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Published ahead of print on May 28, 2003, doi:10.1164/rccm.200207-767OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 3, August 2003, 348-355

A more recent version of this article appeared on August 1, 2003
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Submitted on July 30, 2002
Accepted on May 22, 2003

Influence of Talc Dose on Extrapleural Talc Dissemination after Talc Pleurodesis

Juan F Montes1*, Jaume Ferrer2, Maria A Villarino2, Bernat Baeza1, Marta Crespo1, and Jose Garcia-Valero1

1 Departament de Biologia Cel.lular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain, 2 Servei de Pneumologia, Hospital General Universitari Vall d'Hebron, Barcelona, Spain

* To whom correspondence should be addressed. E-mail: montes{at}porthos.bio.ub.es.

This study was designed to ascertain, in a rabbit model, extrapleural talc deposition and the related inflammatory response following talc slurry pleurodesis with two clinical doses, 200 and 50 mg/kg. Histopathologic evaluations revealed that while numerous rabbits receiving a high dose had talc in the ipsilateral (70%) and contralateral (55%) lung, mediastinum (90%), pericardium (30%) and liver (25%), a small number of animals treated with a low dose showed talc in the ipsilateral lung (10%) and mediastinum (20%), and none in the contralateral lung, pericardium or liver. Hematologic and immunocytochemical analyses showed that a systemic inflammatory response develops shortly after pleurodesis with a high talc dose involving massive accumulation of neutrophils and macrophages in lung tissue. Zymography also revealed that the pulmonary expression of matrix metalloproteinases 2 and 9 was upregulated in both lungs in a dose-dependent manner soon after talc instillation. Furthermore, microscopic examination of lung specimens revealed that the higher the dose of talc, the greater the development of both fibrotic visceral pleural thickening and foreign-body granulomas. These findings show pleurodesis with a high talc dose to be associated with an increased risk of extrapleural talc deposition, which may originate undesirable acute and chronic inflammatory responses.
Key words: granuloma, inflammation, lung, matrix metalloproteinase, surgical trauma




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