阿司匹林三联征

阿司匹林三联征 1 病 因 阿司匹林三联征的病因至今不明确，可能病因如下: 1.1 环氧化酶(cox)假说 1977年Szczeklik等提出这一假说，认为阿司匹林导致哮喘的机制与此药对呼吸道cox的抑制作用有关，使花生四烯酸不能转化为前列腺素，但其在脂氧合酶的作用下生成白细胞三烯而致哮喘。 1.2 白介素(interleukin,IL)炎症介质的释放 炎症释放的IL5等细胞因子经血流刺激骨髓产生嗜酸性粒细胞并使其活化，导致下呼吸道嗜酸性粒细胞浸润增加,IL5参与哮喘急性发作过程，并可能与哮喘气道慢性炎症的持续存在有关。鼻息肉组织中产生大量IL5，且延长嗜酸性粒细胞的寿命。炎症释放的化学递质经血流引起支气管平滑肌收缩。 1.3 嗜酸性粒细胞浸润 Ogata等为了探明阿司匹林诱发的哮喘合并鼻息肉中的嗜酸性粒细胞的聚集情况、经激素治疗后的组织化学结果和复发性息肉的组织化学特点，以及嗜酸性碱性蛋白在分泌物与息肉中的不同分布，采用了抗嗜酸性粒细胞球蛋白(eosinophil globulin，EG)1和抗EG2抗体标记的组织化学方法进行了研究，结果发现，治疗前和复发的息肉中有大量的嗜酸性粒细胞，并且是激活的，而在激素治疗后就变得比较稀少，这些发现表明，嗜酸性粒细胞与合并阿司匹林哮喘的鼻息肉的形成密切相关，嗜酸性粒细胞的激活在鼻息肉形成的早期阶段起着重要的作用。 coupling Centre shall be checked, the second poured concrete strength of more than 70%. In the process of reaming or boring, apart from the special provisions in factory, does not allow any work that may affect the coupling Centre, such as irrigation, to cylinder connections to flood the condenser pipes and so on. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Mounting bolts should be added lubricants, typing gently with a small hammer, not too loose or too tight, packed the bolts with the corresponding seal screw hole should be marked. 6.4.5.4.2 coupling reamed and pairings is close to the diameter of bolt bearing good hinge holes, dressed with a good two coupling bolts before you can move the rotor, boring-reaming hole in turn. Coupling bolts must be tight coupling is symmetrical diameter, in boring, reaming, two bolts out. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Due to the coupling bolts in accordance with hinge holes corresponding to the diameter of the screw holes one by one after processing, processing back bolt installation location cannot be changed, so according to bolt after the actual weight difference of nut and lock washer to match. General requirements for coupling two symmetrical diameter bolt, nut and lock washer's total weight difference should not be greater than 10 g and knocks stamped mark. (See Figure 18) The coupling bolts apply lubricant, and then gently with copper home, not too loose or too tight. Bolt Assembly is finished, symmetrical tightening all bolts to 30%, 50%, 70%, 100% force, and check the coupling flutter and before connecting the circle gradually changes its value should be less than 0.02mm. Tightening torque of the coupling bolts shall comply with the technical requirements manufacturers drawings, with a dynamometric wrench or log tension tools. Three wheel rotor swing test coupling connections should be checked: taking leave, 1.4 花生四烯酸的代谢改变 有充分的证据表明，乙酰水杨酸类药物不耐受与花生四烯酸代谢紊乱导致的白细胞三烯产生过多有关。白细胞三烯收缩平滑肌的作用相当于组胺作用强度的6000倍，又是最强的炎症介质，故可引起严重的哮喘发作。 1.5 特异性IgE介导的I型变态反应 有研究表明，鼻息肉的IgE含量比血清高。由于其临床表现与速发型变态反应相似，且在鼻息肉和支气管黏膜中可查见嗜酸性细胞浸润等，故长期以来认为是免疫学介导的抗原抗体反应(药物超敏反应)。 1.6 N 乙酰 5 甲氧基色胺的表达 阿司匹林三联征患者息肉组织的特征是嗜酸性粒细胞增高与N 乙酰 5 甲氧基色胺的高表达有关。 1.7 呼吸道炎症微环境学说认为鼻息肉为局部微环境下控制的炎症性肉芽肿，鼻息肉中的上皮细胞和成纤维细胞产生的各种细胞因子使炎症细胞增多，并延长嗜酸性粒细胞等炎症细胞的生存周期，嗜酸性粒细胞又产生许多细胞因子，这些细胞因子又可使炎症细胞增多，如此循环不止。 1.8 睡眠体位 从解剖、生理学来看，鼻腔与支气管及肺的关系密切，上、下呼吸道表面都覆盖有纤毛上皮组织，在功能上是相互关联的，仰卧位睡眠时鼻内炎性分泌物流入气道很可能是鼻部炎症发展为哮喘病(特别是夜间哮喘)的重要原因。 1.9 遗传因素 在阿司匹林不耐受和阿司匹林哮喘中扮演着重coupling Centre shall be checked, the second poured concrete strength of more than 70%. In the process of reaming or boring, apart from the special provisions in factory, does not allow any work that may affect the coupling Centre, such as irrigation, to cylinder connections to flood the condenser pipes and so on. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Mounting bolts should be added lubricants, typing gently with a small hammer, not too loose or too tight, packed the bolts with the corresponding seal screw hole should be marked. 