Discussion
In our study, serum levels of NO, as well as SAPS II and APACHE II scores in patients with ARDS caused by influenza A (H1N1) and the 28-day outcome were evaluated. The main finding of this study is that NO serum levels can serve as a biomarker of better clinical outcome in Influenza A (H1N1)-ARDS patients as shown by ROC curve analysis. We demonstrated that Influenza A (H1N1)-ARDS survivors had significantly higher serum levels of NO (metabolites NO2– and NO3–). SAPS II and APACHE II scores were higher among the non-survivors, and difference among survivors and non-survivors was statistically significant (p<0.05). In addition, serum levels of NO positively correlated with the SAPS II and APACHE II score. Several physiological mechanisms of NO might help in explaining our results. Well known effects of the NO on microcirculation is vasodilatation which consequently increases tissue perfusion [16, 17]. Elevation in dead space in ARDS patient is demonstrated in many studies performed in these patients and one of the reasons for this is because some alveoli are being ventilated but not perfused (shunt) [18]. An increase in perfusion in these parts of the lungs leads to better ventilation to perfusion matching. Regarding the alveolar epithelium, NO has been shown to protect type II alveolar cells from stretch injury [19]. Additional explanation for our main findings is that endogenous NO has a beneficial effect in organs other than the lungs during ARDS. Higher serum levels of NO could help prevent further tissue damage by improving oxygen and nutrient delivery to the tissues while helping decrease the amount of toxic oxygen species [20]. Decreasing platelet and leukocyte adhesion to the endothelium caused by serum NO can protect endothelial tissue [21]. NO would thereby decrease multiorgan failure, which contributes to mortality in ARDS. Finally, NO and NOx have antibacterial effects that may be important in infectious conditions that predispose patients to ARDS [22]. Healthy alveolar epithelium, alveolar macrophage and endothelium cells produce NO, so elevated NO serum levels can be an indicator of a greater percentage of intact lung endothelium and epithelium as a result of a less severe initial injury [23]. Some studies in which NO levels in bronchoalveolar lavage (BAL) were observed, show high levels of NO in ARDS non-survivors [24]. The reason for that can be found in the fact that NO found in BAL is produced exclusively by the lungs, while NO serum levels represent the whole-body production of NO. Prior research on animal models demonstrated a worse outcome in ARDS patients in the presence of elevated NO levels. The reason for this can be explained by the difference in human and animal models. There was no significant difference in age and in preexisting comorbidities in ARDS survivors and ARDS non-survivors in this study.
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. Study similar to ours was performed by McClintock et al.and they found that higher urine nitric oxide is associated with improved outcomes in patients with ALI/ARDS [25].
The limitations of the present study are small sample size; we analyze only one potential biomarker (serum levels of NO) in one time point only and this was a single center study.
In conclusion, we have demonstrated that alterations in serum levels of NO mirror the severity of ARDS caused by influenza A (H1N1) quite well and accurately predict clinical or treatment outcome of critically ill patients with this type of ARDS. This is clinically-relevant as it aids medical decision-making and informs therapeutic strategy in the ICU. Our study suggests that the monitoring of serum levels of NO alone or in combination with SAPS II and/or APACHE II scores in critically ill with ARDS (caused by influenza A H1N1) significantly improves the accuracy of predicting the severity of diseases by physicians and shortens the clinical decision-making time. Thus, this study highlights the potential role of serum levels of NO as specific and accurate biomarker for ARDS caused by influenza A (H1N1), and its correlation with predicting the better clinical outcome, including increased survival, in patients with ARDS caused by influenza A (H1N1).
Author Contributions : designed the research study: PK; performed the research SD, DM, MJ; analyzed the data: TK, BZ; wrote the paper: VDJ, RS
Funding: None
Declaration of interest: None