Research and Studies - Recognition by the medical community
Deposition of Aerosolized Particles
Deposition of aerosolized particles in the maxillary sinuses before and after endoscopic sinus surgery
Michele B. St. Martin, M.D.,* Cory J. Hitzman, B.Ch.E.,# Timothy S. Wiedmann, Ph.D.,# and Frank L. Rimell, M.D.§
ABSTRACT
Background: Recent studies suggest that topical therapy is beneficial in many conditions underlying chronic sinusitis. Current literature has documented low aerosolized particle deposition efficiency into the paranasal sinuses. Mathematical modeling suggests that three factors influence the deposition efficiency: particle size, pressure gradient, and size of the sinus ostium. Ostium size is the most dominant factor. Therefore, we sought to determine if maxillary antrostomy and ethmoidectomy would increase the deposition efficiency.
Methods: Five cadavers underwent pre- and post-operative scintigraphy after administration of Tc-99M. Images were obtained with a Υ-camera and regions of interest (ROIs) were drawn around the maxillary sinuses. Counts per minute in the pre- and post-operative ROIs were then compared using the t-test.
Results: Results indicated a significant increase in deposition of radioactivity in the maxillary sinuses in the postoperative state (p < 0.01. Conclusion: Topical therapy for chronic sinusitis may be more feasible in the postoperative population.
(Am J Rhinol 21, 196-197, 2007; doi: 10.2500/ajr.2007.21.2963)
Keywords: Aerosols, ethmoidectomy, maxillary antrostomy, medication delivery, nebulizer, sinusitis, topical administration, uncinectomy
Topical drug delivery is currently under investigation for many diseases of the nose and paranasal sinuses, including cystic fibrosis (CF), immotile cilia syndrome, and allergic fungal sinusitis. Chronic sinusitis related to these conditions is difficult to treat; endoscopic surgery alone is rarely successful. Topical therapy is theoretically appealing because it targets medication directly to its site of action, allowing for higher concentration in the sinuses as well as avoiding systemic side effects. Moss and King have documented a reduced need for surgery in CF patients treated with antimicrobial lavage; Desrosiers and Salas-Prato have shown improvements in quality of life, symptomatology, and endoscopic examinations after nebulization treatment for chronic sinusitis; and Raynor et al. have shown a reduction in edema and nasal polyps in CF patients treated with nasally inhaled dornase alfa.1-3 Topical therapy also has been used with success in various pulmonary conditions.
Nebulization is an effective method of delivering topical medication to the paranasal sinuses and has been shown to be superior to aqueous spray pumps in this regard.4-8 Current literature has documented a low particle deposition efficiency into the paranasal sinuses – Hyo et al. measured a rate of only 3% deposition into the maxillary sinuses in normal volunteers and plastic casts.7 Hyo et al. documented no difference in deposition efficiency between a plastic mold and healthy volunteers, implying that ciliary action and respiration play little to no role in particle deposition.7 This supports the use of cadavers in our study rather than volunteers.
Disagreements exists on the optimal particle size for deposition in the maxillary sinuses, with ranges given from 2 to 5 μm, and 16 to 25 μm.4-5,7 Hyo et .l.'s 7 mathematical modeling suggests that three factors influence deposition efficiency: particle size, pressure gradient between the nasal cavity and the sinus, and the size of the sinus ostium. Of these, ostium size is the most dominant factor. Therefore, we sought to determine if maxillary antrostomy and ethmoidectomy would increase the delivery of aerosolized particles into the maxillary sinuses.
MATERIALS AND METHODS
Five cadaver specimens underwent administration of aerosolized technetium 99M (Tc 99M) via a nasal pillow mask before and after endoscopic uncinectomies, bilateral maxillary antrostomies and anterior and posterior ethmoidectomies. The swirler (AMICI, Spring City, PA) nebulizer was used in this process. Each sinus served as its own control, thereby controlling the septal deviation. Maxillary antrostomies were all 1cm in diameter or larger and middle turbinates were left intact. To create airflow, a suction catheter was placed in the cadaver’s oropharynx during nebulization. Five-minute anterior-posterior static Υ-camera images were then obtained immediately after nebulization. (see Fig. 1 for representative images). Regions of interest (ROIs) were drawn around the right and left maxillary sinuses. Counts were recorded within each ROI, and counts within an identically sized ROI placed on a background region were recorded to control for varying amounts of background radiation. The difference between ROI counts and background counts was recorded as the pre- or postoperative count for the respective maxillary sinus.
