Factors associated with Mycoplasma pneumoniae-induced Lobar pneumonia with mucus plugging and the optimal timing for bronchoalveolar lavage: a retrospective study

Abstract

Background

Lobar pneumonia with mucus plugging (LPMP) caused by Mycoplasma pneumoniae (MP) is a severe form of community-acquired pneumonia in children, often leading to prolonged disease courses and complications. Identifying clinical factors associated with delayed radiographic resolution and determining the optimal timing for bronchoalveolar lavage (BAL) intervention are crucial for improving clinical outcomes.

Methods

We conducted a retrospective analysis of 151 children aged 2–14 years diagnosed with LPMP between November 2023 and July 2024. Patients were divided into two groups based on radiographic resolution at one month: common resolution (n = 83) and delayed resolution (n = 68). Clinical data, laboratory results, and timing of BAL intervention were compared between groups. Multivariate logistic regression identified independent risk factors of delayed resolution, and receiver operating characteristic (ROC) curves assessed predictive performance.

Results

Children in the delayed resolution group had significantly longer fever durations before intervention (P < 0.001), higher C-reactive protein levels (P < 0.001), and elevated lactate dehydrogenase levels (P < 0.001) compared to the common resolution group. Multivariate analysis identified elevated D-dimer levels (P = 0.010), delayed BAL intervention (P < 0.001), and prolonged hospital stay (P = 0.044) as independent risk factors of delayed resolution. ROC analysis showed that BAL intervention within 6 days had excellent predictive accuracy. Early BAL intervention was associated with shorter hospital stays (P < 0.001), faster cough resolution (P < 0.001), lower incidence of atelectasis at one month (P = 0.024), and higher rates of lung consolidation absorption (P < 0.001).

Conclusion

Elevated D-dimer levels, delayed BAL intervention, and prolonged hospital stay are significant associated with delayed radiographic resolution in children with LPMP. Early BAL intervention within 6 days of admission improves clinical outcomes by accelerating recovery and reducing complications. These findings support prompt BAL as a key component in the management of pediatric LPMP.

Introduction

Mycoplasma pneumoniae (MP) is one of the common pathogens causing community-acquired pneumonia in children. Especially in China, MP infection has become an important pathogenic factor for children hospitalized for respiratory diseases [1]. Studies have shown that more than 50% of children hospitalized for respiratory infections are diagnosed with MP pneumonia (MPP), especially during the COVID-19 pandemic, the infection rate of MP has increased [2]. LP is a more severe form of pneumonia caused by MP, characterized by alveolar damage and local inflammation. The lesions may affect one or more lung segments or even the entire lobe [3]. Such patients often have airway mucus accumulation, forming mucus blockage, leading to airway obstruction, ventilation/perfusion mismatch, and respiratory failure in severe cases. Studies have found that more than 30% of patients with refractory MMP will develop bronchial mucus blockage [4]. Although MPP usually presents as a mild respiratory infection, some patients will develop severe pulmonary complications, among which lobar pneumonia (LP) with mucus plugging (LPMP) caused by MP is one of the more common and challenging clinical manifestations. LPMP patients often have a longer course of disease and are more likely to develop extrapulmonary complications, including multiple organ dysfunction [5, 6].

In the current research progress, imaging manifestations are closely related to the clinical prognosis of LPMP infection. Early imaging evaluation can effectively predict the progression of the disease, especially high-resolution CT scans, which are of great value in evaluating the degree of lung involvement, hypoxemia, and changes in inflammatory markers [7]. Comparing changes in the absorption area of ​​lung consolidation, especially comparing initial imaging results during treatment, is one of the common prognostic assessment methods for LPMP patients. Pulmonary consolidation is usually associated with severe pneumonia inflammation and airway obstruction, and changes in its absorption area can reflect the speed of recovery from the disease [7]. In addition, clinical features such as persistent high fever, delayed treatment, bronchial mucus embolism and atelectasis have been identified as risk factors affecting the speed of recovery [8]. Studies have shown that bronchial interventions such as bronchoscopy can significantly improve the condition, especially in cases of significant mucus obstruction [9]. The application of bronchoalveolar lavage (BAL) fluid has also demonstrated the efficacy of relieving inflammation and improving airway patency to a certain extent. However, there is still a lack of uniform clinical guidelines on when to perform bronchial intervention in patients with MPLP.

