Pulmonary Infections After Bone Marrow Transplantation: High-Resolution CT Findings in 111 Patients

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1 Escuissato et al. CT of Pulmonary Infections After Bone Marrow Transplantat ion Chest Imaging Original Research Dante L. Escuissato 1 Emerson L. Gasparetto 1 Edson Marchiori 2 Gabriela de Melo Rocha 1 César Inoue 1 Ricardo Pasquini 3 Nestor L. Müller 4 Escuissato DL, Gasparetto EL, Marchiori E, et al. Received September 13, 2004; accepted after revision November 2, Department of Diagnostic Radiology, the University of Parana, Curitiba, Brazil. 2 Department of Diagnostic Radiology, the University of Rio de Janeiro, Rio de Janeiro, Brazil. 3 Bone Marrow Transplantation Unit, the University of Parana, Curitiba, Brazil. 4 Department of Radiology, Vancouver General Hospital, 899 W 12th Ave., Vancouver, BC V5Z 1M9, Canada. Address correspondence to N. L. Müller (nestor.muller@vch.ca). AJR 2005; 185: X/05/ American Roentgen Ray Society Pulmonary Infections After Bone Marrow Transplantation: High-Resolution CT Findings in 111 Patients OBJECTIVE. The purpose of this study was to review the high-resolution CT findings in patients with pulmonary infection after bone marrow transplantation and to determine distinguishing features among the various types of infection. MATERIALS AND METHODS. This study included 111 consecutive bone marrow transplant recipients who had documented pulmonary infection, high-resolution CT of the chest performed within 24 hr of the beginning of symptoms, and proven diagnosis within 1 week of the onset of symptoms. Two radiologists analyzed the CT scans and reached final decisions regarding the findings by consensus. Statistical analysis was performed using the Fisher s exact test and multivariate analysis; a p value of less than 0.05 was considered statistically significant. RESULTS. The pulmonary infections were due to viruses (n = 57), bacteria (n = 26), fungi (n = 21), and protozoa (n = 1). Six patients had more than one organism responsible for the infection. Nodules that were 1 cm or more in diameter were seen in 13 (62%) of 21 patients with fungal pneumonia, five (19%) of 26 patients with bacterial pneumonia (p = ), three (10%) of 30 with respiratory syncytial virus (RSV) pneumonia (p = ), and three (14%) of 22 with cytomegalovirus pneumonia (p = ). The halo sign was present in 10 of 21 patients with fungal pneumonia, two of 26 with bacterial pneumonia (p = ), three of 30 with RSV pneumonia (p = ), and one of 22 with cytomegalovirus pneumonia (p = ). There was no statistically significant difference in the prevalence of the other CT patterns including small nodules, ground-glass attenuation, and air-space consolidation among viral, bacterial, and fungal infections (all p > 0.05). CONCLUSION. The presence of large nodules and visualization of the halo sign are most suggestive of fungal infection. Other high-resolution CT patterns are not helpful in distinguishing among the various types of infection seen in bone marrow transplant recipients. ulmonary infections are a common cause of morbidity and mor- P tality after bone marrow transplantation [1, 2]. These infections occur despite routine prophylaxis for common pathogenic organisms and empiric therapy of febrile episodes during the early neutropenic period. Pathogens include fungi, bacteria, and viruses. Early and accurate diagnosis of these complications is important because of the high morbidity and mortality associated with infection and because of the frequent complications associated with the treatment of fungal and viral infections [3 5]. Several authors have emphasized the importance of high-resolution CT in the diagnosis of pulmonary infections after bone marrow transplantation [4 11]. High-resolution CT may show pulmonary abnormalities in patients with normal findings on radiographs and is superior to radiography in depicting the pattern and extent of abnormalities [4 7]. Several studies have described the high-resolution CT manifestations of pulmonary infections in bone marrow transplant patients [8 11]. These studies have been limited to a relatively small number of patients and have focused mainly on the description of specific infections. Limited information is available about high-resolution CT features that may allow distinction among the various types of infection. The aim of this study was to review the high-resolution CT findings in 111 patients who had infectious pulmonary complications after bone marrow transplantation and to determine distinguishing imaging features among the various types of infection. 608 AJR:185, September 2005

