Original Article. A 24-month-follow-up Study of Argon Plasma Coagulation of the Inferior Turbinate in Patients with Perennial Nasal Allergy

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1 J Med Dent Sci 2010; 57: Original Article A 24-month-follow-up Study of Argon Plasma Coagulation of the Inferior Turbinate in Patients with Perennial Nasal Allergy Akemi Iwasaki 1, Hisashi Tokano 2, Ryosuke Kamiyama 3, Yasuhiro Suzuki 1 and Ken Kitamura 1 1) Department of Otolaryngology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan 2) Department of Otolaryngology, Toride Kyodo General Hospital, Ibaraki, Japan 3) Department of Head and Neck Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan We report a 24-month-follow-up study of argon plasma coagulation of the inferior turbinate (APC) in patients with perennial nasal allergy. This was a retrospective study, in which 41 patients with perennial allergic rhinitis were treated by inferior turbinate reduction using APC. The grades of nasal stuffiness, rhinorrhea, sneezing and the daily activity impairment caused by these nasal symptoms were evaluated before and then 6, 9, 12, 15, 18, 21, and 24 months after APC, using a questionnaire graded on a four-point scale according to the Severity Criteria of Symptoms of Nasal Allergy issued by the Japanese Society of Allergology. Both nasal stuffiness and any daily activity impairment significantly improved 6 months after APC. Twenty four months after APC, 8/10 (80%) of the patients reported mild or no stuffiness and 9/10 (90%) of the patients reported mild or no daily activity impairement. Neither rhinorrhea nor sneezing were significantly improved during this study. Of the 41 patients 18 (43.9%) received no additional treatment. A second APC treatment was administered to 10/41 (24.4%) patients during f o l l o w - u p p e r i o d. A d d i t i o n a l c o n s e r v a t i v e medications were needed in 15/41 (36.6%) Corresponding Author: Akemi Iwasaki, MD. Dept. of Otolaryngology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Yushima, Bunkyo-ku, Tokyo, , Japan Tel: iwasaki.oto@tmd.ac.jp Received September 7;Accepted November 13, 2009 patients. Among the patients uncontrolled by conservative medical treatment, inferior turbinate reduction using APC provides significant relief in a 24-month-follow-up from nasal stuffiness and daily activity impairment. Key words: Argon plasma coagulation, perennial nasal allergy, conservative medical treatment, daily activity impairment, nasal stuffiness. 1. Introduction The major clinical symptoms of allergic rhinitis are characterized by sneezing, rhinorrhea, and nasal stuffiness. Conservative medical management is employed for these nasal symptoms, but for patients whose symptoms are not relieved by this approach, surgical intervention including inferior turbinate reduction using argon plasma coagulation (APC) is the treatment of choice. APC has been used on gastrointestinal lesions under endoscopy 1,2. Bergler et al. 3,4 first introduced APC treatment for inferior turbinate hypertrophy caused by various diseases such as allergic rhinitis, vasomotor rhinitis, chronic abuse of decongestant nose spray. Furthermore, a long-termfollow-up study of APC has been published 5,6, but there have so far been few studies evaluating the exclusive effectiveness of APC in patients with allergic rhinitis 7. Although Fukazawa et al. reported a 12-month-followup study of patients with perennial allergic rhinitis, they did not perform a statistical analysis. In our previous report, we studied the short-term effect of APC of the inferior turbinate in patients with perennial allergic

