Ferrer-Pargada Diego, Amado Carlos A, Abascal-Bolado Beatriz, Mena Sandra Tello, Lecue Pilar Alonso, Armiñanzas Carlos, de Las Revillas Francisco Arnaiz, Santibáñez Miguel, Agüero Juan, Lobo Víctor Fernández, Ocejo-Vinyals J Gonzalo, Cifrian José Manuel
Department of Pulmonology, Hospital Universitario Marqués de Valdecilla, Av Valdecilla SN, 39005, Santander, Spain.
IDIVAL (Instituto de Investigación Biomédica de Cantabria), Santander, Spain.
Sci Rep. 2025 Jul 16;15(1):25696. doi: 10.1038/s41598-025-09229-y.
Pulmonary fibrosis after severe SARS-CoV-2 pneumonia is a major sequela in surviving patients which requires evaluation. Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation, easy to obtain and available in most functional testing laboratories of pulmonology services. Our objective was to evaluate the capacity of FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia. We recruited 335 patients admitted for severe pneumonia secondary to SARS-CoV-2 who were being followed up at the Diffuse Interstitial Lung Disease unit at Hospital Universitario Marqués de Valdecilla. FeNO levels were higher in patients with fibrotic interstitial sequelae: mean 24.3 vs. 19.8 ppbs, p = 0.002, with an area under the curve (AUC) of 0.63; 95% confidence interval (CI) 0.57-0.69 and an optimal cut-off point of 11 ppb maximizing the weighted combination of Sensitivity and specificity. FeNO ranked 6th among the 18 variables studied using various methods (forward selection, backward elimination, and stepwise regression) in evaluating the predictive ability for fibrotic interstitial sequelae, and it was the 5 th most predictive variable after using the cut-off point of 11 ppb. The joint predictive ability of the overall model with the 6 more predictive variables was higher than 0.8: AUC (Use of systemic corticosteroids + peak C-reactive Protein at admission + Age + Endotracheal intubation + Diffusing Capacity for CO (DLCO) + FeNO as quantitative continuous) = 0.81; 95%CI (0.77-0.86). AUC of the same model with FeNO as dichotomous (11 ppb cut-off point) = 0.82; 95%CI (0.78-0.87). Our study shows an increase in FeNO in patients who, after admission for severe SARS-CoV-2 pneumonia, present fibrotic interstitial sequelae at the three-month follow-up, as one of the different predictive variables related to the presence of these sequelae.
严重新型冠状病毒肺炎后的肺纤维化是存活患者的主要后遗症，需要进行评估。呼出一氧化氮分数（FeNO）是气道炎症的标志物，易于获取，在大多数肺科服务的功能检测实验室中都可进行检测。我们的目的是评估FeNO作为严重新型冠状病毒肺炎患者间质性和纤维化肺后遗症生物标志物的能力。我们招募了335例因新型冠状病毒继发严重肺炎而入院的患者，这些患者在巴尔德西利亚侯爵大学医院弥漫性间质性肺病科接受随访。有纤维化间质性后遗症的患者FeNO水平更高：平均为24.3 ppb，而无后遗症患者为19.8 ppb，p = 0.002，曲线下面积（AUC）为0.63；95%置信区间（CI）为0.57 - 0.69，最佳截断点为11 ppb，此时敏感性和特异性的加权组合最大。在使用各种方法（向前选择、向后排除和逐步回归）研究的18个变量中，FeNO在评估纤维化间质性后遗症的预测能力方面排名第6，在使用11 ppb截断点后，它是第5个最具预测性的变量。包含6个更具预测性变量的总体模型的联合预测能力高于0.8：AUC（使用全身糖皮质激素 + 入院时C反应蛋白峰值 + 年龄 + 气管插管 + 一氧化碳弥散量（DLCO）+ 作为定量连续变量的FeNO）= 0.81；95%CI（0.77 - 0.86）。以二分法（11 ppb截断点）的FeNO作为变量的同一模型的AUC = 0.82；95%CI（0.78 - 0.87）。我们的研究表明，在因严重新型冠状病毒肺炎入院后，三个月随访时出现纤维化间质性后遗症的患者中，FeNO升高，它是与这些后遗症存在相关的不同预测变量之一。
