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Published online before print July 29, 2005, 10.1148/radiol.2363040958
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(Radiology 2005;236:1067-1075.)
© RSNA, 2005

Thoracic Imaging

Pulmonary Sequelae in Convalescent Patients after Severe Acute Respiratory Syndrome: Evaluation with Thin-Section CT1

Yeun-Chung Chang, MD, PhD, Chong-Jen Yu, MD, PhD, Shan-Chwen Chang, MD, PhD, Jeffrey R. Galvin, MD, Hon-Man Liu, MD, Cheng-Hsiang Hsiao, MD, Ping-Hong Kuo, MD, Kuan-Yu Chen, MD, Teri J. Franks, MD, Kou-Mou Huang, MD and Pan-Chyr Yang, MD, PhD

1 From the Departments of Medical Imaging (Y.C.C., H.M.L., K.M.H.), Internal Medicine (C.J.Y., S.C.C., P.H.K., K.Y.C., P.C.Y.), and Pathology (C.H.H.), National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan S Rd, Taipei, Taiwan; and Departments of Radiologic Pathology (J.R.G.) and Pulmonary and Mediastinal Pathology (T.J.F.), Armed Forces Institute of Pathology, Washington, DC. Received May 31, 2004; revision requested August 9; revision received September 24; accepted October 26. Supported by grant NSC92-3112-B-002-042 from the National Science Council, Executive Yuan, Taipei, Taiwan, Republic of China. Address correspondence to P.C.Y. (e-mail: pcyang{at}ha.mc.ntu.edu.tw).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To prospectively evaluate lung parenchyma on paired inspiration-expiration thin-section computed tomographic (CT) scans in patients recovering from severe acute respiratory syndrome (SARS).

MATERIALS AND METHODS: After the institutional review board approved the study and written consent was obtained from patients, 40 patients (25 female, 15 male; mean age, 42.8 years ± 12.3 [standard deviation]) underwent thin-section CT at 51.8 days ± 20.2 after onset of SARS symptoms. Twenty of the 40 patients underwent follow-up thin-section CT at 140.7 days ± 26.7 after symptom onset. Lung findings were scored according to extent and then grouped in three categories (ground-glass opacity, interstitial opacity, and air trapping) for analysis. Mean CT scores for each finding in the various patient subgroups were compared by using the Mann-Whitney test. Clinical parameters and scores were evaluated for correlation by using Spearman rank correlation analysis. Mean scores for each finding were compared between the two serial examinations by using the Wilcoxon matched-pairs signed rank test.

RESULTS: Air trapping, ground-glass opacity, and reticulation were found in 37 (92%), 36 (90%), and 28 (70%) of 40 patients, respectively, at initial thin-section CT examination and in 16 (80%), 14 (70%), and 10 (50%) of 20 patients, respectively, at follow-up examination. Scans from patients with adult respiratory distress syndrome (ARDS) had a significantly higher score for ground-glass opacity than did those from patients without ARDS (P = .009). A comparison of scores for the serial thin-section CT examinations indicated a significant reduction in the extent of ground-glass opacity (P < .001) and interstitial opacity (P < .001) but not in that of air trapping (P = .38) at follow-up examination. At initial thin-section CT, scores for ground-glass opacity, interstitial opacity, and air trapping correlated with age; those for ground-glass opacity and air trapping, with peak C-reactive protein level. At the second examination, scores for ground-glass opacity and interstitial opacity correlated with peak lactate dehydrogenase level; that for air trapping, with age and peak C-reactive protein level.

CONCLUSION: Thin-section CT scores correlated with clinical and laboratory parameters in patients after SARS. Although ground-glass opacity and interstitial opacity resolve over time, air trapping persists.

© RSNA, 2005


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Severe acute respiratory syndrome (SARS) is an infectious disease that was identified in late February 2003. The disease was first reported among people in Guangdong Province, China; Hanoi, Vietnam; and Hong Kong, China. It has since spread across the world to North America, Europe, and Taiwan and other Asian countries (1). The disease is caused by a new coronavirus, SARS-CoV (2). All patients with SARS develop pulmonary complications during the course of the disease. Approximately one-quarter of those affected were admitted to an intensive care unit for respiratory failure after a variable period of fever, shortness of breath, and hypoxemia (3,4).

