Abstract
Background
This study aimed to investigate the clinical features and risk factors of Mycoplasma pneumoniae necrotizing pneumonia (MPNP) in children, providing a scientific basis for early diagnosis, effective treatment, and preventive strategies.
Methods
A retrospective analysis of 138 children diagnosed with Mycoplasma pneumoniae pneumonia (MPP) admitted to the Children’s Hospital Affiliated to Zhengzhou University from August 2023 to December of the same year was performed. The patient population was divided into the MPNP group (41 cases) and the N-NP (N-Necrotizing pneumonia) group (97 cases) based on the presence or absence of comorbid MPNP. Baseline data, laboratory results, and imaging characteristics were compared. Logistic regression was used to identify risk factors for MPNP, and receiver operating characteristic (ROC) curve analysis was applied to evaluate diagnostic efficacy.
Results
Compared with the N-NP group, children in the MPNP group showed older age, longer hospitalization days, higher fever peak and fever days, and higher rates of chest pain, dyspnea, shortness of breath and combined extrapulmonary complications (all P < 0.05). Laboratory findings showed elevated white blood cells (WBC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin−6 (IL−6), serum amyloid A (SAA), serum ferritin (SF), D-dimer (D-D), alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin A (IgA), immunoglobulin M (IgM), and lactate dehydrogenase (LDH). While total protein (TP), Albumin (ALB), complement component 4 (C4) levels were significantly lower (P < 0.05). The proportion of children with combined pleural effusion and the percentage of those who underwent fiberoptic bron-choscopic alveolar lavage (FBAL) with alveolar lavage were higher in the MPNP group than in the N-NP group (P < 0.05). Multivariate logistic regression identified age, fever days, D-D, LDH and pleural effusion as independent risk factors for MPNP. ROC curve analysis indicated that children with MPP who were aged > 5.45 years, fever days > 7.5 days, D-D > 0.73 mg/L, LDH > 399 U/L and concurrent pleural effusion predicted MPNP with a sensitivity of 0.878, specificity of 0.876, and area under the curve (AUC) of 0.940 (95%CI: 0.900−0.979).
Conclusion
Age, fever days, D-D, LDH, and pleural effusion are independent risk factors for MPNP in children. These factors should be closely examined in clinical practice in children with MPP to alert them to the potential risk of NP. Early identification of changes in these risk factors and implementation of timely and effective interventions hold significant clinical value for preventing and controlling the risk of MPP children developing MPNP.
Keywords: Mycoplasma pneumoniae, Necrotizing pneumonia, Children, Risk factor
Background
In the autumn of 2023, a wave of respiratory infections dominated by Mycoplasma pneumoniae (MP) posed a serious challenge to pediatric healthcare systems across China. The distinguishing feature of this MP epidemic in China is the high rate of resistance to macrolide antibiotics, coupled with a tendency to be complicated with severe conditions and the development of critical illnesses [1]. As a serious complication of MPP, Mycoplasma pneumoniae necrotizing pneumonia (MPNP) is characterized by persistent high fever and cough as its main clinical manifestations; severe patients may also present with chest pain, dyspnea, and hypoxemia [2]. Diagnosis relies heavily on chest imaging, with CT as the gold standard for detecting necrotic changes. However, early diagnosis remains challenging, with studies reporting a median delay of 17 days from symptom onset to CT confirmation of NP [3]. Such delays increase medical burden, prolong hospitalization, and may lead to pulmonary sequelae. Therefore, understanding the clinical characteristics and risk factors of MPNP is of great clinical importance. This study retrospectively analyzes the clinical features of MPNP in children and explores its risk factors to improve early diagnosis and management.
Materials and methods
Study population
138 children diagnosed with MPP who were enrolled to Children’s Hospital Affiliated to Zhengzhou University from August to December 2023 were selected. According to whether the children had necrotic lesions in their lungs, they were divided into the MPNP group and the N-NP group.