2 12 A. Iwasaki et al. J Med Dent Sci rhinitis and nasal stuffiness was significantly improved as early as 2 weeks after APC 8. The aim of this study was to update the previous data and to analyze the 24-month-follow-up data of APC of the inferior turbinate in patients with perennial nasal allergy. 2. Patients and Methods APC was administered to 131 patients with perennial allergic rhinitis whose symptoms were not alleviated by m e d i c a l t r e a t m e n t s i n t h e D e p a r t m e n t o f Otolaryngology, Graduate School of Tokyo Medical and Dental University between January 2002 and December Forty-one of 131 patients were followed up closely for more than 6 months after APC, and were the subject of this study. Eighteen other patients were excluded because they had one or multiple of the following conditions: the past history of the inferior turbinate reduction with APC or other instruments, severe nasal septal deviation which precluded effectiveness of APC, psychiatirc disease, or inadequate medical record for evaluation of APC. The 72 other patients were lost during the 6-month-followup period after APC. The patients of the study included 22 males and 19 females, ranging from 12 to 67 years (26.8 ± 13.7, mean ± S.D.) in age, expressing specific IgE antibodies (CAP-RAST) to both house dust (HD1) and house dust mites (Dermatophagoides pteronyssinus; serological scores, 35.6±32.3 and 39.8±34.1 IU/ml, respectively; normal range, <0.34 IU/ ml (SRL Co., Tokyo, Japan)). All the 41 participants were initially treated medically with antihistamines and/or glucocorticoid nasal spray for at least two weeks, but their nasal symptoms proved resistant to these treatments. The procedure of APC treatment has been previously described 8. Briefly, local anesthesia was induced by introducing a small piece of gauze that was soaked with 4% lidocaine and epinephrine (1:5000 dilution) into the nasal cavity. The laser was equipped with an orthogonal monopolar probe, a high-frequency voltage generator ICC-200 and an argon gas supply unit APC-300 (ERBE Elektoromedizin Co. Tübingen, Germany). The power setting was 30 W, and the argon gas flow was set at 0.8 L/min. During follow-up, additional medications and/ or a second APC treatment were administered at patient s request. Subjective findings including nasal stuffiness, rhinorrhea, sneezing and daily activity impairment caused by these nasal symptoms were graded on a four-point scale (severe, moderate, mild and none) according to the Severity Criteria of Symptoms of Nasal Allergy issued by the Japanese Society of Allergology (2005; Table 1) and they were compared before and then 6, 9, 12, 15, 18, 21, and 24 months after APC. Mann Whitney s U-tests were used to analyze the timedependent changes in the aforementioned parameters. Values of p < 0.01 were considered to be significant. The APC of the inferior turbinate has been already established as one of the standard therapy for patients with allergic rhinitis. The informed consent that was prepared in accordance with the institute guideline was obtained for this treatment and all procedures were in accordance with the ethical standards of the Helsinki Declaration. 3. Results 3.1. Numbers of patients Of the original 41 study participants, the number of patients examined before and then 6, 9, 12, 15, 18, 21, 24 months after the APC was 41, 35 (85.4%), 31 (75.6%), 28 (68.3%), 17 (41.5%), 14 (34.1%), 12 (29.3%), and 10 (24.4%) Additional treatment No additional treatment was performed in 18/41(43.9%) of patients during follow-up period. A second APC treatment was administered in 10/41 (24.4%) patients. Nine of 10 patients underwent a second APC treatment at 9-12 months after the initial APC, while the rest of patients received additional APC more than 12 months after the initial APC. Additional conservative medications, including anti-allergy drugs and/or nasal sprays were required in 15/41(36.6%) patients. An additional medication was started less than 6 months after the APC in 8/15 (53.3%) patients, 9-12 months after the APC in 6/15 (40.0%), and more than 12 months after the APC in 1/15 (6.7%) patient. Two patients were administrated a second APC after conservative medications Transition of the grades for nasal stuffiness Prior to the APC, 23/41 (56.1%), 11/41 (26.8%), 5/41 (12.2%), and 2/41 (4.9%) patients reported severe, moderate, mild, and no nasal stuffiness, respectively. Six months after the APC, 3/35 (8.6%), 5/35(14.3%), 9/35 (25.7%), and 18/35 (51.4%) patients reported severe, moderate, mild, and no stuffiness, respectively, indicating statistically significant relief from nasal stuffiness. Nine months after the APC, 3/31 (9.7%), 5/31 (16.1%), 10/31 (32.3%), and 13/31 (41.9%)

