Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature

Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P < 0.05) because of a reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants.     

Temperature and humidity profile of the paranasal sinuses before and after mucosal decongestion by xylometazolin

BACKGROUND: One of the most important functions of the nose is to warm and to humidify air before it reaches the lower respiratory tract. Nasal decongestants as one of the most common drugs used in otorhinolaryngology are often associated with the feeling of a "dry nose". The purpose of this study was to determine the short-term influence of xylometazoline on temperature and humidity in the nasal airways. METHODS: 15 healthy volunteers were enclosed into the study. A miniaturised humidity sensor and thermocouple was used for detection of humidity and airway temperature in the nasal vestibule, at the nasal valve area and in the nasopharynx at the end of inspiration. Measurements were done before and after topical application of xylometazoline. RESULTS: Temperature and relative humidity increase from the anterior parts of the nose to the nasopharynx at the end of inspiration. The temperature and humidity values after nasal decongestion are not significantly different from the values before application of xylometazoline. As a tendency temperature and humidity values after nasal decongestion are even somewhat higher at the nasal valve area compared to the values before application of xylometazoline. CONCLUSIONS: Widening of the nasal airways by mucosal decongestion did not lead to a significant change of the nasal temperature and humidity profile 20-30 min after application of xylometazoline. The use of xylometazoline seems not to influence humidifying and heating of inspired air within a short period after onset of the maximal decongestive effect of xylometazoline.     

The effect of topical xylometazoline on the mucosal temperature of the nasal septum

BACKGROUND: The purpose of this study was to determine the short-term influence of the alpha2-adrenoreceptor agonist xylometazoline on the nasal mucosal temperature. METHODS: Thirty healthy subjects were enrolled into the study. Fifteen of these subjects got xylometazoline and 15 subjects, matched to age, got saline solution as control. A miniaturized thermocouple was used for continuous detection of the septal mucosal temperature without interruption of nasal breathing before and after application of nose spray. RESULTS: In the anterior nasal segment, the mucosal temperatures before decongestion were significantly higher than after decongestion (p < 0.05). These changes could not be found in the control group after saline solution. The mean end-expiratory mucosal temperatures were significantly higher than the end-inspiratory ones in both study groups (p < 0.005). CONCLUSIONS: The reduction of the nasal mucosal bloodflow because of vasoconstriction and the increase of the nasal cavity volume after decongestion with xylometazoline seem to cause a significant decrease of the septal mucosal temperature in the anterior nasal segment. This might be one possible causative factor of the common symptom of the "dry nose" in patients with nasal decongestant abuse.     

Detection of particles within the nasal airways during respiration

This study introduces a new experimental set-up for particle detection within the nasal airways and describes intranasal deposition of particles at various regions of the nasal cavity and the nasopharynx. During respiration of an aerosol of starch particles the nondeposited particles in the air were detected in 11 volunteers by a transnasally placed suction probe at numerous sites of the nasal cavity and nasopharynx. Another, identical suction probe measured the initial number of inhaled particles at the nostril. The two suction probes were connected to two identical laser particle counters and allowed calculation of particle deposition. Particles 1–3 μm in size were deposited to about 60% within the entire nasal cavity, whereas most of the particles 4–30 μm in size were deposited within the entire nasal cavity. Between 80% and 90% of the particles retained in the nasal cavity were deposited at the anterior nasal segment. Studies on deposition of various drugs within the nasal cavity using this experimental set-up are conceivable. Received: 29 May 2000 / Accepted: 10 August 2000     

Manometric rhinometry

A new method of measuring nasal volume is described. It works by extracting air from a closed cavity and measuring the resultant pressure change. To validate this method in the nose, 17 healthy volunteers were examined before and after application of xylometazoline. The apparent volume before decongestion was a mean of 204 ml. After decongestion the average volume was 228 ml. The difference is highly significant (P < 0.01). We conclude that manometric rhinometry is a valid method of investigating the nose and sinuses.     

