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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.

背景与研究目标：肺栓塞（Pulmonary Embolism, PE）是一类潜在危重的病症，以肺部血管阻塞为核心特征，因其临床表现缺乏特异性，临床诊断常面临显著挑战。本研究旨在评估肺泡动脉氧分压差（alveolar-arterial oxygen gradient, A-a梯度）用于PE诊断的应用价值，提出假说：将其与其他临床标志物联合使用，可提升PE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A-a梯度与经CT肺动脉造影（CT pulmonary angiography）确诊的PE进行相关性分析。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（C-reactive protein, CRP）、N末端B型利钠肽原（pro-brain natriuretic peptide, NT-proBNP）、D-二聚体（D-dimer）、高敏肌钙蛋白（high-sensitivity troponin, hs-troponin）及动脉血氧分压（arterial oxygen pressure, PaO2）。
结果：本研究结果显示，PE患者的A-a梯度显著高于非PE患者；PE组的A-a梯度实测值与预测值之比显著升高。此外，PE患者的心率、CRP、NT-proBNP、D-二聚体及hs-troponin水平均显著升高，而PaO2水平明显降低。
结论：本研究证实，升高的A-a梯度可反映PE患者的气体交换受损程度。研究结果提示，将A-a梯度分析与其他临床标志物联合应用，可改善PE的早期诊断，助力实现更高效、及时的临床干预。
详细方法：本研究纳入168例年龄17~91岁的患者，均因急诊入院接受诊疗。首先采集详细病史，重点关注PE的危险因素，记录患者是否存在活动性恶性肿瘤、本次发病相关的咯血、PE或深静脉血栓（Deep Vein Thrombosis, DVT）病史，以及近4周内是否接受过外科手术。对每位患者进行全面体格检查，记录心率，并评估是否存在DVT的临床体征。采集血液样本用于血常规、凝血功能及生化检测。同时采集动脉血样本进行血气分析——该检测操作简便、无痛且可快速获取结果，急诊室中使用雷度（Radiometer）公司的ABL90 FLEX设备完成相关参数计算。本次记录的目标指标包括：动脉血氧饱和度、动脉血氧分压及动脉血二氧化碳分压。当初步临床诊断为PE时，将患者送往CT室，使用欧乃派克（Optiray）造影剂行CT肺动脉造影。A-a梯度采用标准公式计算：A−a=PAO2−PaO2。正常A-a梯度定义为≤（患者年龄+10）/4。验证队列纳入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（Statistical Package for the Social Sciences）26.0版本及R 4.0.5版本完成。由于A-a比值数据呈非对称分布，采用曼-惠特尼U检验（Mann-Whitney U test）比较两组（PE患者与非PE患者）间的差异。曼-惠特尼U检验是一种非参数检验，用于比较两个独立组的中位数差异，以P<0.05作为差异具有统计学意义的判定标准。本研究分析二分类结局的分布时，采用卡方检验，用于评估两个及以上分类变量的频率是否存在统计学差异。为评估实测/预测A-a比值对PE的诊断效能，采用ROC曲线（Receiver Operating Characteristic, 受试者工作特征曲线）分析并计算AUC（Area Under the Curve, 曲线下面积）值。ROC曲线可展示不同阈值（截断值）下灵敏度与1-特异度的比值，AUC值可整体反映模型的诊断准确性。为确定实测/预测A-a比值的最优截断值，采用尤登指数（Youden index, J），该指数可最大化灵敏度与特异度的组合效能。