Study on Mechanism of Local Heated Aerosol Therapy in Perennial Allergic Rhinitis

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1 Study on Mechanism of Local Heated Aerosol Therapy in Perennial Allergic Rhinitis Kazuo Sakurai, Kensei Naito, Kenji Takeuchi, Katsuhiko Komori, Hisayuki Kato, Syoji Saito Department of Otolaryngology, Fujita Health University, School of Medicine, Aichi To detect probable mechanisms of local heated aerosol inhalation in nasal allergy, we measured nasal resistance before and after house dust antigen challenge to the nasal mucosa in 13 patients with perennial allergic rhinitis treated with local hyperthermia for 2 weeks and in 15 untreated patients. Mean nasal resistance either on expiration or inspiration 15 min. and 8 hours after antigen challenge in treated patients was significantly lower than in untreated patients. We measured nasal resistance before and after histamine challenge to the nasal mucosa in 9 perennial allergic rhinitis patients before and after hyperthermial treatment and 6 voluntary healthy subjects. Mean nasal resistance right after histamine challenge either on expiration or inspiration in patients before treatment was significantly higher than in patients after treatment or healthy subjects. The frequency of sneezing due to histamine challenge to the nasal mucosa in patients after treatment was significantly lower than in patients before treatment, and no significant difference in frequency of sneezing was seen between patients after local hyperthermia and healthy subjects. Local heated aerosol therapy for more than 1 week, twice a day, may suppress both early- and late- phase allergic reaction and nonspecific hypersensitivity by histamine in the allergic nasal mucosa. Key words: hyperthermia, nasal allergy, nasal heated aerosol, nasal resistance Introduction The clinical efficacy on local heated aerosol therapy to nasal allergy has been reported1-4). Several therapeutic mechanisms of nasal hyperthermial aerosol acting on the allergic nasal mucosa are suspected4 6). The proposed mechanisms of the efficacy, however, have not been demonstrated until now. Naito et al.7) revealed that only a single dose of 10 min. exposure to heated vapor acted irritable in perennial nasal allergy patients though the warm and moist air was assumed to be a treatment of nasal allergy. The beneficial effectiveness of the heated aerosol to nasal allergy may not be due to normal autonomic nerve reflexes. To detect probable mechanisms of nasal hyperthermial aerosol inhalation in nasal allergy, we compared alterations of nasal resistance before and after antigen or histamine challenge to the nasal mucosa between the perennial nasal allergy patients treated with nasal heated aerosol exposure and untreated patients. Materials and Methods Experiment 1 Thirteen patients (6 males and 7 females, mean age of 26.6 years) with perennial nasal allergy to house dust treated with 10 min. heated aerosol inhalation, twice a day, for two weeks, as a treated group, and 15 untreated patients (7 males and 8 females, mean age of 26.2 years), as an untreated group, were examined for antigen challenge study. During the 2 weeks of heated aerosol therapy, the patients were given any other treatments. These patients had no other nasal diseases and no histories of nasal operation. In this antigen challenge study, house dust antigen paper disks (Torii Co., Ltd.) were placed on the anterior portion of the inferior nasal turbinate bilaterally. Unilateral nasal resistances were

口 measured by Rhinorheograph 鼻蒜き43(2), 2004 MPR-2100 manufactured by Nihon Kohden Co., Ltd. using active anterior rhinomanometry with a nasal nozzle during the period be- tween 10 min.

