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.     

Preparation of nose for nasal endoscopy: cotton pledget packing versus topical spray. A prospective randomized blinded study

During nasal endoscopy it is essential to have proper visualization of structures with minimal discomfort to patient and surgeon. For this it is essential that the nose is well prepared before the procedure. The main objective of the study is to compare and evaluate the efficacy of cotton pledget packing versus topical sprays in preparation of nose for nasal endoscopy. The method includes prospective randomized blinded study on 100 patients. Patients were randomly divided in two groups. In first group the nose was packed with 4% lignocaine with xylometazoline nasal drops and in the other group it was prepared with 10% lignocaine topical spray and xylometazoline nose drops. Following the procedure, patient and the surgeon were asked a pre-formed questionnaire to know their experience during endoscopy. It was observed the packing group required more preparatory time as compared to the spray group. The group which was packed had less discomfort, less pain while endoscopy. The visualization of structures was significantly better in the packed group. Eight patients in the packed group did have some mucosal bleed during the process of packing which was not seen in the spray group. Both methods of preparation have merits and demerits but in terms of discomfort, pain during procedure and visualization of structure, packing of nasal cavity with 4% lignocaine and xylometazoline drops is better than spraying of nose with 10% lignocaine and xylometazoline drops.     

Blood flow measurements in rabbit sinus mucosa. A comparison between fluorescein flowmetry and blood flow measurements with microspheres and Rb86Cl

The blood flow of the sinus mucosa was studied in 14 rabbits of the New Zealand White strain. The blood flow was determined by fluorescein flowmetry and the values were compared with those obtained from the same sinus mucosa with use of Sn113 radioactively labelled microspheres and with Rb86Cl. One sinus cavity in each animal received nose drops prior to the blood flow measurement. The blood flow index in the sinus mucosa was 0.039 +/- 0.019 density units Xs-1 and was significantly reduced to 0.016 +/- 0.011 density units Xs-1 by administration of nose drops. Blood flow in the sinus mucosa was 1.0 +/- 0.53 ml X min-1 X g-1 as measured with microspheres and 0.52 +/- 0.12 ml X min-1 X g-1 with the Rb86Cl method. Following administration of nose drops the values were reduced to 0.29 +/- 0.13 and 0.22 +/- 0.07 ml X min-1 X g-1 respectively. There was a significant difference in blood flow obtained with the Rb86Cl and microsphere methods in the sinus mucosa without decongestion. This might be explained by possible shunting of blood in the mucosa due to hyperaemia caused by the surgical trauma to the sinus.     

Distribution of inhaled aerosol using nasal nebulizer

In this paper, we examined distribution and deposition of inhaled 99mTc aerosols in human respiratory tract, nebulization equipment and expired aerosols. Jet nebulizers were used and aerosols were inhaled through the nose. Results were as follows: 1. On normal breathing, deposition rate of human respiratory tracts in normal subjects were 22% of total dosage and there was no difference from sinusitis group. But, deposition rate of nasal cavity was higher than in sinusitis group normal in group. 2. In normal subjects, there was no influence of breathing pattern to deposition rate of nasal cavity. 3. Distribution of the lung was significantly increased on deep breathing in both groups. 4. Residual volume of nebulizer bottle were about 50% of total dosage.     

An evaluation of the best head position for instillation of steroid nose drops

Steroid nose drops are used frequently to treat rhinosinusitis and nasal polyposis. The middle meatal area is of key importance in the pathophysiology of these conditions. This study assesses which of three head positions commonly used to instil nose drops resulted in the highest coverage of this area. Discomfort levels were also studied using a visual analogue scale for each position. Five volunteers were studied in: (i) head back (HB); (ii) head forward and down (HFD); and (iii) lying head back (LHB) positions. Betamethasone nose drops, dyed with fluorescein, were instilled into each nostril and the distribution was studied endoscopically. The middle meatus area distribution was highest in the LHB position (55.51%), followed by HFD (31.55%) and HB (6.87%) positions. Comparison of distribution between HB and LHB (P = 0.002) and between HB and HFD (P = 0.045) was statistically significant. The HFD position was most uncomfortable (mean discomfort score 8.8) whereas the HB (2.4) and LHB (2.6) were similar. The LHB would, therefore, appear to be the most suitable position for instillation of steroid nose drops.     

