Rheumatoid Arthritis related Lung Diseases: CT Findings 1

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1 Nobuyuki Tanaka, MD Jeung Sook Kim, MD John D. Newell, MD Kevin K. Brown, MD Carlyne D. Cool, MD Richard Meehan, MD Takuya Emoto, MD Tsuneo Matsumoto, MD David A. Lynch, MB Index terms: Arthritis, rheumatoid, Bronchiolitis, Lung, CT, , Lung, interstitial disease, , Pneumonia, interstitial with fibrosis, Published online before print /radiol Radiology 2004; 232:81 91 Abbreviations: DLCO lung diffusing capacity for carbon monoxide DLCO/VA DLCO corrected for alveolar volume FEV 1 forced expiratory volume in 1 second FVC forced vital capacity GGO ground-glass opacity 1 From the Depts of Radiology (N.T., J.S.K., D.A.L.) and Pathology (C.D.C.), Univ of Colorado Health Sciences Ctr, Denver; Depts of Radiology (J.D.N.) and Medicine (K.K.B., R.M.), National Jewish Ctr for Immunology and Respiratory Med, Denver, Colo; and Dept of Radiology, Yamaguchi University School of Medicine, Minamikogushi, Ube, Yamaguchi , Japan (N.T., T.E., T.M.). Received Feb 3, 2003; revision requested Apr 22; final revision received Nov 5; accepted Nov 17. Address correspondence to N.T. ( Rheumatoid Arthritis related Lung Diseases: CT Findings 1 PURPOSE: To evaluate computed tomographic (CT) findings of rheumatoid arthritis related lung disease and categorize findings according to pathologic features. MATERIALS AND METHODS: CT scans obtained in 63 patients (27 men, 36 women; mean age, 61.7 years 11.2 [SD]; range, years) with rheumatoid arthritis were assessed. Mean duration of disease was 7.6 years 9.2. Lung parenchymal abnormalities that included airspace consolidation, ground-glass opacity (GGO), reticulation, honeycombing, nodules, bronchiectasis, and air trapping were assessed retrospectively by two chest radiologists. Final decision was reached with consensus of these radiologists and a third radiologist. Patients were classified according to the predominant CT pattern. One of the chest radiologists and a pulmonary pathologist compared CT findings with pathologic findings in 17 patients. Interobserver agreement between the first two radiologists was assessed. Correlation between CT finding extent score and pulmonary function test results was estimated with Spearman rank correlation coefficient. RESULTS: GGO (57 [90%] patients) and reticulation (62 [98%] patients) were the most common CT features. Four major CT patterns were identified: usual interstitial pneumonia (n 26), nonspecific interstitial pneumonia (n 19), bronchiolitis (n 11), and organizing pneumonia (n 5). Usual interstitial pneumonia and nonspecific interstitial pneumonia CT patterns overlapped; GGO was more extensive in patients with nonspecific interstitial pneumonia CT pattern (P.028). In 17 patients who underwent biopsy, CT findings reflected pathologic findings. Exceptions were two patients classified with usual interstitial pneumonia at CT but with nonspecific interstitial pneumonia at pathologic analysis; one patient, with nonspecific interstitial pneumonia at CT but desquamative interstitial pneumonia at pathologic analysis; and one patient, with lymphoid interstitial pneumonia at CT but nonspecific interstitial pneumonia at pathologic analysis. CONCLUSION: Rheumatoid arthritis is associated with four CT patterns: usual interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis, and organizing pneumonia. The most common CT features of rheumatoid arthritis related lung disease were GGO and reticulation. RSNA, 2004 Author contributions: Guarantors of integrity of entire study, N.T., D.A.L.; study concepts, N.T., D.A.L., J.D.N.; study design, N.T., T.M.; literature research, N.T., T.E.; clinical studies, T.E., R.M., C.D.C., K.K.B., J.S.K.; data acquisition, N.T., T.E., R.M., K.K.B., J.S.K.; data analysis/interpretation, N.T., K.K.B., J.S.K., C.D.C., T.M., D.A.L.; statistical analysis, N.T., D.A.L.; manuscript preparation, N.T.; manuscript definition of intellectual content, D.A.L., J.D.N., T.E., R.M., K.K.B.; manuscript editing, N.T., D.A.L., T.M.; manuscript revision/review and final version approval, all authors RSNA, 2004 Rheumatoid arthritis is a common systemic disease that manifests as inflammatory arthritis of multiple joints and produces a wide variety of intrathoracic lesions, including pleural diseases (1 3), rheumatoid nodules (1 5), diffuse interstitial pneumonia (1 10), pulmonary vasculitis (1,2,10,11), and airway disease that includes bronchiectasis, bronchiolitis obliterans, and follicular bronchiolitis (1,4,6,8,12 19). Yousem et al (20) described a broad range of histopathologic features in the lungs of patients with rheumatoid arthritis; these features include rheumatoid nodules, usual interstitial pneumonia, organizing pneumonia, lymphoid hyperplasia, and nonspecific interstitial pneumonia. Therefore, the term rheumatoid lung is of little use as a descriptor, because it encompasses a large spectrum of morphologic changes that are associated with substantially different prognoses. The purpose of this study was to evaluate the computed tomographic (CT) findings in patients with pulmonary complications of rheumatoid arthritis and to categorize these findings on the basis of pathologic features. 81

