CT Findings In Immunocompromised Hosts With Pulmonary Infections: Clinical And Animal Experimental Study

Part one Comparison with Thin-Section CT Findings of Candida albicans pneumonia,Aspergillus fumigates pneumonia and Cryptococcus neoformans pneumonia in persistently neutropenic rabbits【Background】The incidence of fungal infection increased in the past few years,and occured most commonly after bone marrow and solid organ transplantation and in patients with AIDS. CT examination,especially thin-section CT and postprocessing techniques may show pulmonary abnormalities,which is superior to radiography in depicting the pattern and extent of abnormalities.But most clinic studies have been limited to a relatively small number of patients,little information is available about CT features that may allow distinction among the various types of fungal infections.【Objective】To compare thin-section CT findings of C albicans pneumonia with those of A fumigates pneumonia and C neoformans pneumonia in persistently neutropenic rabbits.【Methods】A total of 72 healthy New Zealand White rabbits were used for all experiments.10~8 blastoconidia of C albicans ATCC10235;C neoforman H99A and 10~7 A fumigates obtained from departmrnt of dermatology of Changzheng hospital were inoculated in persistently neutropenic rabbits.C albicans group(n=19),control group(n=3);A fumigates group(n=19),control group(n=3);C neoformans group(n=19),and control group(n=3) were eventually used except five death before the experiment.C albicans and A fumigates models have especially been predictive of the clinical outcomes of treatments with antifungal agents in neutropenic hosts,but C neoforman pneumonia in persistently neutropenic rabbits were not recorded from the literature,and we operated in the same way with C albicans model.The diagnostic approach was based on the Clinical Pulmonary Infection Score,modified for use in rabbits.Thin-section CT scan was performed before inoculation and at 2,4,6,8,10,12,14d after inoculation respectively.CT scans of each rabbit were retrospectively and independently assessed by two chest radiologists for the pattern of the pulmonary abnormalities(ground-glass attenuation(GGO),consolidation, nodules,reticular or linear opacity,thickening of the bronchovascular bundles,pleural effusion),and the distribution of the lesion(unilateral or bilateral;upper,middle or lower lung lobes;more than one lobe involved).Consensus was reached for disagreements.CT data were entered into a spreadsheet(Excel 2007,Microsoft).Statistical analysis was performed using the x~2 test and the Fisher's exact test,a P value of less than 0.05 was considered statistically significant.【Results】1,Thin-Section CT findings for each type of pneumoniaThe CT manifestations were variable in neutropenic rabbits with C albicans pneumonia,consolidation(10/14) and ground-glass attenuation(8/14) were the most common findings,bronchovascular bundle thickening(3/14),nodule(2/14),and reticular or linear opacity(1/14) followed.Bilateral lung involvement was demonstrated in four cases.GGO(11/15) and consolidation(9/15) were the most common findings in neutropenic rabbits with A fumigates pneumonia.Bronchovascular bundle thickening was seen in four rabbits,and reticular or linear opacity was seen in two.Bilateral lung involvement was seen in nine cases,but nodules were not observed in any case with A fumigates pneumonia.16 rabbits had C neoformans pneumonia.14 of these cases had consolidation,and associated with ground-glass attenuation in 12 cases;ground-glass attenuation was seen in 13 cases.Three cases had bronchovascular bundle thickening,and nodular opacities, pneumothorax,reticular or linear opacity were respectively seen in one rabbit.Bilateral lung involvement was seen in about half of the patients with C neoformans pneumonia,3,Comparison of Thin-Section CT Findings In brief,ground-glass attenuation and air-space consolidation were the most common findings in neutropenic rabbits with these three fungal pneumonias,and occasionally associated with bronchovascular bundle thickening,nodules and reticular or linear opacity. There was no stastistically significant difference in the prevalence of these CT patterns.4,Comparison of frequency of Lobe InvolvementAlthough the presence of pulmonary lesion in middle lobes was higher in rabbits with A fumigates pneumonia and C neoformans pneumonia than in that with C albicans pneumonia,the difference was not statistically significant The frequency of involvement in other lobes and the frequency of involvement in more than one lobe were not statistically different between the three kinds of pneumonia.