In this study, we observed that in children with sCAP, biomarkers of OS, inflammation, and ED were significantly higher than healthy children, and it is also higher in asthmatic children with pneumonia than in non-asthmatic children. This is probably because asthma may exacerbate OS and inflammation in children with pneumonia.
Studies have shown the interaction between pneumonia and cardiovascular diseases (CVDs). According to the cohort study of Yeh et al. 2019, patients with CVDs had a higher risk of CAP, and conversely, CVDs risk was intensified with CAP. In recent years, CVDs were considered as an outcome of patients admitted to hospital with pneumonia infection (17). After recovery of CAP in addition to the period of the acute infection, there is still the risk of acute cardiovascular events due to systematic inflammation (18).
The initial stage of molecular and cellular stages leading to CVDs is ED (19–20). OS and inflammation are the two main causes of its creation (21–22).
Studies indicate the underlying respiratory diseases such as asthma may be effective in the severity of pneumonia injuries. Asthma, whose main feature is chronic inflammation in the airway wall (8), is the most common chronic respiratory disease in children, especially in developing countries.
In this study, TNF-α was significantly higher in children with pneumonia and asthma than pneumonia and healthy children. Studies indicate the inflammatory process associated with ED exacerbates the severity of the consequences of CAP (23). Also, recent evidence suggests a critical role for pneumonia infection in the pathogenesis of atherosclerosis by exacerbating OS, inflammation, and ED. Increasing the pro‐inflammatory cytokine TNF‐α as a consequence of pneumonia induce ED by various mechanisms, such as increasing the endothelial permeability and reducing the endothelium‐dependent relaxation. It increased vascular endothelial growth factor (VEGF) as the endothelial permeability mediator and diminishing the half‐life of mRNA encoding for endothelial nitric oxide synthase and decreasing nitric oxide production (24, 25).
In this study, VCAM-1 and PAI-I as two biomarkers of ED were significantly higher in children with pneumonia and asthma than the children with pneumonia only. Also, they were significantly more in children with pneumonia than healthy children. OS and inflammation are closely linked with each other. Inflammatory mediators lead to OS, and reciprocally, OS increases the production of inflammatory mediators with the activation of NF-kB and AP-1 (26). NF-κB and AP-1 are involved in the activation of pro-inflammatory molecules, such as VCAM-1 and PAI-I (27).
In 2015, Lin et al. indicated that TNF-α-induced VCAM-1 expression in human cardiac fibroblasts was mediated by the activation of NF-κB by c-Src-mediated transactivation of the EGF receptor (EGFR)/PI3K/Akt cascade (28). ROSs regulate several cells signaling pathways, such as expression of VCAM-1, resulting in the release of inflammatory mediators (29).
Zhang et al. (2018) reported an increase in MDA and TNF-α and a decrease TAC in CAP (30). Pikuza et al. (2012) reported an evaluation of the content of MDA as the lipid peroxidation indicator with decreasing of antioxidant activity in CAP patients (31). Majewska et al. (2004) ascertained OS development in the lungs at CAP patients (32). Muravlyova et al. (2016) showed that sCAP patients have more levels of oxidative proteins and MDA in erythrocytes than moderate CAP and healthy volunteers (33).
ROSs concentration and time of exposure are two determining factors in the effects of OS in the airway as well as in other organs. Due to damage in biomolecules and inducing intracellular signaling pathways by ROSs, more concentration and longer exposure of ROSs can lead to cell death by apoptosis (34). Accordingly, studies show that the attenuation of OS alleviates the organ damage.
Zhang et al. in 2018 demonstrated the treatment of CAP patients with N-acetylcysteine (NAC) reduces MDA and increases TAC compared with those in the non-NAC group (30). In asthma as a chronic inflammatory airway disease, OS exacerbates airway inflammation by inducing various pro-inflammatory moderators, boosting bronchial hyperresponsiveness, exciting bronchospasm, and increasing mucin secretion (35).