The impact of expiration on particle deposition within the nasal cavity

One of the most important functions of the nose is cleansing the inspired air. The aim of this study was to compare the intranasal deposition of particles during inspiration and expiration, applying different breathing manoeuvres. In nine subjects, the non-deposited particles during inhalation of an aerosol of starch particles were laser-optically detected by placing a suction probe transnasally in the anterior nasal segment. The particle deposition was measured during cyclical nose-in/nose-out (nose-only) and nose-in/mouth-out breathing. The deposited fraction was calculated in percentages. Active anterior rhinomanometry and acoustic rhinometry were performed. The mean deposited fraction in the anterior nasal segment was statistically significantly higher (P < 0.02) during nose-only breathing (46.0%) compared with nose-in/mouth-out breathing (33.0%). Our results suggest that intranasal particle deposition takes place during inspiration as well as during expiration. The period of expiration does not only seem to be important for water and heat recovery, but also for cleansing of the respiratory air.     

Rhinomanometric measurements in obstructed nasal respiration before and following rhinosurgical interventions

355 patients with nasal obstruction caused by different disease were treated by various nasal operations. Active anterior rhinomanometry was performed before and after operation, both before and after decongestion of the nasal mucosa. 254 patients were reassessed 6 to 9 months later. On average an increase of nasal airway was achieved from V 1.5 = 0.46 1/s before operation to 0.74 1/s after operation (before decongestion) and from V 1.5 = 0.55 1/s before operation to 0.83 1/s after operation (after decongestion of the nasal mucosa). The decongestion effect and the differences between the better worse nasal cavities showed a significant decrease after operation. Rhinomanometric evaluation of the various nasal operations is presented for patients with nasal blockade caused by various diseases.     

Effects of the Cottle's maneuver on the nasal valve as assessed by acoustic rhinometry

BACKGROUND: The nasal valve is the narrowest segment of the nasal cavity and plays an essential role in breathing. There has been plenty of discussion in the literature concerning the location and function of the nasal valve. The Cottle's maneuver (CM) is a test in which the cheek on the side to be evaluated is gently pulled laterally with one to two fingers to open the valve. This test is used to determine if the most significant site of nasal obstruction is at the valve or farther inside the nasal cavity. The aim of this study was to determine the dimensional changes caused by the CM in the nose as measured by acoustic rhinometry (AR). METHODS: Eight adult volunteers with no nasal symptoms were recruited and their nasal cavities were measured by AR. The measurements were done with and without the CM both before and after decongestion with a mixture of 1:1000 epinephrine and 4% lidocaine in cotton pledgets. The MCA1 and MCA2 and their distances from the nostril, as well as the volume-measured from the zero point to the MCA2 point--were determined. RESULTS: The main effect of the CM was a mean increase in MCA1 by 33% (p = 0.001) and 44% (p < 0.001) before and after decongestion, respectively. The distance of MCA1 increased significantly, because of the CM, by 12% (p = 0.006) before and 7% (p = 0.008) after decongestion. The percentage increases in volume were 33% (p = 0.001) and 44% (p < 0.001), respectively. Decongestion of the nasal mucosa induced a statistically significant (p = 0.001) increase in both MCA1 (by 21%) and MCA2 (by 28%). CONCLUSION: The CM significantly increased MCA1 in AR, and the increase was more evident after decongestion of the nasal mucosa. The changes in MCA2 were nonsignificant. We conclude that the value of the CM in investigating a possible valve insufficiency may be greater if the nose is studied both before and after decongestion of the nasal mucosa.     

