침습성 폐 아스페르길루스증의 역학과 임상상: 전국 다기관 연구

Abstract

Background: Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in immunocompromised patients. However, few data on clinical characteristics and outcomes of IPA in Korea have been reported. We conducted a nationwide multicenter study in Korea for evaluation of the epidemiology and clinical outcomes of invasive pulmonary aspergillosis. Materials and Methods: A retrospective cohort study was conducted in 10hospitals in Korea. We reviewed all adult patients who met the revised EORTC/MSG definitions between 2008 and 2010. Results: A total of 334 cases, which included proven (26, 8%), probable (159, 48%),or possible (149, 44%) IPA, were identified. Patients with proven or probable IPA were evaluated, and, of these 185 IPA patients, 105 (57%) had neutropenia, 30 (16%)underwent hematopoietic stem cell transplantation, 25 (14%) underwent solid organ transplantation, and 32 (17%) without neutropenia and transplantation received immunosuppressive agents or corticosteroid. Aspergillus spp. were isolated from 42 patients (23%), and positive fungal culture rates from sterile fluid, sputum, and bronchoalveolar lavage fluid (BAL) were 67% (6/9), 21% (32/150), and 20% (9/44),respectively. Results of assays for sensitivity of serum and BAL galactomannan were 84% (155/184) and 89% (25/28), respectively. Amphotericin-B deoxycholate and itraconazole were most commonly administered as a primary therapy in 107 (58%)and 34 (19%) patients, respectively. Of 133 patients (73%) who received salvage therapy after primary antifungal therapy for a median period of six days (IQR 3-12), 82(62%) patients were treated with voriconazole. Of 185 patients, 82 (44%) died within three months after diagnosis of IPA. CT findings, including small airway lesions and micronodules, ground glass opacities, and pleural effusion and persistent positive galactomannan status showed an independent association with worse outcome, while proven diagnosis of IPA showed an independent association with better outcome. Conclusions: Microbiologic confirmation of IPA was low in Korea; therefore, many Korean physicians were dependent on the galactomannan assay for microbiologic diagnosis. Primary therapy with Amphotericin-B deoxycholate followed by salvage therapy with voriconazole was the most common antifungal strategy for treatment of patients with IPA in Korea. Overall mortality and IPA-related mortality were comparable with data from Western clinical trials.