2 CT of Pulmonary Infections After Bone Marrow Transplantation Materials and Methods This study was retrospective and included 111 consecutive patients who had proven pulmonary infection after bone marrow transplantation and who had high-resolution CT of the chest performed within 24 hr of the onset of symptoms. The patients were selected by a review of the medical records and came from a population of 774 patients who underwent bone marrow transplantation at our institution from January 1993 to December Of these 774 patients, 348 had documented pulmonary complications, 212 of whom underwent high-resolution CT. We reviewed the medical records of all 212 patients and identified 111 patients who had proven pulmonary infection and who had undergone high-resolution CT within 24 hr of the onset of symptoms and proven diagnosis within 1 week of the onset of symptoms. The remaining 101 patients were excluded because they had no definite diagnosis, because they had diagnosis other than infection, or because the high-resolution CT examination was performed more than 24 hr after the onset of symptoms. The symptoms included fever, cough, and dyspnea. The study group was composed of 45 females and 66 males who ranged in age from 1 to 56 years (mean age, 23.7 years; median age, 22 years). All but one patient received allogeneic bone marrow transplantation. The transplantation was performed for the treatment of the following diseases: chronic myelogenous leukemia (n = 42), severe aplastic anemia (n = 33), acute nonlymphocytic leukemia (n = 11), myelodysplastic syndrome (n =8), Fanconi s anemia (n = 8), acute lymphocytic leukemia (n = 7), and Hodgkin s disease (n =2). The infectious complications after bone marrow transplantation were due to respiratory syncytial virus (RSV) (n =30), bacteria (n = 26), fungi (n = 21), cytomegalovirus (CMV) (n =22), herpes simplex virus type 2 (n = 3), influenza virus (n = 1), parainfluenza virus (n = 1), and toxoplasmosis (n = 1). Six patients had more than one organism responsible for the infection, including five cases of fungus and bacteria and one case of fungus and CMV. The bacterial pneumonias were due to Staphylococcus aureus in 12 patients, Pseudomonas aeruginosa in eight patients, Streptococcus viridans in four patients, Klebsiella pneumoniae in one patient, and Enterococcus faecalis in one patient. Fungal infections were caused by Aspergillus species in 17 patients, Candida albicans in three patients, and both Aspergillus and Candida species in one patient (Table 1). The pathogens responsible for the infectious episodes were documented by the following methods: bronchoalveolar lavage (n = 26), sputum culture (n = 22), sputum culture and bronchoalveolar lavage (n = 14), biopsy (n = 8), and autopsy (n =10). Fungal infection was diagnosed from culture and histologic evidence of tissue invasion (n =15). A positive blood culture in the presence of compatible clinical and radiologic findings was considered diagnostic in six cases of fungal pneumonia [11 13]. Diagnosis of RSV pneumonia was based on positive direct fluorescence antibody testing in specimens obtained at nasal washings, nasopharyngeal swab, and bronchoalveolar lavage [14]. The 20 patients with positive direct fluorescence antibody testing in specimens from nasal washings had respiratory symptoms and showed clinical and radiologic improvement after specific treatment [15, 16]. The diagnosis of CMV pneumonia was based on detection of the characteristic inclusion bodies in material obtained at bronchoalveolar lavage, autopsy, or lung biopsy. Positive polymerase chain reaction test results of blood, CMV antigenemia, clinical and imaging evidence of pulmonary