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Thoracic Imaging |
1 From the Departments of Diagnostic Radiology and Organ Imaging (G.E.A., K.T.W., E.H.Y.Y., A.T.A.), Medicine and Therapeutics (D.S.C.H., A.W., N.L., C.B.L., J.J.Y.S.), Accident and Emergency Medicine (T.H.R., P.C.), and Surgery (S.S.C.C.), Prince of Wales Hospital, Chinese University of Hong Kong, 30-32 Ngan Shing St, Shatin, Hong Kong SAR. Received May 7, 2003; revision requested May 14; revision received May 20; accepted May 21. Address correspondence to K.T.W. (e-mail: wongkatakjeffrey@hotmail.com).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Twenty-four patients (10 men, 14 women; mean age, 39 years; age range, 23–70 years) with confirmed SARS underwent follow-up thin-section CT of the thorax. The scans were obtained on average 36.5 days after hospital admission and were analyzed for parenchymal abnormality (ground-glass opacification, consolidation, or interstitial thickening) and evidence of fibrosis (parenchymal band, traction bronchiectasis, irregular interfaces). Patients were assigned to group 1 (with CT evidence of fibrosis) and group 2 (without CT evidence of fibrosis) for analysis. Patient demographics, length of hospital stay, rate of intensive care unit admission, peak lactate dehydrogenase level, pulsed intravenous methylprednisolone therapy, and peak opacification on chest radiographs were compared between the two groups.
RESULTS: Parenchymal abnormality was found in 96% (23 of 24) of patients and ranged from residual ground-glass opacification and interstitial thickening in group 2 (nine of 24, 38%) to fibrosis in group 1 (15 of 24, 62%). Patients in group 1 were older (mean age, 45 vs 30.3 years), had a higher rate of intensive care unit admission (27% [four of 15] vs 11% [one of nine]), more requirement for pulsed intravenous methylprednisolone (87%, [13 of 15] vs 67% [six of nine]), higher peak lactate dehydrogenase level (438.9 vs 355.6 U/L), and higher peak opacification on chest radiographs (estimated area, 14% vs 11%) than patients in group 2.
CONCLUSION: Pulmonary fibrosis may develop early in patients with SARS who have been discharged after treatment. Patients who are older and have more severe disease during treatment are more likely to develop thin-section CT findings of fibrosis.
© RSNA, 2003
Index terms: Lung, CT, 69.12118 • Pneumonia, acute interstitial, 69.21 • Severe acute respiratory syndrome
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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In view of the role of imaging in the diagnosis and management of SARS, we were interested in determining its role, if any, in the evaluation of patients after they have responded to treatment and have been discharged from the hospital. We were particularly interested in determining if thin-section CT demonstrates any residual parenchymal abnormalities or scarring in the early postdischarge period, as this may have implications for future treatment. Thus, the purpose of this study was to report our initial experience regarding the thin-section CT findings in patients with SARS who improved clinically after treatment.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients and CT Imaging
Our study extended from April 7, 2003, to May 6, 2003, and included 24 patients who had been discharged from the hospital after treatment for SARS as inpatients at our institution. Their diagnosis was based on World Health Organization criteria (2). All patients also met specified discharge criteria that included (a) being afebrile for at least 96 hours after the last dose of steroid, (b) resolving respiratory symptoms and oxygen independence, (c) radiologic improvement (based on serial chest radiographs) (4), and (d) improving laboratory parameters. If the patients met the discharge criteria and the date of hospital discharge was less than 21 days since the day of the onset of fever, they were discharged from the SARS hospital ward to a step-down convalescent facility. If the date of the hospital discharge was beyond 21 days since the day of the onset of fever, the patients were discharged home. Infection control protection maneuvers to be followed at home were explained to them. The 24 patients included 10 men and 14 women (age range, 23–70 years; mean age, 39 years).
Although these patients met the discharge criteria and were otherwise well enough to perform their daily activities, they complained of exertional dyspnea and/or reduced exercise tolerance at clinical follow-up. Because this was a new entity with no previous literature about disease progression for guidance, we performed follow-up thin-section CT (in addition to conventional chest radiography) in the patients to document any residual lung abnormalities. An additional 19 patients met our criteria but were not included in our study since thin-section CT, which had been scheduled, had not yet been performed.
Thin-section CT (HiSpeed Advantage; GE Medical Systems, Milwaukee, Wis) was performed (1-mm section thickness with 6-mm gap, supine position, scanning during inspiration, 1 second per scan, 120 kV, 140 mA). The scans were obtained on average 36.5 days (range, 16–56 days) after the initial hospital admission and 17.8 days after discharge (range, 1–33 days).
