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
ObjectiveTo investigate the chest radiographic and computed tomographic manifestations of allergic bronchopulmonary aspergillosis (ABPA). MethodWe retrospectively analyzed the chest radiographic and computed tomographic manifestations of 20 ABPA patients treated between December 2005 and December 2013. ResultsChest radiograph showed that there were 4 negative cases, 14 cases of solid mass, 10 cases of increased and disorder of bronchovascular shadows, and 5 cases of bronchiectasis. Chest computed tomography showed that there were one negative case, 18 cases of bronchiectasis, 17 cases of central bronchiectasis among which central and peripheral bronchi were involved in 6 cases and 1 case presented as pure peripheral bronchiectasis, 11 cases of tree-in-bud signs, 6 cases of mucous embolism, 8 cases of solid mass, 5 cases of ground-glass opacity, 4 cases of pleural thickening, 3 cases of pleural effusion, and 2 cases of atelectasis. ConclusionsFor asthma and cystic fibrosis patients, central bronchiectasis on chest CT indicates the diagnosis of ABPA, but it cannot be considered as a characteristic feature. Bronchiectasis combined with high attenuation mucus may be a characteristic feature of ABPA although it is rare.
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 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 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 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 analyse the clinical characteristics of allergic bronchopulmonary aspergillosis (ABPA). Methods The clinical data of 26 patients diagnosed as ABPA from September 2016 to February 2018 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results Among 26 patients with ABPA, 15 were female, 11 were male, with a mean age of (47.6±11.7) years. Before the diagnosis of ABPA, 13 cases had been misdiagnosed as bronchial asthma, 8 as bronchiectasis, 8 as pulmonary infection, 3 as tuberculosis. All patients had cough, sputum production, wheeze in 2, fever in 5, hemoptysis in 4, chest pain in 4, dyspnea in 2. The wheezing sound were heard in 20 patients and wet rales were heard in 4 cases. All patients had increased total IgE level ［median 5 000 (654 – 5 337)IU/ml］. The eosinophil counts were increased in 23 patients ［median 0.99 (0.50 – 3.69)×109/L］ and percentages of peripheral blood eosinophil were elevated to (0.36±0.10). Skin prink test was positive in 10 cases. All patients had increased Aspergillus fumigatus specific IgE ［median 15.1 (0.4 – 29.6)kU/L). Chest X-ray showed fleeting consolidation. Chest CT showed multiple pachy, central cylindrical bronchiectasis, mucous plugging, band linear or glover-finger opacities. Sixteen cases underwent bronchoscopy, out of them 5 cases underwent transbronchial lung biopsy, 2 cases underwent CT guided percutaneous lung biopsy. Fourteen cases were treated with oral corticosteroids combined with antifungal therapy. Conclusions ABPA is a relatively rare and without specific clinical manifestations. In the early period, it is mostly misdiagnosed as bronchial asthma, so it is necessary to improve the early diagosis of ABPA and give appropriate treatment. Regular follow-up should be made to prevent the recurrence.