台灣耳鼻喉頭頸外科雜誌 The Journal of Taiwan Otolaryngology Head and Neck Surgery 中華郵政台北誌字第 45 號執照登記為雜誌交寄 (Publisher) (Fei-Peng Lee) (Editor-in-Chief) (Tien-Chen

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1 台灣耳鼻喉頭頸外科雜誌 The Journal of Taiwan Otolaryngology Head and Neck Surgery 中華郵政台北誌字第 45 號執照登記為雜誌交寄 (Publisher) (Fei-Peng Lee) (Editor-in-Chief) (Tien-Chen Liu) (Associate Editors) ( ) (Tuan-Jen Fang) (Ching-Yin Ho) (Hung-Ching Lin) (Yen-Liang Chang) (Editors) ( ) (Official Secretary) (Hsin-Te Hsu) (Managing Editor) (Show-Chi Cheng) (Editorial Assistant) (Ya-Chi Lin) (Editorial Office) F-5 (507 ) Taiwan Otolaryngological Society Room 507, 5F-5, 6 Heng Yang Road, Taipei 100, Taiwan [email protected] Homepage TEL (02) FAX (02) (02) ( )

2 2011 台灣鼻炎臨床指引編訂小組 召集人兼主編 : 方深毅 ( 國立成功大學附設醫院 ) 執行編輯 : 戴志展 ( 中國醫藥大學附設醫院 ) 編審委員 :( 依姓氏筆畫排列 ) 江榮山 ( 台中榮民總醫院 ) 許志宏 ( 台北榮民總醫院 ) 黃弘孟 ( 台北市立聯合醫院 ) 黃啟哲 ( 財團法人林口長庚紀念醫院 ) 葉德輝 ( 台灣大學附設醫院 ) 盧盈州 ( 財團法人天主教聖馬爾定醫院 ) 戴志峰 ( 高雄醫學大學附設醫院 ) 編輯顧問 :( 依姓氏筆畫排列 ) 何青吟 ( 台北榮民總醫院 ) 李達人 ( 廈門長庚醫院 ) 林清榮 ( 西園醫院 ) 徐茂銘 ( 台灣大學附設醫院 ) 劉嘉銘 ( 台灣大學附設醫院 )

3 目錄 CONTENTS...01 Sheen-Yie Fang Definition and Classification of Rhinitis Epidemiology and impaction of quality of life of rhinitis Po-Hung Chang, Chi-Che Huang, Ta-Jen Lee Mechanism of Rhinitis Chih-Feng Lin, Te-Huei Yeh Clinical manifestation and diagnosis of rhinitis Complications of rhinitis Allergen avoidance and education of rhinitis...32

4 ...33 Kai-Li Liang and Rong-San Jiang Allergy Immunotherapy Pharmacologic treatment of rhinitis Drug-induced rhinitis Allergic Rhinitis and Asthma Rayleigh Ping-Ying Chiang, M.D., M.M.S. Rhinitis and Sleep-Disordered Breathing...77

5 序 台灣鼻炎臨床指引編訂小組由 1997 年的首版到 2002 年的修定版至今也已多年了, 當時林清榮主任鑑於國內無一標準之臨床指引, 故策劃編訂之, 對於國內鼻科界之提昇貢獻良多 三年前幾位鼻科的同好們聚集在一起, 除了致力於鼻科之發展及再教育以外, 也有感於第二版的指引, 已八年未以更新, 為了延續立意, 鼻科同好會重新啟動 台灣鼻炎臨床指引 之編訂工作 歷經年餘, 多次的聚會討論 修改, 終於定稿 非常感謝各位成員先進的努力與貢獻, 當然更要謝謝前輩們的指導與典範 此指引的內容含括了鼻炎的定義 分類 流行病學 致病機轉 過敏性鼻炎及非過敏性鼻炎的診治等等 標題 大綱雖似, 但究其內容, 均已加入新的資訊及國內學者之寶貴經驗, 藉此, 期望對國內鼻炎之治療品質能有效提昇 召集人兼主編方深毅謹序中華民國一百年七月

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7 (1) 方深毅 摘 要 1994 key words: rhinitis, definition, classification ( ) 定義 1994 (Rhinitis) Coryza 1994 International Consensus Report(ICR) rhinitis is defined as inflammation of the lining of the nose, characterized by one or more of the following symptoms: nasal congestion, rhinorrhea, sneezing and itching 1 Lund International Rhinitis Management Working Group 分類 (Allergic rhinitis, AR) (Non-allergic rhinitis, NAR) (antigen antibody reaction) (cell-mediated mechanism) (immunologically-mediated hypersensitivity) ARIA(Allergic Rhinitis and its Impact on Asthma) [email protected]

8 2 (NAR) ,5,6 : (gustatory rhinitis) NARES(Non-allergic rhinitis with eosinophilia) (vasomotor rhinitis, VMR) VMR AR (work-exacerbated rhinitis) (occupational rhinitis(or)) 7,8 OR OR OR latent period latent period OR 7,8 Reference 1. International Rhinitis Management Working Group. International Consensus Report on the diagnosis and management of rhinitis. Allergy 1994;49(19 Suppl): Wang DY, Niti M, Smith JD, Yeoh KH, Ng TP. Rhinitis: do diagnostic criteria affect the prevalence and treatment? Allergy 2002;57: Storaas T, Steinsvag SK, Florvaag E, Irgens A, Aasen TB. Occupational rhinitis: diagnostic criteria, relation to lower airway symptoms and IgE sensitization in bakery workers. Acta Otolaryngol(Stockh) 2005;125: Kaliner MA. Classification of nonallergic rhinitis syndromes with a focus on vasomotor rhinitis, proposed to be known henceforth as nonallergic rhinopathy. WAO J 2009; 2: Bernstein JA. Nonallergic rhinitis: therapeutic options. Curr Opin Allergry Clin Immunol 2013,13: Bernstein JA. Characterizing rhinitis subtypes. Am J Rhinol Allergy 27, Castano R, Theriault G. Defining and classifying occupational thinitis. J Laryngol Otol. 2006; 120: Gianna M, Oliver V, Roy W, JL Malo, Luca P, Santiago Q, Jolanta W, Roberto C, Gianni P, Denyse G, Hans DG, Ilenia F, MR Yacoub, and Andrea S. EAACI position paper on occupational rhinitis. Respir Res. 2009; 10(1): 16.

9 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), Definition and Classification of Rhinitis Sheen-Yie Fang ABSTRACT The most common accepted definition of rhinitis is that formulated by the ICR(International Consensus Report) of in 1994 stating that rhinitis is defined as inflammation of the lining of the nose, characterized by one or more of the following symptoms: nasal congestion, rhinorrhea, sneezing and itching. A definition of rhinitis based only on the presence of symptoms may be imprecise for clinical practice and epidemiological study. We usually classify rhinitis as allergic and non-allergic groups. There are many subtypes of non-allergic rhinitis such as drug-induced, gustatory, hormonally induced, senile, atrophic and vasomotor rhinitis. Occupational rhinitis is an important issue recently. It should be defined carefully. It is essential to differentiate a work-exacerbated rhinitis from occupational rhinitis. Key words: rhinitis, definition, classification From the Department of Otolaryngology, National Cheng Kung University Hospital, Tainan, Taiwan Send Correspondence to Sheen-Yie Fang, MD. Department of Otolaryngology, National Cheng Kung University Hospital, No. 138, Sheng-Li Road, Tainan 70443, Taiwan [email protected]

10 4 黃啟哲 李達人 摘 要 20-30% Key words: rhinitis, epidemiology, quality of life ( ) 本文 1,2 ; 過敏性鼻炎的流行病學分析 盛行率的研究 2013 (World Allergy Organization (WAO)) 1 10% 30%% 40% 26-50% 3,4 4-32% % % 3, % % % % % 9 1

11 (1) 衛生假說 (Hygiene Hypothesis) (Hygiene Hypothesis) 10 T Th1 Th acetaminophen ( ) 危險因子 11 1,3,13 表一 : 過敏性鼻炎危險因子 IgE 台灣地區過敏原盛行率的研究 ( ) ( ) 非過敏性鼻炎的流行病學分析 % 9.6% 表二 : 過敏性鼻炎和非過敏性鼻炎的區別 性別 發作年齡 80% 在 20 歲前發作 20 症狀長短 ( ) ( ) 誘發物質 (irriatnts)

12 6 鼻炎對生活品質的影響 1,3 鼻炎相關的共病症及併發症 1,3,9,19 40% 80% 1,20 21 社會經濟的影響 %( 125 ) ; 結 論 參考文獻 1. World Allergy organization (WAO) white book on allergy: update ;46 suppl(1): Bousquet J, Khaltaev N, Cruz AA, Denburg J and the Aria Workshop Group. World Health Organization: Allergic Rhinitis and its Impact on Asthma (ARIA). Allergy 2008;63: Robert AN, Eli OM, John CS, et al. Prevalence of allergic rhinitis in the United States. J Allergy Clin Immunol 1997; 99: Allergic rhinitis (hay fever) in Australia. November 2011; Australian Institute of Health and Welfare ( aihw.gov.au/workarea) 6. Magnus P, Jaakkola JJ. Secular trend in the occurrence of asthma among children and young adults: critical appraisal of repeated cross sectional surveys. BMJ 1997;21: ;31: ;34: Liao PF, Sun HL, Lu KH, et al. Prevalence of childhood allergic diseases in central Taiwan over the past 15 years. Pediatr Neonatol 2009;50: Prokopakis E, Vardouniotis A, Kawauchi H, et al.the pathophysiology of the hygiene hypothesis. Int J Pediatr Otorhinolaryngol. 2013;77: Wang JY, Liu LF, Chen CY, et al. Acetaminophen and/ or antibiotic use in early life and the development of childhood allergic diseases. Int J Epidemiol. 2013;42: Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin

13 (1) Immunol 2001;108: Marcon A, Cazzoletti L, Rava M, et al. Incidence of respiratory and allergic symptoms in Italian and immigrant children. Respir Med. 2011;105: ;36: ;4: ;21(4): Bousquet J, Fokkens W, Burney P, et al. Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper. Allergy 2008;63: Bachert C, van Cauwenberge P, Olbrecht J, et al. Prevalence, classification and perception of allergic and nonallergic rhinitis in Belgium. Allergy 2006;61: Hsieh KH, Shen JJ. Prevalence of childhood asthma in Taipei, Taiwan, and other Asian Pacific countries. J Asthma 1988;25: Bourdin A, Gras D, Vachier I, et al. Upper airway x 1: allergic rhinitis and asthma: united disease through epithelial cells. Thorax 2009;64: Yawn BP, Yunginger JW, Wollan PC, et al. Allergic rhinitis in Rochester, Minnesota residents with asthma: frequency and impact on health care charges. J Allergy Clin Immunol 1999;103: Scoenwetter WF, Dupclay L Jr., Appajosyula S, et al. Economic impact and quality of life burden of allergic rhinitis. Curr Med Res Opin 2004; 20: Crystal-Peters J, Crown WH, Goetzel RZ, Schutt DC. The cost of productivity losses associated with allergic rhinitis. Am J Manag Care 2000; 6: Zuberbier T, Lötvall J, Simoens S, et al. Economic burden of inadequate management of allergic diseases in the European Union: a GA(2) LEN review. Allergy. 2014;69:

14 8 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Epidemiology and impaction of quality of life of rhinitis ABSTRACT Rhinitis is a global disease. Based on the difference in pathogenesis, it is classified as allergic or non-allergic rhinitis. In Taiwan, because of industrial development, air pollution, aging society and other environmental factors, prevalence has increased steadily. In Taiwan, epidemiological studies showed that about 20-30% of people suffered from allergic rhinitis. The prevalence of non-allergic rhinitis also increased gradually. Although no exact epidemiological results, but it will certainly become another problem in the future. Although rhinitis is not life-threatening, but it often results in great impaction in work efficiency, social activities, sleep quality, and school learning. It also imposes a heavy burden on the socio-economic costs. Because the inflammatory reactions in rhinitis are not confined to the nasal cavity, a variety of co-morbidity and complications are raised. Asthma, sinusitis, sleep disorders, conjunctivitis, and otitis media, are usually associated and should not to be ignored. Many people in their lives are bothered by rhinitis. Hence, it is an urgent issue to decrease the prevalence of rhinitis and reduce its impaction on quality of life. Key words: rhinitis, epidemiology, quality of life

15 9 張伯宏 1,2 黃啟哲 1,2 李達人 1,2 摘要 IgE Key words: 前言 (innate) (adaptive) (united airway) 本文 (allergic rhinitis) (non-allergic rhinitis) Ext [email protected]