3 Argon Plasma Coagulation with Perennial Nasal Allergy 13 Table 1. Grading of nasal symptoms Nasal symptoms Severe Moderate Mild None Nasal stuffiness Rhinorrhea (blows per a day) Sneezing (attacks per a day) Impaired daily activities A lot of mouth Occasional mouth Without mouth No stuffiness >10 blows 6-10 blows 5-1 blows No blow >10 sneezes 6-10 sneezes 5-1 sneezes No sneeze Quite difficult Between severe and mild Not so much difficulty No difficulty at all patients reported severe, moderate, mild, and no stuffiness, respectively, still indicating statistically significant effect. Twelve, 15, 18, and 24 months after the APC, 21/28 (75%), 15/17 (88.3%), 12/14 (85.7%), and 8/10 (80%) of the patients reported either mild or no stuffiness, respectively (Table 2a) Transition of the grades for rhinorrhea. Prior to the APC, 13/41 (31.7%), 15/41 (36.6%), 7/41 (17.1%), and 6/41 (14.6%) patients reported severe, moderate, mild, and no rhinorrhea, respectively. Six months after the APC, 15/35 (42.9%), and 11/35 (31.4%) were reported mild and no rhinorrhea, respectively, which was not significant improvement. Thereafter, 9, 12, 15, 18, and 24 months after the APC, 20/31 (64.5%), 17/28 (60.7%), 12/17 (70.6%), 11/14 (78.6%), and 7/10 (70%) of the patients, respectively, reported either mild or no rhinorrhea but the effect was not statistically significant (Table 2b) Transition of the grades for sneezing. Prior to the APC, 4/41 (9.8%), 7/41 (17.1%), 16/41 (39.0%), and 14/41 (34.1%) patients reported severe, moderate, mild, and no sneezing, respectively. Six months after the APC, 0/35 (0%), 1/35 (2.9%), 14/35 (40.0%), and 20/35 (57.1%) patients reported severe, moderate, mild, and no sneezing, respectively, but the effect was not statistically significant. Thereafter, 9, 12, 15, 18, and 24 months after the APC, 29/31 (93.5%), 24/28 (85.7%), 16/17 (94.1%), 12/14 (85.7%), and 10/10 (100%) of the patients, respectively, reported either mild or no sneezing but the effect was not statistically significant (Table 2c). Table 2. Transition of nasal stuffiness, rhinorrhea and sneezing (a) Nasal stuffiness Grade before 6M* 9M* 12M 15M 18M 21M 24M Severe Moderate Mild None (b) Rhinorrhea Grade before 6M 9M 12M 15M 18M 21M 24M Severe Moderate Mild None (c) Sneezing Grade before 6M 9M 12M 15M 18M 21M 24M Severe Moderate Mild None

4 14 A. Iwasaki et al. J Med Dent Sci 3.6. Daily activity impairment in nasal symptoms. Prior to the APC, 9/41 (22.0%), 15/41 (36.6%), 12/41 (29.3%), and 5/41 (12.2%) patients reported severe, moderate, mild, and no daily activity impairment in nasal symptoms. Six months after the APC, 1/35 (2.9%), 2/35 (5.7%), 8/35 (22.9%), and 24/35 (68.6%) patients reported severe, moderate, mild, and no daily activity impairment, which was a statistically significant improvement (Table 3). Thereafter, 9, 12, 15, 18, and 24 months after the APC, 25/31 (80.6%), 22/28 (78.6%), 16/17 (94.1%), 13/14 (92.8%), and 9/10 (90%) of the patients, respectively, reported either mild or no daily activity impairment but the effect was not statistically significant. Table 3. Transition of impaired daily activities Grade before 6M* 9M 12M 15M 18M 21M 24M Severe Moderate Mild None * = significance 3.7. Surgical complications No bleeding was observed after the treatment in this study. All 41 patients showed crust formation 7 days after surgery, but none of them showed crust formation on a one-month clinical control examination. Postoperative nasal synechiae between the nasal septum and the surface of the inferior turbinate was observed in one patient without any subjective symptoms. 