6.4.5.4.2 coupling reamed and pairings is close to the diameter of bolt bearing good hinge holes, dressed with a good two coupling bolts before you can move the rotor, boring-reaming hole in turn. Coupling bolts must be tight coupling is symmetrical diameter, in boring, reaming, two bolts out. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Due to the coupling bolts in accordance with hinge holes corresponding to the diameter of the screw holes one by one after processing, processing back bolt installation location cannot be changed, so according to bolt after the actual weight difference of nut and lock washer to match. General requirements for coupling two symmetrical diameter bolt, nut and lock washer's total weight difference should not be greater than 10 g and knocks stamped mark. (See Figure 18) The coupling bolts apply lubricant, and then gently with copper home, not too loose or too tight. Bolt Assembly is finished, symmetrical tightening all bolts to 30%, 50%, 70%, 100% force, and check the coupling flutter and before connecting the circle gradually changes its value should be less than 0.02mm. Tightening torque of the coupling bolts shall comply with the technical requirements manufacturers drawings, with a dynamometric wrench or log tension tools. Three wheel rotor swing test coupling connections should be checked: taking leave, 要角色。最近HLA A74与鼻息肉的关系证明了这一点。 2 发病机制和病理学改变 阿司匹林耐受不良患者的支气管黏膜和鼻、鼻窦黏膜的病理改变表现为慢性炎症反应,即黏膜增厚、基底膜增厚、疏松的无血管水肿基质形成、假复层纤毛柱状上皮化生、纤毛减少或消失及黏膜下炎细胞浸润,以嗜酸性粒细胞为主;此外,尚有中性粒细胞、浆细胞、淋巴细胞等浸润。息肉由疏松的结缔组织、水肿、炎细胞、一些毛细血管和腺体组成，Harlen等注意到支气管哮喘患者鼻窦黏膜的上皮与支气管上皮有相似的组织病理学改变，包括嗜酸性粒细胞浸润程度。与正常鼻黏膜的区别主要是腺体的密度低，形态不规则，为长管状或囊性扩张，没有像中下鼻甲一样的浆液粘液腺。本病的发病机制、病理改变和临床症状上的复杂的内在联系至今尚未充分揭示。 上下气道变应性疾病的相互关系通过流行病学、病理生理学和治疗反应已被证明，事实上，这些气道疾病在组织学上、组织的嗜酸性粒细胞、增生的腺组织和水肿都是相似的。上下气道在功能和疾病上是紧密相连的，近来更倾向于认为是一个连续的气道。 3 临床表现 3.1 分型 根据患者阿司匹林耐受不良、鼻息肉和支气管哮喘出现的先后顺序，以及原先有无支气管哮喘，将阿司匹林三联征分为4型:?阿司匹林耐受不良基础型:服用阿司匹林后首先可能出现鼻炎，表现为多量、浆液性鼻分泌物，当再次口服同一药物出现症状后, 则呈常年性发病。常表现为双侧、持续性鼻塞, 并有嗅觉减退或失嗅。coupling Centre shall be checked, the second poured concrete strength of more than 70%. In the process of reaming or boring, apart from the special provisions in factory, does not allow any work that may affect the coupling Centre, such as irrigation, to cylinder connections to flood the condenser pipes and so on. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Mounting bolts should be added lubricants, typing gently with a small hammer, not too loose or too tight, packed the bolts with the corresponding seal screw hole should be marked. 6.4.5.4.2 coupling reamed and pairings is close to the diameter of bolt bearing good hinge holes, dressed with a good two coupling bolts before you can move the rotor, boring-reaming hole in turn. Coupling bolts must be tight coupling is symmetrical diameter, in boring, reaming, two bolts out. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Due to the coupling bolts in accordance with hinge holes corresponding to the diameter of the screw holes one by one after processing, processing back bolt installation location cannot be changed, so according to bolt after the actual weight difference of nut and lock washer to match. General requirements for coupling two symmetrical diameter bolt, nut and lock washer's total weight difference should not be greater than 10 g and knocks stamped mark. (See Figure 18) The coupling bolts apply lubricant, and