Toxicity of Intratracheally Instilled Cotton Dust, Cellulose and Endotoxin

D.K. Milton, J.J. Godleski, H.A. Feldman, and I.A.Greaves


 
ABSTRACT

Cotton dust contains respirable particles capable of reaching the lung parenchyma. It also contains endotoxin and elastase, both of which are associated with emphysema. Therefore, we designed this study to determine whether the respirable fraction of cotton dust can produce emphysema. We intratracheally instilled hamsters with respirable cotton dust particles, mass median aerodynamic diameter <4.8 pm, twice weekly for six weeks at a dose equivalent to the maximum daily deposition in a high dose aerosol study. Cellulose, endotoxin and saline instilled groups were positive and negative controls. Eight weeks following the last instillation hamsters were sacrificed. Static pressure volume deflation curves of excised lungs inflated with air were analyzed to measure lung distensibility and an index of normal surface forces. Glutaraldehyde inflation fixed lungs were examined morphometrically to obtain surface area and numbers of granulomata.

Endotoxin treated animals had increased distensibility and reduced surface forces, reduced surface to volume (S-V) ratio and morphologically apparent mild centrilobular emphysema. Cellulose treated animals had decreased distensibility with normal surface forces, normal S-V ratio and significant numbers of granulomata. Morphologically the cellulose treated group had patchy areas with thickened interalveolar septa. Cotton dust instilled animals had normal distensibility with reduced stress recovery, reduced S-V ratio, significant numbers of granulomata and morphological appearance of mild centrilobular emphysema. These data suggest that cotton dust may produce a significant parenchymal lesion with elements of both the emphysematous response to endotoxin and the fibrotic response to cellulose. We also observe that respirable cellulose, although reported to have little effect on airways, may not be inert in the lung parenchyma.



Reprinted from Cotton Dust: Proceedings-12th Cotton Dust Research Conference 1988 pp. 163 - 166
©National Cotton Council, Memphis TN

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Document last modified Sunday, Dec 6 1998