2 MATERIALS AND METHODS Patients Between 1991 and 2002, we retrospectively reviewed CT scans obtained in 63 patients with rheumatoid arthritis who underwent a CT examination of the chest at University of Colorado Health Sciences Center, Denver; National Jewish Center for Immunology and Respiratory Medicine, Denver, Colo; and Yamaguchi University School of Medicine, Ube, Japan. These 63 patients were identified from a clinical database. These patients underwent CT examination because they had chest symptoms or abnormal chest radiographic findings. The 63 patients selected for this study fulfilled the revised criteria for rheumatoid arthritis of the American Rheumatism Association (21). Patients who had clinical or laboratory evidence of other collagenous vascular diseases were excluded from this study. Furthermore, patients in whom pulmonary abnormalities were clinically thought to be due to infection or drug toxicity were also excluded. The study was approved by the institutional review boards at our institutions, and informed consent was obtained from the participants. The study group comprised 27 men who ranged in age from 39 to 77 years (mean, 61.9 years 9.4 [SD]) and 36 women who ranged in age from 28 to 81 years (mean, 61.6 years 12.4). The total group of 63 patients ranged in age from 28 to 81 years (mean, 61.7 years 11.2). Smoking history was not available in nine patients. Of the other 54 patients, eight were current smokers, 22 were exsmokers, and 24 had never smoked. The respiratory symptoms, which included dyspnea, cough, sputum, wheezing, and fever, were available from the database or medical chart in 54 patients. Dyspnea was present in 31 (57%) patients, cough in 26 (48%), sputum in 17 (31%), wheezing in eight (15%), and fever in five (9%). Several patients had more than two symptoms. Eleven (20%) patients did not have any of these symptoms. Mean duration of disease was 7.6 years 9.2. CT Scanning CT scans were obtained with one of four units (Somatom Plus 4, Siemens, Erlangen, Germany; TCT-900S, Toshiba Medical Systems, Tokyo, Japan; HiSpeed Advantage or HiSpeed CTi, GE Medical Systems, Milwaukee, Wis). The CT protocol was diverse because of the triinstitutional and retrospective nature of the study. Contiguous scans were obtained with 7- or 10-mm collimation CT through the chest. In 57 of 63 patients, additional thin-section CT scans were obtained with 1- or 2-mm collimation at 10- or 20-mm intervals. Thin-section CT images were reconstructed with a high-spatial-frequency algorithm. CT scans were obtained at suspended end-inspiratory effort with the patients in the supine position and without intravenous contrast material. Additional CT scans were obtained with patients in the prone position (21 patients) and at end expiration (19 patients). All images were obtained at window levels appropriate for lung parenchyma (window width, 1,500 or 1,750 HU; window level, 600 or 700 HU) and mediastinum (window width, HU; window level, HU). Interpretation of CT Scans CT scans were assessed independently in random order by two chest radiologists (N.T., 14 years of experience; J.S.K., 12 years of experience) without knowledge of the patients clinical information except that all patients had rheumatoid arthritis. All scans were reviewed by using only hard-copy images. After analysis of interobserver agreement between the two radiologists, the images were reviewed together with a third chest radiologist (D.A.L., 20 years of experience), and the three radiologists reached a final decision with consensus. Each of the following CT findings was separately coded as present or absent: (a) airspace consolidation; (b) ground-glass opacity (GGO); (c) reticulation (septal lines or nonseptal lines); (d) thickening of bronchovascular bundle; (e) honeycombing; (f) nodules, which included micronodules ( 3 mm in diameter), small nodules (3 10 mm in diameter), and large nodules ( 10 mm in diameter); (g) emphysema; (h) bullae; (i) bronchiectasis or bronchiolectasis; (j) traction bronchiectasis; (k) crazy-paving appearance (the superimposition of areas of GGO and interlobular or intralobular interstitial thickening); (l) treein-bud appearance; (m) mosaic perfusion (a patchwork of regions of inhomogeneous lung attenuation that probably resulted from air trapping or regional differences in lung perfusion); (n) architectural distortion, recognized as the displacement of fissures, bronchi, and vessels; and (o) air trapping, recognized as decreased attenuation of lung parenchyma, which especially manifested as a less than normal increase in attenuation on expiratory images. Distribution of nodules was recorded as centrilobular, peribronchial, and random. Centrilobular distribution was defined when nodules were identified around peripheral pulmonary arterial branches or 3 5 mm away from the pleura, interlobular septa, or pulmonary veins. Peribronchial distribution was defined when