[RinoFlow.sup.TM] Nasal Wash and Sinus System as a mechanism to deliver medications to the paranasal sinuses: Results of a radiolabeled pilot study.

From the University of Pittsburgh Medical Center-Passavant Hospital, Pittsburgh.

Reprint requests: Kelly A. Lama, Respironics HealthScan Asthma and Allergy products, 908 Pompton Ave., Cedar Grove, NJ 07009-1292. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

This study was sponsored by Respironics Inc. of Cedar Grove, N.J.

Abstract

Direct delivery of medication to the sinuses with standard nebulizers is difficult to achieve. The nasal inhalation of aerosolized medications is dependent on the size of the particles and the pressure with which they are delivered; when the particles are too small or the pressure is too low, the drug cannot reach the sinuses. The ability of topical medications to treat sinus disorders can be improved if the medication could be delivered directly to the sinuses.

We tested the ability of the [RinoFlow.sup.TM] nasal aerosol delivery device to deposit aerosoldirectly to the paranasal sinuses. Five normal, healthy subjects used the device to administer technetium Tc 99m nasally. Nuclear scanning was used to detect deposition in the frontal and maxillary sinuses. Three subjects underwent additional testing after administration of a nasal decongestant.

Three of the five subjects showed some evidence of direct delivery to the sinuses, although deposition was not uniform or complete. Pretreatment with a decongestant had no apparent effect on subsequent technetium delivery. We conclude that the results of this study are promising and that further study is warranted.

Introduction

The ability to deliver medications directly into the sinuses could reduce the need for systemic medications and their possible untoward events. Direct delivery might also improve the effectiveness of traditional topical medications and lessen the severity of a wide variety of sinus-related symptoms and diseases.

The ability of nebulizers to deliver medications to the paranasal sinuses can be limited by insufficient particle size and low aerosol pressure. [1] sufficient particle size is essential to assure deposition in the sinuses, [2] and the speed with which the particles are delivered can determine how far through the sinuses they spread. [3] Particles smaller than 5 [micro]m are likely to be deposited in the lower airways. Deposition into the sinuses is best achieved when the aerosolized particles are 16 to 25 [micro]m in size and when the pressure gradient is sufficient according to Laplace's law. [4]

In a study of functional endoscopic sinus surgery combined with an initial topical antimicrobial treatment course and serial long-term monthly sinus antimicrobial lavage, Moss and King demonstrated a reduction in repeat sinus surgery in a population of cystic fibrosis patients who had chronic sinusitis. [5] The success of that regimen in relieving symptoms was apparent both from patient reports and from excellent compliance with the lavage maintenance program by most patients. The researchers concluded, "It seems possible that the ES SAL [endoscopic surgery with serial antimicrobial lavage] program may be applicable to other disease states predisposed to chronic refractory infectious sinusitis." Nevertheless, ESSAL still involves surgery, which could be avoided if nasal lavage could alleviate symptoms on its own.

The purpose of this study was to generate pilot data from which sample size calculations could be made for larger randomized trials. Our study was designed to determine whether aerosolized technetium Tc 99m-labeled normal saline could be deposited into the paranasal sinuses in just one treatment with a delivery device called the [RinoFlow.sup.TM] Nasal Wash and Sinus System.

Materials and methods

Device. The RinoFlow Nasal Wash and Sinus System (Respironics, Inc.; Cedar Grove, N.J.) consists of a portable, sealed, electric (115 or 230 V), lubricant-free, piston compressor and a micronizer chamber (figure 1). The chamber is connected to the compressor by flexible PVC tubing and is made of polycarbonate clear plastic that can be sterilized by boiling. The micronizer chamber is made up of four parts: an outer shell, an inner chamber, a baffle, and the body.

