This rat model evaluated the effectiveness of erythromycin, tetracycline, Aerosil™ 200 and erythromycin plus Aerosil™ 200 as pleural sclerosing agents. This study demonstrated that Aerosil™ 200 with or without erythromycin was more potent pleurodesis agent both grossly and microscopically. To the best of our knowledge, the present study is the first investigation to study the pleurodesing effect of intrapleural Aerosil™ 200. However, there are a few studies on the health effects of Aerosil™ 200. In an animal investigation by Reuzel and colleagues, subchronic inhalation of Aerosil™ 200 induced the most severe changes in the lungs among other examined amorphous silicas . In another study, Johnston et al. observed reversible inflammatory responses in bronchoalveolar lavage after inhalation of amorphous silica (Aerosil™ 200), while no mutagenic events were noted . Likewise, recent experimental studies confirmed the pulmonary fibrogenetic effects of amorphous silica such as Aerosil™ 200 [15–17].
Chemical pleurodesis with silica-containing materials has been of utmost interest. Yeginsu and colleagues found that bioglass was as effective as talc in terms of pleurodesis [7, 8]. It is believed that silicon dioxide or silica contributes to the pleurodesing effect of bioglass, talc and Aerosil™ 200. Silicon dioxide or silica exposure has been found to cause lung damage through direct cytotoxicity, generation of reactive oxygen species from alveolar macrophages, and stimulation of secretion of inflammatory cytokines, chemokines, and fibrogenic factors from alveolar macrophages and/or epithelial cells [7, 18]. Although similar mechanism might be deemed for the Aerosil™ 200 particles, further investigations orchestrated on the mechanisms of Aerosil™ 200-induced pleurodesis are recommended.
Both in gross and microscopic assessments, erythromycin was less potent pleurodesis agent than the Aerosil™ 200. This finding is in contrast to that of the previous experimental study indicating that erythromycin was an ideal pleural sclerosing agent, compared with talc, doxycycline and diazepam . Moreover, in a recent clinical study by Balassoulis et al., erythromycin was found as an effective and safe pleurodesing agent in patients with recurrent malignant pleural effusions . However, we do not have an explanation for such a difference in the pleurodesing effect of erythromycin. Furthermore, tetracycline was not superior to the other pleurodesing agents in the present study. This finding is compatible with that of the previous reports; fibrin tissue adhesive , talc , and mitoxantrone were found as more effective sclerosing agents than tetracycline for pleurodesis . In contrast, Vargas and colleagues found that tetracycline, rather than bleomycin and Corynebacterium parvum, was more potent pleurodesing agent in a rabbit model [23, 24]. In a systematic review, tetracycline was reported to be associated with more recurrences when compared to talc . The available clinical evidence supports the use of talc as the sclerosant of choice rather than other sclerosants (tetracycline, bleomycin, or mustine) .
This study has certain limitations. We did not investigate talc as a sclerosing agent in the present study. The rationale behind this exclusion was the lack of sterile and pure talc in Iran. Moreover, other routinely used pleurodesing agents such as bleomycin and parenteral doxycycline were not available due to their high costs. Therefore, further studies are recommended to be orchestrated in order to investigate the probable advantage of the Aerosil™ 200 over the most commonly used pleurodesis agents such as sterile and pure talc in terms of efficacy, safety, rapidity of action, mechanism of action or cost. In addition, one may consider the rabbit model as generally more established method for experimental pleurodesis. However, there are a number of experimental studies of pleurodesis on the rats [20, 25–27]. Only single dose of 35 mg/kg was studied for each sclerosant, and different doses might have resulted in more favorable responses. However, the applied treatment dosages were based on those of the previous studies. Future studies with larger doses of erythromycin and tetracycline may achieve higher response rates. Furthermore, distant sequelae of the studied pleurodesing agents in the contralateral lung as well as the liver along with their systemic effects were not evaluated. Liver enzyme tests, histopathological assessment of the contralateral lung and the liver, and serum and tissue angiotensin-converting enzyme could have provided precious information regarding the toxicity of the studied pleurodesing agents, in particular the Aerosil™ 200. In addition, grading of the pleurodesis immediately after sacrificing the animals while the tissues were fresh and soft might have yielded to different results. The formalin exposure makes the tissues firm and shrunk, resulting in difficult evaluation of the pleural adhesions .