Review of CT Images
All CT images were reviewed by three radiologists (A.T.A., K.T.W., G.E.A.) using a viewing console, and findings were established by consensus. Each segment of the lung was reviewed for ground-glass opacification, airspace consolidation, interstitial thickening, bronchiectasis, and architectural distortion. Ground-glass opacification was defined as increased lung parenchymal attenuation that did not obscure the underlying vascular architecture (6). Consolidation was defined as opacification in which the underlying vasculature was obscured (6). Abnormalities were magnified by using a zoom function and were examined for intralobular interstitial, interlobular septal, or peribronchovascular interstitial thickening. Attention was also paid to the presence of nodules or masses, cavitation or calcification, and emphysema. The presence of parenchymal bands, irregular interfaces (bronchovascular, pleural, or mediastinal), and traction bronchiectasis were considered as evidence of fibrosis (7–9). Thickened interstitium could not be used as evidence of fibrosis since it may also be present during the acute illness (5).
For patients who underwent an initial examination (conventional or thin-section CT) for diagnosis, the abnormalities were compared with those seen on the follow-up thin-section CT scans.
Chest Radiography and Evaluation
Frontal chest radiographs were obtained during the hospital stay, at discharge, and at follow-up. All radiographic examinations were performed with CT equipment by using standardized techniques, as previously reported (4). The images were assessed by using a picture archiving and communication system viewer with a 2,048 x 2,048-pixel monitor (Magicview version VA22E; Siemens, Erlangen, Germany).
The chest radiographs were retrospectively reviewed by three radiologists (A.T.A., K.T.W., G.E.A.) in consensus by using a method identical to that used in a previous study (4).
Clinical Comparison and Data Analysis
Patients with evidence of pulmonary fibrosis at thin-section CT were designated as group 1, and patients without evidence of fibrosis at thin-section CT were designated as group 2.
Patient age, sex, average hospital stay, rate of intensive care unit admission, peak lactate dehydrogenase level, and the presence and number of doses of pulsed intravenous methylprednisolone were compared between the two groups. The peak opacification on chest radiographs during the hospital stay and the number of abnormal lung segments (showing any form of opacification or evidence of fibrosis) for each patient on follow-up thin-section CT scans were also compared between the two groups.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Chest Radiography at Discharge and Follow-up
At discharge, 20 of the 24 patients still had residual abnormalities on the chest radiographs. These abnormalities included patchy areas of opacification (20 of 24 patients) and signs of volume loss (five of 24 patients). At follow-up (in the review clinic, average of 18 days after discharge), 15 of 24 patients had an abnormal chest radiograph, and nine patients had a normal chest radiograph. Of the 15 patients, 10 showed improvement in the air-space opacification between discharge and follow-up, whereas abnormalities (airspace opacification or volume loss) on the chest radiographs remained static in the other five patients.
Thin-Section CT Abnormalities
The thin-section CT scan was abnormal in 23 (96%) of 24 patients. In all 23 patients, the images showed areas of ground-glass opacification of various sizes, along with thickening of interlobular septa and intralobular interstitium. The mean number of segments showing these abnormalities was 8.7 (range, 1–17). The thin-section CT scan was normal in one patient. There were no masses or nodules, emphysema, cavitation, or calcification.
In nine patients (eight underwent thin-section CT; one, conventional CT) who underwent CT at initial presentation, there was improvement in all patients, with residual ground-glass opacification and thickened interlobular septa in eight of the nine patients (Fig 1). The mean interval between the two CT scans was 23.3 days (range, 14–41 days). In one of the nine patients, there was complete resolution of the lung abnormalities.
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During their hospital stay, more patients in group 1 had received pulsed intravenous methylprednisolone (in addition to oral ribavirin and oral corticosteroid) than did patients in group 2 (87% [13 of 15] vs 67% [six of nine]). Group 1 patients also received a higher number of doses of pulsed intravenous methylprednisolone (average dose, 3.9; range, 1–8) than did group 2 patients (average dose, 3.0; range, 2–4).
The peak opacification on chest radiographs was slightly worse in group 1 patients, showing an average of 14% (range, 1.7%–33%) of the total area of opacification compared with that in group 2 patients (11%; range, 1.7%–28%). More lung segments were abnormal on the follow-up thin-section CT scans in group 1 patients (mean, 10.8; range, three to 17) than in group 2 patients (4.7; range, zero to 11).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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In our study, follow-up thin-section CT scans obtained in discharged patients have shown that fibrosis occurred in more than half (62%) of the patients. Findings of this study have also revealed how rapidly (mean follow-up, 36.5 days after hospital admission and 17.8 days after discharge) fibrosis may begin in patients with SARS. Viral pneumonia usually resolves without any clinical and radiologic sequelae (10). There have been reports of influenza pneumonia causing pulmonary fibrosis (11) and adenovirus pneumonia causing bronchiolitis obliterans (12). SARS may more commonly cause severe parenchymal damage, with imaging changes appearing early. How many of these changes will resolve in the future is unknown, although it is unlikely that the areas of severe architectural distortion will resolve. This damage may be related to the proposed pathogenesis of lung damage by exaggerated cell-mediated host immune response elicited by a viral antigen (13). We believe the presence of pulmonary fibrosis would at least partially account for the patients’ symptoms.
