Abstract

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is abronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthmatreatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect ofTIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilicinflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL)and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (TH2)/TH17 cytokines, and pro-inflammatory cytokine in BAL fluids wereelevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluidsthan the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group butelevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in theTIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airwayresistance in NeuA.