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.     

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.     

Videoendoscopic analysis of nasal steroid distribution.

Topical corticosteroids are one of the main pillars in the treatment of nasal polyps. The exact topography of their intranasal deposition has not yet been adequately visualised. The intranasal distribution of a 1% sodium fluorescein solution applied with original Pulmicort Topinasal (budesonide) metered pump bottles was analysed by videoendoscopy. The study group included eight healthy subjects and ten patients who had undergone endonasal sinus surgery. Videoendoscopy was performed in the study group within the first minute after application of the fluorescein solution. Additionally the deposition pattern of Pulmicort Topinasal was analyzed using a nasal model. The examination showed that the majority of the substance is deposited on the anterior portion of the nasal septum and the head of the inferior turbinate. Only a small fraction actually reaches the middle meatus. The distribution is improved by application during the decongested phase of the nasal cycle, after use of vasoconstricting nasal drops and maintaining a spraying angle of 45 degrees upwards. The development of new delivery techniques and systems could improve the efficacy of intranasally administered corticosteroids and reduce the complication rate.     

The nasal distribution of metered dose inhalers

The intranasal distribution of aerosol from a metered dose inhaler has been assessed using a radiotracer technique. Inhalers were prepared by adding 99Tcm-labelled Teflon particles (simulating the drug particles) to chlorofluorocarbon propellants, and scans of the head (and chest) taken with a gamma camera. Ten healthy subjects (age range 19-29 years) each performed two radioaerosol studies with the inhaler held in two different ways: either in a single position (vial pointing upwards) or in two positions (vial pointing upwards and then tilted by 30 degrees in the sagittal plane). The vast majority of the dose (82.5 +/- 2.8 (mean +/- SEM) per cent and 80.7 +/- 3.1 per cent respectively for one-position and two-position studies) was deposited on a single localized area in the anterior one-third of the nose, the initial distribution pattern being identical for each study. No significant radioaerosol was detected in the lungs. Only 18.0 +/- 4.7 per cent and 15.4 +/- 4.1 per cent of the dose had been removed by mucociliary action after 30 minutes, and it is probable that the remainder had not penetrated initially beyond the vestibule. Since the deposition pattern was highly localized and more than half the dose probably failed to reach the turbinates it is possible that the overall effect of nasal MDIs is suboptimal for the treatment of generalized nasal disorders.     

A comparative distribution study of two procedures for administration of nose drops

The intranasal distribution of nose drops has been studied in 12 healthy subjects, comparing an administration followed by two rapid inhalations through the nose, with an administration followed by turning the head to five positions. Insoluble particles of human serum albumin labelled with 99Tcm were suspended in the liquid before administration. A significantly larger area (p less than 0.05) in the nasal cavity was covered by the labelled nose drops when the subjects used the turning-the-head procedure. It appears that this procedure gave a larger passive distribution of the particles. The differences were about 10 to 15% between 3 and 45 min after administration. Some particles were rapidly transported into the pharynx. The retention of the particles at the initial site of deposition did not differ significantly between the two procedures and about 50% of the particles seemed to have penetrated to the ciliated region in the main nasal passages and were cleared. The results indicate that the procedure for administration of the nose drops influences the distribution in the nasal cavity, but the clinical relevance should be studied with respect to the efficacy of the active drug in patients.     

Dexpanthenol—Nasenspray vs. Nasensalbe

BACKGROUND: Recent technical developments in metered pump systems allow the production and use of preservative-free nasal products. The aim of the current study is to compare the tolerability of a preservative-free dexpanthenol (5%) nasal spray with that of the established dexpanthenol (5%) nasal ointment, also without preservatives. The main outcome measure was in vivo mucociliary clearance. METHOD: Mucociliary clearance was assessed by saccharin migration time in 20 volunteers. Wash-out phases were 7 days and the spray or ointment was always applied 20 min before the saccharin test. The study was designed to test for non-inferiority. RESULTS: Saccharin migration time was slightly longer after ointment administration, however, these were not significantly different to nasal spray. The saccharin migration time showed a significant correlation with the age of the volunteers. The upper confidence limit of dexpanthenol nasal spray was markedly less than that of the ointment. Therefore, dexpanthenol nasal spray is at least equal to if not better than dexpanthenol nasal ointment. CONCLUSIONS: Due to its ease of administration, preservative-free dexpanthenol nasal spray offers a valuable therapeutic alternative.     