The common radiographic manifestation of SARS is consolidation in the lower lobes and peripheral regions of the lungs (5,6). Thin-section computed tomographic (CT) images acquired early in the course of SARS usually show ground-glass opacity in the lower lobes of the lungs, with peripheral distribution (7). In contrast, consolidation and thickening of interlobular septa and intralobular interstices are less common. Early development of pulmonary fibrosis in patients with SARS was reported on the basis of a study of follow-up thin-section CT scans obtained 1 month after onset of the disease (8). Little is known, however, about sequential CT findings during the subsequent course of SARS, especially about sequelae that may occur during convalescence. Thus, the purpose of our study was to prospectively evaluate lung parenchyma on paired inspiration-expiration thin-section CT scans in patients recovering from SARS.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Patients and Sequence of Imaging
Seventy-six patients who received an initial diagnosis of probable SARS at our institution were included in the study. Symptoms in all 76 patients fulfilled the clinical criteria for diagnosis of SARS according to the definition of the World Health Organization and included a temperature of more than 38°C, cough or breathing difficulty, history of exposure to SARS within 10 days prior to the onset of symptoms, and abnormal findings at chest radiography (9). Fifteen patients died during hospitalization. The remaining 61 patients were discharged after clinical improvement. Although all 61 were scheduled for thin-section CT study, 40 patients were enrolled in the study after informed consent was obtained. These included 25 women and 15 men with a mean age of 42.8 years ± 12.3 (standard deviation [SD]) The remaining 21 patients refused to participate in the study after their discharge from the hospital. This study was conducted with institutional review board approval and was performed during the period of convalescence, approximately 3 weeks after the patient's clinical recovery from SARS.

In all 40 patients, a fourfold or greater increase in the serum level of anti–SARS-CoV antibody was found during convalescence. Thirty-nine of the 40 patients were nonsmokers, while one woman consumed half a pack of cigarettes per day for more than 10 years. One woman had a prior history of pulmonary tuberculosis with bronchiectasis of the right lung. The remaining 39 patients had no known prior pulmonary disease, and all 40 had no known history of airflow obstruction. Thirty-eight patients received methylprednisolone at a dosage of 2 mg/kg/d for 5 days, followed by 2 mg/kg/d oral prednisolone for 5 days, with a gradually tapered dose thereafter, for treatment of progressive lung infiltration; 28 received intravenous immunoglobulin at a dosage of 1 mg/kg/d for 2 days; and 11 received pulse therapy with 500 mg/d methylprednisolone for 3 days, as rescue therapy. Ribavirin was administered to 39 patients soon after the diagnosis of SARS was established, with a loading dose of 2000 mg followed by 1200 mg/d if body weight was more than 75 kilograms or by 1000 mg/d if body weight was less than 75 kilograms. The duration of ribavirin therapy was 10 days unless the patient experienced adverse effects. Thin-section CT scans were acquired between May 30, 2003, and November 6, 2003.

All 40 patients underwent thin-section chest CT after clinical recovery and release from quarantine, between 22 and 96 days (mean, 51.8 days ± 20.2) after the onset of symptoms. Adult respiratory distress syndrome (ARDS), defined according to the American-European consensus conference as diffuse pulmonary infiltrates on the chest radiograph, a PaO2/FIO2 ratio of 200 mm Hg or less, and lack of evidence of cardiac failure (10), occurred in 16 (40%) of 40 patients. Twenty of these 40 patients underwent a second examination with thin-section CT between 107 and 202 days (mean, 140.7 days ± 26.7) after symptom onset, and eight (40%) of them had ARDS.

Demographic, Clinical, and Laboratory Data
Data for demographic, clinical, and laboratory parameters, including age, treatment modality (use of intravenous immunoglobulin and pulse steroid therapy), and peak serum levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST), were collected for analysis by one of three authors (C.J.Y., S.C.C., P.H.K.). Age and the specific laboratory parameters (CRP, LDH, and AST levels) were chosen because the results of previous investigations indicated that they were factors related to the severity of respiratory failure in patients with SARS (11–13).

Thin-Section CT Imaging and Scoring
Thin-section CT of the lungs was performed during full inspiration and expiration, with a section collimation of 1 mm and section spacing of 10 mm. All patients were scanned in one of two helical CT scanners (PQ6000, Marconi, Cleveland, Ohio; HiSpeed, GE Medical Systems, Milwaukee, Wis) while lying supine. Thin-section CT scans were reviewed and findings were scored prospectively by two chest radiologists (Y.C.C. and J.R.G., who had 12 and 16 years of experience in thoracic radiology, respectively) in consensus. The thin-section CT findings were described on the basis of the recommendations of the Nomenclature Committee of the Fleischner Society (14). Thin-section CT findings, including ground-glass opacity, reticulation, honeycombing, parenchymal bands, consolidation, air trapping, and bronchiectasis, were recorded. Ground-glass opacity involved an increase in lung parenchymal opacification without obscuration of the underlying vessels, and consolidation involved an increase in parenchymal opacification with obscuration of the underlying vessels. Parenchymal bands were defined as nontapering linear opacities a few millimeters thick and several centimeters long. Air trapping was defined as an area of low attenuation in contrast with the background attenuation of lung parenchyma on images obtained during expiration.

To quantify the extent of disease, a thin-section CT score was assigned on the basis of the area involved (Table 1). There was a score of 0–5 for each lobe, with a total possible score of 0–25, for each of the three findings scored at each thin-section CT examination. This system was an adaptation of a method previously used to describe idiopathic pulmonary fibrosis, and it correlated well with the degree of fibrosis manifested in pathologic specimens (15,16). We summed up the extent of interstitial opacity (including interlobular septal thickening, reticulation, and honeycombing) and the extent of ground-glass opacity. As paired inspiratory-expiratory thin-section CT scans were acquired in this study, we also quantified the extent of hypoattenuation that represented air trapping on expiratory thin-section CT scans. All thin-section CT scans were reviewed at a window width and level of 1000–1500 HU and –500 to –650 HU, respectively, for lung parenchyma, and 300–350 HU and 20–50 HU, respectively, for soft tissue and mediastinum, by using image data that complied with the Digital Imaging and Communications in Medicine standard.


