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1
Department of Radiology, St. Marianna University School of Medicine, 2-16-1
Sugao, Miyamae-Ku, Kawasaki City, 216-8511 Japan.
2
Department of Radiology, Osaka University School of Medicine, 2-2, Yamada-oka,
Suita Osaka, 5650871 Japan.
Received August 21, 2000;
accepted after revision October 3, 2000.
Address correspondence to H. Arakawa.
Abstract
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MATERIALS AND METHODS. We retrospectively reviewed high-resolution CT scans of 38 patients with BOOP and 43 patients with CEP. Without knowledge of the diagnosis, two radiologists evaluated the frequency and distribution of high-resolution CT findings in both groups of patients and made a diagnosis using a three-point scale of confidence.
RESULTS. Nodules, nonseptal linear or reticular opacities, and
bronchial dilatation were significantly more common in BOOP than in CEP (31.6%
vs. 4.7%, p < 0.005; 44.7% vs. 9.3%, p < 0.001; and
57.9% vs. 25.6%, p < 0.005, respectively). Septal line thickening
was more frequent in CEP than in BOOP (72.1% vs. 39.5%, p <
0.005). Peribronchial distribution of consolidation was more frequent in BOOP
than in CEP (28.9% vs. 9.3%, p < 0.05). A correct diagnosis was
made in 69.7% of cases, and the diagnostician was confident in 21.7%.
Interobserver agreement was good (
= 0.6).
CONCLUSION. Although several of the high-resolution CT findings of BOOP and CEP are different, these diseases are differentiated with confidence in only a small percentage of cases.
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Since the first description of BOOP, researchers have suggested some overlapping of the clinical, laboratory, and even pathologic findings of BOOP and CEP in selected cases [5,6,7]. However, response to corticosteroid treatment is generally reported to be more dramatic in CEP than in BOOP [8], and a worse prognosis has been reported in patients with BOOP than in those with CEP [4, 8, 9]. In general, dosage and duration of corticosteroid treatment differs between the two diseases. In BOOP, a high dose (1-1.5 mg/kg per day) of oral corticosteroids is required for a few months, followed by a gradual tapering and maintenance administration for 6-12 months [10]. Some patients do not need treatment because spontaneous regression can occur in BOOP; however, pulse therapy for the initial few days is often required for patients with severe disease [5, 11]. In contrast, most patients with CEP show rapid improvement in a few days with oral corticosteroids, but longterm low-dose corticosteroid treatment is required because more than half of all patients relapse [12, 13]. Although BOOP and CEP share many features and show overlapping characteristics, they are now considered different disorders, and distinguishing the two is important before initiating therapy [8].
In relation to CT findings, these two disorders share many features [12, 14,15,16,17,18,19,20,21], and some authors have concluded that CT cannot differentiate them [5]. However, these previous reports did not always involve high-resolution CT, and the numbers of patients studied was rather small. The objectives of our study were to compare the high-resolution CT findings of BOOP with those of CEP and to determine whether BOOP and CEP can be differentiated with the aid of high-resolution CT.
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High-resolution CT was performed with various scanners (X-Vigor, X-Vision, X-Force, TCT-900S, Toshiba, Tokyo, Japan; or HiSpeed Advantage, General Electric Medical Systems, Milwaukee, WI). Scans were obtained at end inspiration (inspiratory scan) in all patients. In selected patients, additional scans were obtained at end exhalation (expiratory scan). Inspiratory scans were obtained from the thoracic inlet to the lung base with 1.5- or 2-mm collimation and 10- or 20-mm interscan spacing. Expiratory scans were obtained at six evenly divided levels of the whole lung. Both scan types were reconstructed with a high-spatial-resolution algorithm. Images were observed and photographed at lung (level, -700 to -550 H; width, 1200-1600 H) and mediastinal (level, 20-50 H; width, 300-450 H) windows.
