Discussion:
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 infection17. 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 creation21-22.
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, is the most common
chronic respiratory disease in children, especially in developing
countries 8.
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 production24, 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-126. NF-κB and AP-1 are involved in the
activation of pro-inflammatory molecules, such as vascular cell adhesion
molecule one (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 patients31. Majewska et al. (2004) ascertained
OS development in the lungs at CAP patients32. 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.
Conclusions: Significant changes in OS, inflammation, and ED
biomarkers occur in asthma children with pneumonia compared with
pneumonia children without asthma and healthy children. Our findings
amplify the growing evidence supporting the concept that endothelial
activation, inflammation, and OS play an important mechanistic role of
effects asthma in the pathogenesis of pneumonia. Treatment with
antioxidants and anti- VCAM-1 pharmacological agents may help reduce
outcomes in these children.