Advances in the treatment of allergic rhinitis变应性鼻炎的治疗进展Dr Warner Carr MD1Burden of allergic rhinitisARAR对患者及社会造成的严重负担对患者及社会造成的严重负担Allergic rhinitis (AR) occurs in over 500 million people around the world1 （全球约有5亿变应性鼻炎患者） The effects of AR are underestimated （AR的影响被低估）Symptomatic burden2（症状困扰）Reduces patient quality of life3（降低患者生活质量）Impairs school and work performance4,5（导致患者工作和学习成绩下降）AR is a costly disease（经济负担）4260/patient/year in Europe6 （欧洲，4260/患者/年）3.4 billion US$ annually in the United States in direct medical costs alone.7（美国每年直接医疗费用一项约为34亿美元）1. Bousquet et al, Allergy 2008;63:8-160. 2. Meltzer et al, JACI 2009; 124:S43-70. 3. Canonica et al, Allergy 2007;62:17-25. 4. Walket et al, JACI 2007;120:381-7. 5. Vandenplas et al Curr Opin Allergy Clin Immunol 2008;8:145-9. 6. Bousquet et al Allergy 2005;60:788-94. 7. Meltzer & Buckstein AAAI 2011;106:S12-6.Allergic Rhinitis: Affects Quality of Life 生活质量影响生活质量影响Juniper EF, et al. Clin Exp Allergy. 1991;21:77-83. 1. AAAAI. The Allergy Report 2000. . 2. Spector SL. J Allergy Clin Immunol 1997;99:S773-80. 3. Ker & Hartert AAAI 2009;103:282-9. 4. Vandenplais et al, Allergy 2010;65:1290-7. 5. Park et al Asian Pac J Allergy Immunol 2009;27:167-71. 6. Bousquet et al, Allergy 2008;63:8-160. AR: allergic rhinitisCommon Comorbidities1,2（AR常见合并症）常见合并症）AllergicRhinitisUpperRespiratoryInfectionObstructiveSleepDisordersAllergicConjunc-tivitisOtitisMedia With EffusionNasalPolyposisSinusitisAsthmaImportant to treat allergic rhinitis effectively from the start早期有效治疗变应性鼻炎至关重要！早期有效治疗变应性鼻炎至关重要！Allergic march: AR can progress to asthma.3 变应性进程：AR可进一步发展为哮喘。AR and non-AR negatively impact on asthma control and patient quality of life .4,5 变应性鼻炎和非变应性鼻炎不利于控制 哮喘，同时降低患者生活质量Patients treated for AR have a significantly lower risk of subsequent asthma-related events.6 AR治疗患者的后续哮喘相关性事件的危险 性显著降低AR: allergic rhinitisARIA guidelines. Bousquet et al, Allergy 2008; 63: 8-160Treatment of allergic rhinitis ARIAAR的治疗的治疗ARIAAllergen and irritant avoidanceImmunotherapyIntra-nasal decongestant ( 10 days) or oral decongestantLeukotriene-receptor antagonists Oral or local non-sedative H1-blockerIntra-nasal steroidMildintermittentModeratesevereintermittentMildpersistentModerateseverepersistentLocal cromoneARIA update Recommendation 14Should intranasal H1-antihistamines be used for treatment of allergic rhinitis? (鼻内组胺鼻内组胺H1受体拮抗剂应该用来治疗受体拮抗剂应该用来治疗AR吗？吗？)We suggest intranasal H1-antihistamines in adults with seasonal allergic rhinitis and in children with seasonal allergic rhinitis. 建议患SAR的成人和儿童使用鼻内组胺H1受体拮抗剂。In adults and children with persistent allergic rhinitis, we suggest that clinicians do not administer and patients do not use intranasal H1-antihistamines until more data on their relative efficacy and safety are available.对于患PAR的成人和儿童，在获得更多的组胺H1受体拮抗剂相对有效性及安全性的数据之前，建议临床医师不要给予，患者也不要使用鼻内组胺H1受体拮抗剂。ARIA guidelines update. Brozek et al, JACI 2010;126: 466-76Joint Task Force Practice Parameters for Allergic Rhinitis Treatment特别工作小组关于特别工作小组关于ARAR的诊疗指南的诊疗指南Strength of these guidelines 指南的优点指南的优点Allergic rhinitis is one of the most common conditions seen by US health professionals（AR是美国临床医师最常见的疾病之一）Guidelines based on this wealth of clinical experience （指南基于大量临床经验）Evidence-based（循证医学证据）Based on an extensive review of the literature（基于大量文献综述）Evidence subjected to an intensive review process（证据经集中审查）Developed with support and guidance of the AAAAI and the ACAAI. （在AAAAI和ACAAI的支持和指导下）Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.AAAAI: American Academy of Allergy, Asthma & Immunology 美国变态反应、哮喘和免疫学会ACAAI: American College of Allergy, Asthma and Immunology美国变态反应、现场和免疫学院Classification of recommendations and evidence Category of evidence证据分类和推荐强度分级证据分类和推荐强度分级Ia. Evidence from meta-analysis of randomized controlled trialsIb. Evidence from at least 1 randomized controlled trialIIa. Evidence from at least 1 controlled study without randomizationIIb. Evidence from at least 1 other type of quasi-experimentalstudyIII. Evidence from nonexperimental descriptive studies, such as comparative studiesJoint Task Force Practice Parameters for Allergic Rhinitis Treatment 特别工作小组关于特别工作小组关于ARAR的诊疗指南的诊疗指南Strength of Recommendation 推荐强度推荐强度A Directly based on category I evidenceB Directly based on category II evidence or extrapolated recommendation from category I evidenceC Directly based on category III evidence or extrapolated recommendation from category I or II evidenceD Directly based on category IV evidence or extrapolated recommendation from category I, II, or III evidenceWallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.Intranasal antihistamines 鼻喷抗组胺药65. Intranasal antihistamines may be considered for use as first line treatment for allergic and nonallergic rhinitis. A 鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物。A A级证据级证据66. Intranasal antihistamines are efficacious and equal to or superior to oral second-generation antihistamines for treatment of seasonal allergic rhinitis. A 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药。 A A级证据级证据Joint Task Force Practice Parameters for Allergic Rhinitis Treatment ARAR诊疗指南诊疗指南Role of intranasal antihistamines 鼻喷抗组胺药的地位鼻喷抗组胺药的地位Joint Task Force Practice Parameters for Allergic Rhinitis Treatment ARAR诊疗指南诊疗指南Role of intranasal antihistamines 鼻喷抗组胺药的地位鼻喷抗组胺药的地位Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.67. Because systemic absorption occurs, currently available intranasal antihistamines have been associated with sedation and can inhibit skin test reactions. A 因存在全身吸收，目前市场上的鼻喷抗组胺药可能存在镇静作用， 抑制皮肤反应。 A A级证据级证据68. Intranasal antihistamines have been associated with a clinically significant effect on nasal congestion. A 鼻喷抗组胺药对鼻塞有显著临床效果。A A级证据级证据69. Intranasal antihistamines are generally less effective than intranasal corticosteroids for treatment of allergic rhinitis. A 鼻喷抗组胺药疗效略逊于鼻喷激素。A A级证据级证据Advantages of topical application 局部给药的优势局部给药的优势Drug is delivered directly to the site of inflammation where it is needed most. 药物直达病变部位Rapid onset of action 起效快Compared with systemic treatments, higher concentrations can be applied topically 与全身治疗相比，局部药物浓度更高Enhanced therapeutic effects 疗效更强Risk of interaction with concomitant medication is reduced 降低药物相互作用的风险Potential for systemic adverse events is minimized 使全身给药潜在的不良反应最小化Mode of action 作用机制 Intranasal antihistamines may be considered for use as first-line treatment for allergic and non-allergic rhinitis1鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物Azelastine has a triple mode of actionMORE than an antihistamine爱赛平有独特三重作用机制，不仅仅是一种抗组胺药1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.1.Antihistaminic 抗组胺作用抗组胺作用2.Anti-inflammatory 抗炎作用抗炎作用3.Mast cell stabilizing 稳定肥大细胞稳定肥大细胞 Intranasal antihistamines may be considered for use as first-line treatment for allergic and non-allergic rhinitis1鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物Efficacy of Azelastine in all forms of allergic rhinitis2爱赛平对各种爱赛平对各种ARAR的疗效的疗效1.Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.2.Lieberman P et al. Curr Med Res Opin 2005;21:611-18TNSS: Total Nasal Symptom Score; SAR: Seasonal Allergic Rhinitis1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.Patel et al Ann , Americ.Journal of Rhinology 2007,Vol 21,No.4Azelastine: 2 sprays/nostril爱赛平改善SAR症状：起效快Intranasal antihistamines may be considered for use as first-line treatment for allergic and non-allergic rhinitis1鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物Meta-analyses have shown nasal antihistamines to yield lower number need to treat values than oral antihistamines.2,3 Meta-分析显示鼻喷抗组胺药的NNT值（需要治疗的患 者数）比口服抗组胺药的更低Effective in patients who do not respond to oral-antihistamines, 对口服抗组胺药治疗无效的患者有效1. Wallace et al, JACI;2008;122:S1-S84. 2. Lee & Pickard. Pharmacother 2007;27:852-9; 3. Portnoy et al Curr Allergy Asthma Rep 2004;4:429-4666. Intranasal antihistamines are efficacious and equal to or superior to oral second-generation antihistamines for treatment of seasonal allergic rhinitis. A 在在SARSAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代 口服抗组胺药。口服抗组胺药。Favours azelastine2Favours oral antihistamines1. Wallace et al, JACI 2008;122:S1-S84. 2. Lee & Pickard. Pharmacother 2007;27:852-9NNT: number needed to treat; SAR: seasonal allergic rhinitisIntranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在在SARSAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药Berger et al Ann Allergy Asthma Immunol 2006, 97: 375-381Azelastine: 2 sprays/nostril bd1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.TNSS: Total Nasal Symptom ScoreIntranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在在SARSAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药Berger et al Ann Allergy Asthma Immunol 2006, 97: 375-381RQLQ: rhinitis quality of life questionnaire; SAR: Seasonal Allergic RhinitisAzelastine: 2 sprays/nostril bd1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.Intranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在在SARSAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药Azelastine Nasal Spray in patients with unsatisfactory response to oral antihistamines2 爱赛平对于口抗组胺药效果不理想患者爱赛平对于口抗组胺药效果不理想患者Oral Antihistamines 口服抗阻胺药 NON RESPONDER 无反应者20% of patients do not respond to oral antihistamines These patients do respond to intranasal azelastine1. Wallace et al, JACI 2008;122:S1-S842. Berger et al, Ann Allergy Asthma Immunol 2003;91(2):205-11SAR: Seasonal allergic rhinitisIntranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在在SARSAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药Azelastine improves symptoms in non-responders ofLoratadine non-responder氯雷他定无反应者氯雷他定无反应者Fexofenadinenon-responder非索非那定无反应者非索非那定无反应者TNSS: Total Nasal Symptom ScoreAzelastine: 2 sprays/nostril bd1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.Intranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在在SARSAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药Joint Task Force Practice Parameters for Allergic Rhinitis Treatment ARAR诊疗指南诊疗指南Role of intranasal antihistamines 鼻喷抗组胺药的地位鼻喷抗组胺药的地位Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.67. Because systemic absorption occurs, currently available intranasal antihistamines have been associated with sedation and can inhibit skin test reactions. A 因存在全身吸收，目前市场上的鼻喷抗组胺药可能存在镇静作用， 抑制皮肤反应。 A A级证据级证据68. Intranasal antihistamines have been associated with a clinically significant effect on nasal congestion. A 鼻喷抗组胺药对鼻塞有显著临床效果。