4. Discussion APC is a high-frequency electrocoagulation using ionized argon gas without contact with the tissue. The argon plasma energy penetrates the tissue only 1 to 3 mm deep with minimal thermal damage in the surrounding tissue since temperature hardly reaches above 100 with the argon plasma. In contrast, it reaches 500 with the conventional laser applications. Furthermore, APC was characterized by no carbonization, no precaution requirement such as protecting eye shields and goggles, and no bleeding which requires nasal packing after surgery 1-4,9. These advantages enable simple and safe surgical procedure. In otorhinolaryngology, APC has been applied for treatment of telangiectasis 9,10, tonsillectomy 11,12, resection of benign neoplasms of the laryngeal lesion 13 and hypertrophic nasal turbinates 3-6. It has been reported that the inferior turbinate reduction by APC alleviates nasal stuffiness caused by hypertrophic inferior turbinates in patients with allergic rhinitis, vasomotor rhinitis, and chronic abuse of decongestant nose spray 3-6. The beneficial effects have been demonstrated to last as long as 12 to 24 months 4,6. In contrast, very few studies have been performed to evaluate the effect of APC on rhinorrhea and sneezing except for nasal stuffiness in patients with allergic rhinitis. Furthermore, there has been only one study in which the long-term effect of APC on nasal symptoms was evaluated, but not statistically, in patients with allergic rhinitis 7. The short-term effect of APC on nasal symptoms was investigated in patients with allergic rhinitis. Nasal stuffiness and rhinorrhea were significantly improved 2 and 4 weeks after APC, respectively 8. To update these previous data, the present study investigated long-term follow-up effect of APC on nasal symptoms in patients with allergic rhinitis. Both nasal stuffiness and impairment of daily activities were significantly improved 6 months after the APC and these two symptoms remained none or mild in more than 80% of patients 24 months after APC. The significant improvement of nasal stuffiness and daily activity impairment has been demonstrated for the first time in patients with allergic rhinitis. In contrast, neither rhinorrhea nor sneezing were significantly improved 6-24 months after APC, while rhinorrhea was significantly improved 4 weeks after APC in a previous study 8. In summary, nasal stuffiness significantly improved as early as 2 weeks and lasted as long as 6 to 9 months, while rhinorrhea significantly improved 4 weeks after APC, but its improvement was not significant 6 months after APC. APC was re-administered in 10 patients in the present study, and 9 of 10 patients received a second course of APC during the period 9 to 12 months after the initial APC. Additional medication was given in 15 patients. Eight of them started medications less than 6 months after the initial APC. Taken together, patients whose main complaint was nasal stuffiness demonstrated early and long-lasting improvement and additional APC, if necessary, could be administered long after the initial APC. In contrast, the patients whose main complaint was rhinorrhea exhibited an improvement at an early period, but this improvement did not continue and they required additional medication at an earlier period after

5 Argon Plasma Coagulation with Perennial Nasal Allergy 15 APC. Because daily activity impairment, such as sleep quality, learning ability, productivity at work or school, and a quality of life were often impaired in patients with allergic rhinitis, they were one of the most important parameters for evaluating the severity of nasal symptoms 14,15. More than 80% of the patients with moderate or severe allergic rhinitis presented impaired activities, while only 40% with mild rhinitis complained of impaired activities 14. Nasal stuffiness, a common symptom related to allergic rhinitis, is closely associated with daily activity impairment 16,17. The significant improvement in nasal stuffiness as well as daily life activities obtained in the present study supported the close correlation between these two parameters. In the present study, 35 (85.4%) of 41 patients were examined 6 months after APC. Thereafter, over 70% patients failed to complete the study. The results obtained during the period extending from 6 months to 24 months after APC gave us limited value. Further study is therefore required to evaluate the long-term beneficial effect of APC on nasal symptoms. 