disease, or improvement after specific treatment was considered diagnostic of CMV pneumonia in five cases [17]. Diagnosis of bacterial infection was based on a positive culture of sputum or bronchoscopic aspirate in most cases combined with positive blood or pleural fluid cultures. All CT examinations were performed on a Somatom ART scanner (Siemens Medical Solutions). The images were obtained at end-inspiration using a 2-mm collimation at 10-mm intervals and were reconstructed with a high-spatial-frequency algorithm and photographed using window settings appropriate to lung parenchyma (width, 1,500 H; level, 700 H) and mediastinum (width, 400 H; level, 20 H). Two radiologists analyzed the high-resolution CT scans and reached final decisions regarding the findings by consensus. The following high-resolution CT findings were evaluated: pattern of the pulmonary abnormalities (nodules, tree-in-bud pattern, air-space opacities, and ground-glass attenuation), distribution of the lesions (central or peripheral; unilateral or bilateral; symmetric or asymmetric; and upper, middle, or lower zones), bronchial wall thickening, mediastinal lymph node enlargement, and pleural effusions. The nodules were classified as large (1 cm in diameter) or small (< 1 cm in diameter). Ground-glass attenuation was defined as hazy increased attenuation of the lung without obscuration of the bronchial and vascular margins; airspace consolidation, as homogeneous increase in pulmonary parenchymal attenuation that obscured the margins of vessels and airway walls; small nodule, as a round opacity less than 10 mm in diameter; large nodule, as round opacity equal to or greater than 10 mm; tree-in-bud pattern, as centrilobular branching structures that resemble a budding tree; bronchial wall thickening, as thickness of the bronchial wall greater than one sixth of the bronchial diameter; and lymph node enlargement, as lymph nodes with short-axis diameter of greater than 10 mm. The pattern of ground-glass opacities was classified as diffuse, patchy, or focal. The distribution of air-space consolidation was classified as segmental or nonsegmental and as patchy or focal. Criteria for these findings were those defined in the Fleischner Society s glossary of terms [18]. The clinical and high-resolution CT data were entered into a spreadsheet (Excel 2003, Microsoft). Statistical analysis was performed using the Fisher s exact test and multivariate analysis, and a p value of less than 0.05 was considered statically significant. Results One hundred four patients (94%) had parenchymal abnormalities visible on high-resolution CT, and seven patients (6%) had normal findings on CT. Of the patients with normal CT findings, six had RSV infection and one had bacterial pneumonia. These six patients had similar symptoms as the remaining patients namely, fever, cough, and dyspnea. Like the remaining patients, they had high-resolution CT performed within 24 hr of the onset of symptoms. These patients had the infection 17, 20, 31, 34, 62, and 65 days after undergoing bone marrow transplantation. The parenchymal abnormalities seen on high-resolution CT in the various pulmonary infections and their time of occurrence are summarized in Table 1. Pleural effusion was seen in two patients with fungal pneumonia, four with bacterial pneumonia, and two with viral pneumonia. None of the patients had mediastinal lymphadenopathy. Fungal Pneumonia Seventeen of the 21 cases of fungal pneumonias were caused by Aspergillus organisms, three by Candida albicans, and one by both organisms. Nodules were the most common finding in these patients (Table 1). Large nodules were seen in 13 patients (62%); in 10 of these 13 patients, one or more nodules were surrounded by a halo of ground-glass attenuation (halo sign) (Fig. 1). Small nodules in a predominantly centrilobular distribution were noted in eight cases (38%), and a tree-in-bud pattern was seen in three patients (Fig. 2). Nodules were the only abnormality in 11 patients. In five cases, the nodules were associated with areas of air-space consolidation; in one case, with ground-glass opacities; and in one case, with both. AJR:185, September

