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Effects of Chronic Aspergillus Fumigatus Exposure on Epithelial Cell Injury and Expression of Epidermal Growth Factor Receptor in Airways of Asthmatic Rats

Objective To explore the effects of prolonged inhalation of Aspergillus fumigatus ( Af)spores on epithelial cell injury and expression of epidermal growth factor receptor( EGFR) in airways of asthmatic rats. Methods 64 male Wistar rats were randomly divided into 8 groups, ie. chronic asthma group ( group A) , chronic asthma plus Af spores inhalation for 1 week ( group B) , 3 weeks ( group C) and 5 weeks ( group D) , chronic asthma plus saline inhalation for 5 weeks ( group E) , OVA-sensitized and salinechallenged group ( group F) , and OVA-sensitized and saline-challenged plus Af spores inhalation for 5 weeks ( group G) ( each n =8) . The airway resistance ( Raw) and change of Raw after acetylcholine provocation were detected using a computerized system. The concentrations of epidermal growth factor ( EGF) andtransforming growth factor alpha( TGF-α) in BALF were measured by ELISA. The extents of epithelial cell injury and goblet cell hyperplasia were evaluated on hematoxylin and eosin-stained( HE) and periodic acidschiff ( PAS) stained lung sections. The expression of EGFR in airway epithelia was demonstrated byimmunohistochemistry, and the level of EGFR protein in the rat lung tissues was measured by western blot.Results The concentration of EGF( pg/mL) ( 51. 72 ±8. 54, 68. 12 ±7. 85, 86. 24 ±9. 12, respectively)and TGF-α( pg/mL) ( 55. 26 ±9. 30, 75. 58 ±11. 56, 96. 75 ±14. 66, respectively) , detached/ inner perimeter of epithelium( % ) ( 11. 25 ±3. 12, 26. 45 ±5. 56, 28. 50 ±7. 50, respectively) , the ratio of goblet cell area to epithelial cell area ( % ) ( 16. 42 ±5. 24, 22. 64 ±6. 82, 36. 38 ±9. 21, respectively) , the integrated optical density ( IOD) of EGFR positive stain in airway epithelial cells ( 82 ±15,120 ±19, 165 ±21, respectively) , and the EGFR protein levels in lung tissues ( 0. 91 ±0. 26, 1. 61 ±0. 52, 2. 52 ±0. 78,respectively) in group B, C, and D were higher than those in group A, E, F and G( P lt; 0. 05 or P lt;0. 01) .The change rates of Raw( % ) ( 61. 91 ±5. 26, 84. 69 ±6. 38) in group C and D were higher than those in group A, E, F and G ( P lt; 0. 05 or P lt;0. 01) . The IOD of EGFR was positively correlated with detached/inner perimeter of epithelium( % ) and the ratio of goblet cell area to epithelial cell area( % ) ( r = 0. 692,P lt;0. 01; r = 0. 657, P lt; 0. 01, respectively) . Conclusion Prolonged inhalation of Aspergillus fumigatus spores can aggravate airway epithelial cell injury, up-regulate the expression of EGFR in airway epithelial cell and induce goblet cell hyperplasia, thus increase the airway responsiveness in rats with chronic asthma.

Expression of von Willebrand Factor in Human Umbilical Vein Endothelial Cells Infected by Aspergillus Fumigatus Hypha

Objective To observe the levels of von Willebrand factor ( vWF) expressed by human umbilical vein endothelial cells ( HUVECs) infected by aspergillus fumigatus ( AF) alone or treatment with cytochalasin D, N-cadherin monoclonal antibody, dexamethasone, respectively, so as to explore the mechanism of angioinvasion in invasive aspergillosis. Methods An in vitro model of HUVECs infected by AF hypha was established. The experiment included six groups, ie. a sham control group, a TNF-αgroup, an AF hypha group, a cytochalasin D group, a N-cadherin antibody group, and a dexamethasone group. Cell supernatants were collected to detect the levels of vWF at 2 h, 6 h, 12 h, and 18 h by enzyme linked immunosorbent assay ( ELISA) . Results Compared with that of vWF at 2 h, the level was higher at 18 h in the sham controlgroup and the TNF-αgroup, and higher at 6 h, 12 h, and 18 h in the other groups( P lt; 0. 05) . Compared with the sham control group, the level of vWF in each experiment group increased at 2 h, 6 h, 12 h, and 18 h except that in the N-cadherin antibody group at 2 h ( P lt; 0. 05) . The level of vWF in TNF-α group was higher than that in the AF hypha group at 2 h, but lower at 18 h. ( P lt; 0. 05) . The level of vWF was not significantly different between the cytochalasin D group and the AF hypha group at each time point. The level of vWF was lower in the N-cadherin antibody group than that in the AF hypha group at 2 h and 6 h ( P lt;0. 05) . The level of vWF was not significantly different between the dexamethasone group and the AF hypha group at each time point. Conclusion HUVECs infected by AF hypha overexpress vWF. N-cadherinmonoclonal antibody can reduce the expression of vWF, but cytochalasin D or dexamethasone has no significant effect on it.