2 口 measured by Rhinorheograph 鼻蒜き43(2), 2004 MPR-2100 manufactured by Nihon Kohden Co., Ltd. using active anterior rhinomanometry with a nasal nozzle during the period be- tween 10 min. before and 8 hours after the antigen nasal challenge in patients. Total nasal resistance was calcu- lated from the equation of Ohm's law for parallel resistors for excluding the influence on nasal cycle. Values of total nasal resistance at the peak flow point during quiet breathing the nose were determined this study. through in We compared the alterations of nasal resis- tance between untreated and treated patients. Experiment 2: Nine patients (7 males and 2 females, mean age of 28.3 years) with perennial nasal allergy before and after the hyperthermia subjects for two weeks and 6 voluntary healthy (4 males and 2 females, mean age of 27.7 years) were examined for this nasal histamine challenge examination. Nasal resistance was measured before and after histamine nasal challenge according to the same Fig. 1 Skinar steam II manufactured by Esai Co., Ltd. manner of Experiment 1. Moreover, frequency of sneezing was counted after the histamine challenge in five of either on expiration or inspiration in patients before hy- the nine patients before and after treatment, and the 6 perthermial healthy subjects as a contrast. those in patients after treatment In this histamine chal- treatment was significantly higher than or healthy subjects as lenge study, 0.07m1 of 0.01% histamine (2-[4-limida- shown in Fig. 4 and Fig. 5 respectively. zolyl] solution was of sneezing due to histamine challenge to the nasal inu- squirted ethylamine, SIGMA Co., Ltd.) into the each nasal cavity with a portable in- tranasal spray manufactured by Nagashima Co., Ltd. Unpaired t-test cance in this study. age (t-test) was employed for statistical signifi- between the each group Co., Ltd. (Fig. 1) for local heated (43C) tween patients after local hyperthermia rhinomonometric by Esai And, no signifi- and healthy sub- results (luring any time course in Expi- ration I and 2. aerosol ther- Discussion the aim of these investigations Grossman et al.1), Ophir et al.3) and Yerushalmiet and consented to participate with the studies. al.4) reported the clinical effectiveness of heated nasal aerosol for symptoms of perennial allergic rhinitis. Results of heated (43t) Experiment 1: Topical use vapor to the nasal mucosa without any medicine, is a safe treatment for pregnant or hepatic dis- Mean nasal resistance either on expiration or inspiration 15 min. and 8 hours was significantly cant difference in frequency of sneezing was seen be- apy in all studies. And, all voluntary patients and normal subjects well understood after hyperthermia jects as shown in Fig. 6. There were no dropping out of were found in these nasal challenge researches. We employed Skynar steam II manufactured in patients lower than in patients before treatment. And, no significant differences in and sex (x2-lest) cosa The frequency after antigen challenge in treated patients was significantly lower than in untreated ease patients with allergic rhinitis. mechanisms Mean nasal resistance right after histamine challenge for the beneficial efficacy on heated mois- ture to allergic rhinitis have been elusive. The normal nasal mucosa spontaneously patients as shown in Fig. 2 and Fig. 3 respectively. Experiment 2: However, the certain changes the volume due to a reflex upon several stimuli and the rhythm of the autonomic nerve system is mainly regu- -(201)57-

3 Fig. 2 Mean values of nasal resistance on expiration before and after antigen challenge to the nasal mucosa in perennial nasal allergy patients treated with hyperthermia and untreated patients. Fig. 3 Mean values of nasal resistance on inspiration before and after antigen challenge to the nasal mucosa in perennial nasal allergy patients treated with hyperthermia and untreated patients.

4 Fig. 4 Mean values of nasal resistance on expiration before and after histamine challenge to the nasal mucosa in perennial nasal allergy patients before and after hyperthermia and normal subjects. Fig. 5 Mean values of nasal resistance on inspiration before and after histamine challenge to the nasal mucosa in perennial nasal allergy patients before and after hyperthermia and normal subjects.