Acoustic rhinometry in the evaluation of nasal obstruction

Acoustic rhinometry (AR) is a recently developed objective technique for assessment of geometry of the nasal cavity. The technique is based on the analysis of sound waves reflected from the nasal cavities. It measures cross-sectional areas and nasal volume (NV). To obtain dependable assessments of nasal resistance by rhinomanometry or cross-sectional area measurements by AR, it is essential that the structural relations of the compliant vestibular region remain undisturbed by the measuring apparatus. The use of nozzles in making these measurements carries a great risk of direct distortion of the nasal valve. We used a nasal adapter that does not invade the nasal cavity and a chin support that stabilizes the head. In 51 healthy nasal cavities, the average minimum cross-sectional area (MCA) was 0.62 cm² at 2.35 cm from the nostril and 0.67 cm² at 2 cm from the nostril, respectively, before and after topical decongestion of the nasal mucosa. The MCA and NV findings in this group were significantly higher than MCA and NV (P<0.001) in people with structural or mucosal abnormalities before mucosal decongestion. After mucosal decongestion, the MCA and NV were significantly higher in healthy nasal cavities than in nasal cavities with structural abnormalities (P<0.001) but were not higher than nasal cavities with mucosal abnormalities (MCA, P = 0.05; NV, P = 0.06). A nozzle was applied in 20 healthy nasal cavities after mucosal decongestion, and a significantly higher MCA was found compared to measurements made with the nasal adapter (P = 0.02). We conclude that the nasal adapter, which does not invade the nasal cavities, avoids the distortion of the nasal valve and gives more accurate results.     

吸烟对鼻气道阻力影响的初步探讨

目的：探讨吸烟对鼻气道阻力（ＮＡＲ）的影响,方法：采用前鼻测压法,对４０例正常不吸烟者（对照组）,４１例轻度吸烟者（轻度吸烟组）、４２例重度吸烟者（重度吸咽组）的单侧及总鼻腔ＮＡＲ进行测定,比较。结果：重度吸烟组鼻粘膜减充血前单侧及总鼻腔（ＮＡＲ）与对照组比较有显著性差异（Ｐ〈０．０５）,鼻粘膜减充血后则针显著性差异（Ｐ〉０．０５）;轻度吸烟鼻粘膜减充血前后均无显著性差异（Ｐ〉０．０５）。结论：长     

接触性头痛患者手术前后鼻气道阻力变化

目的：研究接触性头痛患者手术前后鼻气道阻力（NAR）的变化。方法：利用前鼻测压法对20例（40侧）接触性头痛患者手术前后、鼻减充血前后的NAR进行研究。结果：随访6个月,痊愈16例（85％）,有效3例（15％）,无效1例（5％）,有效率95％。术后NAR明显下降,手术前术侧喷麻黄碱前后NAR分别为（-0．34土O．23）和（-0．75±0．21）kPa·s／L;手术后分别为（0．68±0．20）和（-0．74±0．16）kPa·s／L,两者相比差异有统计学意义（P％0．05）。结论：内镜手术对接触性头痛患者鼻通气功能的改善主要是由于鼻腔结构的改变和黏膜肿胀的消退,测定NAR对于客观评价接触性头痛患者接触点的解除具有重要临床意义。     

Use of pharmacologic decongestion in the generation of rhinomanometric norms for the nasal airway

It has been reported that nasal decongestion can be more effectively achieved by regulated exercise than by the use of decongestant nose drops. To test this finding, we assessed the relative effectiveness of physical exercise, nose drops, and sprays on 100 consecutive patients with nasal congestion. We found that decongestion was best achieved by spraying the nasal mucosa twice, seven to eight minutes apart, with 0.1% xylometazoline solution (Otrivin; Ciba-Geigy). This study demonstrates that rhinomanometric improvement correlates well with subjective improvement following septoplasty. Rhinomanometric limits for the selection of patients suitable for functional operations of the septum or lateral walls of the nose are presented.     

Acoustic rhinometry: values from adults with subjective normal nasal patency.

The nose with normal feeling of nasal patency, and no gross structural changes has been described in 82 individuals by acoustic rhinometry. Curves for one and both sides of the nasal cavity and before and after decongestion have been recorded. We have found that the minimal cross-sectional area (MCA) is located anteriorly in the nasal cavity; in some subjects it is localized at the head of the inferior turbinate and in other subjects more anteriorly at the nasal valve. After decongestion MCA moves even more anteriorly. Beyond the MCA the dimension of the nasal cavity increases, with maximal effect of decongestion at 4 cm from nostrils. Decongestion increases the total volume of the nasal cavity by 35%.     