nodules were identified around lobar, segmental, or subsegmental bronchi. Random distribution was defined when nodules did not show either centrilobular or peribronchial distribution and did not show any specific distribution within a secondary pulmonary lobule. The distribution of pulmonary disease was evaluated according to zones as follows: The upper zones were above the level of the carina, the middle zones lay between the level of the carina and the level of the inferior pulmonary veins, and the lower zones were below the inferior pulmonary veins. The nine CT findings in categories a i were separately coded as present or absent in the six zones, and thus they defined the vertical distribution of lung changes. The extent of eight CT findings in categories a h was graded subjectively with a five-point scale within the whole lung field. This scale was as follows: grade 0, the finding was absent; grade 1, the percentage of involvement of the lungs was between 1% and 25%; grade 2, the percentage of involvement was between 26% and 50%; grade 3, the percentage of involvement was between 51% and 75%; and grade 4, the percentage of involvement was more than 76%. The extent of bronchiectasis or bronchiolectasis was graded with a three-point scale, as follows: grade 0, none; grade 1, localized bronchiectasis that affects one bronchopulmonary segment; and grade 2, extensive bronchiectasis that affects two or more segments. The overall distribution of abnormalities in each patient was also defined craniocaudally (as predominance in the upper, middle, or lower zone of the lung and diffuse or indeterminate) and transversely (as peripheral, central, or peribronchial and diffuse or indeterminate). In each patient, one or two predominant CT patterns (airspace consolidation, GGO, linear-reticular opacity, honeycombing, nodules, emphysema, bronchiectasis or bronchiolectasis, mosaic perfusion, and air trapping) were defined. The most likely CT diagnosis was defined on the basis of previous CT descriptions of these diseases (22 38) (Table 1). The size of the main pulmonary artery was measured at the widest diameter perpendicular to the long axis of the main 82 Radiology July 2004 Tanaka et al

3 TABLE 1 Summary of CT Features of Interstitial Lung Diseases and Airway Diseases Disease CT Features Reference No. Radiology Usual interstitial pneumonia Nonspecific interstitial pneumonia Organizing pneumonia Diffuse alveolar damage Lymphoid interstitial pneumonia Bronchiolitis obliterans Follicular bronchiolitis Irregular linear opacities and honeycombing that predominantly involve basal and subpleural lung regions; may show traction bronchiectasis, architectural distortion, and GGO (inconspicuous finding) GGO, usually bilateral with some predominance of subpleural and basal regions; may show fine reticulation or traction bronchiectasis within GGO, airspace consolidation, and minor honeycombing Patchy and multiple airspace consolidation usually with subpleural or peribronchial distribution associated with GGO; may show centrilobular nodules or masses Patchy or diffuse GGO sometimes with panlobular distribution associated with airspace consolidation; may show intralobular reticulation or traction bronchiectasis and dependent area predominance Poorly defined centrilobular nodules and GGO that accompany thickening of interlobular septa and/or bronchovascular bundle; may show cystic airspaces and lymph node enlargement Mosaic perfusion with bronchial dilatation on inspiratory CT scans and air trapping on expiratory CT scans; may show centrilobular nodules and branching linear structures Centrilobular and/or peribronchial nodules and branching linear structures; may show bronchial dilatation and bronchial wall thickening ,29, ,23,25, , pulmonary trunk to detect the presence of pulmonary hypertension, as previously described by Kuriyama et al (39). We regarded the upper limit of normal pulmonary artery diameter as 30 mm. The presence or absence of mediastinal lymph node enlargement was recorded by using criteria defined by Glazer et al (40). Findings of pleural and pericardial effusion or thickening and esophageal dilatation were also recorded. Pulmonary Function Tests Spirometry was performed according to American Thoracic Society guidelines (41). Vital capacity, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), FEV 1 /FVC ratio, total lung capacity, residual volume, and maximum expiratory flow at 25% of vital capacity were determined, with subjects tested in the seated position within a volume displacement pressure-compensated body plethysmograph. Lung diffusing capacity for carbon monoxide (DLCO) and DLCO corrected for alveolar volume (DLCO/VA) were measured. Except for the FEV 1 /FVC ratio, all values (eg, vital capacity, total lung capacity, residual volume, maximum expiratory flow at 25% of vital capacity, DLCO, and DLCO/VA) were expressed as a ratio of measured to predicted values (percentage predicted). Measurements were obtained without bronchodilator administration. The patients who did not undergo pulmonary function tests