【Conclusion】C albicans pneumonia demonstrates a wide spectrum of thin-section CT findings that are similar to those of A fumigates and C neoformans;ground-glass attenuation and air-space consolidation are the most common findings,and usually associated with other findings,including bronchovascular bundle thickening,nodules and reticular or linear opacity;the difference of all the CT findings is not statistically significant.Part Two Pulmonary infections after kidney transplantation:Analysis of CT appearance in 121 Patients【Background】Pulmonary infections are a common cause of morbidity and mortality after kidney transplantation.Pathogens include bacteria,fungi,virus,and so on.Early and accurate diagnosis is clinically important,but difficult.CT examination,especially thin-section CT and postprocessing Techniques may show pulmonary abnormalities in patients with normal findings on radiographs and is superior to radiography in depicting the pattern and extent of abnormalities.Several studies have described the thin-section CT manifestations of pulmonary infections in kidney transplant patients.These studied have been limited to a relatively small number of patients and have focused mainly on the description of specific infections,few information is available about CT features that may allow distinction among the various types of infections.【Objective】The purpose of this study was to review the CT findings in patients with pulmonary infection after kidney transplantation and to determine distinguishing features among various types of infection。【Methods】The patients were selected by a review of the medical records at our institution from May 2000 to February 2008 and came from a population Of 446 patients who had been proven pulmonary infection after kidney transplantation.We identified 121 patients who had undergone thin-section CT of the chest and proven diagnosis within 1 week of the CT scans.The Pulmonary infiltration was considered to be infectious when there was clinical suspicion of a lower respiratory tract infection,the.presence of radiologic findings,a microbial agent isolated in respiratory and/or nonrespiratory samples,or improvement after specific treatment.Marconi MxS000(Siemens,Erlangen,Germany),Toshiba Aquilion(Toshiba Medical Systems,Tokyo,Japan),or Lightspeed VCT(General Electric Medical Systems, Milwaukee,WI) were used.The lungs were scanned at end-inspiration from the apex of the lung to the diaphragm.Postprocessing tools,including multiplanar reconstruction (MPR),maximum intensity projection(MIP) and minimum intensity projection(mIP),and volume rendering(VR),were used in some cases.The images were interpreted independently by two radiologists,who were blinded to the findings of other imaging modalities and the final diagnosis.The following CT findings were evaluated:pattern of the pulmonary abnormalities(GGO,reticular or linear opacity,air-space consolidation, nodules,tree-in-bud pattern,bronchovascular bundle thickening,pleural effusion,pleural thickening,and lymphadenopathy);distribution of the lesion(GGO,nodules,reticular or linear opacity).The clinical and CT data were entered into a spreadsheet(Excel 2007, Microsoft).Statistical analysis was performed using the x~2 test and the Fisher's exact test, a P value of less than 0.05 was considered statistically significant.