The mass mean aerodynamic diameter (MMAD) of the particle emitted by the nebulizer was measured using a cascade impactor. Three trials of 5-minute nebulization were conducted and the mean number of counts per each range of particle sizes was calculated. The MMAD produced by the nebulizer was 1.008 μm, with the majority of particles ranging from 0.4 to 4.7 μm (see Fig. 2 for representative droplet size data from the first trial).
RESULTS
Pre- and postoperative counts for each maxillary sinus are listed in Table 1. A paired t-test was conducted that showed that the postoperative counts were significantly higher than preoperative counts. (p < 0.01, see Table 1 for data).
DISCUSSION
Our results indicate that there is a significant improvement in aerosolized particle deposition into the maxillary sinuses after maxillary antrostomy and ethmoidectomy. The results suggest that limitations in using topical therapy may not apply to the postoperative patient. Because most patients with chronic sinusitis eventually undergo endoscopic sinus surgery, topical therapy could potentially play a greater role in this set of patients.
One limitation of our study is that it was conducted in cadavers and not in live volunteers. Hyo et al.’s experiments with plastic casts seem to indicate that physiological respiration is not a significant factor affecting particle deposition; however, before making definitive conclusions about the rate of particle deposition in the postoperative patient, these results should be confirmed in volunteers planning to undergo sinus surgery. Such a study also could be used to calculate the amount of drug delivery to the paranasal sinuses in the postoperative patients.
In conclusion, we have shown that aerosolized particle deposition to the maxillary sinuses improves significantly in the postoperative state, suggesting the topical therapy is feasible for the postoperative patient with chronic rhinosinusitis. Additional studies are ongoing to elucidate the optimal range of particle size for nebulization, with the ultimate goal of determining the feasibility of using nebulized medications to treat refractory chronic sinusitis.
REFERENCES
- Raynor EM, Butler A, Guill A, and Bent JP 3rd. Nasally inhaled dornase alfa in the postoperative management of chronic sinusitis due to cystic fibrosis. Arch Otolaryngol Head Neck Surg 126:581-583, 2000.
- Moss RB, and 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 121:566-572, 1995.
- Desrosiers MY, and Salas-Prato M. Treatment of chronic rhinosinusitis refractory to other treatments with topical antibiotic therapy delivered by means of a large-particle nebulizer: Results of a controlled trial. Otolaryngol Head Neck Surg 125:265-269, 2001.
- Kondo H, Suzuki K, Takagi I, et al. Transitional concentration of antibacterial agent to the maxillary sinus via a nebulizer. Acto Otolaryngol 525(suppl):64-67, 1996.
- Negley JE, Krause H, Pawars S, and Reeves-Hoche MK. RinoFlow nasal wash and sinus system as a mechanism to deliver medications to the paranasal sinuses: Results of a radiolabeled pilot study. Ear Nose Throat J 78:550-554, 1999.
- Suman JD, Laube BL, and Dalby R. Comparison of nasal deposition and clearance of aerosol generated by a nebulizer and an aqueous spray pump. Pharm Res 16:1648-1652, 1999.
- Hyo N, Takano H, and Hyo Y. Particle deposition efficiency of therapeutic aerosols in the human maxillary sinus. Rhinology27:17-26, 1989.
- Durand M, Rusch P, Grandjon D, et al. Preliminary study of the deposition of aerosol in the maxillary sinuses using a plastinated model. J Aerosol Med 14:83-93, 2001.
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Acute bacterial sinusitis is an infection of the sinus cavities caused by bacteria.