The purpose of this study is to explore the factors affecting delayed absorption of LPMP in children through retrospective analysis and to evaluate the optimal timing of BAL intervention. It is hoped that the results of this study can provide a scientific basis for early identification of high-risk patients and optimization of treatment strategies, thereby improving the clinical prognosis of LPMP patients and reducing the occurrence of complications.

Methods

Study population

Children diagnosed with LPMP during hospitalization from November 2023 to July 2024 were retrospectively analyzed. Inclusion criteria were: (1) age 2–14 years; (2) confirmed MP infection by serological testing or polymerase chain reaction (PCR); (3) radiographically confirmed lobar consolidation with mucus plugging; (4) receipt of bronchoscopy with BAL during hospitalization (according to the Guidelines for Diagnosis and Treatment of Mycoplasma Pneumonae Pneumonia in Children [10]); and (5) availability of complete clinical, laboratory, and radiographic data. Exclusion criteria were: (1) congenital or acquired chronic pulmonary diseases, such as bronchiectasis, cystic fibrosis, or recurrent respiratory tract infections; (2) co-infection with other pathogens, including respiratory syncytial virus, influenza virus, adenovirus, or tuberculosis; (3) incomplete clinical or follow-up data; and (4) refusal or inability to undergo bronchoscopy or BAL. All patients received standard macrolide antibiotics as initial treatment, and systemic glucocorticoids were administered in some patients with severe symptoms or poor initial response to antibiotics, oxygen therapy was provided as needed. The final cohort were divided into two groups based on radiographic resolution outcomes at one-month follow-up: common resolution group and delayed resolution group. Common radiographic resolution was defined as a ≥ 50% absorption rate at one month. Further follow-up evaluations were conducted at three months.

Ethical approval for the study was approved by the Affiliated Yongchuan Hospital of Chongqing Medical University. Informed consent was waived due to its retrospective nature. The study adhered to the principles outlined in the Declaration of Helsinki.

Data collection

Clinical and laboratory data were collected retrospectively from electronic medical records. Demographic data included age, sex, history of asthma or rhinitis, and passive smoke exposure. Clinical parameters collected included fever and cough durations before intervention, cough type (dry or productive), dyspnea, decreased breath sounds, extent of lung consolidation (categorized as 1/3–2/3 or > 2/3 based on chest imaging), and atelectasis recurrence. Laboratory parameters included inflammatory markers, such as C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 A (IL-17 A). Hematologic parameters included white blood cell count (WBC), neutrophil count, coagulation markers (D-dimer), and lactate dehydrogenase (LDH) levels. BAL was performed primarily for airway clearance, and detailed BAL fluid analysis was not within the scope of this study. Blood gas analysis results, including partial pressures of oxygen (PaO₂) and carbon dioxide (PaCO₂) were recorded. Timing of intervention (days from admission) was also recorded. The primary outcome was radiographic resolution at one month. Secondary outcomes included length of hospital stay (LOS), time to fever resolution (< 37.3 °C for 24 h), time to cough resolution, atelectasis re-expansion, complications such as atelectasis recurrence and necrotizing pneumonia. Chest X-rays were the primary imaging tool for assessing radiographic resolution. All imaging assessments were based on radiology reports from hospital-based radiologists, as documented in patient medical records. Long-term outcomes were evaluated at 1 and 3 month post-treatment.

Statistical analysis

All statistical analyses were performed using SPSS software (version 26.0; IBM Corp.). Continuous variables were expressed as means ± standard deviations (SD) or medians with interquartile ranges (IQR) and compared using the independent t-test or Mann–Whitney U test. Categorical variables were reported as frequencies and percentages and analyzed using the chi-squared test or Fisher’s exact test. Multivariate logistic regression was performed to identify independent risk factors of delayed radiographic resolution, and receiver operating characteristic (ROC) curves were used to evaluate the predictive performance with the area under the curve (AUC) reported. Results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). A two-tailed P-value < 0.05 was considered statistically significant.

Results

Patient characteristics

From November 2023 to July 2024, a total of 281 hospitalized children were diagnosed with LPMP. Among these, 21 did not receive BAL, 36 had congenital or acquired chronic pulmonary diseases, 32 had co-infections with other pathogens, and 41 had incomplete clinical or follow-up data, as shown in the Fig. 1. Ultimately, 151 children were included in the study. The final cohort was divided into two groups based on radiographic resolution at the three-month follow-up: common resolution group (n = 83) and delayed resolution group (n = 68). Table 1 summarizd the general characteristics of the two groups. There were no significant differences in age, sex, history of asthma, rhinitis, or passive smoke exposure between the groups. However, children in the delayed resolution group had a significantly longer fever duration before intervention (7 [4.00, 10.00] vs. 6 [2.00, 6.00] days, P < 0.001) and elevated CRP levels (45.05 [13.00, 57.08] vs. 7.50 [2.70, 18.70] mg/L, P < 0.001). LDH levels were also significantly higher in the delayed resolution group (353.50 [306.00, 466.00] vs. 285.00 [246.00, 334.00] U/L, P < 0.001). The extent of lung consolidation and other laboratory parameters, including IL-6, IL-10, IL-17, PaO₂, and PaCO₂, did not differ significantly between groups.

