High-Dose versus Low-Dose Methylprednisolone in the Treatment of Pediatric Refractory Mycoplasma Pneumoniae Pneumonia: A Real-World Study

High-Dose versus Low-Dose Methylprednisolone in the Treatment of Pediatric Refractory Mycoplasma Pneumoniae Pneumonia: A Real-World Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article High-Dose versus Low-Dose Methylprednisolone in the Treatment of Pediatric Refractory Mycoplasma Pneumoniae Pneumonia: A Real-World Study Lanlan Meng, Xintan Xu, Jun Ning, Wen Li, Qian Dong, Xueyun Ren, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6379936/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Refractory Mycoplasma pneumoniae pneumonia (RMPP) is a critical pediatric condition with persistent symptoms despite antibiotic treatment. The optimal corticosteroid dosing for RMPP remains controversial. This study evaluates the effectiveness and safety of high and low doses of methylprednisolone for treating pediatric RMPP. Methods This retrospective study included 66 children diagnosed with RMPP between October 2023 and October 2024. Patients were categorized into two groups: high-dose methylprednisolone (≥ 3 mg/kg/day) and low-dose (< 3 mg/kg/day). Clinical outcomes, hospitalization costs, biomarkers, radiological features, and the safety of methylprednisolone therapy were assessed. Results The high-dose group had a significantly shorter time to defervescence (1.47 ± 0.83 days vs. 2.14 ± 1.66 days, P = 0.04), but no significant differences in hospital stay length or costs. Laboratory findings showed higher D-dimer levels in the high-dose group (1.64 mg/L vs. 1.12 mg/L, P = 0.014). ROC analysis identified an LDH cutoff of 333.5 U/L as a potential predictor for high-dose methylprednisolone use (AUC = 0.681, P = 0.036). Both groups demonstrated good tolerability to methylprednisolone, with no severe adverse effects, except for one case of increased intraocular pressure. Conclusion High-dose methylprednisolone reduces defervescence time, but does not decrease hospital stay length or costs in children with RMPP. Elevated LDH and D-dimer levels may serve as biomarkers for disease severity and guide corticosteroid dosing. Refractory Mycoplasma pneumoniae pneumonia Methylprednisolone dosing Corticosteroid therapy Inflammatory biomarkers Figures Figure 1 Figure 2 Background Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children, responsible for approximately 10%-40% of pediatric cases[ 1 ]​​. In school-age children, MP is the leading causative pathogen, with a prevalence rate of 56.7%[ 2 ]. While most MP infections are self-limiting, some cases progress to refractory Mycoplasma pneumoniae pneumonia (RMPP), characterized by persistent clinical symptoms and radiological deterioration despite appropriate antibiotic treatment​[ 3 ]. RMPP is often associated with pulmonary consolidation, atelectasis, and pleural effusion, leading to severe complications such as necrotizing pneumonia and bronchial obliteration​​[ 4 ]. The emergence of macrolide-resistant Mycoplasma pneumoniae (MRMP) has exacerbated this issue, complicating the management of RMPP and leading to prolonged illness and increased morbidity[ 5 ].​​ Currently, treatment strategies for RMPP primarily focus on the use of immune modulators, especially methylprednisolone, to suppress the excessive immune response that exacerbates lung inflammation and tissue damage[ 6 ]​. While corticosteroids are generally effective in reducing inflammation, the optimal dosage, and overall efficacy of corticosteroid therapy remain controversial. Some studies suggest that high-dose methylprednisolone is effective in controlling severe inflammation and shortening the duration of illness, without significantly increasing adverse effects​[ 7 , 8 ]. Conversely, low-dose methylprednisolone has been found to effectively control the inflammatory response while exhibiting a more favorable side-effect profile​[ 6 ]. In addition, the use of corticosteroids in MRMP infections, especially in patients with clinical deterioration despite initial macrolide therapy, remains a crucial area of study​[ 5 ]. Prompt diagnosis and intervention are vital in preventing the progression of the disease and avoiding complications​. Therefore, our study aims to conduct a retrospective analysis of a real-world data to evaluate the effectiveness and safety of different doses of methylprednisolone in treating pediatric RMPP, and to investigate its association with clinical outcomes, immune biomarkers, treatment duration, and hospitalization costs. Methods Study subjects This is a retrospective real-world study conducted at the Pediatric Department of the Affiliated Hospital of Jining Medical University from October 2023 to October 2024. This study was approved by the Institutional Review Board of Affiliated Hospital of Jining Medical University (No: 2023-09-C032), and complies the Declaration of Helsinki. Children diagnosed with RMPP were included. The diagnosis of Mycoplasma pneumoniae pneumonia (MPP) was based on established criteria[ 4 ]: (1) respiratory symptoms, with or without fever; (2) abnormal pulmonary auscultation findings; (3) chest imaging indicating pneumonia; (4) serological evidence of Mycoplasma pneumoniae-specific IgM antibody titer ≥ 1:160 or a 4-fold rise in antibody titers, or positive MP PCR results from throat swabs or bronchoalveolar lavage fluid. The diagnosis of RMPP was defined as MPP cases where[ 9 ]: (1) persistent high fever and worsening clinical symptoms were observed despite at least 7 days of macrolide therapy; (2) radiological progression was evident, characterized by large, dense, and homogeneous consolidation on X-ray or CT imaging. Inclusion criteria: (1) patients aged 2–14 years; (2) diagnosed with RMPP according to the criteria above. Exclusion criteria[ 10 ]: (1) patients who had diseases such as congenital heart conditions, bronchopulmonary dysplasia, congenital bronchopulmonary abnormalities, blood cancers, congenital immune deficiency disorders; (2) patients who received corticosteroids before admission; (3) patients with co-infection of other pathogens; (4) patients treated with tetracycline and quinolone antibiotics after admission; (5) additionally, cases with incomplete information were excluded. Grouping of participants and treatment Eligible RMPP patients were divided into two groups according to the initial methylprednisolone dosage: the high-dose group (≥ 3 mg/kg/day) and the low-dose group (< 3 mg/kg/day). Subsequently, the corticosteroid dose is gradually reduced based on the patient's condition. If the methylprednisolone intravenous infusion duration is less than 7 days, the corticosteroid is discontinued directly. If it is greater than 7 days, the treatment is switched to oral prednisone for sequential therapy, with a total treatment course of less than one month. Patients were screened for mixed infections through comprehensive respiratory pathogen testing. Tuberculin skin tests were performed to exclude tuberculosis before initiating corticosteroid therapy. Patients with positive tuberculin results were excluded. Data collection Data of the medical records were collected using EpiData software (EpiData Association, version 4.6) and cross-checked by two independent reviewers. Data included demographics (age, sex,weight, history of prematurity, and allergy history), clinical characteristics (fever, cough, wheezing, dyspnea, hypoxemia, and respiratory failure), laboratory results, including complete blood count, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), D-dimer, fibrinogen, treatment protocols (methylprednisolone dose, intravenous immune globulin use and other interventions), and outcomes (duration of fever, length of hospital stay, radiological findings, recovery timelines, and hospitalization costs). Statistical analysis Statistical analyses were performed using SPSS (version 25.0, IBM, USA). Continuous variables are presented as mean ± standard deviation (SD) for normal distribution, and as median with interquartile range (IQR) for data that are not normally distributed. Comparisons between groups were made using independent t-tests for continuous variables with a normal distribution, and Mann–Whitney U tests for those without normal distribution. Categorical variables were analyzed using chi-square tests or Fisher’s exact tests depending on the situation. P < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of LDH levels for high-dose methylprednisolone usage, with the area under the curve (AUC) reported. Results Clinical characteristics of children with RMPP Initially a total of 105 children were enrolled in the study. Among these, 39 children were excluded based on the exclusion criteria (Fig. 1 ). Consequently, 66 children diagnosed with RMPP were included in our study and split up into two groups based on the initial methylprednisolone dosage: the low-dose group (n = 51) and the high-dose group (n = 15). Table 1 summarizes the two groups' baseline characteristics. Table 1 Baseline Characteristics of Patients Low-dose group ( n = 51) High-dose group ( n = 15) P General information Sex (male), n(%) 28 (54.90%) 8 (53.33%) 0.915 Age, years 6.76 ± 1.57 5.73 ± 1.87 0.036* Weight, kg 25.64 ± 5.36 22.03 ± 5.66 0.027* Premature 1 (1.96%) 1 (6.67%) 0.350 Allergy history 2 (3.92%) 2 (13.33%) 0.179 Clinical presentation, n (%) Fever 49 (96.1%) 15 (100) 0.585 Cough 51 (100%) 15 (100) 1 Shortness of breath 3 (5.88%) 1 (6.67%) 0.911 Wheeze 1 (1.96%) 0 (0%) 0.585 Hypoxemia 1 (1.96%) 0 (0%) 0.585 Rash 6 (11.76) 2 (13.33) 0.870 Arthritis 0 (0.00) 1 (6.67) 0.063 Management Methylprednisolone dose, mg/kg/day 1.96 (1.27, 2.35) 3.27 (3.16, 3.4) <0.001* Gamma globulin, n (%) 2 (3.92%) 0 (0%) 0.593 Bronchoscopy, n (%) 41 (80.39) 13 (86.67) 0.580 Plastic bronchitis, n (%) 25 (60.98) 10 (76.92) 0.294 Data are presented as mean ± SD or median (25th–75th percentile) or n (%) * represents p < 0.05 The low-dose group received a median methylprednisolone dosage of 1.96 mg/kg/day (IQR: 1.27–2.35), while the high-dose group had a notably greater median dose of 3.27 mg/kg/day (IQR: 3.16–3.4, P < 0.001). The mean age in the low-dose group was significantly greater than that of the high-dose group (6.76 ± 1.57 years vs. 5.73 ± 1.87 years, P = 0.036). Similarly, body weight was also significantly higher in the low-dose group (25.64 ± 5.36 kg vs. 22.03 ± 5.66 kg, P = 0.027). However, there were no significant differences in sex distribution, history of prematurity, or allergy history between the two