Inclusion and exclusion criteria
The inclusion criteria for MPP were as follows: ① Age < 18 years; ② MPP diagnosis followed the Guidelines for the Diagnosis and Treatment of Mycoplasma pneumoniae Pneumonia in Children (2023 Edition) [4], and met the following requirements: (1) with fever, cough, wheezing, dyspnea, pulmonary rales and other respiratory manifestations; (2) chest imaging examinations were consistent with pneumonia; (3) Compliance with ≥ 1 item: A: single serum MP antibody titer ≥ 1:160 (PA method); in the course of disease, the titer of double serum MP antibody increased by four times or more; B: positive MP-DNA or MP-RNA.
The inclusion criteria for the MPNP group were ① Diagnosis followed MPP; ② Met the pulmonary necrosis diagnostic criteria, that is, the results of chest CT plain scan or enhanced scan clearly showed necrotic cavities or necrotic non-enhanced areas within the pulmonary consolidation area; ③ The clinical data of the children were complete.
The exclusion criteria were: ① Children with congenital diseases, asthma, pulmonary tuberculosis, and autoimmune diseases, etc.; ② Children in the recovery period, specifically defined as the disease course has exceeded 4 weeks, body temperature has been stable for more than 1 week, or the imaging examination shows that the lesion has absorbed and shows an improving trend; ③ Children with nucleic acid testing of throat swabs or sputum culture showing co-infection with other pathogens.
Data collection
The patients’ data after admission were collected using the hospital medical record management system. The contents included basic information, clinical symptoms and signs assessment at admission, comprehensive examination of complications, laboratory test indicators within 24 h of admission, lung imaging and FBAL results.
Statistical analysis
Statistical analysis was conducted using SPSS 27.0 software. Quantitative data that were normally distributed and had equal variances between the two groups were expressed as mean ± standard deviation and t-tests were used for comparisons between groups; non-normal distribution data were described by the median P50 (P25, P75), and the Mann-Whitney U test was used for analysis of differences between groups. Categorical variables were presented in the form of number or percentage, and χ2 tests or Fisher’s exact tests were used; multivariate logistic regression analysis was performed to identify independent risk factors for MPNP occurrence. The ROC curve was used to evaluate the predictive effect of each risk factor. P < 0.05 indicated statistical significance.
Ethic approval
All methods were performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments or comparable ethical standards. Written informed consent was obtained from all participants; if the participants were under 18 years of age, consent was obtained from a parent and/or legal guardian. This study was approved by the National Children’s Regional Medical Center, Henan Children’s Medical Center, and Henan Pediatric Disease Clinical Medical Research Center (ethical approval No: 2024-K-028).
Results
Baseline data
A total of 138 children with MPP were enrolled in this study, including 41 cases in the MPNP group and 97 cases in the N-NP group. As shown in Table 1, compared with the N-NP group, the MPNP group had significantly older age, longer fever days, and prolonged hospitalization days (P < 0.05). All enrolled children presented with fever and cough prior to admission. In the MPNP group, 34 cases (80.48%) developed high fever, with a significantly higher proportion than that in the N-NP group; additionally, 3 cases (7.31%) had hyperpyrexia (T > 41℃). The fever peak in the MPNP group was significantly higher than that in the N-NP group (P < 0.001). Furthermore, the proportions of children with dyspnea and chest pain in the MPNP group were notably higher than those in the N-NP group (P < 0.001, Table 1).
Table 1.