then gently with copper home, not too loose or too tight. Bolt Assembly is finished, symmetrical tightening all bolts to 30%, 50%, 70%, 100% force, and check the coupling flutter and before connecting the circle gradually changes its value should be less than 0.02mm. Tightening torque of the coupling bolts shall comply with the technical requirements manufacturers drawings, with a dynamometric wrench or log tension tools. Three wheel rotor swing test coupling connections should be checked: taking leave, 约5,10年后出现鼻息肉和支气管哮喘;?鼻炎基础型:在变态反应性鼻炎基础上因服用阿司匹林药后诱发哮喘急性发作;?支气管哮喘基础型:原来就患有支气管哮喘,以后又发生了阿司匹林耐受不良,哮喘的发作由于阿司匹林或非类固醇抗炎药物引起。阿司匹林哮喘患者的症状较为严重,曾有即刻引起呼吸困难而致死亡的报道;荨麻疹、血管性水肿、低血压和晕厥等可同时发生;?哮喘启动型:既往无支气管哮喘病史,哮喘第一次发作由阿司匹林或非类固醇抗炎药物诱发,以后每次应用此类药物时均可引起哮喘严重发作。 3.2 特点 阿司匹林三联征的特点有:?鼻息肉为双侧、多发性,鼻息肉虽经手术治疗也常有复发趋势，并伴嗅觉异常;?多见于中年人,发病年龄多在20,50岁左右,女性稍多于男性(约为3?2),如无正规治疗，病情可进行性加重;?随病程延长，鼻息肉和支气管哮喘发生率增加;?属于非特异性变应性,为类固醇依赖性;?乙酰甲胆碱和组胺激发试验常显示较一般支气管哮喘患者更高的气道敏感性;?鼻分泌物涂片和痰涂片可见嗜酸粒细胞增多,末梢血中嗜酸性粒细胞也增多;?对某些吸入物或食入物致敏原表现为阳性皮肤试验反应,鼻分泌物和血清中也可能查到特异性IgE抗体;?极少数患者可能有家族阿司匹林耐受不良史;?应用减充血剂和抗组胺药常无效,而停用阿司匹林和应用类固醇药物可能有效，当鼻息肉形成和(或)支气管哮喘发作后,停用阿司匹林对症状的改善也常无明显的效果。 4 诊 断 诊断有:?病史中能提供阿司匹林或非类固醇抗炎剂诱发鼻coupling Centre shall be checked, the second poured concrete strength of more than 70%. In the process of reaming or boring, apart from the special provisions in factory, does not allow any work that may affect the coupling Centre, such as irrigation, to cylinder connections to flood the condenser pipes and so on. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Mounting bolts should be added lubricants, typing gently with a small hammer, not too loose or too tight, packed the bolts with the corresponding seal screw hole should be marked. 6.4.5.4.2 coupling reamed and pairings is close to the diameter of bolt bearing good hinge holes, dressed with a good two coupling bolts before you can move the rotor, boring-reaming hole in turn. Coupling bolts must be tight coupling is symmetrical diameter, in boring, reaming, two bolts out. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Due to the coupling bolts in accordance with hinge holes corresponding to the diameter of the screw holes one by one after processing, processing back bolt installation location cannot be changed, so according to bolt after the actual weight difference of nut and lock washer to match. General requirements for coupling two symmetrical diameter bolt, nut and lock washer's total weight difference should not be greater than 10 g and knocks stamped mark. (See Figure 18) The coupling bolts apply lubricant, and then gently with copper home, not too loose or too tight. Bolt Assembly is finished, symmetrical tightening all bolts to 30%, 50%, 70%, 100% force, and check the coupling flutter and before connecting the circle gradually changes its value should be less than 0.02mm. Tightening torque of the coupling bolts shall comply with the technical requirements manufacturers drawings, with a dynamometric wrench or log tension tools. Three wheel rotor swing test coupling connections should be checked: taking leave, 部症状和支气管哮喘的病史;?阿司匹林或非类固醇抗炎剂在严格控制药物剂量的情况下行激发试验呈阳性反应，因为有可能引起严重的哮喘发作，有学者不主张进行激发试验;?专科查体:双侧鼻腔内充满半透明肿物，表面光滑，质软，鼻道内有粘液样分泌物;双肺可闻及湿罗音及哮鸣音。CT示:双侧鼻息肉、双侧慢性上颌窦炎、筛窦及碟窦炎。X线平片对鼻息肉无诊断价值，但可以显示感染的窦腔。 5 治 疗 5.1 保守治疗 ?避免使用阿司匹林和其他非甾体抗炎药(NSAID);?口服或局部用糖皮质激素;?使用白三烯拮抗剂或合成抑制剂，白三烯受体拮抗剂作为一种新型的治疗药物，由于其特殊的作用机制，可减轻阿司匹林哮喘的临床症状;?乙酰水杨酸脱敏治疗;?白介素(IL)拮抗剂，IL 5是一种嗜酸性粒细胞分化因子(EDF)，其能增强嗜酸性粒细胞对其他刺激的敏感性并延迟这些细胞的凋亡时间，高亲和力IL 5受体只有嗜酸性粒细胞和嗜碱性粒细胞表达，因此中和IL 5是治疗嗜酸性粒细胞疾病的一种有效的方法;?IgE拮抗剂，人源化IgE mAb(omalizumab)治疗过敏性哮喘和鼻炎能使循环游离IgE水平显著降低，使患有过敏性疾病的症状得到改善。 