Screening for Chronic Obstructive Pulmonary Disease .pdf
Unmet Needs and Future Considerations
未满足的需求和未来的考虑
Chronic obstructive pulmonary disease (COPD) is a leading cause of treatable and preventable morbidity worldwide but often remains undiagnosed or incorrectly diagnosed, making it a condition for which screening could enhance disease recognition and diagnosis. Most COPD screening has focused on affluent countries, with little or no attention given to enhancing COPD diagnosis in countries with fewer resources. Routine population-based spirometric screening in asymptomatic individuals has not been endorsed, but screening to identify symptomatic individuals at increased COPD risk may be appropriate.
慢性阻塞性肺病 (COPD) 是世界范围内可治疗和可预防的发病率的主要原因，但通常仍未得到诊断或诊断不正确，因此筛查可以增强疾病识别和诊断。大多数 COPD 筛查都集中在富裕国家，很少或根本没有注意在资源较少的国家加强 COPD 诊断。对无症状个体进行基于人群的常规肺活量筛查尚未得到认可，但筛查以识别具有增加 COPD 风险的有症状个体可能是合适的。
The report by Siddharthan et al in this issue of JAMA provides important information about general population COPD screening in 3 low- or middle-income country (LMIC) settings. This cross-sectional study of 10 709 adults in Nepal, Peru, and Uganda demonstrated substantial variation of spirometry-confirmed COPD prevalence in 3 communities in these regions (2.7% in Lima, Peru; 7.4% in Nakaseke, Uganda; and 18.1% in Bhaktapur, Nepal). Three previously developed screening tools (COPD in Low- and Middle-Income Countries Assessment [COLA-6], COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk [CAPTURE], and Lung Function Questionnaire [LFQ]) exhibited similar operating characteristics (area under the receiver operating characteristic curve [AUC], 0.717-0.791), and time to administer (mean, 7.6 minutes with 99.5% complete data).
悉达多等人在本期 JAMA 上的报告提供了有关 3 个低收入或中等收入国家 (LMIC) 环境中一般人群 COPD 筛查的重要信息。这项对尼泊尔、秘鲁和乌干达 10709 名成年人的横断面研究表明，这些地区 3 个社区的肺活量测定证实的 COPD 患病率存在显着差异（秘鲁利马为 2.7%；乌干达纳卡塞克为 7.4%；和在尼泊尔巴克塔普尔18.1%）。三种先前开发的筛查工具（低收入和中等收入国家的 COPD 评估 [COLA-6]、初级保健中的 COPD 评估以识别未确诊的呼吸系统疾病和恶化风险 [CAPTURE] 和肺功能问卷 [LFQ]）表现出相似的操作 特征（受试者工作特征曲线下面积 [AUC]，0.717-0.791）和给药时间（平均 7.6 分钟，99.5% 完整数据）。
Among the 1003 participants with screen-identified and research spirometry–confirmed COPD, 95.3%were previously undiagnosed and 16.4% had severe or very severe airflow obstruction. The diagnostic accuracy of the instruments was greater (weighted AUC, 0.742-0.895) among individuals with more symptoms (higher scores for the COPD Assessment Test and ModifiedMedical Research Council Dyspnea Scale), greater risk of exacerbation, or both, representing thosemost likely to have the greatest benefit from therapeutic interventions. The study also highlights important unaddressed considerations for the global expansion of COPD screening.
在 1003 名经筛查和研究证实为 COPD 的参与者中，95.3% 之前未确诊，16.4% 有严重或非常严重的气流阻塞。在具有更多症状（COPD 评估测试和改良医学研究委员会呼吸困难量表得分更高）、加重风险或两者兼有的个体中，仪器的诊断准确性更高（加权 AUC，0.742-0.895），代表那些最有可能患有 治疗干预的最大好处。该研究还强调了在全球范围内扩大 COPD 筛查的重要未解决的考虑因素。
Screening tools identify individuals at high risk of having a given health condition and appropriate for further evaluation and diagnosis. When screening tools are developed, sensitivity and specificity are assessed, with the tool “optimized” by adjusting content (questions, tests) and scoring to achieve the appropriate balance of sensitivity and specificity for the target condition and setting. Higher sensitivity ensures that fewer people with the condition are missed but increases the number of false-positive results. The influence and implications of high sensitivity and therefore more falsepositive results will vary by condition and region of the world. Missing the time-sensitive diagnosis of a curable condition is clearly undesirable. However, the implications of high sensitivity for a resource-limited region where higher false-positive rates may require more resources than are available must be considered. Siddharthan et al report the frequency of false-positive results in the 3 LMIC regions studied. In resource-challenged or LMIC regions, these numbers of false-positive results are important because each requires spirometry evaluation to confirm or negate the screening results. Spirometry requires equipment, experienced staff, and bronchodilators; these resources may not be available locally or even regionally.