groups. In terms of clinical presentation, fever and cough were present in most patients in both groups at admission. The incidence of shortness of breath, wheezing, and hypoxemia showed no meaningful variation between the two groups (P > 0.05). Bronchoscopy was performed in 80.39% of patients in the low-dose group and 86.67% of patients in the high-dose group, with no significant difference between the two groups (P = 0.58). The proportion of patients with plastic bronchitis was also similar in both groups (P = 0.294). The use of gamma globulin did not differ significantly between groups (P > 0.05). Comparison of Laboratory tests and Radiological features Table 2 Comparison of Laboratory tests and Radiological features Low-dose group ( n = 51) High-dose group ( n = 15) P Laboratory tests White blood cell, ×10 9 /L 8.02 ± 3.09 8.39 ± 3.93 0.701 Neutrophil, % 66.17 ± 10.29 68.89 ± 11.65 0.387 Lymphocytes, % 25.22 ± 7.76 19.85 ± 4.30 0.013* Platelet, ×10 9 /L 271.14 ± 76.19 309.93 ± 92.28 0.104 CRP, mg/L 23.92 ± 22.76 32.17 ± 26.07 0.238 ΔCRP, mg/L 22.56 ± 22.17 29.73 ± 25.72 0.307 PCT, ng/ml 0.11 (0.1,0.2) 0.13 (0.1,0.5) 0.395 ESR, mm/h 34.50 ± 19.15 28.86 ± 16.19 0.476 LDH, U/L 413.35 ± 147.91 499.73 ± 161.04 0.059 ALT, U/L 19.15 (11.4, 32.5) 20.65 (11.9, 27.6) 0.794 AST, U/L 36.02 ± 20.55 45.36 ± 22.10 0.146 D-D, mg/L 1.12 (0.7, 2.0) 1.64 (1.4, 2.7) 0.014* Fib, g/L 3.92 ± 0.76 3.92 ± 0.64 0.985 Radiological features Pulmonary consolidation, n (%) 50 (98.04) 15 (100.00) 0.585 Pleural effusion, n (%) 14 (27.45) 8 (53.33) 0.062 Lobar atelectasis, n (%) 8 (15.69) 3 (20.00) 0.694 Bronchiolitis, n (%) 5 (9.80) 1 (6.67) 0.710 Data are presented as mean ± SD or median (25th–75th percentile) or n (%) CRP, C-reactive protein; PCT, procalcitonin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase. D-D, D-dimer; Fib, fibrinogen * represents p < 0.05; ΔCRP, refers to the change in CRP levels after the administration of methylprednisolone Table 2 describes the laboratory results and radiological findings of the two groups. No significant differences were found in white blood cell count, neutrophil percentage, platelet count, CRP, PCT, ESR, ALT, or AST levels between the groups (P > 0.05). The percentage of lymphocytes was significantly lower in the high-dose group compared to the low-dose group (19.85 ± 4.30% vs. 25.22 ± 7.76%, P = 0.013). Additionally, D-dimer levels were significantly higher in the high-dose group compared to the low-dose group (1.64 mg/L vs. 1.12 mg/L, P = 0.014). The ΔCRP levels were higher in the high-dose group than in the low-dose group (29.73 ± 25.72 mg/L vs. 22.56 ± 22.17 mg/L), but the difference was not significant (P = 0.307). Similarly, LDH levels were higher in the high-dose group (499.73 ± 161.04 U/L vs. 413.35 ± 147.91 U/L), but this difference was also not significant (P = 0.059). Regarding radiological features, the presence of pulmonary consolidation was observed in nearly all patients in both groups, with no significant difference between the groups (P = 0.585). Pleural effusion was more common in the high-dose group (53.33%) than in the low-dose group (27.45%), though the difference did not reach statistical significance (P = 0.062). The incidence of lobar atelectasis and bronchiolitis was also similar between the two groups (P > 0.05). Comparisons of clinical courses and cost Regarding clinical outcomes (Table 3 ), the high-dose group experienced a significantly shorter time to defervescence (1.47 ± 0.83 days) compared to the low-dose group (2.14 ± 1.66 days, P = 0.040). However, no significant differences were found in the time to improvement in cough (P = 0.316), the length of hospital stay (P = 0.811), or hospitalization costs (P = 0.506). Table 3 Comparisons of clinical courses and cost between the high-dose and low-dose groups Low-dose group ( n = 51) High-dose group ( n = 15) P Days from initiation of methylprednisolone to defervescence 2.14 ± 1.66 1.47 ± 0.83 0.040* Days from initiation of methylprednisolone to improvement in cough 3.27 ± 1.90 2.73 ± 1.53 0.316 Length of hospital, days 8.51 ± 2.36 8.67 ± 1.63 0.811 Hospitalization cost, CNY 9892.06 ± 4808.32 9213.80 ± 2917.32 0.506 CNY, Chinese Yuan Renminbi; * represents p < 0.05 Predictive Value of LDH Levels for High-Dose Methylprednisolone Use ROC curve analysis was conducted to evaluate the predictive ability of LDH for the administration of high-dose methylprednisolone (Fig. 2 ). The results demonstrated that LDH levels had an AUC of 0.681 (P = 0.036), suggesting moderate predictive value. The optimal LDH cutoff for predicting high-dose corticosteroid use was 333.5 U/L, with a sensitivity of 93% and specificity of 39%. Safety and Adverse Events of Methylprednisolone Therapy in RMPP The maximum dose of methylprednisolone used in the high-dose group was 4 mg/kg/day. The safety assessment of this study followed the routine monitoring protocol of our hospital. All patients underwent baseline blood pressure screening upon admission, but routine blood pressure monitoring was not performed thereafter. Blood pressure and blood glucose tests were conducted only if patients developed symptoms such as excessive thirst, frequent urination, fatigue, dizziness, nausea, sweating, trembling, or palpitations, which could indicate potential blood pressure or blood glucose abnormalities. Additionally, no gastrointestinal bleeding or severe secondary infections were observed in any patients. In the 66 children with RMPP, only one 7-year-old male child, who received 3 mg/kg/day of methylprednisolone, developed eye pain after 3 consecutive days of treatment. An ophthalmology consultation revealed increased intraocular pressure (32 mmHg in the right eye and 29.5 mmHg in the left eye). The methylprednisolone dose was rapidly reduced, and the symptoms subsequently improved. Discussion his study assessed the effectiveness and safety of different methylprednisolone doses in children with RMPP. High-dose methylprednisolone (≥ 3 mg/kg/day) significantly shortened the time to defervescence compared to low-dose methylprednisolone (< 3 mg/kg/day). This is consistent with previous studies that have demonstrated the enhanced anti-inflammatory effects of higher corticosteroid doses in reducing excessive immune responses in RMPP[ 7 , 8 ]. These findings support the rationale for using high-dose corticosteroids in severe cases, where rapid control of inflammation is critical. Interestingly, although high-dose methylprednisolone showed superior efficacy in reducing inflammation and symptom duration, there were no significant differences in hospitalization length or total costs between the two groups. This suggests that factors beyond corticosteroid dosage, such as the overall management strategy, including supportive care, co-treatments, and the natural progression of the disease, may play a more significant role in these outcomes[ 11 ]. Future studies should include pharmacoeconomic analyses to identify patient subgroups that are most likely to benefit both clinically and financially from high-dose corticosteroid therapy. Previous studies have used a 2 mg/kg/day dose to distinguish between low-dose and high-dose corticosteroid regimens in the treatment of RMPP[ 7 , 12 ]. However, this study used a 3 mg/kg/day threshold to differentiate between low-dose and high-dose methylprednisolone groups. This decision was based on the understanding that the 2–3 mg/kg/day range represents a transitional zone from conventional doses to higher corticosteroid doses, aligning with the commonly accepted definition of "low-dose corticosteroids" in our clinical practice. According to the Chinese pediatric MPP guidelines[ 13 ], the recommended initial methylprednisolone dose is 1–2 mg/kg/day, with an escalation to 4–6 mg/kg/day if the initial dose proves insufficient. The choice of 3 mg/kg/day in this study aligns with the guideline, aiming to optimize treatment by balancing efficacy and safety. Clinically, this dose is often used as a bridge between conventional treatment and more intensive corticosteroid therapy when needed. Notably, in this study, we did not use doses exceeding 5 mg/kg/day nor employ a "pulse" dose approach (≥ 10mg/kg/day), based on safety concerns and clinical judgment. The decision to limit corticosteroid doses was made with the aim of minimizing potential adverse effects, including immunosuppression, hyperglycemia, and gastrointestinal issues, which are more commonly associated with higher doses, such as the pulse dosing regimen[ 14 ]. Despite concerns about the potential adverse effects of high-dose corticosteroids, we observed no significant differences in the incidence of side effects between the two groups. However, careful monitoring is crucial to minimize risks, especially in patients with underlying conditions or those receiving prolonged treatment. Furthermore, this study focused on non-critically ill pediatric patients with RMPP, excluding those requiring ICU admission. This approach ensured a more homogeneous population, allowing for a more accurate evaluation of moderate-dose corticosteroid therapy's effects and safety. By excluding critically ill patients, the study minimized confounding factors related to severe disease and multi-organ involvement, providing valuable real-world insights into corticosteroid dosing for a broader patient population while prioritizing safety. The study found that age and weight significantly influenced the choice of methylprednisolone dose, with younger and lighter children more likely to receive higher doses due to their increased vulnerability to severe pneumonia. Research by Iqbal et al[ 15 ] and Asmaa et al[ 16 ] showed that underweight children are at higher risk for severe pneumonia, requiring more intensive interventions, such as corticosteroids. These children tend to exhibit a stronger inflammatory response, including hypoxemia and abnormal radiological findings, which supports the use of higher corticosteroid doses. The association between low weight, severe pneumonia, and inflammation highlights the need for individualized treatments in this high-risk group to enhance clinical outcomes and minimize complications. The ROC curve analysis revealed an LDH cutoff of 333 U/L as a predictive marker for high-dose therapy in pediatric RMPP. Elevated LDH in RMPP are indicative of an ongoing inflammatory response, reflecting cellular injury and tissue damage. LDH is a non-specific enzyme released from cells undergoing necrosis or apoptosis, which is common in severe