3 Escuissato et al. TABLE 1: High-Resolution CT Findings in the Major Groups of Pulmonary Infections After Bone Marrow Transplantation High-Resolution CT Findings Fungal Pneumonia (n = 21) Bacterial Pneumonia (n =26) Respiratory Syncytial Virus Pneumonia (n =30) Cytomegalovirus Pneumonia (n = 22) Nodules Small nodules 8 (3/1/4) 13 (3/3/7) 13 (8/3/2) 11 (2/7/2) Large nodules 13 (4/2/7) 5 (1/1/3) 3 (0/0/3) 3 (0/2/1) Tree-in-bud pattern 3 (1/1/1) 3 (1/0/2) 3 (1/2/0) 2 (1/0/1) Ground-glass attenuation Diffuse 1 (0/1/0) 3 (1/1/1) 4 (2/1/1) 7 (0/5/2) Patchy 1 (0/0/1) 3 (1/0/2) 1 (1/0/0) 7 (2/4/1) Focal 3 (1/0/2) 2 (1/0/1) 1 (0/0/1) Air-space consolidation Nonsegmental focal 5 (3/1/1) 8 (1/1/6) 3 (3/0/0) 4 (1/1/2) Nonsegmental multifocal 1 (0/1/0) 5 (2/2/1) 3 (2/1/0) 3 (1/1/1) Segmental 5 (1/2/2) 5 (2/1/2) 4 (3/0/1) Other signs Bronchial wall thickening 3 (0/1/2) 5 (1/1/3) 11 (7/2/2) 3 (0/2/1) Halo sign 10 (3/0/7) 2 (0/0/2) 3 (2/1/0) 1 (1/0/0) Note The numbers in parentheses are related to the frequency of the findings in the neutropenic, early, and late phases, respectively, after bone marrow transplantation. Dash ( ) indicates no cases with that finding. Fig year-old woman with invasive aspergillosis 104 days after bone marrow transplantation. High-resolution CT scan obtained at level of middle lobe shows large nodule surrounded by ground-glass attenuation (arrows) (CT halo sign). Eleven patients had areas of air-space consolidation, which were bilateral and asymmetric, and two patients had bilateral areas of ground-glass attenuation. Bacterial Pneumonia Twenty-six patients had bacterial pneumonia (Table 1). Twenty-one of these patients (81%) had nodular opacities, including 16 patients (61%) with small centrilobular nodules and five (19%) with large nodules (Fig. 3). In three patients, the small centrilobular nodules were associated with a tree-in-bud pattern. Two patients had a halo of ground-glass attenuation surrounding the nodules, and one had large nodule cavitation. Air-space consolidation was seen in 18 patients (69%) with bacterial pneumonia (Fig. 4). The areas of consolidation were focal nonsegmental in eight patients, multifocal nonsegmental in five, and segmental in five patients. The consolidation was bilateral and asymmetric in 11 patients and involved mainly the middle lung zones in nine patients and the lower lung zones in eight patients. Nine patients had areas of ground-glass attenuation, three of which were diffuse; three, patchy; and three, focal. The ground-glass opacities were bilateral symmetric in six patients and asymmetric in three. There was no predominant lung zone distribution. Overall, of the patients with bacterial pneumonia four (15%) had only nodules and three (12%) had only consolidation; the remaining patients (73%) had various combinations of nodules, consolidation, and ground-glass attenuation. Viral Pneumonia RSV pneumonia Six of the 30 patients with RSV pneumonia had normal findings on CT scans. Nodular lesions were seen in 19 patients (63%) (Fig. 5 and Table 1). Sixteen cases (53%) had small centrilobular nodules, three had branching opacities (tree-in-bud pattern), and three had large nodules. Three of the 16 patients with centrilobular nodules had a tree-in-bud pattern. In three patients, the nodules were surrounded by a halo of groundglass attenuation. Areas of air-space consolidation were seen in 10 patients (33%) (Fig. 5). The consolidation was segmental in four patients, patchy nonsegmental in three patients, and focal in three patients. The consolidation was unilateral in three patients, bilateral and asymmetric in distribution in five, and symmetric in two. Seven patients (23%) had areas of ground-glass attenuation, which was diffuse in four cases, focal in two, and patchy in one (Fig. 6). The ground-glass opacities were bilateral and symmetric in four patients and asymmetric in three. Overall, six (20%) of the 30 patients with RSV pneumonia had normal CT scans, six (20%) had only nodules, two (6%) had only ground-glass attenuation, and one (3%) had only consolidation. The remaining patients (50%) had various combinations of nodules, ground-glass attenuation, and consolidation. 610 AJR:185, September 2005