16 10 過敏性鼻炎的致病機轉 (allergen) (sensitization) IgE IgE (cross-linking) (degranulation) (eosinophil) IgE ( ) IgE ( ) 1. 過敏原的暴露 (Der p1) (protease) 1 2. 致敏化及 IgE 產生 IgE (antigen presenting cell, APC) macrophage dendritic cells Langerhans cells 7-14 MHC class II molecules naïve TH0 cell IL-4 IL-22 naïve TH0 cell TH2 TH2 IL-3 IL-4 IL-5 IL-9 IL-10 IL- 13 IL-4 IL-13 B (plasma cell) IgE Th2 IgE IgE (Fc RI) 3. 早期抗原反應 5-15 IgE IgE C(protein kinase C) (degranulation) histamine tryptase chymase kininogenase heparin TNF 15 (phospholipid) (arachidonic acid) prostaglandin D2 leukotriene C4 D4 E4 PAF (platelet activating factor) 4. 晚期抗原反應 4-10 (vascular cell adhesion molecule) (E-selectin) IL-5 eosinophil, neutrophil, basophil, T lymphocyte macrophage eosinophil IL-5 CD34+ eosinophil eosinophil (major basic protein) (eosinophilic cationic protein) 2

17 (1) ,2 1,2 1, 非典型 IgE 反應 Der p1 Der p9 (Proteaseactivated receptor) (tight junction) TSLP (thymic stromal lymphopoietin) 1 ( pathogen-associated molecular patterns) (pattern recognition receptor, PRR) (innate immunity) TSLP 3 TSLP TSLP OX40 ligand Naïve T helper IL-4 IL-5 IL-13 IL-4 TH2 B IL-5 eosinophil TSLP IL-25 IL-33 TH2 IL-25 IL-33 TSLP 4 Histamine-4 H4 ( T eosinophil) H4 H4 H4 3

18 12 6. 神經元反應 (neuropeptide) (norepinephrine) Y (neuropeptide Y) (acetylcholine) ( vasoactive intestinal peptide, VIP) (non-adrenergic non-cholinergic, NANC) C P (substance P) (calcitonin gene related peptide, CGRP) A B (neurokinin A,B) - (nasonasal reflex) 5 (hyperresponsiveness) (neurotrophin) 6 Neurotrophin (Nerve growth factor,ngf) (brain-derived neurotrophin,bdnf) eosinophil neurotrophin Neurotrophin neurotrophin eosinophil eosinophil neurotrophin 6 5

19 (1) ,2 1,2 1, 組織重塑 7 非過敏性鼻炎的致病機轉 (Nonallergic rhinitis with eosinophilia syndrome, NARES) (gustatory rhinitis) 1. 內因性鼻炎 (instrinsic rhinitis) (vasomotor rhinitis) 8 9,10 Entopy ( ) Entopy IgE (eosinophilic cation protein) IgE IgE % ( ) 4 Nociceptive dysfunction ( ) A ( ) C ( ) TRPV1 TRPV1 42 TRP TRP( transient receptor potential) TRP 11

20 14 Autonomic dysfunction 2. 職業性鼻炎 3. 荷爾蒙鼻炎 progesteron estrogen prolactin vasoactive intestinal peptide progesteron - estradiol H 非過敏性鼻炎伴嗜伊紅性白血球增多症候群 eosinophil 20% eosinophil entopy 14 Samter s triad (aspirin sensitivity, asthma and polyposis) 6. 味覺性鼻炎 nociceptive dysfunction (A C ) TRPV1 15 substance P calcitonin gene related peptide(cgrp) 4. 藥物性鼻炎 13 (local inflammatory type) NSAID aspirin cyclooxygenase lipoxygenase leukotriene (neurogenic type) clonidine guanethidine methyldopa (idiopathic) 7. 萎縮性鼻炎 (primary) (secondary) ( ) ( )

21 (1) ,2 1,2 1,2 15 參考文獻 1. Reed CE, Kita H. The role of protease activation of inflammation in allergic respiratory diseases. The Journal of allergy and clinical immunology 2004; 114: ; quiz Hansen I, Klimek L, Mosges R, Hormann K. Mediators of inflammation in the early and the late phase of allergic rhinitis. Current opinion in allergy and clinical immunology 2004; 4: Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet 2011; 378: Broide DH. Allergic rhinitis: Pathophysiology. Allergy Asthma Proc : the official journal of regional and state allergy societies 2010; 31: Van Gerven L, Boeckxstaens G, Hellings P. Up-date on neuro-immune mechanisms involved in allergic and nonallergic rhinitis. Rhinology 2012; 50: Raap U, Braunstahl GJ. The role of neurotrophins in the pathophysiology of allergic rhinitis. Curr Opin Allergy Clin Immunol 2010; 10: Constantino Gde T, Mello Jr JF. Remodeling of the lower and upper airways. Braz J Otorhinolaryngol 2009; 75: Kaliner MA. Nonallergic rhinopathy (formerly known as vasomotor rhinitis). Immunol Allergy Clin North Am 2011; 31: Pattanaik D, Lieberman P. Vasomotor rhinitis. Curr Allergy Asthma Rep 2010; 10: Garay R. Mechanisms of vasomotor rhinitis. Allergy 2004; 59 Suppl 76:4-9; discussion Baraniuk JN. Pathogenic mechanisms of idiopathic nonallergic rhinitis. World Allergy Organ J 2009; 2: Settipane RA. Other causes of rhinitis: mixed rhinitis, rhinitis medicamentosa, hormonal rhinitis, rhinitis of the elderly, and gustatory rhinitis. Immunol Allergy Clin North Am 2011; 31: Varghese M, Glaum MC, Lockey RF. Drug-induced rhinitis. Clin Exp Allergy 2010; 40: Ellis AK, Keith PK. Nonallergic rhinitis with eosinophilia syndrome. Curr Allergy Asthma Rep 2006; 6: Georgalas C, Jovancevic L. Gustatory rhinitis. Curr Opin Otolaryngol Head Neck Surg 2012; 20:9-14.

22 16 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Mechanism of Rhinitis Po-Hung Chang, Chi-Che Huang, Ta-Jen Lee ABSTRACT Nose is the first site of upper airway that constantly contacts with various allergens and environmental stimulants and inflammation may be caused. Symptoms of nasal inflammation include nasal obstruction, sneezing, itchy sensation or rhinorrhea. We can roughly divide rhinitis into allergic rhinitis and non-allergic rhinitis. Allergic rhinitis is mainly type I hypersensitivity reaction. After allergen re-exposure, early-phase response (degranulation reaction caused by IgE cross-linking) and late-phase response (inflammatory cells influx) may be caused. The inflammatory mediators produced can cause symptoms of rhinitis. Other kinds of rhinitis that are not typical allergic rhinitis can be categorized into non-allergic rhinitis which may be caused by drugs, occupation, hormone, temperature, food, emotion and idiopathic cause, etc. Those are frequently related to autonomic dys-regulation and mucosal hyperresponsiveness. Understanding the mechanism will be beneficial to the diagnosis of rhinitis and subsequent treatment. Key words: allergic rhinitis, non-allergic rhinitis, mechanism From the Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan No. 5, Fu Hsing Street, Kwei-Shan, Taoyuan 333, Taiwan Tel: Ext Fax: [email protected]

23 (1) 林志峰 摘 1 葉德輝 要 ARIA (therapeutic trial) : 前言 (1, 2) IgE (trigger) IgE 20 (3) (3, 4) (therapeutic trial) (2,3) (5) (4) (4) 1 : [email protected]

24 18 本文 鼻炎的分類 ARIA Allergic Rhinitis and its Impact on Asthma (1, 6, 7) (1) (Table1.) (Table2.) (occupational rhinitis) (allergic) (non-allergic) : T.B. leprosy sarcoidosis Wegener sgranulomatosis Churg-Strauss syndrome, relapsing polychondritis, amyloidosis 4 5 primary ciliary defect cystic fibrosis (therapeutic trial) (2,3) (5) (4) 診斷 病史 (8) Rhinoconjunctivitis Quality of Life Questionnaire (1, 3, 9, 10) 理學檢查 (allergic shiner) (Dennie-Morgan lines) 過敏原測試 (4) IgE 3~10 (1) IgE IgE 特殊檢查 nasal endoscopy CT MRI nasal smears cytology and pathology exams cultures saccharin test for mucociliary clearance -2-transferrin test peak nasal inspiratory flow(pnif) peak nasal expiratory flow(pnef) anterior rhinomanometry posterior rhinomanometry acoustic-rhinometry olfactory tests pulmonary function tests polysomnography nasal provocation tests

25 (1) 診治流程 (2,3) (Fig.1) 過敏性鼻炎 : 20 allergic shiner allergic salute Dennie-Morgan lines (4) 職業性鼻炎 nasal challenge test (11) 藥物性鼻炎 Hormonal rhinitis 萎縮性鼻炎 (12) 老年性鼻炎 ipratropium bromide Nonallergic Rhinitis with Eosinophilia Syndrome (NARES) 20% eosinophil Samter's triad aspirin sensitivity, asthma, and nasal polyposis Gustatory Rhinitis idiopathic posttraumatic postsurgical gustatory rhinorrhea associated with cranial nerve neuropathy (13) Idiopathic rhinitis

26 20 感染性鼻炎 10 結論 (therapeutic trial) Table 1. Classification of allergic rhinitis(1) Classification Definition Specific Presentations Intermittent Symptoms <4 days/week or for <4 consecutive weeks Persistent Mild severity Moderate/ Severe Symptoms >4 days/week or for >4 consecutive weeks No sleep disturbance; no impairment of daily activities, leisure, or sport; No impairment of school or work; symptoms present but are not troublesome Sleep disturbance; impairment of daily activities, leisure, or sport; impairment of school or work; troublesome symptoms Primary symptoms are sneezing, itching, congestion, and clear rhinorrhea, bilateral symptoms; often associated with eye symptoms (bilateral, itching, red eyes, no photophobia); exposition to allergens triggers symptoms; onset usually before the age of 20 years; positive family history of atopic diseases

27 (1) (1, 2, 11, 14) Table 2. Classification of non-allergic rhinitis Type Classification Definition Presentations Occupational Caused by work Intermittent or persistent symptoms attributable to a particular work environment; can be elicited by single or multiple exposures; Frequently associated with concurrent asthma; nasal challenge tests confirm the diagnosis Agents: grain dust, flour, latex, biological enzymes, fish and seafood proteins, animals, wood dust, metals, drugs, chemicals. Exacerbated by work Preexisting or concurrent rhinitis exacerbated by workplace exposures Druginduced NSAIDs and acetylsalicylic acid Eosinophilic inflammation with an overproduction of cysteinyl leukotrienes and other prostanoids Profuse rhinorrhea, red eyes, periorbital edema, asthma attacks after ingestion; associated with nasal polyposis and asthma Others Beta-blockers, ACE inhibitors, methyldopa, reserpine, guanethidine, phentolamine, alpha-adrenoreceptor antagonists, chlorpromazine, oral contraceptive Medica-mentosa Persistent nasal obstruction after Rebound nasal congestion if the medication using nasal sympatho- is stopped mimetics.5 10 days (oxymetazoline, phenylephrine, xylometazoline Cocaine abuse Septal perforation often associated Hormonal Pregnancy, menstruation, puberty Nasal congestion present during pregnancy without other cause, disappearing within 2 weeks after delivery Hypothyroidism, Edema of turbinate secondary to acromegaly thyrotropic hormone release Idiopathic Vasomotor rhinitis Diagnosis of exclusion, not IgE mediated, not infectious, and not associated with nasal eosinophilia Rhinorrhea and nasal obstruction Nasal congestion Triggered by cold air, change in humidity, exposure to tobacco smoke, strong odor, stress, or exercise Infectious Viral Adenovirus, influenza, RSV, Facial pain and pressure, nasal obstruction parainfluenza, coronavirus Bacterial Streptococcus, Haemophilus Purulent rhinorrhea, fever

28 22 Others NARES (non-allergic rhinitis Rhinitis with eosinophils (5 25/HPF) in nasal smears in Persistent nasal congestion, sneezing, rhinorrhea, nasal pruritus, and hyposmia; no history of atopy with eosinophilia syndrome) the absence of demonstrable allergy; suspect precursor of aspirin triad. Gustatory rhinitis Profuse watery rhinorrhea within few hours of oral Copious rhinorrhea associated with eating, usually spicy food ingestion Atrophic Primary: Klebsiella ozaenae Atrophy of the nasal mucosa with copious smelling crusts Secondary: post-excessive nasal surgery, postradiotherapy or trauma Atrophy of the nasal mucosa Fig.1 (2,3)