Comparison of baseline data between the MPNP group and the N-NP group
| Baseline data | MPNP group (n = 41) | N-NP group (n = 97) | P value |
|---|---|---|---|
| Sex (male) | 22 (53.7%) | 58 (59.8%) | 0.632 |
| Age (years) | 7.0 (5.5, 8.5) | 6.0 (3.9, 7.0) | 0.002 |
| Hospitalization days (days) | 13.0 (11.0, 15.5) | 7.0 (6.0, 9.0) | < 0.001 |
| Fever (N, %) | 41 (100%) | 97 (100%) | NA |
| Fever days (days) | 9.0 (8.0, 13.0) | 7.0 (5.0, 10.0) | < 0.001 |
| Fever peak (℃) | 40.0 (39.55, 40.4) | 39.5 (39.0, 39.8) | < 0.001 |
| Cough (N, %) | 41 (100%) | 97 (100%) | NA |
| Shortness of breath (N, %) | 7 (17.1%) | 2 (2.1%) | 0.004 |
| Dyspnea (N, %) | 11 (26.8%) | 2 (2.1%) | < 0.001 |
| Chest pain (N, %) | 6 (14.6%) | 0 | < 0.001 |
| Extrapulmonary complications (N, %) | 37 (90.2%) | 13 (13.4%) | < 0.001 |
| Circulatory system (N, %) | 14 (34.1%) | 3 (3.1%) | < 0.001 |
| Pericardial effusion (N, %) | 10 (24.4%) | 2 (2.1%) | < 0.001 |
| Myocardial damage (N, %) | 4 (9.8%) | 1 (1.0%) | 0.045 |
| Digestive system (N, %) | 21 (51.2%) | 5 (5.2%) | < 0.001 |
| Hepatic function damage (N, %) | 18 (43.9%) | 2 (2.1%) | < 0.001 |
| Ascites (N, %) | 12 (29.3%) | 10 (10.3%) | 0.005 |
| Blood system (N, %) | 22 (53.7%) | 3 (3.1%) | < 0.001 |
| Coagulation disorder dysfunction (N, %) | 17 (41.5%) | 1 (1.0%) | < 0.001 |
| Hypoproteinemia (N, %) | 5 (12.2%) | 0 | 0.003 |
| Blood platelet disorders (N, %) | 2 (4.9%) | 1 (1.0%) | 0.437 |
| Cutaneous mucosal system (N, %) | 13 (31.7%) | 5 (5.2%) | < 0.001 |
Extrapulmonary complications occurred in 36.2% (50 cases) of children across both groups, with no neurological complications observed. Specifically, circulatory complications were noted in 12.3% (17 cases), including 12 cases of pericardial effusion and 5 cases of myocardial damage. Digestive complications were present in 18.8% (26 cases), comprising 20 cases of hepatic function impairment and 22 cases of ascites. Hematological complications occurred in 18.1% (25 cases), involving 18 cases of coagulation dysfunction, 5 cases of hypoproteinemia, and 3 cases of platelet disorders. Mucocutaneous complications were identified in 13.0% (18 cases). Compared with the N-NP group, the MPNP group had significantly higher incidences of circulatory, digestive, hematological, and mucocutaneous complications (P < 0.001, Table 1).
Laboratory tests
No significant differences were observed in platelet count (PLT), erythrocyte sedimentation rate (ESR), fibrinogen concentration (Fg), globulin (GLB), immunoglobulin G (IgG), immunoglobulin A (IgA), or complement component 3 (C3) between the two groups (P > 0.05). Compared with the N-NP group, the MPNP group had significantly elevated levels of WBC, NLR, CRP, PCT, IL−6, SAA, SF, D-D, LDH, ALT and AST; in contrast, the levels of TP, Alb, and A/G were significantly decreased (P < 0.001; Table 2).
Table 2.