4 CT of Pulmonary Infections After Bone Marrow Transplantation Fig year-old boy with Aspergillus infection 133 days after bone marrow transplantation. High-resolution CT scan obtained at level of pulmonary veins shows large nodule with irregular margins in lingula and several small nodules. Some small nodules are centrilobular (curved arrows), and some are in a random distribution (straight arrow). Fig year-old woman with Staphylococcus aureus pneumonia 46 days after bone marrow transplantation. High-resolution CT scan of right lung shows focal areas of air-space consolidation in right upper lobe. CMV pneumonia All 22 patients with CMV pneumonia had abnormal findings on CT scans. Multiple small nodules were seen in 13 patients (59%), and large nodules were detected in three (14%) (Fig. 7). The distribution of the lesions most commonly was bilateral and symmetric (n = 11) and peripheral (n = 14) and had no zonal predominance. Air-space consolidation was present in seven patients (31%), and in all cases, it involved mainly the peripheral lung regions of the middle and lower zones. Ground-glass opacities were observed in 15 patients (68%), being diffuse in seven patients, patchy in seven patients, and focal in one patient (Fig. 8). Overall, of the patients with CMV pneumonia, four (18%) had only nodules, two (9%) had only consolidation, and two (9%) had only ground-glass attenuation. The remaining patients (64%) had various combinations of nodules, ground-glass attenuation, and consolidation. Other viral pneumonias Three patients had herpes simplex virus type 2 pneumonia. Small centrilobular nodules were seen in two patients, and large nodules with a halo sign were found in one patient. Diffuse or patchy areas of ground-glass attenuation were noted in all patients. Influenza pneumonia was diagnosed in one patient. High-resolution CT showed small centrilobular nodules and patchy nonsegmental consolidation. The patient with parainfluenza B pneumonia presented with focal nonsegmental consolidation and areas of mosaic perfusion. Other Organisms and Mixed Pneumonias One patient had Toxoplasma gondii pneumonia. On high-resolution CT, this patient had diffuse ground-glass attenuation with superimposed smooth interlobular septal thickening and intralobular linear opacities resulting in a crazy paving pattern. Five patients had mixed pneumonia caused by bacteria plus fungi (n = 5). One of these patients had small centrilobular nodules, one had large Fig year-old woman with Pseudomonas aeruginosa pneumonia 18 days after bone marrow transplantation. High-resolution CT scan obtained at level of main bronchi shows multiple bilateral nodules of variable sizes, some of them with surrounding ground-glass attenuation. nodules, two had bilateral ground-glass opacities, and two had bilateral areas of consolidation. One patient had mixed pneumonia caused by CMV plus fungi. The only finding in this patient was diffuse bronchial wall thickening. Comparison of the CT Findings of the Various Infections Large nodules were most common in patients with fungal pneumonia, being seen in 13 (62%) of the 21 patients with fungal pneumonia, five (19%) of 26 with bacterial pneumonia (p = ), three (10%) of 30 with RSV pneumonia (p = ), and three (14%) of 22 with CMV pneumonia (p = ) (Table 2). The halo sign also was more frequent in patients with fungal pneumonia, being seen in 10 (48%) of the 21 patients with fungal pneumonia, two (8%) of 26 with bacterial pneumonia (p = ), three (10%) of 30 with RSV pneumonia (p = ), and one (5%) of 22 with CMV pneumonia (p = ). There was no other statistically significant difference among viral, fungal, and bacterial pneumonias (Table 2). There was a statistical difference in the presence of patchy ground-glass attenuation between CMV and RSV (p = ). However, there was no statistical difference overall in patchy groundglass attenuation between viral pneumonias and fungal or bacterial pneumonias (Table 2). Discussion Infection is the most common cause of pulmonary complication after bone marrow AJR:185, September

