TY - JOUR
T1 - Fractional exhaled Nitric Oxide (FeNO) level as a predictor of COVID-19 disease severity
AU - Lior, Yotam
AU - Yatzkan, Noga
AU - Brami, Ido
AU - Yogev, Yuval
AU - Riff, Reut
AU - Hekselman, Idan
AU - Fremder, Moran
AU - Freixo-Lima, Gabriella
AU - Be'er, Moria
AU - Amirav, Israel
AU - Lavie, Moran
N1 - Funding Information:
Fractional exhaled Nitric Oxide (FeNO) is an easily achievable, noninvasive measurement of exhaled air that is to known to be associated with respiratory dynamics in the clinical setting. For instance, it was shown to be effective in monitoring asthma exacerbations and in assessing the clinical course of various respiratory viral infections [ 9–13]. FeNO is produced in airway epithelial and inflammatory cells mainly by the enzyme inducible nitric oxide synthase (iNOS). Angiotensin-converting enzyme 2 (ACE2) was shown to be involved in airway NO production via downstream effects on iNOS [ 14–17], and to be a significant airway and vascular regulator [18,19]. Much like its counterpart SARS-CoV-1, SARS-CoV-2 was shown to invade respiratory epithelial cells via the ACE2 receptor. Interestingly, ACE2 was shown to be downregulated during a SARS-CoV-1 infection [20]. It is therefore logical to assume the existence of a negative correlation between SARS-CoV-2 infection burden and ACE2 airway expression, representing a correlation that could affect downstream airway NO production and therefore FeNO measurements. Thus, FeNO may serve as an indirect predictor of COVID-19 disease burden, allowing risk stratification and medical decision-making regarding COVID-19 patients. The purpose of this study was to assess the potential use of FeNO as a prognostic biomarker of outcome severity and its application as a tool for risk stratification for supporting management decision-making of COVID-19 patients at admission to the emergency department (ED).Our results suggest that bedside FeNO measurements during hospitalization could serve as a support tool for decision-making among medical personnel when considering home discharge from the ED, COVID-19 ward hospitalization, or ICU admission of confirmed COVID-19 cases. Furthermore, given the portability, ease of use, and rapid results of FeNO measurement devices, the use of FeNO in the context of COVID-19 could be further expanded to community clinics and remote locations where auxiliary tests may not be readily available.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Objective: To assess the feasibility of Fractional exhaled Nitric Oxide (FeNO) as a simple, non-invasive, cost-effective and portable biomarker and decision support tool for risk stratification of COVID-19 patients. Methods: We conducted a single-center prospective cohort study of COVID-19 patients whose FeNO levels were measured upon ward admission by the Vivatmo-me handheld device. Demographics, COVID-19 symptoms, and relevant hospitalization details were retrieved from the hospital databases. The patients were divided into those discharged to recover at home and those who died during hospitalization or required admission to an intensive care unit, internal medicine ward, or dedicated facility (severe outcomes group). Results: Fifty-six patients were enrolled. The only significant demographic difference between the severe outcomes patients (n = 14) and the home discharge patients (n = 42) was age (64.21 ± 13.97 vs. 53.98 ± 15.57 years, respectively, P =.04). The admission FeNO measurement was significantly lower in the former group compared with the latter group (15.86 ± 14.74 vs. 25.77 ± 13.79, parts per billion [PPB], respectively, P =.008). Time to severe outcome among patients with FeNO measurements ≤11.8 PPB was significantly shorter compared with patients whose FeNO measured >11.8 PPB (19.25 ± 2.96 vs. 24.41 ± 1.09 days, respectively, 95% confidence interval [CI] 1.06 to 4.25). An admission FeNO ≤11.8 PPB was a significant risk factor for severe outcomes (odds ratio = 12.8, 95% CI: 2.78 to 58.88, P =.001), with a receiver operating characteristics curve of 0.752. Conclusions: FeNO measurements by the Vivatmo-me handheld device can serve as a biomarker and COVID-19 support tool for medical teams. These easy-to-use, portable, and noninvasive devices may serve as valuable ED bedside tools during a pandemic.
AB - Objective: To assess the feasibility of Fractional exhaled Nitric Oxide (FeNO) as a simple, non-invasive, cost-effective and portable biomarker and decision support tool for risk stratification of COVID-19 patients. Methods: We conducted a single-center prospective cohort study of COVID-19 patients whose FeNO levels were measured upon ward admission by the Vivatmo-me handheld device. Demographics, COVID-19 symptoms, and relevant hospitalization details were retrieved from the hospital databases. The patients were divided into those discharged to recover at home and those who died during hospitalization or required admission to an intensive care unit, internal medicine ward, or dedicated facility (severe outcomes group). Results: Fifty-six patients were enrolled. The only significant demographic difference between the severe outcomes patients (n = 14) and the home discharge patients (n = 42) was age (64.21 ± 13.97 vs. 53.98 ± 15.57 years, respectively, P =.04). The admission FeNO measurement was significantly lower in the former group compared with the latter group (15.86 ± 14.74 vs. 25.77 ± 13.79, parts per billion [PPB], respectively, P =.008). Time to severe outcome among patients with FeNO measurements ≤11.8 PPB was significantly shorter compared with patients whose FeNO measured >11.8 PPB (19.25 ± 2.96 vs. 24.41 ± 1.09 days, respectively, 95% confidence interval [CI] 1.06 to 4.25). An admission FeNO ≤11.8 PPB was a significant risk factor for severe outcomes (odds ratio = 12.8, 95% CI: 2.78 to 58.88, P =.001), with a receiver operating characteristics curve of 0.752. Conclusions: FeNO measurements by the Vivatmo-me handheld device can serve as a biomarker and COVID-19 support tool for medical teams. These easy-to-use, portable, and noninvasive devices may serve as valuable ED bedside tools during a pandemic.
KW - ACE2
KW - COVID-19
KW - FeNO
KW - Prognosis
KW - Scoring
UR - http://www.scopus.com/inward/record.url?scp=85131325134&partnerID=8YFLogxK
U2 - 10.1016/j.niox.2022.05.002
DO - 10.1016/j.niox.2022.05.002
M3 - Article
C2 - 35597408
AN - SCOPUS:85131325134
SN - 1089-8603
VL - 124
SP - 68
EP - 73
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
ER -