Two chest radiologists reviewed the scans without knowledge of the diagnosis, and final decisions were reached by consensus. The observers assessed the presence and distribution of areas of ground-glass attenuation, areas of air-space consolidation, parenchymal nodules or masses, and linear or reticular opacities. When more than one CT pattern was seen, the predominant pattern and the other CT patterns were described. The presence of associated findings such as bronchial dilatation, bronchial wall thickening, lung volume loss, and air trapping was also assessed. Areas with ground-glass attenuation were defined as areas of hazy increased attenuation without obscuration of underlying vascular markings. Air-space consolidation was considered present when the opacities obscured the underlying vessels. Reticular or linear opacities were further subclassified as septal line thickening and as nonseptal linear or reticular opacities. Nonseptal linear or reticular opacities included intralobular reticular opacity and linear or bandlike opacity that was different from septal line thickening. Intralobular reticular opacity was considered present when fine linear opacity was seen in a lobule [24]. Linear or bandlike opacity was considered present when any linear opacity with variable thickness and length that was distinct from interlobular septa or bronchovascular bundles, was seen [24, 25]. Bronchial dilatation was considered present when there was loss of normal tapering of the bronchial lumen; or when bronchi that were identified in the consolidation or ground-glass opacity were visible in the lung periphery within 1 cm of the pleural surface. Lung volume loss was considered present when the interlobar fissures were displaced by abnormal opacity. Air trapping was considered present when the absence of a normal increase in lung attenuation was noted on the expiratory scan in more than five isolated secondary pulmonary lobules or in more than three contiguous secondary pulmonary lobules. Bronchial wall thickening was subjectively assessed by comparing the bronchial walls in normal lung areas with those in areas of abnormal opacity.
The anatomic distribution was noted to be peripheral if a predominance of abnormalities was seen in the outer third of the lung, central if most were in the inner third of the lung, peribronchial if a predominance of abnormalities occurred along the bronchovascular bundle, and random if no predominance was observed. The distribution was further subclassified when possible as patchy or nonsegmental. Zonal predominance was assessed as upper or lower. Upper lung zone predominance was defined as when the abnormalities were above the level of the tracheal carina, and lower zone predominance as when the abnormalities were below that level. Differences in frequencies of abnormalities were tested using the chi-square test, and p values of less than 0.05 were considered significant.
The diagnostic accuracy of high-resolution CT was assessed 6 months after the first review to eliminate recall bias. Seventy-six cases were available for the second review session. The same radiologists independently reviewed the same set of films and diagnosed either BOOP or CEP on the basis of the results of the first review session. Each observer scored each diagnosis on a three-point scale for level of confidence: possible, probable, or definite. Interobserver agreement was evaluated using the kappa statistic.
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High-Resolution CT Findings
The high-resolution CT findings of each disease are listed in Tables
1 and
2. Among the main CT patterns,
the presence of a nodule or mass was significantly more frequent in BOOP than
in CEP (31.6% vs. 4.7%; p < 0.005). The margins of the nodule or
mass were ill defined in seven patients versus one, well defined in four
versus one, and mixed in one versus zero, in patients with BOOP and CEP,
respectively. The size of the mass or nodule ranged from 2 to 40 mm in BOOP
and from 2 to 10 mm in CEP. The presence of air-space consolidation,
ground-glass attenuation, and linear or reticular opacities was not
significantly different between the two groups. The distribution of various
abnormalities of CEP was not different from that of BOOP except for the
distribution of air-space consolidation
(Table 1). Areas of air-space
consolidation predominated in the peribronchial area in BOOP more frequently
than in CEP (28.9% vs. 9.3%; p < 0.05)
(Fig. 3). Bronchial dilatation
was significantly more frequent in BOOP than in CEP (57.9% vs. 25.6%;
p < 0.005) (Fig.
4). Intralobular reticular opacity and linear or bandlike opacity
were seen in 12 (31.6%) and six (15.8%) patients, respectively, with BOOP, and
two (4.7%) and two (4.7%) patients, respectively, with CEP. When these
nonseptal linear opacities were combined, they occurred significantly more
frequently in BOOP than in CEP (44.7% vs. 9.3%; p < 0.001),
whereas septal line thickening was more frequent in CEP than in BOOP (72.1%
vs. 39.5%; p < 0.005) (Figs.
5 and
6). The presence of bronchial
wall thickening, lung volume loss, pleural effusion, lymphadenopathy, or
laterality was not significantly different between the two groups.
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Expiratory high-resolution CT was performed in 14 patients. Although air trapping was seen more frequently in BOOP (four patients [50.0%] with BOOP vs. only one patient [16.7%] with CEP), that finding is not significant (p > 0.05). The patient with CEP who showed air trapping had a clinical history of bronchial asthma.
Diagnostic Accuracy of High-Resolution CT
Of the 76 cases available for the second review session, a correct
diagnosis was made in 55 (72.4%) by the first reviewer and in 51 (67.1%) by
the second reviewer. A correct diagnosis with a high confidence level was
achieved in 21 cases (27.6%) by the first reviewer and in 12 cases (15.8%) by
the second reviewer. Interobserver agreement was good ( = 0.6).