The RinoFlow system generates particles between 20 and 30 [micro]m in size. The device can deliver the particles at two different rates: 8 L/min with turbulent flow (position 1) and 4 L/min with laminar flow (position 2). The rate is controlled by adjusting the position of the outer shell (figure 2). In position 1, a space is formed between the inner and outer shells where mucosecretions can be caught. The delivery pressure of the micronized wash solution prevents the nasal drainage from entering the inner chamber and mixing with the nebulizing solution. A maximum of 40 cm (+/- 6 cm) of water pressure can be delivered to the upper airway at a rate of 8 L/min. In position 2, the gap is closed and the laminar jet reaches the paranasal os at a rate of 4 L/min. To enhance delivery to the paranasal os, patients are instructed to periodically close the opposite nostril, to keep their mouth closed, and to swallow while holding their breath. This maneuver creates a pressure gradient in the upper airway wherein the p ressure in the nasal cavity will be greater than the pressure in the sinuses. The difference in pressure will force the aerosol particles from the high-pressure area (the nasal cavity) toward the low-pressure area (the sinuses) until the pressures equalize.

Subjects. Subjects recruited for the trial were healthy men and women, aged 18 to 40. Women who were pregnant, nursing, or of childbearing potential were excluded. Other exclusion criteria were the presence of moderate to severe septal deviation; a history of seasonal allergies, nasal polyps, or sinusitis; the presence of cystic fibrosis; a history of cigarette smoking; recent use of any drug (prescription, over-the-counter, or illegal); and abnormal computed tomography (CT) results.

All subjects who initially qualified for the trial after telephone screening were scheduled for an ENT examination by an otolaryngologist. Following the ENT history and physical exam, subjects who were still eligible were scheduled for CT of the sinuses. A normal CT scan was required for participation in the study.

A total of 15 subjects passed the history and physical exam portion of the screening and underwent CT. Only five of these subjects had a normal CT result, and they were included in the final technetium trial. The subjects, all men, were aged 21 to 32 (mean: 27.2; SD: +/- 4.92).

Methods. On the day of their intervention, the five subjects reported to the nuclear imaging laboratory at the University of Pittsburgh Medical Center-Passavant Hospital. Initially, the subjects used the RinoFlow device in position 1 to wash the nasal cavity with a solution of buffered 0.9% normal saline. Both nostrils were washed. Subjects were then isolated in a radiation-safe room to proceed with the technetium Tc 99m trial. The technetium solution was compounded under strict nuclear guidelines and placed in the nebulizing chamber. Subjects nebulized the technetium into their nasal cavity with the RinoFlow in position 2. During nebulization of the technetium, subjects were asked to voluntarily occlude the untreated nostril and swallow. This "pinch and swallow" maneuver is similar to the Valsalva's maneuver to open blocked eustachian tubes during airplane decent; it is also called Politzer' s method to force increased pressure through small openings.

Following treatment of the nasal cavity with the technetium, subjects were asked to swallow a small amount of water to flush any excess technetium from the posterior oronasal pharynx. Four radioactive markers were placed on bony landmarks of the face, and a lead drape was placed over the nose to reduce the amount of excessive activity in the nasal cavity that reached the gamma camera detectors. A nuclear scan of the head and neck was then performed to determine whether any technetium had reached the paranasal sinus cavities.

Three of the five subjects underwent a second test that was similar to the first except that they received a single pretreatment nasal spray dose of the decongestant oxymetazoline HC10.05% prior to the technetium trial. It was hypothesized that opening the sinus passages would allow for better deposition.

Results

The results of the technetium trial are shown in the table. Subjects 1 and 5 were evaluated only once, without the oxymetazoline decongestant. Subject 1 showed evidence of paranasal sinus technetium deposition, and subject 5 did not. Subjects 2, 3, and 4 were evaluated with and without oxymetazoline. Subject 2 exhibited no evidence of paranasal sinus deposition with or without the decongestant; subjects 3 and 4 did demonstrate some evidence of sinus deposition both with and without oxymetazoline.

According to our findings, some degree of ventilation was seen in 60% of the subjects, although deposition was incomplete and inconsistent. Moreover, the administration of a single dose of decongestant did not improve the deposition of the technetium.

Discussion

This trial was designed as an observational study to determine whether technetium could be nebulized into the sinuses with the RinoFlow Nasal Wash and Sinus System. The five subjects who met the criteria for inclusion were carefully screened, and none had nasal pathology. Radioactivity was noted in the sinuses of three of the five subjects. This study did not measure the actual amount of technetium that reached the sinuses; the lack of quantification was a limitation inherent in the study design.

