The Impact of Fungal Sensitization and Colonization in Severe Asthma

There is increasing evidence supporting an association between asthma severity and fungal exposure and sensitization. Severe asthma with fungal sensitization (SAFS), a new asthma variant, has been described recently. These patients have severe asthma and are sensitized to one or more fungi, but have normal or only slightly elevated total IgE concentrations. Fungal sensitization is associated with reduced lung function in patients with asthma and more than 60% of fungus-sensitized patients with asthma are culture positive. The administration of anti-fungal agents could improve the quality of life in patients with ASFS. However, it is not clarified whether the pathophysiology of SAFS is caused by colonization of the airways with allergic fungi or an extreme response to exogenous fungi. The aim of the study is to investigate the pathophysiology of fungal sensitization in affecting asthma control. In addition, the role of fungal colonization in fungal sensitization of severe asthma will be elucidated. The study will prospectively recruit patients with severe asthma under regular treatment for 6 months. The possible comorbidities affecting asthma control will be studied and treated respectively in these patients. Those patients with poor asthma control even after adequate treatment of comorbidities will be screened for the presence of fungal sensitization by measuring skin prick test and specific IgE against various fungi. Those patients will receive bronchoscopy for bronchial biopsy and lavage to investigate the immunologic response and presence of fungi colonization. The BAL concentrations of TNF-α, IL-1β, IL-8, IL-13, IL-17, IL-25, IL-33, TSLP, soluble ICAM-1, and eotaxin will also be determined. The expression of Th17, tryptase, IL-17, elastase, ECP, IL-33, CD3, CD4, CD8, CD25, ICAM-1, and Foxp3 on bronchial tissue will be identified by immunohistochemistry. By means of PCR, the mRNA expression of IL-8, IL13, IL-17, IL-25, IL-33, TSLP, and eotaxin in bronchial tissue will be determined. The difference between SAFS patients with and without fungus colonization will be compared. By measuring the immune response of fungal sensitization and colonization, the mechanism for fungal sensitization in patients with severe asthma will be elucidated. In addition, the role of fungal colonization in airway sensitization will be clarified. With all the information from this project, a better understanding of SAFS will be achieved which may toward the searching for possible target in future treatment of severe asthma.

Project ID:PC10207-0332
External Project ID:NSC102-2314-B182-038