Predictive value of bronchoalveolar lavage fluid interleukin-25, interleukin-33, and thymic stromal lymphopoietin levels for asthma development in children with recurrent wheezing.

objectiveTo investigate the predictive value of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) levels in bronchoalveolar lavage fluid (BALF) for the development of asthma in children under 6 years of age with recurrent wheezing.

methodsA prospective cohort study was conducted from May 1 to September 30, 2024. Fifty children under 6 years of age with recurrent wheezing were enrolled as the wheezing group from the Department of Respiratory Medicine at Children's Hospital of Chongqing Medical University, while 51 age-matched children with bronchial foreign bodies were recruited as controls during the same period. Levels of IL-25, IL-33, and TSLP in BALF were measured by enzyme-linked immunosorbent assay (ELISA). Children in the wheezing group were followed for one year and were subsequently categorized into an asthma group or a non-asthma group based on the follow-up outcomes. Integrating these clinical data with BALF cytokine levels, we constructed a predictive model for asthma development using receiver operating characteristic (ROC) curve analysis.

resultsUnivariate analysis revealed significant differences between the wheezing group and the control group in terms of clinical characteristics (the number of wheezing episodes, age, history of allergy, breastfeeding), peripheral blood eosinophil count, BALF parameters (nucleated cells, red blood cells, neutrophils, macrophages), and cytokine levels (IL-25, IL-33, TSLP) (P < 0.05). Of the 47 children in the wheezing group who completed the follow-up, 17 were diagnosed with asthma (asthma group) and 30 did not develop asthma (non-asthma group). Univariable analysis revealed significant differences between these two groups in terms of age, the number of wheezing episodes, levels of IL-25, IL-33, and TSLP in BALF (P < 0.05). Logistic regression analysis confirmed that these factors were significant predictors for the progression to asthma in children with recurrent wheezing (P < 0.05).ROC curve analysis demonstrated that the combination of the number of wheezing episodes with IL-25, IL-33, or TSLP levels yielded higher predictive values, with area under the curve (AUC) values of 0.90 (95% CI: 0.788-1.000), 0.946 (95% CI: 0.855-1.000), and 0.86 (95% CI: 0.698-1.000), respectively. These were superior to predictions based on wheezing episodes alone (AUC: 0.705) or individual cytokine levels (IL-25 AUC: 0.779; IL-33 AUC: 0.857; TSLP AUC: 0.841).

conclusionIn children under 6 years with recurrent wheezing, the levels of IL-25, IL-33, and TSLP in BALF are elevated and hold predictive value for the subsequent development of asthma, providing a reference for the early clinical identification of at-risk children.