5. Conclusion Based on both the previous and present study findings, a significant improvement of nasal stuffiness was obtained as early as 2 weeks and until 6 to 9 months after the APC in patients with allergic rhinitis who were not controlled by conservative medical treatment. Daily activity impairment significantly improved 6 months after APC and its improvement was present in 90% of patients 24 months after APC. In contrast, a significant relief from rhinorrhea was obtained at 4 weeks after APC, but such improvement was not significant based on the long-term follow-up. References 1. Grund KE, Storek D, Farin G. Endoscopic argon plasma coagulation (APC): first clinical experiences in flexible endoscopy. Endosc Surg Allied Technol 1994;2: Grund KE, Storek D, Becker HD. Highly flexible selfexpanding meshed metal stents for palliation of malignant esophagogastric obstruction. Endoscopy 1995;27: Bergler W, Riedel F, Götte K, et al. Argon plasma coagulation for inferior turbinate reduction. Ann Otol Rhinol Laryngol. 2000;109: Bergler WF, Sadick H, Hammerschmitt N, et al. Long-Term results of inferior turbinate reduction with argon plasma coaglation. Laryngoscope 2001;111: Ferri E, Armato E, Cavaleri S, et al. Argon plasma surgery for treatment of inferior turbinate hypertrophy: a longterm follow-up in 157 patients. ORL J Otorhinolaryngol Relat Spec 2003;65: Ottaviani F, Capaccio P, Cesana BM, et al. Argon plasma coagulation in the treatment of nonallergic hypertrophic inferior nasal turbinates. Am J Otolaryngol 2003;24: Fukazawa K, Ogasawara H, Tomofuji S, et al. Argon plasma surgery for the inferior turbinate of patients with perennial nasal allergy. Laryngoscope 2001;111: Tokano H, Maehara H, Nakamura H, et al. Short-term effect of argon plasma coagulation of the inferior turbinate in patients with perennial nasal allergy. Auris Nasus Larynx 2005 ;32: Bergler W, Riedel F, Baker-Schreyer A, et al. Argon plasma coagulation for the treatment of hereditary hemorrhagic telangiectasia. Laryngoscope. 1999;109: Bergler W, Sadick H, Gotte K, et al. Topical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia. Ann Otol Rhinol Laryngol ;111: Skinner LJ, Colreavy MP, Lang E, et al. Randomized controlled trial comparing argon plasma coagulation tonsillectomy with conventional techniques. J Laryngol Otol ;117: Ferri E, Armato E, Capuzzo P. Argon plasma coagulation versus cold dissection tonsillectomy in adults: a clinical prospective randomized study. Am J Otolaryngol. 2007;28: Bergler W, Hönig M, Götte K, et al. Treatment of recurrent respiratory papillomatosis with argon plasma coagulation. J Laryngol Otol. 1997;111: Bousquet J, Neukirch F, Bousquet PJ, et al. Severity and impairment of allergic rhinitis in patients consulting in primary care. J Allergy Clin Immunol. 2006;117: Marple BF, Fornadley JA, Patel AA, et al.; American Academy of Otolaryngic Allergy Working Group on Allergic Rhinitis. Keys to successful management of patients with allergic rhinitis: focus on patient confidence, compliance, and satisfaction. Otolaryngol Head Neck Surg 2007;136:S Craig TJ, McCann JC, Gurevich F, et al. The correlation between allergic rhinitis and sleep disturbance. J Allergy Clin Immunol 2004;114:S Young T, Finn L, Kim H. Nasal obstruction as a risk factor for sleep-disordered. The University of Wisconsin Sleep and Respiratory Research Group. J Allergy Clin Immunol 1997;99: S