哮喘合并变应性鼻炎、慢性鼻窦炎的治疗策略上海专家共识

手术治疗

手术治疗及患者获益 内镜鼻窦手术(endoscopic sinus surgery,ESS)是CRS的基本外科治疗方法。CRS经规范药物治疗(不少于12周)无效或出现颅、眶并发症,应考虑ESS[18]。随着对CRS发病机制的理解不断深入,结合长期随访结果,提倡根据CRS的炎症类型、病变范围、客观检查结果选择不同的手术方式。合并哮喘的鼻息肉患者,推荐进行扩大的鼻窦开放术[69-70]。ESS手术能够显著改善CRS患者鼻腔通气、缓解鼻塞,改善嗅觉,减少合并的哮喘急性发作频率,减少激素使用,从而提高患者的生活质量。对于合并哮喘的CRS患者,治疗鼻窦炎的同时需要优化哮喘的管理;在手术后,结合使用生物制剂可以进一步改善患者的哮喘控制,减少炎症,减少鼻窦炎复发。

外科治疗为AR的辅助治疗方法。中-重度持续性AR伴哮喘,经规范化药物治疗和/或免疫治疗,鼻炎和哮喘控制不良的患者可酌情考虑手术治疗。手术方式主要包括以改善鼻通气功能为目的的下鼻甲成形术及鼻中隔矫正术和以降低鼻黏膜高反应性为目的的神经切断术。应该在个体化的前提下严格掌握适应证和禁忌证,进行充分的术前评估,并进行微创操作。AR的手术治疗有助于控制哮喘[71],但不能预防AR进展为哮喘。难治性AR合并哮喘患者接受双侧翼管神经切断术后,鼻部症状得到控制,哮喘症状评分和药物评分显著降低,减少了哮喘急性发作[72]。AR合并CRSwNP患者行翼管神经切断术,能改善肺功能,降低气道高反应性[73]。

围手术期管理哮喘患者具有气道高反应和可变的气流受限等特点,麻醉、气管插管/拔管、手术操作均有增加哮喘急性发作的风险;而鼻部疾病本身及相关手术操作又可导致局部组织水肿,加重气道炎症

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反应。哮喘影响CRS患者围手术期的气道安全,容易发生不良事件[74]。因此,针对合并哮喘的CRS患者,围手术期气道管理尤为重要。

哮喘未控制或处于急性发作期为手术禁忌。充分细致的术前评估以及哮喘的良好控制是保证围手术期安全的关键。肺功能检查是CRS合并哮喘患者术前必不可少的评估手段,建议术前进行肺功能评估和干预治疗[75-76]。哮喘常常存在阻塞性通气功能障碍,临床上可用FEV1%pred从肺功能角度对手术风险进行评估(表2)。此外,应根据患者哮喘症状、用药情况等评估患者的哮喘控制分级(表3)。

|FEV1%pred|手术风险| |---|---| |FEV1%pred≥80%|手术可考虑| |60%≤FEV1%pred<80%|手术有一定风险| |40%≤FEV1%pred<60%|手术风险较大| |FEV1%pred<40%|手术风险极大|

表3 经治患者的哮喘控制分级

Tab 3 Asthma control grade

|评估项目|哮喘控制分级|哮喘控制分级|哮喘控制分级| |---|---|---|---| |评估项目|良好控制|部分控制|未控制| |过去4周,患者存在|||| |日间哮喘症状|是☐||| |>2次/周|否☐||| |夜间因哮喘感冒|是☐||| ||否☐|无|存在1~2项| |使用SABA次数|是☐||| |>2次/周|否☐||| |哮喘引起的活动受限|是☐||| ||否☐|||

CRS多为择期手术,应结合患者术前肺功能、哮喘控制分级,采取相应的干预措施以降低术中及术后并发症的发生风险:(1)若FEV1%pred≥80%且哮喘部分控制,继续按原有方案治疗哮喘,手术当天可雾化吸入治疗:布地奈德1 mg+沙丁胺醇(或特布他林)2.5~5 mg bid。(2)若60%≤FEV1%pred<80%或哮喘良好控制,建议使用中等剂量ICS联合LABA治疗,并且围手术期3~5天加用雾化吸入治疗,方案同上。(3)若FEV1%pred<60%或哮喘未控制,建议变态反应专科或哮喘专病门诊就诊,在专业医师指导下使用中-高剂量ICS联合LABA

规范治疗1~2个月,再随访肺功能评估哮喘控制水平,必要时加用OCS或生物制剂治疗。此外,考虑到麻醉、气管插管/拔管以及手术操作可能引发哮喘急性发作,而较重的CRSwNP患者本身术前会考虑加用全身糖皮质激素,故对于合并哮喘的CRSwNP患者术前可加用泼尼松20~40 mg qd治疗3~5天。

疗效评估 AR疗效主观评价为症状评分,主要是视觉模拟量表(VAS)、症状总评分(TSS)、症状药物联合评分(CSMS)、鼻结膜炎生活质量评分(RQLQ)。AR客观评价指标包括鼻激发实验、鼻吸气峰流速。VAS与TSS、RQLQ高度正相关。VAS(0~100)分为4个等级[77]:完全控制为0分,控制为1~19分,部分控制为20~49分,未控制为≥50分。中法两国学者曾联合提出AR控制测试(allergic rhinitis control test,ARCT),包含5个问题,分值5~25分,当分值≥20分为AR控制[78]。