29 (1) J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Clinical manifestation and diagnosis of rhinitis Chih-Feng Lin 1, Te-Huei Yeh 1 ABSTRACT Rhinitis has been defined as inflammation of the lining of the nose, manifested by one or more of the following symptoms with nasal congestion, rhinorrhea, sneezing, and itching. ARIA guidelines had reclassified allergic rhinitis on the basis of the severity and duration of symptoms and had been widely accepted internationally. Non-allergic rhinitis is a broad term encompassing a number of nasal conditions, and the definite diagnosis could be complex and difficult. Detailed history and physical examination are still the most important parts in the diagnosis of rhinitis. Therapeutic trial can be started for those patients with uncertain diagnosis. Physicians need to follow the treatment results and timely correct the diagnosis. For patients with uncertain diagnosis and poor response to initial treatment, allergen tests as well as other special examinations as endoscopy, or computed tomography, etc. should be arranged to assist in the differential diagnosis of rhinitis. Key words: rhinitis, allergy, clinical manifestations, diagnosis From the 1Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan Send Correspondence to Te-Huei Yeh, MD. Department of Otolaryngology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan [email protected]

30 24 參考文獻 1. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2) LEN and AllerGen). Allergy 2008;63 Suppl 86: Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol 2008;122(2 Suppl):S Nassef M, Shapiro G, Casale TB. Identifying and managing rhinitis and its subtypes: allergic and nonallergic components--a consensus report and materials from the Respiratory and Allergic Disease Foundation. Curr Med Res Opin 2006;22(12): Seidman MD, Gurgel RK, Lin SY, et al. Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg;152(1 Suppl):S1-S Rondon C, Dona I, Torres MJ, Campo P, Blanca M. Evolution of patients with nonallergic rhinitis supports conversion to allergic rhinitis. J Allergy Clin Immunol 2009;123(5): Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol;126(3): Bousquet J, Schunemann HJ, Samolinski B, et al. Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol;130(5): ARIA in the pharmacy: management of allergic rhinitis symptoms in the pharmacy. Allergic rhinitis and its impact on asthma. Allergy 2004;59(4): Brandt D, Bernstein JA. Questionnaire evaluation and risk factor identification for nonallergic vasomotor rhinitis. Ann Allergy Asthma Immunol 2006;96(4): Bernstein JA, Levin LS, Al-Shuik E, Martin VT. Clinical characteristics of chronic rhinitis patients with high vs low irritant trigger burdens. Ann Allergy Asthma Immunol;109(3): Moscato G, Vandenplas O, Gerth Van Wijk R, et al. Occupational rhinitis. Allergy 2008;63(8): Moore EJ, Kern EB. Atrophic rhinitis: a review of 242 cases. Am J Rhinol 2001;15(6): Jovancevic L, Georgalas C, Savovic S, Janjevic D. Gustatory rhinitis. Rhinology;48(1): Bousquet J, Bachert C, Canonica GW, et al. Unmet needs in severe chronic upper airway disease (SCUAD). J Allergy Clin Immunol 2009;124(3):

31 25 黃得韻 1,2 摘 戴志展 要 1,2, key words : 本文 1 1,2 鼻炎及鼻竇炎 (ostiomeatal complex, OMC)

32 26 Allergic Rhinitis and its Impact on Asthma (ARIA) 2014 Allergy (FESS) (ostiomeatal complex, OMC) 2,3 OMC 2,3 3 (allergic fungal rhinosinusitis) OMC 鼻炎及過敏性結膜炎 (pterygopalatine ganglion) 70% 9 9 (allergic shiner) 鼻炎及中耳炎 中耳積水 ,11 2,10, 鼻炎及腺樣體肥大

33 (1) ,2 1,2, 27 結論 1 參考文獻 1. Greiner AN, Hellings PW, Rotiroti G, Scadding GK: Allergic rhinitis. Lancet 2011;378: Sih T, Mion O: Allergic rhinitis in the child and associated comorbidities. Pediatr Allergy Immunol 2010; 21: e107-e Deliu M, Belgrave D, Simpson A, Murray CS, Kerry G, Custovic A: Impact of rhinitis on asthma severity in school-age children. Allergy 2014; 69: Rhee CS, Wee JH, Ahn JC, et al: Prevalence, risk factors and comorbidities of allergic rhinitis in South Korea: The Fifth Korea National Health and Nutrition Examination Survey. Am J Rhinol Allergy 2014; 28: e107-e Sedaghat AR, Phipatanakul W, Cunningham MJ: Prevalence of and associations with allergic rhinitis in children with chronic rhinosinusitis. Int J Ped Otorhinolaryngology 2014; 78: Frerichs KA, Nigten G, Romeijn K, Kaper NM, Grolman W, van der Heijden GJ: Inconclusive evidence for allergic rhinitis to predict a prolonged or chronic course of acute rhinosinusitis. Otolaryngol Head Neck Surg 2014; 150(1): Chang CC, Tai CJ, Ng TY, Tsou YA, Tsai MH: Can FESS combined with submucosal resection (SMR)/septoplasty reduce revision rate? Otolaryngol Head Neck Surg 2014; 151(4): Holzmann D1, Willi U, Nadal D: Allergic rhinitis as a risk factor for orbital complication of acute rhinosinusitis in children. Am J Rhinol 2001; 15(6): Hom MM, Bielory L: The anatomical and functional relationship between allergic conjunctivitis and allergic rhinitis. Allergy Rhinol 2013; 4: e110 e Luong A1, Roland PS: The link between allergic rhinitis and chronic otitis media with effusion in atopic patients. Otolaryngol Clin N Am 2008; 41: Yeo SG, Park DC, Eun YG, Cha CI: The role of allergic rhinitis in the development of otitis media with effusion: effect on eustachian tube function. Am J Otolaryngol 2007; 28(3):

34 28 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Complications of rhinitis Abstract Rhinitis is a very common clinical disease. Complications or co-morbidities of rhinitis will occur if rhinitis had not been treated properly. The chapter will discuss the complications or co-morbidities of rhinitis including rhinosinusitis, allergic conjunctivitis, otitis media with effusion, adenoid hyperplasia. Rhinitis related asthma or obstructive sleep apnea syndrome will be discussed in other chapters. Keywords: rhinitis, complication, co-morbidity, rhinosinusitis, allergic conjunctivitis, otitis media with effusion, adenoid hyperplasia

35 (1) 廖筱蓁 摘 1 方深毅 要 1 20% 前言 20% 1 ; : 本文 IgE 2 ; (Hay fever) 90%

36 30 1. 塵 25 80% (1) (56 ) (2) (3) (4) (5) 75-80% 50% 50% (6) High-efficiency particulate arrestance (HEPA) 2. 黴菌 (1) (2) (3) (4) High-efficiency particulate arrestance (HEPA) (5) (1) (2) 3. 蟑螂,,, (1) (2) (3) 4. 動物皮屑 (1) (2) (3) (4) (5) 5. 花粉 (1) (2) 10,11 12

37 (1) Allergic Rhinitis and its Impacts on Asthma (ARIA) 13 結論 參考文獻 ;34: Lanny J. Treatment of Allergic Rhinitis. Am J Med. 2002;113(9A):17S 24S. 3. William E. Overview of allergic rhinitis. Ann Allergy Asthma Immunol. 2003;90(Suppl 3): ;31: Sheikh A, Hurwitz B. House dust mite avoidance measures for perennial allergic rhinitis: a systematic review of efficacy Br J Gen Pract Apr;53(489): Muche-Borowski C, Kopp M, Reese I, et al. Allergy prevention J Dtsch Dermatol Ges Sep;8(9): Stillerman A1, Nachtsheim C, Li W, et al. Efficacy of a novel air filtration pillow for avoidance of perennial allergens in symptomatic adults. Ann Allergy Asthma Immunol May;104(5): Kemp AS. Allergic rhinitis. Paediatr Respir Rev Jun;10(2): Susanne H. Prevention of allergic disease in childhood:clinical and epidemiological aspects of primary and secondary allergy prevention. Pediatr Allergy Immunol 2004: 15 (Suppl. 16): Thomas S., Douglas D. Environmental pollutants and allergic rhinitis. Curr Opin Otolaryngol Head Neck Surg 2012, 20: Topp R, Thefeld W, Wichmann HE, Heinrich J.The effect of environmental tobacco smoke exposure on allergic sensitization and allergic rhinitis in adults. Indoor Air Aug;15(4): Gerth van Wijk R1, Patiwael JA, de Jong NW, de Groot H, Burdorf A. Occupational rhinitis in bell pepper greenhouse workers: determinants of leaving work and the effects of subsequent allergen avoidance on health-related quality of life. Allergy Jul;66(7): Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update. Allergy 2008;63(Suppl 86):8-160

38 32 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Allergen avoidance and education of rhinitis Abstract Allergic rhinitis is an IgE-mediated disease that is provoked by either seasonal or perennial inhalant allergens. The most common seasonal allergens in temperate climates are pollens and molds. Perennial allergens commonly include dust mites, molds, cockroaches, and animal dander continually found in the indoor environment. In Taiwan, the prevalence of the allergic rhinitis was 20%, respectively. The most common allergen is mite. Rhinitis symptoms due to inhaled allergens. Therefore, allergen avoidance is an essential step in managing allergies. Identifying the allergen causing symptoms is a vital part of treating allergic diseases. What may be required is total elimination of the allergen which is generally impossible to achieve.

39 (1) 梁凱莉江榮山 摘 要 T 3-5 Key words: allergy, asthma, immunotherapy, rhinitis, subcutaneous, sublingual 引 言 本 文 1, 2 : : subcutaneous (sublingual) 1911 Noon (meta-analysis) 6, , (04)

40 34 IgG4 IgE IgG4 IgE T IgG4 IgE T T (TH1) T (TH2) 10 (interleukin-10, IL-10) TGF- 10 T (regulatory T cell, Treg) (mast cell) (eosinophil) B IgG4 17 (dendritic cell) T T T T T T 18, 19 3% % % ( ) ( ) (systemic reviews) 2, 25, 26 27, 28 (enzyme-linked immunosorbent assay, ELISA) (radioallergosorbent test, RAST) (build up phase): (maintenance phase) 4-6 討論 , 31

41 (1) % 35% 22, 32 ( -blockers) (angiotensin converting enzyme inhibitors) 1 5, , ( ) 33 結論 1. Burks AW, Calderon MA, Casale T, et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol 131: e1283; Compalati E, Braido F, Canonica GW. An update on allergen immunotherapy and asthma. Curr Opin Pulm Med 20: ; Noon L. Prophylactic inoculation against hay fever. Historical document. Ann Allergy 18: ; Erekosima N, Suarez-Cuervo C, Ramanathan M, et al. Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review. Laryngoscope 124: ; Purkey MT, Smith TL, Ferguson BJ, et al. Subcutaneous immunotherapy for allergic rhinitis: an evidence based review of the recent literature with recommendations. Int Forum Allergy Rhinol 3: ; Meadows A, Kaambwa B, Novielli N, et al. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis. Health Technol Assess 17:vi, xi-xiv, 1-322; Petersen KD, Kronborg C, Larsen JN, Dahl R, Gyrd- Hansen D. Patient related outcomes in a real life prospective follow up study: Allergen immunotherapy increase quality of life and reduce sick days. World Allergy Organ J 6:15; Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy 60:4-12; Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 118: ; Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 117: ; Compalati E, Passalacqua G, Bonini M, Canonica GW. The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN metaanalysis. Allergy 64: ; Lin SY, Erekosima N, Kim JM, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA 309: ;2013.