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  		TABLE 1. System for Scoring Ground-Glass Opacity, Interstitial Opacity, and Air Trapping on Thin-Section CT Scans

 
Statistical Analysis
All of the data were analyzed with statistical software (SPSS, version 11.0; SPSS, Chicago, Ill). The Mann-Whitney test was used to analyze differences in ground-glass opacity, interstitial opacity, and air trapping scores between patient subgroups based on binary variables (male vs female sex, with vs without ARDS, with vs without intravenous immunoglobulin therapy, with vs without pulse steroid therapy, and with vs without follow-up thin-section CT scans). Spearman rank correlation was performed to analyze the relationship between continuous variables (age; peak levels of CRP, LDH, and AST) and categoric variables (thin-section CT scores). Changes in score between the first and second thin-section CT examinations were compared by using a Wilcoxon signed rank test. All values were expressed as the mean ± SD. For all test results, a P value of less than .05 was considered to indicate a statistically significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Thin-Section CT Findings in Patients Convalescing after SARS
Demographic and clinical data for the 40 patients who underwent an initial thin-section CT examination are listed in Table 2. Findings at the initial examination in these 40 patients and at follow-up thin-section CT in 20 patients are listed in Table 3. Major findings included air trapping in 37 (92%), ground-glass opacity in 36 (90%), reticulation in 28 (70%), and parenchymal bands in 22 (55%) of 40 patients (Table 3, Figs 1–3). In 36 (90%) of the 40 patients who underwent initial thin-section CT, there were more than two findings on CT scans. Scans from nine of the 36 patients showed ground-glass opacity and air trapping, scans from three patients showed air trapping only, and scans from one patient showed ground-glass opacity only.


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  		TABLE 2. Demographic and Clinical Data for the 40 Patients Who Underwent Initial Thin-Section CT Examination

 

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  		TABLE 3. Comparison of Thin-Section CT Findings and Scores at Two Serial Examinations in Convalescent Patients after SARS

 


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  		Figure 1a. (a, b) Transverse thin-section CT scans obtained at initial examination in convalescent patient 49 days after onset of SARS symptoms and 26 days after removal of endotracheal tube. (a) Scan obtained during suspended full inspiration demonstrates prominent reticulation, traction bronchiectasis (arrows), and ground-glass opacity. (b) Scan obtained during expiration shows mosaic hypoattenuation (arrows) suggestive of air trapping. (c, d) Transverse thin-section CT scans obtained at follow-up examination in the same patient 114 days after symptom onset, during (c) inspiration and (d) expiration, at same level as a and b, show marked decrease in extent of ground-glass opacity and reticulation, milder residual air trapping (arrows), and no bronchiectasis.

 


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  		Figure 1b. (a, b) Transverse thin-section CT scans obtained at initial examination in convalescent patient 49 days after onset of SARS symptoms and 26 days after removal of endotracheal tube. (a) Scan obtained during suspended full inspiration demonstrates prominent reticulation, traction bronchiectasis (arrows), and ground-glass opacity. (b) Scan obtained during expiration shows mosaic hypoattenuation (arrows) suggestive of air trapping. (c, d) Transverse thin-section CT scans obtained at follow-up examination in the same patient 114 days after symptom onset, during (c) inspiration and (d) expiration, at same level as a and b, show marked decrease in extent of ground-glass opacity and reticulation, milder residual air trapping (arrows), and no bronchiectasis.

 


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  		Figure 1c. (a, b) Transverse thin-section CT scans obtained at initial examination in convalescent patient 49 days after onset of SARS symptoms and 26 days after removal of endotracheal tube. (a) Scan obtained during suspended full inspiration demonstrates prominent reticulation, traction bronchiectasis (arrows), and ground-glass opacity. (b) Scan obtained during expiration shows mosaic hypoattenuation (arrows) suggestive of air trapping. (c, d) Transverse thin-section CT scans obtained at follow-up examination in the same patient 114 days after symptom onset, during (c) inspiration and (d) expiration, at same level as a and b, show marked decrease in extent of ground-glass opacity and reticulation, milder residual air trapping (arrows), and no bronchiectasis.

 


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  		Figure 1d. (a, b) Transverse thin-section CT scans obtained at initial examination in convalescent patient 49 days after onset of SARS symptoms and 26 days after removal of endotracheal tube. (a) Scan obtained during suspended full inspiration demonstrates prominent reticulation, traction bronchiectasis (arrows), and ground-glass opacity. (b) Scan obtained during expiration shows mosaic hypoattenuation (arrows) suggestive of air trapping. (c, d) Transverse thin-section CT scans obtained at follow-up examination in the same patient 114 days after symptom onset, during (c) inspiration and (d) expiration, at same level as a and b, show marked decrease in extent of ground-glass opacity and reticulation, milder residual air trapping (arrows), and no bronchiectasis.