A A级证据级证据69. Intranasal antihistamines are generally less effective than intranasal corticosteroids for treatment of allergic rhinitis. A 鼻喷抗组胺药疗效略逊于鼻喷激素。A A级证据级证据 Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81N=3061. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.Intranasal antihistamines have been associated with a clinically significant effect on nasal congestion1鼻喷抗组胺药对鼻塞有显著临床效果鼻喷抗组胺药对鼻塞有显著临床效果Very difficult to avoid certain allergens 一些过敏原很难避免Many patients do not respond sufficiently to treatment. 许多患者对治疗效果不满意Disease severity is frequently under-estimated, and consequently inadequately treated.1 疾病的严重程度被低估，导致治疗不充分Most patients suffer from moderate-to-severe disease.2 大多数患者为中重度变应性鼻炎 Patients frequently experience severe symptoms while on therapy, and are dissatisfied and non-compliant with currently available therapy.3,4患者在治疗情况下症状仍很严重，对现有治疗不满意、依从性不高As many as 74.4% of patients use multiple therapies to achieve symptom control.5 74.4%74.4%进行联合治疗的患者症状得到控制进行联合治疗的患者症状得到控制1. Maurer & Zuberbier Allergy 2007;62:1057-63. 2. Schatz, Allergy 2007;62:9-16. 3. Valovirta et al Curr Opin Allergy Clin Immunol 2008;8:1-9. 4. Loh et al, Allergy 2004;59:1168-72. 5. Demoly et al Allergy 2002;57:546-54. Challenges for allergic rhinitis therapy （AR治疗的挑战）Combination therapy is the way forward（联合治疗是未来发展方向）1. Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81:478-518.2. Settipane RA. Allergy and Asthma Proc 2001; 22:185-189.3. Mosges & Klimek, Allergy 2007;62(9):969-75.N=975A high proportion of patients have mixed rhinitis1,2 很大比例患者是混合性鼻炎Seasonal allergies 季节性过敏Sensitivity to non-allergic triggers (environmental irritants) 对非过敏性激发物过敏（环境刺激物）Many allergic rhinitis patients are sensitized to multiple-triggers.许多AR患者对多种激发物过敏Changes in lifestyle has led to: 生活方式改变导致Perennial exposure to indoor allergens 常年暴露于室内变应原Changes in sensitization patterns 致敏模式改变Polysensitization to a variety of novel cross-reacting food and pet allergens.3 对一些新型相互作用的食物和宠物过敏原多重过敏Challenges for allergic rhinitis therapy （AR治疗的挑战）Combination therapy is the way forward（联合治疗是未来发展方向）Joint Task Force Practice Parameters for Allergic Rhinitis Treatment Step up/Step down approach 逐渐增加治疗药物/减少治疗药物的策略Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.Joint Task Force Practice Parameters for Allergic Rhinitis Treatment ARAR诊疗指南诊疗指南Principal medication options for rhinitis 鼻炎治疗的药物选择原则鼻炎治疗的药物选择原则Oral antihistamines口服抗组胺药Less effective for nasal congestion 对鼻塞效不佳2nd generation agents preferred to avoid sedation 为了避免镇静优先选择第二代抗组胺药Other options better for severe allergic rhinitis 重度AR优先选择其他药物Less effective than intranasal corticosteroids 疗效逊于鼻喷激素Ineffective for non-allergic rhinitis 非变应性鼻炎无效Intranasal antihistamines鼻喷抗组胺药Effective for SAR and PAR 对SAR和PAR有效Rapid onset of action PRN use 起效快按需使用Superior to 2nd generation oral anti-histamines 疗效优于第二代口服抗组胺药Appropriate choice for mixed rhinitis azelastine also approved for vasomotor rhinitis 混合性鼻炎的最佳选择爱赛平同时被批准用于VMRIntranasal corticosteroids鼻喷激素Most effective monotherapy for SAR and PAR 单独治疗SAR和PAR效最佳Slower onset of action than intranasal antihistamines起效比鼻喷抗组胺药慢Growth suppression in children with PAR not shown 未显示抑制PAR儿童生长Local side effects minimal 局部不良反应小Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.SAR: seasonal allergic rhinitis; PAR: perennial allergic rhinitis; PRN: as neededEffective management of allergic rhinitis may require combinations of medications. 