【Results】一,Distributions of pulmonary infections in Kidney Transplant Recipients1,Time distributions:The incidence of pulmonary infections almost the same from 2001 to 2006,and have obviously increase in 2007.July to august and February to march were the most common season for these patients.2,Time Course:Pulmonary infections were diagnosed in 446 cases,which are more likely to occur in the time period between 2 and 4 months posttransplantation,with a peak incidence in the 3 months after the procedure.65(14.6%) episodes occurred in the first 30 days,147(32.9%) cases in the time period between 1 and 3 months,91(20.4%) cases between 3 and 6 months,23(5.2%) cases between 6 and 12 months,120(26.9%) cases after 12 months of transplantation,the mortality rate was 8.5%.In the first month after procedure,bacterial pathogens were predominately.One to 6 months following transplant, bacterial,virus(CMV) and mixed infection are seen commonly.After 12 months of transplantation,bacterial,virus(CMV) and mixed infection remains a concern but mycobacterial and fungal infections should be considered as potential causes for infiltrates.The study group(121 cases) was composed of 28 females and 93 males who ranged in age from 14 to 71 years(mean age 42.7 years).Pulmonary infection Occured from 10 to 4522 days posttransplantation,7 episodes occurred in the first 30 days,36 cases in the time period between 1 and 3 months posttransplantation,19 cases in the time period between 3 and 6 months posttransplantation,8 cases between 6 and 12 months posttransplantation, 51 cases after 12 months of transplantation.3,Infectious Etiologies:In the 121 patients enrolled as having pneumonia,89 patients had a definite etiologic diagnosis.Bacterial(28%) and mixed infections(28%) were the most common causes of pneumonia,followed by fungi(7%),TB(6%) and CMV(4%). More than 2/3rd of pulmonary infections in kidney transplant recipients can be attributed to bacterial organisms,Staphylococcus,Streptococcus pneumonia,and Gram-negative bacilli were the most common bacterial pathogens.All the virus pneumonia was caused by CMV.Candida albicans and Aspergillus were the most common fungal pathogens.二,CT Appearance in Kidney Transplant Recipients1,CT findings of the various infectionsPulmonary tuberculosis was diagnosed in 7 patients,and abnormalities were shown in 6 patients.Tree-in-bud pattem(n=4) was the most common finding in these patients.Small nodules were seen in 4 patients,GGO was seen in three patients,consolidation was seen in two,pleural effusion was seen in three,reticular or linear opacity in two,and mediastinal lymphadenopathy in one.34 cases had bacterial pneumonia.24 of these patients had GGO,twenty of which were diffuse,and four,focal.23 cases had nodular opacities,including 14 patients with centrilobular nodules and nine with random nodules;22 patients with small nodules and one with large nodules;One surround by halo sign.Reticular or linear opacity was seen in 20 patients,seventeen of which were diffuse,and three,patchy.Reticular or linear opacity was involved mainly the lower lung zone in 16 patients,associated with ground-glass attenuation in 11 cases;with consolidation in 4 cases,and both in five.Consolidation was seen in 11 patients and involved mainly the lower lung zone.CMV pneumonia:all 5 patients with CMV pneumonia had abnormal findings on CT scans.GGO was seen in 4 of 5 patients.These areas were all diffuse.In all four cases, ground-glass attenuation was associated with other abnormalities,including reticular or linear opacity(n=2),small nodules(n=2).Reticular or linear opacity were identified in 3 of 5 patients.These areas were all diffuse too.Multiple nodules were identified in 2 of 5 patients.All nodules were smaller than 10mm in diameter.Overall,the major of 5 patients with CMV pneumonia and 12 patients with mixed CMV pneumonia had GGO combined with reticular or linear opacity,nodules,tree-in-bud patterns.Fungal pneumonia:Reticular or linear opacity was the most common finding in these nine patients and associated with ground-glass opacities in two cases.GGO was seen in three patients,diffuse in two cases and focal in one.four cases had nodular opacities.Two large nodules surrounded by halo sign were seen in one patient with Aspergillus organisms. Air-space consolidation was seen in two patients,pleural thickening was seen in six patients,thickening of the bronchovascular bundle was seen in four patients,and tree-in-bud pattern was seen in two.For mixed infections,the CT manifestations were variable,which consisted of reticular or linear opacity,GGO,nodules,consolidation,pleural effusion,thickening of the bronchovascular bundles,or a combination of these patterns.2,comparison of the CT findings of the various infectionsTree-in-bud pattern was seen in 4 of 7 patients with tuberculosis,5 of 34 patients with bacterial pneumonia,2 of 9 patients with