 


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  		Figure 2a. Transverse thin-section CT scans obtained at initial examination 28 days after onset of SARS symptoms. (a) Scan obtained during full inspiration demonstrates no abnormality. (b) Scan obtained during expiration shows substantial mosaic air trapping (arrows).

 


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  		Figure 2b. Transverse thin-section CT scans obtained at initial examination 28 days after onset of SARS symptoms. (a) Scan obtained during full inspiration demonstrates no abnormality. (b) Scan obtained during expiration shows substantial mosaic air trapping (arrows).

 


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  		Figure 3a. (a) Transverse thin-section CT scan obtained during full inspiration, 55 days after onset of SARS symptoms in a patient who had ARDS early in the disease course, demonstrates diffuse fine intralobular reticulation, mild traction bronchiectasis (thin arrow), and honeycombing (thick arrow). (b) Transverse thin-section CT scan obtained during inspiration at follow-up examination, 108 days after symptom onset, shows apparent honeycombing (thick white arrows), parenchymal bands (black arrow), and progressive traction bronchiectasis (thin white arrow).

 


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  		Figure 3b. (a) Transverse thin-section CT scan obtained during full inspiration, 55 days after onset of SARS symptoms in a patient who had ARDS early in the disease course, demonstrates diffuse fine intralobular reticulation, mild traction bronchiectasis (thin arrow), and honeycombing (thick arrow). (b) Transverse thin-section CT scan obtained during inspiration at follow-up examination, 108 days after symptom onset, shows apparent honeycombing (thick white arrows), parenchymal bands (black arrow), and progressive traction bronchiectasis (thin white arrow).

 
Initial thin-section CT findings in the 20 patients who underwent a second thin-section CT examination were similar to those in the whole group of 40 patients: Air trapping was found in 18 (90%) of the 20 patients; ground-glass opacity, in 18 (90%); reticulation, in 15 (75%); one or more parenchymal bands, in 10 (50%); bronchiectasis, in four (20%); consolidation, in one (5%); and honeycombing, in one (5%). In the 20 patients who did not undergo a follow-up thin-section CT examination, imaging findings at the first thin-section CT examination were similar to those in the 20 patients who did undergo a second examination (P > .05 obtained with {chi}2 test for each finding): Air trapping was found in 19 (95%); ground-glass opacity, in 18 (90%); reticulation, in 13 (65%); one or more parenchymal bands, in 12 (60%); bronchiectasis, in three (15%); consolidation, in three (15%); and honeycombing, in two (10%).

Thin-section CT scans from the second examination in 20 patients showed a decreased frequency of most CT findings, including air trapping, ground-glass opacity, reticulation, honeycombing, bronchiectasis, and consolidation (Table 3).

There was mild cylindric or traction bronchiectasis in seven of the 40 patients who underwent initial thin-section CT examination. Only four of the seven patients with bronchiectasis at initial thin-section CT underwent a follow-up thin-section CT examination. Among these four patients, disappearance of bronchiectasis was found in two (Fig 1); progressive traction bronchiectasis in combination with honeycombing, in one (Fig 3); and stationary bronchiectasis preexistent to SARS infection, in one. Parenchymal bands were persistent in nine and new in three (Fig 3) of 20 patients at the follow-up examination. One of the 20 patients who underwent two serial CT examinations had consolidation at the initial examination that was not evident at the second examination, and another patient, who had acute reactivation of pulmonary tuberculosis, had new patchy consolidation at the second CT examination. None of the findings of consolidation in our patient group were directly related to SARS. There were two or more thin-section CT findings in 16 (80%) of the 20 patients who underwent a second examination. Thin-section CT scans in four of these 16 patients showed ground-glass opacity and air trapping. In the remaining four of 20 patients, the only CT finding was ground-glass opacity, air trapping, parenchymal band, or bronchiectasis. None of the 20 patients had pleural effusion, cavitation, or lymphadenopathy on either the initial or the follow-up CT scans.

The average scores from the initial evaluation of 40 patients and those from the follow-up evaluation of the 20 patients are shown in Table 3. The thin-section CT scores for the initial examination in patients who later underwent follow-up examination were comparable to those for patients who did not undergo a second CT examination. The scores for ground-glass opacity, interstitial opacity, and air trapping for patients with follow-up thin-section CT scans were 8.68 ± 6.96 (SD), 5.79 ± 6.13, and 5.37 ± 4.41, respectively. The scores for the same findings in the 20 patients without follow-up CT scans were 5.76 ± 6.43, 4.38 ± 6.74, and 4.24 ± 2.86, respectively. At initial CT, there was no significant difference in scores for ground-glass opacity (P = .18), interstitial opacity (P = .49), or air trapping (P = .34) between patients who underwent a thin-section CT follow-up examination and those who did not (Mann-Whitney test).

