| BackgroundThe development of pulmonary infection in immunosuppressed patients is a particularly ominous sign and remains a diagnostic challenge. Pulmonary complications are a frequent cause of morbidity and mortality in these patients. Mortality rates for bone marrow transplant recipients with pulmonary infiltrates and requiring mechanical ventilation approach 90%. With the expanding use of solid-organ transplantation (SOT) and hematopoietic stem-cell transplantation (HSCT) coupled with increasingly aggressive chemotherapeutic regimens for malignancies, pulmonary and critical care physicians will find themselves more involved in the care of immunosuppressed patients. Fungi are important pathogenic microorganism to result in opportunistic infections, and Aspergillus is one of the most commom fungi to result in opportunistic infections. Therefore,animal experiment part of our study chose Aspergillus fumigatus which is one of the most common opportunistic algogen to establishment animal model of pulmonary infection,and research the CT appearances of them. In the second part, we analyzed the epidemiology characteristics and CT appearance of phymatoid pulmonary mycosis retrospectively, and compared these characteristics with other dieeases (including inflammation, tuberculosis and benign tumor), purpose to summarize the highlights of differential diagnosis of phymatoid pulmonary mycosis.Part I The Animal Model Establishment of Acute Pulmonary Aspergillosis and CT Appears StudyObjectiveTo research the method of establish the animal model of Aspergillus fumigatus pneumonia in New Zealand rabbits,and analyze the appearances of chest CT scanning , compare the results of the two methods and search the difference of their CT appearances, through establish the the animal model with the method of inoculate conidia through trachea with puncture or inoculate conidia through ear vein.Materials and methods1,Experimential animals and their groups: Forty eight New Zealand rabbits which were healthy were divided into 6 groups randomly. Groups 1-4 which were immunosuppression groups there were 9 animals in each group, and groups 5 and 6 which were intact immune groups there were 6 animals in each group. The animals in groups 1, 3, 5 the conidia were inoculated through trachea with puncture, and in groups 2, 4, 6 the conidia were inoculated through ear vein.2,Establishment of immunosuppression state and inoculation of the strain: Arabinosylcytosin was administered for the first 5 days through vein according to the criteria 525mg/m~2 and Prednisolone was administered for the first 2 days according to the criteria 5mg/kg with the animals in immunosuppression groups. Arabinosylcytosin was given with the other dose 484mg/m~2 the eighth and ninth day to maintain hypo-immune state. Vancocin and ceftazidime intravenous injection were given every day for 15mg/kg and 150mg/kg respectively, and gentamicin intravenous injection was adopted every other day for 5mg/kg with all the animals. On the 2nd day of the experiments, rabbits were inoculated with a defined 200ul inoculum containing 108 (group 3-6) or 107 (group 1 and 2) conidia of Aspergillus fumigatus.3,CT examination: Lung CT scan was performed one day pre-infection and 1, 3, 5, 7, 9, 11, 13 post-infection. The features and variation of the CT appearances, the time of the changes appeared were recorded in detail. The CT appearances were identified as four types: nodous GGO, schistic GGO, schistic consolidation and nodule of soft tissue according to the shape and density. And the CT appearances were defined as peripheral or central, single, multiple or asystematic.4,Animal anatomy and pathology examination and fungal culture:The animals which died were dissected at any time, and pathology examination(HE stainning) and fungul culture were performed on each sample. The survival time of the animal and the changes of lung, liver and kidney of each animal were recorded. All of the animals which survived were executed and dissected at the 13th day after inoculated. All the findings of pathological results and fungus cultivation were analysed.Results1,The achievement ratio of model establishment: Forty seven animals received strain innoculation successfullly and one animal in group1 died before innoculation. The achievement ratio of model established of immunosuppression groups was higher than that of intact immune groups(35 VS 3,100% VS 25%,p=0<0.05). In intact immune groups, one animal died on the 8th post-infection, and other 11animals were executed artificially on experimental deadline. The shortest survival time of the animals in immunosuppression groups was 2 days and the longest was 12 days, and the mean time was 6.51±2.34days. The mean survival time of the animals of group 1 was 8.5±1.51days. The mean survival time of the animals of group 2 was 6±1.80 days. The mean survival time of the animals of group 3 was 7.22±2.64 days. The mean survival time of the animals of group 4 was 4.56±1.42days. The survival time of the animals which were inoculated through trachea with puncture was longer than these which were inoculated through ear vein (2×2factorial experiment, F=15.44, P=0.0004<0.05). And the changes of the livers and kidneys in the latter were more conspicuous than those in the former(logistic regression).2,Time of the abnormal CT appearances were detected: Abnormal CT appearances were found in the animals of immunosuppression groups in 1 day to 7 days and the mean