鼻中隔偏曲者鼻腔结构自适应改变的特征分析

目的 对10例鼻中隔偏曲者及20例健康北方人的鼻腔结构进行三维重建,将二者气流流场进行数值模拟,分析二者鼻腔气道气流流场特征,探讨其与鼻腔结构和功能之间的关系.方法 根据10例鼻中隔偏曲者和20例健康人的鼻腔CT影像,应用表面重建的方法对鼻腔气道进行三维重建,用有限元法对气流进行数值模拟,分析二者鼻腔气道气流流场特征.结果 从模拟的速度云图得出鼻中隔偏曲者通过双侧鼻腔的气流量以气道宽敞侧鼻腔为主,以总鼻道中部最为明显.健康人鼻腔气流量以一侧鼻腔为主,以总鼻道中部、总鼻道下部为明显.从模拟的压强云图得出鼻中隔偏曲者在鼻中隔偏曲最为明显处气压下降最快,占气道总压强差值的71.36%;健康人于鼻阈处气压下降最快,占气道总压强差值的58.78%.鼻中隔偏曲者鼻腔气道阻力较健康人增大.结论 数字化三维重建鼻腔气道模型可反映鼻腔气流通道的基本特征,可用于分析因鼻腔解剖结构异常而导致的鼻腔空气动力学特征改变,本实验初步证明鼻腔结构自适应功能的存在,为鼻腔自适应模型的建立打下基础.     

Particle deposition in the nose related to nasal cavity geometry

A number of studies have been made to characterise the deposition-pattern of inhaled airborne particles in the nose. Common to all results has been considerable differences in deposition fractions between normal human subjects. It was the aim of the current study to improve our understanding of individual differences in nasal deposition of inhaled particles. Depositions were measured in ten adult normal subjects and were related to dimensional measurements by acoustic rhinometry. Five litres of a polydisperse aerosol (MMAD = 0.7 micron, sigma g = 1.7) were inhaled through one nostril only during 5 inspirations with flows of 10, 20, and 30 L/min with decongested mucosa. Increasing flow was found to increase the fraction deposited in the nose, while there was an inverse correlation between nasal deposition fraction and minimum cross-sectional area of the nasal cavity (Amin). Information based on acoustic rhinometry measurements significantly reduced the amount of unexplained variation between subjects in nasal deposition fraction. We conclude that an estimate of maximum linear air velocity, calculated as airflow divided by Amin, was the best single predictor of nasal deposition fraction, which was found to increase with increasing air velocity raised to a power of approximately 4/3.     

Inhibitory effects of facemasks and eyeglasses on invasion of pollen particles in the nose and eye: a clinical study

The incidence of Japanese cedar pollinosis is estimated to be about 13% of the Japanese population. In Japan it is generic to wear a facemask and eyeglasses to prevent pollen inhalation. We examined the usefulness of a facemask and eyeglasses in cooperation with volunteers. The number of pollen particles in the nasal cavity and on the conjunctiva was unchanged by wearing a facemask and eyeglasses. However, the pollen invasion rate was lower in subjects with a facemask and eyeglasses than in subjects without a facemask and eyeglasses. The decrease in pollen invasion rate in the nasal cavity due to wearing a facemask was statistically significant. This suggested that wearing a facemask has a protective effect on pollen invasion to the nose. The pollen invasion rate in the nasal cavity and on the conjunctiva was increased with increases in the wind speed. It may be difficult to avoid pollen even when wearing a facemask and eyeglasses when the wind speed is high. Further study is required to clarify the relationship between the amount of allergens and clinical symptoms.     

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     

Detection of particles within the nasal airways before and after nasal decongestion

Cleansing of the air is one of the most important functions of the nose. The aim of this investigation was to determine the influence of decongestion of the nasal mucosa with xylometazoline on the intranasal particle deposition at different sites of the nasal cavity. During respiration of an aerosol of starch particles, the non-deposited particles in the air were laseroptically detected in 10 healthy volunteers by a transnasally placed suction probe at different locations within the nasal cavity. The anterior nasal segment was the main area of intranasal particle deposition before and after decongestion of the nasal mucosa. Particle deposition after nasal decongestion was not significantly different from the values before application of xylometazoline. Decongestion of the nasal mucosa and increase in nasal cavity diameter seems not to influence particle deposition of inhaled and exhaled air within a short period after onset of the maximal decongestive effect of xylometazoline.     