The use of an aerosol decongestant (oxymetazoline) by three of the subjects (subjects 2, 3, and 4) prior to technetium administration had no apparent effect on sinus deposition. The other two subjects (subjects 1 and 5) did not agree to be retested with oxymetazoline, thus we do not know if a single dose of the decongestant would have changed the outcome in subject 5, who did not manifest any evidence of sinus deposition. If our trial had included subjects who did have nasal pathology, we would have used a larger dose of nasal decongestant with the goal of reducing any swelling of the nasal mucosa prior to the nebulization of technetium. It is possible that a larger dose of nasal decongestant would have had a favorable impact on the results of this study. The best results might be obtained by first administering a nasal wash in the position 1 setting, then a topical decongestant, and finally nebulization of the drug with the RinoFlow device set to position 2.

During this study, significant gamma activity within the nasal cavity and nasopharynx completely obscured the regions of the sphenoid and ethmoid sinuses, thus limiting our evaluation of the degree of ventilation. We were aware of this limitation beforehand, but we felt there was no solution or alternative to overcome it. The use of iodinated radiographic contrast material would have been impractical because of its high viscosity, the osmolarity of most of the agents, and the potential for a severe allergic reaction. The use of a colored vital dye would have required an endoscopic confirmation of agent delivery to the paranasal sinuses, which we also considered to be impractical.

Although Hyo et a1 [3] reported that pretreatment of the nasal cavity with a decongestant can improve deposition to the sinuses, we did not find this to be the case in our study. However, the dosage of decongestant we used was less than optimal.

Passali et al reported that lavage with the RinoFlow device resulted in a reduction--and in some cases an elimination--of bacterial colonies on nasal swabs taken from patients who used the device to douche the nasal cavity. [1] However, they did not report on cost-effectiveness or long-term outcomes.

Our study provides initial pilot data on the use of the RinoFlow Nasal Wash and Sinus System as a drug delivery device. Its potential applications include the irrigation of paranasal cavities following sinus surgery, the delivery of enzymatic medications to cystic fibrosis patients, and the delivery of mucolytic solutions to dilute the thick, tenacious secretions that some patients experience. In an acute inflammatory sinus disease, the delivery of even a small amount of pharmaceutical agent might complement systemic anti-inflammatory and antibiotic therapy.

Based on the results of this feasibility study, we conclude that the RinoFlow Nasal Wash and Sinus System can deliver aerosol directly to the sinuses in some patients. Our work was intended to provide data from which larger, more generalized studies could be designed, and our results suggest that further study is warranted.

References

(1.) Passali D, Bellussi L, Ferrara Gorga A. The treatment of rhinopathies with the atomized nasal douche. Rivista Italiana di Otorinolaringologia Audiologia e Fontiatra 1995;45(4):1-3.

(2.) Christoforidis AJ, Tomashefski JF, Mitchell RI. Use of an ultrasonic nebulizer for the application of oropharyngeal, laryngeal and tracheobronchial anesthesia. Chest 1971;59:629-33.

(3.) Hyo N, Takano H, Hyo Y. Particle deposition efficiency of therapeutic aerosols in the human maxillary sinus. Rhinology 1989;27:17-26.

(4.) Bonsetti GL. Treatment of mucopurulent rhinosinusitis with a new method of nasal irrigation. L'Arcipedale S. Anna Di Ferrara 1993;43(4):1-4.

(5.) Moss RB, King VV. Management of sinusitis in cystic fibrosis by endoscopic surgery and serial antimicrobial lavage: Reduction in recurrence requiring surgery. Arch Otolaryngol Head Neck Surg 1995;121:566-72.

         Location of technetium Tc 99m deposition in the sinuses,
               with and without prior decongestant therapy.

    Without decongestant                With decongestant
Pt. Maxillary            Frontal        Maxillary         Frontal
 1  Right side           Both sides     Not tested        Not tested
 2  None                 None           None              None
 3  None                 Both sides [*] None              Both sides
 4  Both sides [+]       Both sides [+] Left side         Both sides
 5  None                 None           Not tested        Not tested


(*.)Deposition was also reported in the ethmoid sinus.
(+.)The original report indicated no deposition, but further review
demonstrated otherwise.