H. Hallén

Effect on the Nasal Mucosa of Long-Term Treatment With Oxymetazoline, Benzalkonium Chloride, and Placebo Nasal Sprays†

A parallel, randomized, double‐blind study was performed in 30 healthy subjects to investigate the effects on the nasal mucosa of a 1‐month treatment with nasal sprays. Ten subjects received oxymetazoline nasal spray; 10 subjects used a nasal spray containing the preservative benzalkonium chloride, and the others were treated with a placebo nasal spray. The three variables that were studied‐nasal mucosal swelling, symptom scores, and nasal reactivity‐were estimated by histamine challenge before and after 28 days of treatment. Rhinostereometry was used to measure nasal mucosal swelling and nasal reactivity.

Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers

A randomized double‐blind parallel study with 20 healthy volunteers was performed to research the effect of a preservative in a decongestant nasal spray on the development of rhinitis medicamentosa. Ten subjects received oxymetazoline nasal spray with benzalkonium chloride and the others used oxymetazoline nasal spray without the preservative three times daily for 30 days. Before starting the course of treatment and after its conclusion, recordings of the mucosal surface positions were made with rhinostereometry followed by histamine challenge tests. Symptoms of nasal stuffiness were estimated on visual analogue scales (0–100) in the morning and the evening just before using the nasal spray. After 30 days, rebound swelling and nasal stuffiness were found in both groups. In the group receiving oxymetazoline nasal spray with benzalkonium chloride the mean rebound swelling was 1.1 mm and the estimated mean evening symptom score for nasal stuffiness was 43. In the group without benzalkonium chloride the corresponding variables were significantly less marked, with a mean rebound swelling of 0.5 mm (P<0.05) and a mean evening symptom score of 25 (P<0.05). The increase in histamine sensitivity in both groups was interpreted as a sign of nasal hyperreactivity. A new type of nasal spray bottle was used that has been shown to prevent bacterial contamination. In conclusion, the long‐term use of benzalkonium chloride in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers.

Four-week use of oxymetazoline nasal spray (Nezeril®) once daily at night induces rebound swelling and nasal hyperreactivity

A randomized double-blind parallel study with 20 healthy volunteers was performed to examine the effect of oxymetazoline nasal spray on the development of rhinitis medicamentosa. For 30 days, 10 subjects were given oxymetazoline nasal spray once daily at night and placebo in the morning and at noon, while the others used oxymetazoline nasal spray three times daily. Before and after the course of treatment, the mucosal surface positions were determined with rhinostereometry, followed by histamine challenge tests. In the morning and the evening just before use of the nasal spray, symptoms of nasal stuffiness were evaluated on visual analogue scales (0-100). After 30 days, rebound swelling and nasal stuffiness were found in both groups. In the group receiving oxymetazoline nasal spray once daily at night, the mean rebound swelling was 0.8 mm (p < 0.01) and the estimated mean symptom score for nasal stuffiness in the evening was 43 (p < 0.05). In the group receiving the same nasal spray three times daily, the mean rebound swelling was 1.1 mm (p < 0.01) and the mean evening symptom score was 43 (p < 0.05). The finding of an increase in histamine sensitivity in both groups was taken to indicate nasal hyperreactivity. There was no significant difference in the investigated variables between the two groups. It is concluded that the risk of developing rebound swelling and nasal hyperreactivity remains, whether oxymetazoline nasal spray is used once or three times a day for 30 days.

Nasal mucosal swelling and reactivity during a menstrual cycle.

Introduction: Nasal stuffness is a great problem for many women in the later part of pregnancy. Objective: This study was performed to evaluate whether oestrogen causes nasal congestion and/or a hyperreactive reaction of the nasal mucosa. Material and Methods: Ten healthy fertile women were examined during menstruation. Nasal mucosal congestion was studied with rhinostereometry and acoustic rhinometry. The nasal mucosa was challenged with 3 doses of histamine solution to study nasal reactivity. Measurements were made 3 times during menstruation. To find the exact time of ovulation, when oestrogen reaches its peak value, intravaginal ultrasound tests were done and blood samples taken, to determine the oestrogen and progesterone levels. Results: The nasal mucosa became hyperreactive to histamine in connection with ovulation, when the blood level of oestrogen reached its peak. This does not occur during the menstrual or the luteal phase. No significant alteration was found in the baseline position during the menstruation. Conclusion: There is a connection between high oestrogen level and nasal mucosal reactivity.

Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa

Background Controversy still exists about the treatment of rhinitis medicamentosa and treatment has never been objectively evaluated.