5.2 手术治疗 随着功能性内镜鼻窦手术(functional endoscopic sinus surgery, FESS)的广泛开展，Harlen等注意到设法减轻组织水肿、去除炎症病灶、开放阻塞的鼻窦开口是一种积极有效的治疗方法。广大鼻科医师已认识到，解除阻塞、促进引流、加强鼻窦通气、恢复嗅觉是慢性鼻窦炎鼻息肉手术的基本原则。 coupling Centre shall be checked, the second poured concrete strength of more than 70%. In the process of reaming or boring, apart from the special provisions in factory, does not allow any work that may affect the coupling Centre, such as irrigation, to cylinder connections to flood the condenser pipes and so on. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Mounting bolts should be added lubricants, typing gently with a small hammer, not too loose or too tight, packed the bolts with the corresponding seal screw hole should be marked. 6.4.5.4.2 coupling reamed and pairings is close to the diameter of bolt bearing good hinge holes, dressed with a good two coupling bolts before you can move the rotor, boring-reaming hole in turn. Coupling bolts must be tight coupling is symmetrical diameter, in boring, reaming, two bolts out. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Due to the coupling bolts in accordance with hinge holes corresponding to the diameter of the screw holes one by one after processing, processing back bolt installation location cannot be changed, so according to bolt after the actual weight difference of nut and lock washer to match. General requirements for coupling two symmetrical diameter bolt, nut and lock washer's total weight difference should not be greater than 10 g and knocks stamped mark. (See Figure 18) The coupling bolts apply lubricant, and then gently with copper home, not too loose or too tight. Bolt Assembly is finished, symmetrical tightening all bolts to 30%, 50%, 70%, 100% force, and check the coupling flutter and before connecting the circle gradually changes its value should be less than 0.02mm. Tightening torque of the coupling bolts shall comply with the technical requirements manufacturers drawings, with a dynamometric wrench or log tension tools. Three wheel rotor swing test coupling connections should be checked: taking leave, 阿司匹林三联征是鼻科治疗中最困难的问题之一。抗过敏药物和脱敏疗法不能解决鼻息肉引起的鼻阻塞和鼻涕倒流;支配鼻腔和鼻窦的主要副交感神经来源于翼管神经，它支配黏膜腺体分泌和血管扩张，行翼管神经电灼术可去除过敏性反应的神经支配因素，对部分支气管哮喘亦有较好的疗效。一次性完成翼管神经电灼切断、鼻息肉及全组筛窦切除、蝶窦开放、中鼻道开窗等五个部位的手术，按照翼管神经电灼鼻息肉及筛窦切除、蝶窦开放、中鼻道开窗的先后顺序进行，在实行这种联合手术后，鼻黏膜腺体分泌减少，鼻和鼻窦的炎症治愈或明显好转，避免了鼻分泌物倒流对下呼吸道黏膜产生的刺激，在某种程度上缓解了哮喘的发作，从而解决了本病治疗的难点,27,。 5.3 术后修复 鼻内镜手术已经成为治疗鼻息肉的重要方法，但术后术腔长时间的换药是影响其疗效的重要因素之一，术后黏膜的修复近年来成为临床研究的热点。韩德民提到鼻内镜手术后期(术后恢复期)为2,8周。许庚等(1999年)将FESS术后术腔黏膜的转归分为术腔清洁阶段，多在术后2周内，黏膜转归竞争阶段和上皮化完成阶段，其中黏膜转归竞争阶段是影响术腔上皮化最关键的时期，在此阶段组织学表现比较复杂，以组织增生和炎症为主，且一直存在于黏膜恢复过程的始终，局部的处理及全身抗炎的治疗在此阶段是很重要的，Schapowal等术后进一步抗炎是必须的，否则几周或数月后90%的患者可复发鼻息肉。 术后术腔的处理目前多用生理盐水冲洗、局部糖皮质激素喷雾治coupling Centre shall be checked, the second poured concrete strength of more than 70%. In the process of reaming or boring, apart from the special provisions in factory, does not allow any work that may affect the coupling Centre, such as irrigation, to cylinder connections to flood the condenser pipes and so on. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Mounting bolts should be added lubricants, typing gently with a small hammer, not too loose or too tight, packed the bolts with the corresponding seal screw hole should be marked. 6.4.5.4.2 coupling reamed and pairings is close to the diameter of bolt bearing good hinge holes, dressed with a good two coupling bolts before you can move the rotor, boring-reaming hole in turn. Coupling bolts must be tight coupling is symmetrical diameter, in boring, reaming, two bolts out. