治疗流程
请注意药品名称和品牌、药品处方或地区之间的配方/用药途径和剂量可能有所不同。治疗建议针对患者特定群体提出:查看免责声明
GOLD A 组:初始治疗
GOLD B 组:初始治疗
GOLD E 组:初始治疗
GOLD A、B 或 E 组:初始治疗后呈持续性呼吸困难/活动受限
GOLD A、B 或 E 组:初始治疗后持续加重
慢性阻塞性肺疾病全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)A 组患者的特点是症状少(改良版英国医学研究委员会 [Modified British Medical Research Council, mMRC] 分级为 0-1 或 COPD 评估测试 [COPD Assessment Test, CAT]<10)且急性加重风险低(每年急性加重 0-1 次,无需住院)。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
应将短效或长效支气管舒张剂用作一线治疗药物。首选长效 β2 受体激动剂(long-acting beta-2 agonist, LABA)和长效毒蕈碱受体拮抗剂(long-acting muscarinic antagonist, LAMA)而非短效支气管舒张剂,但仅偶尔出现呼吸困难的患者除外。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ LABA 和 LAMA 均可显著改善肺功能、呼吸困难和健康状况,还能减少加重频率。 [ ]How does umeclidinium bromide compare with placebo for people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.1829/full展示答案[证据 A]81c5e462-8f36-4687-93b0-cd4b9989ab2accaA对于慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)患者,乌美铵与安慰剂相比效果如何? 与 LABA 相比,LAMA 能更有效地减少急性加重。[100]Vogelmeier C, Hederer B, Glaab T, et al; POET-COPD Investigators. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011 Mar 24;364(12):1093-103.https://www.nejm.org/doi/full/10.1056/NEJMoa1008378http://www.ncbi.nlm.nih.gov/pubmed/21428765?tool=bestpractice.com[101]Decramer ML, Chapman KR, Dahl R, et al; INVIGORATE investigators. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study. Lancet Respir Med. 2013 Sep;1(7):524-33.http://www.ncbi.nlm.nih.gov/pubmed/24461613?tool=bestpractice.com
如果开处长效支气管舒张剂,还应开处短效支气管舒张剂作为挽救治疗。一般不推荐常规使用短效支气管舒张剂。
短效 β-2 受体激动剂(short-acting beta-2 agonist, SABA)和短效毒蕈碱受体拮抗剂(short-acting muscarinic antagonist, SAMA)能够改善肺功能、减轻呼吸困难和提升生活质量。异丙托溴铵(一种 SAMA)在改善健康相关生活质量方面的益处略高于 SABA。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com
如果开处了 LAMA,则应停用 SAMA。
SABA 包括沙丁胺醇。异丙托溴铵是一种 SAMA。LABA 包括沙美特罗、arformoterol、奥达特罗。LAMA 包括噻托溴铵、乌美溴铵、aclidinium 和格隆溴铵。 [ ]How does umeclidinium bromide compare with placebo for people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.1829/full展示答案
第一选择
SABA
吸入性沙丁胺醇 : 需要时(100 μg/定量吸入器)100-200 μg(1-2 喷),每 4-6 小时一次
或
SAMA
吸入性异丙托溴铵 : 需要时(20 μg/定量吸入器)40 μg(2 喷),每日最多 4 次
或
LABA
吸入性沙美特罗 : (50 µg/定量吸入器)50 µg(1 喷),每日两次
或
LABA
吸入性福莫特罗 : 15 μg,雾化吸入,每日两次
或
LABA
吸入性奥达特罗 : (2.5 μg/定量吸入器)5 μg(2 喷),每日 1 次
或
LAMA
吸入性噻托溴铵 : (18 μg/胶囊吸入器)18 μg(1 粒胶囊),每日一次;(2.5 μg/定量吸入器)5 μg(2 喷),每日一次
或
LAMA
吸入性芜地溴铵 : (62.5 μg/定量吸入器)62.5 μg(1 喷),每日一次
或
LAMA
吸入性阿地溴铵 : (400 μg/定量吸入器)400 μg(1 喷),每日 2 次
或
LAMA
吸入性格隆溴铵 : (55 μg/胶囊吸入器)55 μg(1 粒胶囊),每日一次
更多 吸入性格隆溴铵每粒胶囊递送 55 µg 格隆溴铵化合物(相当于 44 µg 格隆溴铵 [glycopyrronium])。
针对特定患者群中所有患者的治疗建议
应鼓励所有患者戒烟,并接受指导,避免职业或环境烟草烟雾暴露和其他刺激物暴露。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115 戒烟可显著降低 COPD 的进展速度和恶性肿瘤风险。请参阅“戒烟(治疗流程)” 。
根据本地指南,患者应接种流感病毒疫苗、肺炎链球菌疫苗、百日咳疫苗、水痘带状疱疹病毒疫苗、呼吸道合胞病毒疫苗和 2019 冠状病毒病(coronavirus disease 2019, COVID-19)疫苗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html 接种流感疫苗可减少 COPD 急性加重次数。[182]Walters JA, Tang JN, Poole P, et al. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Jan 24;(1):CD001390.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001390.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28116747?tool=bestpractice.com[183]Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018 Jun 26;(6):CD002733.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002733.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29943802?tool=bestpractice.com [ ]What are the effects of influenza vaccine in people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.2235/full展示答案 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)还建议在青春期未接种破伤风/白喉/百日咳疫苗的 COPD 患者补种。[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html
使用吸入治疗的患者应接受吸入器装置使用方法培训。多数患者在使用吸入器时至少犯一次错误,并且错误使用吸入器与疾病控制能力下降有关。[155]Cho-Reyes S, Celli BR, Dembek C, et al. Inhalation technique errors with metered-dose inhalers among patients with obstructive lung diseases: a systematic review and meta-analysis of US Studies. Chronic Obstr Pulm Dis. 2019 Jul 24;6(3):267-80.https://journal.copdfoundation.org/jcopdf/id/1241/Inhalation-Technique-Errors-with-Metered-Dose-Inhalers-Among-Patients-with-Obstructive-Lung-Diseases-A-Systematic-Review-and-Meta-Analysis-of-US-Studieshttp://www.ncbi.nlm.nih.gov/pubmed/31342732?tool=bestpractice.com[156]Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011 Jun;105(6):930-8.https://www.resmedjournal.com/article/S0954-6111(11)00009-6/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21367593?tool=bestpractice.com 临床医生演示吸入器用法、选用合适的装置以及在后续复诊时检查使用方法均可改善吸入器使用技术。[158]Price D, Keininger DL, Viswanad B, et al. Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey. Int J Chron Obstruct Pulmon Dis. 2018 Feb 26;13:695-702. [Erratum in: Int J Chron Obstruct Pulmon Dis. 2018 Jul 25;13:2253-4.]https://www.dovepress.com/factors-associated-with-appropriate-inhaler-use-in-patients-with-copd--peer-reviewed-fulltext-article-COPDhttp://www.ncbi.nlm.nih.gov/pubmed/29520137?tool=bestpractice.com
对所有患者进行关于病程以及加重或失代偿症状的宣教。他们对疾病、治疗和预后的预期应符合实际。研究显示,目前没有药物能改善长期减退的肺功能,药物治疗的主要目标是控制症状和预防并发症。自我管理教育应包括提供书面行动计划。推荐所有 COPD 患者进行体力活动。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
慢性阻塞性肺疾病全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)B 组患者的特点是症状较多(改良版英国医学研究委员会 [Modified British Medical Research Council, mMRC] ≥2 或 COPD 评估测试 [COPD Assessment Test, CAT]≥10)而急性加重风险低(每年急性加重 0-1 次,无需住院)。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
如果不存在不良反应或药物可及性问题,应将长效毒蕈碱受体拮抗剂(long-acting muscarinic antagonist, LAMA)/长效 β2 受体激动剂(long-acting beta-2 agonist, LABA)联合治疗作为一线治疗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
乌美溴铵/维兰特罗、格隆溴铵/福莫特罗、噻托溴铵/奥达特罗和 aclidinium/福莫特罗是获批用于治疗 COPD 的 LABA/LAMA 复方制剂。[113]Wedzicha JA, Banerji D, Chapman KR, et al; FLAME Investigators. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016 Jun 9;374(23):2222-34.https://www.nejm.org/doi/10.1056/NEJMoa1516385http://www.ncbi.nlm.nih.gov/pubmed/27181606?tool=bestpractice.com[227]Radovanovic D, Mantero M, Sferrazza Papa GF, et al. Formoterol fumarate + glycopyrrolate for the treatment of chronic obstructive pulmonary disease. Expert Rev Respir Med. 2016 Oct;10(10):1045-55.http://www.ncbi.nlm.nih.gov/pubmed/27552524?tool=bestpractice.com 乌美溴铵/维兰特罗可降低轻度/中度 COPD 患者的急性加重风险。[107]Maqsood U, Ho TN, Palmer K, et al. Once daily long-acting beta2-agonists and long-acting muscarinic antagonists in a combined inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2019 Mar 6;(3):CD012930.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012930.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/30839102?tool=bestpractice.com [ ]How does a combined inhaler with once‐daily long‐acting beta2‐agonist (LABA) plus a long‐acting muscarinic antagonist (LAMA) compare with placebo for adults with chronic obstructive pulmonary disease (COPD)?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2551/full展示答案
第一选择
LABA/LAMA 二联疗法
吸入性芜地溴铵 (umeclidinium)/维兰特罗 (vilanterol) : (62.5/25 μg/定量吸入器)1 喷,每日一次
或
LABA/LAMA 二联疗法
格隆溴铵/福莫特罗 : (7.2 μg/5 μg 定量吸入器)每次 2 揿,每日两次
或
LABA/LAMA 二联疗法
吸入性噻托溴铵/奥达特罗 : (2.5/2.5 μg/定量吸入器)2 喷,每日一次
或
LABA/LAMA 二联疗法
吸入性阿地溴铵/福莫特罗 : (每剂吸入剂 400/12 μg)1 喷,每日两次
针对特定患者群中所有患者的治疗建议
对于所有诊断为 COPD 的患者,均应开处短效支气管舒张剂,以立即缓解症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 短效 β-2 受体激动剂(short-acting beta-2 agonist, SABA)和短效毒蕈碱受体拮抗剂(short-acting muscarinic antagonist, SAMA)能够改善肺功能、减轻呼吸困难和提升生活质量。
异丙托溴铵(一种 SAMA)在改善健康相关生活质量方面的益处略高于 SABA。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com 如果开处了 LAMA,则应停用 SAMA。SABA 包括沙丁胺醇。
一般不推荐常规使用短效支气管舒张剂。短效支气管舒张剂无效可能意味着急性加重。
第一选择
吸入性沙丁胺醇 : 需要时(100 μg/定量吸入器)100-200 μg(1-2 喷),每 4-6 小时一次
或
吸入性异丙托溴铵 : 需要时(20 μg/定量吸入器)40 μg(2 喷),每日最多 4 次
针对特定患者群中所有患者的治疗建议
应鼓励所有患者戒烟,并接受指导,避免职业或环境烟草烟雾暴露或其他刺激物暴露。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115 戒烟可显著降低 COPD 的进展速度和恶性肿瘤风险。请参阅“戒烟(治疗流程)” 。
根据本地指南,患者应接种流感病毒疫苗、肺炎链球菌疫苗、百日咳疫苗、水痘带状疱疹病毒疫苗、呼吸道合胞病毒疫苗和 2019 冠状病毒病(coronavirus disease 2019, COVID-19)疫苗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html 接种流感疫苗可减少 COPD 急性加重次数。[182]Walters JA, Tang JN, Poole P, et al. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Jan 24;(1):CD001390.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001390.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28116747?tool=bestpractice.com[183]Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018 Jun 26;(6):CD002733.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002733.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29943802?tool=bestpractice.com [ ]What are the effects of influenza vaccine in people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.2235/full展示答案 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)还建议在青春期未接种破伤风/白喉/百日咳疫苗的 COPD 患者补种。[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html
使用吸入治疗的患者应接受吸入器装置使用方法培训。多数患者在使用吸入器时至少犯一次错误,并且错误使用吸入器与疾病控制能力下降有关。[155]Cho-Reyes S, Celli BR, Dembek C, et al. Inhalation technique errors with metered-dose inhalers among patients with obstructive lung diseases: a systematic review and meta-analysis of US Studies. Chronic Obstr Pulm Dis. 2019 Jul 24;6(3):267-80.https://journal.copdfoundation.org/jcopdf/id/1241/Inhalation-Technique-Errors-with-Metered-Dose-Inhalers-Among-Patients-with-Obstructive-Lung-Diseases-A-Systematic-Review-and-Meta-Analysis-of-US-Studieshttp://www.ncbi.nlm.nih.gov/pubmed/31342732?tool=bestpractice.com[156]Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011 Jun;105(6):930-8.https://www.resmedjournal.com/article/S0954-6111(11)00009-6/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21367593?tool=bestpractice.com 临床医生演示吸入器用法、选用合适的装置以及在后续复诊时检查使用方法均可改善吸入器使用技术。[158]Price D, Keininger DL, Viswanad B, et al. Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey. Int J Chron Obstruct Pulmon Dis. 2018 Feb 26;13:695-702. [Erratum in: Int J Chron Obstruct Pulmon Dis. 2018 Jul 25;13:2253-4.]https://www.dovepress.com/factors-associated-with-appropriate-inhaler-use-in-patients-with-copd--peer-reviewed-fulltext-article-COPDhttp://www.ncbi.nlm.nih.gov/pubmed/29520137?tool=bestpractice.com