Fig. 1

Flow chart of patient enrollment

Table 1 General characteristics between common resolution and delayed resolution groups

Risk factors of delayed radiographic resolution

Multivariate logistic regression analysis identified D-dimer levels, time to BAL intervention, and length of hospital stay as independent risk factors of delayed radiographic resolution (Table 2). Elevated D-dimer levels were associated with a higher risk of delayed resolution (OR: 1.938, 95% CI: 1.168–3.215, P = 0.010). Time to BAL intervention was the most significant factor, with an OR of 3.531 (95% CI: 1.901–6.559, P < 0.001). Longer hospital stays also significantly increased the likelihood of delayed resolution (OR: 1.376, 95% CI: 1.008–1.877, P = 0.044).

Table 2 Multivariate logistic regression analysis of delayed resolution

ROC analysis

ROC analysis was conducted to evaluate the predictive performance of D-dimer levels, time to BAL intervention, and length of hospital stay for delayed radiographic resolution (Fig. 2; Table 3). The AUC for time to BAL intervention was 0.944 (95% CI: 0.894–0.975, P < 0.001), indicating excellent predictive accuracy. The optimal cut-off value was 6.0 days, with a sensitivity of 91.18% and specificity of 85.54%. D-dimer levels demonstrated strong predictive capabilities, with an AUC of 0.852 (95% CI: 0.785–0.905, P < 0.001). The cut-off value was 1.7 µg/ml, showing a sensitivity of 76.47% and specificity of 89.16%. Length of hospital stay also showed good predictive accuracy with an AUC of 0.923 (95% CI: 0.968–0.960, P < 0.001). The cut-off value was 9.0 days, with a sensitivity of 82.35% and specificity of 86.75%.

Fig. 2

Result of receiver operating characteristic curves

Table 3 Receiver operating characteristic threshold values of predictive indexes of delayed radiographic recovery

Outcomes based on intervention timing

We divided the cochort into an early BAL intervention (≤ 6 days) group and a late BAL intervention (> 6 days) group based on the cut-off value of the intervention timing. As shown in Table 4, children who received early BAL intervention (≤ 6 days) had a shorter length of hospital stay (7.00 [7.00, 9.00] vs. 12.00 [10.00, 15.00] days, P < 0.001) and cough relief time (8.00 [7.00, 9.00] vs. 11.00 [10.00, 12.00] days, P < 0.001) compared to those with late intervention (> 6 days). No significant difference was observed in fever relief time (P = 0.294).

Table 4 Postoperative outcome between children with early or late time to BAL intervention

At one month, the early intervention group had a significantly lower incidence of atelectasis (2.6% vs. 12.2%, P = 0.024) and higher rates of lung consolidation absorption (92.2% vs. 16.2% achieving common resolution, P < 0.001). The incidence of necrotizing pneumonia was lower in the early intervention group but did not reach statistical significance (19.5% vs. 32.4%, P = 0.069).

At three months, the incidence of atelectasis (2.6% vs. 9.5%, P = 0.094) and necrotizing pneumonia (24.7% vs. 37.8%, P = 0.081) showed no statistically significant differences. Lung consolidation absorption rates remained higher in the early intervention group but were not significantly different (94.8% vs. 87.8%, P = 0.127).

Discussion

The course and prognosis of LPMP are often affected by multiple factors, and early intervention is crucial to improve clinical outcomes. This study analyzed the factors that affect the degree of delayed remission of pneumonia in children with LPMP and the optimal time for BAL intervention. Among the patients included in this study, children with LPMP with delayed remission had longer fever duration, higher CRP levels, and LDH levels compared with the normal remission group. This is consistent with the results of previously published literature [11]. This may be the reason why children with delayed remission of LPMP have a longer hospital stay and cause a certain burden on patients [12].