Comparison of Thin-Section CT Scores between Sequential Scans in 20 Patients
Among the 20 patients who underwent two thin-section CT examinations, eight were convalescing after ARDS, while the other 12 did not have ARDS. Among all 20 patients who underwent a second thin-section CT examination, there were significant improvements in the CT scores for ground-glass opacity (from 8.7 ± 6.9 to 4.4 ± 5.1; P < .001) and for interstitial opacity (from 5.8 ± 6.1 to 3.1 ± 5.8; P < .001). No significant difference was found in the CT scores for air trapping (5.4 ± 4.4 vs 5.1 ± 5.2; P = .45) (Fig 4). The results of subgroup analyses for these 20 patients were similar: In the subgroup of patients with ARDS, the CT score for ground-glass opacity decreased from 13.1 ± 7.5 to 6.5 ± 6.7 (P = .008), and that for interstitial opacity decreased from 8.4 ± 7.7 to 4.9 ± 8.3 (P = .016). No significant change was noted in the scores for air trapping (6.6 ± 1.9 vs 6.1 ± 4.3; P = .58). In the subgroup of patients without ARDS, the CT score for ground-glass opacity decreased from 5.5 ± 4.5 to 2.9 ± 3.2 (P = .002), and that for interstitial opacity decreased from 3.9 ± 4.2 to 1.7 ± 2.9 (P = .004). No significant change was noted in the scores for air trapping (4.5 ± 5.5 vs 4.3 ± 5.8; P = .69).



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  		Figure 4. Graph of thin-section CT scores for 20 SARS patients at initial (1st) and follow-up (2nd) examinations shows significant decreases at follow-up in the scores for ground-glass opacity (CT-GGO) and interstitial opacity (CT-int) but no significant change in the score for air trapping (CT-air trap). Bars represent the mean, and whiskers represent the standard error of the mean.

 
Correlation and Comparison between Clinical Laboratory Variables and CT Scores
The subgroup of patients with ARDS (n = 16) differed from the subgroup without ARDS (n = 24) in sex distribution, peak CRP level, and history of pulse steroid therapy (Table 2). At the first thin-section CT examination, a significant difference was found in the mean scores for ground-glass opacity (11.1 ± 8.3 vs 4.4 ± 3.9; P = .009) between the subgroup of patients with ARDS and the subgroup without ARDS (Table 4). In contrast, there were no significant differences in the scores for interstitial opacity (7.5 ± 8.7 vs 3.3 ± 3.7; P = .213) and air trapping (5.1 ± 3.1 vs 4.4 ± 4.1; P = .309). At the second thin-section CT examination, no significant difference was found between the two patient subgroups in scores for ground-glass opacity, interstitial opacity, and air trapping (Table 5).


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  		TABLE 4. Comparison of Initial Thin-Section CT Scores between Patient Subgroups

 

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  		TABLE 5. Comparison of Follow-up Thin-Section CT Scores between Patient Subgroups

 
There was no significant difference in thin-section CT scores between patients who underwent intravenous immunoglobulin therapy (n = 28) and those who did not (n = 12) (Tables 4, 5). For the 11 patients who underwent pulse steroid therapy, the score for ground-glass opacity on initial thin-section CT scans was significantly higher than that for patients who did not undergo pulse steroid therapy (Table 4). No similar difference, however, was found at the second thin-section CT examination (Table 5).

Table 6 lists the results of correlation analyses among age, laboratory parameters, and thin-section CT scores. For the first thin-section CT examination, the scores for all three types of findings were correlated with age (ground-glass opacity, P = .012; interstitial opacity, P = .001; air trapping, P = .006), and those for ground-glass opacity and air trapping also were correlated with the peak CRP level (ground-glass opacity, P = .048; air trapping, P = .005). For the second thin-section CT examination, the scores for both ground-glass opacity and interstitial opacity were correlated with the peak LDH level (ground-glass opacity, P = .038; air trapping, P = .009), and that for air trapping was correlated with both age and peak CRP level (age, P = .007; peak CRP level, P = .034).


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  		TABLE 6. Results of Spearman Rank Correlation of Clinical Variables with Thin-Section CT Scores for Serial Examinations

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
The primary radiographic appearance of SARS at the onset is a combination of patchy ground-glass opacities and focal areas of consolidation predominantly affecting the lower lobes (5,6). Wong and colleagues evaluated 73 patients with thin-section CT during the acute phase of SARS (at an average of less than 1 week after onset of symptoms) (7). They demonstrated common findings, including ground-glass opacity, sometimes with consolidation, and interlobular and intralobular septal thickening. Similar thin-section CT findings in the early disease stage (16–56 days after onset) were also reported (8). Thin-section CT is more sensitive than chest radiography and can disclose abnormal lung parenchymal change in patients with normal chest radiographs (7,17). However, as caution must be exercised when transporting possible SARS patients for CT examination (18), for fear of spreading disease, and because a negative thin-section CT scan may not definitively exclude SARS in patients with acute respiratory illness, the use of thin-section CT is not recommended for imaging examinations in the early phase of SARS at our institution. Nevertheless, thin-section CT still serves as a very important tool for understanding serial lung parenchymal changes in SARS. The thin-section CT examinations in this study were performed at a later stage of the disease than those reported in previous studies (7,8). Our study demonstrated longitudinal change of lung parenchyma in SARS. According to a recent report by Ooi et al (19), ground-glass opacity with or without septal thickening or reticulation was the commonest pattern during the first 2 weeks of illness. Consolidation also was common during the 1st week in the study by Ooi et al (19), but it was an uncommon manifestation in early convalescence, as shown in our study. The findings of our study confirm a progressive resolution of consolidation in SARS. No CT evidence of consolidation related to SARS was found at approximately day 140 except in one patient with reactivation of pulmonary tuberculosis. In contrast, ground-glass opacity was still a major finding at approximately day 50 and with a decreased extent even at approximately day 140. Our study provided additional information for understanding the continuous temporal change of lung parenchyma in SARS.