within 2 months of the CT examination were excluded from the evaluation of pulmonary function test results. Vital capacity, FEV 1 /FVC ratio, total lung capacity, residual volume, maximum expiratory flow at 25% of vital capacity, DLCO, and DLCO/VA were available in 43, 42, 27, 27, 18, 29, and 29 patients, respectively. Pathologic Findings and Correlation with CT Findings Seventeen pathologic specimens were available in 16 patients (obtained at 15 surgical biopsies that included open-lung or video-assisted thoracoscopic biopsy and one transbronchial lung biopsy) and in one autopsy case. Correlation between CT findings and pathologic analysis results was possible in these patients. The time from CT examination to pathologic procedure ranged from 6 days to 2 years (median, 27 days). In the five patients in whom the interval between biopsy and CT exceeded 1 month, the main reason was that the CT images obtained at the time of biopsy were not available because those CT images were returned to outside hospitals where patients had undergone CT. In these patients, however, review of the CT reports confirmed that the findings on CT images used for the study were essentially unchanged from those on the images obtained at the time of the biopsy. These CT reports were reviewed by one radiologist (N.T.). CT findings, which included GGO, reticulation, honeycombing, and nodules, were correlated with pathologic findings in 17 patients by the same radiologist and one pulmonary pathologist (C.D.C.). The pulmonary pathologist assessed the presence, extent, and intensity of findings, which included interstitial inflammation, fibrosis, fibroblastic foci, organization, honeycombing, bronchiolar changes, and vascular changes. She also evaluated the cellularity and spatial or temporal homogeneity of the lesions. The pathologic diagnosis of interstitial pneumonia was made according to the current classification published by the American Thoracic Society and the European Respiratory Society (22). Nonspecific interstitial pneumonia was subclassified according to the classification of Katzenstein and Fiorelli (42): group 1, inflammation without fibrosis; group 2, mixture of inflammation and fibrosis; and group 3, fibrosis alone. Statistical Analysis Interobserver agreement between the first two radiologists was assessed by calculating the value concerning parenchymal CT findings in categories a o and other findings including the presence or absence of pulmonary artery enlargement, esophageal dilatation, lymph node enlargement, and pleural and pericardial effusion or thickening. We used the following scale for evaluation of agreement with values: , fair agreement; , moderate agreement; , good agreement; greater than 0.81, excellent agreement. Clinical features (age, cigarette consumption), pulmonary function test results (vital capacity, FEV 1 / FVC ratio, total lung capacity, residual volume, maximum expiratory flow at 25% of vital capacity, DLCO, and DLCO/VA Volume 232 Number 1 Rheumatoid Arthritis related Lung Diseases at CT 83

4 [all except FEV 1 /FVC ratio expressed as percentage predicted]), and pulmonary artery diameter were compared among groups by using the Fisher protected least significant difference test. Correlation between the extent score of CT findings (airspace consolidation, GGO, reticulation, thickening of bronchovascular bundle, honeycombing, nodules, and bronchiectasis) and results of the same pulmonary function tests just mentioned was estimated with a nonparametric test (Spearman rank correlation coefficient) by using commercially available software (StatView, version 4.5; Abacus Concepts, Berkeley, Calif). A correlation was considered present when there was a difference with a P value of less than.05. These statistical analyses were evaluated after we consulted a statistician at our institution who had 28 years of experience. RESULTS CT Findings The frequency of CT findings is summarized in Table 2. GGO (91%) and reticulation (98%) were the most frequent findings in patients. Honeycombing (60%), traction bronchiectasis (75%), and architectural distortion (62%) were also frequently seen. Nodules were observed in 31 (49%) patients; these were centrilobular in 23 (37%) patients and indeterminate in eight (13%). There were no cavitated nodules. Interobserver agreement for determination of the CT features was mostly good (moderate to excellent agreement) except for the evaluation of crazy-paving appearance (fair agreement). Four predominant CT patterns were identified: usual interstitial pneumonia (26 patients), nonspecific interstitial pneumonia (19 patients), bronchiolitis (11 patients), and organizing pneumonia (five patients). In the other two patients, imaging diagnoses were diffuse alveolar damage and lymphoid interstitial pneumonia. Enlargement of the pulmonary artery was observed in 26 (46%) of 57 patients in whom the pulmonary artery diameter was measurable. The CT pattern in these 26 patients was usual interstitial pneumonia in 13 patients, nonspecific interstitial pneumonia in 10, organizing pneumonia in one, and