筛查工具可识别具有特定健康状况的高风险个体，并适合进一步评估和诊断。在开发筛选工具时，会评估敏感性和特异性，通过调整内容（问题、测试）和评分来“优化”工具，以针对目标条件和设置实现敏感性和特异性的适当平衡。更高的灵敏度可确保漏诊的人更少，但会增加假阳性结果的数量。高灵敏度以及更多假阳性结果的影响和含义将因世界条件和地区而异。错过对可治愈疾病的时间敏感诊断显然是不可取的。但是，必须考虑高灵敏度对资源有限地区的影响，因为较高的误报率可能需要比可用资源更多的资源。悉达多等人报告了所研究的 3 个 LMIC 地区的假阳性结果频率。在资源挑战或 LMIC 地区，这些假阳性结果的数量很重要，因为每个都需要肺活量评估来确认或否定筛查结果。肺活量测定需要设备、经验丰富的工作人员和支气管扩张剂；这些资源可能无法在当地甚至区域获得。
The social, emotional, and economic effects of falsepositive test results on patients and families must also be addressed. Assessments will need to include the possible concern, fear, or stigma associated with a positive (including false-positive) test result and the economic costs for the patient and community. These considerations highlight the need for careful decision-making regarding the selection of threshold values for “positive” test results, including the idea of equalizing sensitivity and specificity and the potential influence on the rate of false-positive results.
还必须解决假阳性检测结果对患者和家属的社会、情感和经济影响。评估将需要包括与阳性（包括假阳性）测试结果相关的可能的担忧、恐惧或污名以及患者和社区的经济成本。 这些考虑强调了在选择“阳性”检测结果阈值时需要谨慎决策，包括平衡敏感性和特异性的想法以及对假阳性结果率的潜在影响。
Several tools are available for COPD screening. How and where the tools were developed likely influence content and will need to be a consideration in selecting tools that can be tailored for specific regions. Knowing the COPD risk factors and perhaps the sex-specific risk factors for a region may be important in the selection of specific screening tools. Siddharthan et al did not describe an assessment of potential sex differences in screening results, but this may be an important factor based on the regions where women may be more likely to have greater biomass fuel exposure or on regions where primarily men smoke. The LFQ relies heavily on smoking and age. The COLA-6 adds a question about biomass fuel that is not used in the other screening tools and includes questions about hospitalization, where hospitals may be not be equally available in all health care systems. Candidate content for CAPTURE was based on data from the literature, prospective qualitative data from the target population in the US, and quantitative data from a US sample. Some of these differences may explain the variations in AUC of the tools in the 3 study regions.
有几种工具可用于 COPD 筛查。这些工具的开发方式和地点可能会影响内容，并且在选择可针对特定区域定制的工具时需要考虑。了解 COPD 风险因素以及某个地区的特定性别风险因素可能对选择特定筛查工具很重要。悉达多等人没有描述对筛查结果中潜在性别差异的评估，但这可能是一个重要因素，基于女性可能更可能接触更多生物质燃料的地区或男性主要吸烟的地区。LFQ 严重依赖吸烟和年龄。COLA-6 增加了一个关于生物质燃料的问题，该问题未在其他筛查工具中使用，并包括有关住院的问题，在这些问题中，医院可能并非在所有医疗保健系统中均等可用。CAPTURE 的候选内容基于文献数据、美国目标人群的前瞻性定性数据和美国样本的定量数据。其中一些差异可以解释 3 个研究区域中工具的 AUC 差异。
The findings of Siddharthan et al suggest that different tools are likely to variably affect resource use. Resource utilization will be influenced by the number, length, and complexity of questions in the tools; administration setting(s); ease ofscoring; and action steps. Short single-focus questions are likely easier to answer and translate to other languages. For example, compare “How often do you cough upmucus” (a singledomain question) with “Have you brought up phlegm from your chest on most day or nights of the week during at least 3 months in a row in at least 2 years in a row?” (a question with stacked domains for mucus, days, months, and years). Results by Siddharthan et al support findings from previous studies that suggested that the addition of a peak flow assessment improves test specificity, at a cost of greater resource use (time, materials, complexity), suggesting that a stepwise screening process, with peak flow measurement only for some groups, may be an option in resource-limited environments.
悉达多等人的研究结果表明，不同的工具可能会不同地影响资源使用。资源利用将受到工具中问题的数量、长度和复杂性的影响；管理设置；易于评分；和行动步骤。简短的单一焦点问题可能更容易回答并翻译成其他语言。例如，比较“你多久咳一次粘液”（一个单域问题）和“你有没有在一周中的大多数白天或晚上从胸口吐痰至少连续 3 个月连续至少 2 年排？”（关于粘液、天、月和年的堆叠域的问题）。悉达多等人的结果支持先前研究的结果，即增加峰值流量评估可以提高测试特异性，但代价是更多的资源使用（时间、材料、复杂性），这表明逐步筛选过程，峰值流量测量仅适用于某些群体，在资源有限的环境中可能是一种选择。
In LMIC regions COPD diagnostic confirmation with spirometry assessment is often not readily available. It is possible that in such regions “screening” tests could become the equivalent of a “diagnostic” test for COPD. The data reported by Siddharthan et al6help focus this concern. If a COPD screening test becomes a default diagnostic test, all personswith falsepositive results would be considered to have COPD, and the limited resources for caring for people with COPD would be disproportionally given to the higher number of those with falsepositive “COPD” compared with true-positive results. Introducing screening in any region must take this potential outcome into account, along with consideration of the implications for individuals with false-negative results.
