Respiratory MUC5B disproportion is involved in severe community-acquired pneumonia

Mucus production is a process involved in the pathogenesis of Community-acquired pneumonia (CAP). The study is to determine Mucin 5B (MUC5B) protein concentration and its proportion in the bronchoalveolar lavage fluid (BALF) of CAP patients and evaluate its value to help assess disease severity.

A total of 118 patients were enrolled in this cross-sectional study, including 45 with severe CAP (SCAP) and 73 with non-severe CAP (NSCAP). MUC5B concentration in BALF were determined by immunoblotting analysis. Total protein concentration of BALF was detected by Pierce BCA kit. Cytokines IL6, IL10, IFNγ, IL13, and IL17 in BALF were measured using commercial enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was applied to evaluate the relationships between MUC5B concentration or MUC5B/total protein ratio and the CURB-65 score, as well as cytokines. Logistic regression analysis was used to identify the independent factors associated with severe CAP. Receiver operating characteristic (ROC) curve was used to evaluate the assessment value of MUC5B/total protein ratio and other indexes for CAP severity.

MUC5B concentration in the BALF of NSCAP group was higher than that in SCAP group [NSCAP 13.56 µg/ml (IQR 5.92-25.79) vs. SCAP 8.20 µg/ml (IQR 4.97-14.03), p = 0.011]. The total protein concentration in the BALF of NSCAP group was lower than that in SCAP group [NSCAP 0.38 mg/ml (IQR 0.15-1.10) vs. SCAP 0.68 mg/ml (IQR 0.46-1.69), p = 0.002]. The MUC5B/total protein ratio was remarkably higher in NSCAP group than that in SCAP groups [NSCAP 3.66% (IQR 1.50-5.56%) vs. SCAP 1.38% (IQR 0.73-1.76%), p < 0.001]. MUC5B/total protein ratio was negatively correlated with total protein concentration (r_s = - 0.576, p < 0.001), IL6 (r_s = - 0.312, p = 0.001), IL10 (r_s = - 0.228, p = 0.013), IL13 (r_s = - 0.183, p = 0.048), IL17 (r_s = - 0.282, p = 0.002) and CURB-65 score (r_s = - 0.239, p = 0.009). Logistic regression identified that MUC5B/total protein ratio, IL6 level and CURB-65 score as independent variables related to CAP severity. ROC curve demonstrated best assessment value of MUC5B/total protein ratio for SCAP (AUC 0.803, p < 0.001), with a sensitivity of 88.9% and a specificity of 64.4%.

Respiratory MUC5B disproportion is related to CAP severity. MUC5B/total protein ratio may serve as an assessment marker and a potential therapeutic target for severe CAP.