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.