無哮喘的變應性支氣管肺曲霉病一例

目的 報道并分析1例變應性支氣管肺曲霉病（allergic bronchopulmonary aspergillosis，ABPA）的臨床特點、診斷及治療方法。方法 結合文獻資料分析我科2019年診治的1例ABPA的病例。結果 該患者診斷明確，治療稍有曲折。ABPA常發生于肺部有基礎疾病者，尤其是支氣管哮喘或囊性纖維化者。臨床表現主要是咳嗽、咳痰、喘息、胸悶；實驗室檢查血清總IgE水平和曲霉特異性IgE水平上升，以及嗜酸性粒細胞數增加；胸部影像學表現為反復的肺部游走性浸潤影和中心性支氣管擴張等。治療包括糖皮質激素和抗真菌治療，對于不能耐受糖皮質激素的患者，抗IgE抗體治療有益。結論 臨床上ABPA容易誤診、誤治，特別是無哮喘病史時，其診斷更加困難。因此早期診斷和正確治療可以減少ABPA造成的肺損傷，改善患者的預后。

非免疫缺陷患者確診為縱隔黃曲霉膿腫一例報道并文獻復習

目的 總結分析縱隔曲霉病的臨床特征，以提高臨床醫生對縱隔曲霉病的認識。方法 回顧性分析1例縱隔黃曲霉膿腫患者的臨床資料、實驗室檢查、影像學檢查、治療方案及預后，并復習國內外相關文獻。結果 患者男，68歲，其胸部CT示縱隔腫塊，伴氣管、右主支氣管復雜狹窄，纖維支氣管鏡及經超聲支氣管鏡針吸活檢（endobronchial ultrasound-guided transbronchial needle aspiration，EBUS-TBNA）及宏基因組二代測序（metagenomic next-generation sequencing，mNGS）診斷為縱隔黃曲霉膿腫。予伏立康唑及激素治療后病情好轉，4個月后隨訪患者病情穩定。以“縱隔曲霉病、縱隔膿腫”與“非免疫缺陷者”為關鍵詞檢索中國知網醫學數據庫和維普網數據庫，國內尚無文獻報道。使用“mediastinal aspergillosis”、“aspergillus mediastinitis”、“mediastinal aspergilloma”檢索PubMed數據庫中的英文文獻，共檢索到文獻17篇，均為個案報道。結論 非免疫缺陷患者出現縱隔腫物時，需警惕曲霉感染的可能，早期及時的診斷及治療尤為重要。EBUS-TBNA聯合mNGS可作為縱隔曲霉病的診斷方法之一。伏立康唑聯合小劑量激素（0.5 mg/kg）治療方案，可能為縱隔曲霉病提供新的治療思路。

Invasive aspergillosis in nonneutropenic patients：risk factors，clinical features and outcome

Objective To investigate the risk factors，clinical features and outcome of invasive aspergillosis（IA） in nonneutropenic patients.Methods Fifty-four patients with IA at the First Affiliated Hospital of Zhengzhou University from Jan 2001 to Dec 2006 were analyzed retrospectively.According to the definitions of EORTC/MSG，proven diagnosis was made in 9 cases，probable diagnosis in 30 cases and possible diagnosis in 15 cases.Results In the neutropenic group（n=24），hematological malignancies were the major underlying conditions（n=20）.In nonneutropenic group（n=30），the main underlying condition was steroid-treated COPD（n=11）.Fever，dyspnea，cough，chest pain and haemoptysis were commonly symptoms.Thoracic computed tomography showed that segmental consolidation occurred more frequently in neutropenic patients，whereas diffuse nodules more frequently in nonneutropenic patients.Nodules or consolidation with evidence of cavity lesion had a higher sensitivity than the halo sign or air crescent sign in both groups.The total mortality of IA was 72.2%.The mortality of nonneutropenic group was higher than that of neutropenic group（83.3% vs 58.3%，P=0.042）.Multivariate analysis showed that secondary central nerves system IA and delayed diagnosis were associated with poor outcome of IA.Conclusion There were high incidence and mortality of IA among nonneutropenic patients，especially those with COPD treated with long-term corticosteroids.

