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Effect of low-level NO2 chronic exposure on elastase-induced emphysema
Abstract:
The effect of chronic exposure to 2 ppm nitrogen dioxide (NO2) for 8 hr a day, 5 days a week, for 8 weeks was assessed in normal and emphysematous hamsters by measuring (1) lung morphometry (mean linear intercept [Lm] and internal surface area [ISA]), (2) lung mechanics (lung volume, compliance and coefficient of static deflation, pressure-volume curve fitted to an exponential equation), and (3) serum elastolytic activity and protease inhibitor capacity. Emphysema was induced by a single intratracheal injection of 6 IU porcine pancreatic elastase. Four groups of animals were used; Control, NO2-exposed, elastase-treated, and NO2-exposed postelastase. Our results show that NO2 exposure alone induced mild emphysematous lesions whose degree of severity estimated by morphometry increase in Lm and decrease in ISA. P less than 0.01) was of the same order as that of the lesions induced by 6 IU elastase. Exposure to 2 ppm NO2 enhanced elastase-induced emphysema (further increased Lm and further reduced ISA. P less than 0.01). By contrast, study of lung mechanics revealed no difference between the control and NO2-exposed groups or between the elastase-treated animals exposed to NO2 and those not so exposed. This apparent discrepancy between results of morphometry and lung mechanics may be due to the lower sensitivity of lung mechanics parameters and their consequent inability to reflect changes in the emphysematous lesions induced by elastase injection or 2 ppm NO2 inhalation. In vivo, serum elastolytic activity and protease inhibitor capacity were not modified in any group, indicating that either serum does not reflect the degree of protease inhibitor capacity in the alveolar spaces or chronic inhalation of low concentrations of NO2 is not sufficient to cause elastase/antielastase imbalance. Lastly, our results suggest that chronic exposure to 2 ppm NO2 may cause individuals with inherited or acquired emphysematous lesions to develop more severe emphysema.