42 Radulovic S, Wilson D, Calderon M, Durham S. Systematic reviews of sublingual immunotherapy (SLIT). Allergy 66: ; Lin SY. Sublingual immunotherapy: current concepts for the U.S. practitioner. Int Forum Allergy Rhinol 4 Suppl 2:S55-59; Dretzke J, Meadows A, Novielli N, Huissoon A, Fry-Smith A, Meads C. Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison. J Allergy Clin Immunol 131: ; Nelson HS. Subcutaneous immunotherapy versus sublingual immunotherapy: which is more effective? J Allergy Clin Immunol Pract 2: ; quiz ; Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol 133: ; Scadding G, Durham S. Mechanisms of sublingual immunotherapy. J Asthma 46: ; Frew AJ. Sublingual immunotherapy. N Engl J Med 358: ; Moffitt JE, Golden DB, Reisman RE, et al. Stinging insect hypersensitivity: a practice parameter update. J Allergy Clin Immunol 114: ; Antolin-Amerigo D, Moreno Aguilar C, Vega A, Alvarez- Mon M. Venom immunotherapy: an updated review. Curr Allergy Asthma Rep 14:449; Frew AJ. Allergen immunotherapy. J Allergy Clin Immunol 125:S ; Naclerio RM, Proud D, Moylan B, et al. A double-blind study of the discontinuation of ragweed immunotherapy. J Allergy Clin Immunol 100: ; Durham SR, Varney VA, Gaga M, et al. Grass pollen immunotherapy decreases the number of mast cells in the skin. Clin Exp Allergy 29: ; Abramson M, Puy R, Weiner J. Immunotherapy in asthma: an updated systematic review. Allergy 54: ; Penagos M, Passalacqua G, Compalati E, et al. Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Chest 133: ; Marogna M, Colombo F, Spadolini I, et al. Randomized open comparison of montelukast and sublingual immunotherapy as add-on treatment in moderate persistent asthma due to birch pollen. J Investig Allergol Clin Immunol 20: ; Garcia-Robaina JC, Sanchez I, de la Torre F, Fernandez- Caldas E, Casanovas M. Successful management of mite-allergic asthma with modified extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae in a double-blind, placebo-controlled study. J Allergy Clin Immunol 118: ; Inal A, Altintas DU, Yilmaz M, Karakoc GB, Kendirli SG, Sertdemir Y. Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite. J Investig Allergol Clin Immunol 17:85-91; Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 341: ; Eng PA, Borer-Reinhold M, Heijnen IA, Gnehm HP. Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood. Allergy 61: ; Bukantz SC, Bagg AS, Lockey RF. Adverse effects and fatalities associated with subcutaneous allergen immunotherapy. Clin Allergy Immunol 21: ; Rank MA, Bernstein DI. Improving the safety of immunotherapy. J Allergy Clin Immunol Pract 2: ;2014.

43 (1)

44 38 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Allergy Immunotherapy Kai-Li Liang and Rong-San Jiang ABSTRACT Allergy immunotherapy (AIT) is defined as the repeated administration of specific allergens to patients with IgE-mediated conditions for the purpose of providing protection against the allergic symptoms and inflammatory reactions associated with natural exposure to these allergens. Both subcutaneous and sublingual immunotherapies induce changes in T cells and antibody response. AIT is effective in treatment of venom hypersensitivity, allergic rhinitis, allergic asthma, and atopic dermatitis related to inhalant allergens. AIT can modify the course of allergic disease by reducing the risk of new allergic sensitization and inhibiting the development of asthma in children treated for allergic rhinitis. It also achieves long-lasting relief of allergic symptoms after stop treatment. The main risk of AIT is that of provoking a systemic allergic reaction. When used in carefully selected patients, AIT is effective and safe.

45 (1) 葉德輝 1 摘 要 H1 H1 ARIA Key words: rhinitis, pharmacologic treatment, ARIA, clinical practice guideline( ARIA ) 前言 ARIA (Allergic Rhinitis and its Impact on Asthma) (1-3) (4-6) ARIA 本文 藥物治療的基本考量 1. 藥物的選擇 (7) (1, 6) 2. 用藥途徑 1 2 Cromone rhinitis medicamentosa : [email protected]

46 40 3. 階梯式治療 (1) (.1) 常用藥物種類 1. 類固醇鼻噴劑 (sneezing,itching, rhinorrhea, and congestion) (8) (1) - (9) (10) betamethasone (hypothalamic-pituitary-adrenal axis) (11) fluticasone propionate monetasone furoate (12, 13) (14) 3~8 1~2 fluticasone propionate (15) H1 (8) (anti-leukotriene (16) 4~ 20% (6) 2. 口服類固醇 (17) 3. 口服 H1 型抗組織胺 (H1-antihistamine) ( ) (8) (1) (18) chemotaxis NF- kb (19) inverse angonist antagonist (19) (Blood- Brain-Barrier) cytochrome P450 cytochrome P450 QT interval macrolide ketaconazole (19) astemizole terfenadine (6) Loratadine

47 (1) desloratadine mizolastine ebastine fexofenadine (19) (1, 23) (1) 4. 局部 H1 型抗組織胺 FDA Azelastine olopatadine (6) H1 H1 (20) 15~30 azelastine (6, 19) H1 H1 (19) 8. 局部 Cromone 4~7 (24) 9. 抗膽鹼鼻噴劑 (anticholinergic agents) 5. 口服白三烯素受體拮抗劑 (anti-leukotriene) (6) H1 (21) (22) neuropsychiatric events (6) 合併療法 (COMBINATION THERAPY) (1, 6) (.2) 1. 類固醇鼻噴劑合併口服抗組織胺 (25) 6. 去充血鼻噴劑 (23) 7. 口服去充血劑 2. 口服抗組織胺合併口服去充血劑 (26) (27) (tolerance) 3. 口服抗組織胺合併口服白三烯素受體拮抗劑 (28)

48 42 4. 類固醇鼻噴劑合併口服白三烯素受體拮抗劑 (29) 5. 類固醇鼻噴劑合併局部 H1 型抗組織胺 (30) 結論 ARIA 6. 類固醇鼻噴劑合併去充血鼻噴劑 (31) 3 1. (1)

49 (1) (6) Medication Bioavailability Age (y/o) Dose Fluticasone furoate (27.5 ug/spray) <1% >2 1-2 sprays each nostril QD Fluticasone propionate (50 ug/spray) <5% >4 1-2 sprays each nostril QD Mometasone (50 ug/spray) <0.1% sprays each nostril QD >12 2 sprays each nostril QD Beclomethasone (42 ug/spray) >40% >6 1-2 sprays each nostril Bid Budesonide (32 ug/spray) 30-40% sprays each nostril QD > sprays each nostril QD Ciclesonide (37 ug/spray) <0.1% >12 1 spray each nostril QD Flunisolide (25 ug/spray) >40% sprays each nostril Bid >14 2 sprays each nostril Bid/Tid

50 44 參考文獻 1. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*. Allergy 2008;63: Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol;126(3): Bousquet J, Schunemann HJ, Samolinski B, et al. Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol;130(5): Angier E, Willington J, Scadding G, Holmes S, Walker S. Management of allergic and non-allergic rhinitis: a primary care summary of the BSACI guideline. Prim Care Respir J;19(3): Okubo K, Kurono Y, Fujieda S, et al. Japanese Guideline for Allergic Rhinitis Allergol Int;63(3): Seidman MD, Gurgel RK, Lin SY, et al. Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg;152(1 Suppl):S1-S Bousquet J, van Cauwenberge P, Ait Khaled N, et al. Pharmacologic and anti-ige treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN). Allergy 2006;61(9): Yanez A, Rodrigo GJ. Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol 2002;89(5): Christodoulopoulos P, Cameron L, Durham S, Hamid Q. Molecular pathology of allergic disease. II: Upper airway disease. J Allergy Clin Immunol 2000;105(2 Pt 1): Herman H. Once-daily administration of intranasal corticosteroids for allergic rhinitis: a comparative review of efficacy, safety, patient preference, and cost. Am J Rhinol 2007;21(1): Ratner PH, Miller SD, Hampel FC, Jr., Melchior A, Dunbar SA, Tantry SK. Once-daily treatment with beclomethasone dipropionate nasal aerosol does not affect hypothalamicpituitary-adrenal axis function. Ann Allergy Asthma Immunol;109(5): Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics 2000;105(2):E Allen DB, Meltzer EO, Lemanske RF, Jr., et al. No growth suppression in children treated with the maximum recommended dose of fluticasone propionate aqueous nasal spray for one year. Allergy Asthma Proc 2002;23(6): Blaiss MS. Management of rhinitis and asthma in pregnancy. Ann Allergy Asthma Immunol 2003;90(6 Suppl 3): Jen A, Baroody F, de Tineo M, Haney L, Blair C, Naclerio R. As-needed use of fluticasone propionate nasal spray reduces symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol 2000;105(4): Benninger M, Farrar JR, Blaiss M, et al. Evaluating approved medications to treat allergic rhinitis in the United States: an evidence-based review of efficacy for nasal symptoms by class. Ann Allergy Asthma Immunol;104(1): Laekeman G, Simoens S, Buffels J, et al. Continuous versus on-demand pharmacotherapy of allergic rhinitis: evidence and practice. Respir Med;104(5): Thomson L, Blaylock MG, Sexton DW, Campbell A, Walsh GM. Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells. Clin Exp Allergy 2002;32(8): Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol;128(6): e Kaliner MA, Berger WE, Ratner PH, Siegel CJ. The efficacy of intranasal antihistamines in the treatment of allergic rhinitis. Ann Allergy Asthma Immunol;106(2 Suppl):S6-S Grainger J, Drake-Lee A. Montelukast in allergic rhinitis: a systematic review and meta-analysis. Clin Otolaryngol 2006;31(5): Wilson AM, O Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis. Am J Med 2004;116(5): Graf P. Rhinitis medicamentosa: aspects of pathophysiology and treatment. 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51 (1) J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Pharmacologic treatment of rhinitis ABSTRACT Pharmacologic therapy is a key part of rhinitis control and can roughly divided into two categories of oral and intranasal or topical use. Oral drugs include H1 antihistamine (including a first and second generation), decongestant, steroids, leukotriene receptor antagonists and others; topical including steroids, H1 antihistamine, decongestant, mast cell stabilizers, and anti-choline nasal spray. ARIA consensus and subsequent clinical practice guidelines provide us the instructions of pharmacologic therapy of rhinitis. We must be familiar with the route, dosage, and side effects of each drug as well as having a full understanding of the combination therapy while failing in monotherapy, in order to provide the best medical and personalized therapy for our patients. Key words: rhinitis, pharmacologic treatment, ARIA, clinical practice guideline From the 1 Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan Send Correspondence to Te-Huei Yeh, MD. Department of Otolaryngology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan [email protected]

52 46 王瀛標 摘 要 20 / / 本文 (Lateralization outfracture): Killian (Inferior turbinate reduction): (internal nasal valve) 1 :

53 (1) (Classic submucosal resection) Passali ( ) 4 IgE (Laser turbinoplasty): 6 KTP (potassium-titanyl phosphate) Nd: YAG (neodymium-yttrium aluminum garnet) Argon Ho: YAG (holium-yttrium aluminum garnet) (diode) 7 Caffier Cassano (mucociliary clearance time) (radiofrequency ablation and coblation) : 12 (coagulative necrosis) / 12, , 12, % (Microdebriderassisted turbinoplasty): 19 Cingi

54 48 ( ) 20 3, (Endoscopic vidian neurectomy): 1961 Golding-Wood 21 Kamel Zaher Robinson Wormald (intractable) % 90% ( 6 23 ) % 1 2.5% 6 7, ,28, / / 參考資料 1. Nathan RA, Meltzer EO, Derebery J, et al. The prevalence of nasal symptoms attributed to allergies in the United States: findings fromthe burden of rhinitis in an America survey. Allergy Asthma Proc. 2008;29: Bousquet PJ, Demoly P, Devillier P, et al. Impact of allergic rhinitis symptoms on quality of life in primary care. Int Arch Allergy Immunol. 2013;160: Aksoy F, Yıldırım YS, Veyseller B, et al. Midterm outcomes of outfracture of the inferior turbinate. Otolaryngol Head Neck Surg. 2010;143(4): Passali D, Lauriello M, Anselmi M, et al. Treatment of hypertrophy of the inferior turbinate: long-term results in 382 patients randomly assigned to therapy.ann Otol Rhinol Laryngol. 1999;108(6): Mori S, Fujiea S, Yamada T, et al. Long-term effect of submucosal turbinectomy in patients with perennial allergic rhinitis. Laryngoscope 2008; 118: Volk GF, Pantel M, Guntinas-Lichius O, et al. Prognostic -4value of anterior rhinomanometry in diode laser turbinoplasty. Arch Otolaryngo Head Neck Surg 2010; 136: Wu AW, Ting JY. Indications for surgery in refractory rhinitis. Curr Allergy Asthma Rep 2014; 14: Caffier PP, Scherer H, Neumann K, et al. Diode laser treatment in therapy-resistant allergic rhinitis: impact on nasal obstruction and associated symptoms. Lasers Med Sci. 2011;26: Cakli H, Cingi C, Guven E, Gurbuz MK, Kaya E. Diode laser treatment of hypertrophic inferior turbinates and evaluation of the results with acoustic rhinometry. Eur

