Toxicity of intratracheally instilled cotton dust, cellulose, and endotoxin

Cotton dust includes respirable particles containing endotoxin and elastase, agents associated with emphysema. To examine whether a respirable fraction of cotton dust could produce emphysema in an animal model, we intratracheally instilled hamsters with respirable cotton dust particles (0.75 mg/100-g animal), mass median aerodynamic diameter less than or equal to 4.8 microns, twice weekly for 6 wk. We also examined whether instilled endotoxin (255 micrograms/100-g animal) could produce emphysema in hamsters and whether cellulose (0.75 mg/100-g animal) is an appropriate inert comparison dust. A saline-instilled group was the control. Hamsters were killed 8 wk after the last instillation. Static pressure-volume deflation curves of air-filled excised lungs were analyzed to measure lung distensibility. Lungs were fixed in inflation using glutaraldehyde and were examined morphometrically to obtain surface area and numbers of granulomata. Endotoxin-treated animals had increased distensibility, reduced surface-to-volume (S/V) ratio, and morphologically apparent mild centrilobular emphysema. Cellulose-treated animals had decreased distensibility, normal S/V ratio, and significant numbers of granulomata with patchy areas of thickened interalveolar septa. Cotton-dust-instilled animals had normal distensibility, reduced S/V ratio, significant numbers of granulomata, and mild centrilobular emphysema. These data suggest that cotton dust produces a significant parenchymal lesion with elements similar to both the emphysematous response to endotoxin and the fibrotic nodular response to cellulose.