对所有患者进行关于病程以及加重或失代偿症状的宣教。他们对疾病、治疗和预后的预期应符合实际。研究显示,目前没有药物能改善长期减退的肺功能,药物治疗的主要目标是控制症状和预防并发症。自我管理教育应包括提供书面行动计划。推荐所有 COPD 患者进行体力活动。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
针对特定患者群中所有患者的治疗建议
肺康复项目包括有氧运动、力量训练和宣教,应在病程早期开始。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[189]Rochester CL, Alison JA, Carlin B, et al. Pulmonary rehabilitation for adults with chronic respiratory disease: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2023 Aug 15;208(4):e7-26.https://www.atsjournals.org/doi/10.1164/rccm.202306-1066SThttp://www.ncbi.nlm.nih.gov/pubmed/37581410?tool=bestpractice.com[190]Man W, Chaplin E, Daynes E, et al. British Thoracic Society Clinical Statement on pulmonary rehabilitation. Thorax. 2023 Oct;78(suppl 5):s2-15.https://thorax.bmj.com/content/78/Suppl_5/s2http://www.ncbi.nlm.nih.gov/pubmed/37770084?tool=bestpractice.com GOLD 指南推荐 B 组和 E 组患者参与肺康复项目。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
肺康复训练可缓解呼吸困难和疲劳、改善情绪功能,并能在较大程度增强控制感,将其改善到具有临床意义的程度。[191]McCarthy B, Casey D, Devane D, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015 Feb 23;(2):CD003793.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003793.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25705944?tool=bestpractice.com
美国一项大型队列研究发现,COPD 急性加重后出院 90 日内开始肺康复,与 1 年死亡率降低和 1 年再住院率降低具有显著相关性。[194]Lindenauer PK, Stefan MS, Pekow PS, et al. Association between initiation of pulmonary rehabilitation after hospitalization for COPD and 1-year survival among medicare beneficiaries. JAMA. 2020 May 12;323(18):1813-23.https://jamanetwork.com/journals/jama/fullarticle/2765730http://www.ncbi.nlm.nih.gov/pubmed/32396181?tool=bestpractice.com[195]Stefan MS, Pekow PS, Priya A, et al. Association between initiation of pulmonary rehabilitation and rehospitalizations in patients hospitalized with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2021 Nov 1;204(9):1015-23.https://www.atsjournals.org/doi/10.1164/rccm.202012-4389OChttp://www.ncbi.nlm.nih.gov/pubmed/34283694?tool=bestpractice.com 然而,出院前开始进行肺康复可能导致 12 个月死亡率升高,因此不受推荐。[196]Greening NJ, Williams JE, Hussain SF, et al. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial. BMJ. 2014 Jul 8;349:g4315.https://www.bmj.com/content/349/bmj.g4315http://www.ncbi.nlm.nih.gov/pubmed/25004917?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
慢性阻塞性肺疾病全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)B 组患者的特点是症状较多(改良版英国医学研究委员会 [Modified British Medical Research Council, mMRC] ≥2 或 COPD 评估测试 [COPD Assessment Test, CAT]≥10)而急性加重风险低(每年急性加重 0-1 次,无需住院)。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
如果存在不良反应或药物可及性问题,可开具 LAMA 或 LABA 单药治疗处方。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 对于该组患者的初始治疗,尚无证据推荐使用某一类长效支气管扩张剂,而非另一类。选择应取决于患者对症状缓解的感受。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
LABA 和 LAMA 均可显著改善肺功能、呼吸困难和健康状况,还能减少加重频率。 [ ]How does umeclidinium bromide compare with placebo for people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.1829/full展示答案
LABA 包括沙美特罗、arformoterol、奥达特罗。LAMA 包括噻托溴铵、乌美溴铵、aclidinium 和格隆溴铵。 [ ]How does umeclidinium bromide compare with placebo for people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.1829/full展示答案 revefenacin 是一种雾化 LAMA,已获批用于中至重度 COPD 的维持治疗。
第一选择
LABA
吸入性沙美特罗 : (50 µg/定量吸入器)50 µg(1 喷),每日两次
或
LABA
吸入性福莫特罗 : 15 μg,雾化吸入,每日两次
或
LABA
吸入性奥达特罗 : (2.5 μg/定量吸入器)5 μg(2 喷),每日 1 次
或
LAMA
吸入性噻托溴铵 : (18 μg/胶囊吸入器)18 μg(1 粒胶囊),每日一次;(2.5 μg/定量吸入器)5 μg(2 喷),每日一次
或
LAMA
吸入性芜地溴铵 : (62.5 μg/定量吸入器)62.5 μg(1 喷),每日一次
或
LAMA
吸入性阿地溴铵 : (400 μg/定量吸入器)400 μg(1 喷),每日 2 次
或
LAMA
吸入性格隆溴铵 : (55 μg/胶囊吸入器)55 μg(1 粒胶囊),每日一次
更多 吸入性格隆溴铵每粒胶囊递送 55 µg 格隆溴铵化合物(相当于 44 µg 格隆溴铵 [glycopyrronium])。
或
LAMA
吸入用 revefenacin : 175 μg,雾化吸入,每日一次
针对特定患者群中所有患者的治疗建议
对于所有诊断为 COPD 的患者,均应开处短效支气管舒张剂,以立即缓解症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 短效 β-2 受体激动剂(short-acting beta-2 agonist, SABA)和短效毒蕈碱受体拮抗剂(short-acting muscarinic antagonist, SAMA)能够改善肺功能、减轻呼吸困难和提升生活质量。
异丙托溴铵(一种 SAMA)在改善健康相关生活质量方面的益处略高于 SABA。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com 如果开处了 LAMA,则应停用 SAMA。SABA 包括沙丁胺醇。
一般不推荐常规使用短效支气管舒张剂。短效支气管舒张剂无效可能意味着急性加重。
第一选择
吸入性沙丁胺醇 : 需要时(100 μg/定量吸入器)100-200 μg(1-2 喷),每 4-6 小时一次
或
吸入性异丙托溴铵 : 需要时(20 μg/定量吸入器)40 μg(2 喷),每日最多 4 次
针对特定患者群中所有患者的治疗建议
应鼓励所有患者戒烟,并接受指导,避免职业或环境烟草烟雾暴露或其他刺激物暴露。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115 戒烟可显著降低 COPD 的进展速度和恶性肿瘤风险。请参阅“戒烟(治疗流程)” 。
根据本地指南,患者应接种流感病毒疫苗、肺炎链球菌疫苗、百日咳疫苗、水痘带状疱疹病毒疫苗、呼吸道合胞病毒疫苗和 2019 冠状病毒病(coronavirus disease 2019, COVID-19)疫苗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html 接种流感疫苗可减少 COPD 急性加重次数。[182]Walters JA, Tang JN, Poole P, et al. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Jan 24;(1):CD001390.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001390.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28116747?tool=bestpractice.com[183]Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018 Jun 26;(6):CD002733.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002733.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29943802?tool=bestpractice.com [ ]What are the effects of influenza vaccine in people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.2235/full展示答案 CDC 还建议在青春期未接种破伤风/白喉/百日咳疫苗的 COPD 患者补种。[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html
使用吸入治疗的患者应接受吸入器装置使用方法培训。多数患者在使用吸入器时至少犯一次错误,并且错误使用吸入器与疾病控制能力下降有关。[155]Cho-Reyes S, Celli BR, Dembek C, et al. Inhalation technique errors with metered-dose inhalers among patients with obstructive lung diseases: a systematic review and meta-analysis of US Studies. Chronic Obstr Pulm Dis. 2019 Jul 24;6(3):267-80.https://journal.copdfoundation.org/jcopdf/id/1241/Inhalation-Technique-Errors-with-Metered-Dose-Inhalers-Among-Patients-with-Obstructive-Lung-Diseases-A-Systematic-Review-and-Meta-Analysis-of-US-Studieshttp://www.ncbi.nlm.nih.gov/pubmed/31342732?tool=bestpractice.com[156]Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011 Jun;105(6):930-8.https://www.resmedjournal.com/article/S0954-6111(11)00009-6/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21367593?tool=bestpractice.com 临床医生演示吸入器用法、选用合适的装置以及在后续复诊时检查使用方法均可改善吸入器使用技术。[158]Price D, Keininger DL, Viswanad B, et al. Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey. Int J Chron Obstruct Pulmon Dis. 2018 Feb 26;13:695-702. [Erratum in: Int J Chron Obstruct Pulmon Dis. 2018 Jul 25;13:2253-4.]https://www.dovepress.com/factors-associated-with-appropriate-inhaler-use-in-patients-with-copd--peer-reviewed-fulltext-article-COPDhttp://www.ncbi.nlm.nih.gov/pubmed/29520137?tool=bestpractice.com
对所有患者进行关于病程以及加重或失代偿症状的宣教。他们对疾病、治疗和预后的预期应符合实际。研究显示,目前没有药物能改善长期减退的肺功能,药物治疗的主要目标是控制症状和预防并发症。自我管理教育应包括提供书面行动计划。推荐所有 COPD 患者进行体力活动。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
针对特定患者群中所有患者的治疗建议
肺康复项目包括有氧运动、力量训练和宣教,应在病程早期开始。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[189]Rochester CL, Alison JA, Carlin B, et al. Pulmonary rehabilitation for adults with chronic respiratory disease: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2023 Aug 15;208(4):e7-26.https://www.atsjournals.org/doi/10.1164/rccm.202306-1066SThttp://www.ncbi.nlm.nih.gov/pubmed/37581410?tool=bestpractice.com[190]Man W, Chaplin E, Daynes E, et al. British Thoracic Society Clinical Statement on pulmonary rehabilitation. Thorax. 2023 Oct;78(suppl 5):s2-15.https://thorax.bmj.com/content/78/Suppl_5/s2http://www.ncbi.nlm.nih.gov/pubmed/37770084?tool=bestpractice.com GOLD 指南推荐 B 组和 E 组患者参与肺康复项目。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
肺康复训练可缓解呼吸困难和疲劳、改善情绪功能,并能在较大程度增强控制感,将其改善到具有临床意义的程度。[191]McCarthy B, Casey D, Devane D, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015 Feb 23;(2):CD003793.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003793.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25705944?tool=bestpractice.com
美国一项大型队列研究发现,COPD 急性加重后出院 90 日内开始肺康复,与 1 年死亡率降低和 1 年再住院率降低具有显著相关性。[194]Lindenauer PK, Stefan MS, Pekow PS, et al. Association between initiation of pulmonary rehabilitation after hospitalization for COPD and 1-year survival among medicare beneficiaries. JAMA. 2020 May 12;323(18):1813-23.https://jamanetwork.com/journals/jama/fullarticle/2765730http://www.ncbi.nlm.nih.gov/pubmed/32396181?tool=bestpractice.com[195]Stefan MS, Pekow PS, Priya A, et al. Association between initiation of pulmonary rehabilitation and rehospitalizations in patients hospitalized with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2021 Nov 1;204(9):1015-23.https://www.atsjournals.org/doi/10.1164/rccm.202012-4389OChttp://www.ncbi.nlm.nih.gov/pubmed/34283694?tool=bestpractice.com 然而,出院前开始进行肺康复可能导致 12 个月死亡率升高,因此不受推荐。[196]Greening NJ, Williams JE, Hussain SF, et al. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial. BMJ. 2014 Jul 8;349:g4315.https://www.bmj.com/content/349/bmj.g4315http://www.ncbi.nlm.nih.gov/pubmed/25004917?tool=bestpractice.com
慢性阻塞性肺疾病全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)E 组患者的特点是急性加重风险高(每年急性加重≥2 次,或需要住院≥1 次)且有任何严重程度的症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
GOLD 建议首先采用长效 β2 受体激动剂(long-acting beta-2 agonist, LABA)/长效毒蕈碱受体拮抗剂(long-acting muscarinic antagonist, LAMA)联合治疗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
