Reply

Abstract

The chief purpose of the Rostrum review was to focus awareness of the medical community concerning the potential adverse effects of BKC, a commonly used preservative in nasal preparations. The article also adequately stressed current disparities and interpretative limitations between animal in vitro/in vivo data and several human clinical studies. As correctly noted by Richards, the degree of absorption of BKC by nasal mucus/protein is a key determinant in the development of possible BKC toxicity.1Ainge G Bowles JAK McCormick SG Richards DH Scales MDC Lack of deleterious effects of corticosteroid sprays containing benzalkonium chloride on nasal ciliated epithelium: in vivo results in laboratory animals.Drug Invest. 1994; 8: 127-133Crossref Scopus (24) Google Scholar He is incorrect, however, in stating that the in vivo rat study by Berg et al was flawed because the micropipette technique of exposure may wash away nasal mucus.2Berg OH Lie K Steinsvag SK The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride.Allergy. 1997; 52: 627-632Crossref PubMed Scopus (47) Google Scholar In these experiments several topical nasal steroids (with and without BKC) were sprayed into rat nares through a micropipette twice daily for 21 days, a technique that mimics human exposure. To the best of my knowledge, there is no “acknowledged” precise method that detects significant changes in the mucociliary blanket before and after such applications. Nonetheless, even if it is assumed that each of the nasal applications would lavage away some mucus/protein, it can also be postulated that the mucociliary layer would be replenished before the next application. Regardless of the theoretic possibility that insufficient mucus was available for neutralization of BKC, Berg et al found unequivocal features of squamous cell metaplasia only in the nostrils treated with BKC-containing preparations. Concerning Richards’ assertion about “omitted or distorted issues,” it was not possible to include all publications because of the Journal’s editorial policy that restricts the number of Rostrum references. Moreover, several abstract articles cited by Richards did not investigate the effects of a BKC-placebo solution.3Klossek JM Mounedji N Bousquet J Long term treatment with triamcinolone acetonide aqueous nasal spray and its effect on mucociliary function in patients [abstract].J Allergy Clin Immunol. 2000; 105: S201Abstract Full Text PDF Google Scholar, 4Laliberte F Laliberte MF Bousquet J et al.A long term local safety study: effect of triamcinolone acetonide on the nasal mucosa [abstract].J Allergy Clin Immunol. 2000; 105: S382Abstract Full Text PDF Google Scholar In a 2-week study Hallen et al5Hallen H Enerdal J Graf P Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa.Clin Exp Allergy. 1997; 27: 552-558Crossref PubMed Scopus (46) Google Scholar demonstrated that symptoms and objective index values of nasal obstruction in patients with rhinitis medicamentosa treated with BKC-formulated fluticasone propionate improved more and faster than in patients receiving the BKC-formulated placebo. It was noteworthy that improvement, as indexed by symptoms and objective tests, was slower in the BKC-placebo group, although symptom scores were lower in this group at the beginning of randomization. Although these results indicated that topical steroids were effective agents in this situation, they did not exclude the possibility that BKC might have been partially responsible for a slower response in the placebo group. Thus, in contrast to Richards’ contention, this particular study did not demonstrate to my satisfaction that BKC was unequivocally nontoxic. Anecdotally, I continue to receive personal communications about patients who have epistaxis or irritant-like symptoms after use of nonsteroidal BKC-nasal preparations (eg, Ocean™) and I personally have observed similar clinical events. The “cautionary note” expressed in the Rostrum article is fully justified on the basis of current clinical evidence combined with complementary in vivo animal models that directly investigated histopathologic changes after exposure to BKC in a manner similar to clinical usage.2Berg OH Lie K Steinsvag SK The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride.Allergy. 1997; 52: 627-632Crossref PubMed Scopus (47) Google Scholar Ultimately, the controversial issue of BKC toxicity in nasal preparations will only be resolved by a long-term, controlled investigation of BKC in 0.9% saline solution compared with 0.9% saline solution alone. 1/8/109174