病史
COPD 起病隐匿,通常见于老年患者。典型病史有咳痰、喘息、呼吸短促,特别是运动时。其他症状包括频繁发生支气管炎、运动耐量降低、夜间因呼吸困难醒来、踝部水肿和疲劳。[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
患者可能诉睡眠中断导致的疲劳,睡眠中断是由于不停的夜间咳嗽以及持续性缺氧和高碳酸血症。应当确定患者的吸烟史、职业暴露、合并症以及肺病家族史。还应询问既往加重病史和入院史。
COPD 患者在感染性急性加重时也可表现出急性、重度呼吸急促、发热和胸痛。请参阅“慢性阻塞性肺疾病急性加重” 。
体格检查
体格检查不能诊断 COPD,但仍是患者诊疗的重要组成部分。[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/ 查体可见呼吸急促、呼吸窘迫、辅助呼吸肌参与和肋间隙回缩。视诊常见桶状胸。叩诊可见过清音,听诊可闻及呼吸音低和气流运动减低。可能出现哮鸣、粗湿罗音、杵状指和发绀以及右心衰竭体征(颈静脉扩张、P2 音亮、肝肿大、肝颈静脉反流征和下肢水肿)。患者偶尔可能出现扑翼样震颤,也就是高碳酸血症导致双臂伸展时失去姿势控制能力(通常称为扑动)。这是由于肺实质气体交换障碍所致,运动时加重,提示呼吸衰竭。
初始检查
肺量测定是 COPD 诊断所必需,亦可用于监测疾病进展。[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[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 这是测量气流受限最为客观且可重复性最好的方法。应在足量给予至少一种短效吸入性支气管舒张剂后进行肺量测定,以最大程度减小可变性。[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/ COPD 患者的肺量测定可见特征性改变,表现为 FEV₁ 和 FEV₁ /FVC 比值降低。慢性阻塞性肺疾病全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)定义气流受限的标准是使用支气管舒张剂后 FEV₁/FVC<0.7。[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 FVC 难以测定,可以采用第 6 秒用力呼气容积 (forced expiratory volume at 6 seconds, FEV6)。[62]Jing JY, Huang TC, Cui W, et al. Should FEV1/FEV6 replace FEV1/FVC ratio to detect airway obstruction? A metaanalysis. Chest. 2009 Apr;135(4):991-8.http://www.ncbi.nlm.nih.gov/pubmed/19349398?tool=bestpractice.com 肺量测定还可指示气流阻塞的严重程度。在 FEV₁/FVC 比值 <0.7 的患者中:[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/
FEV₁≥80% 预测值提示轻度 COPD(GOLD 1)
FEV₁<80% 且≥50% 预测值提示中度 COPD(GOLD 2)
FEV₁<50% 且≥30% 预测值提示重度 COPD(GOLD 3)
FEV₁<30% 预测值提示极重度 COPD(GOLD 4)。
虽然胸部 X 线检查(chest x-ray, CXR)很少有诊断意义,但应行此检查以排除其他诊断,并评估是否存在重大合并症。[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/
对于有呼吸衰竭或右心衰竭征象的所有患者,应使用脉搏血氧仪筛查有无缺氧。如果外周动脉血氧饱和度≤92%,则应进行动脉血气分析。[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/
除了气流受限之外,GOLD 指南认为急性加重对COPD自然病程有重要影响,并强调评估急性加重及共病症状和危险因素的重要性。[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/
推荐采用改良版英国医学研究委员会 (Modified British Medical Research Council, mMRC) 问卷或慢性阻塞性肺疾病评估测试 (COPD Assessment Test, CAT) 评估症状。可在 GOLD 指南中找到。[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 提出警告,勿将 mMRC 呼吸困难量表单独用于患者评估,因为 COPD 症状不仅仅是呼吸困难。由于该原因,倾向于使用 CAT。然而,GOLD 承认,mMRC 量表的使用非常广泛,因此仍将 mMRC 评级 ≥2 的阈值包括在对“呼吸更困难”患者进行定义的评估标准中(区别于“呼吸困难程度较低”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/
频繁急性加重(每年发作两次或以上)的最佳预测因子为既往有急性加重治疗史。[63]Hurst JR, Vestbo J, Anzueto A, et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16;363(12):1128-38.https://www.nejm.org/doi/full/10.1056/NEJMoa0909883http://www.ncbi.nlm.nih.gov/pubmed/20843247?tool=bestpractice.com 此外,气流受限 <50%(重度或极重度 COPD)的患者发生急性加重风险显著升高。[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 指南根据患者的症状严重程度和急性加重既往史,采用“ABE”综合评估方法。采用 mMRC 或 CAT 量表评估症状。将急性加重评估与症状评估分开,以突显其临床意义。[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/
A 组:低风险(每年急性加重 0-1 次,无需住院治疗)且症状较少(mMRC 0-1 或 CAT<10)
B 组:低风险(每年急性加重 0-1 次,无需住院治疗)且症状较多(mMRC≥2 或 CAT≥10)
E 组:高风险(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。
英国指南建议对所有新确诊患者进行全血细胞计数(full blood count, FBC),以筛查贫血或红细胞增多症。[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
其他检查
在专科肺功能检查实验室进行的详细肺功能试验可以检测流速-容量环和吸气量。这些指标不需要常规检测,但在诊断不明确或进行术前评估时有帮助。肺一氧化碳弥散量(diffusing capacity of the lung for carbon monoxide, DLCO)既往只能在专科实验室进行检查;然而,现在有了便携式系统,可以随时随地进行检查。如果 COPD 患者出现与其气流阻塞程度不成比例的呼吸困难,则 GOLD 国际指南推荐进行 DLCO 检查。COPD 患者 DLCO 值过低(<60% 预测值)与运动能力下降、健康状况恶化和死亡风险升高具有相关性。[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/ 如果存在诊断不确定性,可使用连续峰流速测定鉴别 COPD 与哮喘。[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