Filtration of Particulates in the Human Nose

This report reviews the current theories on the deposition of inhaled particulates in the human nose. The inhalation of particulates represents a challenge to the upper respiratory tract. The concentration of airborne particulates and pollutants varies between occupational and nonoccupational exposure. Regional deposition of potentially hazardous inhaled material determines the local and systemic toxicity. In vitro experiments using casting and molding techniques with water dye models or laser Doppler anemometry indicate that nasal airflow is determined by the size of the nasal valve and the turbinates. The main airstream during inspiration passes through the lower nasal passage. Filtration capacity of the human nose can be expressed mathematically or experimentally. In vivo experiments applying monodisperse or polydisperse aerosols during single or multiple respiratory cycles have shown by using microscopic or laser-optic identification that particles larger than 3µm have a maximum deposition in the anterior part of the nose (nasal valve). Particles smaller than 3 µm and larger than 0.5 µm are filtered by the nasal mucosa and transported by cilia propulsion to the nasopharynx. The filtration for particles smaller than 0.5 µm is low. They seem to pass easily into the lower respiratory tract. This knowledge has an impact on nasal septal surgery and rhinoplasty. By influencing the structure of the nasal valve and the lower turbinates, the filtration capacity of the nose can be significantly decreased.     

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.     

Balanced physiological saline in the treatment of chronic rhinitis

The effects of a special balanced physiological saline on nasal symptoms of 93 patients with chronic rhinitis were studied. The main diagnoses of the patients were allergic rhinitis, atrophic rhinitis and ozaena, rhinitis sicca, chronic sinusitis, nasal polyposis and postoperative condition after nasal surgery. The tested solution was administered by a simple metered dose pump. 85 (91%) of the patients reported beneficial effects of the tested solution on nasal symptoms. In addition, 22 (71%) of those patients who used continuous anti-allergic medication, mainly intranasal steroids, reported that the tested solution improved the efficacy of their ordinary drug. So the tested solution proved to be beneficial in humidifying atrophic or otherwise dry mucosa, douching crusty nose and as adjuvant therapy in the treatment of allergic rhinitis.     

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.     

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.     

Topical liquid nasal gel, its anatomical distribution and transport

The objectives of this study are: 1) to assess the anatomical distribution of a topical liquid nasal gel in patients with and without rhinitis using a metered dose nasal pump, and 2) to determine whether the distribution pattern is influenced by dosage and delivery technique. Thirty-nine volunteers were evaluated, 26 without nasal inflammation and 13 with rhinitis. Patients self-administered the nasal spray according to the specifications in one fossa and incorrectly in the other one (sniffing and double doses). The findings showed that the nasal gel delivered by spray did not penetrate beyond the inferior part of the middle turbinate, regardless of delivery technique (double dose with sniffing or single dose without sniffing) and the presence or absence of inflammation.     

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.     

