Immune activation and mucin dysregulation in pediatric refractory Mycoplasma pneumoniae pneumonia with mucus plugs.

Objective: Children with refractory Mycoplasma pneumoniae pneumonia (RMPP) experience a prolonged disease course and frequent complications, posing a serious threat to pediatric health. Bronchial mucus plugs appear to play a key role; however, their risk factors and underlying mechanisms remain incompletely defined. We sought to characterize clinical, serologic, and bronchoalveolar lavage fluid (BALF) features associated with mucus plugs in RMPP, assess serum-BALF correlations, and identify independent determinants. Methods: From January 2022 to December 2023, children meeting the criteria for RMPP and requiring bronchoscopy were enrolled, and BALF samples were collected for analysis. Patients were stratified according to the presence or absence of mucus plugs. Clinical features, serologic parameters, BALF cytokine profiles, macrolide-resistance mutations, and epithelial and mucin biomarkers were compared between groups. Correlations between systemic inflammatory markers and BALF markers were analyzed, followed by enrichment analyses of differentially expressed BALF markers. Finally, factors independently associated with mucus plug formation were identified. Results: Eighty-eight children with RMPP were enrolled, including 37 with mucus plugs and 51 without. The mucus plug group required more frequent bronchoscopy and exhibited lower lymphocyte, monocyte, platelet, total protein, albumin, sodium, and potassium levels. Conversely, C-reactive protein (CRP), procalcitonin (PCT), creatine kinase (CK), lactate dehydrogenase (LDH), and serum ferritin levels were markedly elevated. BALF analysis revealed significantly higher levels of interleukin (IL)-2, IL-4, IL-6, IL-12p70, IL-17, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), Krebs von den Lungen-6 (KL-6), surfactant protein A (SP-A), and MUC5B in the mucus plug group. Rates of macrolide-resistance mutations were comparable between groups. Serum LDH, CRP, and CK levels correlated positively with BALF pro-inflammatory cytokines (IL-6, IFN-γ, and TNF-α), whereas albumin and sodium levels showed inverse correlations with these cytokines and with epithelial injury markers (KL-6 and SP-A). Enrichment analyses indicated that differentially expressed cytokines and mucins were primarily involved in inflammation-related pathways and immune effector processes. In multivariable analysis, only serum total protein remained independently associated with mucus plug formation. Conclusions: Children with RMPP and mucus plugs exhibited higher BALF cytokine levels, elevated epithelial injury markers (KL-6 and SP-A), and relatively increased MUC5B expression. Lower serum total protein was independently associated with mucus plug formation. These findings refine the pathophysiological understanding of RMPP with mucus plugs and may inform targeted anti-inflammatory and mucus-modulating therapeutic strategies.