Quartz But Not Iron Oxide Causes Air-Flow Obstruction, Emphysema, and Small Airways Lesions in the Rat

Abstract

Recent epidemiologic studies have suggested that some workers exposed to inorganic dusts develop air-flow obstruction independent of or greater than that produced by cigarette smoke; the morphologic basis of this effect is unknown. To investigate this problem, we administered saline alone, 10 mg iron oxide (an inert dust), or 10 or 30 mg of quartz to rats by intratracheal instillation. Animals were killed after 30 days, and pulmonary function and morphologic changes were examined. The iron oxide group was similar to the saline control group in all functional and morphometric parameters. However, both quartz-exposed groups showed evidence of air-flow obstruction, with more severe abnormalities in the high dose group. These findings correlated with morphometric observations of emphysema and thickened airway walls, with changes again more severe in the high dose group. Early silicotic nodules were also present in the latter animals. We conclude that in addition to the classic lesions of nodular silicosis, quartz can produce morphologic and functional changes of air-flow obstruction; no such changes are seen with iron oxide. These observations may explain the air-flow obstruction seen in workers exposed to mineral dusts.

Combined effect of silica dust exposure and tobacco smoking on the prevalence of respiratory impairments among gold miners.

“…Experimental evidence from rats also indicates that exposure to crystalline silica causes emphysema and abnormally thick walls in the small airways with associated functional changes of airflow obstruction in rats (5,6).…”

Functional and Morphologic Comparison of Silica- and Elastase-Induced Airflow Obstruction

“…Again, there is overlap between the lesions caused by dust and those caused by cigarette smoke in the airways, but careful morphometric studies make it clear that the dust lesions are distinct from the cigarette lesions [4, 51 and that they appear to be associated with some degree of airflow obstruction. In a previously reported experiment, we found that silica (quartz) administered to rats by intratracheal instillation produced not only silicotic nodules, but also functional and morphologic evidence of emphysema and smallairway changes [6]. In that study we measured only two morphologic parameters: the thickness of the walls of small airways, and mean linear intercept, a very general parameter of airspace size.…”

“…The fact that mineral dusts might also be associated with elastic fiber destruction has not been previously demonstrated. However, if, as we have previously suggested [6], mineral dusts produce emphysema by evoking a long-standing inflammatory response, then elastic fiber destruction is not surprising, and the process is in many ways analogous to the chronic inflammatory response thought to be crucial to the development of cigarette smoke-induced emphysema in humans [14-161. The major difference is the greatly compressed time scale seen in the mineral dust-treated animals.…”

“…The morphologic bases of this process are poorly defined and greatly disputed; both small-airway changes and emphysema have been . Using an animal model, we have recently shown that intratracheally instilled silica in the form of quartz produces airflow obstruction, and that this process appears to correlate with the presence of both emphysema and small-airway lesions [6].…”

O efeito da exposição a níveis ambientais de material particulado no desenvolvimento do enfisema pulmonar em camundongos

“…Dependendo da dose e do tempo de avaliação após a instilação desta substância elastolítica, consegue-se reproduzir enfisema em porções diferentes dos pulmões, podendo-se obter destruição do parênquima pulmonar mais próxima aos brônquios, enfisema centroacinar, que se aproxima mais ao enfisema que ocorre em seres humanos ocasionado pelo tabagismo, ou um enfisema em porções mais distais dos pulmões, de distribuição panacinar, mais semelhante ao observado em pessoas que apresentam deficiência em α1-antitripsina (138,139,140,141 A presença do material particulado na câmara sem filtros foi fundamental para o aumento do estresse oxidativo, levando a uma piora do enfisema e indução de remodelamento nos animais que receberam papaína.…”