加味玉屏风散对变应性鼻炎鼻粘膜中P物质作用的实验与临床观察

目的：研究加味玉屏风散对变应性鼻炎鼻粘膜中P物质的影响。方法：变应性鼻炎动物模型用甲苯－2，4－二异氰酸酯（toluene-2,4-diisocyanate,TDI)致敏法制作。经鼻腔给予加味玉屏风散后，作鼻粘膜组织病理学和P物质免疫组织化学的观察。临床变应性鼻炎患者的治疗也用加味玉屏风散经鼻腔给药，给药前后采用放射免疫法测定鼻分泌物中P物质的变化。结果：动物治疗组鼻粘膜细胞中所表达的P物质明显减少，对照组中明显啬 ，临床患者用药前后鼻分泌物中P物质含量的比较有显著差异。结论：加味玉屏风散能减少鼻粘膜细胞内P物质的含量，及鼻分泌物中P物质的含量，从而达到治疗变应性鼻炎的目的。     

Vascular effects of phenylpropanolamine on human nasal mucosa

The duration of the decongestant effect of phenylpropanolamine 2.5% as nose drops as well as the effect of the drug on nasal mucosal blood flow was studied in man. The nasal patency was significantly improved for up to three hours in patients with nasal congestion, while no effect on nasal mucosal blood flow was achieved. These results were discussed in relation to other more long-lasting nose-drops with blood flow-reducing effects.     

Breath actuated device improves delivery to target sites beyond the nasal valve

OBJECTIVES: The objective was to compare nasal deposition patterns achieved with a conventional hand actuated spray pump and a novel breath actuated bidirectional prototype device housing the same spray pump (OptiMist, OptiNose AS, Oslo, Norway). STUDY DESIGN AND METHODS: The bidirectional delivery device exploits the posterior connection between the nasal passages persisting when the velum automatically closes during oral exhalation. The deposition and clearance patterns achieved with the two devices were compared in nine healthy subjects by scintigraphy after administration of Tc-aerosols. RESULTS: Compared with traditional spray pump delivery, the OptiMist device provided significantly (P < .004) larger initial and cumulative deposition (area under the deposition vs. time curve) in the upper posterior segment of the nasal passage, housing the sinus ostia and the olfactory region, and significantly lower deposition (P < .004) in the anterior segment, lined by nonciliated squamous epithelium. Furthermore, intersubject reproducibility of the initial and cumulative deposition was higher for the OptiMist device both in the upper posterior segment and the entire nose. CONCLUSIONS: Compared with a spray pump, the novel breath actuated bidirectional device provides significantly larger deposition in the clinically important regions beyond the nasal valve and reduced anterior deposition. These striking differences provide new opportunities for improved therapy of chronic rhinosinusitis and polyposis as well as extended use of the nose for delivery of drugs from the nose into the brain.     

Physiological change in nasal patency in response to changes in posture, temperature, and humidity measured by acoustic rhinometry

BACKGROUND: Acoustic rhinometry has been used to assess nasal patency and to calculate nasal cavity volume. This study used acoustic rhinometry to assess changes in nasal patency after alterations in posture, unilateral mechanical obstruction, temperature, and humidity. METHODS: Eight healthy adult volunteer subjects underwent acoustic rhinometry during the following conditions: (1) sitting position (control), (2) supine position, (3) left lateral recumbent position, (4) nostril unilaterally mechanically blocked, (5) ice pack on neck, (6) drinking cold water, (7) drinking hot water, (8) nasal nebulizer, and (9) oxymetazoline decongestant. RESULTS: Two distinct patterns emerged based on the total nasal cavity volumes in response to the decongestant. Subjects with initial unilateral nasal cavity volumes near the mean had an expected increase in total volume after the topical decongestant administration. There were two subjects with initial volumes of 1 SD above the mean that had a paradoxical decrease in total volume in response to the decongestant. In all subjects, there was a significant decrease in the volume of each of the nasal cavities in response to ingestion of hot water at 1 minute. There was a significant decrease in the volume of the smaller of the two nasal cavities in response to nebulizer treatment and hot water ingestion at 5 minutes. Total nasal cavity volume changes were not significant for any of the variables. CONCLUSION: Changes in nasal cavity volumes were detected by acoustic rhinometry after alterations in posture, unilateral mechanical obstruction, temperature, and humidity. Nebulizer treatment and hot water ingestion caused a significant decrease in nasal volume. The nose of a healthy patient was able to adapt to environmental and physiological changes to maintain a consistent total nasal volume within 15 minutes.     