A comparison of the sensitivity of manometric rhinometry,acoustic rhinometry,rhinomanometry and nasal peak flow to detect the decongestant effect of xylometazoline

A study has been undertaken to compare the sensitivity of manometric rhinometry, rhinomanometry, nasal peak flow and acoustic rhinometry to detect the decongestant effect of xylometazoline. Twenty healthy volunteers were investigated before and after decongestion. The sensitivity of all four methods varied from 80 to 95%. These differences were not significant. Manometric rhinometry, a new method of investigating nasal physiology, is as sensitive as more established methods.     

Investigating the nasal cycle using endoscopy,rhinoresistometry, and acoustic rhinometry

OBJECTIVES: Cyclic congestion and decongestion in the two nasal cavities is seen in connection with the respiratory function of the nose. The turbulent behavior of nasal airflow is a prerequisite for adequate contact of inspired air particles with the mucosa. The aim of this study was to gain insight into this turbulent behavior of nasal airflow during the nasal cycle. METHODS: The nasal cycle in 10 healthy human subjects was investigated using endoscopic imaging, rhinoresistometry, and acoustic rhinometry every 20 minutes over a time period of up to 15 hours. The following parameters were recorded for each nasal cavity: airflow resistance, hydraulic diameter, friction coefficient lambda as an indicator for the wall configuration triggering turbulence, transition from laminar to turbulent flow, and the minimal cross-sectional areas. RESULTS: In addition to the known cyclic change of flow resistance and nasal width, a periodic change in the turbulence behavior was observed. In the resting phase, mainly laminar flow was found. During the working phase, the onset of turbulence occurred already at low flow velocities. The increase of turbulence during the working phase is caused by the increase in cross-sectional area in the anterior cavum due to decongestion of the mucosa of the head of the inferior turbinate and the septal tuberculum. CONCLUSIONS: Rhinoresistometry and acoustic rhinometry complement each other. The combination of the two methods provides insight into the functional changes during the nasal cycle and into nasal physiology in general. The authors therefore advocate a combination of the two methods for functional evaluation of the nasal airway.     

Function and structure of the nasal mucosa after 6 weeks' use of nose-drops

The nasal mucosa of 20 healthy subjects were examined before, during and after 6 weeks of regular use of xylometazoline nose-drops (1 mg/ml) 0.15 ml three times daily. The subjects, except those affected by common colds, did not suffer any diminished mucociliar function during or after the trial. The surface structures were not found to have changed when examined with scanning electron microscopy. No morphological changes were observed in the intercellular space, basal membrane or tunica propria when using transmission electron microscopy. During the test period 5 of the subjects developed upper respiratory infections which temporarily prolonged the mucociliar transport time tested with small particles of saccharin. In some of these subjects a reduction in the number of ciliated cells was observed as well as an inflammatory reaction close to the epithelial cells. It is concluded that the use of xylometazoline over a 6-week period does not provoke any major functional or structural changes in a normal nasal mucosa.     

Comparison of decongestive capacity of xylometazoline and pseudoephedrine with rhinomanometry and MRI

Topical and systemic sympathicomimetics have been used for many years as a treatment of nasal congestion in diseases such as coryza and sinusitis. The aim of this study was to perform an objective measurement of the decongestive capacity of topical xylometazoline and oral pseudoephedrine in normal subjects and patients with chronic sinusitis. Ten healthy subjects and 10 patients with chronic sinusitis were included in this study. Xylometazoline (0.1%) and pseudoephedrine (120 mg) were each administered to 5 healthy subjects and to 5 patients with chronic sinusitis. Decongestion was measured with active anterior rhinomanometry before, 15 minutes, 30 minutes and 1, 2, 4, 6 and 8 hours after administration. Before and about 90 minutes after drug administration a MRI was performed to visualize the decongestive effect on the turbinates and the mucosa of the sinuses. Xylometazoline reduces the nasal airway resistance for an average 37.3% in all patients and healthy subjects during 8 hours. Pseudoephedrine does not show a clear and long lasting decongestive effect on the turbinates. Important interindividual differences are also noted. MRI clearly shows a clear cut superiority of xylometazoline over pseudoephedrine concerning decongestion of the nasal mucosa. However, there was no decongestive effect whatsoever on the mucosa of the sinuses with either sympathicomimetic.     

