Structural Changes in Airways of Rats Exposed to Nitrogen Dioxide Intermittently for Seven Days: Comparison between Major Bronchi and Terminal Bronchioles

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Abstract
Structural changes caused by exposure to NO2 were compared between the largest intrapulmonary bronchi (major bronchi) and the terminal bronchioles. Rats were exposed to 50 ppm NO2 for 5 h a day for 7 consecutive days, and microscopic findings were assessed subjectively and quantitatively. Destruction of airway epithelium was present on Day 1, and the reparative phase was observed between Days 3 and 7. Light microscopy showed that on Day 1, loss of cilia and disintegration of epithelium occurred, and that the latter was worse in major bronchi than in terminal bronchioles; apical projections of Clara cells in terminal bronchioles were lost almost totally. Recovery of epithelium began by Day 3 and cilia by Day 5, and ciliogenesis progressed less promptly in terminal bronchioles. Clara cells did not return to normal during the experiment. Furthermore, a decrease in the airway diameter occurred in peripheral airways along with an increase in mural thickness in terminal bronchioles. Mural inflammation was also seen more conspicuously in terminal bronchioles. Electron microscopy revealed that epithelial cells lost secretory granules on Day 1 and began to repair them by Day 5 in major bronchi and by Day 7 in terminal bronchioles. It is likely that epithelium in terminal bronchioles is not particularly sensitive to NO2 compared with that in major bronchi, but that recovery occurs more promptly in major bronchi than in terminal bronchioles. Mechanisms underlying bronchoconstriction occurring preferentially in peripheral airways are also discussed.