bronchiolitis in two. Usual Interstitial Pneumonia CT Pattern In the 26 patients with the usual interstitial pneumonia CT pattern, reticulation, honeycombing, and GGO were the Figure 1. (a) Transverse thin-section CT scan obtained at level of lower lobe of right lung in 65-year-old man with biopsy-proved usual interstitial pneumonia. Reticulation and honeycombing are seen in posterior subpleural lower lobe of right lung. Small right pneumothorax (*) resulted from video-assisted thoracoscopic biopsy. Both independent chest radiologists classified CT pattern as usual interstitial pneumonia. (b) Photomicrograph of surgical specimen shows extensive interstitial fibrosis with collagen adjacent to large cystic airspace (*). (Hematoxylin-eosin stain; original magnification, 40.) most frequent findings. One patient without honeycombing was classified with the usual interstitial pneumonia CT pattern because of subpleural reticulation and the lack of GGO. Reticulation, honeycombing, and areas of GGO were bilateral in most of the cases and showed predominance in the lower zone of the lung (Fig 1). Areas of GGO and reticulation were observed in all lung zones in 11 (42%) and 17 (65%) patients, respectively. The median extent of reticulation Figure 2. (a) Transverse thin-section CT scan obtained at level of lower lobe of right lung in 64-year-old woman with biopsy-proved nonspecific interstitial pneumonia (Katzenstein and Fiorelli classification group 2). GGO and reticulation are seen in subpleural areas of lower lobe of right lung. Honeycombing is not seen; traction bronchiectasis (arrows) is present. Both independent chest radiologists classified this CT pattern as nonspecific interstitial pneumonia. (b) Photomicrograph of surgical specimen shows thickening of alveolar septa (arrows) with mixture of chronic inflammatory cell infiltrates and fibrosis. Changes appear uniform throughout specimen and indicate spatial homogeneity. (Hematoxylin-eosin stain; original magnification, 40.) and honeycombing was grade 1. The extent of GGO was grade 1 in 22 (85%) patients and grade 2 in two (8%) patients. Traction bronchiectasis and architectural distortion, when present, were always observed concomitantly with reticulation and honeycombing. Consolidation, when 84 Radiology July 2004 Tanaka et al

5 TABLE 2 Summary of CT Findings according to CT Pattern Radiology Finding Total (n 63) Usual Interstitial Pneumonia Pattern (n 26) Nonspecific Interstitial Pneumonia Pattern (n 19) Bronchiolitis Pattern (n 11) Organizing Pneumonia Pattern (n 5) Other Patterns (n 2) Consolidation 22 (35) 8 (31) 3 (16) 6 (55) 4 (80) 1 (50) GGO 57 (90) 24 (92) 19 (100) 7 (64) 5 (100) 2 (100) Reticulation 62 (98) 26 (100) 19 (100) 11 (100) 4 (80) 2 (100) Bronchovascular bundle thickening 14 (22) 2 (8) 6 (32) 1 (9) 4 (80) 1 (50) Honeycombing 38 (60) 25 (96) 10 (53) 1 (9) 1 (20) 1 (50) Nodules 31 (49) 10 (38) 7 (37) 9 (82) 5 (100) 0 (0) Emphysema 15 (24) 10 (38) 1 (5) 1 (9) 1 (20) 2 (100) Bullae 9 (14) 6 (23) 1 (5) 0 (0) 0 (0) 2 (100) Bronchiectasis or bronchiolectasis 14 (22) 1 (4) 3 (16) 10 (91) 0 (0) 0 (0) Traction bronchiectasis 47 (75) 23 (88) 17 (89) 1 (9) 5 (100) 1 (50) Crazy-paving appearance 1 (2) 0 (0) 1 (5) 0 (0) 0 (0) 0 (0) Tree-in-bud sign 6 (10) 0 (0) 1 (5) 5 (45) 0 (0) 0 (0) Mosaic perfusion 15 (24) 8 (31) 4 (21) 3 (27) 0 (0) 0 (0) Air trapping 10/23 (43) 1/7 (14) 3/9 (33) 6/6 (100) 0/1 (0) 0/0 (0) Architectural distortion 39 (62) 18 (69) 17 (89) 0 (0) 3 (60) 1 (50) Pulmonary artery enlargement 26/57 (46) 13/24 (54) 10 (53) 2/8 (25) 1/4 (25) 0 (0) Esophageal dilatation 12 (19) 4 (15) 6 (32) 1 (9) 1 (20) 0 (0) Lymph node enlargement 12/61 (20) 5/25 (20) 6 (32) 1 (9) 0/4 (0) 0 (0) Pleural or pericardial effusion or thickening 18 (29) 9 (35) 7 (37) 1 (9) 0 (0) 1 (50) Value* Note. Data are numbers of patients. Numbers of patients differ for some entries because number of available patients was different, expiratory CT was not performed in some patients, and calculation of the pulmonary artery diameter and size of the lymph nodes was not possible in some patients. Numbers in parentheses are percentages. Biopsy results were as follows: for patients with usual interstitial pneumonia CT pattern, usual interstitial pneumonia (two patients) and nonspecific interstitial pneumonia (two patients); for those with nonspecific interstitial pneumonia CT pattern, nonspecific interstitial pneumonia (seven patients) and desquamative interstitial pneumonia (one patient); for those with bronchiolitis CT pattern, lymphocytic bronchiolitis (one patient); for those with organizing pneumonia CT pattern, organizing pneumonia (two patients); for those with other CT patterns, diffuse alveolar damage (one patient) and nonspecific interstitial pneumonia and bronchiolitis obliterans (one patient). * The scale for values was as follows: , fair agreement; , moderate agreement; , good agreement; greater than 0.81, excellent agreement. present, was minor in extent (grade 1). Nodules were observed in 10 (39%) patients; centrilobular nodules, in four patients; indeterminate nodules, in