Deposition pattern of nasal sprays in man

The intranasal distribution from an aqueous pump spray has been assessed in 13 normal subjects, using insoluble Teflon particles labelled with 99Tcm which were intended to simulate a suspension of drug particles. Three different combinations of metered volume and spray cone angle were compared. The main deposition of particles was in the anterior, non-ciliated, part of the nose, but some particles also penetrated more posteriorly into the main nasal passages and were cleared subsequently to the nasopharynx. No particles were detected in the lungs. With a single puff of 100 microliters volume, 46.5 +/- 4.4 (mean +/- SEM)% of the spray was retained in the anterior part of the nose after 30 minutes, but this was increased to 57.1 +/- 4.5% (P less than 0.05) with two puffs of 50 microliters. The latter were deposited over a significantly (P less than 0.05) smaller area in the nasal cavity. There was a trend towards lower particle retention and a greater area of deposition when the spray cone angle was decreased from 60 degrees to 35 degrees. These results indicate that the drug particles released from nasal pump sprays are distributed both to ciliated and non-ciliated zones, and that the choice of metered volume and possibly spray cone angle may play a role in determining the amount which penetrates to the main nasal passages.     

Deposition pattern from a nasal pump spray

The initial distribution and subsequent clearance of aerosol from a hand-operated nasal pump spray has been assessed from gamma camera scans in ten normal subjects, following labelling of placebo sprays with 99Tcm labelled Teflon particles (mean diameter 2 micron). Aerosol was concentrated chiefly in the anterior part of the nose, but the area of deposition varied between subjects. No particles reached the lungs. A mean 56% of the dose was retained at the initial site of deposition 30 minutes after administration, while the remaining 44% of the dose had cleared to the nasopharynx. The initial partitioning of nasal pump sprays between ciliated and non-ciliated zones is relevant both for effective topical therapy of the nasal cavity, and for possible systemic drug delivery by the intranasal route.     

Nasal nitric oxide is independent of nasal cavity volume.

This study was performed to evaluate the relationship between nasal nitric oxide (NO) and changes in nasal cavity volume resulting from the topical application of xylometazoline and saline and between upright and supine posture. Nasal NO was measured using a fixed high flow technique that avoids contamination with lower airways NO. In nine healthy subjects nasal NO concentration was measured by a rapid response chemiluminescent analyzer. A tapered tube was inserted in one nostril, into which room air was insufflated to produce a constant flow of 100 mL/second; another tube was inserted into the opposite nostril for NO sampling (air exit side). Subjects were instructed to keep the vellum closed while NO was sampled through a sideport connected to the analyzer. Nasal cavity volume was measured by acoustic rhinometry from a segment of the acoustic pathway, 2 to 5 cm from the nostril. Nasal cavity volume and NO measurements were made at baseline, 15 minutes, and 60 minutes after intervention (administration of saline 0.9%, xylometazoline or posture changes on 3 consecutive days). Xylometazoline produced a significant increase in nasal cavity volume, together with a significant reduction in NO level at 15 and 60 minutes after intervention. In addition, the change from seated to supine position decreased the total nasal volume significantly, but without changes in nasal NO. No correlation was found between the magnitudes of changes in nasal NO and the changes in nasal volume. Topical application of xylomethazoline resulted in increased nasal cavity volume and reduced NO output. In contrast to previous published reports, a technique using high flow rate insufflation demonstrated an abscence of correlation between the magnitudes of changes in nasal NO and nasal cavity volume brought about by decongestant, saline, or posture.