如果患者的血嗜酸性粒细胞计数≥300 个细胞/μL,则应考虑在 LABA/LAMA 联合治疗的基础上加用吸入皮质类固醇(inhaled corticosteroid, ICS)。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 含 ICS 的治疗方案对于具有加重高风险(前一年出现两次或两次以上加重和/或一次因加重而住院)的患者效力较高。[84]Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018 Mar 17;391(10125):1076-84.http://www.ncbi.nlm.nih.gov/pubmed/29429593?tool=bestpractice.com[86]Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018 May 3;378(18):1671-80.https://www.nejm.org/doi/10.1056/NEJMoa1713901http://www.ncbi.nlm.nih.gov/pubmed/29668352?tool=bestpractice.com[113]Wedzicha JA, Banerji D, Chapman KR, et al; FLAME Investigators. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016 Jun 9;374(23):2222-34.https://www.nejm.org/doi/10.1056/NEJMoa1516385http://www.ncbi.nlm.nih.gov/pubmed/27181606?tool=bestpractice.com 血嗜酸性粒细胞计数可预测常规长效支气管舒张剂治疗联合吸入皮质类固醇用于预防急性加重的疗效。[71]Harries TH, Rowland V, Corrigan CJ, et al. Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. Respir Res. 2020 Jan 3;21(1):3.https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1268-7http://www.ncbi.nlm.nih.gov/pubmed/31900184?tool=bestpractice.com[72]Oshagbemi OA, Odiba JO, Daniel A, et al. Absolute blood eosinophil counts to guide inhaled corticosteroids therapy among patients with COPD: systematic review and meta-analysis. Curr Drug Targets. 2019;20(16):1670-9.http://www.ncbi.nlm.nih.gov/pubmed/31393244?tool=bestpractice.com[73]Pascoe S, Barnes N, Brusselle G, et al. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med. 2019 Sep;7(9):745-56.http://www.ncbi.nlm.nih.gov/pubmed/31281061?tool=bestpractice.com 血嗜酸性粒细胞计数<100 个细胞/μL 时,疗效甚微或无效,而血嗜酸性粒细胞计数≥300 个细胞/μL 时,疗效最佳。[70]Bafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018 Feb;6(2):117-26.http://www.ncbi.nlm.nih.gov/pubmed/29331313?tool=bestpractice.com[74]Cazzola M, Rogliani P, Calzetta L, et al. Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis. Eur Respir J. 2018 Dec 13;52(6):1801586.https://erj.ersjournals.com/content/52/6/1801586http://www.ncbi.nlm.nih.gov/pubmed/30309975?tool=bestpractice.com 这些阈值是可能有助于临床医师预测治疗获益可能性的近似临界值。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 对于血嗜酸性粒细胞增多的轻至中度 COPD 患者,使用 ICS 还可减缓加重后肺功能减退的速度。[128]Kerkhof M, Voorham J, Dorinsky P, et al. Association between COPD exacerbations and lung function decline during maintenance therapy. Thorax. 2020 Sep;75(9):744-53.https://thorax.bmj.com/content/75/9/744http://www.ncbi.nlm.nih.gov/pubmed/32532852?tool=bestpractice.com 无论嗜酸性粒细胞计数如何,既往曾吸烟者都要比当前吸烟者对皮质类固醇的反应更强。[73]Pascoe S, Barnes N, Brusselle G, et al. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med. 2019 Sep;7(9):745-56.http://www.ncbi.nlm.nih.gov/pubmed/31281061?tool=bestpractice.com 以肺功能和加重率而言,罹患 COPD 的当前吸烟者和既往曾吸烟者均可获益于 ICS 治疗,然而,与轻度吸烟者和既往曾吸烟者相比,其对重度吸烟者或当前吸烟者效力较轻。[86]Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018 May 3;378(18):1671-80.https://www.nejm.org/doi/10.1056/NEJMoa1713901http://www.ncbi.nlm.nih.gov/pubmed/29668352?tool=bestpractice.com[114]Sonnex K, Alleemudder H, Knaggs R. Impact of smoking status on the efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review. BMJ Open. 2020 Apr 15;10(4):e037509.https://bmjopen.bmj.com/content/10/4/e037509http://www.ncbi.nlm.nih.gov/pubmed/32300001?tool=bestpractice.com
ICS 会增加某些患者患肺炎的风险,因此仅应在评估可能的临床风险和益处后,才可用作初始治疗。
乌美溴铵/维兰特罗、格隆溴铵/福莫特罗、噻托溴铵/奥达特罗和 aclidinium/福莫特罗是获批用于治疗 COPD 的 LABA/LAMA 复方制剂。[113]Wedzicha JA, Banerji D, Chapman KR, et al; FLAME Investigators. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016 Jun 9;374(23):2222-34.https://www.nejm.org/doi/10.1056/NEJMoa1516385http://www.ncbi.nlm.nih.gov/pubmed/27181606?tool=bestpractice.com[227]Radovanovic D, Mantero M, Sferrazza Papa GF, et al. Formoterol fumarate + glycopyrrolate for the treatment of chronic obstructive pulmonary disease. Expert Rev Respir Med. 2016 Oct;10(10):1045-55.http://www.ncbi.nlm.nih.gov/pubmed/27552524?tool=bestpractice.com 乌美溴铵/维兰特罗可降低轻度/中度 COPD 患者的急性加重风险。[107]Maqsood U, Ho TN, Palmer K, et al. Once daily long-acting beta2-agonists and long-acting muscarinic antagonists in a combined inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2019 Mar 6;(3):CD012930.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012930.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/30839102?tool=bestpractice.com [ ]How does a combined inhaler with once‐daily long‐acting beta2‐agonist (LABA) plus a long‐acting muscarinic antagonist (LAMA) compare with placebo for adults with chronic obstructive pulmonary disease (COPD)?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2551/full展示答案
现有含氟替卡松/乌美溴铵/维兰特罗(一种 LABA/LAMA/ICS 复方制剂)的专利复方吸入器。
第一选择
LABA/LAMA 二联疗法
吸入性芜地溴铵 (umeclidinium)/维兰特罗 (vilanterol) : (62.5/25 μg/定量吸入器)1 喷,每日一次
或
LABA/LAMA 二联疗法
格隆溴铵/福莫特罗 : (7.2 μg/5 μg 定量吸入器)每次 2 揿,每日两次
或
LABA/LAMA 二联疗法
吸入性噻托溴铵/奥达特罗 : (2.5/2.5 μg/定量吸入器)2 喷,每日一次
或
LABA/LAMA 二联疗法
吸入性阿地溴铵/福莫特罗 : (每剂吸入剂 400/12 μg)1 喷,每日两次
第二选择
LABA/LAMA/ICS 三联疗法
吸入用糠酸氟替卡松/芜地溴铵 (umeclidinium) /维兰特罗 (vilanterol) : (92/55/22 μg/定量吸入器)1 喷,每日一次
更多 吸入用糠酸氟替卡松/芜地溴铵 (umeclidinium) /维兰特罗 (vilanterol)每一次吸入可提供 92 μg 糠酸氟替卡松、65 μg 芜地溴铵化合物(相当于 55 μg 芜地溴铵 [umeclidinium])和 22 μg 维兰特罗(三氟甲磺酸盐形式)的递送剂量。
或
LABA/LAMA/ICS 三联疗法
吸入性糠酸氟替卡松/维兰特罗 : (100/25 μg/定量吸入器)1 喷,每日 1 次
或
吸入性丙酸氟替卡松/沙美特罗 : (250/50 μg/定量吸入器)1 喷,每日 2 次
或
吸入性布地奈德/福莫特罗 : (160/4.5 μg/定量吸入器)2 喷,每日 2 次
或
吸入性莫米松/福莫特罗 : (100/5 μg/定量吸入器;200/5 μg/定量吸入器)2 喷,每日 2 次
-- 和 --
吸入性噻托溴铵 : (18 μg/胶囊吸入器)18 μg(1 粒胶囊),每日一次;(2.5 μg/定量吸入器)5 μg(2 喷),每日一次
或
吸入性芜地溴铵 : (62.5 μg/定量吸入器)62.5 μg(1 喷),每日一次
或
吸入性阿地溴铵 : (400 μg/定量吸入器)400 μg(1 喷),每日 2 次
或
吸入性格隆溴铵 : (55 μg/胶囊吸入器)55 μg(1 粒胶囊),每日一次
更多 吸入性格隆溴铵每粒胶囊递送 55 µg 格隆溴铵化合物(相当于 44 µg 格隆溴铵 [glycopyrronium])。
针对特定患者群中所有患者的治疗建议
对于所有诊断为 COPD 的患者,均应开处短效支气管舒张剂,以立即缓解症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 短效 β-2 受体激动剂(short-acting beta-2 agonist, SABA)和短效毒蕈碱受体拮抗剂(short-acting muscarinic antagonist, SAMA)能够改善肺功能、减轻呼吸困难和提升生活质量。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com
异丙托溴铵(一种 SAMA)在改善健康相关生活质量方面的益处略高于 SABA。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com 如果开处了 LAMA,则应停用 SAMA。SABA 包括沙丁胺醇。
一般不推荐常规使用短效支气管舒张剂。短效支气管舒张剂无效可能意味着急性加重。
第一选择
吸入性沙丁胺醇 : 需要时(100 μg/定量吸入器)100-200 μg(1-2 喷),每 4-6 小时一次
或
吸入性异丙托溴铵 : 需要时(20 μg/定量吸入器)40 μg(2 喷),每日最多 4 次
针对特定患者群中所有患者的治疗建议
应鼓励所有患者戒烟,并接受指导,避免职业或环境烟草烟雾暴露或其他刺激物暴露。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115 戒烟可显著降低 COPD 的进展速度和恶性肿瘤风险。请参阅“戒烟(治疗流程)” 。
根据本地指南,患者应接种流感病毒疫苗、肺炎链球菌疫苗、百日咳疫苗、水痘带状疱疹病毒疫苗、呼吸道合胞病毒疫苗和 2019 冠状病毒病(coronavirus disease 2019, COVID-19)疫苗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html 接种流感疫苗可减少 COPD 急性加重次数。[182]Walters JA, Tang JN, Poole P, et al. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Jan 24;(1):CD001390.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001390.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28116747?tool=bestpractice.com[183]Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018 Jun 26;(6):CD002733.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002733.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29943802?tool=bestpractice.com [ ]What are the effects of influenza vaccine in people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.2235/full展示答案 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)还建议在青春期未接种破伤风/白喉/百日咳疫苗的 COPD 患者补种。[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html
使用吸入治疗的患者应接受吸入器装置使用方法培训。多数患者在使用吸入器时至少犯一次错误,并且错误使用吸入器与疾病控制能力下降有关。[155]Cho-Reyes S, Celli BR, Dembek C, et al. Inhalation technique errors with metered-dose inhalers among patients with obstructive lung diseases: a systematic review and meta-analysis of US Studies. Chronic Obstr Pulm Dis. 2019 Jul 24;6(3):267-80.https://journal.copdfoundation.org/jcopdf/id/1241/Inhalation-Technique-Errors-with-Metered-Dose-Inhalers-Among-Patients-with-Obstructive-Lung-Diseases-A-Systematic-Review-and-Meta-Analysis-of-US-Studieshttp://www.ncbi.nlm.nih.gov/pubmed/31342732?tool=bestpractice.com[156]Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011 Jun;105(6):930-8.https://www.resmedjournal.com/article/S0954-6111(11)00009-6/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21367593?tool=bestpractice.com 临床医生演示吸入器用法、选用合适的装置以及在后续复诊时检查使用方法均可改善吸入器使用技术。[158]Price D, Keininger DL, Viswanad B, et al. Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey. Int J Chron Obstruct Pulmon Dis. 2018 Feb 26;13:695-702. [Erratum in: Int J Chron Obstruct Pulmon Dis. 2018 Jul 25;13:2253-4.]https://www.dovepress.com/factors-associated-with-appropriate-inhaler-use-in-patients-with-copd--peer-reviewed-fulltext-article-COPDhttp://www.ncbi.nlm.nih.gov/pubmed/29520137?tool=bestpractice.com
对所有患者进行关于病程以及加重或失代偿症状的宣教。他们对疾病、治疗和预后的预期应符合实际。研究显示,目前没有药物能改善长期减退的肺功能,药物治疗的主要目标是控制症状和预防并发症。自我管理教育应包括提供书面行动计划。推荐所有 COPD 患者进行体力活动。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
针对特定患者群中所有患者的治疗建议
肺康复项目包括有氧运动、力量训练和宣教,应在病程早期开始。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[189]Rochester CL, Alison JA, Carlin B, et al. Pulmonary rehabilitation for adults with chronic respiratory disease: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2023 Aug 15;208(4):e7-26.https://www.atsjournals.org/doi/10.1164/rccm.202306-1066SThttp://www.ncbi.nlm.nih.gov/pubmed/37581410?tool=bestpractice.com[190]Man W, Chaplin E, Daynes E, et al. British Thoracic Society Clinical Statement on pulmonary rehabilitation. Thorax. 2023 Oct;78(suppl 5):s2-15.https://thorax.bmj.com/content/78/Suppl_5/s2http://www.ncbi.nlm.nih.gov/pubmed/37770084?tool=bestpractice.com GOLD 指南推荐 B 组和 E 组患者参与肺康复项目。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
肺康复训练可缓解呼吸困难和疲劳、改善情绪功能,并能在较大程度增强控制感,将其改善到具有临床意义的程度。[191]McCarthy B, Casey D, Devane D, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015 Feb 23;(2):CD003793.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003793.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25705944?tool=bestpractice.com
美国一项大型队列研究发现,COPD 急性加重后出院 90 日内开始肺康复,与 1 年死亡率降低和 1 年再住院率降低具有显著相关性。[194]Lindenauer PK, Stefan MS, Pekow PS, et al. Association between initiation of pulmonary rehabilitation after hospitalization for COPD and 1-year survival among medicare beneficiaries. JAMA. 2020 May 12;323(18):1813-23.https://jamanetwork.com/journals/jama/fullarticle/2765730http://www.ncbi.nlm.nih.gov/pubmed/32396181?tool=bestpractice.com[195]Stefan MS, Pekow PS, Priya A, et al. Association between initiation of pulmonary rehabilitation and rehospitalizations in patients hospitalized with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2021 Nov 1;204(9):1015-23.https://www.atsjournals.org/doi/10.1164/rccm.202012-4389OChttp://www.ncbi.nlm.nih.gov/pubmed/34283694?tool=bestpractice.com 然而,出院前开始进行肺康复可能导致 12 个月死亡率升高,因此不受推荐。[196]Greening NJ, Williams JE, Hussain SF, et al. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial. BMJ. 2014 Jul 8;349:g4315.https://www.bmj.com/content/349/bmj.g4315http://www.ncbi.nlm.nih.gov/pubmed/25004917?tool=bestpractice.com