Value of acoustic rhinometry for measuring nasal valve area

OBJECTIVE: To assess the validity of acoustic rhinometry for measuring nasal valve area in human subjects. STUDY DESIGN: A comprehensive study that compared acoustic rhinometry data with computed tomography findings from scans obtained perpendicular to the acoustic axis and perpendicular to the floor of the nose. METHODS: Fifty nasal passages of 25 healthy adults with no nasal disease were examined by acoustic rhinometry and computed tomography. In each case, the area of the nasal valve as measured by acoustic rhinometry was compared with the area calculations from computed tomography sections taken in two different coronal planes, one perpendicular to the acoustic axis and one perpendicular to the floor of the nose. Computed tomography slices perpendicular to the floor of the nose were obtained at two different locations, a specific distance from the tip of the nose and a specific distance from the anterior nasal spine. RESULTS: There was a significant correlation between the nasal valve areas determined by acoustic rhinometry and computed tomography when imaging was obtained perpendicular to the acoustic axis. In contrast, when scanning was obtained perpendicular to the straight axis of the floor of the nose, the correlations between the acoustic rhinometry and computed tomography data were weak. CONCLUSIONS: When any type of imaging is used for comparison with nasal valve areas determined by acoustic rhinometry, the cross-sections should be perpendicular to the acoustic pathway. The results of the study show that acoustic rhinometry is a valuable method for measuring nasal valve area.     

Ventilation and drug delivery to the paranasal sinuses: studies in a nasal cast using pulsating airflow

BACKGROUND: Although there is a high incidence of nasal disorders including chronic sinusitis, there is limited success in the topical drug delivery to the nose and the paranasal sinuses. This is caused by the nose being an efficient filter for inhaled aerosol particles and the paranasal sinuses being virtually non ventilated METHOD: The objective of this study was to visualize the efficiency of sinus ventilation in a nasal cast using dynamic 81mKr-gas imaging in combination with pulsating airflows. Furthermore, the efficiency of the deposition of radiolabelled aerosol was assessed. RESULTS: Pulsation increased ventilation efficiency of the sinuses more than fivefold and aerosol deposition efficiency more than twentyfold, compared to delivery without pulsation. Furthermore pulsation increased aerosol deposition in the nasal airways by a factor of three. Using pulsating airflow Kr-gas ventilation and aerosol deposition efficiencies increased with increasing sinus volume. Pulsating airflow resulted in a deposition of up to 8% of the nebulized drug within the sinuses compared to 0.2% without pulsation. CONCLUSIONS: The study demonstrates the high efficiency of a pulsating airflow in paranasal sinus ventilation and aerosolized drug delivery. This proves that topical drug delivery to the paranasal sinuses in relevant quantities is possible.     

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.     

Elevation of nasal mucosal temperature increases the ability of the nose to warm and humidify air

The nose functions to warm and humidify inspired air. The factors that influence these functions have been studied to a limited degree. We have developed a method for measuring the temperature and relative humidity of the air before and after nasal conditioning to study nasal function. In this experiment we studied the effects of raising the mucosal surface temperature by immersion of the feet in warm water. Six subjects (avg. age = 27.0 years) were randomized to immersion of the feet in 30 degrees C and 40 degrees C water. The nasal mucosal temperature increased significantly from the 32.2+/-1.3 degrees C during immersion in the 30 degrees C water to the 33.1+/-1.2 degrees C during immersion in 40 degrees water (p < 0.05). No significant difference in nasal volume was noted between the 30 degrees (17.8+/-4.5 cc) and the 40 degrees (17.7+/-5.3 cc) immersions. There was a significant increase in the conditioning capacity of the nose (as measured by total water content of inspired air) in response to cold-air challenge during the 40 degrees immersion (1669+/-312 mg water) when compared to the 30 degrees immersion (1324+/-152 mg water). From these data we deduce that warming of the nasal mucosa improves the ability of the nose to condition inspired air without a significant change in the volume of the nasal cavity.     

Comparison of once- versus twice-daily use of beclomethasone dipropionate aqueous nasal spray in the treatment of allergic and non-allergic chronic rhinosinusitis

