Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma (SSA).The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma (SRA) and to identify the potential mechanisms underlying these effects.Methods Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,respectively.Airway hyperresponsiveness,inflammation,remodeling,expression of interleukin (IL)-25,IL-33,thymic stromal lymphopoietin (TSLP),high mobility group box-1 (HMGB1),and IL-17 in bronchoalveolar lavage fluid (BALF),and the role of dexamethasone (DXM) were compared between these two asthmatic rat models.The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was evaluated.Results SRA rats developed neutrophil-dominated airway inflammation ((29.5±4.1)% of the total cell numbers in BALF),whereas SSA rats developed eosinophil-dominated airway inflammation ((24.0±6.1)% of the total cell numbers in BALF).Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 ((33.6±10.3) vs.(104.8±24.9) pg/ml),IL-33 ((87.5±25.0) vs.(226.6±40.7) pg/ml),and TSLP ((1 933.2±899.5) vs.(7 224.0±992.1) pg/ml),and higher levels of HMGB1 ((21.2±4.5) vs.(5.4±1.6) ng/ml) and IL-17 ((780.5±261.7) vs.(291.4±76.4) pg/ml) in BALF (all P <0.05).However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two groups.Compared with control SSA rats,airway hyp