慢性阻塞性肺疾病全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)A 组患者的特点是症状少(改良版英国医学研究理事会 [Modified British Medical Research Council, mMRC]分级为 0-1 或 COPD 评估测试 [COPD Assessment Test, CAT]<10)且急性加重风险低(每年急性加重 0-1 次,无需住院);B 组患者的特点是症状较多(mMRC≥2 或 CAT≥10)而急性加重风险低(每年急性加重 0-1 次,无需住院);E 组患者的特点是急性加重风险高(每年急性加重≥2 次,或≥1 次需要住院)且有任何严重程度的症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
GOLD 建议,如果患者在进行初始治疗后有持续性症状和急性加重,则临床医生应遵循持续性加重治疗路径进行处理。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
仅使用长效 β2 受体激动剂(long-acting beta-2 agonist, LABA)或长效毒蕈碱受体拮抗剂(long-acting muscarinic antagonist, LAMA)但出现持续性呼吸困难/活动受限的患者,应改用长效支气管舒张剂二联治疗(LABA/LAMA 联合治疗)。如果症状无改善,可考虑更换吸入器装置或药物颗粒大小。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
使用 LABA/LAMA 二联治疗可能获得更好的治疗效果,且不会增加其中各类药物的不良反应。[99]Rabe KF, Timmer W, Sagkriotis A, et al. Comparison of a combination of tiotropium plus formoterol to salmeterol plus fluticasone in moderate COPD. Chest. 2008 Aug;134(2):255-62.http://www.ncbi.nlm.nih.gov/pubmed/18403672?tool=bestpractice.com[103]Tashkin DP, Littner M, Andrews CP, et al. Concomitant treatment with nebulized formoterol and tiotropium in subjects with COPD: a placebo-controlled trial. Respir Med. 2008 Apr;102(4):479-87.http://www.ncbi.nlm.nih.gov/pubmed/18258423?tool=bestpractice.com[104]Tashkin DP, Pearle J, Iezzoni D, et al. Formoterol and tiotropium compared with tiotropium alone for treatment of COPD. COPD. 2009 Feb;6(1):17-25.http://www.ncbi.nlm.nih.gov/pubmed/19229704?tool=bestpractice.com[105]Vogelmeier C, Kardos P, Harari S, et al. Formoterol mono- and combination therapy with tiotropium in patients with COPD: a 6-month study. Respir Med. 2008 Nov;102(11):1511-20.http://www.ncbi.nlm.nih.gov/pubmed/18804362?tool=bestpractice.com[106]Maltais F, Bjermer L, Kerwin EM, et al. Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial. Respir Res. 2019 Oct 30;20(1):238.https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1193-9http://www.ncbi.nlm.nih.gov/pubmed/31666084?tool=bestpractice.com 系统评价和荟萃分析发现,LABA/LAMA 联合治疗:
与单药治疗相比,可降低急性加重率
与安慰剂相比,可为轻度/中度 COPD 患者带来有显著临床意义的肺功能和健康相关的生存质量改善[107]Maqsood U, Ho TN, Palmer K, et al. Once daily long-acting beta2-agonists and long-acting muscarinic antagonists in a combined inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2019 Mar 6;(3):CD012930.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012930.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/30839102?tool=bestpractice.com [ ]How does a combined inhaler with once‐daily long‐acting beta2‐agonist (LABA) plus a long‐acting muscarinic antagonist (LAMA) compare with placebo for adults with chronic obstructive pulmonary disease (COPD)?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2551/full展示答案
可改善稳定期 COPD 患者的 FEV₁ 并小幅降低其肺炎风险,但使全因死亡率从 1% 增至 1.4%。[108]Fukuda N, Horita N, Kaneko A, et al. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2023 Jun 5;6(6):CD012066.https://www.doi.org/10.1002/14651858.CD012066.pub3http://www.ncbi.nlm.nih.gov/pubmed/37276335?tool=bestpractice.com [ ]How does long‐acting muscarinic antagonist (LAMA) plus long‐acting beta‐agonist (LABA) compare with LABA plus inhaled corticosteroid (ICS) for people with stable chronic obstructive pulmonary disease (COPD)?https://www.cochranelibrary.com/cca/doi/10.1002/cca.4356/full展示答案
对于由其他原因引起的呼吸困难应予以考虑、检查和治疗。吸入器使用技术和依从性也应进行再评估,因其可能导致治疗反应不足。
第一选择
LABA/LAMA 二联疗法
吸入性芜地溴铵 (umeclidinium)/维兰特罗 (vilanterol) : (62.5/25 μg/定量吸入器)1 喷,每日一次
或
LABA/LAMA 二联疗法
格隆溴铵/福莫特罗 : (7.2 μg/5 μg 定量吸入器)每次 2 揿,每日两次
或
LABA/LAMA 二联疗法
吸入性噻托溴铵/奥达特罗 : (2.5/2.5 μg/定量吸入器)2 喷,每日一次
或
LABA/LAMA 二联疗法
吸入性阿地溴铵/福莫特罗 : (每剂吸入剂 400/12 μg)1 喷,每日两次
针对特定患者群中所有患者的治疗建议
对于所有诊断为 COPD 的患者,均应开处短效支气管舒张剂,以立即缓解症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
短效 β-2 受体激动剂(short-acting beta-2 agonist, SABA)和短效毒蕈碱受体拮抗剂(short-acting muscarinic antagonist, SAMA)能够改善肺功能、减轻呼吸困难和提升生活质量。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com
一般不推荐常规使用短效支气管舒张剂。短效支气管舒张剂无效可能意味着急性加重。
不应同时开处 LAMA 和 SAMA。SABA 包括沙丁胺醇。
第一选择
吸入性沙丁胺醇 : 需要时(100 μg/定量吸入器)100-200 μg(1-2 喷),每 4-6 小时一次
针对特定患者群中所有患者的治疗建议
应鼓励所有患者戒烟,并接受指导,避免职业或环境烟草烟雾暴露或其他刺激物暴露。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115 戒烟可显著降低 COPD 的进展速度和恶性肿瘤风险。请参阅“戒烟(治疗流程)” 。
根据本地指南,患者应接种流感病毒疫苗、肺炎链球菌疫苗、百日咳疫苗、水痘带状疱疹病毒疫苗、呼吸道合胞病毒疫苗和 2019 冠状病毒病(coronavirus disease 2019, COVID-19)疫苗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html 接种流感疫苗可减少 COPD 急性加重次数。[182]Walters JA, Tang JN, Poole P, et al. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Jan 24;(1):CD001390.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001390.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28116747?tool=bestpractice.com[183]Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018 Jun 26;(6):CD002733.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002733.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29943802?tool=bestpractice.com [ ]What are the effects of influenza vaccine in people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.2235/full展示答案 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)还建议在青春期未接种破伤风/白喉/百日咳疫苗的 COPD 患者补种。[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html
使用吸入治疗的患者应接受吸入器装置使用方法培训。多数患者在使用吸入器时至少犯一次错误,并且错误使用吸入器与疾病控制能力下降有关。[155]Cho-Reyes S, Celli BR, Dembek C, et al. Inhalation technique errors with metered-dose inhalers among patients with obstructive lung diseases: a systematic review and meta-analysis of US Studies. Chronic Obstr Pulm Dis. 2019 Jul 24;6(3):267-80.https://journal.copdfoundation.org/jcopdf/id/1241/Inhalation-Technique-Errors-with-Metered-Dose-Inhalers-Among-Patients-with-Obstructive-Lung-Diseases-A-Systematic-Review-and-Meta-Analysis-of-US-Studieshttp://www.ncbi.nlm.nih.gov/pubmed/31342732?tool=bestpractice.com[156]Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011 Jun;105(6):930-8.https://www.resmedjournal.com/article/S0954-6111(11)00009-6/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21367593?tool=bestpractice.com 临床医生演示吸入器用法、选用合适的装置以及在后续复诊时检查使用方法均可改善吸入器使用技术。[158]Price D, Keininger DL, Viswanad B, et al. Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey. Int J Chron Obstruct Pulmon Dis. 2018 Feb 26;13:695-702. [Erratum in: Int J Chron Obstruct Pulmon Dis. 2018 Jul 25;13:2253-4.]https://www.dovepress.com/factors-associated-with-appropriate-inhaler-use-in-patients-with-copd--peer-reviewed-fulltext-article-COPDhttp://www.ncbi.nlm.nih.gov/pubmed/29520137?tool=bestpractice.com
对所有患者进行关于病程以及加重或失代偿症状的宣教。他们对疾病、治疗和预后的预期应符合实际。研究显示,目前没有药物能改善长期减退的肺功能,药物治疗的主要目标是控制症状和预防并发症。自我管理教育应包括提供书面行动计划。推荐所有 COPD 患者进行体力活动。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
针对特定患者群中部分患者治疗的附加建议
肺康复项目包括有氧运动、力量训练和宣教,应在病程早期开始。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[189]Rochester CL, Alison JA, Carlin B, et al. Pulmonary rehabilitation for adults with chronic respiratory disease: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2023 Aug 15;208(4):e7-26.https://www.atsjournals.org/doi/10.1164/rccm.202306-1066SThttp://www.ncbi.nlm.nih.gov/pubmed/37581410?tool=bestpractice.com[190]Man W, Chaplin E, Daynes E, et al. British Thoracic Society Clinical Statement on pulmonary rehabilitation. Thorax. 2023 Oct;78(suppl 5):s2-15.https://thorax.bmj.com/content/78/Suppl_5/s2http://www.ncbi.nlm.nih.gov/pubmed/37770084?tool=bestpractice.com GOLD 指南推荐 B 组和 E 组患者参与肺康复项目。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
肺康复训练可缓解呼吸困难和疲劳、改善情绪功能,并能在较大程度增强控制感,将其改善到具有临床意义的程度。[191]McCarthy B, Casey D, Devane D, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015 Feb 23;(2):CD003793.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003793.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25705944?tool=bestpractice.com
美国一项大型队列研究发现,COPD 急性加重后出院 90 日内开始肺康复,与 1 年死亡率降低和 1 年再住院率降低具有显著相关性。[194]Lindenauer PK, Stefan MS, Pekow PS, et al. Association between initiation of pulmonary rehabilitation after hospitalization for COPD and 1-year survival among medicare beneficiaries. JAMA. 2020 May 12;323(18):1813-23.https://jamanetwork.com/journals/jama/fullarticle/2765730http://www.ncbi.nlm.nih.gov/pubmed/32396181?tool=bestpractice.com[195]Stefan MS, Pekow PS, Priya A, et al. Association between initiation of pulmonary rehabilitation and rehospitalizations in patients hospitalized with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2021 Nov 1;204(9):1015-23.https://www.atsjournals.org/doi/10.1164/rccm.202012-4389OChttp://www.ncbi.nlm.nih.gov/pubmed/34283694?tool=bestpractice.com 然而,出院前开始进行肺康复可能导致 12 个月死亡率升高,因此不受推荐。[196]Greening NJ, Williams JE, Hussain SF, et al. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial. BMJ. 2014 Jul 8;349:g4315.https://www.bmj.com/content/349/bmj.g4315http://www.ncbi.nlm.nih.gov/pubmed/25004917?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
GOLD 指南的建议指出,如果患者符合以下条件且病情稳定,则应进行长期氧疗:PaO₂ ≤7.3 kPa(55 mmHg)或 SaO₂ ≤88%(无论是否在 3 周内确认出现了两次高碳酸血症);或者如果有证据表明患者有肺动脉高压、提示充血性心力衰竭的外周水肿或红细胞增多症(血细胞比容 >55%),PaO₂ 介于 7.3 kPa(55 mmHg)至 8.0 kPa(60 mmHg)或 SaO₂ 为 88%。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
美国胸科学会(American Thoracic Society, ATS)指南建议,对于静息状态下呼吸室内空气时有重度慢性低氧血症的 COPD 成人,建议给予长期氧疗,每日至少供氧 15 小时。ATS 将重度低氧血症定义为(以下两者任一):PaO₂ ≤7.3 kPa(55 mmHg)或脉搏血氧测定氧饱和度(SpO₂)≤88%;或 PaO₂ 7.5-7.9 kPa(56-59 mmHg)或 SpO₂ 89% 加以下任一:水肿、血细胞比容≥55%,或 ECG 呈现肺型 P 波。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com
对于接受家庭氧疗的患者,ATS 建议患者及其照护者应接受所有氧气设备使用和维护的指导和培训,以及接受用氧安全教育,包括戒烟、防火和绊倒风险。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com
辅助供氧应滴定至实现 SaO₂ ≥90%。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 60-90 天后应对患者进行再评估,确定给氧是否仍有指征,并仍具有治疗作用。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 在 COPD 多个不同的治疗方法中,只有两个因素可以改善存活情况,即戒烟和氧疗。
氧疗有助于通过降低肺动脉压力而最大程度减低肺动脉高压,改善运动耐量,以及提高生活质量。已经证明它能改善生存情况。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[61]Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.https://www.acpjournals.org/doi/10.7326/0003-4819-155-3-201108020-00008http://www.ncbi.nlm.nih.gov/pubmed/21810710?tool=bestpractice.com