The aim of the study was to assess the efficacy and safety of nasal aqueous beclomethasone dipropionate (BDP), 400 micro g/day, given via a metered pump in a once-daily or twice-daily regimen following a double-blind, parallel group design over a 12-week period. Adult patients (n=112) with allergic or non-allergic chronic rhinosinusitis recorded their nasal and ocular symptoms for the 7-day run-in period and for the first 4 weeks of treatment. At baseline and after 4 weeks the airways' resistance via active anterior rhinomanometry and the volume and area section via acoustic rhinometry were measured. Morning serum cortisol was measured at baseline and at week 12. Adverse events were to be reported at each visit. Of the 112 randomised patients, three did not enter the ITT analysis and another 13 in total discontinued the treatment. Significant improvements over the baseline were reported in both groups for the primary variable sum of nasal scores (-53.7% in the once-daily group and -59.7 in the twice-daily group), as well as for each nasal and ocular symptoms, without differences between the groups. Because of a wider variability than expected, the 95% confidence interval (C.I.) for the difference between the least square means exceeded the pre-defined limit of +/-10% of the reference mean. Similar improvements in both groups were also reported for the nasal airway patency's parameters. The total number of drug-related adverse events was 26 in the once-daily group and 32 in the twice-daily group, with most of the events consisting of local effects at the site of application. No signs of adrenal suppression were observed, and serum morning cortisol values did not significantly change. The once-daily BDP dosing (400 micro g/day) therefore has a similar efficacy and safety profile as the same daily dose given in a twice-daily regimen.     

Effects of endoscopic sinus surgery on nasal spray deposition using dye-based methods for humans and a human silicone sinonasal cavity model

ObjectiveWe have evaluated that the deposition patterns of corticosteroid nasal spray in the sinonasal cavity of both post-operated human cases, which were further compared with a computed tomography-based sinonasal airway model.MethodsFifty-one patients with chronic rhinosinusitis following an endoscopic sinus surgery were enrolled in this study. Nasal spray mometasone furoate hydrate (Nasonex®) containing 0.1% indigocarmine was applied to the patients' nasal cavities and the sinonasal cavity was observed by endoscopy and video documentation. A single plaster sinonasal model was used to quantify the sinonasal deposition of nasal sprays containing 10% red ink solution using 12 round paper strips.ResultsThe predominant areas of the spray deposition of the operated sinonasal cavities were recognized in the ethmoid sinus and the olfactory cleft in the human study. The droplets were mainly deposited in the inferior turbinate followed by the posterior part of the ethmoid sinus, the olfactory cleft, and anterior part of the ethmoid sinus in a sinonasal model.ConclusionThe corticosteroid nasal spray efficiently reached the olfactory cleft and the ethmoid sinus in post-operative conditions, which was demonstrated by post-operated human cases and a computed tomography-based sinonasal airway model.     

局部糖皮质激素对慢性鼻炎患者鼻腔菌群及pH值的影响

目的观察糖皮质激素鼻喷剂对慢性单纯性和慢性肥厚性鼻炎患者鼻腔菌群(需氧菌及真菌)及酸碱度的影响。同时评价其临床疗效。方法对42例慢性单纯性和慢性肥厚性鼻炎患者单纯接受局部糖皮质激素鼻喷剂(布地奈德,BUDESONIDE,商品名:雷诺考特)治疗8周(256ΜG/D),检测其治疗前后鼻腔菌群(需氧菌及真菌)分布情况、PH值及症状体征分级记分。结果①鼻炎组42例标本中,治疗前细菌检出率为88%,共检出需氧菌53株,分别归7属9种;治疗后检出率为90·47%,检出需氧菌46株,分别归8属10种;需氧菌群总体分布结果和同种细菌配对样本的统计结果显示,治疗前后差异无统计学意义(Χ2=0·416,P>0·05);②治疗前后的真菌培养均为阴性;③鼻炎组治疗后鼻腔黏液PH值(X-±S)为7·70±0·23,与治疗前的7·90±0·39相比,明显下降(T=2·72,P<0·05);④症状评分中治疗后与治疗前相比较差异均有统计学意义,而体征评分治疗前后对比则无明显变化。结论糖皮质激素鼻喷剂局部应用8周是比较安全的,一般不会引起鼻腔需氧菌群的改变和真菌生长,可以部分纠正慢性单纯性和慢性肥厚性鼻炎患者鼻腔黏液PH值,改善患者的临床症状。