Of the nine patients with both predischarge and follow-up thin-section CT scans, all showed improvement after a mean of 23 days, with residual ground-glass opacification and thickened septa in eight patients and a complete resolution in one patient. Although the number of patients is small, this observation suggests that initial lung parenchymal changes are of an inflammatory nature and improve after successful therapy. In patients with evidence of fibrosis at thin-section CT, the importance of concomitant presence of ground-glass opacification is not clear. If bronchiolitis obliterans organizing pneumonia, or BOOP, or forms of idiopathic interstitial pneumonia are used as a frame of reference (14,15), these changes may represent persistent inflammation that is potentially reversible at treatment. Currently, treatment with corticosteroids or other steroid-sparing immunomodulating agents (such as cyclophosphamide) has been used in BOOP (16,17). These are being tried in our institution for SARS-induced fibrosis. Hence, we believe the role of thin-section CT in follow-up of patients with SARS is to assess the extent of long-term lung parenchymal injury and/or fibrosis and to identify these potentially reversible components early so that appropriate treatment may be instituted to prevent further lung damage.
Comparison of the follow-up thin-section CT findings with clinical data has revealed differences between patients with thin-section CT evidence of fibrosis and those without in terms of age, sex distribution, intensive care unit admission rate, peak lactate dehydrogenase level, doses of pulsed intravenous methylprednisolone, and peak opacification on chest radiographs during treatment. There is a predominance of men and older patients with evidence of fibrosis. The higher intensive care unit admission rate and the peak extent of changes on chest radiographs during treatment in patients with evidence of fibrosis are most likely a reflection of the severity of disease experienced by these patients.
Patients with evidence of fibrosis at thin-section CT also had a higher requirement of pulsed intravenous methylprednisolone during treatment. Nearly all patients with a clinical diagnosis of SARS were treated initially with a combination of orally administered ribavirin and corticosteroid. In patients not responsive to initial treatment, high-dose corticosteroid in the form of pulsed therapy was administered. In our initial cohort, 107 of 138 patients had received pulsed steroid therapy (13). The need for pulsed steroid therapy may reflect the magnitude of the cytokine "storm" elicited by the viral antigen, which in fact may be the underlying pathogenesis of lung damage and subsequent development of fibrosis.
The peak lactate dehydrogenase level is higher in patients with evidence of fibrosis. Lactate dehydrogenase is an indicator of tissue destruction (presumably lung tissue in SARS) and has been shown to be a good independent predictor of worse clinical outcome (13). This parameter may be helpful in predicting which patients have a higher risk of developing pulmonary fibrosis after discharge so that early appropriate therapy and the follow-up protocol can be tailored accordingly. As this is a new entity, much is still to be learned about this potentially fatal, highly infectious disease.
There are limitations to our study. First, on the basis of the number of patients and the relatively short follow-up period, the full spectrum of disease appearance has likely not been demonstrated. These patients have not been followed up for a long period of time, and it is possible that many of the clinical and thin-section CT findings may still be reversible. Second, there is no histologic confirmation of fibrosis in any of the patients, although the signs on thin-section CT scans are convincing. Third, there is no comparison with clinical information, such as results from lung function tests and objective assessment of exercise tolerance. Fourth, no thin-section CT was performed in treated patients who were asymptomatic, and, thus, residual abnormalities in these patients cannot be excluded.
In conclusion, on thin-section CT scans, fibrosis was seen in 62% of the 24 symptomatic patients with SARS after treatment, with symptoms of exertional shortness of breath and reduced exercise tolerance. There is a difference between patients with evidence of fibrosis at thin-section CT and those without in terms of intensive care unit admission rate, peak lactate dehydrogenase level, number of doses of pulsed intravenous methylprednisolone, and peak opacification on chest radiographs during treatment, which suggests that fibrosis is more likely to develop in patients with more severe disease. However, we wish to clearly state that our findings are only preliminary, and larger studies with longer follow-up will be necessary to better determine the long-term outcome for patients with SARS.
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, A.T.A.; study concepts, A.T.A., G.E.A., K.T.W., J.J.Y.S.; study design, A.T.A., G.E.A., K.T.W.; literature research, G.E.A., K.T.W.; clinical studies, D.S.C.H., A.W., N.L., C.B.L., T.H.R., P.C., S.S.C.C., J.J.Y.S.; data acquisition, A.T.A., K.T.W., G.E.A., E.H.Y.Y.; data analysis/interpretation, K.T.W., G.E.A.; statistical analysis, K.T.W., G.E.A.; manuscript editing, K.T.W., G.E.A., A.T.A., J.J.Y.S., D.S.C.H.; manuscript preparation, definition of intellectual content, revision/review, and final version approval, K.T.W., G.E.A., A.T.A.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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