ATS 建议对伴 COPD 的重度劳力性室内空气低氧血症成人,进行动态给氧(活动或日常生活时给氧)。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com 但 ATS 建议,对于有中度慢性休息室空气低氧血症(SpO₂ 为 89%-93%)的 COPD 成人,勿给予长期氧疗。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com
罹患 COPD 和阻塞性睡眠呼吸暂停的患者,采用持续气道正压通气(continuous positive airway pressure, CPAP)进行通气支持,可改善生存率,并减少住院率。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[67]Marin JM, Soriano JB, Carrizo SJ, et al. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010 Aug 1;182(3):325-31.https://www.atsjournals.org/doi/10.1164/rccm.200912-1869OChttp://www.ncbi.nlm.nih.gov/pubmed/20378728?tool=bestpractice.com 无创通气偶用于病情非常严重但稳定的 COPD 患者,但选择适合患者的最佳标准尚未明确。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[208]Wilson ME, Dobler CC, Morrow AS, et al. Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2020 Feb 4;323(5):455-65.https://jamanetwork.com/journals/jama/fullarticle/2760390http://www.ncbi.nlm.nih.gov/pubmed/32016309?tool=bestpractice.com
ATS 指南建议,对于稳定的有慢性高碳酸血症的 COPD 患者,在常规治疗基础上增加夜间 NIV。[211]Macrea M, Oczkowski S, Rochwerg B, et al. Long-term noninvasive ventilation in chronic stable hypercapnic chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice fuideline. Am J Respir Crit Care Med. 2020 Aug 15;202(4):e74-87.https://www.atsjournals.org/doi/10.1164/rccm.202006-2382SThttp://www.ncbi.nlm.nih.gov/pubmed/32795139?tool=bestpractice.com 欧洲呼吸学会和加拿大胸科协会已发布相似指南。[212]Ergan B, Oczkowski S, Rochwerg B, et al. European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD. Eur Respir J. 2019 Sep 28;54(3):1901003.https://erj.ersjournals.com/content/54/3/1901003http://www.ncbi.nlm.nih.gov/pubmed/31467119?tool=bestpractice.com[213]Kaminska M, Rimmer KP, McKim DA, et al. Long-term non-invasive ventilation in patients with chronic obstructive pulmonary disease (COPD): 2021 Canadian Thoracic Society clinical practice guideline update. Can J Respir Crit Care Sleep Med. 2021 May 7;5(3):160-83.https://www.tandfonline.com/doi/full/10.1080/24745332.2021.1911218
针对特定患者群中部分患者治疗的附加建议
存在 COPD 慢性支气管炎表型的患者经常频繁出现浓痰。化痰药物可使急性加重频率和每月出现失能的天数略微减少,但不能改善肺功能或生活质量。[186]Poole P, Sathananthan K, Fortescue R. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2019 May 20;(5):CD001287.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001287.pub6/fullhttp://www.ncbi.nlm.nih.gov/pubmed/31107966?tool=bestpractice.com 一项 meta 分析对厄多司坦、羧甲司坦和乙酰半胱氨酸进行了比较,得出的结论为,厄多司坦的安全性和有效性最好。厄多司坦降低了因急性加重而住院的风险,它和乙酰半胱氨酸都缩短了急性加重的持续时间。[187]Rogliani P, Matera MG, Page C, et al. Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir Res. 2019 May 27;20(1):104.https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1078-yhttp://www.ncbi.nlm.nih.gov/pubmed/31133026?tool=bestpractice.com 因此,厄多司坦对于有条件的国家是推荐选择。另一项荟萃分析发现,与安慰剂相比,乙酰半胱氨酸可显著降低急性加重发病率,而不良反应风险未见升高。作者得出结论,3 个月低剂量治疗具有疗效。[188]Wei J, Pang CS, Han J, et al. Effect of orally administered N-acetylcysteine on chronic bronchitis: a meta-analysis. Adv Ther. 2019 Dec;36(12):3356-67.http://www.ncbi.nlm.nih.gov/pubmed/31598901?tool=bestpractice.com 使用化痰药物(例如羧甲司坦和乙酰半胱氨酸)进行治疗,可减少未接受 ICS 的患者发生急性加重,并适度改善健康状况。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 但是,无论患者是否正在使用吸入性皮质类固醇,厄多司坦对于轻度加重具有显著效果。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
第一选择
厄多司坦 : 咨询专科医生,获得剂量指导
或
乙酰半胱氨酸 : 咨询专科医生,获得剂量指导
或
羧甲司坦 : 咨询专科医生,获得剂量指导
针对特定患者群中部分患者治疗的附加建议
茶碱(一种甲基黄嘌呤剂)的效价有限、治疗窗窄、风险高,并且与其他药物有频繁的相互作用,因此不常使用。茶碱对中至重度 COPD 患者的肺功能有轻微作用。[144]Ram FSF, Jones P, Jardim J, et al. Oral theophylline for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2002;(4):CD003902.http://www.ncbi.nlm.nih.gov/pubmed/12519617?tool=bestpractice.com 一项大型随机对照试验发现,单纯口服茶碱,或联合使用泼尼松龙,对于重度 COPD 急性加重无治疗效果。[145]Jenkins CR, Wen FQ, Martin A, et al; TASCS study investigators. The effect of low-dose corticosteroids and theophylline on the risk of acute exacerbations of COPD: the TASCS randomised controlled trial. Eur Respir J. 2021 Jun 10;57(6):2003338.https://erj.ersjournals.com/content/57/6/2003338http://www.ncbi.nlm.nih.gov/pubmed/33334939?tool=bestpractice.com 如果所有吸入治疗选择均无效,专家可能开具茶碱。其毒性具有剂量依赖性。除非没有或负担不起其他长效支气管舒张剂治疗,否则不建议使用茶碱。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
第一选择
茶碱 : 咨询专科医生,获得剂量指导
针对特定患者群中部分患者治疗的附加建议
手术干预是 COPD 治疗的最后一步,包括肺大疱切除术、肺减容术和肺移植。[214]van Agteren JE, Hnin K, Grosser D, et al. Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Feb 23;(2):CD012158.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012158.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28230230?tool=bestpractice.com[215]van Agteren JE, Carson KV, Tiong LU, et al. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev. 2016 Oct 14;(10):CD001001.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001001.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27739074?tool=bestpractice.com [ ]How does bronchoscopic lung volume reduction compare with medical therapy in people with chronic obstructive pulmonary disease?https://cochranelibrary.com/cca/doi/10.1002/cca.1680/full展示答案 这些手术是用于改善肺动力学、运动依从性和生活质量。[215]van Agteren JE, Carson KV, Tiong LU, et al. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev. 2016 Oct 14;(10):CD001001.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001001.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27739074?tool=bestpractice.com 气流受限非常严重的患者需接受肺减容术,特别是局限性上叶病变且运动耐量低于正常的患者。[214]van Agteren JE, Hnin K, Grosser D, et al. Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Feb 23;(2):CD012158.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012158.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28230230?tool=bestpractice.com [ ]How does bronchoscopic lung volume reduction compare with medical therapy in people with chronic obstructive pulmonary disease?https://cochranelibrary.com/cca/doi/10.1002/cca.1680/full展示答案 一项荟萃分析发现,与标准治疗相比,接受肺减容术的患者早期死亡风险增加;然而,观察到总体死亡率差异无统计学意义。[216]van Geffen WH, Slebos DJ, Herth FJ, et al. Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis. Lancet Respir Med. 2019 Apr;7(4):313-24.http://www.ncbi.nlm.nih.gov/pubmed/30744937?tool=bestpractice.com 对于存在呼吸困难且 CT 检查发现巨型肺大疱占据胸腔容积至少 30% 的 COPD 患者,可采取肺大疱切除术。严重的功能状态不良和 FEV₁ 重度下降 (<500 mL) 使得这些方案不太有利。对于经适当选择的 COPD 患者,支气管内活瓣置入术可带来有临床意义的改善。[216]van Geffen WH, Slebos DJ, Herth FJ, et al. Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis. Lancet Respir Med. 2019 Apr;7(4):313-24.http://www.ncbi.nlm.nih.gov/pubmed/30744937?tool=bestpractice.com[217]Klooster K, Slebos DJ, Zoumot Z, et al. Endobronchial valves for emphysema: an individual patient-level reanalysis of randomised controlled trials. BMJ Open Respir Res. 2017 Nov 2;4(1):e000214.https://bmjopenrespres.bmj.com/content/4/1/e000214http://www.ncbi.nlm.nih.gov/pubmed/29441206?tool=bestpractice.com[218]Labarca G, Uribe JP, Pacheco C, et al. Bronchoscopic lung volume reduction with endobronchial zephyr valves for severe emphysema: a systematic review and meta-analysis. Respiration. 2019 May 22;98(3):268-78.http://www.ncbi.nlm.nih.gov/pubmed/31117102?tool=bestpractice.com 该手术可能对主要由终末细支气管远端气腔过度充气和气体滞留所致呼吸困难的患者(表现为肺气肿伴残气量显著增加)最有益。禁忌证包括活动性肺感染和不完全肺叶裂(<80%)。[219]Abia-Trujillo D, Johnson MM, Patel NM, et al. Bronchoscopic lung volume reduction: a new hope for patients with severe emphysema and air trapping. Mayo Clin Proc. 2021 Feb;96(2):464-72.http://www.ncbi.nlm.nih.gov/pubmed/32829903?tool=bestpractice.com 支气管内活瓣置入术相关性最常见不良事件为气胸和急性加重。[216]van Geffen WH, Slebos DJ, Herth FJ, et al. Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis. Lancet Respir Med. 2019 Apr;7(4):313-24.http://www.ncbi.nlm.nih.gov/pubmed/30744937?tool=bestpractice.com
肺移植转诊标准包括:[220]Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: an update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021 Nov;40(11):1349-79.https://www.jhltonline.org/article/S1053-2498(21)02407-4/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/34419372?tool=bestpractice.com
体重指数、气流阻塞、呼吸困难和运动(Body mass index, airflow Obstruction, Dyspnoea, Exercise,BODE)评分为 5-6 分伴其他因素,表明死亡风险升高:频繁出现急性加重、过去 24 个月内 BODE 评分增加 >1 分、CT 扫描显示肺动脉与主动脉直径比>1、FEV₁ 为 20%-25%预测值。
尽管给予了最大程度治疗,包括药物治疗、肺康复、氧疗和酌情进行夜间无创正压通气,但仍呈现临床恶化。
生活质量低劣,患者无法接受。
对于适合进行支气管镜或手术肺减容(lung volume reduction, LVR)的患者,可同时转诊进行肺移植评估和 LVR 评估。
预测慢性阻塞性肺疾病 (COPD) 患者生存期的 BODE 指数
肺移植可以改善生活质量和功能容量。[215]van Agteren JE, Carson KV, Tiong LU, et al. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev. 2016 Oct 14;(10):CD001001.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001001.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27739074?tool=bestpractice.com 但是,肺移植似乎不能产生生存获益。[221]Stavem K, Bjørtuft Ø, Borgan Ø, et al. Lung transplantation in patients with chronic obstructive pulmonary disease in a national cohort is without obvious survival benefit. J Heart Lung Transplant. 2006 Jan;25(1):75-84.http://www.ncbi.nlm.nih.gov/pubmed/16399534?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
使用缓和治疗来改善呼吸困难症状、提供营养支持、治疗焦虑和抑郁以及减轻疲劳,可能对接受最佳药物治疗后仍有这些问题的 COPD 患者有益。 对于极晚期 COPD 患者,应考虑临终关怀和安宁疗护。应该对患者和家属进行疾病进程的教育,并建议在疾病早期,尚未发展成急性呼吸衰竭前进行讨论。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[222]Janssen DJA, Bajwah S, Boon MH, et al. European Respiratory Society clinical practice guideline: palliative care for people with COPD or interstitial lung disease. Eur Respir J. 2023 Aug;62(2):2202014.https://erj.ersjournals.com/content/62/2/2202014http://www.ncbi.nlm.nih.gov/pubmed/37290789?tool=bestpractice.com 阿片类镇痛药、扇风、神经肌肉电刺激和胸壁振动疗法可缓解呼吸困难。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 一项研究显示低剂量阿片类镇痛药和苯二氮䓬类是安全的,与住院率和死亡率的增加无关。[223]Ekström MP, Bornefalk-Hermansson A, Abernethy AP, et al. Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study. BMJ. 2014 Jan 30;348:g445.https://www.bmj.com/content/348/bmj.g445.longhttp://www.ncbi.nlm.nih.gov/pubmed/24482539?tool=bestpractice.com 另一项研究发现,常规、低剂量、口服缓释吗啡 4 周,可改善 COPD 和难治性呼吸困难患者的疾病特异性健康状况。[224]Verberkt CA, van den Beuken-van Everdingen MHJ, Schols JMGA, et al. Effect of sustained-release morphine for refractory breathlessness in chronic obstructive pulmonary disease on health status: a randomized clinical trial. JAMA Intern Med. 2020 Oct 1;180(10):1306-14.https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2769373http://www.ncbi.nlm.nih.gov/pubmed/32804188?tool=bestpractice.com