infections. Previous studies have shown that serum LDH and its isoenzymes are valuable biomarkers for RMPP in children[ 17 ]. Specifically, LDH2 and LDH5 demonstrate good diagnostic value for RMPP, with their combined levels offering the highest predictive power[ 18 ]. A prior meta-analysis also identified inflammatory markers, such as serum tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as potential diagnostic indicators for RMPP[ 19 ]. However, due to their high cost, TNF-α and IFN-γ are unlikely to be widely adopted in clinical practice, whereas LDH is more commonly used across various medical institutions. As a result, serum LDH levels have been proposed as a valuable biomarker for predicting the severity of RMPP and determining the need for corticosteroid therapy. Chen et al[ 20 ] reported that LDH levels ≥ 379 U/L are a useful predictor of RMPP severity, while Yan et al[ 21 ] found that LDH levels ≥ 545.7 U/L are a significant predictor of corticosteroid-resistant RMPP. This study observed significantly elevated D-dimer levels in the high-dose methylprednisolone treatment group, indicating a potential link between an imbalance in the coagulation-fibrinolysis system and the severity of disease as well as therapeutic decisions in RMPP. Elevated D-dimer levels indicate a hypercoagulable state, reflecting ongoing systemic inflammation and endothelial damage[ 22 ]. Recent studies have demonstrated that increased D-dimer levels are strongly associated with more severe clinical outcomes, prolonged hospital stays, and higher incidences of extrapulmonary complications in children with RMPP, highlighting its predictive value for disease progression[ 23 , 24 ]. Studies suggest that D-dimer serves as a biomarker for disease severity and complications, such as necrotizing pneumonia and pulmonary embolism[ 25 ]. Additionally, D-dimer, when combined with other biomarkers such as CRP and LDH, has been identified as a reliable tool for stratifying treatment intensity, helping clinicians determine the appropriate corticosteroid dosage for severe cases of RMPP[ 20 ]. High doses of corticosteroids may increase the incidence of venous thromboembolism (VTE) and other thrombotic complications, particularly in critically ill patients. Therefore, it is essential to balance the benefits of high-dose corticosteroids with the potential risks of thrombosis and consider anticoagulation therapy when managing patients on such treatments. This study excluded patients who had received tetracyclines after admission to ensure homogeneity by focusing on macrolide-based regimens (azithromycin/ erythromycin). However, this design inherently raises questions about MP antibiotic resistance. The prevalence of MRMP infections has been steadily increasing, especially in East Asia. Countries such as China, Japan and Korea have reported high rates of resistance, with some regions showing resistance rates of up to 70–80%[ 26 ]. The emergence of MRMP strains has been closely linked to prolonged fever and more severe disease presentations in children with RMPP, necessitating alternative treatment options, such as corticosteroids, tetracyclines, or fluoroquinolones[ 27 ]​​. Notably, this study did not routinely test for MP resistance to antibiotics, which limits the ability to accurately determine the true prevalence of resistant strains in the cohort. A study by Zhan et al[ 28 ] found that although macrolide resistance in MP is common, the presence of resistance genes does not always correlate with RMPP. This indicates that factors beyond the genetic resistance of Mycoplasma pneumoniae, such as the immune response and inflammatory loading, may play a more significant role in the development of RMPP. Limitation This study has several limitations. First, as a real-world investigation with a non-randomized, retrospective design, it inherently lacks the rigor of controlled experimental conditions. Patients were assigned to the high- or low-dose methylprednisolone groups based on clinical judgment rather than randomization, which may introduce selection bias. However, this approach reflects real-world clinical practice, where treatment decisions are tailored to individual patient severity, providing valuable insights into therapeutic outcomes in heterogeneous clinical settings. Second, although the exclusion of critically ill patients requiring ICU admission limits the generalizability to severe RMPP cases, it ensured a more homogeneous study population, allowing for a clearer evaluation of corticosteroid effects in non-severe cases. This design choice prioritized internal validity over broader applicability. Third, the absence of routine testing for MRMP precluded direct analysis the role of antibiotic resistance. However, this study began in October 2023, after which the number of MP cases in mainland China significantly increased compared to 2022. Multicenter study results showed that the mutation rate of macrolide-resistant genes was 88.10%, all of which were A2063G mutations[ 29 ]. Furthermore, a survey conducted in Beijing on pediatric MP infections found that the resistance rate of MP to macrolides was 100%[ 30 ]. Given the high prevalence of MRMP in China during this period, the observed therapeutic effects of methylprednisolone may still reflect real-world efficacy, as resistance was already a widespread factor in this population. Fourth, although no significant intergroup differences were observed for adjunct therapies, such as bronchoscopy and intravenous immunoglobulin, the small sample size in the high-dose group (n = 15) limits the ability to rule out potential confounding effects from these interventions. Therefore, larger studies are needed to better understand their potential interactions with corticosteroid dosing. Conclusion This study demonstrates that high-dose methylprednisolone effectively reduces the time to defervescence in children with RMPP. However, no significant differences were observed in hospital stay duration or costs between the high- and low-dose groups. Elevated LDH levels were identified as a potential predictor for high-dose corticosteroid use, while higher D-dimer levels were associated with increased disease severity. Abbreviations RMPP: Refractory Mycoplasma pneumoniae pneumonia; MP: Mycoplasma pneumoniae ; MRMP: macrolide-resistant Mycoplasma pneumoniae ; MPP: Mycoplasma pneumoniae pneumonia; CRP: C-reactive protein; PCT: procalcitonin; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase. D-D: D-dimer; Fib: fibrinogen; CNY, Chinese Yuan Renminbi; AUC: area under the receiver; ROC: operating characteristic curve; CI: confidence interval. Declarations Acknowledgments We thank Dr. Changqing Shen, Dr. Yuyan Zhang, and Dr. Weihao Duan for their efforts in performing electronic bronchoscopy for the pediatric patients and polishing the manuscript. Author contributions GQ and XX designed and conceived the study; LM wrote the manuscript; QD performed the statistical analysis; NJ and XR revised and edited the manuscript critically; MX and WL completed the collection of data. All authors read and approved the final manuscript. Funding No external funding was received for the analysis or drafting of this study. Clinical trial number Not applicable. Data availability The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Ethical approval and consent to participate This study was approved by the Institutional Review Board of Affiliated Hospital of Jining Medical University (No: 2023-09-C032) Consent for publication Not applicable. Competing interests The authors declare that there are no potential conflicts of interests to disclose. References Yang TI, Chang TH, Lu CY, Chen JM, Lee PI, Huang LM, et al. Mycoplasma pneumoniae in pediatric patients: Do macrolide-resistance and/or delayed treatment matter? J Microbiol Immunol Infect 2019;52:329-35. Li ZJ, Zhang HY, Ren LL, Lu QB, Ren X, Zhang CH, et al. Etiological and epidemiological features of acute respiratory infections in China. Nat Commun 2021;12:5026. Zhu Z, Zhang T, Guo W, Ling Y, Tian J, Xu Y. Clinical characteristics of refractory mycoplasma pneumoniae pneumonia in children treated with glucocorticoid pulse therapy. BMC Infect Dis 2020;21:1-8. Wang X, Zhong LJ, Chen ZM, Zhou YL, Ye B, Zhang YY. Necrotizing pneumonia caused by refractory Mycoplasma pneumonia pneumonia in children. World J Pediatr 2018;14:344-9. Han HY, Park KC, Yang E, Lee K. Macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in children treated using early corticosteroids. J Clin Med 2021;10:1309. Zhang L, Wang L, Xu S, Li H, Chu C, Liu Q, et al. Low-Dose Corticosteroid Treatment in Children With Mycoplasma pneumoniae Pneumonia: A Retrospective Cohort Study. Front Pediatr 2020;8:566371. Okumura T, Kawada JI, Tanaka M, Narita K, Ishiguro T, Hirayama Y, et al. Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children. J Infect Chemother 2019;25:346-50. doi:/10.1016/j.jiac.2019.01.003. Sun L, Ye C, Zhou Y, Zuo S, Deng Z, Wang C. Meta-analysis of the clinical efficacy and safety of high-and low-dose methylprednisolone in the treatment of children with severe Mycoplasma pneumoniae pneumonia. The Pediatric Infectious Disease Journal 2020;39:177-83. Huang W, Xu X, Zhao W, Cheng Q. Refractory Mycoplasma Pneumonia in Children: A Systematic Review and Meta-analysis of Laboratory Features and Predictors. J Immunol Res 2022;2022:9227838. Zhai YY, Wu SZ, Yang Y, Yang LY, Xu JX, Huang ZH, et al. An analysis of 20 clinical cases of refractory mycoplasma pneumonia in children. Ann Palliat Med 2020;9:2592-9. Ding G, Zhang X, Vinturache A, van Rossum A, Yin Y, Zhang Y. Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia. Eur J Pediatr 2024;183:3001-11. Wei D, Zhao Y, Zhang T, Xu Y, Guo W. The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia. Respir Res 2024;25:266. National Health Commission. Evidence-based guideline for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023). Zhonghua Er Ke Za Zhi 2023;62:1137-44. doi:/10.3760/cma.j.cn112140-20240722-00503. Koshi EJ, Young K, Mostales JC, Vo KB, Burgess LP. Complications of Corticosteroid Therapy: A Comprehensive Literature Review. J Pharm Technol 2022;38:360-7. Iqbal N, Zafar F, Iqbal M. Factors Influencing The Outcome Of Severe Pneumonia Among Children Having Age From 2 Months To 5 Years In A Tertiary Healthcare Hospital. Pakistan Journal of Health Sciences 2023:60-5. Asmaa Y, Kakalia S, Irtza M, Malik R. The Diagnostic Association of Radiological and Clinicopathological Parameters in Community-Acquired Pneumonia in Children: A Cross-Sectional Study. Cureus 2024;16:e53626. Wang S, Jiang Z, Li X, Sun C, Zhang Y, Xiao Z. Diagnostic value of serum LDH in children with refractory Mycoplasma pneumoniae pneumoniae: A systematic review and meta-analysis. Front Pediatr 2023;11:1094118. Lv J, Wan Y, Jiang F, Fan F. Serum LDH and its isoenzymes (LDH2 and LDH5) associated with predictive value for refractory mycoplasma pneumoniae pneumonia in children. J Lab Med 2024. Wang Y, Zhang Y, Lu W, Wang L. Serum Tumor Necrosis Factor-α and Interferon-γ Levels in Pediatric Mycoplasma pneumoniae Pneumonia: A Systematic Review and Meta-Analysis. Can Respir J 2018;2018:8354892. Chen Q, Hu T, Wu L, Chen L. Clinical features and biomarkers for early prediction of refractory Mycoplasma pneumoniae pneumonia in children. Emerg Med Int 2024;2024:9328177. Yan Y, Wei Y, Jiang W, Hao C. The clinical characteristics of corticosteroid-resistant refractory Mycoplasma Pneumoniae pneumonia in children. Sci Rep 2016;6:39929. Huang X, Li D, Liu F, Zhao D, Zhu Y, Tang H. Clinical significance of D-dimer levels in refractory Mycoplasma pneumoniae pneumonia. BMC Infect Dis 2021;21:1-8. Wen J, Su Y, Sun H, Zhang H, Li H. The combination of initial markers to predict refractory Mycoplasma pneumoniae pneumonia in Chinese children: a case control study. Respir Res 2021;22:89. Zheng Y, Hua L, Zhao Q, Li M, Huang M, Zhou Y, et al. The Level of D-Dimer Is Positively Correlated With the Severity of Mycoplasma pneumoniae Pneumonia in Children. Front Cell Infect Microbiol 2021;11:687391. Wang C, Li L, Xiao G, Chen Y, Wang Y, Chen Z, et al. Characteristics and Outcomes of Mycoplasma Pneumoniae Pneumonia Associated with Pulmonary Embolism and Necrotizing Pneumonia in Children. Infect Drug Resist 2024;17:1961-9. Oishi T, Ouchi K. Recent trends in the epidemiology, diagnosis, and treatment of macrolide-resistant Mycoplasma pneumoniae. J Clin Med 2022;11:1782. Dai FF, Liu FQ, Chen X, Yang J, Wang K, Guo CY. The treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. J Clin Pharm Ther 2021;46:705-10. Zhan XW, Deng LP, Wang ZY, Zhang J, Wang MZ, Li SJ. Correlation between Mycoplasma pneumoniae drug resistance and clinical characteristics in bronchoalveolar lavage fluid of children with refractory Mycoplasma pneumoniae pneumonia. Ital J Pediatr 2022;48:190. Chen Y, Li X, Fu Y, Yu Y, Zhou H. Whole-genome sequencing unveils the outbreak of Mycoplasma pneumoniae in mainland China. Lancet Microbe 2024;5:100870. Jia X, Chen Y, Gao Y, Ren X, Du B, Zhao H, et al. Increased in vitro antimicrobial resistance of Mycoplasma pneumoniae isolates obtained from children in Beijing, China, in 2023. Front Cell Infect Microbiol 2024;14:1478087. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6379936","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453942118,"identity":"a59789e3-8746-4482-a27f-c336691ac61f","order_by":0,"name":"Lanlan Meng","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lanlan","middleName":"","lastName":"Meng","suffix":""},{"id":453942119,"identity":"f2579d47-22db-4dfd-9270-43f92ad57ba7","order_by":1,"name":"Xintan Xu","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xintan","middleName":"","lastName":"Xu","suffix":""},{"id":453942120,"identity":"de02a738-3512-4a76-8b78-b965aa088e0b","order_by":2,"name":"Jun Ning","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Ning","suffix":""},{"id":453942121,"identity":"451d1e58-ba88-4748-a46d-6b9cfe78cb19","order_by":3,"name":"Wen Li","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wen","middleName":"","lastName":"Li","suffix":""},{"id":453942122,"identity":"985bdd75-0044-46e9-aa1a-18dc283c5277","order_by":4,"name":"Qian Dong","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Dong","suffix":""},{"id":453942123,"identity":"69e7ab1e-fd3f-452e-b223-b8aa1d4748c7","order_by":5,"name":"Xueyun Ren","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xueyun","middleName":"","lastName":"Ren","suffix":""},{"id":453942124,"identity":"8fb37547-e0b1-4da0-acf0-1f0689349205","order_by":6,"name":"Meiqin Xiang","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Meiqin","middleName":"","lastName":"Xiang","suffix":""},{"id":453942125,"identity":"1ace405d-9c59-4dff-a432-7bdf2a3e3aa8","order_by":7,"name":"Guangfeng Qiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYLCCBDYGfgYGHhDThoefvYE4LZINEC1pMpI9B4ixBqHlsI3BDQf8inXb269JPCizkeDvP3vwc8Gv8zwMNxgYP3zMwa3F7MyZMomEc2kSEgfOJUvP7LvNwzi7gVly5jY8Wm7kpEkkth2uYzjYYyDN23Obh1nmABszL2Et/yXkD/MY/+btOcfDJpFASEv6MaCWAxIGx3jMpHl+HODhIajlzBlmi4RzyRKGZ3jMrHkbknkkeA424/fL8faHN3+U2UnInT9jfJvnj529/fHmgx8+4tECjHQDBJuxDUw24FMPBOwPkDh/CCgeBaNgFIyCEQkAYSxS57Dq9nIAAAAASUVORK5CYII=","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":true,"prefix":"","firstName":"Guangfeng","middleName":"","lastName":"Qiang","suffix":""}],"badges":[],"createdAt":"2025-04-05 05:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6379936/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6379936/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82582586,"identity":"9e2a8182-fb00-406e-aff8-368791c11859","added_by":"auto","created_at":"2025-05-13 06:46:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57240,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient recruitment and group assignment in the study\u003c/p\u003e\n\u003cp\u003eRMPP, refractory \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e pneumonia; ADV, adenovirus; MRSA, methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e; S. pneumoniae, \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e; RSV, Respiratory syncytial virus\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6379936/v1/57db0a3ff5d3ad1e253e1e66.png"},{"id":82584566,"identity":"a7be915a-bddd-47c1-bb2b-93ae739d0ac5","added_by":"auto","created_at":"2025-05-13 06:54:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":30797,"visible":true,"origin":"","legend":"\u003cp\u003ePredictive Ability of LDH for High-Dose Methylprednisolone Use\u003c/p\u003e\n\u003cp\u003eLDH, lactate dehydrogenase\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6379936/v1/94005c85b87deb491baa2821.png"},{"id":105365266,"identity":"21452497-e1f0-4af7-bf29-262a8801da06","added_by":"auto","created_at":"2026-03-25 08:28:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":858817,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6379936/v1/f225ef27-a5f7-4488-9570-5604570877ba.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"High-Dose versus Low-Dose Methylprednisolone in the Treatment of Pediatric Refractory Mycoplasma Pneumoniae Pneumonia: A Real-World Study","fulltext":[{"header":"Background","content":"\u003cp\u003e \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e (MP) is a leading cause of community-acquired pneumonia in children, responsible for approximately 10%-40% of pediatric cases[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]​​. In school-age children, MP is the leading causative pathogen, with a prevalence rate of 56.7%[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. While most MP infections are self-limiting, some cases progress to refractory \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e pneumonia (RMPP), characterized by persistent clinical symptoms and radiological deterioration despite appropriate antibiotic treatment​[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. RMPP is often associated with pulmonary consolidation, atelectasis, and pleural effusion, leading to severe complications such as necrotizing pneumonia and bronchial obliteration​​[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The emergence of macrolide-resistant \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e (MRMP) has exacerbated this issue, complicating the management of RMPP and leading to prolonged illness and increased morbidity[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].​​\u003c/p\u003e \u003cp\u003eCurrently, treatment strategies for RMPP primarily focus on the use of immune modulators, especially methylprednisolone, to suppress the excessive immune response that exacerbates lung inflammation and tissue damage[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]​. While corticosteroids are generally effective in reducing inflammation, the optimal dosage, and overall efficacy of corticosteroid therapy remain controversial. Some studies suggest that high-dose methylprednisolone is effective in controlling severe inflammation and shortening the duration of illness, without significantly increasing adverse effects​[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Conversely, low-dose methylprednisolone has been found to effectively control the inflammatory response while exhibiting a more favorable side-effect profile​[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In addition, the use of corticosteroids in MRMP infections, especially in patients with clinical deterioration despite initial macrolide therapy, remains a crucial area of study​[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Prompt diagnosis and intervention are vital in preventing the progression of the disease and avoiding complications​.\u003c/p\u003e \u003cp\u003eTherefore, our study aims to conduct a retrospective analysis of a real-world data to evaluate the effectiveness and safety of different doses of methylprednisolone in treating pediatric RMPP, and to investigate its association with clinical outcomes, immune biomarkers, treatment duration, and hospitalization costs.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy subjects\u003c/h2\u003e \u003cp\u003eThis is a retrospective real-world study conducted at the Pediatric Department of the Affiliated Hospital of Jining Medical University from October 2023 to October 2024.\u003c/p\u003e \u003cp\u003e This study was approved by the Institutional Review Board of Affiliated Hospital of Jining Medical University (No: 2023-09-C032), and complies the Declaration of Helsinki. Children diagnosed with RMPP were included. The diagnosis of \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e pneumonia (MPP) was based on established criteria[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]: (1) respiratory symptoms, with or without fever; (2) abnormal pulmonary auscultation findings; (3) chest imaging indicating pneumonia; (4) serological evidence of Mycoplasma pneumoniae-specific IgM antibody titer\u0026thinsp;\u0026ge;\u0026thinsp;1:160 or a 4-fold rise in antibody titers, or positive MP PCR results from throat swabs or bronchoalveolar lavage fluid. The diagnosis of RMPP was defined as MPP cases where[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]: (1) persistent high fever and worsening clinical symptoms were observed despite at least 7 days of macrolide therapy; (2) radiological progression was evident, characterized by large, dense, and homogeneous consolidation on X-ray or CT imaging.