5 Escuissato et al. Fig year-old man with respiratory syncytial virus pneumonia 57 days after bone marrow transplantation. High-resolution CT scan obtained at level of main bronchi shows multiple small nodules in right upper lobe (arrows) and areas of airspace consolidation associated with ground-glass attenuation in left upper lobe. Fig year-old man with cytomegalovirus pneumonia 49 days after bone marrow transplantation. High-resolution CT scan obtained at level of pulmonary veins shows multiple small nodules (arrows). transplantation. The course of immunosuppression and recovery in these patients influences the type of infection. During the period before engraftment (0 30 days) that is, before successful establishment of the graft in patients after bone marrow transplantation profound neutropenia and damaged mucosal membranes are the main abnormalities in host defense. These predispose patients to fungal, bacterial, and RSV pneumonias [19, 20]. During the period after engraftment ( days), there is impairment of both cellular and humoral immunity that predisposes the patient to mainly CMV and RSV infections [19, Fig year-old woman with respiratory syncytial virus pneumonia 33 days after bone marrow transplantation. High-resolution CT scan obtained at level of left upper lobe bronchus shows bronchial wall thickening (arrowheads). Fig year-old man with cytomegalovirus pneumonia 62 days after bone marrow transplantation. High-resolution CT scan obtained at level of main bronchi shows diffuse ground-glass attenuation superimposed on mild centrilobular emphysema. 21]. During the late posttransplantation period (> 100 days), infection in the absence of graft-versus-host disease is uncommon because of the relative normal immunologic function at this phase. However, in patients with graft-versus-host disease, the defects may persist indefinitely, and patients remain susceptible to bacterial, fungal, and viral infections [1, 4, 7, 19 22]. Patients with graftversus-host disease have increased susceptibility to infection because graft-versus-host disease involves the mucosal surfaces, the reticuloendothelial system, and bone marrow, causing an immunodeficient state, and because these patients require immunosuppressive agents [6]. Fungal pneumonia is one of the main causes of morbidity and mortality after bone marrow transplantation [13, 23, 24]. The most common organism of fungal pneumonia is Aspergillus species, being responsible for 90% of such infections [7]. Candida species, usually Candida albicans, is the second most frequent fungal organism and is seen most commonly in patients with leukemia and lymphoma [25]. The lung lesions in invasive pulmonary aspergillosis are characterized by vascular invasion and occlusion of small- to medium-sized 612 AJR:185, September 2005

6 CT of Pulmonary Infections After Bone Marrow Transplantation TABLE 2: p Values for the Comparison of the Frequency of the Various High-Resolution CT Findings in Pulmonary Infections After Bone Marrow Transplantation High-Resolution CT Findings Fungal and Bacterial Infections Fungal Infection Bacterial Infection Fungal Infection Bacterial Infection Respiratory Syncytial Virus Nodules Small nodules Large nodules Tree-in-bud pattern Ground-glass attenuation Diffuse Patchy Focal Air-space consolidation Nonsegmental focal Nonsegmental patchy Segmental or lobar Other signs Bronchial wall thickening Halo sign Note The values of p that are statistically significant are shown in bold. pulmonary arteries by fungal hyphae [26]. The resulting areas of hemorrhagic infarction are seen on CT as nodules surrounded by areas of ground-glass attenuation (halo sign) [11, 27, 28]. Several studies have shown the value of high-resolution CT in the diagnosis of invasive pulmonary aspergillosis. Common findings include large nodules, frequently with a halo of ground-glass attenuation, and focal areas of consolidation [11, 27, 28]. Although the halo sign in immunocompromised patients is most suggestive of invasive aspergillosis, this sign has also been described in patients with Candida infection, cryptococcosis, CMV pneumonia, herpes simplex virus infection, and Kaposi s sarcoma [12, 27, 29]. Pulmonary candidiasis may spread to the