一项 Cochrane 评价得出结论,没有证据支持或反对苯二氮卓类药物可缓解晚期癌症患者和 COPD 患者的呼吸困难。[225]Simon ST, Higginson IJ, Booth S, et al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016 Oct 20;(10):CD007354.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007354.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27764523?tool=bestpractice.com
针刺和指压亦可对晚期 COPD 患者的呼吸困难和生活质量加以改善。[226]von Trott P, Oei SL, Ramsenthaler C. Acupuncture for breathlessness in advanced diseases: a systematic review and meta-analysis. J Pain Symptom Manage. 2020 Feb;59(2):327-38.e3.http://www.ncbi.nlm.nih.gov/pubmed/31539602?tool=bestpractice.com
慢性阻塞性肺疾病全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)A 组患者的特点是症状少(改良版英国医学研究理事会 [Modified British Medical Research Council, mMRC]分级为 0-1 或 COPD 评估测试 [COPD Assessment Test, CAT]<10)且急性加重风险低(每年急性加重 0-1 次,无需住院);B 组患者的特点是症状较多(mMRC≥2 或 CAT≥10)而急性加重风险低(每年急性加重 0-1 次,无需住院);E 组患者的特点是急性加重风险高(每年急性加重≥2 次,或≥1 次需要住院)且有任何严重程度的症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
仅采用长效 β2 受体激动剂(long-acting beta-2 agonist, LABA)或长效毒蕈碱受体拮抗剂(long-acting muscarinic antagonist, LAMA)且出现持续性加重患者,应升级为 LABA/LAMA 联合治疗。
血嗜酸性粒细胞计数有助于识别哪些患者更有可能对吸入皮质类固醇(inhaled corticosteroid, ICS)有反应。[70]Bafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018 Feb;6(2):117-26.http://www.ncbi.nlm.nih.gov/pubmed/29331313?tool=bestpractice.com[71]Harries TH, Rowland V, Corrigan CJ, et al. Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. Respir Res. 2020 Jan 3;21(1):3.https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1268-7http://www.ncbi.nlm.nih.gov/pubmed/31900184?tool=bestpractice.com[72]Oshagbemi OA, Odiba JO, Daniel A, et al. Absolute blood eosinophil counts to guide inhaled corticosteroids therapy among patients with COPD: systematic review and meta-analysis. Curr Drug Targets. 2019;20(16):1670-9.http://www.ncbi.nlm.nih.gov/pubmed/31393244?tool=bestpractice.com 对于血嗜酸性粒细胞增多的轻至中度 COPD 患者,使用 ICS 还可减缓急性加重后肺功能减退的速度。[128]Kerkhof M, Voorham J, Dorinsky P, et al. Association between COPD exacerbations and lung function decline during maintenance therapy. Thorax. 2020 Sep;75(9):744-53.https://thorax.bmj.com/content/75/9/744http://www.ncbi.nlm.nih.gov/pubmed/32532852?tool=bestpractice.com 无论嗜酸性粒细胞计数如何,既往曾吸烟者都要比当前吸烟者对皮质类固醇的反应更强。[73]Pascoe S, Barnes N, Brusselle G, et al. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med. 2019 Sep;7(9):745-56.http://www.ncbi.nlm.nih.gov/pubmed/31281061?tool=bestpractice.com
如果接受长效支气管舒张剂单药治疗的患者外周血嗜酸性粒细胞计数≥300 个细胞/μL,则可以考虑升级至 LABA/LAMA/ICS 三联疗法。对于血嗜酸性粒细胞计数<100 个细胞/μL 的患者,ICS 不太可能有益。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
采用 LABA/LAMA 后持续加重,且血液嗜酸性粒细胞 ≥100 个细胞/μl 的患者,应升级治疗,给予 LABA/LAMA/ICS。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 多项研究认为,在中度至重度 COPD 加重率和住院率方面,LABA/LAMA/ICS 三联疗法优于单药治疗或者 LABA/LAMA 或 LABA/ICS 二联疗法。[74]Cazzola M, Rogliani P, Calzetta L, et al. Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis. Eur Respir J. 2018 Dec 13;52(6):1801586.https://erj.ersjournals.com/content/52/6/1801586http://www.ncbi.nlm.nih.gov/pubmed/30309975?tool=bestpractice.com[82]Singh D, Papi A, Corradi M, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting beta2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016 Sep 3;388(10048):963-73.http://www.ncbi.nlm.nih.gov/pubmed/27598678?tool=bestpractice.com[83]Vestbo J, Papi A, Corradi M, et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Lancet. 2017 May 13;389(10082):1919-29.http://www.ncbi.nlm.nih.gov/pubmed/28385353?tool=bestpractice.com[84]Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018 Mar 17;391(10125):1076-84.http://www.ncbi.nlm.nih.gov/pubmed/29429593?tool=bestpractice.com[85]Lipson DA, Barnacle H, Birk R, et al. FULFIL Trial: once-daily triple therapy for patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017 Aug 15;196(4):438-46.https://www.atsjournals.org/doi/full/10.1164/rccm.201703-0449OChttp://www.ncbi.nlm.nih.gov/pubmed/28375647?tool=bestpractice.com[86]Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018 May 3;378(18):1671-80.https://www.nejm.org/doi/10.1056/NEJMoa1713901http://www.ncbi.nlm.nih.gov/pubmed/29668352?tool=bestpractice.com[87]Rojas-Reyes MX, García Morales OM, Dennis RJ, et al. Combination inhaled steroid and long-acting beta₂-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2016 Jun 6;(6):CD008532.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008532.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27271056?tool=bestpractice.com[88]Lai CC, Chen CH, Lin CYH, et al. The effects of single inhaler triple therapy vs single inhaler dual therapy or separate triple therapy for the management of chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials. Int J Chron Obstruct Pulmon Dis. 2019 Jul 11;14:1539-48. [Erratum in: Int J Chron Obstruct Pulmon Dis. 2020 Jan 21;15:155-6.]https://www.dovepress.com/the-effects-of-single-inhaler-triple-therapy-vs-single-inhaler-dual-th-peer-reviewed-fulltext-article-COPDhttp://www.ncbi.nlm.nih.gov/pubmed/31371939?tool=bestpractice.com[89]Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020 Jul 2;383(1):35-48.http://www.ncbi.nlm.nih.gov/pubmed/32579807?tool=bestpractice.com 一项随机对照试验报告,在有急性加重风险的患者中,与使用乌美溴铵/维兰特罗的患者相比,使用糠酸氟替卡松/乌美溴铵/维兰特罗患者的全因死亡率降低。[129]Lipson DA, Crim C, Criner GJ, et al. Reduction in all-cause mortality with fluticasone furoate/umeclidinium/vilanterol in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1508-16.https://www.atsjournals.org/doi/10.1164/rccm.201911-2207OChttp://www.ncbi.nlm.nih.gov/pubmed/32162970?tool=bestpractice.com 另一项随机对照试验中,对于三联治疗组(布地奈德/格隆溴铵/福莫特罗)死亡率而言,具有相似发现,但仅在 ICS 剂量较高时。[89]Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020 Jul 2;383(1):35-48.http://www.ncbi.nlm.nih.gov/pubmed/32579807?tool=bestpractice.com[130]Martinez FJ, Rabe KF, Ferguson GT, et al. Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease. A randomized, double-blind, multicenter, parallel-group study. Am J Respir Crit Care Med. 2021 Mar 1;203(5):553-64.https://www.atsjournals.org/doi/10.1164/rccm.202006-2618OChttp://www.ncbi.nlm.nih.gov/pubmed/33252985?tool=bestpractice.com 这两项研究中,与 LABA/ICS 治疗相比的死亡率差异无统计学意义。[89]Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020 Jul 2;383(1):35-48.http://www.ncbi.nlm.nih.gov/pubmed/32579807?tool=bestpractice.com[129]Lipson DA, Crim C, Criner GJ, et al. Reduction in all-cause mortality with fluticasone furoate/umeclidinium/vilanterol in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1508-16.https://www.atsjournals.org/doi/10.1164/rccm.201911-2207OChttp://www.ncbi.nlm.nih.gov/pubmed/32162970?tool=bestpractice.com[130]Martinez FJ, Rabe KF, Ferguson GT, et al. Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease. A randomized, double-blind, multicenter, parallel-group study. Am J Respir Crit Care Med. 2021 Mar 1;203(5):553-64.https://www.atsjournals.org/doi/10.1164/rccm.202006-2618OChttp://www.ncbi.nlm.nih.gov/pubmed/33252985?tool=bestpractice.com 一项包含 3 项临床试验(关于有重度气道受限和急性加重史的 COPD 患者采取三联疗法)的事后分析发现, 与非 ICS 治疗相比,三联疗法降低死亡率的趋势并不明显。[131]Vestbo J, Fabbri L, Papi A, et al. Inhaled corticosteroid containing combinations and mortality in COPD. Eur Respir J. 2018 Dec 13;52(6):1801230.https://erj.ersjournals.com/content/52/6/1801230http://www.ncbi.nlm.nih.gov/pubmed/30209195?tool=bestpractice.com 对 200 多项研究进行的荟萃分析证实了这些结果:与二联治疗相比,三联治疗显著降低了死亡率,但与肺炎风险升高具有相关性。在肺功能或健康相关性生活质量方面,未观察到不同给药方案之间具有差异。[132]Axson EL, Lewis A, Potts J, et al. Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis. BMJ Open. 2020 Sep 29;10(9):e036455.https://bmjopen.bmj.com/content/10/9/e036455http://www.ncbi.nlm.nih.gov/pubmed/32994234?tool=bestpractice.com
美国胸科学会指南建议,对于接受 LABA/LAMA 二联疗法后,在过去一年中仍因一次或多次加重而需要口服皮质类固醇、抗生素或住院的患者,以及仍有呼吸困难症状或运动耐量减低的患者,应使用 LABA/LAMA/ICS 三联疗法。[90]Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 May 1;201(9):e56-69.https://www.atsjournals.org/doi/10.1164/rccm.202003-0625SThttp://www.ncbi.nlm.nih.gov/pubmed/32283960?tool=bestpractice.com 英国指南建议,对于接受 LABA/LAMA 二联疗法后在一年内仍出现需要住院治疗的加重,或者出现两次中度加重的患者,应使用 LABA/LAMA/ICS 三联疗法。[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115
GOLD 不推荐使用 LABA/ICS。但是,如果无哮喘特征的 COPD 患者已接受 LABA/ICS 治疗且控制良好,则可以继续使用。如果患者有进一步加重,则应加用 LAMA,升级为三联疗法。如果患者出现严重症状,可改用 LABA/LAMA。停用 ICS 后,血嗜酸性粒细胞≥300 个细胞/μL 的患者出现急性加重的风险最高。[75]Chapman KR, Hurst JR, Frent SM, et al. Long-term triple therapy de-escalation to indacaterol/glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): a randomized, double-blind, triple-dummy clinical trial. Am J Respir Crit Care Med. 2018 Aug 1;198(3):329-39.https://www.atsjournals.org/doi/10.1164/rccm.201803-0405OChttp://www.ncbi.nlm.nih.gov/pubmed/29779416?tool=bestpractice.com
第一选择
LABA/LAMA 二联疗法
吸入性芜地溴铵 (umeclidinium)/维兰特罗 (vilanterol) : (62.5/25 μg/定量吸入器)1 喷,每日一次
或
LABA/LAMA 二联疗法
格隆溴铵/福莫特罗 : (7.2 μg/5 μg 定量吸入器)每次 2 揿,每日两次
或
LABA/LAMA 二联疗法
吸入性噻托溴铵/奥达特罗 : (2.5/2.5 μg/定量吸入器)2 喷,每日一次
或
LABA/LAMA 二联疗法
吸入性阿地溴铵/福莫特罗 : (每剂吸入剂 400/12 μg)1 喷,每日两次
或
LABA/LAMA/ICS 三联疗法
吸入用糠酸氟替卡松/芜地溴铵 (umeclidinium) /维兰特罗 (vilanterol) : (92/55/22 μg/定量吸入器)1 喷,每日一次
更多 吸入用糠酸氟替卡松/芜地溴铵 (umeclidinium) /维兰特罗 (vilanterol)每一次吸入可提供 92 μg 糠酸氟替卡松、65 μg 芜地溴铵化合物(相当于 55 μg 芜地溴铵 [umeclidinium])和 22 μg 维兰特罗(三氟甲磺酸盐形式)的递送剂量。
或
LABA/LAMA/ICS 三联疗法
吸入性糠酸氟替卡松/维兰特罗 : (100/25 μg/定量吸入器)1 喷,每日 1 次
或
吸入性丙酸氟替卡松/沙美特罗 : (250/50 μg/定量吸入器)1 喷,每日 2 次
或
吸入性布地奈德/福莫特罗 : (160/4.5 μg/定量吸入器)2 喷,每日 2 次
或
吸入性莫米松/福莫特罗 : (100/5 μg/定量吸入器;200/5 μg/定量吸入器)2 喷,每日 2 次
-- 和 --
吸入性噻托溴铵 : (18 μg/胶囊吸入器)18 μg(1 粒胶囊),每日一次;(2.5 μg/定量吸入器)5 μg(2 喷),每日一次
或
吸入性芜地溴铵 : (62.5 μg/定量吸入器)62.5 μg(1 喷),每日一次
或
吸入性阿地溴铵 : (400 μg/定量吸入器)400 μg(1 喷),每日 2 次
或
吸入性格隆溴铵 : (55 μg/胶囊吸入器)55 μg(1 粒胶囊),每日一次
更多 吸入性格隆溴铵每粒胶囊递送 55 µg 格隆溴铵化合物(相当于 44 µg 格隆溴铵 [glycopyrronium])。
针对特定患者群中所有患者的治疗建议
对于所有诊断为 COPD 的患者,均应开处短效支气管舒张剂,以立即缓解症状。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