Clinicopathologic study on fungal necrcotizing retinochoroiditis

Objective To investigate the clinical manifestation and histopathologic changes of the fungal necrotizing retinochoroiditis. Methods Collecting 7 cases of fungal retinochoroiditis with severe immunodepression and loss of visual acuity.Seven removed eyeballs were stained with HE,PAS and silver methenamine,and observed by light microscopy,and in addition,2 of them examined by electron microscopy.Also fungal cultures of blood and affected tissues were performed. Results The chief clinical macnifestation included ciliary injection of conjunctiva,opaque aqueous fluid and vitreous and diffuse hemorrhage and greyt white opacity with retinal detachment in severe cases.Pathologic changes included hemorrhage in the retina,chorioretinal tissue necrosis,hyphae in the blood vessels,affected tissue and vitreous.Fungal culture of blood was positive in three cases.Culture of affected tissues was positive in all cases. Conclusions Eedogenous fungal infection of choroid and retina may be due to the severe immunodepression of the sufferers and usually causes chorioretinal tissue destruction and blind. (Chin J Ocul Fundus Dis, 1999, 15: 235-237)

The Interpretation of Diagnosis and Treatment Guidelines of Aspergillosis from Infectious Diseases Society of America in 2008

變應性支氣管肺曲霉病一例報告并文獻復習

目的提高對變應性支氣管肺曲霉病（ABPA）的認識。 方法結合文獻回顧分析近期我科診斷的1例ABPA的臨床表現、實驗室檢查、影像特點、肺功能變化及治療情況。 結果ABPA常表現為咳嗽、喘息、氣促、咳痰栓、發熱等，血嗜酸粒細胞、總IgE、煙曲霉特異性IgE升高，典型胸部CT表現包括中心型支氣管擴張和游走性浸潤影等，給予糖皮質激素聯合伊曲康唑治療臨床癥狀緩解快，肺功能明顯改善，但中心型支氣管擴張不易恢復。 結論ABPA臨床癥狀不典型，晚期病例具有相對典型影像改變，對"難治性哮喘"等患者早期篩查有助于避免誤診。

變應性支氣管肺曲霉病合并肺諾卡菌感染一例并文獻復習

目的提高對變應性支氣管肺曲霉病（allergic bronchopulmonary aspergillosis，ABPA）合并諾卡菌感染的認識。方法回顧我科診斷的1例ABPA合并諾卡菌感染的臨床資料，結合文獻復習ABPA和諾卡菌病的宿主特征、臨床表現、影像特點等。結果患者男，79歲，退休工人，咳嗽、咳痰、喘息、胸悶20余年，有影像資料記錄至少漏診ABPA 6年。血嗜酸性粒細胞計數和比例升高，血清總IgE升高，胸部CT表現為中心型支氣管擴張和浸潤影，誘導痰中性粒細胞和嗜酸性粒細胞比例升高，肺泡灌洗液淋巴細胞和嗜酸性粒細胞比例升高，灌洗液mNGS、灌洗液和痰培養證實有諾卡菌和煙曲霉。給予糖皮質激素、伏立康唑、伊曲康唑和復方磺胺甲噁唑治療，短期內臨床癥狀減輕，血嗜酸性粒細胞下降，肺部影像有所好轉，但血清總IgE無明顯下降。復習文獻，有3例個案報道。其中，2例ABPA治療中繼發諾卡菌感染，與應用糖皮質激素治療引起免疫抑制有關，1例確診ABPA前應用多種抗生素引起諾卡菌“二重感染”。結論ABPA和諾卡菌病的免疫狀態不同，前者引起的支氣管擴張可能是合并諾卡菌感染的危險因素。

變態反應性支氣管肺曲霉病一例及文獻復習

目的　報道并分析1例變態反應性支氣管肺曲霉病（ABPA）的診斷和治療。 方法　采用病例報告的方式對2010年10月至2011年9月1例ABPA病例進行分析。 結果　患者診斷ABPA明確，治療效果明顯。 結論　ABPA臨床早期診斷困難，需要盡早進行痰培養、血清總IgE等相關檢查以明確診斷，激素和抗真菌藥物是目前有效的治療方法，早期診斷、早期治療能改善患者預后。