美国布列根和妇女医院Matthew Moll团队将多基因风险评分添加到常规病例发现中，以识别未诊断的慢性阻塞性肺疾病。相关论文于2025年1月22日发表在《美国医学会杂志》上。

慢性阻塞性肺病（COPD）通常无法确诊。尽管遗传风险在COPD易感性中起着重要作用，但其在指导肺活量测定和识别未确诊病例方面的实用性尚不清楚。

为了确定COPD多基因风险评分（PRS）是否可以使用常规风险因素和呼吸道症状，在病例调查问卷（如肺功能问卷）之外增强对未确诊COPD的识别，研究组进行了一项对35岁或以上未被医生诊断为COPD病史的参与者的横断面分析，使用2项观察性研究数据：基于社区的弗雷明汉心脏研究（FHS）和COPD富集遗传流行病学（COPDGene）研究。

暴露因素为改良肺功能问卷（mLFQ）评分和COPD PRS。主要结局为肺活量测定法定义的中度至重度COPD（呼气第一秒的用力呼气量/用力肺活量[FEV1/FVC]<0.7，FEV1[预测百分比]<80%）。使用PRS、mLFQ评分和PRS加mLFQ得分来评估逻辑模型的性能，以预测肺活量测定定义的COPD。

在3385名没有COPD病史的FHS参与者（中位年龄为52.0岁；45.9%为男性）和4095名COPDGene参与者（中位数年龄为56.8岁；55.5%为男性）中，160名（4.7%）FHS和775名（18.9%）COPDGene参与者患有肺活量测定定义的COPD。将PRS添加到mLFQ评分中，显著改善了FHS患者的曲线下面积，从0.78增加到0.84（P<.001），COPDGene非西班牙裔非裔美国人从0.69增加到0.72（P=.04），COPDGene非西班牙裔白人参与者从0.75增加到0.78（P<0.001）。

研究结果表明，COPD PRS增强了对普通人群中未确诊COPD的识别，超越了传统的病例发现方法。需要进一步的研究来评估其对COPD诊断和结果的影响。

附：英文原文

Title: Polygenic Risk Score Added to Conventional Case Finding to Identify Undiagnosed Chronic Obstructive Pulmonary Disease

Author: Jingzhou Zhang, Brian D. Hobbs, Edwin K. Silverman, David Sparrow, Victor E. Ortega, Hanfei Xu, Chengyue Zhang, Josée Dupuis, Allan J. Walkey, George T. O’Connor, Michael H. Cho, Matthew Moll

Issue&Volume: 2025-01-22

Abstract:

Importance  Chronic obstructive pulmonary disease (COPD) is often undiagnosed. Although genetic risk plays a significant role in COPD susceptibility, its utility in guiding spirometry testing and identifying undiagnosed cases is unclear.

Objective  To determine whether a COPD polygenic risk score (PRS) enhances the identification of undiagnosed COPD beyond a case-finding questionnaire (eg, the Lung Function Questionnaire) using conventional risk factors and respiratory symptoms.

Design, Setting, and Participants  This cross-sectional analysis of participants 35 years or older who reported no history of physician-diagnosed COPD was conducted using data from 2 observational studies: the community-based Framingham Heart Study (FHS) and the COPD-enriched Genetic Epidemiology of COPD (COPDGene) study.

Exposures  Modified Lung Function Questionnaire (mLFQ) scores and COPD PRS.

Main Outcomes and Measures  The primary outcome was spirometry-defined moderate to severe COPD (forced expiratory volume in the first second of expiration/forced vital capacity [FEV1/FVC] <0.7 and FEV1 [percent predicted] <80%). The performance of logistic models was assessed using the PRS, mLFQ score, and PRS plus mLFQ score for predicting spirometry-defined COPD.

Results  Among 3385 FHS participants (median age, 52.0 years; 45.9% male) and 4095 COPDGene participants (median age, 56.8 years; 55.5% male) who reported no history of COPD, 160 (4.7%) FHS and 775 (18.9%) COPDGene participants had spirometry-defined COPD. Adding the PRS to the mLFQ score significantly improved the area under the curve from 0.78 to 0.84 (P<.001) in FHS, 0.69 to 0.72 (P=.04) in COPDGene non-Hispanic African American, and 0.75 to 0.78 (P<.001) in COPDGene non-Hispanic White participants. At a risk threshold for spirometry referral of 10%, the addition of the PRS to the mLFQ score correctly reclassified 13.8% (95% CI, 6.6%-21.0%) of COPD cases in FHS, but not in COPDGene.

Conclusions and Relevance  A COPD PRS enhances the identification of undiagnosed COPD beyond a conventional case-finding approach in the general population. Further research is needed to assess its impact on COPD diagnosis and outcomes.

DOI: 10.1001/jama.2024.24212

Source: https://jamanetwork.com/journals/jama/fullarticle/2829529