time was 3.057 days. And the mean time of group 1 was 3.5 days, group 2 was 3.22 days, group 3 was 3.22 days, group 4 was 2.33 days. And the time of abnormal CT appearances were found in different groups had no statistical discrepancy (2×2 factorial experiment analysis of variance).3,Variation of the CTappearances: The four types of CT appearances were ordered with the time to appear as schistic GGO, nodous GGO, nodule of soft tissue density and schistic consolidation, and the mean time was 3.12,4.69,5.33,7.31 days respectively(F=14.783,P=0). The time to appear of schistic GGO was shorter than nodous GGO, nodule of soft tissue density and schistic consolidation (P=0.017, 0.000, 0.014 respectively ). The time to appear of schistic consolidation was longer than nodous GGO and nodule of soft tissue(P=0.000,0.046). In the end stage, new schistic GGO was found in 4 animals, new nodous GGO was found in 4 animals, new schistic consolidation was found in 13 animals, new nodule of soft tissue density was found in 3 animals, and diffuse abnormality was found in 20 animals. And schistic consolidation and diffuse abnormality were not appeared in the former CT exam.4,Features of the CT appearances: The most common initiatory CT appearances of the immunosuppression animals were schistic GGO at the periphery of the lung(32/35,91.4%). And there were no statistical difference among CT appearances of the 4 groups (logistic regression). Schistic GGO was found in 34 animals(97.1%), nodous GGO was found in 13 animals(38.2%), schistic consolidation was found in 13 animals(38.2%) and nodule of soft tissue density was found in 6 animals(17.1%) in the whole course. Moreover there are 34 animals (97.1%) in which multiple abnormalities were found. And there were no statistical difference among the 4 groups (logistic regression). 5,Pathologic foundation of CT appearances: There are 16 GGO and 19 Solid density specimens were selected for pathologic examination. Hemorrhage could be seen in 9 of the 16 GGO specimens, infl.cells exudation could be seen in 15, interstitial hyperplasy could be seen in 11, embolism could be seen in 8, alveolar consolidation could be seen in 1, alveolar hemorrhage could be seen in 9 specimens. Hemorrhage could be seen in 13 of the 19 Solid density specimens. Infl.cells exudation without alveolar consolidation could be seen in 1, interstitial hyperplasy could be seen in 16, embolism could be seen in 13, alveolar consolidation can be seen in 18, alveolar hemorrhage could be seen in 13 specimens. There was relatively high consistency between CT appearances and pathological findings.Conclusion1. The animal models of acute Aspergillus fumigatus pneumonia in New Zealand rabbits can be established with the conidia are inoculated through trachea or vein. Immunosuppression is crucial to establish the model. The state of immunosuppressive rabbits with aspergillus pneumonia aggravates rapidly, and the survival time is short, about a week. The survival of the rabbits inoculated through vein is shorter than inoculated through trachea.2. The CT abnormality of the animal models of acute Aspergillus fumigatus pneumonia in immunosuppressive New Zealand rabbits can be found in about 3 days after infection. There are no significant difference of the time of CT appearences appear between the animals inoculated through trachea and vein.3. The CT appearances of the animal models of acute Aspergillus fumigatus pneumonia in immunosuppressive New Zealand rabbits are nonspecific, and the most common appearance is schistic GGO at the periphery of the lung.4. There are no significant difference of the CT appearences between the animals inoculated through trachea and vein. Diffuse abnormality and schistic consolidation are the signals of aggravated and worse prognosis.5,There was relatively high consistency between CT appearance and pathological findings in the Aspergillus fumigatus pneumonia models of immunosuppressive New Zealand white rabbits. GGO in CT represents hemorrhage, inflammatory cell infiltration, and interstitium hyperplasy. Consolidations in CT represent consolidation, and interstitium hyperplasy. Embolism can be seen in both the two kind of specimen. Part II The CT morphological appearance and differential diagnosisof phymatoid pulmonary mycosisObjectiveStudy the epidemiology and CT morphological features of phymatoid pulmonary mycosis and compare with other benign dieeases (including inflammation, tuberculosis and benign tumor), purpose to summarize the highlights of differential diagnosis of phymatoid pulmonary mycosis.Materials and methodsThe clinical records and CT images of 173 cases with 214 pulmonary benign nodules/masses were studied, including 38 phymatoid mycosises with 67 nodules/masses, 43 inflammation patients with 46 nodules/masses, 55 tuberculosises with 64 nodules/masses and 37 benign tumors with 37 nodules/masses were studied. The age, gender of the patients and the CT appearance of the phymatoid pulmonary mycosis including the long diameter, shape(round or oval, irregular, wedge shaped), interface(smooth, clear, fuzzy), margin(superficial lobulation, prefound lobulation, rectus margin, spike, speculate protuberanc, halo sign), inner structure(cavitation, cavitation with thick wall, cavitation with irregular inner wall, calcification, fat, cresent sign,marginal fissure) and the satellites, changes of pleura nearby the nodules/masses were analyzed. And these features were compared with