Objective To investigate the clinical characteristics of patients with COVID-19 associated pulmonary aspergillosis (CAPA). Methods The clinical data of patients diagnosed with CAPA admitted to the First Affiliated Hospital of Soochow University from December 16, 2022 to February 2, 2023 were collected and analyzed. Results Among the 43 enrolled patients,16 patients required invasive mechanical ventilation, 44.19% (19/43) of them with critical novel coronavirus pneumonia, and 86.05% (37/43) had underlying diseases. The peak period of CAPA was 14 - 28 days after SARS-CoV-2 infection (48.84%, 21/43). In the laboratory results, 86.05% (37/43) of patients had varying degrees of lymphocyte reduction, with a lymphocyte count of 0.63 (0.33, 0.96) × 109/L, the median levels of procalcitonin, CRP, and erythrocyte sedimentation rate were all higher than the reference values. 38.89% (14/36) of patients tested positive for serum GM test, and 75.00% (9/12) of patients tested positive for bronchoalveolar lavage fluid GM test. Aspergillus fumigatus is the most common strain. Voriconazole is the most commonly used antifungal drug (86.05%), and other drugs used include caspofungin, posaconazole, isavuconazonium, and amphotericin B. Two patients received local treatment with amphotericin B under bronchoscopy. After treatment, 27 patients improved and were discharged. Conclusions The symptoms, signs, and imaging manifestations of CAPA are not significantly specific, and are prone to misdiagnosis and missed diagnosis. The mortality rate is high. For patients suspected of CAPA and those with CAPA risk factors, relevant examinations should be promptly improved to improve diagnosis and treatment efficiency.
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
ObjectiveTo analyze the clinical characteristics, prognosis and predisposing factors of coronavirus disease 2019 (COVID-19) associated pulmonary mucormycosis (CAPM), so as to improve people's understanding of the disease.MethodsFrom from September 1, 2021 to July 31, 2024, 11 patients with CAPM who were hospitalized in Beijing Chaoyang Hospital affiliated to Capital Medical University were retrospectively collected, and 22 patients with non-CAPM were included after matching according to the ratio of 1:2. The clinical manifestations, laboratory examinations, imaging features, tracheoscopy, treatment and prognosis of the two groups were analyzed. ResultsThe average age of patients in CAPM group was 59.5 ± 10.6 years, with 81.8% of males; diabetes mellitus (90.9%) was the most common complication. In CAPM group, the median time after the occurrence of mucor after COVID-19 was 13.0 (10.0, 24.0) days. The utilization rate of glucocorticoids in the CAPM group was 63.6% (7/11), which was significantly higher than that in non-CAPM group [13.6% (3/22)], and the difference between the groups was statistically significant (P=0.006). The C-reactive protein level in CAPM group was significantly higher at 93.90 (75.00, 129.00) mg/L than that in non-CAPM group at 26.10 (4.83, 114.03) mg/L, with a statistically significant difference (P=0.040). The CD4+T lymphocyte counts and B lymphocyte counts in CAPM group were 223.00 (66.75, 336.75)/µL and 32.00 (21.75, 55.25)/µL, respectively, which were significantly lower than those in the non-CAPM group 394.00 (206.00, 610.00)/µL and 112.50 (56.00, 159.25)/µL, with statistical differences between the groups (P=0.040, P=0.040). In terms of imaging, the main imaging findings were the involvement of multiple lobes in both groups. 63.6% (7/11) of patients with pulmonary aspergillosis in CAPM group were significantly higher than those(4/22, 18.2%) in non-CAPM group (P=0.017). The incidence of dyspnea in CAPM group was significantly higher than that in non-CAPM group (90.9% vs. 50.0%, 0.027%).ConclusionThe proportion of glucocorticoid use and the proportion of pulmonary aspergillosis in CAPM group are significantly higher, and they are in a more serious state of immunosuppression. Once combined with pulmonary aspergillus , the mortality rate is higher.