\u003c/p\u003e \u003cp\u003eInclusion criteria: (1) patients aged 2\u0026ndash;14 years; (2) diagnosed with RMPP according to the criteria above.\u003c/p\u003e \u003cp\u003eExclusion criteria[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]: (1) patients who had diseases such as congenital heart conditions, bronchopulmonary dysplasia, congenital bronchopulmonary abnormalities, blood cancers, congenital immune deficiency disorders; (2) patients who received corticosteroids before admission; (3) patients with co-infection of other pathogens; (4) patients treated with tetracycline and quinolone antibiotics after admission; (5) additionally, cases with incomplete information were excluded.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eGrouping of participants and treatment\u003c/h3\u003e\n\u003cp\u003eEligible RMPP patients were divided into two groups according to the initial methylprednisolone dosage: the high-dose group (\u0026ge;\u0026thinsp;3 mg/kg/day) and the low-dose group (\u0026lt;\u0026thinsp;3 mg/kg/day). Subsequently, the corticosteroid dose is gradually reduced based on the patient's condition. If the methylprednisolone intravenous infusion duration is less than 7 days, the corticosteroid is discontinued directly. If it is greater than 7 days, the treatment is switched to oral prednisone for sequential therapy, with a total treatment course of less than one month. Patients were screened for mixed infections through comprehensive respiratory pathogen testing. Tuberculin skin tests were performed to exclude tuberculosis before initiating corticosteroid therapy. Patients with positive tuberculin results were excluded.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eData of the medical records were collected using EpiData software (EpiData Association, version 4.6) and cross-checked by two independent reviewers. Data included demographics (age, sex,weight, history of prematurity, and allergy history), clinical characteristics (fever, cough, wheezing, dyspnea, hypoxemia, and respiratory failure), laboratory results, including complete blood count, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), D-dimer, fibrinogen, treatment protocols (methylprednisolone dose, intravenous immune globulin use and other interventions), and outcomes (duration of fever, length of hospital stay, radiological findings, recovery timelines, and hospitalization costs).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS (version 25.0, IBM, USA). Continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for normal distribution, and as median with interquartile range (IQR) for data that are not normally distributed. Comparisons between groups were made using independent t-tests for continuous variables with a normal distribution, and Mann\u0026ndash;Whitney U tests for those without normal distribution. Categorical variables were analyzed using chi-square tests or Fisher\u0026rsquo;s exact tests depending on the situation. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of LDH levels for high-dose methylprednisolone usage, with the area under the curve (AUC) reported.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eClinical characteristics of children with RMPP\u003c/h2\u003e\n \u003cp\u003eInitially a total of 105 children were enrolled in the study. Among these, 39 children were excluded based on the exclusion criteria (Fig. \u003cspan\u003e1\u003c/span\u003e). Consequently, 66 children diagnosed with RMPP were included in our study and split up into two groups based on the initial methylprednisolone dosage: the low-dose group (n\u0026thinsp;=\u0026thinsp;51) and the high-dose group (n\u0026thinsp;=\u0026thinsp;15). Table \u003cspan\u003e1\u003c/span\u003e summarizes the two groups\u0026apos; baseline characteristics.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline Characteristics of Patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLow-dose group\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHigh-dose group\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGeneral information\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex (male), n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (54.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (53.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.915\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.036*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight, kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.03\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.027*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePremature\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.96%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllergy history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (13.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical presentation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49 (96.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCough\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShortness of breath\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.911\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWheeze\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.96%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypoxemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.96%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (11.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (13.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.870\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eManagement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMethylprednisolone dose, mg/kg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.96 (1.27, 2.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.27 (3.16, 3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma globulin, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.593\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBronchoscopy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (80.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (86.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.580\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlastic bronchitis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (60.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (76.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.294\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (25th\u0026ndash;75th percentile) or n (%)\u003c/p\u003e\n \u003cp\u003e* represents p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e\n \u003cp\u003eThe low-dose group received a median methylprednisolone dosage of 1.96 mg/kg/day (IQR: 1.27\u0026ndash;2.35), while the high-dose group had a notably greater median dose of 3.27 mg/kg/day (IQR: 3.16\u0026ndash;3.4, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean age in the low-dose group was significantly greater than that of the high-dose group (6.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57 years vs. 5.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87 years, P\u0026thinsp;=\u0026thinsp;0.036). Similarly, body weight was also significantly higher in the low-dose group (25.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.36 kg vs. 22.03\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66 kg, P\u0026thinsp;=\u0026thinsp;0.027). However, there were no significant differences in sex distribution, history of prematurity, or allergy history between the two groups. In terms of clinical presentation, fever and cough were present in most patients in both groups at admission. The incidence of shortness of breath, wheezing, and hypoxemia showed no meaningful variation between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Bronchoscopy was performed in 80.39% of patients in the low-dose group and 86.67% of patients in the high-dose group, with no significant difference between the two groups (P\u0026thinsp;=\u0026thinsp;0.58). The proportion of patients with plastic bronchitis was also similar in both groups (P\u0026thinsp;=\u0026thinsp;0.294). The use of gamma globulin did not differ significantly between groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eComparison of Laboratory tests and Radiological features\u003c/h3\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of Laboratory tests and Radiological features\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLow-dose group\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHigh-dose group\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLaboratory tests\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhite blood cell, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.39\u0026thinsp;\u0026plusmn;\u0026thinsp;3.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.701\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeutrophil, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.17\u0026thinsp;\u0026plusmn;\u0026thinsp;10.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.89\u0026thinsp;\u0026plusmn;\u0026thinsp;11.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.387\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphocytes, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.013*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatelet, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e271.14\u0026thinsp;\u0026plusmn;\u0026thinsp;76.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e309.93\u0026thinsp;\u0026plusmn;\u0026thinsp;92.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.92\u0026thinsp;\u0026plusmn;\u0026thinsp;22.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.17\u0026thinsp;\u0026plusmn;\u0026thinsp;26.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026Delta;CRP, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.56\u0026thinsp;\u0026plusmn;\u0026thinsp;22.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.73\u0026thinsp;\u0026plusmn;\u0026thinsp;25.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCT, ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11 (0.1,0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13 (0.1,0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.395\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eESR, mm/h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.50\u0026thinsp;\u0026plusmn;\u0026thinsp;19.