Children with severe or refractory MPP who underwent BAL in the Department of Pediatrics, Fuyang People's Hospital between May 1, 2023, and April 30, 2024, were retrospectively identified. The children were divided according to the number of BAL procedures performed during the course of their disease into a single-treatment group (STG, n = 219) and a multiple-treatment group (≥ 2 times; MTG, n = 52) (Figure 1). Informed consent was obtained from each child’s guardian before performing fiberoptic bronchoscopy.

Figure 1.

Flow diagram showing the process used to select the study participants. BAL, bronchoalveolar lavage; RMMP, refractory Mycoplasma pneumoniae pneumonia; SMMP, severe Mycoplasma pneumoniae pneumonia.

• (1)

  Age 28 days to 16 years.

• (2)

  Diagnostic criteria for severe or refractory MPP met according to the 2023 guidelines for the diagnosis and treatment of MPP in children (https://www.gov.cn/zhengce/zhengceku/2023-02/16/content_5741770.htm). Severe MPP is defined as follows: persistent high fever (39°C) for ≥ 5 days or fever lasting ≥ 7 days with no downward trend in peak temperature; presence of one or more of wheezing and tachypnea, dyspnea, chest pain, and hemoptysis; extrapulmonary complications not meeting the criteria for critical illness; resting fingertip SpO2 of ≤ 0.93 on room air; imaging demonstrating involvement of two-thirds or more of a single lung lobe with homogeneous high-density consolidation or high-density consolidation in two or more lung lobes (regardless of size of the affected area); moderate to large pleural effusion or localized manifestations of bronchiolitis (diffuse bronchiolitis observed in one or both lungs or ≥ 4/5 lobes, potentially complicated by bronchitis and formation of mucus plugs leading to atelectasis); progressively worsening clinical symptoms, with imaging demonstrating an increase in the extent of lesions by more than 50% within 24–48 hours; and a significant elevation in one of CRP, LDH, or D-dimer. Refractory MPP in pediatric patients is defined as persistent fever, progressive deterioration of clinical signs and pulmonary imaging findings, or development of extrapulmonary complications despite receiving standard macrolide antibiotic treatment for ≥ 7 days.

• (3)

  Detection of M. pneumoniae as the main pathogen in BAL fluid by multiple targeted next-generation sequencing technology.

• (1)

  An underlying condition, such as immunodeficiency, hematological disease, cardiovascular disease, or renal disease.

• (2)

  Incomplete data.

• (3)

  Refusal to undergo BAL.

• (4)

  Fungal infection or pathogens such as Mycobacterium tuberculosis.

Demographics (including age, sex, and season of onset) and clinical data (including duration of fever and length of hospital stay) were collected from the electronic medical records. Laboratory data obtained on the first day of admission were also collected, including the white blood cell count, neutrophil percentage, myocardial enzymes, liver function, coagulation status, and CRP, LDH, and D-dimer levels. Imaging data, including for pleural effusion, atelectasis, pulmonary consolidation, and inflammation involving the lung lobes, were also retrieved, as were the results of bronchoscopy, including the presence or absence of mucus plugs.

All patients scheduled for BAL at the studied institution receive conventional anti-infective and anti-inflammatory therapy after admission. BAL via bronchoscopy is recommended for children presenting with evidence of atelectasis or impaired ventilation on chest radiographs or pulmonary computed tomography scans and those meeting the diagnostic criteria for refractory or severe MPP. If the patient still has a fever with no improvement of clinical symptoms or progressive worsening of pulmonary imaging findings 5 days after the initial BAL, a second BAL is performed. The patient is then evaluated by two pediatricians with qualifications of attending physician or above to reduce the risk of subjective judgment based on symptoms. In principle, BAL is performed no more than three times during the entire course of treatment. Children fast for 6–8 hours before the procedure, and routine pre-procedure examinations are performed to rule out any contraindications. The most severely affected lung segment or lobe is identified based on findings from chest radiography or computed tomography to guide targeted lavage. A bronchoscope (Pentax, Tokyo, Japan) with an external diameter of 2.8 mm, 3.6 mm, or 4.9 mm is selected according to the patient’s age and body weight. A combined anesthesia regimen of “progressive local anesthesia during bronchoscope insertion” (topical local anesthesia) and conscious sedation is used during the procedure. Patients receive 2% lidocaine via a nebulizer before the insertion of the bronchoscope. After the bronchoscope is inserted, 1–2 mL of 2% lidocaine is sprayed sequentially on the larynx, glottis, trachea, and left and right main bronchi; local administration can be repeated if necessary, with the total dose of lidocaine not exceeding 7 mg/kg. Midazolam (0.1–0.3 mg/kg, maximum dose 10 mg) is administered intravenously for sedation. Spontaneous breathing is maintained throughout the procedure. The bronchoscope is inserted through one nostril, and oxygen supplementation is provided via a nasal catheter in the other nostril. The total lavage volume is determined according to the patient’s body weight. For children weighing <20 kg, the total volume is 3 mL/kg, divided into three equal aliquots for instillation; for children weighing ≥ 20 kg, each aliquot is 20 mL, with the maximum total lavage volume not exceeding 3 mL/kg. After negative pressure suction, 5–10 mL of BAL fluid is collected in a sterile container and transported at 2–8°C to the laboratory for testing. The primary purpose of BAL is to clear the airways, whereas pathogen detection assists clinicians with the identification of causative pathogens. After BAL treatment, significant improvement in pulmonary lesions was observed in the pediatric patient (Figure 2). All BAL procedures described above comply with the requirements of the Clinical Practice Guideline for Bronchoalveolar Lavage in Chinese Children (2024) [14].