Changes in Nasal Reactivity in Patients with Rhinitis medicamentosa after Treatment with Fluticasone Propionate and Placebo Nasal Spray

Aim of the Study: To study the changes in nasal reactivity in patients with rhinitis medicamentosa during treatment with placebo or fluticasone propionate, in order to better understand the mechanisms of nasal congestion in such patients. Study Design: A parallel, double-blind study. Twenty patients with rhinitis medicamentosa were randomized to either placebo or fluticasone treatment during 14 days. Material and Methods: Nasal mucosa reactivity was studied with a histamine challenge model using three concentrations of histamine to challenge the nasal mucosa (1, 2 and 4 mg histamine/ml). Recordings of the nasal mucosa response were made 5 min after each challenge, using rhinostereometry and acoustic rhinometry, before and after the period of treatment. Results: The fluticasone group had a significantly increased histamine sensitivity after treatment, unlike the placebo group who had an unchanged or slightly decreased histamine sensitivity after treatment. Conclusions: The results of this study support the theory that the nasal obstruction in rhinitis medicamentosa is due to interstitial oedema rather than to vasodilatation. On the first day of vasoconstrictor withdrawal, the inferior concha was congested and oedematous with a limited capacity to respond to histamine challenge. However, after 14 days of treatment with a corticosteroid nasal spray, the oedema was reduced and the increase in histamine sensitivity reflected the persistence of nasal hyperrreactivity. In the placebo group, histamine sensitivity remains unchanged with the measuring technique we used. This probably indicates that oedema was still present after treatment.

An Objective Method to Record Changes in Nasal Reactivity during Treatment of Non-Allergic Nasal Hyperreactivity

Non-allergic nasal hyperreactivity is a common problem and many patients suffer from daily symptoms demanding medication. Hitherto there exists no objective method to study congestional changes in clinical practice, to evaluate the efficacy of different therapies. This study is an attempt to develop a method for this purpose. Eleven patients with non-allergic nasal hyperreactivity entered the trial. A histamine challenge model with three different histamine concentrations was used. Recordings of the reactivity of the nasal mucosa were made with rhinostereometry before and after 14 days of topical treatment with budesonide 200 micrograms/day. The results were compared to symptom scores before and after treatment. It was found that there was a significant improvement after treatment both with regard to symptom score and to the recorded reactivity of the nasal mucosa. There was a correlation between symptom score and recorded reactivity before treatment, but not after treatment. The results indicate that the symptom score technique is sufficient in situations where only a semiquantitative method is required. However, when studying changes in the degree of hyperreactivity, the demands for an objective measuring method is greater. The study indicates that the presented method may be adapted for this purpose.

One Year Follow-Up of Patients with Rhinitis Medicamentosa After Vasoconstrictor Withdrawal

The aim of the study was to systematically follow-up 10 patients with rhinitis medicamentosa for at least 1 year after vasoconstrictor withdrawal. During withdrawal of the decongestants the patients used budesonide nasal spray, 400 μg/day, for 6 weeks. The thickness of the nasal mucosa, the decongestive effect of oxymetazoline, and the histamine sensitivity were measured with rhinostereometry during the period. The thickness of the nasal mucosa and the symptom scores of nasal stuffiness were reduced considerably 6 and 12 months after vasoconstrictor withdrawal. The histamine sensitivity reflecting nasal hyperreactivity was still increased after 6 months, but not after 1 year. The decongestive effect of oxymetazoline increased after 6 months, indicating reversible tolerance. We conclude that when given adequate treatment and information about nose-drop overuse, all patients were able to stop using the vasoconstrictors and no one relapsed into a daily long-term overuse of vasoconstrictors during the 1-year follow-up period.

One-week use of oxymetazoline nasal spray in patients with rhinitis medicamentosa 1 year after treatment.

The aim of the present study was to investigate whether patients with rhinitis medicamentosa who stopped using the topical vasoconstrictors may use these drugs again more than 1 year later. Eight patients received oxymetazoline nasal spray containing benzalkonium chloride 3 times daily for 7 days, 13-19 months after they had stopped using nasal decongestant sprays containing benzalkonium chloride. Before starting the course of treatment and after its conclusion, recordings of the mucosal surface positions were made with rhinostereometry, followed by histamine challenge tests. Symptoms of nasal stuffiness were estimated on visual analogue scales (0-100). After 7 days, nasal stuffiness, estimated by symptom scores and measurements of nasal mucosa swelling, was found, as well as an increased histamine sensitivity, which was interpreted as a sign of nasal hyperreactivity. In conclusion, patients with rhinitis medicamentosa who overuse topical decongestants and are able to stop using such drugs should be careful about taking these drugs again, even for a few days. They must be informed about the fast onset of rebound congestion upon repeated use in order to avoid the return of the vicious circle of nose drop abuse.

Airway Reactivity of Nose and Bronchi in Patients with Nasal

The aim of the study was to determine whether patients with nasal polyps have a hyperreactive nasal mucosa and/or bronchi and whether there is any correlation between nasal and bronchial hyperreactivity. Twenty-six healthy volunteers and 10 consecutive patients with nasal polyps participated in the study. They were challenged with increasing concentrations of histamine. The nasal mucosa response was studied with rhinostereometry and the bronchial response was estimated by peak flow. One of the patients was mildly hyperreactive in the nose and 6 patients were hyperreactive in the bronchi. There was no correlation between nasal and bronchial hyperreactivity. Patients with nasal polyps do not have a hyperreactive nasal mucosa but there seems to be a high incidence of bronchial hyperreactivity in patients with nasal polyps.