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Background/Objectives: Pulmonary embolism (PE) is a potentially serious condition characterized by the blockage of blood vessels in the lungs, often presenting significant diagnostic challenges due to its non-specific symptoms. This study aimed to evaluate the utility of the alveolar-arterial (A-a) oxygen gradient as a diagnostic tool for PE, hypothesizing that it could enhance early detection when combined with other clinical markers. Methods: We conducted a retrospective analysis of 168 patients at the University Hospital Center Split. The study correlated A-a gradients with PE confirmed by CT pulmonary angiography. Key clinical and biochemical markers, including heart rate, C-reactive protein (CRP), pro-brain natriuretic peptide (NT-proBNP), D-dimer, high-sensitivity troponin (hs-troponin), and arterial oxygen pressure (PaO2), were assessed. Results: Our findings revealed that patients with PE had significantly higher A-a gradients compared to those without PE. The observed-to-expected ratio for A-a gradient was notably increased in the PE group. Additionally, patients with PE exhibited elevated levels of heart rate, CRP, NT-proBNP, D-dimer, and hs-troponin, while PaO2 levels were notably lower. Conclusions: This study demonstrates that an elevated A-a gradient reflects the severity of gas exchange impairment in PE. The results suggest that early diagnosis of PE may be improved by incorporating A-a gradient analysis alongside other clinical markers, potentially leading to more effective and timely interventions.
Methods (detailed): The study included 168 patients aged 17 to 91 years. The patients were examined upon emergency admission. The examination included a detailed anamnesis with a focus on risk factors for pulmonary embolism, where it was noted whether the patient had active cancer, hemoptysis related to the current condition, a history of pulmonary embolism or deep vein thrombosis, or any surgical procedures within the last 4 weeks. Each patient underwent a clinical examination, where heart rate was recorded, along with the presence of clinical signs of DVT. Blood was drawn for hematology, coagulation, and biochemistry tests. An arterial blood sample was taken for gas analysis, which is simple, painless, and provides immediate results. The ABL90 FLEX device from Radiometer was used for this calculation in the emergency department. The recorded data of interest included: oxygen saturation of arterial blood, arterial oxygen pressure, and arterial carbon dioxide pressure. When a working diagnosis of PE was made, the patient was sent for CT pulmonary angiography with Optiray contrast. A-a gradients were calculated using the standard equation: A−a=PAO2−PaO2. A normal gradient is defined as being less than or equal to the sum of the patient’s age plus 10, divided by 4. The validation set consisted of patients who had nor-mal CT angiography results from 2019 to 2023. All statistical calculations and analyses were performed using SPSS (Statistical Package for the Social Sciences) version 26.0 and R version 4.0.5. To assess differences between groups (patients with and without PE), the Mann-Whitney U test was used, as the data on the A-a ratio values showed an asymmetric distribution. The Mann-Whitney U test is a non-parametric test that compares the medians of two in-dependent groups. The significance of differences between groups was assessed at a significance level of P < 0.05. For analyzing the distribution of binary outcomes in this study we used the chi-square test, which assesses whether there is a statistically significant difference in frequency between two or more categorical variables. To evaluate the diagnostic accuracy of the ratio of expected and observed A-a values in predicting PE, a ROC curve (Receiver Operating Characteristic) analysis was used, and the AUC (Area Under the Curve) value was calculated. The ROC curve shows the ratio of sensitivity and 1-specificity across different threshold values (cut-off), and the AUC value serves as an overall measure of the model's diagnostic accuracy. To determine the optimal cut-off for the ratio of expected and observed A-a values, the Youden index (J) was used, which maximizes the combination of sensitivity and specificity.

背景与目标：肺栓塞（PE）是一类以肺部血管阻塞为特征的潜在危重疾病，由于其症状缺乏特异性，往往给临床诊断带来极大挑战。本研究旨在评估肺泡-动脉（A-a）氧梯度用于肺栓塞诊断的应用价值，假设将其与其他临床标志物联合检测，可提升肺栓塞的早期检出效能。
方法：本研究对斯普利特大学医院中心的168例患者开展回顾性分析，将肺泡-动脉氧梯度与经CT肺动脉造影确诊的肺栓塞病例进行关联分析。本研究评估了多项关键临床与生化标志物，包括心率、C反应蛋白（CRP）、N末端B型利钠肽原（NT-proBNP）、D-二聚体、高敏肌钙蛋白（hs-troponin）以及动脉血氧分压（PaO2）。
结果：本研究结果显示，肺栓塞患者的肺泡-动脉氧梯度显著高于非肺栓塞患者；肺栓塞组的实测/预期肺泡-动脉氧梯度比值显著升高。此外，肺栓塞患者的心率、CRP、NT-proBNP、D-二聚体及hs-troponin水平均显著升高，而PaO2水平则明显降低。
结论：本研究证实，升高的肺泡-动脉氧梯度可反映肺栓塞患者的气体交换损伤程度。研究结果提示，将肺泡-动脉氧梯度分析与其他临床标志物联合应用，可优化肺栓塞的早期诊断流程，有望实现更及时且有效的临床干预。
详细方法：本研究纳入168例年龄介于17~91岁的患者，所有患者均于急诊入院时接受评估。评估内容包括详细的病史采集，重点关注肺栓塞的危险因素，记录患者是否存在活动性恶性肿瘤、与当前病情相关的咯血、肺栓塞或深静脉血栓病史，以及近4周内是否接受过外科手术。
所有患者均接受体格检查，记录心率并评估深静脉血栓的临床体征。采集血液样本用于血常规、凝血功能及生化指标检测；同时采集动脉血样本进行血气分析，该检测操作简便、无痛且可快速获得结果。本研究于急诊科室使用雷度（Radiometer）公司的ABL90 FLEX分析仪完成相关计算。
本次研究采集的目标数据包括：动脉血氧饱和度、动脉血氧分压及动脉血二氧化碳分压。当初步诊断为肺栓塞时，患者将接受欧乃派克（Optiray）造影剂增强CT肺动脉造影检查。肺泡-动脉氧梯度采用标准公式计算：A-a = 肺泡氧分压（PAO2）− 动脉血氧分压（PaO2）。正常肺泡-动脉氧梯度的定义为：≤（患者年龄+10）/4。
验证集纳入2019年至2023年间CT血管造影结果正常的患者。所有统计计算与分析均采用SPSS（社会科学统计软件包，Statistical Package for the Social Sciences）26.0版本及R 4.0.5版本完成。
为比较肺栓塞组与非肺栓塞组的组间差异，本研究采用曼-惠特尼U检验，原因是肺泡-动脉氧梯度比值的数据呈非对称分布。曼-惠特尼U检验是一种非参数检验方法，用于比较两个独立样本的中位数差异，本研究以P<0.05作为组间差异具有统计学意义的判定标准。
针对本研究中的二分类结局分布分析，本研究采用卡方检验，该方法用于评估两个及以上分类变量的频率分布是否存在统计学差异。
为评估实测/预期肺泡-动脉氧梯度比值对肺栓塞的诊断效能，本研究采用受试者工作特征（ROC，Receiver Operating Characteristic）曲线分析，并计算曲线下面积（AUC，Area Under the Curve）值。ROC曲线可展示不同截断值（cut-off）下的灵敏度与1−特异度的比值，而AUC值可作为模型诊断效能的综合评价指标。
为确定实测/预期肺泡-动脉氧梯度比值的最佳截断值，本研究采用尤登指数（J），该指标可最大化灵敏度与特异度的综合取值。