Comparison of laboratory test results between the MPNP group and the N-NP group
| Laboratory tests | MPNP group (n = 41) | N-NP group (n = 97) | P value |
|---|---|---|---|
| WBC (10^9/L) | 9.83 (6.99, 12.86) | 7.51 (6.05, 10.34) | 0.003 |
| PLT (10^9/L) | 320 (258, 418.5) | 314 (243.5, 367.5) | 0.462 |
| NLR | 3.47 (2.15, 6.48) | 2.02 (1.36, 2.95) | < 0.001 |
| CRP (mg/L) | 28.32 (15.61, 65.26) | 9.68 (3.24, 20.40) | < 0.001 |
| ESR (mm/h) | 31.0 (23.0, 47.5) | 29.0 (17.5, 47.0) | 0.339 |
| PCT (ng/mL) | 0.16 (0.09, 0.35) | 0.08 (0.05, 0.12) | < 0.001 |
| IL−6 (pg/mL) | 10.19 (4.43, 50.08) | 6.32 (2.78, 10.74) | 0.003 |
| SAA (mg/L) | 483.43 (328.80, 1261.91) | 135.61 (44.29, 270.38) | < 0.001 |
| SF (ng/mL) | 210.50 (141.35, 517.50) | 78.60 (53.45, 108.35) | < 0.001 |
| D-D (mg/L) | 1.61 (0.78, 3.50) | 0.44 (0.33, 0.62) | < 0.001 |
| Fg (mg/dL) | 3.47 (2.99, 4.12) | 3.56 (2.90, 3.92) | 0.445 |
| LDH (U/L) | 515.00 (353.30, 774.00) | 310.00 (278.00, 393.50) | < 0.001 |
| ALT (U/L) | 40.60 (14.45, 80.00) | 14.90 (11.35, 23.00) | < 0.001 |
| AST (U/L) | 38.90 (27.00, 86.90) | 27.90 (23.65, 35.40) | < 0.001 |
| TP (g/L) | 63.50 (58.45, 67.70) | 68.30 (65.90, 70.85) | < 0.001 |
| ALB (g/L) | 36.20 (32.80, 39.60) | 39.60 (39.55, 44.35) | < 0.001 |
| GLB (g/L) | 26.90 (23.90, 30.05) | 26.62 (23.55, 28.85) | 0.213 |
| A/G | 1.34 (1.19, 1.49) | 1.53 (1.42, 1.81) | < 0.001 |
| IgG (g/L) | 9.33 (8.06, 11.35) | 9.81 (8.19, 10.90) | 0.549 |
| IgM (g/L) | 1.64 (1.26, 2.69) | 1.27 (1.01, 1.79) | 0.007 |
| IgA (g/L) | 1.29 (0.98, 2.08) | 1.26 (0.94, 1.90) | 0.273 |
| C3 (g/L) | 1.24 (1.05, 1.50) | 1.33 (1.22, 1.46) | 0.054 |
| C4 (g/L) | 0.27 (0.19, 0.36) | 0.33 (0.26, 0.40) | 0.005 |
Imaging findings and bronchoscopic manifestations
In children with MPP, pulmonary inflammatory changes are often characterized by extensive pulmonary consolidation, accompanied by atelectasis and other manifestations. The median duration from symptom onset to the diagnosis of pulmonary necrosis via chest CT in the MPNP group was 16 ± 4.7 days. The incidence of pleural effusion in the MPNP group was 92.7% (38/41), which was significantly higher than that in the N-NP group [37.1% (36/97)] (P < 0.001). However, no significant differences were observed between the two groups regarding consolidation location, pulmonary atelectasis, diaphragmatic lymphadenopathy, pleural thickening, bronchial stenosis, bronchiectasis, or pulmonary abscess (Table 3).
Table 3.
Comparison of imaging between MPNP group and N-NP group
| Imaging results | MPNP group (n = 41) |
N-NP group (n = 97) |
P value |
|---|---|---|---|
| Bilateral lung consolidation (N, %) | 25 (60.98%) | 57 (58.76%) | 0.478 |
| Consolidation left lung lobe (N, %) | 32 (78.04%) | 58 (59.79%) | 0.651 |
| Consolidation right lung lobe (N, %) | 34 (82.92%) | 65 (67.01%) | 0.342 |
| Pulmonary atelectasis (N, %) | 2 (4.9%) | 3 (3.1%) | 0.988 |
| Diaphragmatic lymph node enlargement (N, %) | 4 (9.8%) | 6 (6.2%) | 0.704 |
| Pleural effusion (N, %) | 38 (92.7%) | 36 (37.1%) | < 0.001 |
| Pleural thickening (N, %) | 6 (14.6%) | 5 (5.2%) | 0.125 |
| Pulmonary embolism (N, %) | 5 (12.2%) | 0 | 0.003 |
| Bronchial stenosis (N, %) | 3 (7.3%) | 1 (1.0%) | 0.145 |
| Bronchiectasis (N, %) | 0 | 1 (1.0%) | 1.0 |
| Pulmonary abscess (N, %) | 1 (2.4%) | 0 | 0.656 |
| Duration from symptom onset to CT diagnosis of pulmonary necrosis (days) | 16 ± 4.7 | NA | NA |
All cases in the MPNP group underwent FBAL. Among them, 3 cases received three bronchoscopic lavage sessions, 38 cases underwent the procedure within 7 days of admission, and only 3 cases were examined after 7 days (the hospitalization days of these 3 cases exceeded 20 days). Fiberoptic bronchoscopy findings were mainly bronchial endothelitis, including plastic bronchitis and other conditions. Compared with the N-NP group, the MPNP group had a significantly higher proportion of patients who underwent FBAL and those who received two or more FBAL sessions (P < 0.05). No significant differences were noted between the two groups in other endoscopic observation indicators (Tables 3 and 4).
