FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia

Abstract 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. O...

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Main Authors: Diego Ferrer-Pargada, Carlos A. Amado, Beatriz Abascal-Bolado, Sandra Tello Mena, Pilar Alonso Lecue, Carlos Armiñanzas, Francisco Arnaiz de las Revillas, Miguel Santibáñez, Juan Agüero, Víctor Fernández Lobo, J. Gonzalo Ocejo-Vinyals, José Manuel Cifrian
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Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-09229-y
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author Diego Ferrer-Pargada
Carlos A. Amado
Beatriz Abascal-Bolado
Sandra Tello Mena
Pilar Alonso Lecue
Carlos Armiñanzas
Francisco Arnaiz de las Revillas
Miguel Santibáñez
Juan Agüero
Víctor Fernández Lobo
J. Gonzalo Ocejo-Vinyals
José Manuel Cifrian
author_facet Diego Ferrer-Pargada
Carlos A. Amado
Beatriz Abascal-Bolado
Sandra Tello Mena
Pilar Alonso Lecue
Carlos Armiñanzas
Francisco Arnaiz de las Revillas
Miguel Santibáñez
Juan Agüero
Víctor Fernández Lobo
J. Gonzalo Ocejo-Vinyals
José Manuel Cifrian
author_sort Diego Ferrer-Pargada
collection DOAJ
description Abstract 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.
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spelling doaj-art-7298e22cc3c6448889fa7ca5a4bd17142025-08-20T04:01:51ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-09229-yFeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumoniaDiego Ferrer-Pargada0Carlos A. Amado1Beatriz Abascal-Bolado2Sandra Tello Mena3Pilar Alonso Lecue4Carlos Armiñanzas5Francisco Arnaiz de las Revillas6Miguel Santibáñez7Juan Agüero8Víctor Fernández Lobo9J. Gonzalo Ocejo-Vinyals10José Manuel Cifrian11Department of Pulmonology, Hospital Universitario Marqués de ValdecillaDepartment of Pulmonology, Hospital Universitario Marqués de ValdecillaDepartment of Pulmonology, Hospital Universitario Marqués de ValdecillaDepartment of Pulmonology, Hospital Universitario Marqués de ValdecillaIDIVAL (Instituto de Investigación Biomédica de Cantabria)IDIVAL (Instituto de Investigación Biomédica de Cantabria)University of CantabriaUniversity of CantabriaDepartment of Pulmonology, Hospital Universitario Marqués de ValdecillaDepartment of Radiology, Hospital Universitario Marqués de ValdecillaIDIVAL (Instituto de Investigación Biomédica de Cantabria)Department of Pulmonology, Hospital Universitario Marqués de ValdecillaAbstract 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.https://doi.org/10.1038/s41598-025-09229-yFeNOCOVID-19SARS-CoV-2SequealeILDPulmonary fibrosis
spellingShingle Diego Ferrer-Pargada
Carlos A. Amado
Beatriz Abascal-Bolado
Sandra Tello Mena
Pilar Alonso Lecue
Carlos Armiñanzas
Francisco Arnaiz de las Revillas
Miguel Santibáñez
Juan Agüero
Víctor Fernández Lobo
J. Gonzalo Ocejo-Vinyals
José Manuel Cifrian
FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia
Scientific Reports
FeNO
COVID-19
SARS-CoV-2
Sequeale
ILD
Pulmonary fibrosis
title FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia
title_full FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia
title_fullStr FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia
title_full_unstemmed FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia
title_short FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia
title_sort feno as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe sars cov 2 pneumonia
topic FeNO
COVID-19
SARS-CoV-2
Sequeale
ILD
Pulmonary fibrosis
url https://doi.org/10.1038/s41598-025-09229-y
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