有效治疗AR需要联合使用多种药物Several studies have examined the benefit of combining a nasal steroid with an oral antihistamine or leukotriene antagonist in rhinitis1-7许多研究考察鼻喷激素联合口服抗组胺药物或 口服白三烯拮抗剂的疗效Beclomethasone + astemizole Budesonide + terfenadine Flunisolide + terfenadine Fluticasone + loratadine /terfenadine/levocetirizine/cetirizine Fluticasone + montelukastNone concluded that the combination was better than the nasal steroid alone 没有一项研究证明联合使用能优于单独使用鼻喷激素1.Juniper EF, et al. J Allergy Clin Immunol. 1989;83:627-633. 2.Ratner PH, et al. J Fam Pract. 1998;47:118-125. 3.Simpson RJ. Ann Allergy. 1994;73:497-502. 4.Backhouse CI, et al. J Int Med Res. 1986;14:35-41. 5. Juniper EF, et al. CMAJ. 1997;156:1123-1131. 6. Barnes ML, et al. Clin Exp Allergy. 2006;36:676-684. 7. Di Lorenzo G, et al. Clin Exp Allergy. 2004;34:259-267.Combination Trials: Lack of Additive Benefit激素联合口服抗组胺药未见增加疗效Combination therapy: the way forward 联合治疗：未来发展方向联合治疗：未来发展方向Objective:To determine, if greater efficacy could be achieved with Azelastine nasal spray plus Fluticasone nasal spray versus both treatments alone in the treatment of allergic rhinitis试验目的试验目的: :确定联合使用氮卓斯汀鼻喷剂氟替卡松鼻喷剂与各自单独使用治疗变应性鼻炎疗效的比较Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81Combination therapy with azelastine NS and fluticasone propionate NS in the treatment of patients with SAR爱赛平和苯丙酸氟替卡松鼻喷剂联合治疗爱赛平和苯丙酸氟替卡松鼻喷剂联合治疗SARSAR患者患者Study Design 试验设计试验设计Randomized, double-blind, parallel-group 随机、双盲、平行组conducted during the 2005/2006 allergy season 在2005/2006年过敏性季节期间，5个中心进行Primary efficacy variable 主要疗效参数主要疗效参数Change from baseline to day 14 in the total nasal symptom score (TNSS) 治疗14天后，TNSS较基线的改善TNSS = sneezing, itchy nose, rhinorrhea and congestion TNSS= 喷嚏、鼻痒、流涕、鼻塞Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81NS: nasal spray; SAR: seasonal allergic rhinitisRandomization and Treatment Groups随机化和分组情况Azelastine 2 sprays/nostril bd Fluticasone 2 sprays/nostril qdPlacebo Saline Nasal Spray(n=151)Azelastine + Placebo Spray (AM)/Azelastine (PM) (n=49)Fluticasone + Placebo Spray (AM) /Placebo Spray (PM) (n=50)Azelastine + Fluticasone (AM) /Azelastine (PM) (n=52)Day 1Day 14Day 5 Daily TNSS Diary AssessmentsRatner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81TNSS: Total Nasal Symptom Score; bd: twice daily; qd: once dailyCombination therapy the way forward联合治疗：未来发展方向Azelastine plus Fluticasone: Percentage Improvement in TNSS爱赛平联合氟替卡松：TNSS改善百分比 *40% improvement relative to fluticasone Least Squares Mean Values for 14 Study Days; * p=0.035 vs fluticasone; * p=0.011 vs azelastineRatner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81; TNSS: Total Nasal Symptom ScoreAzelastine and Fluticasone nasal sprays in combination deliver the greatest benefit 爱赛平联合氟替卡松治疗爱赛平联合氟替卡松治疗AR提高提高40%疗效疗效Combination therapy the way forward 联合治疗：未来发展方向Azelastine plus Fluticasone: Rapid onset of action and sustained symptom improvement 爱赛平联合氟替卡松：起效快、症状改善作用持续 40% more improvement than fluticasone alone与氟替卡松比较，联合治疗与氟替卡松比较，联合治疗TNSS平均改善提高平均改善提高40%* p0.05 vs azelastine; p=0.05 vs fluticasoneRatner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81TNSS: Total Nasal Symptom ScoreCombination therapy the way forward联合治疗：未来发展方向Azelastine plus Fluticasone: Percentage Improvement in Nasal Itch & congestion爱赛平联合氟替卡松：Nasal Itch & Nasal congestion 改善百分比 Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81Data presented as Least Square Mean for 14 Study Days*56 % improvement relative to fluticasone * p=0.04 vs fluticasone; * p=0.03 vs azelastineNasal Itch 鼻痒*48 % improvement relative to fluticasone Congestion 鼻塞* p=0.04 vs fluticasone; * p=0.02 vs azelastine56% more relief from nasal itching and 48% more relief from nasal congestion vs fluticasone与氟替卡松相比，联合治疗鼻痒改善增加与氟替卡松相比，联合治疗鼻痒改善增加56%56%，鼻塞改善增加，鼻塞改善增加48%48%Combination therapy the way forward 联合治疗：未来发展方向Azelastine plus Fluticasone: Percentage Improvement in Runny Nose & Sneezing爱赛平联合氟替卡松：Runny Nose & Sneezing 改善百分比 Runny nose 流涕Sneezing 喷嚏58% improvement relative to fluticasone 46 % improvement relative to fluticasone * p=0.05 vs azelastine* p=0.04 vs fluticasone*Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81Data presented as Least Square Mean for 14 Study Days58% more relief from runny nose and 46% more relief from nasal sneezing vs fluticasone与氟替卡松相比，联合治疗时流涕改善增加与氟替卡松相比，联合治疗时流涕改善增加56%56%，喷嚏改善增加，喷嚏改善增加48%48%No other AE was reported by more than one patient in any treatment group 在各治疗组中没有患者报道除上述以外的不良事件No discontinuations dues to AEs 没有因不良事件而中止治疗Azelastine + FluticasoneFluticasoneAzelastineBitter Taste味苦13.5%2.0%8.2%Headache头痛5.8%4.0%4.1%Combination therapy: the way forward 联合治疗：未来发展方向Safety Information: Most common adverse events (AEs) 安全性信息：常见不良事件（AEs）Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81Combination therapy: the way forward 联合治疗：未来发展方向联合治疗：未来发展方向Ratner et al Study Conclusions 研究结论研究结论Azelastine in combination with fluticasone provided 爱赛平和氟替卡松联合治疗40% more relief from overall nasal symptoms than fluticasone 与氟替卡松相比，鼻部症状总评分改善增加40%56% more relief from nasal itching than fluticasone鼻痒改善增加56%48% more relief from nasal congestion than fluticasone鼻塞改善增加48%58% more relief from runny nose than fluticasone 流涕改善增加58%46% more relief from sneezing than fluticasone 喷嚏改善增加40%Response to azelastine & fluticasone was rapid and sustained 爱赛平和氟替卡松联合治疗起效快，作用稳定持久Azelastine & fluticasone was well-tolerated 爱赛平和氟替卡松联合治疗耐受性好Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81Combination therapy is the way forward 联合治疗：未来发展方向联合治疗：未来发展方向Other combinations 其他联合其他联合A combination of azelastine and budesonide has recently been assessed. 最近有评价爱赛平和布地奈德的联合治疗12h environmental exposure chamber study in 173 patients. 173名患者在环境暴露室中12hConclusion结论The novel combination product CDX-313 solubilised azelastine & budesonide provided fast, long-lasting relief for allergic rhinitis symptoms. 新型复方制剂CDX-313水溶性氮卓斯汀和布地奈德能更快、更 持久缓解AR症状Salapatek et al, Allergy Asthma Proc 2011;32:221-29Joint Task Force Practice Parameters for Allergic Rhinitis Treatment Step up/Step down approach 逐渐增加治疗药物/减少治疗药物的策略Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.Proposed treatment algorithm 推荐治疗方案推荐治疗方案 MildModerateSevereIntranasal antihistamineIntranasal antihistamineIntranasal anti-histamine & intranasal corticosteroidIntranasal antihistamine for first line treatment for mild-to-moderate rhinitis patientsOr insufficient responseOr increased allergen exposureConsider step-down once control has been achievedOverall conclusions 总结总结AR affect over 500 million people worldwide 全世界约有5亿AR患者 disease severely underestimated 疾病被严重低估 significant impact on cost & co-morbid disease 可并发多种疾病，增加经济负担Guidelines recommend intranasal anti-histamines as first line therapy 诊疗指南推荐鼻喷抗组胺药为AR的一线治疗药物Intranasal combination therapy significantly better than monotherapy 鼻内联合治疗显著优于单药治疗 oral antihistamine + intranasal therapy no different than intranasal therapy alone 口服抗组胺药+鼻内治疗与鼻内单独治疗相比没有显著差异 QUESTIONS?