Table 4.
Comparison of bronchoscopic manifestations between MPNP group and N-NP group
| Bronchoscopic manifestations | MPNP group (n = 41) | N-NP group (n = 97) | P value |
|---|---|---|---|
| FBAL (N, %) | 41 (100%) | 61 (62.89%) | < 0.001 |
| more than 2 times FBAL (N, %) | 38 (92.68%) | 9 (9.28%) | < 0.001 |
| bronchitis endothelitis (N, %) | 22 (53.66%) | 62 (63.92%) | 0.262 |
| plasticbronchitis (N, %) | 9 (22.0%) | 1 (1.0%) | < 0.001 |
In this study, children with MPP complicated by NP routinely received macrolide antibiotics for a 5–7-day course. For patients with poor treatment response, second-line agents (e.g., tetracyclines, levofloxacin) were administered. All patients received corticosteroids and FBAL. Nine patients required airway support (including oxygen therapy and mechanical ventilation), and one patient underwent closed-chest drainage. Thirteen patients received intravenous immunoglobulin.
Logistic regression analysis
Based on the results of univariate analysis (t-tests, Mann-Whitney U tests, and χ² tests), variables with clinical relevance and statistical significance (P < 0.05) were selected for further multivariate logistic regression analysis. The results indicated that age, fever days, D-D, LDH, and pleural effusion were independent risk factors for NP in children with MPP (Table 5).
Table 5.
Logistic regression analysis results of MPNP group
| Variables | Univariate logistic regression | Multivariate logistic regression | ||||
|---|---|---|---|---|---|---|
| OR | 95%CI | P | OR | 95%CI | P | |
| Age | 1.284 | 1.090–1.513 | 0.003 | 1.346 | 1.041–1.739 | 0.023 |
| Fever days | 1.284 | 1.205–1.585 | < 0.001 | 1.3523 | 1.116–1.641 | 0.002 |
| Fever peak | 4.331 | 2.111–8.888 | < 0.001 | |||
| Shortness of breath | 0.102 | 0.020–0.516 | 0.006 | |||
| Dyspnea | 0.057 | 0.012–0.274 | < 0.001 | |||
| Chest pain | 0.000 | NA | 0.999 | |||
| Complication | 0.017 | 0.005–0.055 | < 0.001 | |||
| Circulatory system | 0.062 | 0.016–0.230 | < 0.001 | |||
| Digestive system | 0.052 | 0.017–0.154 | < 0.001 | |||
| Blood system | 0.028 | 0.007–0.101 | < 0.001 | |||
| Cutaneous mucosal system | 0.117 | 0.038–0.357 | < 0.001 | |||
| WBC | 1.116 | 1.057–1.285 | 0.002 | |||
| PCT | 50.710 | 3.471−740.835 | 0.004 | |||
| NLR | 1.414 | 1.174–1.702 | < 0.001 | |||
| CRP | 1.057 | 1.032–1.083 | < 0.001 | |||
| IL−6 | 1.045 | 1.018–1.073 | < 0.001 | |||
| SAA | 1.004 | 1.002–1.005 | < 0.001 | |||
| SF | 1.003 | 1.001–1.005 | 0.002 | |||
| D-D | 2.303 | 1.544–3.436 | < 0.001 | 1.4156 | 1.027–1.952 | 0.034 |
| ALT | 1.032 | 1.105–1.049 | < 0.001 | |||
| AST | 1.028 | 1.012–1.045 | < 0.001 | |||
| TP | 0.885 | 0.827–0.948 | < 0.001 | |||
| ALB | 0.713 | 0.631–0.807 | < 0.001 | |||
