The role of exhaled nitric oxide (FeNO) in the evaluation of lung parenchymal involvement in COVID-19 patients

Abstract

The inflammatory balance is an important factor in the clinical course of COVID-19 (SARS-CoV-2) infection, which has affected over 300 million people globally since its appearance in December 2019. This study aimed to evaluate the correlation between exhaled nitric oxide (FeNO) level and parenchymal involvement in COVID-19. The study included 106 patients with the delta variant of COVID-19 identified by real-time PCR as well as 40 healthy control groups between October 2021 and March 2022. The patients were analyzed in three groups: moderate COVID-19 (group 1), severe COVID-19 without macrophage activation syndrome (MAS) (group 2), and severe COVID-19 with MAS (group 3). FeNO and CT scores were significantly higher in groups 2 and 3 at admission and discharge compared to group 1 (p = 0.001 for all). In addition, CT score at admission and CT score and FeNO level at discharge were higher in group 3 than in group 2 (p = 0.001 for all). It was found that the FeNO levels were higher in Groups 2 and 3 than in the control group (p = 0.001) during the admission. FeNO and CT scores showed strong positive correlation at admission and discharge (r = 0.917, p = 0.001; r = 0.790, p = 0.001). In receiver operating characteristic curve analysis for prediction of MAS, FeNO at a cut-off of 10.5 ppb had 66% sensitivity and 71% specificity. COVID-19 causes more severe lung involvement than other viral lower respiratory tract infections, leading to the frequent use of chest CT in these patients. FeNO assessment is a practical and noninvasive method that may be useful in evaluating for parenchymal infiltration in the diagnosis and follow-up of COVID-19 patients.

Distal Lung Inflammation Assessed by Alveolar Concentration of Nitric Oxide Is an Individualised Biomarker of Severe COVID-19 Pneumonia

“…Many already published studies only investigated FeNO [ 33 , 34 , 35 , 36 , 37 ], a biomarker of proximal bronchial inflammation [ 10 ], that is unlikely to occur 6 to 52 weeks after the acute phase in those COVID-19 patients without a medical history of asthma. That FeNO remained within normal ranges and did not differ between different groups of patients, as observed in our study and many others [ 7 , 8 , 33 , 34 , 35 , 36 , 37 ], is also consistent with the relatively low percentage of patients with bronchial obstructive patterns during COVID-19 follow-up studies [ 3 , 5 , 6 ], and the hypothesis that bronchial obstructive lung disease is an unlikely feature of PASC [ 3 ]. Of greater concern, however, is the risk of pulmonary fibrosis that might occur as a long-term complication of COVID-19 even in those patients free of ILD prior to infection by SARS-CoV-2 [ 30 , 32 ].…”

“…Although many studies measuring pulmonary function tests (PFTs) have either reported the existence of transient pulmonary obstructive or restrictive patterns [ 5 , 6 ] and concurred on the high frequency of lung gas exchange impairment [ 3 ], only a few have monitored airway inflammation in COVID-19 survivors [ 7 , 8 ]. Among all the available biomarkers that are readily available, the noninvasive measurement of exhaled nitric oxide (NO) is commonly used to assess the inflammation of the lungs in patients with various respiratory diseases [ 9 ].…”

Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases?

“…It has been suggested that FeNO levels are elevated in COVID-19 patients compared to healthy individuals. Kerget et al concluded that FeNO levels can be used to assess lung parenchymal involvement in COVID-19 patients and that patients with cytokine storms have higher levels of FeNO ( Kerget et al, 2022 ). Whereas the results of a single-center prospective study showed that the more severe the disease, the lower the FeNO levels in those with COVID-19, with patients with measurements ≤ 11.8 PPB having worse clinical outcomes ( Lior et al, 2022 ).…”

Can Fractional Exhaled Nitric Oxide (FeNO) Serve as a Clinical Indicator for Patients Hospitalized with Crimean-Congo Hemorrhagic Fever?

“…Tumor necrosis factor alpha and interleukin 6, which play an important role in the development of SIRS in CCHF (6), also induce the synthesis of nitric oxide (NO), which blocks virus replication and promotes viral clearance early in the infection (7,8). NO is a component of natural immunity, and while its defensive role against bacterial, fungal, and parasitic infections is known, the mechanism by which it exerts its anti-viral activity is not clear (9,10).…”