fungal pneumonia,2 of 5 patients with CMV pneumonia,1 of 34 patients with mixed infections.Tree-in-bud pattern(P=0.049) was significantly more frequent in patients with tuberculosis than in those with bacterial pneumonia.GGO was present in 24 of 34 patients with bacterial pneumonia,diffuse in 20 cases and focal in four.4 of 5 patients with CMV pneumonia and 3 of 9 patients with fungal pneumonia were diffuse.20 of 34 patients with mixed infection,diffuse in 17 cases and focal in three.3 of 7 patients with pulmonary tuberculosis,diffuse in one case and focal in two.Nodules were present in 23 of 34 patients with bacterial pneumonia,centrilobular in 14 cases and random in 9.4 of 7 patients with pulmonary tuberculosis,centrilobular in three cases and random in one.19 of 34 patients with mixed infection,random in 13 cases.4 of 9 patients had fungal pneumonia.2 of 5 patients had CMV pneumonia.Reticular or linear opacity was present in 23 of 34 patients with mixed infection, diffuse in 20 cases and focal in three.3 of 5 patients with CMV pneumonia and 6 of 9 patients with fungal pneumonia were all diffuse.20 of 34 patients had bacterial pneumonia, diffuse in 17 and focal in 3.3 of 7 patients had tuberculosis.Air-space consolidation was present in 2 of 7 patients with tuberculosis and 2 of 9 patients with fungal pneumonia,11 of 34 patients with bacterial pneumonia,focal in 8 cases and multifocal in three,patchy in seven and Segmental in three.7 of 34 patients with mixed infection,focal in one case and multifocal in seven,patchy in five cases and Segmental in five.Consolidation was not present in patient with CMV pneumonia.There was no stastistically significant difference in the prevalence of the CT patterns including GGO,reticular or linear opacity,nodules,air-space consolidation,pleural effusion,bronchovascular bundle thickening,Tree-in-bud pattern,and pleural thickening, among tuberculosis,bacterial,viral,fungal,mixed infections(all P＞0.05).【Conclusion】Our study shows that bacterial infection is the commonest cause of post kidney transplant pulmonary infection and more than 1/4rd of pulmonary infections can be attributed to multiple organisms.Pulmonary infections are more likely to occur in the time period between 2 and 4 months posttransplantation,with a peak incidence in the 3 months. In the first month after procedure,bacterial pathogens were predominately.One to 6 months following transplant,bacterial,virus(CMV) and mixed infection are commonly observed.After 12 months of transplantation,bacterial,virus(CMV) pneumonia and mixed infection remains a concern but mycobacterial and fungal infections should be considered as potential causes for infiltrates.The CT manifestations consist of reticular or linear opacity,GGO,nodules,consolidation,pleural effusion,bronchovascular bundle thickening,or a combination of these patterns;Tree-in-bud pattern were significantly more frequent in patients with tuberculosis than in those with bacterial pneumonia.Other CT patters are not helpful in distinguish among the various types of infection seen in kidney transplant recipients.The presence of large nodules surrounded by halo sign is most suggestive of Aspergillus infection.MDCT angiography has been shown to be a feasible technique to depict directly vessel occlusion in the setting of suspected fungal infections, especially for early diagnosis of angioinvasive pulmonary Aspergillosis in renal transplant recipients.Ground-glass attenuation is commonly seen in CMV pneumonia,and Reticular or linear opacity is common observed in fungal infection.Air-space consolidation is relatively common seen in bacterial,fungal and mixed pneumonia than other pathogens. Segmental consolidation in posterior of lower lung zone may gradually vanished by reversion to linear opacity,GGO.Pleural thickening is a valuable sign to judge the pulmonary infection.MDCT allows contiguous visualization of the lung parenchyma,the blood vessels and the airways.Postprocessing tools,including MPR,MIP,mIP,and VR, are used to help quantify the various patterns(MIP permits the detection and characterization of micronodules and tree-in-bud pattern;quantification the extent of air-space consolidation),assess the distribution and extent of these signs to help differentiate different type infections.