lung via a hematogenic or endobronchial route. When from endobronchial seeding, candidiasis is limited usually to the lungs, may present with consolidation or nodules, and tends to involve mainly the lower lobes. Hematogenic dissemination results in symmetric nodular lesions throughout the lungs and often is associated with extrapulmonary disease. The characteristic pathologic findings consist of hemorrhagic nodules that usually measure 2 4 mm in diameter and frequently have a necrotic center containing the Respiratory Syncytial Virus and organisms [30]. The high-resolution CT findings that are suggestive of pulmonary candidiasis include solitary or multiple nodules, ground-glass opacities, and areas of air-space consolidation [7, 25, 30]. The most common finding of fungal infection in the current study was large nodules and masses, which were seen in 13 (62%) of 21 patients. Small nodules were identified in eight patients. Cavitation was seen in only one patient. Large nodules were more common in patients with fungal pneumonia than in those with bacterial or viral pneumonia. The halo sign was also more frequent in patients with fungal pneumonia than in other pneumonias. The most common organisms resulting in bacterial pneumonia in bone marrow transplant patients before marrow engraftment are gram-negative bacteria from the intestinal flora or oral mucosa and gram-positive organisms, particularly Staphylococcus and Streptococcus species. During the early phase after bone marrow transplantation, the most frequent causes of bacterial pneumonia are gram-negative organisms including Pseudomonas aeruginosa and Escherichia coli [7, 10, 19]. Six months after bone marrow transplantation bacterial sinopulmonary infections are caused most frequently by gram-positive Cytomegalovirus and organisms, such as Streptococcus pneumoniae and Staphylococcus aureus. Gram-negative bacteria, most commonly Haemophilus influenzae and Pseudomonas species, are found in patients with obstructive airway disease [7]. Limited information is available concerning the high-resolution CT findings of bacterial pneumonia in bone marrow transplantation patients. The chest radiography findings in this group of patients have been described as being similar to those seen in immunocompetent patients, with predominance of focal areas of air-space consolidation [10, 19]. Lossos et al. [31], in a study of 52 episodes of bacterial pneumonia after bone marrow transplantation, observed 12 cases (23%) with involvement of only one lobe or segment. Reittner et al. [32] studied the high-resolution CT findings of 114 patients with pneumonia. That study included 35 cases of bacterial pneumonia (five of them in immunocompromised patients), and the most common findings were air-space consolidation (85%), ground-glass opacities (31%), reticular opacities (22%), and small centrilobular nodules (17%). The frequency of air-space consolidation and ground-glass opacities in the current study was similar, being present in 69% and 35% of patients, respectively. However, AJR:185, September

7 Escuissato et al. small centrilobular nodules were seen more frequently in our study, being observed in 13 (50%) of 26 cases. Five patients (19%) presented with large nodules. In most of the patients with bacterial pneumonia (21/26, 81%), the abnormalities involved more than one lung segment; in five cases (19%), they were observed in only one segment or lobe. Viral infections usually occur in seasonal outbreaks in the community. The most common organisms in bone marrow transplantation patients are RSV, adenovirus, influenza virus, and parainfluenza virus [9, 16]. The dissemination of these infections to the lower respiratory tract is associated with a significant increase in mortality [15]. Ko et al. [14] reviewed the high-resolution CT of patients with RSV pneumonia after lung transplantation. The most common findings were airspace consolidation and areas of ground-glass attenuation [14]. Gasparetto et al. [33] reviewed the high-resolution CT features of 20 patients with RSV pneumonia after bone marrow transplantation. The predominant findings were small centrilobular nodules and patchy