55 (1) Arch Otorhinolaryngol. 2012; 269: Cassano M, Granieri C, Del Giudice AM, et al. Restoration of nasal cytology after endoscopic turbinoplasty versus laser-assisted turbinoplasty. Am J Rhinol Allergy. 2010; 24: Sapci T, Sahin B, Karavus A, et al, Comparison of the effects of radiofrequency tissue ablation, CO2 laser ablation, and partial turbinectomy applications on nasal mucociliary functions. Laryngoscope. 2003; 113: Hytonen ML, Back LJ, Malmivaara AV, et al. Radiofrequency thermal ablation for patients with nasal symptoms: a systemic review of effectiveness and complications. Eur Arch Otorhinolaryngol. 2009; 266: Li KK, Powell NB, Riley RW, et al. Radiofrequency volumetric tissue reduction for treatment of turbinate hypertrophy: a pilot study. Otolaryngol Head Neck Surg. 1998; 119: Simeon R, Soufflet B, Souchal Delacour I. Coblation turbinate reduction in childhood allergic rhinitis. Eur Ann Otorhinolaryngol Head Neck Dis. 2010; 127: Bahadir O, Kosucu P. Quantitative measurement of radiofrequency volumetric tissue reduction by multidetector CT in patients with inferior turbinate hypertrophy. Auris Nasus Larynx. 2012; 39(6): Kisser U, Stelter K, Gürkov R, et al. Diode laser versus radiofrequency treatment of the inferior turbinate - a randomized clinical trial. Rhinology. 2014; 52(4): Kamel R, Zaher S. Endoscopic transnasal vidian neurectomy. Laryngoscope. 1991;101: Robinson SR, Wormald PJ. Endoscopic vidian neurectomy. Am J Rhinol. 2006;20: Lee JC, Hsu CH, Kao CH, Lin YS. Endoscopic transsphenoidal vidian neurectomy. Eur Arch Otorhinolaryngol. 2011;268: Su W, Liu S, Chiu F, Lee C. Antegrade transsphenoidal vidian neurectomy: short-term surgical outcome analysis. Am J Rhinol Allergy. 2011;25(6): Tan G, Ma Y, Li H, et al. Results of bilateral endoscopic vidian neurectomy in the management of moderate to severe persistent allergic rhinitis. Arch Otolaryngol Head Neck Surg. 2012; 138(5): Ikeda K, Oshima T, Suzuki M, et al. Functional inferior turbinoplasty (FITS) for the treatment of resistant chronic rhinitis. Acta Otolaryngol. 2006; 126(7): Bleier BS, Schlosser RJ. Endoscopic anatomy of the postganglionic pterygopalatine innervation of the posterolateral nasal mucosa. Int Forum Allergy Rhinol. 2011; 1(2): Lin HC, LinPW, FriedmanM, ChangHW, et al. Long-term results of radiofrequency turbinoplasty for allergic rhinitis refractory to medical therapy. Arch Otolaryngol Head Neck Surg. 2010;136: Liu CM, Tan CD, Lee FP, Lin KN, Huang HM. Microdebriderassisted versus radiofrequncy-assisted inferior tubinoplasty. Laryngoscope. 2009;119: Chen YL, Tan CT, Huang HM. Long-term efficacy of microdebrider-assisted inferior turbinoplasty with lateralization for hypertrophic inferior turbinates in patients with perennial allergic rhinitis. Laryngoscope. 2008;118: Cingi C, Ure B, Cakli H, Ozudogru E. Microdebriderassisted versus radiofrequency-assisted inferior turbinoplasty: a prospective study with objective and subjective outcome measures. Acta Otorhinolaryngol Ital. 2010;30: Golding-Wood PH. Observations on petrosal and vidian neurectomy in chronic vasomotor rhinitis. J Laryngol Otol. 1961;75:232.

56 50 孩童 懷孕婦女 及老年人的鼻炎 王凌峰 1, 2 摘 戴志峰 1, 3 要 孩童鼻炎以過敏性鼻炎為主 較常發生於男孩 且常伴有異位性皮膚炎與氣喘 兒童常因嚴重的鼻子癢及 鼻塞 而需搓揉鼻子及扭動臉部 長久下來易造成臉部發育的改變 如 allergic shiner 及 adenoid face 孩童的 過敏性鼻炎通常較為難纏 需要長期的治療與追蹤 目前用於治療大人過敏性鼻炎的藥物皆能用於孩童 很少 有藥物是特別針對孩童的過敏性鼻炎而設計 在懷孕期間常會發生阻塞性或過敏性鼻炎 且症狀會加重 大部分懷孕的婦女 即便懷孕之前沒有鼻炎的 情況 在懷孕的後期也常有鼻塞的情形 此稱為懷孕性鼻炎 和女性賀爾蒙有關 懷孕性鼻炎通常對藥物治療 沒有反應 但生產後即消失 若婦女在懷孕前即有過敏性鼻炎時 在懷孕後過敏性鼻炎症狀可能會加重 減輕 或不變 在治療有過敏性鼻炎的懷孕婦女時 我們必須考慮到藥物可能對腹中胎兒或哺乳中的嬰兒的影響 特 別在懷孕初期及器官形成時期 更須小心謹慎 老年人常會有鼻子的問題 但並不是所有老年性鼻炎的原因皆為過敏 老年性鼻炎最好以鼻腔生理老化的 觀點來探討 當老化過程中 鼻腔通道會因周圍軟骨支撐力不夠而變得狹窄 老化同時也會造成鼻黏膜腺體的 萎縮退化 和血流的減少 除此之外 許多老年人常服用的藥物 如利尿劑 beta-blocker 抗焦慮劑 及抗暈 眩藥物等 皆會進一步造成鼻腔的乾燥與阻塞 本文即將探討當治療此三個特別族群的鼻炎病人時 有哪些事情是值得注意的地方 前 言 各種鼻炎的症狀表現會隨著個人年齡的不同 生 理狀況的不同 而有一些差異 因此治療的方法也應 有所調整 本文將就兒童的鼻炎 懷孕婦女的鼻炎與 老年性鼻炎 分別做介紹 孩童的過敏性鼻炎 孩童的過敏性鼻炎 較常發生於男孩 且常伴 隨 著 其 他 異 位 性 atopy 體 質 的 表 現 如 異 位 性 皮膚炎和氣喘 孩童們常因嚴重搔癢 鼻子 眼睛 或喉嚨 或鼻塞 導致常搓揉鼻頭與眼睛 或伴隨 著不自主的臉部扭動 張口呼吸 長期下來會有一 些 臉 部 發 育 的 異 常 如 黑 眼 圈 allergic shiner 鼻 頭 有 橫 紋 皺 褶 或 腺 樣 體 臉 adenoid face 等 孩 童 的 過 敏 性 鼻 炎 常 較 頑 強 故 需 長 期 規 律 的 治 療 應 避 免 無 效 率 的 治 療 導 致 病 人 常 需 逛 醫 院 治 療 的 方 法 包 括 1. 減少與避免過敏原 塵螨是孩童常見的過敏原 減少與避免塵螨的接 觸 可減少過敏性鼻炎的發作 需教導孩童遠離易有 塵螨滋生的寵物與布偶 或是定期需清理寵物或布 偶 市面上常見一些打著防塵螨招牌的頭套 被單等 寢具相關用品 這些防塵螨寢具到底有沒有用處呢 以下是幾個較大型研究的結論 (1) Gebring 等 1 學者收集了屬於過敏高危險群的 新兒生 媽媽有異位性體質 來做隨機的診察 研究組給予防塵 被套 對照組則給予一般被套 1 高雄醫學大學 醫學院 醫學系 耳鼻喉學科 高雄市立大同醫院 ( 委託高雄醫學大學經營 ) 耳鼻喉科 3 高雄市立小港醫院 ( 委託高雄醫學大學經營 ) 耳鼻喉科 王凌峰 1, 2 戴志峰 1, 3 通訊作者 戴志峰 醫師 高雄醫學大學附設中和紀念醫院 高雄市三民區十全一路 100 號 20ES 耳鼻喉科 2 耳鼻喉科

57 (1) , 2 1, IgE bronchial hyper-responsiveness 8 Der f1 Der p1 Der f1 2 (2) 另一個則為 meta-analysis 2, 探討防塵螨被套是否能避免產生過敏性疾病 ( 共 7 篇文章 ) 或減少過敏性疾病的症狀 ( 共 17 篇文章 ) 他們的結論為 : 防塵螨被套可減少被套中塵螨的量, 但它們並無法避免或減少過敏性疾病的症狀 故避免過敏原必需多管齊下, 只用單一方法無法有效減少過敏的症狀 2. 藥物治療 : (1) (2) anti- leukotriene: anti- leukotriene (3) 50% 0.1% 6 2 ( ) 3,4 (4) (5) : (6) : 3. 免疫治療 : Kim 5 subcutaneous injection immunotherapy SCIT sublingual immunotherapy SLIT the strength of evidence moderate SCIT SLIT (1) (Immunosenescence) T-cell B-cell B-cell IgG isotype class switching 7-9

58 52 (2) 6,10 11 (3) 12 (4) : 13 (5) : Ho 14 6 (6) % % % IgE IgE 16 Immunosenescence Vasomotor rhinitis gustatory rhinitis 1. 血管運動性鼻炎 : \ 味覺性鼻炎 (gustatory rhinitis): 藥物性鼻炎 : ( ) 4. 萎縮性鼻炎 : (1) 19 (2) 20

59 (1) , 2 1, 3 53 評估與診斷 : Aspirin NSAID- Non-Steroidal Anti-Inflammatory Drug / / adrenergic blockers angiotensin-converting enzyme (ACE) inhibitor Viagra sildenafil 21 IgE 22 antihistamine tricyclic antidepressant 治療方法 : ( ) ARIA 1. 避免過敏原 : 塵螨 2. 藥物治療 : Anticholinergic or sedation 免疫治療 : ( ) 1. 血管運動性鼻炎 : Anti-cholinergic cromolyn Azelastine FDA vasomotor rhinitis 27,28 2. 味覺性鼻炎 : intranasal anticholinergic agent intranasal ipratropium 29 30,31 3. 萎縮性鼻炎 : 手術方面 :

60 54 其他應考慮事項 : 結論 懷孕性鼻炎 Pregnancy Rhinitis: ( ) 32 ( ) Pregnancy rhinitis % 治療 : FDA A B C FDA ( ) Teratogen Information system, TERIS ( depts.washington.edu/terisweb/teris/preamble.htm) ( ) chlorpheniramine(b) Tripelennamine(B) The American College of Obstetricians and Gynecologists(ACOG) The American College of Allergy, Asthma and Immunology(ACAAI) 37 Loratadine B cetirizine(b) ( ) budesonide FDA category B 38 ( ) pseudoephedrine C gastroschisis 39,40 uteroplacental blood flow Oxymetazoline C 41

61 (1) , 2 1, 3 55 ( ) Cromolyn Cromolyn B UpToDate ( ) Nasal dilator 4. 結論 表三 FDA 懷孕期用藥分級的定義 Category Interpretation A Controlled studies showed no risk. Adequate, well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester of pregancy B No evidence of risk in human. Adequate, well-controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies shown no fetal risk. The chance of fetal harm is remote, but remains a possibility. C Risk cannot be ruled out. Adequate, controlled human studies are lacking, and animal studies have shown a risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is administered during pregnancy, but the potential benefits may outweigh the potential risk. D Positive evidence of risk. Studies in humans, or investigational or postmarketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. X Contraindicated in pregnancy. Studies in animals or humans, or investigational or postmarketing reports, have demonstrated positive evidence of fetal abnormalities or risk that clearly outweighs any possible benefit to the patient.