不同部位和大小的鼻中隔穿孔对鼻腔气流影响的数值模拟分析

目的运用数值模拟的方法探讨不同部位和大小的鼻中隔穿孔对鼻腔气流的影响。方法选取2名健康成年人的鼻腔CT数据,例1为45岁男性,例2为36岁女性,分别构建出不同部位(前端低位、中部低位、后端低位和前端高位)和尺寸(直径分别为10 mm和5 mm)的鼻中隔穿孔的鼻腔气流模型,数值模拟分析不同部位和大小的鼻中隔穿孔鼻腔数值模型的鼻腔容积、鼻腔壁面积、压强、鼻阻力、温度、气流速度、壁面剪切力、双侧鼻腔气流分配比、涡流等情况。分别将鼻阻力和气流温度差与鼻腔壁面积作Pearson相关性分析。结果在压强和鼻阻力方面,位于前端低位且较大尺寸的鼻中隔穿孔对局部的压强梯度影响更明显;前中部低位的鼻中隔穿孔可导致鼻腔阻力增加。在温度方面,前端低位和高位较大尺寸以及前端高位较小尺寸的鼻中隔穿孔对局部温度影响更明显;位于前端且具有较大尺寸的鼻中隔穿孔模型的鼻加热效率低于正常模型;前鼻孔至鼻中隔后缘的温度差与鼻腔壁面积之间存在正相关关系(例1和例2的R2值分别为0.69、0.41,P值均<0.01)。在气流平均速度方面,位于鼻腔前端低位和高位的不同尺寸穿孔相对于其他部位穿孔,对鼻腔局部的气流平均速度影响更明显。在气流的分配和涡流方面,前中部低位的鼻中隔穿孔可使原本气流分布不对称的双侧鼻腔内的气流分布更加趋于不均衡;位于鼻腔前端和中部的穿孔较鼻腔后端的穿孔会导致更加明显的涡流分布。结论鼻中隔穿孔所造成的影响与其发生的部位和大小有关,偏前端和较大的鼻中隔穿孔相对于偏后端和较小的穿孔对鼻腔内压强、鼻阻力、温度调节、气流分配等方面表现出更多的负面影响。     

Measurements of the air conditioning capacity of the nose during normal and pathological conditions and pharmacological influence

A simple method is introduced for measuring the air conditioning capacity of the nose. A flow of 8 1/min dry air is introduced by a catheter into the nasopharynx, while 5 1/min is sucked out from the investigated nasal cavity through a psychrometer. The additional 3 1/min passes down into the pharynx, thus reducing the intermingling with expiratory air. By using CO2 as a tracer, this error was found to be maximally 15% and often about 1%. The three different enthalpy factors: increase in enthalpy of dry air, vaporization, and increase in enthalpy of water vapour, were calculated separately and the vaporization was found to be the dominant factor. The calculated total supply of humidity showed that the method presented causes at least a slight stress on the humidifying capacity. Pharmacological studies have shown that subcutaneously injected atropine decreased the total enthalpy and that of water vapour, while nasal administration of oximetazoline also decreased the total enthalpy. Nasal administration of homatropine or pilocarpine had no effect on the air conditioning. In comparison with normal subjects, those with vasomotor rhinitis had an increased enthalpy of the air, while the same enthalpy factor was reduced in cases with atrophic rhinitis. Laryngectomized patients had no significant difference in the air conditioning capacity of the nose in relation to normal subjects, while patients operated with partial maxillectomy had a considerable reduction in vaporization and total enthalpy.     

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.     

Heating of air in the nasal airways in patients with chronic sinus disease before and after sinus surgery

The main goal of this study was to determine the influence of sinus surgery on the heating of inspired air in the nose. Intranasal temperature values of 22 patients with chronic sinus disease were measured after inspiration at different locations in the nasal cavity. Measurements were done before and 6-8 weeks after sinus surgery. The patients were compared to 22 healthy control subjects. Nasal airway temperature did not differ between the two study groups at any location in the nasal cavity. Nasal decongestion was without significant influence on temperature values in the patients and the volunteers. There was no significant difference of nasal airway temperature before and after sinus surgery. Even after sinus surgery the main area of heating of inspired air seemed to be the anterior part of the nose. Sinus surgery in patients with chronic sinus disease does not seem to influence heating of air in the nasal cavity.