5 Fig. 6 Frequency of sneezing after histamine challenge to the nasal mucosa in patients before and after local hyperthermial therapy and in normal subjects. lated by blood flow in the mucosa8). Ambient air-conditions, for example temperature and humidity, influence the alterations of the nasal passage9). Allergic nasal mucosa responds more to various ambient irritants10). Naito et al.7) reported that the resistances in perennial allergy patients were increased after a local heated moisturized aerosol stimulation, while there were no changes of nasal resistance in patients without the stimulation and in normal subjects either with or without the hyperthermial stimulation. According to these results, the beneficial effectiveness of the heated aerosol to nasal allergy may not be due to normal autonomic nerve reflexes. Other probable therapeutic mechanisms of nasal hyperthermial aerosol acting on the allergic nasal mucosa are suspected. It is possible that nasal lavage washes out antigens from the nasal cavity6), but heated stimulus is not required only for washing out by intranasal aerosol inhalation. On the other hand, histamine release from mast cell might be influenced by temperatures6), and 45t could significantly suppress the release in comparison with 37t11). Hyperthermia also could inhibit release of other newly generated mediators concerning late phase allergic reactions5). In our present study of nasal antigen challenge, local hyperthermial therapy for two weeks decreased nasal congestion due to antigen exposure to the allergic nasal mucosa in both early- and late-phases. It is considered that 10 min. topical use of heated (43) vapor to the allergic nasal mucosa, twice a day, for at least one week might diminish both earlyphase concerning preformed mediators, i.e. histamine and tryptase, release and late-phase concerning newly generated mediators, i.e. leukotrienes and prostaglandins, release. Then, it is suspected that the suppression of degranulation of mast cells in the allergic mucosa is one of possible mechanisms of exposure to local heated moisture vapor for at least one week. To determine whether hyperthermia actually suppress antigen-induced degranulation of mast cells, we propose further fundamental animal studies concerning inhibition IgE antibody dependent chemical mediators release from mast cell by hyperthermial (43t) stimulation. Furthermore, our present histamine challenge studies demonstrated that the local heated aerosol treatment suppressed congestion of nasal mucosa during earlyphase and frequency of sneezing in nasal allergy. There were no late-phase reaction after histamine challenge before and after heated aerosol treatment. No heated stimulation may reduce the sensitivity of the vasculature

6 and sensory nerve to inflammatory mediators2). We believe that local hyperthermia for perennial nasal allergy patient may suppress allergic reaction and consequently nonspecific hypersensitivity by histamine in the allergic nasal mucosa. Acknowledgments We would like to dedicate this paper to the late Dr. Sho Miyata (Department of Otolaryngology, Aichi Prefectural Hospital). References 1) Grossman J, Shyulan D, Porcella J: Treatment of seasonal allergic rhinitis with vapour induced nasal hyperthermia (Abstract). J Allergy Clin Immunol 81: 175, ) Narita S, Asakawa K, Kataura A: Local hyperthermia for allergic rhinitis in pregnancy (in Japanese with English abstract). Practica Otologica , ) Ophir D, Elad Y, Fink A, et al: Effects of elevated intranasal temperature on subjective and objective findings in perennial rhinitis. Ann Otol Rhinol Laryngol 97: , ) Yerushalmi A, Karman S, Lwoff A.: Treatment of perennial allergic rhinitis by local hyperthermia. Prc Nat Acad Sci USA 79: , ) Johnston SL, Price JN, Lau LCK, et al: The effect of local hyperthermia on allergen-induced nasal congestion and mediator release. J Allergy Clin Immunol 92: , ) Monger JL, Schild HO: Effect of temperature on the anaphylactic reaction. J Physiol 135: , ) Naito K, Miyata S, Baba R, et al: The alteration of nasal resistance before and after local exposure to heated aerosol in perennial allergic rhinitis. Rhinology 37: 66-68, ) Olsson P, Bende M: Influence of environmental temperature on human nasal mucosa. Ann Otol Rhinol Laryngol 94: , ) Salman SD, Proctor DF, Swift DL, et al: Nasal resistance: description of a method and effect of temperature and humidity changes. Ann Otol 80: , ) Proud D, Bailey GS, Naclerio RM, et al: Tryptase and histamines as markers to evaluate mast cell activation during the responses to nasal challenge with allergen, cold, dry air, and hyperosmolar solutions. J Allergy Clin Immunol 89: , ) Siraganian RP, Hazard KA.: Mechanisms of mouse mast cell activagtion for IgE-mediated Histamine release. J Immunol 122: , Reprint and correspondence Kazuo Sakurai, M.D. address: Department of Otolaryngology, Fujita Health University, School of Medicine 1-98 Kutsukake Toyoake, Aichi Japan Tel: Fax:

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