Interestingly, the common thin-section CT findings in our study were air trapping, ground-glass opacity, and reticulation. Ground-glass opacity and reticulation are common findings at follow-up CT examination in survivors of ARDS, and a correlation can be established between the extent of reticulation and ground-glass opacity, on the one hand, and the extent of airflow obstruction, on the other (20). This correlation was difficult to explain, because the relationships between pathologic and radiologic findings and function rarely have been explored in ARDS survivors. However, ground-glass opacity and air trapping are common thin-section CT findings in patients with small-airway disease, while small-airway obstruction may accompany lung fibrosis (21,22). Although air trapping can be observed in 50%–60% of asymptomatic subjects with normal pulmonary function (23,24), the extent of air trapping better predicts a finding of obstruction at pulmonary function testing than does the lung attenuation. Significant correlations have been shown between the extent of air trapping at expiratory CT and the indexes of airflow obstruction at pulmonary function testing in patients with various types of small-airway disease (25–27). The strong relationship between CT abnormalities and functional alterations of the small airways was between the inspiratory CT features of bronchiolitis and the airflow at low lung volumes (28). In this study, a high frequency of air trapping and ground-glass opacity on thin-section CT scans suggested the involvement of small airways in the process of SARS-CoV infection. Small-airway damage also has been reported in prior publications about histopathologic investigations in SARS patients (29,30). Small-airway dysfunction is a known complication of pulmonary infection by respiratory viruses (31,32). Wheezing and lower respiratory tract involvement also have been demonstrated in children with coronavirus infection (33,34). The physiologic significance of air trapping in patients recovering from SARS is unclear, and its clarification will require long-term follow-up.

Bronchial dilatation or bronchiectasis with architectural distortion in patients with SARS was reported (7,19). Reversible traction bronchiectasis with surrounding reticulation and progressive traction bronchiectasis with surrounding honeycombing were noted in our patients. Although CT evidence of lung fibrosis (eg, parenchymal bands and traction bronchiectasis) has been demonstrated in SARS (8), the reversibility of traction bronchiectasis and reticulation in our study probably indicates that the findings did not signify actual pathologic fibrosis. Long-term follow-up with CT is required to obtain a definitive answer.

The differing severity of lung parenchymal change could be related to the use of immunomodulatory treatment, the severity of underlying disease, or the variable immune reactions of the individuals. In this study, besides the clinical identification of ARDS, parameters indicating the severity of systemic reaction (peak level of CRP) or tissue damage (peak level of LDH) were also shown to correlate with higher thin-section CT scores.

With regard to the changes seen in lung parenchyma during convalescence, the study failed to demonstrate the benefits of immunomodulatory agents in the treatment of SARS. Pulse steroid therapy was associated with a higher score for ground-glass opacity at follow-up CT. This observation, however, does not refute the potential effectiveness of pulse steroid therapy for SARS (35,36). As in our treatment protocol, we implemented pulse steroid therapy only when respiratory distress did not respond to initial lower-dose steroid therapy (37,38). Only patients with a more severe respiratory condition received pulse steroid therapy, and higher scores for ground-glass opacity in those patients may merely reflect the underlying severity of the lung condition. A randomized controlled trial is necessary to validate the effect of immunomodulatory therapy in SARS.

The results of a correlation analysis of thin-section CT findings with patient age demonstrated higher scores for ground-glass opacity and interstitial opacity in older patients at the first thin-section CT examination, but this correlation disappeared by the follow-up examination. Older age has been identified as a risk factor for more severe lung damage and a worse outcome in SARS (6), but the reason is unclear. The degree of air trapping was correlated with patient age, regardless of the timing of thin-section CT examination. It is speculated that CT evidence of inflammatory change (ground-glass opacity) and interstitial opacity (interlobular septal thickening and reticulation) might resolve over time, but the sequelae of small-airway damage (eg, air trapping during expiration) persist, especially in elderly patients. Although the frequency of air trapping was reported to increase with age (24), we suspected that possible sequelae of small-airway injury might be a contributing factor to the very high frequency of air trapping in SARS patients, because most of our patients (98%) were nonsmokers and all had no known disease associated with airflow obstruction. Long-term follow-up is necessary to clarify the clinical implications of this thin-section CT finding.

