting on a 
basement membrane; (2) a sleeve of smooth muscle cells; and (3) an outer 
tube of connective tissue matrix that includes islands of cartilage and 
submucosal glands that open onto the epithelial surface. The epithelial 
layer is columnar and pseudostratif ied; all components abut the underlying 
basement membrane. On the average, the bronchial epithelium is about 20 /xm 
thick. The entire mass of a large bronchus is about 60 /xm in thickness. The 
submucosal glands are in highest concentration in the trachea, where there 
is approximately one gland per mm 2 of epithelial surface area. The number 
of glands becomes sparser toward the periphery, and are absent in the 
bronchioles. In cross section, the submucosal glands are about 200 /xm in 
width. From the opening of a submucosal gland on the epithelial surface, 
the gland continues into a 250-500 /xm collecting duct lined by columnar 
epithelium (Figure 1.9.1-C). Up to 13 tubules arise from the collecting 
duct; these tubules branch extensively and are closely intertwined. The 
entire submucosal gland is internal to a basement membrane that is continu- 
ous with the basement membrane of the airway epithelial cell layer. 
The walls of the bronchioles are composed of the same three concentric 
tubes as the bronchi, but with some differences (Figure 1.9.1-D): (1) a 
mucosa composed of an epithelial cell layer resting on a basement membrane; 
(2) a thin sleeve of smooth muscle cells; and (3) a delicate tube of con- 
nective tissue matrix, but without cartilage or submucosal glands. Like the 
bronchial epithelium, the epithelium of the bronchioles are 1 cell thick. 
The cells are columnar, but less so than in the bronchi. 
The blood supply to the airways is primarily from the bronchial arteries, 
derived from the aorta and intercostal arteries. The bronchioles also 
derive some blood from the pulmonary artery. Except for a few bronchial 
veins in the hilar region, the bronchial circulation drains into the pulmo- 
nary veins. Together, the anatomic features of the blood supply to the 
airways make it very difficult to strategize a means to target vectors for 
gene transfer directly to the bronchial and bronchiolar epithelium by means 
of the circulation. 
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Recombinant DNA Research, Volume 16 