短效 β-2 受体激动剂(short-acting beta-2 agonist, SABA)和短效毒蕈碱受体拮抗剂(short-acting muscarinic antagonist, SAMA)能够改善肺功能、减轻呼吸困难和提升生活质量。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com 异丙托溴铵(一种 SAMA)在改善健康相关生活质量方面的益处略高于 SABA。[91]Appleton S, Jones T, Poole P, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001387.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001387.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16625543?tool=bestpractice.com 如果开处了 LAMA,则应停用 SAMA。SABA 包括沙丁胺醇。
一般不推荐常规使用短效支气管舒张剂。短效支气管舒张剂无效可能意味着急性加重。
第一选择
吸入性沙丁胺醇 : 需要时(100 μg/定量吸入器)100-200 μg(1-2 喷),每 4-6 小时一次
或
吸入性异丙托溴铵 : 需要时(20 μg/定量吸入器)40 μg(2 喷),每日最多 4 次
针对特定患者群中所有患者的治疗建议
应鼓励所有患者戒烟,并接受指导,避免职业或环境烟草烟雾暴露或其他刺激物暴露。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115 戒烟可显著降低 COPD 的进展速度和恶性肿瘤风险。请参阅“戒烟(治疗流程)” 。
根据本地指南,患者应接种流感病毒疫苗、肺炎链球菌疫苗、百日咳疫苗、水痘带状疱疹病毒疫苗、呼吸道合胞病毒疫苗和 2019 冠状病毒病(coronavirus disease 2019, COVID-19)疫苗。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html 接种流感疫苗可减少 COPD 急性加重次数。[182]Walters JA, Tang JN, Poole P, et al. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Jan 24;(1):CD001390.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001390.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28116747?tool=bestpractice.com[183]Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018 Jun 26;(6):CD002733.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002733.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29943802?tool=bestpractice.com [ ]What are the effects of influenza vaccine in people with chronic obstructive pulmonary disease (COPD)?https://cochranelibrary.com/cca/doi/10.1002/cca.2235/full展示答案 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)还建议在青春期未接种破伤风/白喉/百日咳疫苗的 COPD 患者补种。[181]Centers for Disease Control and Prevention. Recommended vaccines for adults: lung disease (including asthma and COPD). Sep 2023 [internet publication].https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/lung-disease.html
使用吸入治疗的患者应接受吸入器装置使用方法培训。多数患者在使用吸入器时至少犯一次错误,并且错误使用吸入器与疾病控制能力下降有关。[155]Cho-Reyes S, Celli BR, Dembek C, et al. Inhalation technique errors with metered-dose inhalers among patients with obstructive lung diseases: a systematic review and meta-analysis of US Studies. Chronic Obstr Pulm Dis. 2019 Jul 24;6(3):267-80.https://journal.copdfoundation.org/jcopdf/id/1241/Inhalation-Technique-Errors-with-Metered-Dose-Inhalers-Among-Patients-with-Obstructive-Lung-Diseases-A-Systematic-Review-and-Meta-Analysis-of-US-Studieshttp://www.ncbi.nlm.nih.gov/pubmed/31342732?tool=bestpractice.com[156]Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011 Jun;105(6):930-8.https://www.resmedjournal.com/article/S0954-6111(11)00009-6/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21367593?tool=bestpractice.com 临床医生演示吸入器用法、选用合适的装置以及在后续复诊时检查使用方法均可改善吸入器使用技术。[158]Price D, Keininger DL, Viswanad B, et al. Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey. Int J Chron Obstruct Pulmon Dis. 2018 Feb 26;13:695-702. [Erratum in: Int J Chron Obstruct Pulmon Dis. 2018 Jul 25;13:2253-4.]https://www.dovepress.com/factors-associated-with-appropriate-inhaler-use-in-patients-with-copd--peer-reviewed-fulltext-article-COPDhttp://www.ncbi.nlm.nih.gov/pubmed/29520137?tool=bestpractice.com
对所有患者进行关于病程以及加重或失代偿症状的宣教。他们对疾病、治疗和预后的预期应符合实际。研究显示,目前没有药物能改善长期减退的肺功能,药物治疗的主要目标是控制症状和预防并发症。自我管理教育应包括提供书面行动计划。推荐所有 COPD 患者进行体力活动。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
针对特定患者群中部分患者治疗的附加建议
肺康复项目包括有氧运动、力量训练和宣教,应在病程早期开始。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[189]Rochester CL, Alison JA, Carlin B, et al. Pulmonary rehabilitation for adults with chronic respiratory disease: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2023 Aug 15;208(4):e7-26.https://www.atsjournals.org/doi/10.1164/rccm.202306-1066SThttp://www.ncbi.nlm.nih.gov/pubmed/37581410?tool=bestpractice.com[190]Man W, Chaplin E, Daynes E, et al. British Thoracic Society Clinical Statement on pulmonary rehabilitation. Thorax. 2023 Oct;78(suppl 5):s2-15.https://thorax.bmj.com/content/78/Suppl_5/s2http://www.ncbi.nlm.nih.gov/pubmed/37770084?tool=bestpractice.com GOLD 指南推荐 B 组和 E 组患者参与肺康复项目。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
肺康复训练可缓解呼吸困难和疲劳、改善情绪功能,并能在较大程度增强控制感,将其改善到具有临床意义的程度。[191]McCarthy B, Casey D, Devane D, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015 Feb 23;(2):CD003793.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003793.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25705944?tool=bestpractice.com
美国一项大型队列研究发现,COPD 急性加重后出院 90 日内开始肺康复,与 1 年死亡率降低和 1 年再住院率降低具有显著相关性。[194]Lindenauer PK, Stefan MS, Pekow PS, et al. Association between initiation of pulmonary rehabilitation after hospitalization for COPD and 1-year survival among medicare beneficiaries. JAMA. 2020 May 12;323(18):1813-23.https://jamanetwork.com/journals/jama/fullarticle/2765730http://www.ncbi.nlm.nih.gov/pubmed/32396181?tool=bestpractice.com[195]Stefan MS, Pekow PS, Priya A, et al. Association between initiation of pulmonary rehabilitation and rehospitalizations in patients hospitalized with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2021 Nov 1;204(9):1015-23.https://www.atsjournals.org/doi/10.1164/rccm.202012-4389OChttp://www.ncbi.nlm.nih.gov/pubmed/34283694?tool=bestpractice.com 然而,出院前开始进行肺康复可能导致 12 个月死亡率升高,因此不受推荐。[196]Greening NJ, Williams JE, Hussain SF, et al. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial. BMJ. 2014 Jul 8;349:g4315.https://www.bmj.com/content/349/bmj.g4315http://www.ncbi.nlm.nih.gov/pubmed/25004917?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
GOLD 指南的建议指出,如果患者符合以下条件且病情稳定,则应进行长期氧疗:PaO₂ ≤7.3 kPa(55 mmHg)或 SaO₂ ≤88%(无论是否在 3 周内确认出现了两次高碳酸血症);或者如果有证据表明患者有肺动脉高压、提示充血性心力衰竭的外周水肿或红细胞增多症(血细胞比容 >55%),PaO₂ 介于 7.3 kPa(55 mmHg)至 8.0 kPa(60 mmHg)或 SaO₂ 为 88%。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
美国胸科学会(American Thoracic Society, ATS)指南建议,对于静息状态下呼吸室内空气时有重度慢性低氧血症的 COPD 成人,建议给予长期氧疗,每日至少供氧 15 小时。ATS 将重度低氧血症定义为(以下两者任一):PaO₂ ≤7.3 kPa(55 mmHg)或脉搏血氧测定氧饱和度(SpO₂)≤88%;或 PaO₂ 7.5-7.9 kPa(56-59 mmHg)或 SpO₂ 89% 加以下任一:水肿、血细胞比容≥55%,或 ECG 呈现肺型 P 波。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com
对于接受家庭氧疗的患者,ATS 建议患者及其照护者应接受所有氧气设备使用和维护的指导和培训,以及接受用氧安全教育,包括戒烟、防火和绊倒风险。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com
辅助供氧应滴定至实现 SaO₂ ≥90%。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 60-90 天后应对患者进行再评估,确定给氧是否仍有指征,并仍具有治疗作用。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 在 COPD 多个不同的治疗方法中,只有两个因素可以改善存活情况,即戒烟和氧疗。
氧疗有助于通过降低肺动脉压力而最大程度减低肺动脉高压,改善运动耐量,以及提高生活质量。已经证明它能改善生存情况。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[61]Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.https://www.acpjournals.org/doi/10.7326/0003-4819-155-3-201108020-00008http://www.ncbi.nlm.nih.gov/pubmed/21810710?tool=bestpractice.com
ATS 建议对伴 COPD 的重度劳力性室内空气低氧血症成人,进行动态给氧(活动或日常生活时给氧)。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com 但 ATS 建议,对于有中度慢性休息室空气低氧血症(SpO₂ 为 89%-93%)的 COPD 成人,勿给予长期氧疗。[204]Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-41. [Erratum in: Am J Respir Crit Care Med. 2021 Apr 15;203(8):1045-6.]https://www.atsjournals.org/doi/10.1164/rccm.202009-3608SThttp://www.ncbi.nlm.nih.gov/pubmed/33185464?tool=bestpractice.com
罹患 COPD 和阻塞性睡眠呼吸暂停的患者,采用持续气道正压通气(continuous positive airway pressure, CPAP)进行通气支持,可改善生存率,并减少住院率。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[67]Marin JM, Soriano JB, Carrizo SJ, et al. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010 Aug 1;182(3):325-31.https://www.atsjournals.org/doi/10.1164/rccm.200912-1869OChttp://www.ncbi.nlm.nih.gov/pubmed/20378728?tool=bestpractice.com 无创通气偶用于病情非常严重但稳定的 COPD 患者,但起始治疗的最佳时机,以及选择适合患者的最佳标准尚未明确。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[208]Wilson ME, Dobler CC, Morrow AS, et al. Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2020 Feb 4;323(5):455-65.https://jamanetwork.com/journals/jama/fullarticle/2760390http://www.ncbi.nlm.nih.gov/pubmed/32016309?tool=bestpractice.com[209]Raveling T, Vonk J, Struik FM, et al. Chronic non-invasive ventilation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2021 Aug 9;(8):CD002878.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002878.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/34368950?tool=bestpractice.com
ATS 指南建议,对于稳定的有慢性高碳酸血症的 COPD 患者,在常规治疗基础上增加夜间 NIV。[211]Macrea M, Oczkowski S, Rochwerg B, et al. Long-term noninvasive ventilation in chronic stable hypercapnic chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice fuideline. Am J Respir Crit Care Med. 2020 Aug 15;202(4):e74-87.https://www.atsjournals.org/doi/10.1164/rccm.202006-2382SThttp://www.ncbi.nlm.nih.gov/pubmed/32795139?tool=bestpractice.com 欧洲呼吸学会和加拿大胸科协会已发布相似指南。[212]Ergan B, Oczkowski S, Rochwerg B, et al. European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD. Eur Respir J. 2019 Sep 28;54(3):1901003.https://erj.ersjournals.com/content/54/3/1901003http://www.ncbi.nlm.nih.gov/pubmed/31467119?tool=bestpractice.com[213]Kaminska M, Rimmer KP, McKim DA, et al. Long-term non-invasive ventilation in patients with chronic obstructive pulmonary disease (COPD): 2021 Canadian Thoracic Society clinical practice guideline update. Can J Respir Crit Care Sleep Med. 2021 May 7;5(3):160-83.https://www.tandfonline.com/doi/full/10.1080/24745332.2021.1911218
针对特定患者群中部分患者治疗的附加建议
对于使用 LABA/LAMA 后持续加重且血嗜酸性粒细胞 <100 个细胞/μL 的患者,以及使用 LABA/LAMA/ICS 后持续加重的患者,可能开处 roflumilast,这是一种口服磷酸二酯酶-4 抑制剂。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
对于 FEV₁<50% 预测值且有慢性支气管炎的患者,应考虑使用罗氟司特,尤其是这些患者在过去一年至少有一次因加重而住院治疗时。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
第一选择
罗氟司特 : 500 μg,口服,每日 1 次
针对特定患者群中部分患者治疗的附加建议
对于使用 LABA/LAMA 二联疗法后持续加重且血嗜酸性粒细胞 <100 个细胞/μL 的患者,以及使用 LABA/LAMA/ICS 三联疗法后持续加重的患者,可能开处阿奇霉素。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
阿奇霉素会增加大环内酯类抗生素耐药性微生物的定植风险,因此不应对有听力障碍、静息心动过速或明显 QTc 延长风险的患者开处此药。[141]Albert RK, Connett J, Bailey WC, et al; COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011 Aug 25;365(8):689-98.https://www.nejm.org/doi/full/10.1056/NEJMoa1104623http://www.ncbi.nlm.nih.gov/pubmed/21864166?tool=bestpractice.com 对于已接受适当治疗但仍持续加重的既往曾吸烟患者,应考虑优先使用阿奇霉素,但不仅限于此类患者)。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