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In our series, consolidation was the most frequent high-resolution CT finding in both BOOP (86.8%) and CEP (74.4%), followed by linear and reticular opacity (63.2% in BOOP and 76.7% in CEP) and ground-glass opacity (57.9% in BOOP and 65.1% in CEP). The frequency of these findings did not differ significantly between the two groups. Among the high-resolution CT findings, the presence of parenchymal nodules was the unique difference between BOOP and CEP (31.6% vs. 4.7%; p < 0.005). The nodules in BOOP are designated as well defined or ill defined, and the diameter ranges from 8 to 40 mm [20, 26]. In a report of 12 patients with BOOP, nodular or masslike opacity was the most common finding in five patients [14]. In that series, nodules or masses were mostly located in the lung periphery. In our series, they were mostly ill defined, were usually located in the lung periphery, and ranged from 2 to 40 mm in diameter. Although nodules are rarely reported in CEP, two patients showed nodules in our series. In those two patients, the nodules were small (<10 mm) and randomly distributed. The presence of nodules or masses is considered useful in differentiating the two diseases.
If only the predominant CT pattern was considered, ground-glass opacity was significantly more common in CEP than in BOOP (34.9% vs. 10.5%; p < 0.01). BOOP showed various CT patterns including, in decreasing order, consolidation, reticular or linear opacities, ground-glass opacity, and nodules or masses. However, CEP showed only consolidation or ground-glass opacity as the main CT finding.
Regarding the distribution of abnormal opacities, peribronchial distribution of consolidation was seen more frequently in BOOP than in CEP (28.9% vs. 9.3%; p < 0.05). Otherwise, no significant difference in distribution was noted between BOOP and CEP. In previous reports, consolidation was usually described in the subpleural or peribronchial regions in BOOP patients and apparently was predominantly in the lower lung zones [14, 20]. In patients with CEP, consolidation is reported to predominate in the lung periphery on CT and in the upper zones on chest radiography [12, 15]. In our study, consolidation was noted most frequently in the lung periphery in both diseases, and the distribution itself did not seem important for differentiating the two.
Nonseptal linear or reticular opacities were significantly more common in BOOP than in CEP (44.7% vs. 9.3%; p < 0.001). In a report of 11 patients with BOOP who had linear opacities on high-resolution CT, Murphy et al. [25] indicated that linear or bandlike opacities in BOOP occur in two fashions: namely, linear opacity along the line of the bronchi towards the pleura, and linear opacity in the subpleural location with no relation to the bronchi. Irregular lines were also described in BOOP [20]. In one report of 43 cases of BOOP [20], three patients (7%) showed irregular lines in the subpleural region of the lower lung zones. In our study, we included all linear and irregular opacities that differed from interlobular septal lines and found that they were commonly identified in BOOP. However, they were uncommon in CEP. This finding was considered important for differentiating the two diseases.
Thickening of septal lines is rarely reported in either CEP or BOOP [21, 26], partly because previous reports were based on CT scans obtained using thick collimation. In our study, this finding was observed more frequently in CEP than in BOOP (p < 0.005). The thickening of septal lines can be attributed to the infiltration into the interstitium of eosinophils in patients with CEP [12, 17] or of mononuclear cells in patients with BOOP [4], or it may be associated with abnormal lymphatic flow from an exudative lesion [26]. Although the difference was significant, the finding was seen in both diseases with a sufficiently high frequency that we do not consider septal line thickening important in differentiating the two diseases.
In our series, bronchial dilatation was seen significantly more often in BOOP than in CEP (57.9% vs. 25.6%; p < 0.005). Bronchial dilatation is considered to represent organization and fibrosis of the lung around the bronchi [27, 28]. Organization of exudate is the pathologic hallmark of BOOP. In addition, one report of CEP noted that one half of the cases were associated with interstitial fibrosis and one quarter were associated with bronchiolitis obliterans [12]. Our CT findings may match those pathologic results. Although the presence of bronchial dilatation showed strong significance, it was seen in a significant number of patients with both diseases, and thus we do not consider it important for differentiation.
Our study has several limitations. First, most cases were diagnosed on the basis of a pathologic specimen obtained at transbronchial biopsy. From an academic point of view, the pathologic diagnosis of BOOP should be made on the basis of a large specimen obtained at surgical biopsy. However, as Colby stated in a review [22, 29], when the clinician is fully cognizant of the limitations of transbronchial biopsy and in the appropriate clinical setting, a clinicopathologic diagnosis of BOOP can be made using transbronchial biopsy. Second, ours is a review of the findings of high-resolution CT from two different universities; we used different scanners and protocols.
In conclusion, the most important findings for differentiating BOOP and CEP are the presence or absence of a nodule or a mass followed by nonseptal linear or reticular opacities, which are more common in BOOP. The presence or absence of bronchial dilatation and septal line thickening may be other discriminating high-resolution CT findings. In many cases, the discrimination between BOOP and CEP is possible on high-resolution CT scans; however, the distinction can be made with confidence in only a small percentage of cases.
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