areas of consolidation and groundglass opacities in a bilateral asymmetric distribution [33]. In the current study, small centrilobular nodules were seen in 16 (53%) of 30 patients, air-space consolidation in 10 patients (33%), and ground-glass opacities in seven patients (23%). CMV is one of the most common causes of viral infection after bone marrow transplantation [8, 21]. The infection is caused by reactivation of the latent virus at a time of profound immunosuppression or infusion of CMV-seropositive marrow or blood products into a CMV-seronegative recipient [1, 3]. The most common high-resolution CT manifestations of CMV pneumonia are small centrilobular nodules, air-space consolidation, and groundglass opacities [9, 17, 34]. Similar findings were seen in the current study, ground-glass opacities being seen in 68% of patients, small centrilobular nodules in 50%, and areas of air-space consolidation in 32%. These abnormalities usually are bilateral, diffuse, and asymmetric in distribution. Less common findings included large nodules and a tree-inbud pattern. Our study has several limitations. It is retrospective and includes a relatively small number of patients with each type of infection. The study included consecutive patients who underwent CT within 24 hr of the onset of symptoms and who had proven diagnosis. Although the study included nearly equal subsets of fungal, bacterial, and CMV and RSV pneumonias, it cannot be inferred that these infections are equally common. We believe that bacterial and fungal infections are more common than viral pneumonias in patients with bone marrow transplant. However, many of these patients are treated empirically on the basis of clinical and radiologic findings and do not have a definitive diagnosis. In conclusion, there is a considerable overlap among the high-resolution CT manifestations of viral, bacterial, and fungal pneumonias in bone marrow transplant patients. Large nodules and the halo sign are findings that are statistically more common in patients with fungal pneumonia. Ground-glass opacities, air-space consolidation, and small nodules are not helpful in the differential diagnosis of various pulmonary infections after bone marrow transplantation. References 1. Soubani AO, Miller KB, Hassoun PM. Pulmonary complications of bone marrow transplantation. Chest 1996; 109: Krowka MJ, Rosenow EC 3rd, Hoagland HC. Pulmonary complications of bone marrow transplantation. Chest 1985; 87: Breuer R, Lossos IS, Berkman N, Or R. Pulmonary complications of bone marrow transplantation. 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8 CT of Pulmonary Infections After Bone Marrow Transplantation FOR YOUR INFORMATION tomography in acute diffuse lung disease in the immunocompromised patient. Radiol Clin North Am 1994; 32: Franquet T, Müller NL, Gimenéz A, Guembe P, de La Torre J, Baguè S. Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic findings. RadioGraphics 2001; 21: Primack SL, Hartman TE, Lee KS, Müller NL. Pulmonary nodules and the CT halo sign. Radiology 1994; 190: Kuhlman JE, Fishman EK, Burch PA, Zerhouni EA, Siegelman SS. CT of invasive pulmonary aspergillosis. AJR 1988; 150: Zinck SE, Leung AN, Frost M, Berry GJ, Müller NL. Pulmonary cryptococcosis: CT and pathologic findings. J Comput Assist Tomogr 2002; 26: Dubois PJ, Myerowitz RL, Allen CM. Pathoradiologic correlation of pulmonary candidiasis in immunosuppressed patients. Cancer 1977; 40: Lossos IS, Breuer R, Or R, et al. Bacterial pneumonia in recipients of bone marrow transplantation. Transplantation 1995; 60: Reittner P, Ward S, Heyneman L, Johkoh T, Müller NL. Pneumonia: high-resolution CT findings in 114 patients. Eur Radiol 2003; 13: Gasparetto EL, Escuissato DL, Marchiori E, Ono S, Frare e Silva RL, Müller NL. High-resolution CT findings of respiratory syncytial virus pneumonia after bone marrow transplantation. AJR 2004; 182: Franquet T, Lee KS, Müller NL. Thin-section CT findings in 32 immunocompromised patients with cytomegalovirus pneumonia who do not have AIDS. AJR 2003; 181: The full text and images from the American Journal of Roentgenology may also be viewed online at AJR:185, September