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Chun-Yu Lin,1,2 Yu-Chen Huang,1,2 Hung-Yu Huang,1,2 Fu-Tsai Chung,1,2 Yu-Lun Lo,1,2 Shu-Min Lin,1,2 Chun-Hua Wang,1,2 Han-Pin Kuo3 1Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3College of Medicine, Taipei Medical University, Taipei, TaiwanCorrespondence: Chun-Hua WangDepartment of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kweishan, Taoyuan 33305, TaiwanTel +8863-3281200 ext.8467Fax +8863-3287787Email wchunhua@ms7.hinet.netBackground: The efficacy of antifungal therapy in fungal-associated severe asthma remains controversial.Objective: We aimed to evaluate the differences in the clinical presentation and response to antifungal therapy between severe asthmatics with fungal sensitization and positive fungal isolates.Methods: This retrospective study included 73 patients with severe asthma from January 2004 to December 2017. We examined the presentation, medication, exacerbations, pulmonary function, serum IgE, blood eosinophils, and sputum culture results. Follow-up care was provided to each patient for minimum 3 years.Results: We classified the patients into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n=16); group 2, positive fungal sensitization (n=16); group 3, positive fungal isolates (n=31); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n=10). There were four participants in group 2, 15 in group 3, and 6 in group 4 had received itraconazole therapy for 3 months. Patients in group 3 presented with lower serum IgE level than those in groups 2 and 4. Antifungal therapy significantly improved ACT score during the first year in groups 3 (from 18 [15– 22] to 24 [23– 24], p=0.0004) and resulted in a long-lasting ACT improvement till the third year in group 3 (from 18 [15– 22] to 24 [22– 24], p=0.0013).Conclusion: Antifungal therapy could effectively control the symptoms in patients with severe asthma with positive fungal isolates, contrary to those with merely fungal sensitization; therefore, highlighting the need for a more precise treatment strategy in future for fungal-associated severe asthma.Keywords: fungal-associated asthma, severe asthma, fungal sensitization, antifungal therapy, itraconazole