62 56 表四 常用藥物的 FDA 懷孕期用藥分級 Medications Risk Category Category B Categories C and D Antibiotics Penicillin(including Sulbactam/ Clarithromycin clavulanate) Vancomycin Cephalosporins Fluoroquinolones Clindamycin Aminoglycosides Erythromycin Sulfonamides Azithromycin Tetracycline Antihistamines Chlorpheniramine Brompheniramine Loratadine Fexofenadine Cetirizine Desloratadine Clemastine Hydroxyzine Diphenhydramine Intranasal steroid spray Budesonide Mometasone Fluticasone Beclomethasone Triamcinolone Decongestant Oxymetazoline Pseudoephedrine Cromones Leukotriene modifier Cromolyn Nedocromil Montelukast 參考文獻 1. Gehring U, de Jongste JC, Kerkhof Met al. The 8-year follow-up of the PIAMA intervention study assessing the effect of mite-impermeable mattress covers. Allergy; 67: Arroyave WD, Rabito FA, Carlson JC, Friedman EE, Stinebaugh SJ. Impermeable dust mite covers in the primary and tertiary prevention of allergic disease: a metaanalysis. Ann Allergy Asthma Immunol 2014; 112: Allen DB, Meltzer EO, Lemanske RF, Jr.et al. No growth suppression in children treated with the maximum recommended dose of fluticasone propionate aqueous nasal spray for one year. Allergy Asthma Proc 2002; 23: Murphy K, Uryniak T, Simpson B, O Dowd L. Growth velocity in children with perennial allergic rhinitis treated with budesonide aqueous nasal spray. Ann Allergy Asthma Immunol 2006; 96: Kim JM, Lin SY, Suarez-Cuervo Cet al. Allergenspecific immunotherapy for pediatric asthma and rhinoconjunctivitis: a systematic review. Pediatrics; 131: Edelstein DR. Aging of the normal nose in adults. Laryngoscope 1996; 106: Bellanti JA, Azem M, MacDowell-Carneiro AL, Tutuncuoglu SO, Wallerstedt DB. Possible mechanisms of late-life-onset allergic diseases and asthma in the senior citizen. Allergy Asthma Proc 2000; 21: Ostan R, Bucci L, Capri Met al. Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation 2008; 15: Hwang KA, Kim HR, Kang I. Aging and human CD4(+) regulatory T cells. Mech Ageing Dev 2009; 130: Patterson CN. The aging nose: characteristics and

63 (1) , 2 1, 3 57 correction. Otolaryngol Clin North Am 1980; 13: Reiss M, Reiss G. [Rhinitis in old age]. Praxis (Bern 1994) 2002; 91: Schrodter S, Biermann E, Halata Z. Histological evaluation of age-related changes in human respiratory mucosa of the middle turbinate. Anat Embryol (Berl) 2003; 207: Lindemann J, Sannwald D, Wiesmiller K. Age-related changes in intranasal air conditioning in the elderly. Laryngoscope 2008; 118: Ho JC, Chan KN, Hu WHet al. The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia. Am J Respir Crit Care Med 2001; 163: Seiberling KA, Conley DB. Aging and olfactory and taste function. Otolaryngol Clin North Am 2004; 37: , vii. 16. Jackola DR, Pierson-Mullany LK, Daniels LR, Corazalla E, Rosenberg A, Blumenthal MN. Robustness into advanced age of atopy-specific mechanisms in atopy-prone families. J Gerontol A Biol Sci Med Sci 2003; 58: Lal D, Corey JP. Vasomotor rhinitis update. Curr Opin Otolaryngol Head Neck Surg 2004; 12: Salib RJ, Harries PG, Nair SB, Howarth PH. Mechanisms and mediators of nasal symptoms in non-allergic rhinitis. Clin Exp Allergy 2008; 38: Jordan JA, Mabry RL. Geriatric rhinitis: what it is, and how to treat it. Geriatrics 1998; 53:76, Dutt SN, Kameswaran M. The aetiology and management of atrophic rhinitis. J Laryngol Otol 2005; 119: Slavin RG. Treating rhinitis in the older population: special considerations. Allergy Asthma Clin Immunol 2009; 5: King MJ, Lockey RF. Allergen prick-puncture skin testing in the elderly. Drugs Aging 2003; 20: Plaut M, Valentine MD. Clinical practice. Allergic rhinitis. N Engl J Med 2005; 353: Li J, Tripathi RC, Tripathi BJ. Drug-induced ocular disorders. Drug Saf 2008; 31: Rosenwasser LJ. Treatment of allergic rhinitis. Am J Med 2002; 113 Suppl 9A:17S-24S. 26. Asero R. Efficacy of injection immunotherapy with ragweed and birch pollen in elderly patients. Int Arch Allergy Immunol 2004; 135: Ciprandi G. Treatment of nonallergic perennial rhinitis. Allergy 2004; 59 Suppl 76:16-22; discussion Banov CH, Lieberman P. Efficacy of azelastine nasal spray in the treatment of vasomotor (perennial nonallergic) rhinitis. Ann Allergy Asthma Immunol 2001; 86: Naclerio RM. Optimizing treatment options. Clin Exp Allergy 1998; 28 Suppl 6: Naumann M, Jost W. Botulinum toxin treatment of secretory disorders. Mov Disord 2004; 19 Suppl 8:S Laing TA, Laing ME, O Sullivan ST. Botulinum toxin for treatment of glandular hypersecretory disorders. J Plast Reconstr Aesthet Surg 2008; 61: Mazzotta P, Loebstein R, Koren G. Treating allergic rhinitis in pregnancy. Safety considerations. Drug Saf 1999; 20: Ellegard E, Hellgren M, Toren K, Karlsson G. The incidence of pregnancy rhinitis. Gynecol Obstet Invest 2000; 49: Ellegard EK. Special considerations in the treatment of pregnancy rhinitis. Womens Health (Lond Engl) 2005; 1: Philpott CM, Conboy P, Al-Azzawi F, Murty G. Nasal physiological changes during pregnancy. Clin Otolaryngol Allied Sci 2004; 29: Franklin KA, Holmgren PA, Jonsson F, Poromaa N, Stenlund H, Svanborg E. Snoring, pregnancy-induced hypertension, and growth retardation of the fetus. Chest 2000; 117: The use of newer asthma and allergy medications during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) and The American College of Allergy, Asthma and Immunology (ACAAI). Ann Allergy Asthma Immunol May;84(5): Kallen BA, Otterblad Olausson P. Maternal drug use in early pregnancy and infant cardiovascular defect. Reprod Toxicol 2003; 17: Werler MM, Mitchell AA, Shapiro S. First trimester maternal medication use in relation to gastroschisis. Teratology 1992; 45: Torfs CP, Katz EA, Bateson TF, Lam PK, Curry CJ. Maternal medications and environmental exposures as risk factors for gastroschisis. Teratology 1996; 54: Incaudo GA. Diagnosis and treatment of allergic rhinitis and sinusitis during pregnancy and lactation. Clin Rev Allergy Immunol 2004; 27: Metzger WJ, Turner E, Patterson R. The safety of immunotherapy during pregnancy. J Allergy Clin Immunol 1978; 61: Shaikh WA. A retrospective study on the safety of immunotherapy in pregnancy. Clin Exp Allergy 1993; 23: Stroud RH, Wright ST, Calhoun KH. Nocturnal nasal congestion and nasal resistance. Laryngoscope 1999; 109:

64 58

65 (1) 徐欣健 1 盧盈州 2 黃弘孟 1,3 摘 要 (Drug-induced rhinitis) (Drug-induced rhinitis) (Non-allergic rhinitis) : (1) (Local inflammatory type) ; (2) (Neurogenic type); (3) (Idiopathic type) ; (4) (Rhinitis Medicamentosa) (Topical decongestants) (Aspirin) (NSAIDs) (Anti-hypertensives) (Anti-psychotics) (Hormones) (Vasodilators) key word : Drug-induced rhinitis, Non-allergic rhinitis, Rhinitis Medicamentosa, ARIA & ACAAI & AAAI ( ARIA& ACAAI & AAAI) 前言 (Drug-induced rhinitis) 2008 ARIA (Allergic Rhinitis and its Impact on Asthma) 1 the American College of Allergy, Asthma & Immunology (ACAAI)/the American Academy of Allergy, Asthma & Immunology (AAAI) 2 (Drug-induced rhinitis) (Non-allergic rhinitis) : (1) (Local inflammatory type) ; (2) (Neurogenic type); (3) (Idiopathic type) ; (4) (Rhinitis Medicamentosa) 3 Rhinitis Medicamentosa (Drug-induced rhinitis) Rhinitis Medicamentosa (Topical decongestants) (Aspirin) (NSAIDs) (Anti- hypertensives) (Antipsychotics) (Hormones) (Vasodilators) 藥物性鼻炎分類及機轉 (1) (Local inflammatory type) (Aspirin) (NSAIDs) ( : [email protected]

66 60 1) (Asthma) Samter s triad (Chronic rhinosinusitis with nasal polyps + Asthma + Aspirin/ NSAIDs sensitivity) 4 5-1(Cyclooxygenase-1;COX-1) (Prostaglandin;PGs) (Arachidonic acid) (Lipooxygenase;LOX) (Leukotriene;LTs) C4(LTC4) 3,6 (2) (Neurogenic type) (Antihypertensives) (Anti-psychotics) (Vasodilators) Methyldopa( ) Reserpine( ) Guanethidine( ) Phentolamine ( ) Prazosin/Terazosin( ) Sildenafil (Viagra ; ) ( 1) 3 (3) (Idiopathic type) (Antihypertensives) (Anti-psychotics) (Hormones) (Miscellaneous) Amiloride( ) Angiotensinconverting-enzyme inhibitor(ace inhibitor; ) Oral blocker( ) Calcium channel blocker( ) Exogenous estrogens( ) Oral contraceptives( ) Risperidone( ) Gabapentin ( ; ) ( 1) 3 (4) (Rhinitis Medicamentosa) 1887 (Ephedrine) ( ) Fox Feinberg & Friedlaender (Rebound congestion) ( Privine; Naphazoline hydrochloride ) Lake Rhinitis medicamentosa 10 (Rebound or Chemical rhinitis) Rhinitis Medicamentosa ( 10 ) Naphazoline Oxymetazoline Xylometazoline( 2) 1. ; 2. ; ~7% 12,13 Rhinitis Medicamentosa - ( 1 2 receptors) - ( receptors) ! - (Negative feedback) (Norepinephrine) (Tachyphylaxis) - Rhinitis medicamentosa 12,15

67 (1) ,3 61 診斷 (Drug-induced rhinitis) (Allergic and non-allergic rhinitis) Samter s triad (Chronic rhinosinusitis with nasal polyps + Asthma + Aspirin/ NSAIDs sensitivity) Rhinitis Medicamentosa 3 Medicamentosa 17 總結 Rhinitis Medicamentosa 治療 ( ) (Intranasal cortosteroid spray) 12 3,16 Rhinitis Medicamentosa 5~7 3 Rhinitis

68 62 l 3 2 Rhinitis Medicamentosa 3 3 Category Cardiovascular Drug Beta-blocker Alpha-blocker Centrally acting antihypertensives (methyldopa, reserpine) Angiotensin converting enzyme inhibitors Niacin Central Nervous System Endocrine Other Typical/atypical antipsychotics Chlormethiazole Citalopram Gabapentin Oral Contraceptives Estrogens Sildenafil Aspirin/NSAIDs Mycophenolate mofetil Penicillamine Lamivudine

69 (1) ,3 63 參考文獻 1. Bousquet J, Khaltaev N, Cruz AAet al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2) LEN and AllerGen). Allergy 2008; 63 Suppl 86: Wallace DV, Dykewicz MS, Bernstein DIet al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol 2008; 122:S Varghese M, Glaum MC, Lockey RF. Drug-induced rhinitis. Clin Exp Allergy 2010; 40: Szczeklik A, Nizankowska E. Clinical features and diagnosis of aspirin induced asthma. Thorax 2000; 55 Suppl 2:S Eriksson J, Ekerljung L, Bossios Aet al. Aspirin-intolerant asthma in the population: prevalence and important determinants. Clin Exp Allergy 2015; 45: Stevenson DD, Szczeklik A. Clinical and pathologic perspectives on aspirin sensitivity and asthma. J Allergy Clin Immunol 2006; 118: ; quiz Baldwin RL. Rhinitis medicamentosa (an approach to treatment). J Med Assoc State Ala 1975; 47: Fox. The chronic effect of epinephrine and ephedrine on the nasal mucosa. Arch Otolaryngol 1931; 13: Feinberg S, Friedlaender S. Nasal congestion from frequent use of privine hydrochloride. J Am Med Assoc 1945; 128: Lake CF. Rhinitis medicamentosa. Proc Staff Meet Mayo Clin 1946; 21: Milosevic D, Janosevic L, Dergenc R, Vasic M. [Pathologic conditions associated with drug-induced rhinitis]. Srpski arhiv za celokupno lekarstvo 2004; 132: Graf P. Rhinitis medicamentosa: a review of causes and treatment. Treat Respir Med 2005; 4: Toohill RJ, Lehman RH, Grossman TW, Belson TP. Rhinitis medicamentosa. Laryngoscope 1981; 91: Ramey JT, Bailen E, Lockey RF. Rhinitis medicamentosa. J Investig Allergol Clin Immunol 2006; 16: Lacroix JS. Adrenergic and non-adrenergic mechanisms in sympathetic vascular control of the nasal mucosa. Acta physiologica Scandinavica Supplementum 1989; 581: Ratner PH, Hampel F, Van Bavel Jet al. Combination therapy with azelastine hydrochloride nasal spray and fluticasone propionate nasal spray in the treatment of patients with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2008; 100: Graf PM. Rhinitis medicamentosa. Clin Allergy Immunol 2007; 19:

