Introduction
Acute respiratory distress syndrome (ARDS) is not only a global health issue, but also a global health priority, as morbidity and mortality rates remain high. This syndrome (ARDS) was first recognized in the late nineteen-sixties [1]. It is characterized by hypoxemia and bilateral radiographic opacities, with diffuse alveolar damage as main pathological hallmark (i.e., alveolar edema with or without focal hemorrhage, acute inflammation of the alveolar walls, and hyaline membranes) [2]. Most patients who present with an acute, diffuse, inflammatory lung injury that leads to increased pulmonary vascular permeability, increased lung weight, and a loss of aerated tissue need mechanical ventilation as a rescue therapy [3]. ARDS represents a common clinical problem in critically ill patients, especially today in pandemic circumstances (COVID 19); this syndrome is associated with a short‐term risk of mortality as well as significant long‐term risk of morbidity [4-5]. It is well known that lung endothelial and alveolar epithelial damage in ARDS are often caused by oxidative injury [6]. Many biomarkers and mediators of oxidative injury and inflammation have a significant role in this process; some of them such as interferon-γ, interleukin-1β (IL-1β), and tumor necrosis factor-α, lead to increased production of nitrogen oxide species (NOx), particularly nitric oxide (NO), nitrite (NO2-), and nitrate (NO3-) which all cause oxidative injury [7-9]. Once declared “molecule of the year,” NO is involved in multiple pathophysiological processes in ARDS. Nitric oxide readily reacts with superoxide ion to form a highly reactive oxidizing and nitrating intermediate product - peroxynitrite. Peroxynitrite performs rapid oxidation and nitration of proteins α1antitrypsin and surfactant protein A, thereby inhibiting their function. Inhibition of these proteins may create the proinflammatory environment which can lead to development of ARDS. Peroxynitrite cannot be measured directly because of its short half-life, but its presence can be inferred by measuring metabolites such as NO2- and NO3- [10-13]. Therefore, for clinical decision-making and ARDS treatment, accurate prediction of ARDS severity in the early stage and administration of appropriate therapy are the keys to improving therapeutic success in these patients. However, at present an objective and effective clinical outcome predictor or prognosticator of ARDS (especially caused by influenza A H1N1) remains unknown. Many studies have been undertaken till date, and no single biomarker has been identified as a predictor for the outcome in ARDS (caused by influenza A H1N1), rather a combination of biomarkers and scoring systems was suggested to predict the patients’ outcomes [14]. There is a small number of studies which investigated serum levels of NO in patients with ARDS caused by H1N1 pneumonia in relation to survival. Hence, the present study was created to investigate serum levels of NO, age, gender, and comorbid conditions including: Simplified Acute Physiology Score (SAPS II), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, in patients with ARDS (caused by influenza A H1N1) and its ability to predict the patients’ outcomes.