Bronchiolar region

Recent studies in healthy subjects have suggested that a sizeable If action of particles deposited in the bronchiolar region is retained for more than 72-96 hr, and that these particles clear more similarly to alveolarly deposited particles. An increased deposition with retentions in the smallest ciliated airways is supported by the similarity in the clearance patterns from these airways, by healthy subjects, for particles inhaled by bolus and particles inhaled expemely slowly (0.05 L/sec), with an intermediate phase of continued clearance between 24 and 96 hr (17,54). From these studies, clearance in the smallest ciliated airways seems to be incomplete, with retentions of about 40% of the particles assumed to have been deposited in the tracheobronchial region, probably because of ineffective mucociliary transport and cough clearance in small airways. Clearance from the bronchiolar region may have features in common with alveolar clearance (65). This region may thus eonstitute a vulnerable zone in which small airway diseases eventually may arise after repeated exposures to noxious agents. 

Dixon D, Bowser AD, Badgett A, et al. 1995. Incorporation of bromodeoxyuridine (BrdU) in the bronchiolar-alveolar regions of the lungs following two inhalation exposures to chyrsotile asbestos in strain A/J mice. J Environ Pathol Toxicol Oncol 14 205-213. 

McGavran PD, Butterick CJ, Brody AR. 1989. Tritiated thymidine incorporation and the development of an interstitial lesion in the bronchiolar-alveolar regions of the lungs of normal and complement deficient mice after inhalation of chrysotile asbestos. JEPTO 9 377-391. 

Particles ranging between 0.1 and 1.0 pm in diameter reach the alveolar region, where they finally hit cellular walls as a result of their random movement within minute air sacs. Removal of particles in this region of the lung is much less efficient. Some of the particles may eventually reach the tracheo-bronchiolar escalator system, either as engulfed... 

It has been considered that, in contrast with nNOS and iNOS, which are expressed in diverse tissues and cell types, ecNOS is relatively restricted to vascular endothelial cells. However, recent evidence suggests the existence of ecNOS in pyramidal neurons ofthe hippocampus (CAl region) (Dinerman et al., 1994 O Dell et al., 1994), syncytiotrophoblasts (Myatt et al., 1993), the LLC-PK] cell line derived from the kidneys (proximal tubule-like) (Tracey et al., 1994), NCI-H441 human bronchiolar epithelial cells (Shaul et al., 1994), and human platelets (Mehta et al., 1995). The molecular basis for the restricted cell-specific expression of this mRNA transcript remains to be determined. 

Figures 5.2 and 5.3 show the effective dose per unit exposure of the tracheo-bronchial (bronchial and bronchiolar) and pulmonary or alveolar region as a function of aerosol particle diameter calculated for the radon decay products Po, " Pb, and " Po and the thoron decay products Pb, Bi and Po. A tissue weighting factor of the lung and the radiation weighting factor of 0.12 and 20, respectively, are taken into account. The effective dose from a radioactive mixture can be deduced by adding the effective doses of each decay product.

Fig. 5.4. Effective dose by the inhalation of radon decay products as a function of the particle diameter at different relative cancer sensitivity distributions between the bronchial, wbb, bronchiolar, Wbb, and alveolar, wai, region of the thoracic lung (wr = 20, U) = 0.12). v = 0.75 (basal cells + secretory cells).

Brody AR, Overby LH. Incorporation of tritiated thymidine by epithelial and interstitial cells in bronchiolar-alveolar regions of asbestos-exposed rats. Am J Pathol 1989 134(1) 133-140. 

Liu JY, Morris GF, Lei WH, et al. Up-regulated expression of transforming growth factor-alpha in the bronchiolar-alveolar duct regions of asbestos-exposed rats. Am J Pathol 1996 149(1) 205-217. 

FIG. 3. Respiratory tract regions defined in the new ICRP model [19], The extrathoracic (ET) airways are divided into Ef, the anterior nasal passage, and ET2, which consists of the posterior nasal and oral passages, the pharynx and larynx. The thoracic regions are bronchial (BB trachea, and main bronchi), bronchiolar (bb bronchioles) and alveolar-interstitial (AT the gas exchange region). Lymphatic tissue is associated with the extrathoracic and thoracic airways (LN j and LNj.jj respectively). 

With prolonged exposure to particulate matter at sufficiently high concentrations, the particulate matter continuously deposited in the alveolar spaces can trigger a sustained inflammatory reaction. The inflammation can alter particle clearance, initially increase the rate of clearance, and then later canse inhibition of clearance. This, in turn, intensifies the inflammatory reaction, which further impairs clearance and enhances the rate of particle accumulation in the alveolar region. Some of these particles are found in the interstitial areas and others in the alveolar spaces, where aggregates of macrophages, particles, and proteinaceous material may be observed. Adjacent epithelial cells become hypertrophic, hyperplastic, and occasionally, metaplastic. Freqnently, bronchiolar epithelium may appear to be extending down into the alveoli. This pattern of particle-indnced overload disease has been described in detail in rats chronically exposed to diesel exhaust or carbon black particles (39,40). The extent to which similar lesions are produced in humans exposed to similar levels of diesel soot or carbon black is not well understood. 

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