70 64 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Drug-induced rhinitis ABSTRACT Drug-induced rhinitis is characterized by inflammation of the mucous membranes lining the nose and related to the abuse or overuse of drugs. Drug-induced rhinitis is a type of non-allergic rhinitis. The cause of drug-induced rhinitis still not yet fully clarified. There were three main types and one special type of drug-induced rhinitis based on the possible pathophysiology, including inflammatory, neurogenic, idiopathic and special (Rhinitis Medicamentosa) types. Many drugs can cause drug-induced rhinitis, such as topical decongestants, aspirin, NSAIDs, oral decongestants, anti-hypertensives, anti-psychotics, hormones and vasodilators. A careful medical history and physical examination are most important in diagnosing drug-induced rhinitis, with particular attention to the chronic use of topical nasal decongestants or other medications. The main treatment should be to discontinue the use of the medicine, and commence on a course of intranasal cortosteroid spray. The use of an intranasal antihistamine in combination with intranasal corticosteroid therapy may be considered as step-up therapy if the intranasal corticosteroid alone is ineffective. Occasionally, a short course of systemic corticosteroids for severe drug-induced rhinitis may be indicated. Key words: Drug-induced rhinitis, Non-allergic rhinitis, Rhinitis Medicamentosa, ARIA & ACAAI & AAAI From the 1 Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan Send Correspondence to Dr. Hung-Meng Huang, Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, 250, WuXing Street, Taipei, Taiwan. [email protected]

71 (1) 藍敏瑛 1,2 何青吟 1,2 許志宏 1,2 摘要 Key words 前言 IgE 1,2 (wheeze) 3 (remodeling) 3 4 (unified airway model) , 流行病學 過敏性鼻炎與氣喘相關性 30 7 ~8 10,24,25 75 ~ ~ % 3 8,9, , ext [email protected]

72 66 14, ,23 23 (occupational triggers) 病理生理學 發炎反應 (crosstalk) 自主神經系統 (neuroregulatory) 35,36 P(substance P) (calcitonin gene-related peptide) (histamine) bradykinin cholinergic (neurotransmitters) 組織病理學 6 (eosinophils) (cytokines) 42 (cavernous sinusoids) 1 (remodeling) 4 T 2 Th2 interleukin, IL -4 IL-5 IL (intercellular adhesion molecule)-1 (vascular cell adhesion molecule)-1 4,43 (mast cell) (degranulation) (leukotrienes) (basic protein) ,37 治療 15,16,44 IgE (IgE-mediated sensitization) 45 (intranasal corticosteroids)

73 (1) ,2 1,2 1,2 67 (bronchial hyperresponsiveness, BHR) 15,16 inhaled corticosteroids, ICS 3 ICS BHR 3 1,3,4 omalizumab IgE 46,47 (immunotherapy) 48 結論 參考文獻 1. Bousquet J, Van Cauwenberge P, Khaltaev N, ARIA Workshop Group, World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108(5): Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization. GA(2) LEN and AllerGen). Allergy 2008;63(86): Global initiative for asthma: global strategy for asthma management and prevention Available at: www. ginasthma.org. 4. Georgopoulos R, Krouse JH, Toskala E. Why otolaryngologists and asthma are a good match: the allergic rhinitis-asthma connection. Otolaryngol Clin North Am 2014;47(1): Krouse JH. The unified airway conceptual framework. Otolaryngol Clin North Am 2008;41: Krouse JH, Brown RW, Fineman SM, et al. Asthma and the unified airway. Otolaryngol Head Neck Surg 2007;136(5):S Feng CH, Miller MD, Simon RA. The united allergic airway: connections between allergic rhinitis, asthma, and chronic sinusitis. Am J Rhinol Allergy 2012;26(3): Guerra S, Sherrill DL, Martinez FD, et al. Rhinitis as an independent risk factor for adult-onset asthma. J Allergy Clin Immunol 2002;109: Corren J. Allergic rhinitis and asthma: how important is the link? J Allergy Clin Immunol 1997;99:S Blomme K, Tomassen P, Lapeere H. Prevalence of allergic sensitization versus allergic rhinitis symptoms in an unselected population. Int Arch Allergy Immunol 2013;160(2): Settipane RJ, Hagy GW, Settipane GA. Long-term risk factors for developing asthma and allergic rhinitis: a 23-year follow-up of college students. Allergy Proc 1994;15: Leynaert B, Bousquet J, Neukirch C, et al. Perennial rhinitis: an independent risk factor for asthma in nonatopic subjects: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol 1999;104(2): Meltzer EO, Hamilos DL, Hadley JA, et al. Rhinosinusitis: establishing definitions for clinical research and patient care. Otolaryngol Head Neck Surg 2004;131(6): S Linneberg A, Henrick Nielsen N, Frolund L, et al. The link between allergic rhinitis and asthma: a prospective,

74 68 population-based study, the Copenhagen Allergy Study. Allergy 2002;57: Stelmach R, do Patrocinio T Nunes M, Ribeiro M, et al. Effect of treating allergic rhinitis with corticosteroids in patients with mild-to-moderate persistent asthma. Chest 2005;128(5): Watson WT, Becker AB, Simons FE. Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: effect on lower airway responsiveness. J Allergy Clin Immunol 1993;91: Jani A, Hamilos DL. Current thinking on the relationship between rhinosinusitis and asthma. J Asthma 2005;42(1): Lund V. The effect of sinonasal surgery on asthma. Allergy 1999;57: Aubier M, Neukirch C, Peiffer C, et al. Effect of cetirizine on bronchial hyperresponsiveness in patients with seasonal allergic rhinitis and asthma. Allergy 2001;56: Mo ller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhino-conjunctivitis (the PAT study). J Allergy Clin Immunol 2002;109(2): Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children A 14 year study. Pediatrics 1968;42: Jacobsen L, Nuchel Petersen B, Wihl HA, et al. Immunotherapy with partially purified and standardized tree pollen extracts. IV: results from long-term (6 year) follow-up. Allergy 1997;52: Huse DM, Harte SC, Russel MW, et al. Allergic rhinitis may worsen asthma symptoms in children: the international Asthma Outcomes registry. Am J Respir Crit Care Med 1996;153:A Akinbami LJ. Asthma prevalence, health care use, and mortality: United States, Natl Health Stat Report 2011;(32): Schiller JS, Lucas JW, Peregoy JA. Summary health statistics for U.S. adults: National Health Interview Survey, National Center for Health Statistics. US Department of Health and Human Services Centers for Disease Control and Prevention. Vital Health Stat 2012;(252): Prieto J, Gutierrez V, Berto JM, et al. Sensitivity and maximal response to methacholine in perennial and seasonal allergic rhinitis. Clin Exp Allergy 1996;26: Strachan DP, Cook DG. Health effects of passive smoking. 6. Parental smoking and childhood asthma: longitudinal and case control studies. Thorax 1998;53(3): Eisner MD, Yelin EH, Henke J, et al. Environmental tobacco smoke and adult asthma. The impact of changing exposure status on health outcomes. Am J Respir Crit Care Med 1998;158: Ford ES. The epidemiology of obesity and asthma. J Allergy Clin Immunol 2005;115(5): Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 1999;354(9178): Johnston SL, Pattemore PK, Sanderson G, et al. Community study of role of viral infections in exacerbations of asthma in 9 11 year old children. BMJ 1995;310(6989): Braunstahl GJ, Kleinjan A, Overbeek SE, et al. Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients. Am J Respir Crit Care Med 2000;161: Braunstahl GJ, Overbeek SE, Kleinjan A, et al. Nasal allergen provocation induces adhesion molecule expression and tissue eosinophila in upper and lower airways. J Allergy Clin Immunol 2001;107(3): Braunstahl GJ, Overbeek SE, Fokkens WJ, et al. Segmental bronchoprovocation in allergic rhinitis patients affects mast cell and basophil numbers in nasal and bronchial mucosa. Am J Respir Crit Care Med 2001;164: Fontanari P, Burnet H, Zatarra-Hartmann MC, et al. Changes in airway resistance induced by nasal inhalation of cold dry, dry, or moist air in normal individuals. J Appl Physiol 1996;81(4): Sarin S, Undem B, Sanico A, et al. The role of the nervous system in rhinitis. J Allergy Clin Immunol 2006;118(5): Lemanske RF, Busse WW. Asthma. J Allergy Clin Immunol 2003;111(2): Erjavec F, Lembeck F, Florjanc-Irman T, et al. Release of histamine by substance P. Naunyn Schmiedebergs Arch Pharmacol 1981;317: Piotrowski W, Foreman JC. Some effects of calcitonin gene-related peptide in human skin and on histamine release. Br J Dermatol 1986;114(1): Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev 2006;86(1): Canning BJ. Reflex regulation of airway smooth muscle tone. J Appl Phys 2006;101(3): Togias A. Rhinitis and asthma: evidence for respiratory system integration. J Allergy Clin Immunol 2003;111(6): Bachert C, Vignola AM, Gevaert P, et al. Allergic rhinitis,

75 (1) ,2 1,2 1,2 69 rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am 2004;24(1): Taramarcaz P, Gibson PG. Intranasal corticosteroids for asthma control in people with coexisting asthma and rhinitis. Cochrane Database Syst Rev 2003;(4):CD Bush RK. The use of anti-ige in the treatment of allergic asthma. Med Clin North Am 2002;86: Dimov VV, Casale TB. Immunomodulators for asthma. Allergy Asthma Immunol Res 2010;2(4): Nelson HS, Weiss ST, Bleeker ER, et al. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006;129(5): Stokes JR, Casale TB. Allergic rhinitis and asthma: celebrating 100 years of Immunotherapy. Curr Opin Immunol Dec;23(6):

76 70 J Taiwan Otolaryngol Head Neck Surg Vol., Suppl (1), 2015 Allergic Rhinitis and Asthma ABSTRACT Nowadays, the nose, the paranasal sinuses, and the respiratory bronchi are considered as constituents of one functional unit, referred to as the unified airway model. The upper and lower airways have many similarities in anatomic structures and physiologic functions. They are all lined by a pseudostratified ciliated columnar epithelium, and have similar inflammatory cell profile. Allergic rhinitis has been proved to be associated with asthma in both epidemiological and pathophysiological studies, and also as a risk factor for asthma development. Two mechanisms are proposed to explain the link between allergic rhinitis and asthma: one is through a complex interaction of inflammatory mediators and another is through the autonomic system. Studies found that local irritation within the respiratory tract can result in upregulation of many kinds of inflammatory mediators at a distal site and neuronal stimulation in the nose can lead to contraction of the bronchial smooth muscle by releasing of cholinergic neurotransmitters. It has been shown that proper management of allergic rhinitis can improve asthma control. Therefore, it is important to be familiar with the diagnosis and management of asthma while treating patients with allergic rhinitis. Key words : allergic rhinitis asthma inflammatory mediators autonomic system

77 (1) 江秉穎 1,2,3 摘 要 (sleepdisordered breathing) key words : 前言 68% 48% 1 鼻炎與睡眠障礙的相關性 Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines 2010 (sleep disturbance) 2 3 (sleep-disordered breathing) (simple snoring) (upper airway resistance syndrome, UARS) (obstructive hypoventilation, OH) (obstructive sleep apnea syndrome, OSAS) 鼻炎引起睡眠障礙的機轉 9,10 (cytokines) 11 (cortisol) , 14 ( 1.) (cortisol) (ISSTA) : [email protected]

78 72 13 (microarousals) , , ,25 (inflammatory mediators) histamine, interleukin (IL)-1 IL-4 IL Histamine (neurotransmitter) 26 interleukin (IL)-1 IL-4, IL-10 (REM latency) (REM duration) Interleukin-1 tumor necrosis factor (TNF) and IL-6 (OSA) OSA TNF IL-6 IL 鼻炎, 睡眠與生活品質 ,37 38 (overnight polysomnography) 7,11,16,17,28,39,40,41 療效 ( TNF ) (topical nasal corticosteroid) SSRI(selective serotonergic reuptake inhibitor) protriptyline, methylxanthine estrogen 42 AASM Practice Parameters 42 3, 43 44,45 44,45 (oral decongestants) ( ) 43 (topcial decongestants) (rhinitis medicamentosa) 43 (anticholinergic agent ) ipratropium bromide 46 (leukotriene receptor antagonists), montelukast 47,48