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.86\u0026thinsp;\u0026plusmn;\u0026thinsp;16.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.476\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLDH, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e413.35\u0026thinsp;\u0026plusmn;\u0026thinsp;147.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e499.73\u0026thinsp;\u0026plusmn;\u0026thinsp;161.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALT, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.15 (11.4, 32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.65 (11.9, 27.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.794\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAST, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.02\u0026thinsp;\u0026plusmn;\u0026thinsp;20.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.36\u0026thinsp;\u0026plusmn;\u0026thinsp;22.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-D, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.12 (0.7, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64 (1.4, 2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.014*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFib, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.985\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRadiological features\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePulmonary consolidation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50 (98.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePleural effusion, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (27.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (53.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLobar atelectasis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (15.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (20.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.694\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBronchiolitis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (9.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.710\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (25th\u0026ndash;75th percentile) or n (%)\u003c/p\u003e\n\u003cp\u003eCRP, C-reactive protein; PCT, procalcitonin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase. D-D, D-dimer; Fib, fibrinogen\u003c/p\u003e\n\u003cp\u003e* represents p\u0026thinsp;\u0026lt;\u0026thinsp;0.05; \u0026Delta;CRP, refers to the change in CRP levels after the administration of methylprednisolone\u003c/p\u003e\n\u003cp\u003eTable \u003cspan\u003e2\u003c/span\u003e describes the laboratory results and radiological findings of the two groups. No significant differences were found in white blood cell count, neutrophil percentage, platelet count, CRP, PCT, ESR, ALT, or AST levels between the groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The percentage of lymphocytes was significantly lower in the high-dose group compared to the low-dose group (19.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30% vs. 25.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.76%, P\u0026thinsp;=\u0026thinsp;0.013). Additionally, D-dimer levels were significantly higher in the high-dose group compared to the low-dose group (1.64 mg/L vs. 1.12 mg/L, P\u0026thinsp;=\u0026thinsp;0.014). The \u0026Delta;CRP levels were higher in the high-dose group than in the low-dose group (29.73\u0026thinsp;\u0026plusmn;\u0026thinsp;25.72 mg/L vs. 22.56\u0026thinsp;\u0026plusmn;\u0026thinsp;22.17 mg/L), but the difference was not significant (P\u0026thinsp;=\u0026thinsp;0.307). Similarly, LDH levels were higher in the high-dose group (499.73\u0026thinsp;\u0026plusmn;\u0026thinsp;161.04 U/L vs. 413.35\u0026thinsp;\u0026plusmn;\u0026thinsp;147.91 U/L), but this difference was also not significant (P\u0026thinsp;=\u0026thinsp;0.059).\u003c/p\u003e\n\u003cp\u003eRegarding radiological features, the presence of pulmonary consolidation was observed in nearly all patients in both groups, with no significant difference between the groups (P\u0026thinsp;=\u0026thinsp;0.585). Pleural effusion was more common in the high-dose group (53.33%) than in the low-dose group (27.45%), though the difference did not reach statistical significance (P\u0026thinsp;=\u0026thinsp;0.062). The incidence of lobar atelectasis and bronchiolitis was also similar between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003ch3\u003eComparisons of clinical courses and cost\u003c/h3\u003e\n\u003cp\u003eRegarding clinical outcomes (Table \u003cspan\u003e3\u003c/span\u003e), the high-dose group experienced a significantly shorter time to defervescence (1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83 days) compared to the low-dose group (2.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66 days, P\u0026thinsp;=\u0026thinsp;0.040). However, no significant differences were found in the time to improvement in cough (P\u0026thinsp;=\u0026thinsp;0.316), the length of hospital stay (P\u0026thinsp;=\u0026thinsp;0.811), or hospitalization costs (P\u0026thinsp;=\u0026thinsp;0.506).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparisons of clinical courses and cost between the high-dose and low-dose groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLow-dose group\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHigh-dose group\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDays from initiation of methylprednisolone to defervescence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.040*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDays from initiation of methylprednisolone to improvement in cough\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.316\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength of hospital, days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.51\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.811\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospitalization cost, CNY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9892.06\u0026thinsp;\u0026plusmn;\u0026thinsp;4808.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9213.80\u0026thinsp;\u0026plusmn;\u0026thinsp;2917.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.506\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eCNY, Chinese Yuan Renminbi; * represents p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003ePredictive Value of LDH Levels for High-Dose Methylprednisolone Use\u003c/h2\u003e\n \u003cp\u003eROC curve analysis was conducted to evaluate the predictive ability of LDH for the administration of high-dose methylprednisolone (Fig. \u003cspan\u003e2\u003c/span\u003e). The results demonstrated that LDH levels had an AUC of 0.681 (P\u0026thinsp;=\u0026thinsp;0.036), suggesting moderate predictive value. The optimal LDH cutoff for predicting high-dose corticosteroid use was 333.5 U/L, with a sensitivity of 93% and specificity of 39%.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eSafety and Adverse Events of Methylprednisolone Therapy in RMPP\u003c/h2\u003e\n \u003cp\u003eThe maximum dose of methylprednisolone used in the high-dose group was 4 mg/kg/day. The safety assessment of this study followed the routine monitoring protocol of our hospital. All patients underwent baseline blood pressure screening upon admission, but routine blood pressure monitoring was not performed thereafter. Blood pressure and blood glucose tests were conducted only if patients developed symptoms such as excessive thirst, frequent urination, fatigue, dizziness, nausea, sweating, trembling, or palpitations, which could indicate potential blood pressure or blood glucose abnormalities. Additionally, no gastrointestinal bleeding or severe secondary infections were observed in any patients. In the 66 children with RMPP, only one 7-year-old male child, who received 3 mg/kg/day of methylprednisolone, developed eye pain after 3 consecutive days of treatment. An ophthalmology consultation revealed increased intraocular pressure (32 mmHg in the right eye and 29.5 mmHg in the left eye). The methylprednisolone dose was rapidly reduced, and the symptoms subsequently improved.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ehis study assessed the effectiveness and safety of different methylprednisolone doses in children with RMPP. High-dose methylprednisolone (\u0026ge;\u0026thinsp;3 mg/kg/day) significantly shortened the time to defervescence compared to low-dose methylprednisolone (\u0026lt;\u0026thinsp;3 mg/kg/day). This is consistent with previous studies that have demonstrated the enhanced anti-inflammatory effects of higher corticosteroid doses in reducing excessive immune responses in RMPP[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These findings support the rationale for using high-dose corticosteroids in severe cases, where rapid control of inflammation is critical.\u003c/p\u003e \u003cp\u003eInterestingly, although high-dose methylprednisolone showed superior efficacy in reducing inflammation and symptom duration, there were no significant differences in hospitalization length or total costs between the two groups. This suggests that factors beyond corticosteroid dosage, such as the overall management strategy, including supportive care, co-treatments, and the natural progression of the disease, may play a more significant role in these outcomes[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Future studies should include pharmacoeconomic analyses to identify patient subgroups that are most likely to benefit both clinically and financially from high-dose corticosteroid therapy.\u003c/p\u003e \u003cp\u003ePrevious studies have used a 2 mg/kg/day dose to distinguish between low-dose and high-dose corticosteroid regimens in the treatment of RMPP[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, this study used a 3 mg/kg/day threshold to differentiate between low-dose and high-dose methylprednisolone groups. This decision was based on the understanding that the 2\u0026ndash;3 mg/kg/day range represents a transitional zone from conventional doses to higher corticosteroid doses, aligning with the commonly accepted definition of \"low-dose corticosteroids\" in our clinical practice. According to the Chinese pediatric MPP guidelines[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], the recommended initial methylprednisolone dose is 1\u0026ndash;2 mg/kg/day, with an escalation to 4\u0026ndash;6 mg/kg/day if the initial dose proves insufficient. The choice of 3 mg/kg/day in this study aligns with the guideline, aiming to optimize treatment by balancing efficacy and safety. Clinically, this dose is often used as a bridge between conventional treatment and more intensive corticosteroid therapy when needed.