Jan-Erik Juto

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.

Rhinostereometry and Laser Doppler Flowmetry in Human Nasal Mucosa: Changes in Congestion and Microcirculation during Intranasal Histamine Challenge

The nasal mucosa of 10 healthy volunteers was studied with the combination of rhinostereometry and laser Doppler flowmetry during a challenge with 0.14 ml histamine dihydrochloride in stepwise increasing concentrations of 0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 mg/ml. Five and 10 min after each challenge the degree of congestion and the microcirculatory parameters perfusion, velocity of flow and concentration of moving blood cells were recorded. A complex reaction pattern was seen. It was possible to measure simultaneously the degree of congestion and the microcirculatory parameters. With this combination of methods, it seemed possible to identify the effects of histamine on the different components of the nasal mucosa. The combination of the two methods appears to make possible detailed studies of the relationship between changes in congestion and microcirculation during intranasal challenges in humans.

Decongestion Effect and Rebound Swelling of the Nasal Mucosa during 4-Week Use of Oxymetazoline

The aim of this study was to investigate whether long-term use of oxymetazoline induces a rebound swelling of the nasal mucosa and whether the decongestion effect is altered during medication. Eight healthy volunteers had oxymetazoline nasal spray (0.5 mg/ml; 0.1 ml in each nostril, three times daily) for 30 days and registrations of the mucosal surface positions were made using rhinostereometry. Compared to the registrations before the start of medication, no rebound swelling was registered after 10 days. After 30 days, however, a rebound swelling was registered in all subjects (p < 0.001). All of them, then, also reported nasal stuffiness. The decongested position of the nasal mucosa after one single dose of oxymetazoline was the same in the whole study. It is concluded that rhinitis medicamentosa develops after a relatively short time on oxymetazoline, even in healthy volunteers, and that the swelling probably is due to a vasodilatation rather than an edema. The study supports the recommendation that the drug should not be used over periods > 10 days.

Nasal hyperreactivity among teachers in a school with a long history of moisture problems.

Upper airway symptoms have frequently been reported in people working or residing in damp buildings. However, little information has been available on objective pathophysiologic findings in relation to these environments. Twenty-eight teachers, who had worked for at least five years in a recently renovated school that had had severe moisture problems for years, were randomly selected for this study. Eighteen teachers, who had worked in another school that had no moisture problems, were randomly selected to serve as the control group. Although remedial measures had been taken, an increase in the prevalence of mucous membrane irritations was still reported by the teachers in the target school. We used a nasal challenge test with three concentrations of histamine (1, 2 and 4 mg/mL). Recordings of swelling of the nasal mucosa were made with rhinostereometry, a very accurate optical non-invasive method. The growth curves of mucosal swelling induced by the three concentrations of histamine differed significantly between the two groups (p < 0.01). The frequencies of atopy, evaluated with the skin-prick test, were almost identical in both groups. The study indicates that long-term exposure to indoor environments with moisture problems may contribute to mucosal hyperreactivity of the upper airways. Such hyperreactivity also seems to persist for at least one year after remedial measures have been taken.

Nasal histamine provocation of tenants in a sick-building residential area.

Health problems associated with the indoor climate have aroused an increasing scientific interest, and the term “sick-building syndrome” (SBS), which describes the most frequent symptoms in this context, has been coined. However, it has been difficult to demonstrate objectively any pathophysiological changes in the subjects affected. Thirty-three healthy and nonatopic persons were randomly selected on the basis of answers in a postal questionnaire dealing with discomfort or health symptoms experienced in their home environment. Twenty-three lived in a residential area with indoor climate problems (SBS area) and 10 lived in an area without climate problems (non-SBS area). Twelve persons from the SBS area reported nasal symptoms, which they ascribed to their home environment. The remaining 11 persons from the same area, as well as the 10 subjects from the non-SBS area, had no nasal distress. They were examined with rhinostereometry during histamine provocation. Hyperreactivity, defined as mucosal swelling exceeding 0.4 mm at 5 and 10 minutes after provocation with 0.14 ml of 2 mg/ml histamine chloride, was frequent in the symptomatic SBS group as well as in the asymptomatic SBS group. The analysis of the increment of mucosal swelling for the whole range of histamine chloride concentrations (0.1 mg/ml to 16 mg/ml) showed significantly different growth curves for the three groups in the residential areas and an external reference group, (p < 0.0001). Subjects living in the SBS area were prone to nasal hyperreactivity, whether they reported symptoms from the upper airways or not. The results support the hypothesis that living in an SBS area increases the risk of developing nonspecific nasal hyperreactivity.