| A/G | 0.006 | 0.001–0.055 | < 0.001 | |||
| IgM | 1.848 | 1.247–2.738 | 0.002 | |||
| Complement C4 | 0.008 | 0.001–0.334 | 0.011 | |||
| LDH | 1.004 | 1.002–1.007 | < 0.001 | 1.005 | 1.001–1.009 | 0.013 |
| Pleural effusion | 0.047 | 0.013–0.163 | < 0.001 | 0.102 | 0.0178−0.590 | 0.011 |
| Plasticbronchitis | 0.037 | 0.005–0.304 | 0.002 | |||
ROC curve
A ROC curve analysis was further performed to verify the predictive efficacy of the identified independent risk factors. The results indicated that age, fever days, D-D, LDH, and pleural effusion each exhibited significant clinical value in predicting MPNP in children with MPP (Fig. 1). The optimal cut-off values determined by the ROC curve were as follows: age > 5.45 years, fever days > 7.5 days, D-D > 0.73 mg/L, LDH > 399 U/L, and concurrent pleural effusion. Children meeting these criteria were at a significantly higher risk of developing MPNP. Furthermore, the combined use of the aforementioned indicators further improved the predictive efficacy for MPNP [area under the curve (AUC) = 0.940, 95%CI: 0.900−0.979] (Table 6).
Fig. 1.
The results of ROC curve
Table 6.
Results of the ROC curve
| Variable | AUC | Cut-off value | Youden index | Sensitivity | Specificity | 95%CI | P value |
|---|---|---|---|---|---|---|---|
| Age (years) | 0.691 | 5.45 | 0.352 | 0.878 | 0.474 | 0.602–0.780 | < 0.001 |
| Fever days (days) | 0.786 | 7.50 | 0.509 | 0.829 | 0.680 | 0.710–0.862 | < 0.001 |
| D-D (mg/L) | 0.889 | 0.73 | 0.699 | 0.854 | 0.845 | 0.826–0.952 | < 0.001 |
| LDH (U/L) | 0.848 | 399 | 0.582 | 0.829 | 0.753 | 0.952−0.919 | < 0.001 |
| Pleural effusion | 0.778 | - | 0.556 | 0.927 | 0.629 | 0.699–0.857 | < 0.001 |
| Joint variable | 0.940 | - | 0.754 | 0.878 | 0.876 | 0.900−0.979 | < 0.001 |
Discussion
MP is a key pathogen of respiratory infections in children and a major cause of community-acquired pneumonia (CAP), accounting for 32.4% of CAP cases in children aged 6 months to 14 years in China [5]. It has gradually become one of the leading etiologies of NP in children in China [6]. NP is characterized by necrosis and liquefaction of lung tissue; delayed diagnosis and treatment may lead to severe sequelae such as bronchopleural fistula, pyothorax, respiratory failure, and septic shock [7]. Therefore, actively exploring the risk factors of MPNP, achieving early diagnosis and intervention, and avoiding serious sequelae have become the focus of clinical research. This study systematically analyzed the clinical characteristics of MPNP in children with MPP through retrospective analysis and explored its independent risk factors, aiming to provide a reference for the early identification and treatment of MPNP.
