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Journal of Clinical Medicine Research

Letter to the Editor

Volume 14, Number 7, July 2022, pages 291-292

Fractional Exhaled Nitric Oxide in Normoxic Adult Patients With COVID-19 Infection in the Emergency Department: A Preliminary Observation

Current concepts suggest that local elaboration of nitric oxide (NO) modulates, in part, the intense pro-inflammatory phenomena observed in lungs of patients with certain respiratory viral infections [1]. To that end, fractional exhaled NO (FeNO) monitoring is proposed as simple, portable, noninvasive, cost-effective, point-of-care biomarker of pulmonary inflammation in patients with viral-induced acute lung injury [1-3]. However, the effects of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 (COVID-19)) infection on FeNO levels in human subjects requiring supplemental oxygen therapy is controversial. For instance, Exline et al [2] reported high FeNO levels in hospitalized, mechanically-ventilated patients with COVID-19 infection. By contrast, Lior et al [3] showed recently that FeNO levels were decreased in hospitalized patients with severe COVID-19 infection and that admission FeNO < 11.8 ppb heralded adverse outcomes.

To the best of our knowledge, no studies to date have determined FeNO levels in normoxic patients with COVID-19 infection seen in the emergency department. We posit that under these circumstances FeNO could be used as noninvasive biomarker to identify infected patients at greater risk of disease progression and/or worse prognosis and to devise a care plan accordingly. To begin to address these issues, we determined FeNO levels in normoxic adult patients with rapid polymerase chain reaction (PCR) test-documented COVID-19 infection seen in the emergency department of a large, tertiary care hospital in Chicago, IL, USA. None required supplemental oxygen nor received COVID-19-related medications at the time FeNO was determined.

A hand-held NIOX VERO^® Airway Inflammation Monitor (Circassia Pharmaceuticals Inc., Morrisville, NC, USA) was used to determine FeNO levels in 18 eligible patients, 64 ± 15 years (mean ± standard deviation (SD); 17 males) presenting to the Emergency Department of Jesse Brown VA Medical Center and in 18 healthy, non-smoking volunteers between December 2020 and June 2021. The US Food and Drug Administration (FDA)-cleared NIOX VERO^® monitor deploys an electrochemical sensor technology as analytical method and an external quality control procedure to ascertain reliability of measured values [4]. In each subject, FeNO determination conformed with the American Thoracic Society (ATS) clinical practice guidelines [5]. Although these patients presented with respiratory complaints, such as persistent cough and dyspnea, all were able to perform adequate FeNO measurements as instructed.

Data are reported as means ± SD. Statistical analysis was performed using paired Student’s t-test. P < 0.05 was considered statistically significant. The study was approved by Jesse Brown VA Medical Center institutional review board (IRB) (approval number: 1574706-1).

Arterial oxygen saturation (SpO₂) in patients with COVID-19 was 96±3% during FeNO testing. FeNO levels in patients and healthy volunteers were 18.11 ± 10.07 and 13.33 ± 4.64 ppb, respectively (P = not significant (NS)). Fourteen patients (78%) were subsequently hospitalized of which one died.

Our small, single-site, prospective study shows that FeNO levels in normoxic adult patients presenting to the emergency department with COVID-19 infection are similar to those of healthy, non-smoking volunteers. This observation is noteworthy because most our patients (14/18) were subsequently hospitalized attesting to the severity of their illness. However, the small sample size precludes meaningful evaluation of FeNO as a simple, bedside, noninvasive biomarker of risk stratification of normoxic patients with COVID-19 infection seen in the emergency department.

The reason(s) underlying the discrepant reports about FeNO levels in hospitalized patients with COVID-19 infection is uncertain [2, 3]. Conceivably, differences in patient characteristics, such as age, sex, race/ethnicity, disease severity, and therapeutic interventions at the time of FeNO testing could account, in part, for these observations. For instance, hypoxia has been shown to increase FeNO levels while short-term hyperoxia decreases FeNO levels for several hours in human subjects [6, 7].

In summary, we propose that larger, well-controlled, prospective studies are warranted to determine the utility of point-of-care FeNO monitoring as noninvasive biomarker of risk stratification of patients with COVID-19 infection seen in the emergency department.

Acknowledgments

We thank physicians and nursing staff at the Emergency Department of the Jesse Brown VA Medical Center for their cooperation and support. We thank Circassia Pharmaceuticals, Inc. for providing free NIOX VERO^® Airway Inflammation Monitor and supplies for the study. The company was not involved in study design, data collection and analysis, and writing the manuscript. This material is the result of work supported with resources and the use of facilities at the Jesse Brown VA Medical Center, Chicago, Illinois, USA. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

Financial Disclosure

No external funding was provided to conduct the study.

Conflict of Interest

The authors declare no conflicts of interest.

Informed Consent

All the informed consents were obtained.

Author Contributions

Zane Z. Elfessi: literature review, study design, investigation, data curation, analysis, interpretation, writing and editing. Brendan K Steadman: investigation, data curation, and editing. Israel Rubinstein: conceptualization, supervision, analysis, interpretation, writing and editing.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.

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Journal of Clinical Medicine Research is published by Elmer Press Inc.