在开始预防性使用抗生素之前,应检查基线 ECG 和肝功能,采集痰液标本进行培养和药敏性试验(包括结核病检查),应优化患者的排痰方法,并通过 CT 扫描排除支气管扩张。[2]National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Jul 2019 [internet publication].https://www.nice.org.uk/guidance/ng115[142]Smith D, Du Rand I, Addy CL, et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease. Thorax. 2020 May;75(5):370-404.https://thorax.bmj.com/content/75/5/370http://www.ncbi.nlm.nih.gov/pubmed/32303621?tool=bestpractice.com 治疗 1 个月后应再次进行 ECG 和肝脏检查。应在 6 个月和 12 个月时评估预防性抗生素治疗,以确定是否可降低急性加重发生率。[142]Smith D, Du Rand I, Addy CL, et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease. Thorax. 2020 May;75(5):370-404.https://thorax.bmj.com/content/75/5/370http://www.ncbi.nlm.nih.gov/pubmed/32303621?tool=bestpractice.com 如果抗生素治疗无效,应停止使用。
第一选择
阿奇霉素 : 250 mg,口服,每日一次;或 500 mg,口服,每周 3 次
针对特定患者群中部分患者治疗的附加建议
存在 COPD 慢性支气管炎表型的患者经常频繁出现浓痰。化痰药物可使急性加重频率和每月出现失能的天数略微减少,但不能改善肺功能或生活质量。[186]Poole P, Sathananthan K, Fortescue R. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2019 May 20;(5):CD001287.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001287.pub6/fullhttp://www.ncbi.nlm.nih.gov/pubmed/31107966?tool=bestpractice.com 一项 meta 分析对厄多司坦、羧甲司坦和乙酰半胱氨酸进行了比较,得出的结论为,厄多司坦的安全性和有效性最好。厄多司坦降低了因急性加重而住院的风险,它和乙酰半胱氨酸都缩短了急性加重的持续时间。[187]Rogliani P, Matera MG, Page C, et al. Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir Res. 2019 May 27;20(1):104.https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1078-yhttp://www.ncbi.nlm.nih.gov/pubmed/31133026?tool=bestpractice.com 因此,厄多司坦对于有条件的国家是推荐选择。另一项荟萃分析发现,与安慰剂相比,乙酰半胱氨酸可显著降低急性加重发病率,而不良反应风险未见升高。作者得出结论,3 个月低剂量治疗具有疗效。[188]Wei J, Pang CS, Han J, et al. Effect of orally administered N-acetylcysteine on chronic bronchitis: a meta-analysis. Adv Ther. 2019 Dec;36(12):3356-67.http://www.ncbi.nlm.nih.gov/pubmed/31598901?tool=bestpractice.com 使用化痰药物(例如羧甲司坦和乙酰半胱氨酸)进行治疗,可减少未接受 ICS 的患者发生急性加重,并适度改善健康状况。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 但是,无论患者是否正在使用吸入性皮质类固醇,厄多司坦对于轻度加重具有显著效果。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
第一选择
厄多司坦 : 咨询专科医生,获得剂量指导
或
乙酰半胱氨酸 : 咨询专科医生,获得剂量指导
或
羧甲司坦 : 咨询专科医生,获得剂量指导
针对特定患者群中部分患者治疗的附加建议
茶碱(一种甲基黄嘌呤剂)的效价有限、治疗窗窄、风险高,并且与其他药物有频繁的相互作用,因此不常使用。茶碱对中至重度 COPD 患者的肺功能有轻微作用。[144]Ram FSF, Jones P, Jardim J, et al. Oral theophylline for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2002;(4):CD003902.http://www.ncbi.nlm.nih.gov/pubmed/12519617?tool=bestpractice.com 一项大型随机对照试验发现,单纯口服茶碱,或联合使用泼尼松龙,对于重度 COPD 急性加重无治疗效果。[145]Jenkins CR, Wen FQ, Martin A, et al; TASCS study investigators. The effect of low-dose corticosteroids and theophylline on the risk of acute exacerbations of COPD: the TASCS randomised controlled trial. Eur Respir J. 2021 Jun 10;57(6):2003338.https://erj.ersjournals.com/content/57/6/2003338http://www.ncbi.nlm.nih.gov/pubmed/33334939?tool=bestpractice.com 如果所有吸入治疗选择均无效,专家可能开具茶碱。其毒性具有剂量依赖性。除非没有或负担不起其他长效支气管舒张剂治疗,否则不建议使用茶碱。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/
第一选择
茶碱 : 咨询专科医生,获得剂量指导
针对特定患者群中部分患者治疗的附加建议
手术干预是 COPD 治疗的最后一步,包括肺大疱切除术、肺减容术和肺移植。[214]van Agteren JE, Hnin K, Grosser D, et al. Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Feb 23;(2):CD012158.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012158.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28230230?tool=bestpractice.com[215]van Agteren JE, Carson KV, Tiong LU, et al. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev. 2016 Oct 14;(10):CD001001.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001001.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27739074?tool=bestpractice.com [ ]How does bronchoscopic lung volume reduction compare with medical therapy in people with chronic obstructive pulmonary disease?https://cochranelibrary.com/cca/doi/10.1002/cca.1680/full展示答案 这些干预措施是用于改善肺活量、运动依从性和生存质量。[215]van Agteren JE, Carson KV, Tiong LU, et al. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev. 2016 Oct 14;(10):CD001001.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001001.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27739074?tool=bestpractice.com 气流受限非常严重的患者需接受肺减容术,特别是局限性上叶病变且运动耐量低于正常的患者。[214]van Agteren JE, Hnin K, Grosser D, et al. Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Feb 23;(2):CD012158.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012158.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28230230?tool=bestpractice.com [ ]How does bronchoscopic lung volume reduction compare with medical therapy in people with chronic obstructive pulmonary disease?https://cochranelibrary.com/cca/doi/10.1002/cca.1680/full展示答案 一项荟萃分析发现,与标准治疗相比,接受肺减容术的患者早期死亡风险增加;然而,观察到总体死亡率差异无统计学意义。[216]van Geffen WH, Slebos DJ, Herth FJ, et al. Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis. Lancet Respir Med. 2019 Apr;7(4):313-24.http://www.ncbi.nlm.nih.gov/pubmed/30744937?tool=bestpractice.com 对于存在呼吸困难且 CT 检查发现巨型肺大疱占据胸腔容积至少 30% 的 COPD 患者,可采取肺大疱切除术。严重的功能状态不良和 FEV₁ 重度下降 (<500 mL) 使得这些方案不太有利。对于经适当选择的 COPD 患者,支气管内活瓣置入术可带来有临床意义的改善。[216]van Geffen WH, Slebos DJ, Herth FJ, et al. Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis. Lancet Respir Med. 2019 Apr;7(4):313-24.http://www.ncbi.nlm.nih.gov/pubmed/30744937?tool=bestpractice.com[217]Klooster K, Slebos DJ, Zoumot Z, et al. Endobronchial valves for emphysema: an individual patient-level reanalysis of randomised controlled trials. BMJ Open Respir Res. 2017 Nov 2;4(1):e000214.https://bmjopenrespres.bmj.com/content/4/1/e000214http://www.ncbi.nlm.nih.gov/pubmed/29441206?tool=bestpractice.com[218]Labarca G, Uribe JP, Pacheco C, et al. Bronchoscopic lung volume reduction with endobronchial zephyr valves for severe emphysema: a systematic review and meta-analysis. Respiration. 2019 May 22;98(3):268-78.http://www.ncbi.nlm.nih.gov/pubmed/31117102?tool=bestpractice.com 该手术可能对主要由终末细支气管远端气腔过度充气和气体滞留所致呼吸困难的患者(表现为肺气肿伴残气量显著增加)最有益。禁忌证包括活动性肺感染和不完全肺叶裂(<80%)。[219]Abia-Trujillo D, Johnson MM, Patel NM, et al. Bronchoscopic lung volume reduction: a new hope for patients with severe emphysema and air trapping. Mayo Clin Proc. 2021 Feb;96(2):464-72.http://www.ncbi.nlm.nih.gov/pubmed/32829903?tool=bestpractice.com 支气管内活瓣置入术相关性最常见不良事件为气胸和急性加重。[216]van Geffen WH, Slebos DJ, Herth FJ, et al. Surgical and endoscopic interventions that reduce lung volume for emphysema: a systemic review and meta-analysis. Lancet Respir Med. 2019 Apr;7(4):313-24.http://www.ncbi.nlm.nih.gov/pubmed/30744937?tool=bestpractice.com
肺移植转诊标准包括:[220]Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: an update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021 Nov;40(11):1349-79.https://www.jhltonline.org/article/S1053-2498(21)02407-4/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/34419372?tool=bestpractice.com
体重指数、气流阻塞、呼吸困难和运动(Body mass index, airflow Obstruction, Dyspnoea, Exercise,BODE)评分为 5-6 分伴其他因素,表明死亡风险升高:频繁出现急性加重、过去 24 个月内 BODE 评分增加 >1 分、CT 扫描显示肺动脉与主动脉直径比>1、FEV₁ 为 20%-25%预测值。
尽管给予了最大程度治疗,包括药物治疗、肺康复、氧疗和酌情进行夜间无创正压通气,但仍呈现临床恶化。
生活质量低劣,患者无法接受。
对于适合进行支气管镜或手术肺减容(lung volume reduction, LVR)的患者,可同时转诊进行肺移植评估和 LVR 评估。
预测慢性阻塞性肺疾病 (COPD) 患者生存期的 BODE 指数
肺移植可以改善生活质量和功能容量。[215]van Agteren JE, Carson KV, Tiong LU, et al. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev. 2016 Oct 14;(10):CD001001.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001001.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27739074?tool=bestpractice.com 但是,肺移植似乎不能产生生存获益。[221]Stavem K, Bjørtuft Ø, Borgan Ø, et al. Lung transplantation in patients with chronic obstructive pulmonary disease in a national cohort is without obvious survival benefit. J Heart Lung Transplant. 2006 Jan;25(1):75-84.http://www.ncbi.nlm.nih.gov/pubmed/16399534?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
使用缓和治疗来改善呼吸困难症状、提供营养支持、治疗焦虑和抑郁以及减轻疲劳,可能对接受最佳药物治疗后仍有这些问题的 COPD 患者有益。 对于极晚期 COPD 患者,应考虑临终关怀和安宁疗护。应该对患者和家属进行疾病进程的教育,并建议在疾病早期,尚未发展成急性呼吸衰竭前进行讨论。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/[222]Janssen DJA, Bajwah S, Boon MH, et al. European Respiratory Society clinical practice guideline: palliative care for people with COPD or interstitial lung disease. Eur Respir J. 2023 Aug;62(2):2202014.https://erj.ersjournals.com/content/62/2/2202014http://www.ncbi.nlm.nih.gov/pubmed/37290789?tool=bestpractice.com 阿片类镇痛药、扇风、神经肌肉电刺激和胸壁振动疗法可缓解呼吸困难。[1]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report. 2024 [internet publication].https://goldcopd.org/2024-gold-report/ 一项研究显示低剂量阿片类镇痛药和苯二氮䓬类是安全的,与住院率和死亡率的增加无关。[223]Ekström MP, Bornefalk-Hermansson A, Abernethy AP, et al. Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study. BMJ. 2014 Jan 30;348:g445.https://www.bmj.com/content/348/bmj.g445.longhttp://www.ncbi.nlm.nih.gov/pubmed/24482539?tool=bestpractice.com 另一项研究发现,常规、低剂量、口服缓释吗啡 4 周,可改善 COPD 和难治性呼吸困难患者的疾病特异性健康状况。[224]Verberkt CA, van den Beuken-van Everdingen MHJ, Schols JMGA, et al. Effect of sustained-release morphine for refractory breathlessness in chronic obstructive pulmonary disease on health status: a randomized clinical trial. JAMA Intern Med. 2020 Oct 1;180(10):1306-14.https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2769373http://www.ncbi.nlm.nih.gov/pubmed/32804188?tool=bestpractice.com
一项 Cochrane 评价得出结论,没有证据支持或反对苯二氮卓类药物可缓解晚期癌症患者和 COPD 患者的呼吸困难。[225]Simon ST, Higginson IJ, Booth S, et al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016 Oct 20;(10):CD007354.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007354.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27764523?tool=bestpractice.com
针刺和指压亦可对晚期 COPD 患者的呼吸困难和生活质量加以改善。[226]von Trott P, Oei SL, Ramsenthaler C. Acupuncture for breathlessness in advanced diseases: a systematic review and meta-analysis. J Pain Symptom Manage. 2020 Feb;59(2):327-38.e3.http://www.ncbi.nlm.nih.gov/pubmed/31539602?tool=bestpractice.com
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