Previous studies [8, 9] have reported that MPP is more common in preschool and school-age children; especially severe MPP (SMPP) is prevalent in preschool children, while children under 3 years old with MPP rarely present with severe conditions such as pulmonary consolidation and MPNP. This phenomenon is attributed to the body’s immune response mechanism: older children typically exhibit a stronger immune response. Upon MP infection, the immune system is strongly activated, releasing a large number of inflammatory cells and mediators, activating coagulation factor XII, and initiating the intrinsic coagulation pathway. This leads to the formation of microthrombi in pulmonary capillaries and subsequent ischemic necrosis, which is consistent with the “immune overactivation-coagulation disorder” theoretical framework, thereby increasing the risk of MPNP [10]. In this study, the median age of children in the MPNP group was 7.0 (5.5, 8.5) years, which is consistent with domestic and international studies. For example, Xue et al. [11, 12] found that the median age of children with MPP complicated by MPNP was 84.00 months, and age > 7.5 years was an independent risk factor for MPNP. Logistic regression analysis in our study also confirmed that age is an independent risk factor for MPNP in children with MPP, with older children facing a higher risk of developing the condition. Notably, the duration of fever has also been identified as an independent risk factor for MPNP in previous studies [13], which coincides with our findings.
The pathogenesis of MPNP involves direct invasion by NP and triggered immune damage effects [14], these processes activate the coagulation cascade, leading to a hypercoagulable state; simultaneously, the body’s fibrinolytic, kinin, and complement systems are sequentially activated, disrupting the coagulation-fibrinolysis balance [15]. This contributes to the formation of emboli in pulmonary capillaries, ultimately resulting in ischemia and necrosis of lung parenchyma [16]. D-D, a fibrin degradation product, directly reflects the hypercoagulable state and microthrombosis in vivo, which is an inevitable consequence of coagulation mechanism involvement in necrotic processes. Elevated D-D levels are closely associated with the severity of clinical symptoms and chest imaging changes in MPP patients [10]. Wen et al. [17] also pointed out that D-D is a biomarker for predicting MPNP, which was verified in our study: D-D levels in the MPNP group were significantly higher than those in the N-NP group, and D-D > 0.75 mg/L was an independent risk factor for MPNP in children with MPP. Therefore, close monitoring of D-D levels in children with MPP is recommended in clinical practice, with early anticoagulant intervention when appropriate. LDH is a biomarker of tissue damage, widely distributed in various tissues. MP infection-induced lung tissue damage increases cell membrane permeability, leading to elevated serum LDH [18]. Studies [19, 20] have noted that LDH levels are associated with the development of pulmonary complications in MPP, which is consistent with our results: LDH levels in the MPNP group were significantly higher than those in the N-NP group, and LDH > 399 U/L was an independent risk factor for pulmonary necrosis in children with refractory MPP (RMPP).
Imaging analysis of children with MPP in this study showed that the incidence of pleural effusion in the MPNP group (38 cases, 92.7%) was significantly higher than that in the N-NP group (36 cases, 37.1%). Logistic regression analysis further identified pleural effusion as an independent risk factor for MPNP in children with MPP, which was confirmed by ROC curve analysis. This is consistent with the findings of Yoon et al. [21, 22], who reported that lung imaging findings are associated with the prognosis of MPP: children with concurrent pleural effusion have longer hospitalization days, delayed absorption of lung lesions, and a higher risk of intrapulmonary and extrapulmonary complications. This phenomenon is attributed to MP infection-induced pleural involvement, which triggers an inflammatory response and exudation, increased capillary permeability, and leakage of proteins and fluids into the pleural cavity, leading to pleural effusion. The severity of the inflammatory response is positively correlated with the amount of pleural effusion [8, 23]. However, it is important to note the limitations of pleural effusion as a predictive indicator: both pleural effusion and MPNP are diagnosed via chest CT. Once pleural effusion is detected, the patient has typically already undergone CT scanning, which can directly confirm the presence of MPNP; thus limiting the practical predictive value of pleural effusion, as the predictive indicator loses its significance after the disease has been diagnosed. Nevertheless, the high correlation between pleural effusion and MPNP still suggests that children with pleural effusion detected on lung imaging should receive early intervention, especially fiberoptic bronchoscopic alveolar lavage (FBAL), to promote the absorption of lung inflammation and shorten the disease course.
