Lack of Deleterious Effects of Corticosteroid Sprays Containing Benzalkonium Chloride on Nasal Ciliated Epithelium

Abstract

SummaryCynomolgus monkeys were treated for 28 days with fluticasone propionate aqueous nasal spray (FPANS) 8 x 0.1 ml/day, which contained 0.02% benzalkonium chloride (BKC). Rats were treated for 1 hour/day for 28 days with a bec1o-methasone dipropionate aqueous nasal spray (BDPANS) essentially similar to the commercial preparation (Allen and Hanburys Ltd, Middlesex, England), which contained 0.01 % BKe. Control animals received 5% glucose (monkeys) or air (rats). Sections of nasal mucosa were examined at 4 different levels by light microscopy. Counts of ciliated cells were made and scanning and transmission electron microscopy was performed on target sites that had been directly exposed to treatment (inferior turbinate of monkeys and intermediate turbinate of rats). No reduction in the number of ciliated cells or microscopical changes were seen in the nasal epithelium of the animals, and in particular there was no damage to the ultrastructure of the ciliated cells, the cilia themselves or their basal bodies that was related to treatment. The findings were compared with the results of previous in vitro and in vivo studies. Although ciliostasis has been reported with BKC in in vitro models, where mucus is relatively depleted, such results should be interpreted with caution since BKC repeatedly applied to the nasal respiratory epithelium in vivo has not caused damage to the ciliated epithelial cells. The animals received greater exposure to BKC-containing corticosteroids than patients who are treated with the aqueous nasal sprays for allergic rhinitis. The lack of any morphological damage supports previous findings that no damage to ciliated cells occurs in patients treated with FPANS or BDPANS.

The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride

“…Ainge et al failed to show any adverse effects of benzalkonium chloride on the epithelium covering the turbinates in monkeys (13). Information about the mucosal structure in other parts of the nose is lacking.…”

“…Several in vitro studies have shown that benzalkoniurn chloride may induce unfavorable alterations in the mucosal membrane (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). These results have been disputed by others (13,14). It has been argued that observations in vitro have limited relevance to the corresponding phenomena in vivo.…”

The lack of effect of benzalkonium chloride on the cilia of the nasal mucosa in patients with perennial allergic rhinitis: a combined functional, light, scanning and transmission electron microscopy study

“…No evidenee of damage was seen. It is considered unlikely that the use of patietits suffering from allergic rhinitis would have masked deleterious effects of BKC since 28 days intranasal treatment of normal laboratory animals with either bedomethasonc dipropionate aqueous nasal spray (BDPANS) or FPANS also showed no uUrastructural changes in ciliated cells [18].…”

Effects of Benzalkonium Chloride on Innate Immunity Physiology of the Human Nasal Mucosa In Vivo

“… 9–12 Berg et al 13 also reported that treatment of the rat nasal mucosa with a BC‐containing glucocorticosteroid formulation in vivo resulted in marked morphological changes. On the other hand, studies by Ainge et al 14 and Braat et al 15 failed to show any mucosal disease in biopsy specimens from the inferior turbinates in monkeys and humans after nasal treatment with a glucocorticosteroid containing BC in vivo. Furthermore, McMahon et al, 16 in a study involving healthy subjects, reported no immediate or short‐term effects of BC on acoustic rhinometry findings, saccharine clearance time, and ciliary beat frequency.…”