在 LMIC 地区，通过肺活量测定法进行 COPD 诊断确认通常不容易获得。 在这些地区，“筛查”测试可能等同于 COPD 的“诊断”测试。悉达多等人报告的数据帮助关注了这一问题。如果 COPD 筛查测试成为默认诊断测试，所有假阳性结果的人都将被视为患有 COPD，而用于照顾 COPD 患者的有限资源将不成比例地分配给假阳性“COPD”患者的数量高于真 -阳性结果。在任何地区引入筛查都必须考虑到这种潜在的结果，同时考虑到对假阴性结果的个体的影响。
Concerns about false-negative results are often dismissed by assuming that these individuals will likely be identified in repeat screening episodes. The assumptions that future screening will occur and what it will entail are seldom addressed with any evidence basis.When rescreening a population, the target cases are not the prevalent “missed cases” identified during initial screening events but rather are primarily incident cases and potentially the false-negative prevalent cases. Inmost regions of the world, incident rates aremuch lower than the COPD missed prevalent case rates targeted in initial screening. Thus, the positive predictive value and negative predictive value must be reassessed along with resource use or costs per case identified in rescreening and are important aims for future translational studies.
假设这些人很可能会在重复筛查事件中被识别出来，通常会消除对假阴性结果的担忧。 很少有任何证据基础来说明未来筛查将会发生以及它将带来什么的假设。在重新筛查人群时，目标 病例不是在初始筛查事件中发现的普遍的“漏诊病例”，而是主要是事件病例，并且可能是假阴性的普遍病例。在世界大部分地区，发病率远低于初始筛查中针对 COPD 漏诊的普遍病例率。因此，必须重新评估阳性预测值和阴性预测值以及在重新筛选中确定的每个病例的资源使用或成本，并且是未来转化研究的重要目标。
A key question that remains unanswered is the feasibility and ultimate effects on patient and health care outcomes of implementing large-scale screening approaches across populations and health care systems. Prior work with targeted case finding has been encouraging, with questions raised as to its overall clinical benefit. The GECo (Global Excellence in COPD Outcomes) investigators have proposed a next phase, testing a self-care approach that includes COPD education, facilitated self-management action plans for COPD exacerbations, andmonthly visits by community health workers for newly diagnosed patients identified using one of this study’s screening strategies and confirmed by spirometry. In countries with low health care resources, self-care may be an important part of COPD management, but first it is necessary to understand if implementing screening can result in necessary COPD diagnostic evaluations that are feasible and acceptable in the community. A comprehensive approach to COPD screening validation includes region-specific adjustments to existing local systems as well as assessment of acceptability to patients and clinicians. An important step in the validation process will be testing the ability of screening and diagnostic confirmation to occur and be adapted to using local health care staff rather than research staff.
一个尚未得到解答的关键问题是在人群和医疗保健系统中实施大规模筛查方法对患者和医疗保健结果的可行性和最终影响。先前的有针对性的病例发现工作令人鼓舞，但对其整体临床益处提出了质疑。GECo（全球 COPD 结果卓越）研究人员提出了下一阶段，测试一种自我保健方法，包括 COPD 教育、促进 COPD 恶化的自我管理行动计划，以及社区卫生工作者每月对使用一种方法确定的新诊断患者进行访问。本研究的筛选策略并通过肺活量测定法证实。在医疗资源匮乏的国家，自我保健可能是 COPD 管理的重要组成部分，但首先有必要了解实施筛查是否可以导致必要的 COPD 诊断评估，这些评估在社区中是可行和可接受的。COPD 筛查验证的综合方法包括对现有本地系统进行区域特定的调整以及评估患者和临床医生的可接受性。验证过程中的一个重要步骤将是测试筛查和诊断确认发生的能力，并适应使用当地医疗保健人员而不是研究人员的能力。
The results of the study by Siddharthan et al in this issue of JAMA represent a crucial step in the development of feasible COPD screening programs in LMIC regions. Next steps will include understanding and communicating patient- and society-level risks and benefits; developing and testing an effective and efficient locally based and administered screening procedure that reflects country-specific needs, risk factors, and action steps; ensuring commitment of the health care system and clinical staff; and engaging the patient community by raising awareness of undiagnosed COPD and the importance of prevention and treatment. As with most published research, Siddharthan et al have identified meaningful problems, opportunities, and issues for future studies.
悉达多等人在本期 JAMA 上的研究结果代表了在 LMIC 地区制定可行的 COPD 筛查计划的关键步骤。下一步将包括了解和交流患者和社会层面的风险和收益；开发和测试有效且高效的基于当地和管理的筛查程序，以反映国家特定的需求、风险因素和行动步骤；确保卫生保健系统和临床工作人员的承诺； 通过提高对未确诊 COPD 以及预防和治疗重要性的认识，让患者社区参与进来。与大多数已发表的研究一样，悉达多等人已经确定了有意义的问题、机会和未来研究的问题。
