MPP is a common respiratory disease in children. In recent years, the prevalence of RMPP has been increasing, particularly in Asian countries [7, 8]. The specific pathogenesis of RMPP remains unclear, however, pathogenic substances or other host factors may be the cause of lung injury associated with an excessively strong immune response [9–11]. Previous studies have reported that RMPP is associated with more serious lung injury and higher levels of clinical indicators such as CRP, ESR, and LDH, as well as longer recovery time [8, 10, 12]. Therefore, early use of immune modulators is recommended in RMPP rather than waiting for antibiotic treatment to exert an effect; this approach can reduce MP-mediated immune injury and improve treatment efficacy [13–15]. However, there is no specificity in early clinical manifestations of RMPP and early diagnosis is difficult, meaning that early predictors need to be identified.
Clinical cases of MPP complicated with thrombosis are not unusual, and MPP complicated with deep vein thrombosis is frequently reported [4–5]. At present, the mechanism by which Mycoplasma pneumoniae pneumonia causes vascular embolization is not fully understood, and it is primarily considered to be related to immune mediation after vascular injury . Under normal circumstances, the coagulation and fibrinolytic systems are in a dynamic equilibrium state. When coagulation occurs in vivo, thrombin acts on fibrin to activate the fibrinolytic system, and D-D can be formed . D-D is primarily used in clinical settings for the initial diagnosis of pulmonary embolism, and shows diagnostic accuracy in the diagnosis of acute pulmonary embolism. However, D-D has been shown not only to be a special marker of fibrinolytic system but also to be an indicator for monitoring inflammation and severe infection . Levels of D-D are also closely related to the inflammatory response and may reflect the effects of infection on coagulation in infectious diseases. Some studies have reported that the levels of D-D are closely related to the severity of CAP .
Previous studies [19, 20] have reported that levels of D-D in children with MPP were higher than those in healthy children and were also higher in severe cases of MPP compared with mild cases, especially in severe MPP with extrapulmonary complications . However, few studies have reported on D-D levels in RMPP or on the monitoring of D-D levels after treatment. Consistent with previous reports, we found that levels of D-D in the GMPP and RMPP groups were all above the normal range, and that levels in the RMPP group were significantly higher than those in the GMPP group. Elevated D-D levels may imply that hypercoagulability is prevalent in children with MPP and is more severe in children with RMPP, and that vascular endothelial cell injury caused by an excessive inflammatory response may be involved in the mechanism of lung injury in RMPP. In a previous study, the levels of D-D were found to have decreased significantly after a period of treatment, and the final levels after treatment were higher in a group with severe pneumonia compared with a group having mild pneumonia . Our study found 1 week of treatment was associated with a significant decrease in D-D level, although levels remained abnormal in most cases, indicative of a prolonged state of high coagulation and endothelial injury in RMPP.
LDH and CRP, which are elevated in several pulmonary diseases, have previously been associated with RMPP and can be used as early predictors of the condition [10, 11, 21]. In the present study, D-D level was positively correlated with WBC, CRP, and ESR. The increased levels of these analytes may represent a stronger systemic inflammatory response in RMPP, while the positive correlation of D-D with these inflammatory indicators means that D-D level may be used to evaluate the inflammatory response and jointly evaluate the severity of the disease. The average age of patients in the RMPP group was 5.7 years, which was older than that in the GMPP group and was consistent with previous studies , indicating that older children have a stronger immune inflammatory response that can more readily lead to refractory conditions. A previous study showed that CRP ≥ 50 mg/L and LDH ≥ 480 U/L were associated with longer time to radiographic clearance , while the percentage of neutrophils, CRP, and LDH were found in ROC curve analysis to be useful in differentiating patients with RMPP from those with GMPP . In the present study, we found that D-D levels and LDH were positively correlated, and after comparing the predictive value of WBC, CRP, ESR, LDH, and D-D for RMPP by AUC analysis, we found that D-D was better able to predict RMPP compared with the other indexes and may therefore be used in the early detection of refractory cases.
Regarding complications, previous studies have reported that D-D level was positively correlated with extra-pulmonary complications in pediatric patients with MPP ; however, extensive research on D-D level and complications has not been reported to date. In a previous study, a higher level of D-D was associated with more extensive and serious thrombosis . Our results show that elevated levels of D-D had a good predictive ability for pleural effusion and liver injury and that the incidence of pleural effusion increased with increasing D-D level. However, there was no significant difference between the moderately elevated group and the severely elevated group. The incidence of atelectasis was only significantly different between the normal D-D level group and the mildly elevated group and the incidence of rash and myocardial damage did not differ significantly between the four groups, which suggested that severely elevated D-D might not be associated with more complications. However, further research including case studies is needed to verify this hypothesis and thus avoid overtreatment.
At present, controversy remains over the use of anticoagulant treatment in pneumonia . Further research on D-D and pneumonia is therefore needed to clarify the relationship between dynamic changes in D-D and the course and progression of disease, thus allowing the appropriate anticoagulant treatment strategy to be selected.