    流感相關(guān)性侵襲性肺曲霉病和COVID-19相關(guān)性肺曲霉病的可能病理機(jī)制 4. 侵襲性曲霉病宿主因素
 侵襲性曲霉病和毛霉病危險(xiǎn)因素/宿主人群[10-15] 注：紅色區(qū)域?yàn)榍忠u性曲霉病危險(xiǎn)因素；黃色區(qū)域?yàn)槊共∥ｋU(xiǎn)因素，橙色區(qū)域?yàn)榍忠u性曲霉病和侵襲性毛霉病混合危險(xiǎn)因素。 危險(xiǎn)因素的疊加增加了COVID-19患者罹患毛霉病風(fēng)險(xiǎn)。Seidel等[16]對(duì)德國(guó)6家教學(xué)醫(yī)院2020年3月至2021年6月期間的COVID-19感染患者進(jìn)行了回顧，在13例COVID-19并發(fā)毛霉病的患者中，5例為免疫抑制宿主（白血病或器官移植），3例患者伴有于毛霉病相關(guān)的高危因素（糖尿?。鄶?shù)患者接受了糖皮質(zhì)激素治療（84.6%）。13例患者基礎(chǔ)疾病狀態(tài)和治療過(guò)程如下圖所示。    注：左圖可見(jiàn)銳角分支曲霉菌絲，右圖可見(jiàn)直角分支毛霉菌絲。 一項(xiàng)亞洲侵襲性霉菌感染流行病學(xué)研究中，155例罹患侵襲性霉菌感染中，最常見(jiàn)的致病霉菌病原菌為曲霉菌（81%，含8%混合感染中包含的曲霉菌）和毛霉菌（10%），多數(shù)患者侵襲性霉菌感染累及肺部（78.7%，122/155）[17]。在另外兩項(xiàng)重癥患者的曲霉菌和毛霉菌流行病學(xué)研究中，肺部同為主要累及器官[20,21]。 1. 侵襲性霉菌感染的臨床表現(xiàn)和微生物證據(jù) 侵襲性霉菌病的診斷標(biāo)準(zhǔn)[10]： （1）確診： （2）臨床診斷： 2. 侵襲性肺曲霉病和肺毛霉病影像學(xué)表現(xiàn)[22]
 3. 侵襲性肺曲霉病與肺毛霉病的影像學(xué)差異  4. 非血液惡性腫瘤/非粒細(xì)胞缺乏侵襲性肺曲霉病患者肺部影像學(xué)表現(xiàn)缺乏特異性 5. 培養(yǎng)和（熒光染色）直接鏡檢診斷侵襲性霉菌感染 國(guó)際指南對(duì)于培養(yǎng)和鏡檢在霉菌感染診斷中的推薦[14, 27] 6. BALF-GM試驗(yàn)診斷侵襲性霉菌感染 7. GM試驗(yàn)診斷侵襲性霉菌感染 ESCMID-ECMM-ERS曲霉病指南中推薦GM試驗(yàn)抗原檢測(cè)用于侵襲性曲霉病的診斷，對(duì)應(yīng)不同人群指南在標(biāo)本選擇上給予了區(qū)別推薦。由于受限于血清GM試驗(yàn)的敏感性，對(duì)于接受抗霉菌預(yù)防治療患者，非粒細(xì)胞缺乏患者，ICU患者和實(shí)體器官移植患者指南更傾向于選擇支氣管肺泡灌洗液標(biāo)本進(jìn)行侵襲性肺曲霉病的診斷。 8. PCR診斷侵襲性霉菌感染 9. NGS診斷侵襲性霉菌感染 注：VITAL研究中曲霉合并毛霉菌屬真菌感染患者接受艾沙康唑初始或挽救治療42天時(shí)臨床結(jié)局。 艾沙康唑安全性好，肝膽異常不良事件發(fā)生率顯著低于伏立康唑。SECURE研究中對(duì)接受伏立康唑治療（n=259）和艾沙康唑治療（n=257）的藥物相關(guān)不良反應(yīng)進(jìn)行了比較，艾沙康唑藥物相關(guān)不良事件發(fā)生率顯著低于伏立康唑（42% vs 60%，P<0.001）。其中艾沙康唑組肝膽異常發(fā)生率顯著低于伏立康唑組（9% vs 16%，P=0.016）。該研究還發(fā)現(xiàn)，艾沙康唑組眼部不良事件發(fā)生率顯著低于伏立康唑組（15% vs 27%，P=0.002）。 艾沙康唑較其他廣譜三唑類藥物QTc間期延長(zhǎng)發(fā)生率顯著降低。Van Matre等[35]開展的一項(xiàng)單中心回顧性隊(duì)列研究比較了伏立康唑、泊沙康唑和艾沙康唑治療侵襲性真菌病的療效和安全性，共納入100例患者，接受艾沙康唑治療組相較于其他兩組QTc延長(zhǎng)的發(fā)生率顯著降低（P=0.037）。 參考文獻(xiàn) [1] Montagna M T, Lovero G, Coretti C, et al. SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients[J]. Infection, 2014, 42(1):141-151. [2] Hammond E E, McDonald C S, Vestbo J, et al. The global impact of Aspergillus infection on COPD[J]. BMC Pulm Med, 2020, 20(1):241. [3] He H, Ding L, Li F, et al. 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Mycoses, 2018, 61(7):485-497. [35] Van Matre E T, Evans S L, Mueller S W, et al. Comparative evaluation of isavuconazonium sulfate, voriconazole, and posaconazole for the management of invasive fungal infections in an academic medical center[J]. Ann Clin Microbiol Antimicrob, 2019, 18(1):13. 作者簡(jiǎn)介
崔俊昌 教授
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