79 (1) ,2, ,52 53~ ,60 61 (verbal memory) 62 (apnea) (hypopnea) (alertness) (immunotherapy) 1. Reinberg et al. 13 Craig et al. 14 環境控制法 (Environmental Control Intervention) 2 64,65 ( 4/9 12/14) 65 ARIS 2 結論 Montelukast 參考文獻 1. Blaiss M, Reigel T, Philpot E. A study to determine the impact of rhinitis on sufferers sleep and daily routine. J Allergy Clin Immunol 2005;115:S Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol; 2010; 126(3): Lunn M, Craig T. Rhinitis and sleep. Sleep Med Rev Oct;15(5): International Classification of Sleep Disorders -3rd edition, 2014, American Academy of Sleep Medicine, Suratt PM, Turner BL, Wilhoit SC. Effect of intranasal obstruction on breathing during sleep. Chest 1986;90: Millman RP, Acebo C, Rosenberg C, Carskadon MA. Sleep, breathing, and cephalometrics in older children and young adults. Part II - response to nasal occlusion. Chest 1996;109: Young T, Finn L, Palta M. Chronic nasal congestion at night is a risk factor for snoring in a population-based cohort study. Arch Intern Med 2001;161:

80 74 8. Rappai M, Collop N, Kemp S. The nose and sleepdisordered breathing. What we know and what we do not know. Chest 2003;124: Craig TJ, McCann JL, Gurevich F, et al. The correlation between allergic rhinitis and sleep disturbance. J Allergy Clin Immunol 2004;114:S Craig TJ, Teets S, Lehman EB, et al. Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids. J Allergy Clin Immunol 1998;101: Stuck BA, Czajkowski J, Hagner AE, Klimek L, Verse T, Hörmann K, et al. Changes in daytime sleepiness, quality of life, and objective sleep patterns in seasonal allergic rhinitis: a controlled clinical trial. J Allergy Clin Immunol 2004;113: Rundcrantz H. Postural variations of nasal patency. Acta Otolaryngol 1969;68: Reinberg A, Gervais P, Levi F, Smolensky M, Del Cerro L, Ugolini C. Circadian and circannual rhythms of allergic rhinitis: an epidemiologic study involving chronobiologic methods. J Allergy Clin Immunol 1988;81: Craig TJ, Ferguson BJ, Krouse JH. Sleep impairment in allergic rhinitis, rhinosinusitis, and nasal polyposis. Am J Otolaryngol 2008 May-Jun;29(3): Landstra AM, Postma DS, Boezen HM, van Aalderen WM. Role of serum cortisol levels in children with asthma. Am J Respir Crit Care Med 2002;165: Lavie P, Gertner R, Zomer J, Podoshin L. Breathing disorders in sleep associated with microarousals in patients with allergic rhinitis. Acta Otolaryngol 1981;92: McNicholas WT, Tarlo S, Cole P, Zamel N, Rutherford R, Griffin D, et al. Obstructive sleep apneas during sleep in patients with seasonal allergic rhinitis. Am Rev Respir Dis 1982;126: Suratt PM, Turner BL, Wilhoit SC. Effect of intranasal obstruction on breathing during sleep. Chest 1986;90: Millman RP, Acebo C, Rosenberg C, Carskadon MA. Sleep, breathing, and cephalometrics in older children and young adults. Part II - response to nasal occlusion. Chest 1996;109: Meltzer EO. Quality of life in adults and children with allergic rhinitis. J Allergy Clin Immunol 2001;108:S Canova CR, Downs SH, Knoblauch A, Andersson M, Tamm M, Leuppi JD.Increased prevalence of perennial allergic rhinitis in patients with obstructive sleep apnea. Respiration 2004;71: Storms WW. Pharmacologic approaches to daytime and nighttime symptoms of allergic rhinitis. J Allergy Clin Immunol 2004;114:S Camhi SL, Morgan WJ, Pernisco N, Quan SF. Factors affecting sleep disturbances in children and adolescents. Sleep Med 2000;1: Pitt AD, Smith AF, Lindsell L, Voon LW, Rose PW, Bron AJ. Economic and quality-of-life impact of seasonal allergic conjunctivitis in Oxfordshire. Ophthalmic Epidemiol 2004 Feb;11(1): Sack R, Conradi L, Beaton A, Sathe S, McNamara N, Leonardi A. Antibody array characterization of inflammatory mediators in allergic and normal tears in the open and closed eye environments. Exp Eye Res 2007 Oct.;85(4): Tashiro M, Mochizuki H, Iwabuchi K, Sakurada Y, Itoh M, Watanabe T, et al. Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain. Life Sci 2002;72: Mullington JM, Hinze-Selch D, Pollmacher T. Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions. Ann N Y Acad Sci 2001;933: Krouse HJ, Davis JE, Krouse JH. Immune mediators in allergic rhinitis and sleep. Otolaryngol Head Neck Surg 2002;126: Aoyagi M, Watanabe H, Sekine K, Nishimuta T, Konno A, Shimojo N, et al. Circadian variation in nasal reactivity in children with allergic rhinitis:correlation with the activity of eosinophils and basophilic cells. Int Arch Allergy Immunol 1999;120: Vgontzas AN, Zoumakis E, Bixler EO, Lin HM, Follett H, Kales A, et al. Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab 2004 May.;89(5): Woodson BT, Brusky LT, Saurajen A, Jaradeh S. Association of autonomic dysfunction and mild obstructive sleep apnea. Otolaryngol - Head Neck Surg 2004 Jun;130(6): Marshall PS, O Hara C, Steinberg P. Effects of seasonal allergic rhinitis on selected cognitive abilities. Ann Allergy Asthma Immunol 2000;84: Wilken JA, Berkowitz R, Kane R. Decrements in vigilance and cognitive functioning associated with ragweedinduced allergic rhinitis. Ann Allergy Asthma Immunol 2002;89:

81 (1) ,2, Kessler RC, Almeida DM, Berglund P, Stang P. Pollen and mold exposure impairs the work performance of employees with allergic rhinitis. Ann Allergy Asthma Immunol 2001;87: Lack G. Pediatric allergic rhinitis and comorbid disorders. J Allergy Clin Immunol 2001;108:S Vuurman EF, van Veggel LM, Uiterwijk MM, Leutner D, O Hanlon JF. Seasonal allergic rhinitis and antihistamine effects on children s learning. Ann Allergy 1993;71: Simons FE. Learning impairment and allergic rhinitis. Allergy Asthma Proc 1996;17: Flemons WW, Tsai W. Quality of life consequences of sleep-disordered breathing. J Allergy Clin Immunol 1997;99:S Young T, Finn L, Kim H, The University of Wisconsin Sleep and Respiratory Research Group. Nasal obstruction as a risk factor for sleep-disordered breathing. J Allergy Clin Immunol 1997;99:S Mansfield LE, Diaz G, Posey CR, Flores-Neder J. Sleep disordered breathing and daytime quality of life in children with allergic rhinitis during treatment with intranasal budesonide. Ann Allergy Asthma Immunol 2004;92: Craig TJ, Mende C, Hughes K, et al. The effect of topical nasal fluticasone on objective sleep testing and the symptoms of rhinitis, sleep, and daytime somnolence in perennial allergic rhinitis. Allergy Asthma Proc 2003;24: Morgenthaler TI; Kapen S; Lee-Chiong T et al. Practice parameters for the medical therapy of obstructive sleep apnea. SLEEP 2006;29(8): American Academy of Allergy. Asthma and Immunology. The Allergy report. Available at: theallergyreport.com/reportindex.html [accessed ]. 44. Murray JJ, Nathan RA, Bronsky EA, et al. Comprehensive evaluation of cetirizine in the management of seasonal allergic rhinitis: impact on symptoms, quality of life, productivity, and activity impairment. Allergy Asthma Proc 2002;23: Golden S, Teets SJ, Lehman EB, et al. Effect of topical nasal azelastine on the symptoms of rhinitis, sleep, and daytime somnolence in perennial allergic rhinitis. Ann Allergy Asthma Immunol 2000;85: Milgrom H, Biondi R, Georgitis JW, et al. Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children. Ann Allergy Asthma Immunol 1999;83: Goldbart AD, Goldman JL, Veling MC, Gozal D. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med 2005;172: Ohta N, Sakuri S, Yoshitake H, et al. Study of the effects of anti-leukotriene receptor antagonists on chronic allergic rhinitis using QOL as an index. Presented at: World Allergy Congress; June 26-July 1; 2005; Munich, Germany. 49. Chen ST, Lu KH, Sun HL, Chang WT, Lue KH, Chou MC. Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2-6 yr. Pediatr Allergy Immunol 2006;17(1): Santos CB, Hanks C, McCann J, Lehman EB, Pratt E, Craig TJ. The role of montelukast on perennial allergic rhinitis and associated sleep disturbances and daytime somnolence. Allergy Asthma Proc 2008, Apr;29(2): van Cauwenberge P, Bachert C, Passalacqua G, Bousquet J, Canonica GW, Durham SR, et al. Consensus statement on the treatment of allergic rhinitis.european Academy of Allergology and Clinical Immunology. Allergy 2000;55: Bousquet J, van Cauwenberge P, Khaltaev N. ARIAWorkshop Group, World Health Organization: allergic rhinitis and its impact on asthma (ARIA). J Allergy Clin Immunol 2001;108:S Gawchik S, Goldstein S, Prenner B, John A. Relief of cough and nasal symptoms associated with allergic rhinitis by mometasone furoate nasal spray. Ann Allergy Asthma Immunol 2003;90: Mandl M, Nolop K, Lutsky BN Study Group: comparison of once daily mometasone furoate (Nasonex) and fluticasone propionate aqueous nasal sprays for the treatment of perennial rhinitis. Ann Allergy Asthma Immunol 1997;79: Meltzer EO, Staudinger H, Bloom M, et al. Efficacy of once-daily mometasone furoate in patients with seasonal allergic rhinitis and severe nasal congestion. Presented at: World Allergy Congress; June 26-July 1, 2005; Munich, Germany (abstract 710). 56. Bende M, Carrillo T, Vóna I, da Castel-Branco MG, Arheden L. A randomized comparison of the effects of budesonide and mometasone furoate aqueous nasal sprays on nasal peak flow rate and symptoms in perennial allergic rhinitis. Ann Allergy Asthma Immunol 2002;88: Wilson AM, Orr LC, Sims EJ, et al. Effects of monotherapy with intra-nasal corticosteroid or combined oral antihistamine and leukotriene receptor antagonists in seasonal allergic rhinitis. Clin Exp Allergy 2001;31:61-8.

82 Mansfield LE, Posey CR. Daytime sleepiness and cognitive performance improve in seasonal allergic rhinitis treated with intranasal fluticasone propionate. Allergy Asthma Proc 2007 MareApr;28(2): Hughes K, Glass C, Ripchinski M, et al. Efficacy of the topical nasal steroid budesonide on improving sleep and daytime somnolence in patients with perennial allergic rhinitis. Allergy 2003;58: Craig TJ, Gurevich F, Glass C, et al. The effect of intranasal steroid budesonide on sleep disturbance and daytime somnolence in patients with perennial allergic rhinitis. J Allergy Clin Immunol 2004;113:S332 (abstract 1227). 61. Kamenov S, Kamenov B, Moskovljevic J, et al. Intranasal budesonide treatment of rhino-sinusitis improves quality of life in school children. Presented at: World Allergy Congress; June 26-July 1, 2005; Munich, Germany. 62. Bender BG, Milgrom H. Comparison of the effects of fluticasone propionate aqueous nasal spray and loratadine on daytime alertness and performance in children with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2004;92: Kiely JL, Nolan P, McNicholas WT. Intranasal corticosteroid therapy for obstructive sleep apnoea in patients with co-existing rhinitis. Thorax 2004;59: Bjornsdottir US, Jakobinudottir S, Runarsdottir V, Juliusson S. The effect of reducing levels of cat allergen (Fel d 1) on clinical symptoms in patients with cat allergy. Ann Allergy Asthma Immunol 2003;91(2): Wood RA, Johnson EF, Van-Natta ML, Chen PH, Eggleston PA. A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy. Am J Respir Crit Care Med 1998;158(1):

83 (1) Rhinitis and Sleep-Disordered Breathing Rayleigh Ping-Ying Chiang, M.D., M.M.S. ABSTRACT The rhinitis patients often suffer from sleep problems, including difficulty in falling asleep, sleep interruption, and sleep-disordered breathing. The consequences of obstructive sleep apnea includes cardiovascular diseases, hypertension, poor blood sugar control, cerebral-vascular diseases, etc, and also the impacts on daytime sleepiness, fatigue, poor concentration, memory, performance, and even the psychiatric symptoms, such as depression. Therefore, the management of rhinitis should not only focus on the improvement of nasal symptoms, but also the quality of sleep, leading to the wellness and good quality of life. Send Correspondence to Rayleigh Ping-Ying Chiang, M.D., M.M.S., Department of Otolaryngology Head and Neck Surgery, Taipei Veterans General Hospital. No.201, Sec. 2, Shipai Rd., Beitou District, Taipei City, Taiwan Key words: rhinitis, sleep, quality of sleep, quality of life, sleep-disordered breathing, treatment, clinical practice guideline

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