Nasal and bronchial histamine reactivity in patients with allergic rhinitis out of season.

BACKGROUND The correlation between non-specific hyperreactivity of upper and lower airways in pathologic conditions has not been studied extensively. OBJECTIVE To investigate the occurrence of nasal and bronchial hyperreactivity in patients with allergic rhinitis studied out-of-season. METHODS From patients admitted to the Allergy Unit at Stockholm Söder Hospital, 12 individuals with allergic rhinitis due to grass or birch pollen were selected. The nasal mucosa was exposed to increasing concentrations of histamine chloride and the response was recorded by rhinostereometry, an optical method that exclusively measures changes in nasal congestion. Bronchial histamine challenge was performed in connection with the nasal tests, but on different days. RESULTS The nasal histamine response was significantly greater than in a reference group of healthy volunteers (P < .01). Nasal hyperreactivity was demonstrated in 9 of 12 patients. No clear relation between the magnitude of nasal and bronchial histamine responses was seen in the study group. CONCLUSIONS In allergic rhinitis studied out-of-season, airway hyperreactivity is common in both upper and lower airways, but does not necessarily occur together in the same individual.

Studies of spontaneous fluctuations in congestion and nasal mucosal microcirculation and the effects of oxymetazoline using rhinostereometry and micromanipulator guided laser Doppler flowmetry.

The mucosa of the inferior turbinate was studied using rhinostereometry and micromanipulator-guided laser Doppler flowmetry in 10 healthy volunteers. First, spontaneous fluctuations were studied measuring congestion and multiple microcirculatory parameters simultaneously every 2 minutes. The subjects were then challenged with oxymetazoline using the same measuring technique studying the effects of the challenge during 12 minutes. There were spontaneous variations in congestion of up to 2.1 mm and variations in perfusion from 38% to 175% of average. There was no correlation between congestion in itself, or change in congestion, to perfusion or any other microcirculatory parameter. After challenge with oxymetazoline there was a rapid decrease in perfusion at 3 minutes after which there were no significant changes. The congestion decreased gradually throughout the procedure. Because congestion reflects the filling of the venous sinusoids and the flowmetry the state of the superficial vessels, we conclude that there are spontaneous short-term fluctuations in the sympathetic tone with independent actions on the different vessels. After challenge with a sympathomimetic drug, there was a decrease in both swelling and flow, but not synchronized. The combination of rhinostereometry and micromanipulator-guided laser Doppler flowmetry is a useful tool to study the dynamics of intranasal challenge reactions.

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.

Intranasal Histamine Challenge in Normal Subjects and Allergic Rhinitis before and after Intranasal Budesonide Studied with Rhinostereometry and Micromanipulator-Guided Laser D oppler Flowmetry

Ten healthy subjects and 10 patients suffering from allergic rhinitis to birch pollen were investigated with the combination of rhinostereometry and laser Doppler flowmetry, thus simultaneously measuring changes in mucosal swelling and microcirculation, following intranasal histamine challenge. Compared to normals, the allergics had a higher degree of congestion and a lower increase in perfusion and velocity of flow. In the allergics there was a decrease in CMBC (concentration of moving blood cells) that was not seen in normals. The decrease in CMBC seen in allergics could be attributed to an increase in vascular permeability producing an interstitial edema, a well-known effect of histamine. After treatment with 1 week of intranasal steroid, most of the differences in the reaction pattern between normals and allergics had disappeared.