six patients. Enlargement of the pulmonary artery was seen in 13 (54%) of 24 patients, and the mean diameter of the main pulmonary artery was 30.2 mm 4.0. The overall abnormalities were predominant in the lower zone of the lung in 23 (89%) patients. All patients showed peripheral area predominance. Nonspecific Interstitial Pneumonia CT Pattern In the 19 patients with the nonspecific interstitial pneumonia CT pattern, areas of GGO and reticulation were observed bilaterally in all cases and showed predominance in the lower zone of the lung (Fig 2). However, areas of GGO and reticulation were seen in all lung zones in as many as 13 (68%) and 15 (79%) patients, respectively. The extent of GGO and reticulation were grade 1 in 12 (63%) and 16 (84%) patients, respectively, and grade 2 in seven (37%) and three (16%) patients, respectively. The extent of GGO of a grade higher than grade 2 was more frequent in patients with the nonspecific interstitial pneumonia CT pattern than it was in patients with the usual interstitial pneumonia CT pattern (P.028, Fisher exact probability test). Honeycombing was seen in 10 (53%) patients, was always bilateral, and showed predominance in the lower zone of the lung. The extent of honeycombing was grade 1 in all 10 patients, which was in keeping with the CT definition of nonspecific interstitial pneumonia. Both traction bronchiectasis and architectural distortion were frequently seen and were bilateral in most of the cases. They were observed concomitantly with reticulation. Nodules were observed in seven (37%) patients: centrilobular nodules in five patients and indeterminate nodules in two patients. Enlargement of the pulmonary artery was seen in 10 (53%) patients. The mean diameter of the main pulmonary artery was 30.0 mm 4.7, which was almost identical to that in patients with the usual interstitial pneumonia CT pattern. The abnormalities were predominant in the lower zone of the lung in all cases. Sixteen patients had a predominantly peripheral distribution, and three had a predominantly peribronchial distribution. Bronchiolitis CT Pattern In the 11 patients with the bronchiolitis CT pattern, nodules and bronchiectasis or bronchiolectasis were the most common findings, which were seen in nine (82%) and 10 (91%) patients, respectively. Nodules were identified as centrilobular micronodules in all nine patients; the nodules were bilateral in eight patients with no zonal predominance and were always seen in patients with bronchiectasis (Fig 3). The extent of nodules was grade 1 in all but one patient. Bronchiectasis was localized in seven patients and extensive in three patients. Bronchiectasis was cylindric in all patients. Bilateral air trapping was observed in all six patients who underwent expiratory CT. The tree-in-bud sign was seen in five (46%) patients. Reticulation, GGO, and airspace consolidation, when Volume 232 Number 1 Rheumatoid Arthritis related Lung Diseases at CT 85

6 Figure 3. Transverse thin-section CT scans obtained at level of lower lobe of right lung in 28-year-old woman with bronchiolitis. (a) Inspiratory scan shows mosaic attenuation (*), centrilobular nodules (arrows), bronchial wall thickening, and cylindric bronchiectasis (arrowheads). FEV 1 /FVC ratio was 78.7%, and maximum expiratory flow at 25% of vital capacity was 23.3% predicted. Both independent chest radiologists classified CT pattern as bronchiolitis. (b) Expiratory scan shows extensive air trapping (*). present, were typically minor and unilateral. No predominant craniocaudal or transverse distribution was identified. Organizing Pneumonia CT Pattern In the five patients with the organizing pneumonia CT pattern, airspace consolidation, GGO, reticulation, and centrilobular micronodules were the predominant findings. Airspace consolidation and areas of GGO were bilateral and were located in the subpleural areas in most of the cases and showed no zonal predominance (Fig 4). The extent of airspace consolidation and GGO were grade 1 in two and four patients, respectively, and grade 2 in two patients and one patient, respectively. Thickening of bronchovascular bundle was frequently observed. Centrilobular nodules were observed in all five patients. Four patients showed predominance in the lower lung zone and a craniocaudal distribution. Three patients had a predominantly peripheral distribution, and one had a predominantly peribronchial distribution. Other CT Patterns In one patient who met CT criteria for diffuse alveolar damage, airspace consolidation, GGO, reticulation, and honeycombing were seen in all lung zones. Traction bronchiectasis was also seen bilaterally. The extent of airspace consolidation was grade 2. In one patient with the lymphoid interstitial pneumonia CT pattern, multiple cysts of several centimeters in size were scattered within the lung parenchyma. GGO and reticulation were also seen to a minimal extent. Pathologic Findings Pathologic diagnoses in 17 patients included usual interstitial pneumonia in two, nonspecific interstitial pneumonia in 10, organizing pneumonia in two, diffuse