如果较年轻患者(<45 岁)有家族史或有快速进展的疾病,且影像学检查显示下叶改变,则应测定 α-1 抗胰蛋白酶水平。[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/ 所有诊断为 COPD 的患者都应接受一次筛查,尤其是在 α-1 抗胰蛋白酶缺乏症高发地区。[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/[64]World Health Organization. Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ. 1997;75(5):397-415.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2487011/pdf/bullwho00396-0013.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/9447774?tool=bestpractice.com[65]Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α(1)-antitrypsin deficiency. Eur Respir J. 2017 Nov;50(5).https://www.doi.org/10.1183/13993003.00610-2017http://www.ncbi.nlm.nih.gov/pubmed/29191952?tool=bestpractice.com 这可能有助于进行家系筛查和提供咨询。[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/
计算机体层成像(computed tomography, CT)扫描可显示解剖学变化,并且在 COPD 患者中的应用日益增加。GOLD 指南建议,对于持续加重患者、症状与肺功能检测所示疾病严重程度不符的患者、FEV₁<45% 预测值合并显著过度充气的患者、符合肺癌筛查标准的患者,考虑进行 CT 扫描。[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/ 美国预防服务工作组(US Preventive Services Task Force, USPSTF)建议每年进行一次低剂量 CT 扫描(low-dose CT scan, LDCT),对因吸烟导致的 COPD 患者进行肺癌筛查。[66]Krist AH, Davidson KW, Mangione CM, et al; US Preventive Services Task Force. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021 Mar 9;325(10):962-70.https://jamanetwork.com/journals/jama/fullarticle/2777244http://www.ncbi.nlm.nih.gov/pubmed/33687470?tool=bestpractice.com
阻塞性睡眠呼吸暂停与 COPD 患者的死亡和住院风险增加相关,应考虑进行睡眠检查。[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
对于呼吸困难程度不成比例的患者,运动试验会有用。[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/ 可以采用脚踏车或活动平板测力计完成,或进行简单的计时步行试验(例如,6 分钟或持续时间<6 分钟)。[68]Johnston KN, Potter AJ, Phillips A. Measurement properties of short lower extremity functional exercise tests in people with chronic obstructive pulmonary disease: systematic review. Phys Ther. 2017 Sep 1;97(9):926-43.https://academic.oup.com/ptj/article/97/9/926/3866635http://www.ncbi.nlm.nih.gov/pubmed/28605481?tool=bestpractice.com 运动试验也可用于选择适合接受康复治疗的患者。当呼吸困难或高碳酸血症加重与 FEV₁ 不成比例时,应进行呼吸肌功能测定,营养不良患者和皮质类固醇肌病患者也应进行呼吸肌功能测定。[69]Siafakas NM, Vermeire P, Pride NB, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J. 1995 Aug;8(8):1398-420.https://erj.ersjournals.com/content/erj/8/8/1398.full.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/7489808?tool=bestpractice.com
对于频繁急性加重、严重气流受限和/或急性加重以致需要机械通气的患者,应将痰液送去培养。[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/
COPD 与缺血性心脏病的的危险因素类似,因此合并症较常见。ECG 可检测到右心室肥大、心律失常或缺血。超声心动图可评估疑似心脏病或肺动脉高压。[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
WHO 已明确了初级卫生保健机构诊断 COPD 的最低限干预措施。WHO: package of essential noncommunicable (PEN) disease interventions for primary health care
循环中大量嗜酸性粒细胞预示着更高的急性加重风险,并预示皮质类固醇的预防和治疗效果良好。通过血嗜酸性粒细胞计数可识别吸入性皮质类固醇(inhaled corticosteroid, ICS)治疗更可能有效的患者。[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 该计数可预测常规长效支气管舒张剂治疗加用 ICS 对预防急性加重的有效性。[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,使用 ICS 的疗效甚微或无效,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 这些阈值可作为大致的临界值,帮助临床医师预测 ICS 治疗获益的可能性。[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/ 血嗜酸性粒细胞 ≥300 个细胞/μL 的患者停用 ICS 后,病情最易加重。[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