This prospective study had several limitations. First, the study was conducted during convalescence, which made it difficult to correlate findings on images both with peak levels of laboratory parameters retrieved and with treatment modalities used during the acute phase of SARS. Because of concerns about the possible transmission of infection, CT examination during the acute phase of SARS was prohibited at our institution. Therefore, no CT images obtained in the acute phase were available in our hospital. Second, because of the lack of randomized controlled studies, no conclusions about the effectiveness of any SARS treatment strategy may be derived from our study results. Third, because of the small numbers in each patient subgroup, the results of our comparisons of imaging and clinical findings may be biased.

However, the study results still provide important information not reported before. This is, to our knowledge, the first longitudinal study of the use of thin-section CT in which changes in pulmonary sequelae were evaluated up to 140 days after symptom onset. Moreover, our evaluation of inspiratory-expiratory thin-section CT scans in this study provided findings that were not reported before, and the clinical significance of these findings still needs to be clarified.

In summary, the study provided thin-section CT evidence of pulmonary improvement in most patients recovering from the acute stage of this potentially fatal disease. The extent of lung parenchymal changes was correlated with age, markers of inflammation (CRP level and neutrophil count), and markers of tissue damage (LDH level). Our data suggest that thin-section CT could serve as a useful tool for evaluating pulmonary sequelae in patients recovering from SARS. Thin-section CT evidence shows that ground-glass opacity and interstitial opacity in the lung parenchyma of convalescent patients usually resolve over time but that air trapping may persist. The clinical importance of the subclinical airway damage is not clear and remains to be clarified after long-term follow-up.


   ACKNOWLEDGMENTS
 
The authors thank Chee-Jen Chang, PhD, Department of Medical Research, National Taiwan University Hospital, for help in the statistical review.


   FOOTNOTES
 

Abbreviations: ARDS = adult respiratory distress syndrome • AST = aspartate aminotransferase • CRP = C-reactive protein • LDH = lactate dehydrogenase • SARS = severe acute respiratory syndrome • SD = standard deviation

Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, S.C.C.; study concepts, K.M.H., P.C.Y.; study design, Y.C.C., C.J.Y., P.C.Y.; literature research, Y.C.C., C.J.Y., J.R.G., H.M.L., T.J.F.; clinical studies, C.J.Y., K.Y.C., P.H.K., S.C.C.; data acquisition, Y.C.C., C.J.Y., C.H.H.; data analysis/interpretation, Y.C.C., C.J.Y., J.R.G., C.H.H.; statistical analysis, C.J.Y.; manuscript preparation, definition of intellectual content, and editing, Y.C.C., C.J.Y.; manuscript revision/review, Y.C.C., J.R.G., T.J.F.; manuscript final version approval, P.C.Y.Y.C.C. and C.J.Y. contributed equally to this work.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. World Health Organization. Severe acute respiratory syndrome (SARS). Wkly Epidemiol Rec 2003; 78:81–83.[Medline]
  2. Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003;348:1953–1966.[Abstract/Free Full Text]
  3. Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 2003;289:2801–2809.[Abstract/Free Full Text]
  4. Fowler RA, Lapinsky SE, Hallett D, et al. Critically ill patients with severe acute respiratory syndrome. JAMA 2003;290:367–373.[Abstract/Free Full Text]
  5. Wong KT, Antonio GE, Hui DS, et al. Severe acute respiratory syndrome: radiographic appearances and pattern of progression in 138 patients. Radiology 2003;228:401–406.[Abstract/Free Full Text]
  6. Grinblat L, Shulman H, Glickman A, Matukas L, Paul N. Severe acute respiratory syndrome: radiographic review of 40 probable cases in Toronto, Canada. Radiology 2003;228:802–809.[Abstract/Free Full Text]
  7. Wong KT, Antonio GE, Hui DS, et al. Thin-section CT of severe acute respiratory syndrome: evaluation of 73 patients exposed to or with the disease. Radiology 2003;228:395–400.[Abstract/Free Full Text]
  8. Antonio GE, Wong KT, Hui DS, et al. Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience. Radiology 2003;228:810–815.[Abstract/Free Full Text]
  9. World Health Organization. Case definitions for surveillance of severe acute respiratory syndrome (SARS). World Health Organization Web site. http://www.who.int/csr/sars/casedefinition/en. Revised May 1, 2003. Accessed October 22, 2003.
  10. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818–824.[Abstract]
  11. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003;348:1986–1994.[Abstract/Free Full Text]
  12. Ooi CG, Khong PL, Lam B, et al. Severe acute respiratory syndrome: relationship between radiologic and clinical parameters. Radiology 2003;229:492–499.[Abstract/Free Full Text]
  13. Wang JT, Sheng WH, Fang CT, et al. Clinical pictures, temporal progression of laboratory findings, and treatment outcome of patients with severe acute respiratory syndrome. Emerg Infect Dis 2004;10:818–824.[Medline]
  14. Austin JH, Müller NL, Friedman PJ, et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 1996;200:327–331.[Free Full Text]
  15. Kazerooni EA, Martinez FJ, Flint A, et al. Thin-section CT obtained at 10-mm increments versus three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. AJR Am J Roentgenol 1997;169:977–983.[Abstract/Free Full Text]
  16. Flaherty KR, Colby TV, Travis WD, et al. Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease. Am J Respir Crit Care Med 2003;167:1410–1415.[Abstract/Free Full Text]
  17. Müller NL, Ooi GC, Khong PL, Nicolaou S. Severe acute respiratory syndrome: radiographic and CT findings. AJR Am J Roentgenol 2003;181:3–9.[Abstract/Free Full Text]
  18. King AD, Ching AS, Chan PL, et al. Severe acute respiratory syndrome: avoiding the spread of infection in a radiology department. AJR Am J Roentgenol 2003;181:25–27.[Free Full Text]
  19. Ooi GC, Khong PL, Müller NL, et al. Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients. Radiology 2004;230:836–844.[Abstract/Free Full Text]
  20. Desai SR, Wells AU, Rubens MR, Evans TW, Hansell DM. Acute respiratory distress syndrome: computed tomographic abnormalities at long-term follow-up. Radiology 1999;210:29–35.[Abstract/Free Full Text]
  21. Grenier PA, Beigelman-Aubry C, Fétita C, Prêteux F, Brauner MW, Lenoir S. New frontiers in CT imaging of airway disease. Eur Radiol 2002;12:1022–1044.[CrossRef][Medline]
  22. Leung AN, Fisher K, Valentine V, et al. Bronchiolitis obliterans after lung transplantation: detection using expiratory HRCT. Chest 1998;113:365–370.[Abstract/Free Full Text]
  23. Tanaka N, Matsumoto T, Miura G, et al. Air trapping at CT: high prevalence in asymptomatic subjects with normal pulmonary function. Radiology 2003;227:776–785.[Abstract/Free Full Text]
  24. Lee KW, Chung SY, Yang I, Lee Y, Ko EY, Park MJ. Correlation of aging and smoking with air trapping at thin-section CT of the lung in asymptomatic subjects. Radiology 2000;214:831–836.[Abstract/Free Full Text]
  25. Hansell DM, Wells AU, Padley SP, Müller NL. Hypersensitivity pneumonitis: correlation of individual CT patterns with functional abnormalities. Radiology 1996;199:123–128.[Abstract/Free Full Text]
  26. Lucidarme O, Coche E, Cluzel P, Mourey-Gerosa I, Howarth N, Grenier P. Expiratory CT scans for chronic airway disease: correlation with pulmonary test results. AJR Am J Roentgenol 1998;170:301–307.[Abstract/Free Full Text]
  27. Arakawa H, Niimi H, Kurihara Y, Nkajima Y, Webb WR. Expiratory high-resolution CT: diagnostic value in diffuse lung disease. AJR Am J Roentgenol 2000;175:1537–1543.[Free Full Text]
  28. Mastora I, Remy-Jardin M, Sobaszek A, Boulenguez C, Remy J, Edme JL. Thin-section CT finding in 250 volunteers: assessment of the relationship of CT findings with smoking history and pulmonary function test results. Radiology 2001;218:695–702.[Abstract/Free Full Text]
  29. Nicholls JM, Poon LL, Lee KC, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet 2003;361:1773–1778.[CrossRef][Medline]
  30. Franks TJ, Chong PY, Chui P, et al. Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore. Hum Pathol 2003;34:743–748.[CrossRef][Medline]
  31. Smyth A. Pneumonia due to viral and atypical organisms and their sequelae. Br Med Bull 2002;61:247–262.[Abstract/Free Full Text]
  32. Wennergren G, Kristjánsson S. Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases. Eur Respir J 2001;18:1044–1058.[Abstract/Free Full Text]
  33. McIntosh K, Ellis EF, Hoffman LS, Lybass TG, Eller JJ, Fulginiti VA. The association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J Pediatr 1973;82:578–590.[CrossRef][Medline]
  34. McIntosh K, Chao RK, Krause HE, Wasil R, Mocega HE, Mufson MA. Coronavirus infection in acute lower respiratory tract disease in infants. J Infect Dis 1974;130:502–507.[Medline]
  35. Ho JC, Ooi GC, Mok TY, et al. High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome. Am J Respir Crit Care Med 2003;168:1449–1456.[Abstract/Free Full Text]
  36. So LK, Lau AC, Yam LY, et al. Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet 2003;361:1615–1617.[CrossRef][Medline]
  37. Department of Internal Medicine. Guidelines for management of severe acute respiratory syndrome (SARS). National Taiwan University Hospital Web site. http://ntuh.mc.ntu.edu.tw/med/sars. Published May 30, 2003. Accessed October 5, 2003.
  38. Sun HY, Fang CT, Wang JT, Chen YC, Chang SC. Treatment of severe acute respiratory syndrome in health-care workers. Lancet 2003;362:2025–2026.[CrossRef][Medline]




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