alveolar damage in one, desquamative interstitial pneumonia in one, and lymphocytic bronchiolitis in one. Findings of nonspecific interstitial pneumonia were associated with histologic findings of alveolar proteinosis, bronchiolitis obliterans, and lymphocytic bronchiolitis in one, two, and one patient, respectively. Furthermore, the patient with desquamative interstitial pneumonia had associated findings of lymphocytic bronchiolitis. In total, bronchiolitis was seen in five patients. Pathologic diagnosis was available in Figure 4. (a) Transverse thin-section CT scan obtained through lower lung zone in 70-yearold woman with biopsy-proved organizing pneumonia. Multiple patches of consolidation are seen in subpleural area of lung. Both independent chest radiologists classified CT pattern as organizing pneumonia. (b) Photomicrograph of surgical specimen shows numerous polyps (arrows) of granulation tissue within bronchiolar lumina and peribronchiolar airspaces. Interstitial response is observed and consists of thickening of alveolar septa and chronic inflammatory interstitial infiltrates. (Hematoxylin-eosin stain; original magnification, 40.) four of 26 patients with the usual interstitial pneumonia CT pattern. In two patients, the disease was pathologically diagnosed as usual interstitial pneumonia; in another two patients, the disease was diagnosed as nonspecific interstitial pneumonia (Fig 5). In the two patients with biopsy-proved usual interstitial pneumonia, bandlike dense fibrosis or fi- 86 Radiology July 2004 Tanaka et al

7 Figure 5. (a) Transverse thin-section CT scan obtained at level of lower lobe of left lung in 67-year-old man with biopsy-proved nonspecific interstitial pneumonia (Katzenstein and Fiorelli classification group 3). Mixed areas of GGO and reticular abnormalities (arrows) are seen extensively. Honeycombing and traction bronchiectasis (arrowheads) are well demonstrated. Both chest radiologists classified CT pattern as usual interstitial pneumonia because of presence of moderate honeycombing. (b) Photomicrograph of surgical specimen shows interstitial thickening with deposition of dense collagen and honeycombing (*). Because of temporal homogeneity and lack of conspicuous fibroblastic foci, pathologic diagnosis was nonspecific interstitial pneumonia. (Hematoxylin-eosin stain; original magnification, 40.) brous thickening of interlobular septa and subpleural cystic airspaces were seen in lung specimens (Fig 1). Pathologic diagnosis was available in eight of 19 patients with the nonspecific interstitial pneumonia CT pattern, and findings in these eight patients were available for pathologic review. Seven of eight patients had histologically proved nonspecific interstitial pneumonia. One patient with the lymphoid interstitial pneumonia CT pattern and two patients with the usual interstitial pneumonia CT pattern proved to have nonspecific interstitial pneumonia at pathologic analysis (surgical biopsy). Therefore, in total, biopsy-proved nonspecific interstitial pneumonia was identified in 10 patients. The nonspecific interstitial pneumonia was graded according to the Katzenstein and Fiorelli classification as follows: group 1, one patient; group 2, five patients; and group 3, four patients. In all patients with biopsy-proved nonspecific interstitial pneumonia, pathologic thickening of alveolar septa caused by interstitial inflammation and/or fibrosis (Fig 2) was observed. GGO and reticulation were observed in all 10 patients. All five patients with honeycombing at CT had subpleural cystic airspaces at biopsy. The diameter of cystic airspaces at biopsy was greater in patients with the group 3 classification than in those with the group 2 classification. Airspace consolidation was observed at CT in two patients with biopsy-proved nonspecific interstitial pneumonia; both patients had group 2 classification nonspecific interstitial pneumonia, with dense fibrosis or honeycombing containing mucin. Lymphoid follicles were observed histologically in three of four patients with nodules at thin-section CT. Two patients with biopsy-proved nonspecific interstitial pneumonia (one with group 2 classification and the other with group 3 classification) were classified with the usual interstitial pneumonia CT pattern and showed extensive reticulation within areas of GGO and subpleural honeycombing, although areas of GGO were more conspicuous than they were in typical cases of usual interstitial pneumonia (Fig 5). In patients with histologically proved usual interstitial pneumonia and nonspecific interstitial pneumonia, honeycombing was observed in two (100%) and five (50%) patients, respectively; reticulation was observed in all patients. Areas of GGO were also observed in all patients with histologically proved usual interstitial pneumonia and nonspecific interstitial pneumonia. There was a difference, however, in the extent of GGO between the two groups; GGO was observed in all lung zones in seven patients with histologically proved nonspecific interstitial pneumonia and in none with histologically proved