\u003c/p\u003e \u003cp\u003eNotably, in this study, we did not use doses exceeding 5 mg/kg/day nor employ a \"pulse\" dose approach (\u0026ge;\u0026thinsp;10mg/kg/day), based on safety concerns and clinical judgment. The decision to limit corticosteroid doses was made with the aim of minimizing potential adverse effects, including immunosuppression, hyperglycemia, and gastrointestinal issues, which are more commonly associated with higher doses, such as the pulse dosing regimen[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Despite concerns about the potential adverse effects of high-dose corticosteroids, we observed no significant differences in the incidence of side effects between the two groups. However, careful monitoring is crucial to minimize risks, especially in patients with underlying conditions or those receiving prolonged treatment.\u003c/p\u003e \u003cp\u003eFurthermore, this study focused on non-critically ill pediatric patients with RMPP, excluding those requiring ICU admission. This approach ensured a more homogeneous population, allowing for a more accurate evaluation of moderate-dose corticosteroid therapy's effects and safety. By excluding critically ill patients, the study minimized confounding factors related to severe disease and multi-organ involvement, providing valuable real-world insights into corticosteroid dosing for a broader patient population while prioritizing safety.\u003c/p\u003e \u003cp\u003eThe study found that age and weight significantly influenced the choice of methylprednisolone dose, with younger and lighter children more likely to receive higher doses due to their increased vulnerability to severe pneumonia. Research by Iqbal et al[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and Asmaa et al[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] showed that underweight children are at higher risk for severe pneumonia, requiring more intensive interventions, such as corticosteroids. These children tend to exhibit a stronger inflammatory response, including hypoxemia and abnormal radiological findings, which supports the use of higher corticosteroid doses. The association between low weight, severe pneumonia, and inflammation highlights the need for individualized treatments in this high-risk group to enhance clinical outcomes and minimize complications.\u003c/p\u003e \u003cp\u003eThe ROC curve analysis revealed an LDH cutoff of 333 U/L as a predictive marker for high-dose therapy in pediatric RMPP. Elevated LDH in RMPP are indicative of an ongoing inflammatory response, reflecting cellular injury and tissue damage. LDH is a non-specific enzyme released from cells undergoing necrosis or apoptosis, which is common in severe infections. Previous studies have shown that serum LDH and its isoenzymes are valuable biomarkers for RMPP in children[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Specifically, LDH2 and LDH5 demonstrate good diagnostic value for RMPP, with their combined levels offering the highest predictive power[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A prior meta-analysis also identified inflammatory markers, such as serum tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as potential diagnostic indicators for RMPP[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, due to their high cost, TNF-α and IFN-γ are unlikely to be widely adopted in clinical practice, whereas LDH is more commonly used across various medical institutions. As a result, serum LDH levels have been proposed as a valuable biomarker for predicting the severity of RMPP and determining the need for corticosteroid therapy. Chen et al[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] reported that LDH levels\u0026thinsp;\u0026ge;\u0026thinsp;379 U/L are a useful predictor of RMPP severity, while Yan et al[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] found that LDH levels\u0026thinsp;\u0026ge;\u0026thinsp;545.7 U/L are a significant predictor of corticosteroid-resistant RMPP.\u003c/p\u003e \u003cp\u003eThis study observed significantly elevated D-dimer levels in the high-dose methylprednisolone treatment group, indicating a potential link between an imbalance in the coagulation-fibrinolysis system and the severity of disease as well as therapeutic decisions in RMPP. Elevated D-dimer levels indicate a hypercoagulable state, reflecting ongoing systemic inflammation and endothelial damage[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Recent studies have demonstrated that increased D-dimer levels are strongly associated with more severe clinical outcomes, prolonged hospital stays, and higher incidences of extrapulmonary complications in children with RMPP, highlighting its predictive value for disease progression[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Studies suggest that D-dimer serves as a biomarker for disease severity and complications, such as necrotizing pneumonia and pulmonary embolism[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Additionally, D-dimer, when combined with other biomarkers such as CRP and LDH, has been identified as a reliable tool for stratifying treatment intensity, helping clinicians determine the appropriate corticosteroid dosage for severe cases of RMPP[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. High doses of corticosteroids may increase the incidence of venous thromboembolism (VTE) and other thrombotic complications, particularly in critically ill patients. Therefore, it is essential to balance the benefits of high-dose corticosteroids with the potential risks of thrombosis and consider anticoagulation therapy when managing patients on such treatments.\u003c/p\u003e \u003cp\u003eThis study excluded patients who had received tetracyclines after admission to ensure homogeneity by focusing on macrolide-based regimens (azithromycin/ erythromycin). However, this design inherently raises questions about MP antibiotic resistance. The prevalence of MRMP infections has been steadily increasing, especially in East Asia. Countries such as China, Japan and Korea have reported high rates of resistance, with some regions showing resistance rates of up to 70\u0026ndash;80%[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The emergence of MRMP strains has been closely linked to prolonged fever and more severe disease presentations in children with RMPP, necessitating alternative treatment options, such as corticosteroids, tetracyclines, or fluoroquinolones[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]​​. Notably, this study did not routinely test for MP resistance to antibiotics, which limits the ability to accurately determine the true prevalence of resistant strains in the cohort. A study by Zhan et al[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] found that although macrolide resistance in MP is common, the presence of resistance genes does not always correlate with RMPP. This indicates that factors beyond the genetic resistance of Mycoplasma pneumoniae, such as the immune response and inflammatory loading, may play a more significant role in the development of RMPP.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitation\u003c/h2\u003e \u003cp\u003eThis study has several limitations. First, as a real-world investigation with a non-randomized, retrospective design, it inherently lacks the rigor of controlled experimental conditions. Patients were assigned to the high- or low-dose methylprednisolone groups based on clinical judgment rather than randomization, which may introduce selection bias. However, this approach reflects real-world clinical practice, where treatment decisions are tailored to individual patient severity, providing valuable insights into therapeutic outcomes in heterogeneous clinical settings. Second, although the exclusion of critically ill patients requiring ICU admission limits the generalizability to severe RMPP cases, it ensured a more homogeneous study population, allowing for a clearer evaluation of corticosteroid effects in non-severe cases. This design choice prioritized internal validity over broader applicability. Third, the absence of routine testing for MRMP precluded direct analysis the role of antibiotic resistance. However, this study began in October 2023, after which the number of MP cases in mainland China significantly increased compared to 2022. Multicenter study results showed that the mutation rate of macrolide-resistant genes was 88.10%, all of which were A2063G mutations[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Furthermore, a survey conducted in Beijing on pediatric MP infections found that the resistance rate of MP to macrolides was 100%[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Given the high prevalence of MRMP in China during this period, the observed therapeutic effects of methylprednisolone may still reflect real-world efficacy, as resistance was already a widespread factor in this population. Fourth, although no significant intergroup differences were observed for adjunct therapies, such as bronchoscopy and intravenous immunoglobulin, the small sample size in the high-dose group (n\u0026thinsp;=\u0026thinsp;15) limits the ability to rule out potential confounding effects from these interventions. Therefore, larger studies are needed to better understand their potential interactions with corticosteroid dosing.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates that high-dose methylprednisolone effectively reduces the time to defervescence in children with RMPP. However, no significant differences were observed in hospital stay duration or costs between the high- and low-dose groups. Elevated LDH levels were identified as a potential predictor for high-dose corticosteroid use, while higher D-dimer levels were associated with increased disease severity.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRMPP: Refractory \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e pneumonia; MP: \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e;\u0026nbsp;MRMP: macrolide-resistant \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e;\u0026nbsp;MPP:\u003cem\u003e\u0026nbsp;Mycoplasma pneumoniae\u003c/em\u003e pneumonia; CRP: C-reactive protein; PCT: procalcitonin; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase. D-D: D-dimer; Fib: fibrinogen; CNY, Chinese Yuan Renminbi; AUC: area under the receiver; ROC: operating characteristic curve; CI: confidence interval.