ObjectiveTo investigate the clinical manifestations, diagnosis and treatments of allergic bronchopulmonary aspergillosis (ABPA). MethodsThe clinical data of four cases of ABPA diagnosed in our department between 2009 and 2014 were analyzed. The related literature was also reviewed. ResultsABPA tends to occur in people with chronic lung diseases, such as asthma and cystic fibrosis. The main clinical manifestations are wheezing, fever, cough, and sputum production. Laboratory examinations include immediate Aspergillus skin test reactivity, elevated total serum IgE and Aspergillus specific IgE and IgG antibodies, and peripheral blood eosinophilia. Radiological findings include recurrent chest roentgenographic infiltrates and central bronchiectasis. Treatments involve corticosteroids and antifungal therapy with itraconazole. ConclusionsABPA is easy to misdiagnosis clinically. It should be considered in patients with poor controlled asthma and asthmatic patients with acute pulmonary infiltrates. Early diagnosis and proper treatment can minimize lung injury from ABPA and improve outcomes.
Objective To improve the diagnosis and treatment of pulmonary infiltration with eosinophilia (PIE). Methods Patients who were diagnosed with PIE in the First Affiliated Hospital of Guangzhou Medical University from January 2004 to December 2013 were recruited and retrospectively analyzed. Data of etiology, clinical manifestation, imaging and pathological features were recorded. Results pulmonary eosinophilic granuloma (PEG) (n=2), eosinophilic granulomatosis with polyangiitis (EGPA) (n=7), Löffler syndrome (n=4), allergic bronchopulmonary aspergillosis (ABPA) (n=16), and chronic eosinophilic pneumonia (CEP) (n=19). There were 27 males and 21 females. 47.9% of the PIE patients were diagnosed as asthma and treated with regular treatment but had not been controlled well. PEG was characterized with wheeze and anhelation in clinical manifestations, unelevated blood eosinophil counts and percentage, significant small airway abnormalities in lung function, diffuse pneumonectasis in Chest CT, and appearance of eosinophil cells in alveole. EGPA shows dyspnea and cough in clinical manifestations, as well as other organs function damaged, unelevated blood eosinophil counts and percentage, significant FEV1/FVC and small airway abnormalities in lung function, tree-in-bud in Chest CT, appearance of eosinophilic granuloma outside blood vessels. Löffler syndrome also showed cough, shorter course of disease, normal lung function and diffusion. ABPA showed wheeze and cough, 31.3% of them with hemoptysis, normal blood eosinophil count, central bronchiectasis in Chest CT. CEP also showed dyspnea and cough. 21.1% of CEP patientshad chest pain, increasing sputum eosinophil percentage compare with blood eosinophil percentage, and small airway abnormalities in lung function. Conclusions Most of PIE patients are diagnosed as asthma but haven’t gotten well controlled under the regular anti-asthmatic treatment. Patients with PIE have increasing eosinophil counts and decreasing lung function. The diagnosis of PIE still depends on clinical manifestation, laboratory test, imaging and pathological examination.
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.
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 describe the underlying conditions of chronic pulmonary aspergillosis (CPA). Methods A retrospective study was performed. Details of the clinical, imaging features, and the underlying conditions of CPA patients admitted to a tertiary university teaching hospital from January 2009 to December 2016 were extracted from clinical records. The classification distribution of CPA, and underlying conditions were analyzed. Results Among the 108 CPA patients, 87 cases had underlying conditions, 21 cases had no underlying conditions. Seventy two (66.7%) patients were engaged in agriculture, the proportion of which was significantly higher in the cases without underlying conditions (85.7% vs. 62.1%). Chronic necrotizing pulmonary aspergillosis (CNPA) was the most common type of these CPA cases. The cases without underlying conditions had significantly more proportion of CNPA than the cases with underlying conditions (85.7% vs. 62.1%). The cases with systemic underlying conditions had significantly more proportion of CNPA than the cases only with pulmonary underlying conditions (82.8% vs. 51.7%). Chronic cavity pulmonary aspergillosis (24/108, 22.2%) only existed in the cases with pulmonary underlying conditions. Underlying conditions were identified in 87 cases of CPA, with 85.1% (74/87) pulmonary and 33.3% (29/87) systemic underlying diseases. Previous tuberculosis mycobacterial infection, bronchiectasis and chronic obstructive pulmonary disease were the most common pulmonary underlying conditions (40.2%, 39.1% and 35.6%, respectively). Diabetes (16.1%) and glucocorticoid using (13.8%) were the most two common systemic underlying conditions. Conclusions CPA can occur in patients with and without underlying diseases. CNPA is the most common type of these CPA, the proportion of which is higher in cases without underlying conditions and cases with systemic underlying conditions. Farming maybe the risk factors of CPA. Chronic pulmonary primary diseases are the most common underlying conditions. The most common systemic factors are diabetes and glucocorticoid using.
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.