Through further logistic regression analysis, we identified elevated D-dimer levels and prolonged hospitalization as independent risk factors for delayed resolution, both demonstrating excellent diagnostic performance. It is well recognized that longer hospital stays increase the likelihood of adverse outcomes, particularly in critically ill children with MPP, aligning with current clinical observations [13]. D-dimer, a fibrin degradation product indicative of thrombus formation and fibrinolytic activity, has been widely employed in the clinical assessment of various infectious diseases, including pneumonia. A meta-analysis revealed that D-dimer’s prognostic capability could effectively identify high-risk populations prone to poor outcomes in community-acquired pneumonia [14]. Similarly, another study suggested that D-dimer levels outperform total fever duration and leukocyte counts in predicting the progression of LP [15]. In our findings, a D-dimer level exceeding 1.7 mg/L may serve as a critical threshold warranting attention in children with LPMP. In parallel, Zheng and colleagues demonstrated that D-dimer levels above 0.55 mg/L in MPP patients were associated with more severe clinical presentations and prolonged treatment durations [16]. They further proposed that this association could be closely related to the severity of pulmonary inflammation following MP infection [16]. Taken together with our data, monitoring D-dimer levels could emerge as a valuable tool for predicting delayed recovery and clinical outcomes in patients with LPMP.

The timing of BAL intervention represents another critical predictive factor in our study. ROC analysis revealed a significant association between the timing of BAL intervention and delayed resolution in LPMP patients. Airway mucus plugging caused by MMP infection is a primary contributor to impaired pulmonary ventilation and hypoxemia. This issue is particularly pronounced in patients with LP, where mucus plugs may exacerbate the condition and prolong recovery. Several studies have demonstrated that BAL intervention significantly improves therapeutic outcomes in patients with MMP-associated airway mucus plugging, especially those with prolonged disease courses or severe clinical manifestations [4, 9]. However, the optimal timing for BAL remains a matter of debate. Previous research has shown that BAL within 24 h of intubation benefits clinical outcomes in mechanically ventilated patients with aspiration pneumonia [17]. Nonetheless, no studies have yet explored the optimal timing of BAL in LPMP patients. Our study is the first to identify that early BAL intervention (≤ 6 days) significantly outperforms late intervention (> 6 days) in reducing hospital stay duration and alleviating cough in LPMP patients. These findings provide critical empirical evidence to guide clinical decision-making regarding the optimal timing of BAL intervention. They further underscore the importance of BAL intervention in enhancing airway clearance and expediting recovery. Moreover, one month after intervention, the incidence of atelectasis was significantly lower, and the resolution rate of pulmonary consolidation was higher in the early intervention group. These results align with prior studies [7, 18]. At the 3-month follow-up, the early BAL intervention group continued to exhibit a higher consolidation resolution rate, suggesting that early BAL may accelerate the resolution of pulmonary consolidation, promote faster recovery, and reduce the risk of persistent lung injury. However, while the incidence of atelectasis and necrotizing pneumonia remained lower in the early intervention group, there was no significant difference between the two groups, indicating that early BAL intervention may not completely prevent long-term complications. This could be partly due to the relatively small sample size of our study, and further research is needed to clarify the relationship between BAL intervention and long-term complications. Additionally, in clinical practice, bronchoscopy and anesthesia in children carry inherent risks. The decision to perform early bronchoscopy should be made after careful consideration of multiple factors, including disease severity, clinical indications, and potential benefits versus risks. Therefore, while early BAL intervention may aid in faster recovery, its necessity in each case should be carefully evaluated.

This study has several limitations that should be acknowledged. First, as a retrospective study conducted at a single center, selection bias and potential confounding factors may affect the generalizability of our findings. A multicenter prospective study with a larger sample size would help validate our conclusions. Second, although our results indicate that early BAL intervention has obvious clinical advantages in the short term, longer follow-up is needed to draw more definitive conclusions in terms of long-term prognosis. Future studies should further explore the sustained effects of BAL intervention, especially in terms of the complete absorption of atelectasis and consolidation, long-term growth and development, and recovery of lung function. In addition, it is also necessary to evaluate the efficacy and indications of BAL intervention in different pathophysiological backgrounds in order to provide more precise treatment guidance for the clinic.

Conclusion

In conclusion, this study highlights that elevated D-dimer levels, delayed invasive BAL examination, and prolonged hospital stay were associated with delayed resolution of pneumonia in children with LPMP. Early BAL examination performed within 6 days of hospitalization was associated with better clinical outcomes, including faster recovery, lower incidence of atelectasis, and higher absorption rate of lung consolidation.