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Changqing Shen, Dr. Yuyan Zhang, and Dr. Weihao Duan for their efforts in performing electronic bronchoscopy for the pediatric patients and polishing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGQ and XX designed and conceived the study; LM wrote the manuscript; QD performed the statistical analysis; NJ and XR revised and edited the manuscript critically; MX and WL completed the collection of data. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo external funding was received for the analysis or drafting of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of Affiliated Hospital of Jining Medical University (No: 2023-09-C032)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no potential conflicts of interests to disclose.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYang TI, Chang TH, Lu CY, Chen JM, Lee PI, Huang LM, et al. Mycoplasma pneumoniae in pediatric patients: Do macrolide-resistance and/or delayed treatment matter? J Microbiol Immunol Infect 2019;52:329-35. \u003c/li\u003e\n\u003cli\u003eLi ZJ, Zhang HY, Ren LL, Lu QB, Ren X, Zhang CH, et al. Etiological and epidemiological features of acute respiratory infections in China. Nat Commun 2021;12:5026.\u003c/li\u003e\n\u003cli\u003eZhu Z, Zhang T, Guo W, Ling Y, Tian J, Xu Y. Clinical characteristics of refractory mycoplasma pneumoniae pneumonia in children treated with glucocorticoid pulse therapy. BMC Infect Dis 2020;21:1-8. \u003c/li\u003e\n\u003cli\u003eWang X, Zhong LJ, Chen ZM, Zhou YL, Ye B, Zhang YY. Necrotizing pneumonia caused by refractory Mycoplasma pneumonia pneumonia in children. World J Pediatr 2018;14:344-9. \u003c/li\u003e\n\u003cli\u003eHan HY, Park KC, Yang E, Lee K. Macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in children treated using early corticosteroids. J Clin Med 2021;10:1309.\u003c/li\u003e\n\u003cli\u003eZhang L, Wang L, Xu S, Li H, Chu C, Liu Q, et al. Low-Dose Corticosteroid Treatment in Children With Mycoplasma pneumoniae Pneumonia: A Retrospective Cohort Study. Front Pediatr 2020;8:566371.\u003c/li\u003e\n\u003cli\u003eOkumura T, Kawada JI, Tanaka M, Narita K, Ishiguro T, Hirayama Y, et al. Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children. J Infect Chemother 2019;25:346-50. doi:/10.1016/j.jiac.2019.01.003.\u003c/li\u003e\n\u003cli\u003eSun L, Ye C, Zhou Y, Zuo S, Deng Z, Wang C. Meta-analysis of the clinical efficacy and safety of high-and low-dose methylprednisolone in the treatment of children with severe Mycoplasma pneumoniae pneumonia. The Pediatric Infectious Disease Journal 2020;39:177-83. \u003c/li\u003e\n\u003cli\u003eHuang W, Xu X, Zhao W, Cheng Q. Refractory Mycoplasma Pneumonia in Children: A Systematic Review and Meta-analysis of Laboratory Features and Predictors. J Immunol Res 2022;2022:9227838. \u003c/li\u003e\n\u003cli\u003eZhai YY, Wu SZ, Yang Y, Yang LY, Xu JX, Huang ZH, et al. An analysis of 20 clinical cases of refractory mycoplasma pneumonia in children. Ann Palliat Med 2020;9:2592-9. \u003c/li\u003e\n\u003cli\u003eDing G, Zhang X, Vinturache A, van Rossum A, Yin Y, Zhang Y. Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia. Eur J Pediatr 2024;183:3001-11. \u003c/li\u003e\n\u003cli\u003eWei D, Zhao Y, Zhang T, Xu Y, Guo W. The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia. Respir Res 2024;25:266. \u003c/li\u003e\n\u003cli\u003eNational Health Commission. Evidence-based guideline for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023). Zhonghua Er Ke Za Zhi 2023;62:1137-44. doi:/10.3760/cma.j.cn112140-20240722-00503.\u003c/li\u003e\n\u003cli\u003eKoshi EJ, Young K, Mostales JC, Vo KB, Burgess LP. Complications of Corticosteroid Therapy: A Comprehensive Literature Review. J Pharm Technol 2022;38:360-7. \u003c/li\u003e\n\u003cli\u003eIqbal N, Zafar F, Iqbal M. Factors Influencing The Outcome Of Severe Pneumonia Among Children Having Age From 2 Months To 5 Years In A Tertiary Healthcare Hospital. Pakistan Journal of Health Sciences 2023:60-5.\u003c/li\u003e\n\u003cli\u003eAsmaa Y, Kakalia S, Irtza M, Malik R. The Diagnostic Association of Radiological and Clinicopathological Parameters in Community-Acquired Pneumonia in Children: A Cross-Sectional Study. Cureus 2024;16:e53626. \u003c/li\u003e\n\u003cli\u003eWang S, Jiang Z, Li X, Sun C, Zhang Y, Xiao Z. Diagnostic value of serum LDH in children with refractory Mycoplasma pneumoniae pneumoniae: A systematic review and meta-analysis. Front Pediatr 2023;11:1094118. \u003c/li\u003e\n\u003cli\u003eLv J, Wan Y, Jiang F, Fan F. Serum LDH and its isoenzymes (LDH2 and LDH5) associated with predictive value for refractory mycoplasma pneumoniae pneumonia in children. J Lab Med 2024. \u003c/li\u003e\n\u003cli\u003eWang Y, Zhang Y, Lu W, Wang L. Serum Tumor Necrosis Factor-\u0026alpha; and Interferon-\u0026gamma; Levels in Pediatric Mycoplasma pneumoniae Pneumonia: A Systematic Review and Meta-Analysis. Can Respir J 2018;2018:8354892. \u003c/li\u003e\n\u003cli\u003eChen Q, Hu T, Wu L, Chen L. Clinical features and biomarkers for early prediction of refractory Mycoplasma pneumoniae pneumonia in children. Emerg Med Int 2024;2024:9328177.\u003c/li\u003e\n\u003cli\u003eYan Y, Wei Y, Jiang W, Hao C. The clinical characteristics of corticosteroid-resistant refractory Mycoplasma Pneumoniae pneumonia in children. Sci Rep 2016;6:39929. \u003c/li\u003e\n\u003cli\u003eHuang X, Li D, Liu F, Zhao D, Zhu Y, Tang H. Clinical significance of D-dimer levels in refractory Mycoplasma pneumoniae pneumonia. BMC Infect Dis 2021;21:1-8. \u003c/li\u003e\n\u003cli\u003eWen J, Su Y, Sun H, Zhang H, Li H. The combination of initial markers to predict refractory Mycoplasma pneumoniae pneumonia in Chinese children: a case control study. Respir Res 2021;22:89.\u003c/li\u003e\n\u003cli\u003eZheng Y, Hua L, Zhao Q, Li M, Huang M, Zhou Y, et al. The Level of D-Dimer Is Positively Correlated With the Severity of Mycoplasma pneumoniae Pneumonia in Children. Front Cell Infect Microbiol 2021;11:687391.\u003c/li\u003e\n\u003cli\u003eWang C, Li L, Xiao G, Chen Y, Wang Y, Chen Z, et al. Characteristics and Outcomes of Mycoplasma Pneumoniae Pneumonia Associated with Pulmonary Embolism and Necrotizing Pneumonia in Children. Infect Drug Resist 2024;17:1961-9. \u003c/li\u003e\n\u003cli\u003eOishi T, Ouchi K. Recent trends in the epidemiology, diagnosis, and treatment of macrolide-resistant Mycoplasma pneumoniae. J Clin Med 2022;11:1782.\u003c/li\u003e\n\u003cli\u003eDai FF, Liu FQ, Chen X, Yang J, Wang K, Guo CY. The treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. J Clin Pharm Ther 2021;46:705-10.\u003c/li\u003e\n\u003cli\u003eZhan XW, Deng LP, Wang ZY, Zhang J, Wang MZ, Li SJ. Correlation between Mycoplasma pneumoniae drug resistance and clinical characteristics in bronchoalveolar lavage fluid of children with refractory Mycoplasma pneumoniae pneumonia. Ital J Pediatr 2022;48:190. \u003c/li\u003e\n\u003cli\u003eChen Y, Li X, Fu Y, Yu Y, Zhou H. Whole-genome sequencing unveils the outbreak of Mycoplasma pneumoniae in mainland China. Lancet Microbe 2024;5:100870. \u003c/li\u003e\n\u003cli\u003eJia X, Chen Y, Gao Y, Ren X, Du B, Zhao H, et al. Increased in vitro antimicrobial resistance of Mycoplasma pneumoniae isolates obtained from children in Beijing, China, in 2023. Front Cell Infect Microbiol 2024;14:1478087.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Refractory Mycoplasma pneumoniae pneumonia, Methylprednisolone dosing, Corticosteroid therapy, Inflammatory biomarkers","lastPublishedDoi":"10.21203/rs.3.rs-6379936/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6379936/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRefractory \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e pneumonia (RMPP) is a critical pediatric condition with persistent symptoms despite antibiotic treatment. The optimal corticosteroid dosing for RMPP remains controversial. This study evaluates the effectiveness and safety of high and low doses of methylprednisolone for treating pediatric RMPP.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 66 children diagnosed with RMPP between October 2023 and October 2024. Patients were categorized into two groups: high-dose methylprednisolone (\u0026ge;\u0026thinsp;3 mg/kg/day) and low-dose (\u0026lt;\u0026thinsp;3 mg/kg/day). Clinical outcomes, hospitalization costs, biomarkers, radiological features, and the safety of methylprednisolone therapy were assessed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe high-dose group had a significantly shorter time to defervescence (1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83 days vs. 2.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66 days, P\u0026thinsp;=\u0026thinsp;0.04), but no significant differences in hospital stay length or costs. Laboratory findings showed higher D-dimer levels in the high-dose group (1.64 mg/L vs. 1.12 mg/L, P\u0026thinsp;=\u0026thinsp;0.014). ROC analysis identified an LDH cutoff of 333.5 U/L as a potential predictor for high-dose methylprednisolone use (AUC\u0026thinsp;=\u0026thinsp;0.681, P\u0026thinsp;=\u0026thinsp;0.036). Both groups demonstrated good tolerability to methylprednisolone, with no severe adverse effects, except for one case of increased intraocular pressure.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eHigh-dose methylprednisolone reduces defervescence time, but does not decrease hospital stay length or costs in children with RMPP. Elevated LDH and D-dimer levels may serve as biomarkers for disease severity and guide corticosteroid dosing.\u003c/p\u003e","manuscriptTitle":"High-Dose versus Low-Dose Methylprednisolone in the Treatment of Pediatric Refractory Mycoplasma Pneumoniae Pneumonia: A Real-World Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 06:46:10","doi":"10.21203/rs.3.rs-6379936/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"18804534-9a21-4dde-af93-ef3b506bb8a7","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T08:26:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 06:46:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6379936","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6379936","identity":"rs-6379936","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}