inflammation, tuberculosis and benign tumor, to summarize the highlights of differential diagnosisof phymatoid pulmonary mycosis.Results1,General information in patients : 173 patients, 99 male, 74 female, 18-79 years old, mean age 49.65±11.92 years. Mycosis: 38 patients, 25 male, 13 female, 26-77 years old, mean age 47.50±11.43 years; inflammation: 43 patients, 27 male, 16 female, 31-76 years old, mean age 52.14±11.30 years; tuberculosis: 55 patients, 36 male, 19 female; 18-79 years old, mean age 48.60±12.67 years; benign tumor: 37 patients, 11 male, 26 female, 32-78 years old, mean age 50.49±11.84 years. There were no statistical differences among the age distribution of the four categories diseases(ANOVA, F=1.240,P=2.297>0.05). And there were statistical differences among the gender distribution of the four categories diseases (χ2=14.632,P=0.002<0.05). And benign tumors were more prone to occur in female (P=0.003, 0.001, 0.002).2,Size: The range if the long diameters of the 214 nodules/masses was 0.5-8.1 cm, the mean long diameter was 3.04±1.62cm. The 4 categories diseases were arrowed by the long diameter as follows: Benign tumor(0.7-7.8cm, mean 2.14±1.34cm) < tuberculosis(0.5-7.6cm, mean 2.86±1.54cm)< phymatoid mycosis(0.5-7.3cm, mean 3.37±1.50cm)< inflammation(0.5-8.1cm, mean 3.55±1.78cm). There were statistical differences among the long diameter of the four categories diseases (ANOVA, F=7.065,P=0.000<0.05). The long diameter of benign tumor was shorter than the others (P=.000,0.000,0.026), and the long diameter of tuberculosis was shorter than inflammation (P=0.023<0.05), and there were no statistical differences between the long diameter of phymatoid mycosis and inflammation or tuberculosis(P>0.05).3,Features of the Morphology: The CT appearances of phymatoid pulmonary mycosis were round or oval shape(37, 55.2%), irregular shape(30, 44.8%), clear interface(57, 85.1%), fuzzy interface(7, 10.4%), smooth interface(3, 4.5%), speculate protuberanc(36, 53.7%), superficial lobulation(29, 43.3%), prefound lobulation(23, 34.4%), halo sign(14, 20.9%), spike(9,13.4%), rectus margin(6,9.0%); cavitation (10, 14.9%), 7 cavitations with thick wall, 5 with irregular inner wall and 5 with smooth inner wall; calcification(2, 3.0%), cresent sign(9, 13.4%), marginal fissure(7, 10.4%). And there were no fat in phymatoid pulmonary mycosis. Marginal fissure only could be seen in aspergillosis.4,Differential diagnosis: The incidence of irregular shape, round or oval shape, wedge shape, smooth interface, clear interface, fuzzy interface, speculate protuberanc, superficial lobulation, prefound lobulation, halo sign, cavitation, calcification, rectus margin, satellite, pleural thick and pleural indentation were different among the four categories diseases(p<0.05). The CT appearances of phymatoid pulmonary mycosis were compared with inflammation, tuberculosis and benign tumor separately. The clear interface was more common in phymatoid mycosis than in inflammation (P<0.0071). And the wedge shaped, fuzzy interface, speculate protuberanc, rectus margin, halo sign and cavitation were less commom in phymatoid mycosis than in inflammation (P<0.0071). The prefound lobulation was more common in phymatoid mycosis than in tuberculosis (P<0.0071). And superficial lobulation, cavitation, calcification, pleural thick were less common phymatoid mycosis than in tuberculosis (P<0.0071). The irregular shape, clear interface, speculate protuberanc, halo sign, prefound lobulation, satellite, pleural thick, pleural indentation were more commom in phymatoid mycosis than in benign tumor (P<0.0071). And the smooth interface, calcification were less common in phymatoid mycosis than in benign tumor (P<0.0071).Conclusion1. The susceptible crowd of phymatoid pulmonary mycosis is 40-60 years old males.2. The sizes of long diameter of phymatoid pulmonary mycosis are disparity. And the range of commom size is 2-4cm. The correct diagnosis of phymatoid pulmonary mycosis should not be carried out only according to the size.3. The common CT appearances of phymatoid pulmonary mycosis are round, oval shape or irregular shape; clear interface; speculate protuberanc, superficial lobulation or prefound lobulation, halo sign. There are usually thick wall with cavitation. The cresent sign and marginal fissure are specific signs of phymatoid pulmonary mycosis.4. Although overlay of the CT appearance are common, there are difference in the detail features of the signs, which make them an important evidence for the differential diagnosis of these diseases. The value of a single sign in the differential diagnosis is limited and multi-signs analysis in the differential diagnosis process tends to achieve the correct conclusion. The detection of wedge shaped, clear interface, fuzzy interface, speculate protuberanc, rectus margin, halo sign and cavitation conduce to differential diagnosis between phymatoid pulmonary mycosis and inflammation. And the detection of prefound lobulation, superficial lobulation, cavitation, calcification and pleural thick conduce to differential diagnosis between phymatoid pulmonary mycosis and tuberculosis. And the detection of irregular shape, clear interface, speculate protuberanc, halo sign, prefound lobulation, satellite, pleural thick, pleural indentation, smooth interface and calcification conduce to differential diagnosis between phymatoid pulmonary mycosis and benign tumor.
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