曲霉在自然界中广泛分布，约20种曲霉能感染人类和动物，其中最常见的有烟曲霉、黄曲霉、土曲霉和黑曲霉等。曲霉孢子在空气中传播，人吸入后曲霉可以在气道内定植、致敏、感染，当人体免疫功能低下时可产生危及生命的侵袭性肺曲霉病（IPA）。近年来IPA发病率呈上升趋势，已成为仅次于念珠菌病的主要肺部真菌感染性疾病[1]。虽然IPA已成为器官移植受者、恶性血液病和恶性肿瘤患者等高危人群的重要死因，但对其发病机制了解甚少。本文着重论述近年来IPA发病机制的研究进展。
Objective To evaluate the efficacy and safety of inhaled amphotericin B ( AmB) in prophylaxis of invasive pulmonary aspergillosis ( IPA) in both animal studies and clinical researches. Methods MEDLINE, ISI, EMBASE and Wanfang Periodical Databases were searched until march 2011 for case-control study on the efficacy and safety of inhaled AmB in prophylaxis of IPA. The articles were evaluated according to inclusion criteria. Poor-quality studies were excluded, and RevMan 4. 22 sofeware was applied for investigating the heterogeneity among individual studies and calculating the pooled odds ratio ( OR) and 95% confidence interval ( CI) . Results Five animal studies with a total of 626 animals were included. The overall survival rate of the immunosuppressed animals with pulmonary aspergillosis treated with nebulized AmB was increased ( 38.3% vs. 9.7% , OR=13.93, 95% CI 7.46 ～26.01, Plt;0. 000 01) . Six clinical trials including 1354 patients were considered. Our meta-analysis showed that inhaled AmB could significantly reduce the incidence rate of IPA ( 2.6% vs. 9.2% , OR=0.27, 95% CI 0.16 ～0.46, P lt;0. 000 01) , but had no definite benefit on mortality. Four studies evaluated the potential side effects of nebulized AmB and showed that there were no significant adverse events. Conclusions Empirical inhaled AmB is associated with a lower rate of IPA but no significant
Objective To investigate the blood clotting dysfunction of invasive pulmonary aspergillosis(IPA)and the therapeutic effect of low molecular hepafin in a mouse model．Methods The neutropenic IPA mouse model was constructed by being given cyclophosphamide to depress immunologic function，and then intranasally challenged with Aspergillus fumigatus conidia．(1)Blood clotting function were assessed by bleeding time，clotting time，platelet count and antithrombase-III(AT-III)activity．Seventy-two mice were randomly assigned into 4 groups．Group A received only normal saline．group B received normal saline to substitute the cycloph0sphamide，and the rest equal to group D．Group C received normal saline to substitute the AspergiUus fumigatus conidia suspension，and the rest equal to group D．Group D(model group)received cyclophosphamide(intraperitoneally，150 mg／kg，d4，d1)and Aspergillus fumigatus conidia suspension(intranasally，40 μL／mouse，1．5×10∧5／mL，d0)．Six mice were randomly sacrificed in each group for analysis of blood clotting function per 24 h after inoculation for 3 times．(2)Therapeutic effect of low molecular heparin was determined by survival time of IPA mice．One hundred and eighteen mice were randomly assigned into 4 groups after challenged with 6×10 conidia／mouse and received one of the following regimens daily from dl to d7 after challenge，vehicle(group E，n=29)，low molecular heparin(group F，n=30，subcutaneous injection，1000 IU／kg，qd×7 d)，amphotericin B(group G，n=29，intraperitoneal，1 m kg，qd×7 d)，low molecular heparin plus amphotericin B(group H，n=30)．Mice survivals were recorded once daily to d21 after innoculation．Results (1)AT-III activity of group D decreased significantly 24 h after innoculation．Bleeding time and clotting time decreased significantly and AT—III activity decreased sequentially 48 h after innoculation．The platelet decreased significantly 72 h after innoculation，and bleeding time shoaened further．Clotting time was longer than that 0f 48 h．but still shorter than norm al and AT-III activity decreased sequentially．There were significant differences when comparing group D with group A，B and C(all Plt;0.01)．And there was no significant difference between group A，B and C(all Pgt;0．05)．(2)Survival analysis indicated that the therapeutic effect of low molecular hepafin plus amphotericin B was better than that of amphotericin B or low molecular heparin alone．No therapeutic effect was found in group F(group E vs group F，Pgt;0．05，both group E and group F compared with group H，P lt;0．01．Group H vs group G，P lt;0．05．Both group E and group F compared with group G，P lt;0．05)．Conclusions The results suggest that there is blood clotting dysfunction in IPA mice and AT—III activity may be an early index to monitor the disfunction．Compared with the therapeutic effect of amphoterinein B alone，low molecular hepafin plus amphoterincin B can prolong survival of neutropenic IPA mice
