Preservative in Steroid Nasal Sprays Reduces Mucous Clearance

Nasal sprays containing steroids have become quite popular for the treatment for allergic rhinitis, inflammation of the nasal mucous membrane due to hay fever. They alleviate symptoms and cause a dramatic reduction of inflammation, demonstrating the beneficial effects of corticosteroids (steroids produced by the adrenal cortex). However, there are side effects, most notably local irritation and bleeding.

Most preparations of intranasal steroids in liquid form contain benzalkonium chloride to prevent microbial contamination. In vitro evidence suggests that benzalkonium chloride interferes with cilia function. In vivo, trapped foreign particles in nasal mucus are removed by ciliary action towards the nasopharynx. This adverse effect may contribute to the side effect of local irritation, and potentially to long-term sequelae such as recurrent infections.

One leading pharmaceutical manufacturer has developed a topical intranasal steroid preparation that does not contain benzalkonium chloride and is effective in the treatment of allergic rhinitis. The absence of benzalkonium chloride in this steroid preparation should be an advantage, because the beneficial effects remain without the adverse effects of the preservative on cilia and, potentially, nasal clearance.

A research team from the University of Chicago hypothesized that subjects with perennial allergic rhinitis treated with a topical steroid nasal spray without benzalkonium chloride would have reduced nasal inflammation, improved quality of life, and unaffected nasal clearance. They also suggested that another popular intranasal steroid preparation with benzalkonium chloride would similarly reduce nasal inflammation and improve quality of life, but reduce nasal clearance (both products are FDA approved for the treatment of seasonal and perennial allergic rhinitis).

The authors of "A Comparison of Nasal Clearance after Treatment of Perennial Allergic Rhinitis with Budesonide and Mometasone," are Robert M. Naclerio MD, Fuad M. Baroody MD, and Marcy deTineo BSN, from the Section of Otolaryngology-Head and Neck Surgery; and Nalini Bidani MD, and Bill C. O'Brien-Penney PhD, from the Section of Nuclear Medicine, all at the The Pritzker School of Medicine, The University of Chicago, Chicago, IL. Their findings are to be presented at the American Academy of Otolaryngology--Head and Neck Surgery Foundation Annual Meeting and OTO EXPO, September 22-25, 2002, at the San Diego Convention Center, San Diego, CA.

Methodology: This research was a parallel, randomized study comparing two nasal sprays containing steroids: one prepared without benzalkonium chloride (one spray per nostril, daily) and another with benzalkonium chloride (two sprays per nostril daily), the standard recommended starting doses for these drugs. Before and after two weeks of treatment, 20 subjects with perennial allergic rhinitis, older than 18 years, completed a Rhinitis Quality of Life Questionnaire (RQLQ), and underwent a nasal lavage (washing the nasal cavity) for the assessment of the number of eosinophils and the levels of eosinophil cationic protein (ECP) and albumin in nasal secretions, and a measurement of nasal clearance of a radioactive colloidal sprayed into the nose.

On the first visit, subjects were stable for 15 minutes so that equilibration of the nasal mucosa with the environmental condition of the laboratory was achieved. The RQLQ was completed; then, a nasal lavage was performed. Nasal clearance was then measured using radiotracer methods in the nuclear medicine section of the department of radiology. A solution containing small radioactively tagged particles was sprayed in each nostril, and a sequence of images was taken of the subject in a supine position with a dual detector gamma camera system. Nasal clearance was determined from the rate of decrease of radioactivity in the regions cleared by mucociliary transport. The volume of the lavage was recorded, and then the sample was vigorously shaken and stored in plastic tubes on ice. ECP, a marker of eosinophil secretion, was assayed.

After baseline measurements, subjects were randomly assigned to receive two puffs of a spray containing 50 micrograms of mometasone (total dose = 200 micrograms/ day/with benzalkonium chloride) or one puff of a nasal spray without benzalkonium chloride and containing 64 micrograms of budesonide (total dose = 128 micrograms/ day). The primary parameter analyzed was the change in nasal clearance rate between baseline and the final visit in each group. The secondary variables were RQLQ, number of eosinophils, ECP and albumin levels.

Results: Twenty subjects completed the protocol. There was no significant difference between the groups in the measurement of clearance at the end of treatment. Since the effect of allergic rhinitis and the effect of treatment were unknown, the researchers examined the amount of clearance change (change from pre to post-treatment). This analysis showed a significant difference (p<0.05) favoring spray without the antimicrobial agent.

Patients taking the nasal spray with benzalkonium chloride reported a significant improvement overall and in all of the individual domains of the quality of life survey. The other group reported an improvement in the overall domain but the individual domains such as activity, sleep, and emotions did not change significantly. After treatment, the statistical differences between the two groups were insignificant. The data obtained from the lavage was difficult to interpret, primarily because there was an insufficient baseline from which to detect a treatment-induced change. The levels of albumin tended to go down after both treatments with no statistical differences between groups. The ECP levels were less than the detection limits of the assay in almost everyone.

Conclusion: Using a patient survey, the researchers demonstrated that both treatments had a positive effect on nasal symptoms and quality of life with perennial allergic rhinitis. These findings are consistent with the previously demonstrated efficacy and safety of these drugs in the treatment of allergic rhinitis.

The use of lavage to detect objective measures of the inflammatory state associated with perennial allergic rhinitis provided little information in this study. This problem occurred because the levels of the biomarkers selected (albumin, ECP and the number of eosinophils) were low in most subjects at baseline, making it difficult to detect a decrease with effective treatment. Any changes that occurred after treatment were in the direction of improvement.

The comparison of mucociliary clearance between two intranasal corticosteroid preparations, one with and one without benzalkonium chloride, found that ex vivo effects on mucociliary clearance could be demonstrated in vivo. Both groups had comparable clearance at initiation and after treatment. Comparing the change in clearance between before and after treatment favored the preparation without benzalkonium chloride.

Visit http://www.entnet.org/healthinfo/sinus/allergic_rhinitis.cfm for more information on the diagnosis and treatment of these upper-respiratory disorders.