Association of airway CCL28 with type 2 inflammation and secretory IgA in patients with asthma

OBJECTIVE: This study aimed to investigate sputum CCL28 expression in patients with acute asthma exacerbations and its association with type 2 airway inflammation and secretory IgA. We further evaluated whether sputum CCL28, alone or in combination with routine clinical indicators, could assist in identifying eosinophilic asthma. METHODS: This study included 75 patients with non-severe acute asthma and 27 healthy controls. Induced sputum samples were collected, and the levels of CCL28, IL-4, IL-5, IL-10, IL-13, and secretory immunoglobulin A (sIgA) were measured in both sputum and serum samples. Sputum cytology was performed to classify airway inflammatory phenotypes as eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma (MA), and paucigranulocytic asthma (PA). Intergroup differences were analyzed using nonparametric tests, and correlations between variables were assessed using Spearman's rank correlation analysis. A predictive model for asthma phenotype identification was subsequently developed, and its predictive performance and potential clinical utility were further evaluated. RESULTS: CCL28 levels in induced sputum were significantly higher in patients with asthma than in healthy controls (P < 0.01), while the correlation between sputum and serum CCL28 levels was weak (ρ = 0.29). Sputum levels of IL-4, IL-5, IL-13, and secretory immunoglobulin A (sIgA) were significantly increased, whereas IL-10 levels were decreased (P < 0.01). CCL28 levels were significantly higher in the EA group than in the NA and PA groups (P < 0.05) and were positively correlated with IL-5, IL-13, sIgA, and sputum eosinophils (r = 0.83, 0.75, 0.66, and 0.55). In the EA prediction model, the combination of CCL28, fractional exhaled nitric oxide (FeNO), and lung function parameters showed the best predictive performance (AUC = 0.79). Incorporation of CCL28 improved model discrimination and reclassification performance (IDI = 0.246, continuous NRI = 0.880, P < 0.001) suggesting additional predictive value beyond routine clinical indicators, and decision curve analysis demonstrated a greater net clinical benefit. CONCLUSION: Sputum CCL28 was associated with type 2 inflammation and airway mucosal immunity in patients with asthma. An exploratory prediction model incorporating sputum CCL28 showed potential value in assisting the identification of eosinophilic asthma.