Objective To analyze the risk factors of invasive pulmonary aspergillosis (IPA) in patients with interstitial pneumonia. Methods The clinical data of 770 cases of interstitial pneumonia admitted between December 2010 and August 2015 were collected. Among them, 46 cases were combined with IPA and 724 cases were not ombined with IPA. The clinical data was analyzed to explore the risk factors of IPA in patients with interstitial pneumonia. Results Univariate analysis showed that in the aspects of age (t=3.348, P=0.001), serum albumin level (t=8.381, P < 001), broad-spectrum antibiotic used within 3 months (χ2=87.157, P < 001), long-term administration of glucocorticoid (χ2=57.462, P < 001), long-term administration of immunosuppressive agents (χ2=31.715, P < 001), imaging in UIP type (χ2=20.632, P < 001), diabetes mellitus (χ2=9.737, P=0.002) and heart failure (χ2=9.300, P=0.002), there were significant differences between two groups. After multivariate logistic regression analysis, broad-spectrum antibiotic used within 3 months (OR=4.773, P < 001), long-term administration of glucocorticoid (OR=9.195, P < 001), long-term administration of immunosuppressive agents (OR=2.662, P=0.046), imaging in UIP type (OR=5.725, P < 001), and diabetes mellitus (OR=3.847, P=0.003) were found to be the risk factors of IPA in patients with interstitial pneumonia. Serum albumin level was negatively correlated with the occurrence of IPA in patients with interstitial pneumonia. Conclusions Various factors contribute to the occurrence of IPA in patients with interstitial pneumonia. Miscellaneous appropriate measures should be taken to reduce the incidence of IPA.
ObjectiveTo investigate the clinical features of patients who went through Nocardia co-infection with Aspergillus in lung.MethodsClinical data of 3 pulmonary nocardiosis patients complicated with aspergillosis from China-Japan Hospital during June 2015 and May 2016 were retrospectively analyzed. Nine related literatures found at PubMed were reviewed and they all were case report. No Chinese literature was found at Wanfang data and Chinese Journal Fulltext Database.ResultsAll of the 3 patients were diagnosed as pulmonary nocardiosis by etiological detection, at the same time meeting the diagnostic criteria of invasive pulmonary aspergillosis. Two cases were infected with Aspergillus fumigatus. Aspergillus was not detected in the third case, but the galactomannan of serum and bronchoalveolar lavage fluid significantly increased.ConclusionPulmonary nocardiosis complicated with aspergillosis trends to occur in immunocompromised patients, and pathogen detection is important for diagnosis.
Objective To retrospectively analyze the clinical features of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU), so as to improve the level of clinical diagnosis and treatment. Methods A total of 81 patients diagnosed as IPA from March, 2017 to March, 2022 in the ICU of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China were selected as infection group. A total of 81 non-IPA patients with pulmonary infection and Aspergillus negative sputum culture were selected as the control group. The host factors, Acute Physiology and Chronic Health Assessment Ⅱ score at admission, underlying diseases, clinical symptoms and signs, relevant laboratory test results, and lung CT findings were compared between the two groups. Univariate analysis and multivariate conditional logistic regression analysis were used to identify the risk factors for the occurrence of pulmonary aspergillosis in IPA patients in ICU. At the same time, the types of aspergillus in the IPA group and the outcomes of the two groups at 28 days after ICU admission were analyzed. Results Of the 81 IPA patients, 4 were proven diagnosed and 77 were putative diagnosed. IPA patients were mainly infected with Aspergillus fumigatus and Aspergillus flavus. Symptoms and signs such as fever, cough and expectoration, dyspnea and pulmonary rales occurred in both groups. The level of procalcitonin in IPA group was higher than that in non-IPA group, and the difference was statistically significant (P=0.016). The positive rate of serum galactomannan antigen test (GM test) in the IPA group was higher than that in the non-IPA group, and the differences was statistically significant (P=0.000). The incidence of pulmonary imaging cavities in IPA group was higher than that in non-IPA group, and the difference was statistically significant (P=0.022). Univariate analysis showed that central venous catheterization, septic shock, complete parenteral nutrition, chronic obstructive pulmonary disease, and immunosuppression were risk factors for IPA (P<0.05); Multivariate conditional logistic regression analysis showed that complete parenteral nutrition, chronic obstructive pulmonary disease, and immunosuppression were independent risk factors for IPA (P<0.05). The 28-day fatality rate in IPA group was higher than that in non-IPA group (55.6% vs. 34.6%, P=0.007). Conclusions IPA patients have no specific clinical symptoms and signs, and are mainly infected with Aspergillus fumigatus and Aspergillus flavus; GM test has guiding significance for the diagnosis of IPA. Serum GM test and pulmonary imaging have cavity findings that are helpful for the diagnosis of IPA. Patients with a history of chronic obstructive pulmonary disease, immunosuppression, or complete parenteral nutrition need to be on high alert for the possibility of IPA during ICU stay.