对于CRS的病情评估包括主观和客观两方面[18]。主观评价包括VAS、鼻腔鼻窦结局测试22(SNOT-22)、健康调查简表(SF-36)。客观评价推荐鼻内镜检查Lund-Kennedy评分、鼻息肉评分和鼻窦CT病变Lund-Mackay评分。经过规范治疗,CRS的临床疗效可分为病情完全控制、部分控制和未控制[79]。评价指标包括7项:鼻塞、流涕/鼻后滴漏、头面部胀痛、嗅觉下降、睡眠障碍或疲乏、鼻内镜检查黏膜异常、需要系统性药物挽救治疗。不具备任何1项为“完全控制”,具备1~2项为“部分控制”,具备≥3项为“未控制”。

根据哮喘患者的症状、使用SABA情况、哮喘活动受限情况将经治患者分为良好控制、部分控制、未控制(表3)。肺通气功能指标FEV₁反映气道阻塞的严重程度,是客观判断哮喘病情最常用的评估指标。哮喘控制测试(asthma control test, ACT)问卷用于评估患者既往4周哮喘控制情况,在缺乏肺功能设备的基层医院更适宜推广使用。

综合管理 哮喘合并AR、CRS患者需要对其上下气道病情共同评估,进行综合治疗管理。哮喘、AR和CRS均属于需要长期管理的慢性病,患者在治疗过程中可能出现依从性差的情况,需要更好的患者教育,提高依从性。药物治疗在哮喘合并AR、CRS的综合治疗中占据核心地位。在治疗时要兼顾上下气道同病共治的原则,局部和全身药物

叶伶,等.哮喘合并变应性鼻炎、慢性鼻窦炎的治疗策略上海专家共识

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联合应用。糖皮质激素、抗组胺药、白三烯受体拮抗剂、AIT、生物制剂等药物的联合应用能够有效改善患者的症状、减少急性发作,并提高生活质量。症状控制时应降级治疗,减少联合及维持用药;症状控制不佳时应升级治疗,增加维持及联合用药。通过综合治疗管理,可以显著提高患者的生活质量并改善疾病控制。

当GINA4、5级治疗控制不佳的重度哮喘可选择生物制剂治疗,合并AR的过敏性哮喘患者可以在3级治疗控制不佳时加用生物制剂[80]。AIT作为一种长期治疗手段,应答者出现免疫耐受,减少对过敏原的敏感性,从而预防哮喘的发生和进展。将AIT与生物制剂结合使用,可以提高AIT的安全性,减少不良反应,增加达到最大维持剂量的患者人数。哮喘合并CRSwNP患者,应用生物制剂显示出良好疗效[81]。生物制剂联合ESS治疗,可以持续改善CRSwNP合并哮喘患者的SNOT-22评分,优于单纯ESS治疗的远期效果[82]。对于合并哮喘的鼻息肉患者,靶向2型炎症的生物制剂展现了良好的前景。

哮喘、AR与CRS是相互关联的常见慢性疾病,需要多学科协作以实现长期规范化管理。变态反应科、呼吸科、耳鼻喉科联合随访、定期检测肺功能、呼出气一氧化氮,评估鼻部症状,哮喘症状评分,调整治疗方案时兼顾上下呼吸道指标。长期治疗过程中需要监测药物不良反应(如鼻出血、口腔念珠菌感染)。医患教育同样是综合管理中重要的一环。卫生健康管理部门要建立规范的公共卫生策略,推动过敏原防控政策(如公共场所尘螨控制标准)。对医务人员开展继续教育,提高基层医师对共病的识别与管理能力。

总结与展望 哮喘合并AR、CRS需综合考虑上下呼吸道的炎症反应,采取联合治疗策略,进行综合管理:环境控制为基础,药物治疗为核心,生物制剂为突破,免疫治疗为对因,长期随访为保障。尽管哮喘和AR、CRS的共病治疗方面取得了显著进展,但个体化治疗仍是治疗的关键。随着对2型免疫反应机制的深入理解,未来的研究可能会发现更多的靶点,开发新型生物制剂和更精确的治疗方案。小分子抑制剂(如JAK抑制剂)在难治性上下呼吸道炎症共病中具有研究潜力。此外,探索生物标志物预测疗效将是未来的研究重点。尽管生物制剂在哮喘合并AR、CRSwNP治疗中展现了良

好的效果,但仍然面临一些挑战。个体化的治疗方案显得尤为重要。未来研究需更加聚焦精准分型与个体化干预,以优化治疗方案,实现症状控制与疾病修饰的双重目标。

作者贡献声明 叶伶,娄鸿飞 执笔。施劲东,程克斌,陈敏,丁国强,郭胤仕,黄新生,刘宏炜,宁显会,商艳,邵莉,沈瑶,汤葳,王珮华,谢晓凤,余少卿,张锋英,张治军,赵可庆,庄亚琴 参与编写。李华斌,金美玲 牵头人。

利益冲突声明 所有作者均声明不存在利益冲突。

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(收稿日期:2025-07-05; 编辑:王蔚)

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