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Due to the coupling bolts in accordance with hinge holes corresponding to the diameter of the screw holes one by one after processing, processing back bolt installation location cannot be changed, so according to bolt after the actual weight difference of nut and lock washer to match. General requirements for coupling two symmetrical diameter bolt, nut and lock washer's total weight difference should not be greater than 10 g and knocks stamped mark. (See Figure 18) The coupling bolts apply lubricant, and then gently with copper home, not too loose or too tight. Bolt Assembly is finished, symmetrical tightening all bolts to 30%, 50%, 70%, 100% force, and check the coupling flutter and before connecting the circle gradually changes its value should be less than 0.02mm. Tightening torque of the coupling bolts shall comply with the technical requirements manufacturers drawings, with a dynamometric wrench or log tension tools. Three wheel rotor swing test coupling connections should be checked: taking leave, 疗，可以预防复发，但是临床中一些患者的疗效欠佳，并不能明显缩短术腔黏膜的上皮化时间。白永等提出术后糖皮质激素联合应用阿奇霉素对促进术腔黏膜的上皮化具有协同作用。 6 展 望 鼻息肉和哮喘常同时存在，世界卫生组织提出了“一个呼吸道，一种疾病”的概念。随着对呼吸道疾病发病机制认识的深入，治疗策略已有所改进，新的治疗方法、给药途径以及证实有效。最近慢性炎症鼻窦病理如鼻息肉与哮喘的关系研究证实，控制鼻息肉对稳定和改善哮喘疾病具有重要的价值。韩德民提出，在成功开展鼻内镜外科技术的过程中还应注意克服“一种方法治疗所有患者或多种方法治疗一个患者”的不良倾向，注重综合治疗，更多地体现多层面、多样化、个体化的发展趋势。王忠植等提出，最理想的治疗措施是内科保守治疗代替外科手术，这种想法也不无根据，因为国外专家已开始研究鼻窦炎鼻息肉的基因治疗方法，应用于临床的可能性已指日可待。 coupling Centre shall be checked, the second poured concrete strength of more than 70%. In the process of reaming or boring, apart from the special provisions in factory, does not allow any work that may affect the coupling Centre, such as irrigation, to cylinder connections to flood the condenser pipes and so on. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Mounting bolts should be added lubricants, typing gently with a small hammer, not too loose or too tight, packed the bolts with the corresponding seal screw hole should be marked. 6.4.5.4.2 coupling reamed and pairings is close to the diameter of bolt bearing good hinge holes, dressed with a good two coupling bolts before you can move the rotor, boring-reaming hole in turn. Coupling bolts must be tight coupling is symmetrical diameter, in boring, reaming, two bolts out. Well boring, hinge bolt hole flange with coupling of vertical, not oblique. Due to the coupling bolts in accordance with hinge holes corresponding to the diameter of the screw holes one by one after processing, processing back bolt installation location cannot be changed, so according to bolt after the actual weight difference of nut and lock washer to match. General requirements for coupling two symmetrical diameter bolt, nut and lock washer's total weight difference should not be greater than 10 g and knocks stamped mark. (See Figure 18) The coupling bolts apply lubricant, and then gently with copper home, not too loose or too tight. Bolt Assembly is finished, symmetrical tightening all bolts to 30%, 50%, 70%, 100% force, and check the coupling flutter and before connecting the circle gradually changes its value should be less than 0.02mm. Tightening torque of the coupling bolts shall comply with the technical requirements manufacturers drawings, with a dynamometric wrench or log tension tools. Three wheel rotor swing test coupling connections should be checked: taking leave,