Figure 2.

Findings on chest computed tomography before and after BAL. (1A) Case 1 (pre-BAL). (1B) Case 1 (2 weeks post-BAL). (2A) Case 2 (pre-BAL). (2B) Case 2 (1 week post-BAL). (3A) Case 3 (pre-BAL). (3B) Case 3 (2 weeks post-BAL). BAL, bronchoalveolar lavage

Continuous data conforming to a normal distribution are expressed as the mean ± standard deviation and were compared between the study groups using the t-test. Continuous data that were not normally distributed are shown as the median and interquartile range [IQR] and were compared between groups using the Mann–Whitney U test. Numerical data are expressed as the rate (percentage) and were compared between groups using the chi-squared test or Fisher’s exact test. Potential risk factors for multiple BAL procedures identified to be statistically significant in univariate analysis (P < 0.05) were entered into a multivariate logistic regression model. The prediction performance of each risk factor identified by multivariate logistic regression was assessed using receiver-operating characteristic (ROC) curve analysis. The ROC curves were plotted using GraphPad (GraphPad Software Inc., San Diego, CA, USA), and the cut-off values for maximum sensitivity and specificity were computed using Youden’s method. All statistical analyses were performed using SPSS 25.0 (IBM Corp., Armonk, NY, USA). A P-value of < 0.05 was considered statistically significant.

The study included 271 children, comprising 145 boys and 126 girls (male-to-female ratio, 1.11:1). There were 219 patients in the STG (114 boys, 105 girls; average age 6.55 ± 2.71 years) and 52 in the MTG (31 boys, 21 girls; average age 7.02 ± 2.06 years). There was no statistically significant difference in sex, age, season of onset, duration of disease before the first bronchoscopic intervention, or M. pneumoniae DNA load between the two study groups (all P > 0.05). However, there were significant between-group differences in peak body temperature, duration of fever, pulmonary consolidation, complications of pleural effusion, atelectasis, and mucus plug formation, and pulmonary lesions involving two or more lung lobes (P < 0.05) (Table 1).

The white blood cell count, neutrophil percentage, and CRP, LDH, fibrinogen, and D-dimer levels were significantly higher, and the lymphocyte percentage was significantly lower in the MTG than in the STG (all P < 0.05). There was no significant between-group difference in hemoglobin, platelet count, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase isoenzyme, prothrombin time, or activated partial thromboplastin time (all P > 0.05) (Table 2).

Multivariate logistic regression analysis revealed that mucus plug formation and elevated CRP, LDH, and D-dimer levels were strong risk factors for multiple BAL procedures in children with severe or refractory MPP (Table 3).

ROC curve analysis confirmed that mucus plug formation and CRP, LDH, and D-dimer levels had good efficacy for predicting the need for multiple BAL procedures. The cut-off values were ≥ 25.68 mg/L for CRP, ≥ 374.90 U/L for LDH, and ≥ 1.22 mg/L for D-dimer; the corresponding areas under the curve were 0.819, 0.871, 0.845, and 0.885 with respective values of 0.827, 0.769, 0.788, and 0.904 for sensitivity and 0.812, 0.885, 0.757, and 0.794 for specificity (Figure 3, Table 4).

Figure 3.

Receiver-operating characteristic curves for mucus plug formation and CRP, LDH, and D–D levels as predictors of multiple bronchoalveolar lavage procedures. CRP, C-reactive protein; D–D, D-dimer; LDH, lactate dehydrogenase.