In this study, IL−6, SAA, and SF were significantly elevated in the MPNP group, indicating that the degree of systemic inflammatory response is associated with lung necrosis. Additionally, studies [24] have found that children with MPP accompanied by elevated ALT, persistent fever, and dyspnea have an increased risk of progressing to severe or critical conditions. Elevated ALT levels reflect the binding of MP to hepatocyte surface fibronectin via the pyruvate dehydrogenase pathway, making it a sensitive indicator of hepatocyte damage and providing prognostic value for assessing children with MPP [25]. However, due to the small sample size of this study, these indicators were not identified as independent risk factors and require further validation in larger cohorts.
Furthermore, the combined use of age, fever duration, D-D, LDH, and pleural effusion for predicting MPNP yielded a sensitivity of 0.878, specificity of 0.876, and area under the AUC of 0.940, which is higher than the predictive efficacy of individual indicators. This suggests that the combined model has superior clinical value for early identification of MPNP.
Limitations
① This study is a single-center retrospective analysis with a limited sample size. The high incidence of pulmonary necrosis may be associated with the peak prevalence period of MP infection and the concentration of medical resources at the study center. ② Cases of MPP complicated by other pathogens were excluded, potentially overlooking co-infection as a key pathogenic factor and failing to fully elucidate the mechanisms of multi-pathogen synergy. Future large-scale, multicenter prospective studies are needed to validate the association between these indicators and disease progression stages, thereby comprehensively characterizing the clinical features of MPP complicated by MPNP and better guiding clinical management.
Conclusion
School-age children with MPP who have persistent high fever after active treatment, accompanied by significant elevations in D-D and LDH levels as well as pleural effusion, require close attention to the possibility of concurrent MPNP. Early identification and effective clinical intervention are essential; enhanced chest CT examination should be performed when necessary to clarify the extent of lung necrosis.
Acknowledgements
All the authors are grateful to the data collectors and study participants.
Abbreviations
- MP
Mycoplasma pneumoniae
- MPP
Mycoplasma pneumoniae pneumonia
- NP
Necrotizing pneumonia
- MPNP
Mycoplasma pneumoniae necrotizing pneumonia
- SMPP
Severe Mycoplasma pneumoniae pneumonia
- RMPP
Refractory Mycoplasma pneumoniae pneumonia
- ROC
Receiver operating characteristic
- WBC
White blood cells
- NLR
Neutrophil-to-lymphocyte ratio
- PLT
Platelet count
- CRP
C-reactive protein
- ESR
Erythrocyte sedimentation rate
- PCT
Procalcitonin
- IL−6
Interleukin−6
- SAA
Serum amyloid A
- SF
Serum ferritin
- D-D
D-Dimer
- LDH
Lactate dehydrogenase
- ALT
Alanine aminotransferase
- AST
Aspartate aminotransferase
- ALB
Albumin
- A/G
Albumin/Globulin ratio
- GLB
Globulin
- IgG
Immunoglobulin G
- IgM
Immunoglobulin M
- IgA
Immunoglobulin A
- C3
Complement component 3
- C4
Complement component 4
- TP
Total protein
- Fg
Fibrinogen Concentration
- FBAL
Fiberoptic bron-choscopic alveolar lavage
- CAP
Community-acquired pneumonia
Author contributions
YJG: Conceptualization, Supervision. YHZ and TF: Data curation, Methodology, Writing-Original draft preparation. LNX: Supervision, Writing- Reviewing and Editing. All authors contributed to and reviewed the final submitted manuscript.
Funding
No funding was secured for this study.
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
All methods were performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments or comparable ethical standards. Written informed consent was obtained from all participants; if the participants were under 18 years of age, consent was obtained from a parent and/or legal guardian. This study was approved by the National Children’s Regional Medical Center, Henan Children’s Medical Center, and Henan Pediatric Disease Clinical Medical Research Center (ethical approval No: 2024-K-028).
Consent for publication
Not applicable.
Conference presentation
None of the study findings have been presented at any conference previously. This research is not part of a PhD thesis.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.