usual interstitial pneumonia. This difference was not significant (P.152, Fisher exact probability test). Among 11 patients with the bronchiolitis CT pattern, correlation between CT findings and pathologic findings was available in one patient who received a histologic diagnosis of lymphocytic bronchiolitis. Centrilobular nodules at thinsection CT appeared to reflect marked lymphocyte infiltration without germinal centers surrounding the bronchioles. A pathologic diagnosis was available in two of five patients with the organizing pneumonia CT pattern. Airspace consolidation in one patient was associated with histologic findings of extensive organizing pneumonia and concomitant fibrosis (Fig 4). In another patient in whom the predominant finding was GGO, the histologic findings were patchy organizing pneumonia and fibrotic alveolar septal thickening, with preservation of alveolar spaces. One patient with the CT pattern of diffuse alveolar damage proved to have organizing diffuse alveolar damage at pathologic analysis of a specimen. One patient with the lymphoid interstitial pneumonia CT pattern due to perivascular cysts proved to have cellular nonspecific interstitial pneumonia (group 1 classification) associated with constrictive bronchiolitis. It was unclear whether or not the cystic airspaces identified at CT were caused by bronchial obstruction. Assessment of Patient Characteristics and Pulmonary Function Test Results The age distribution according to sex and CT pattern (usual interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis, and organizing pneumonia) was evaluated by using the twofactor factorial analysis of variance method. This analysis showed that the differences in sex (P.445) and CT pattern (P.095) did not significantly influence the age distribution. In this study, female predominance was seen with the nonspecific interstitial pneumonia and bronchiolitis CT patterns, which contributed to the female predominance in the total cases. In regard to the duration of rheumatoid arthritis, patients with the bronchiolitis CT pattern had longer duration of rheumatoid arthritis than did those with the usual interstitial pneumonia and organizing pneumonia CT patterns (Table 3). Because of the retrospective nature of the study, the number of patients who underwent each type of physiologic test Volume 232 Number 1 Rheumatoid Arthritis related Lung Diseases at CT 87

8 TABLE 3 Patient Characteristics and Pulmonary Function Test Results in Each Group Radiology Characteristic Usual Interstitial Pneumonia (n 26) Nonspecific Interstitial Pneumonia (n 19) Bronchiolitis (n 11) Organizing Pneumonia (n 5) Age Both sexes (n 26)* (n 19) (n 11) (n 5) M (n 16) (n 6) 64 (n 1) (n 2) F (n 10) (n 13) (n 10) (n 3) Duration of rheumatoid arthritis (y) (n 25) (n 17) (n 11) (n 4) # Cigarette consumption (pack-years) (n 20)** (n 15) (n 11) (n 3) Vital capacity (percentage predicted) (n 21) (n 14) (n 5) (n 3) FEV 1 /FVC ratio (%) (n 20) (n 14) (n 5) (n 3) Total lung capacity (percentage predicted) (n 14) (n 11) 66.0 (n 1) 51.0 (n 1) Residual volume (percentage predicted) (n 14) (n 11) 77.0 (n 1) 66.0 (n 1) Maximum expiratory flow at 25% of vital capacity (percentage predicted) (n 9) (n 3) (n 4) (n 2) DLCO (percentage predicted) (n 13) (n 11) ## (n 3)*** (n 2) DLCO/VA (percentage predicted) (n 12) (n 11) (n 3) (n 2) Pulmonary artery diameter (mm) (n 24) (n 19) (n 8) (n 4) Note. Data are the mean SD except as otherwise indicated. Fisher protected least significant difference test was used for all comparisons. * P.05, usual interstitial pneumonia versus bronchiolitis group and usual interstitial pneumonia versus nonspecific interstitial pneumonia group. P.05, usual interstitial pneumonia versus nonspecific interstitial pneumonia group. P.05, usual interstitial pneumonia versus bronchiolitis group. Data are means. P.05, usual interstitial pneumonia versus bronchiolitis group and bronchiolitis versus organizing pneumonia group. # P.05, bronchiolitis versus organizing pneumonia group. ** P.01, usual interstitial pneumonia versus bronchiolitis group; P.001, usual interstitial pneumonia versus nonspecific interstitial pneumonia group. P.001, usual interstitial pneumonia versus nonspecific interstitial pneumonia group. P.01, usual interstitial pneumonia versus bronchiolitis group. P.05, nonspecific interstitial pneumonia versus bronchiolitis group. P.001, usual interstitial pneumonia versus bronchiolitis group. ## P.001, nonspecific interstitial pneumonia versus bronchiolitis group. *** P.001, usual interstitial pneumonia versus bronchiolitis group and nonspecific interstitial pneumonia versus bronchiolitis group; P.01, organizing pneumonia versus bronchiolitis group. P.01, organizing pneumonia versus bronchiolitis group. was variable. The physiologic indices that showed air flow obstruction (FEV 1 /FVC ratio and maximum expiratory flow at 25% of vital capacity [expressed as percentage predicted]) in patients with the bronchiolitis CT pattern tended to show more impairment than they did in patients with the other CT patterns. The physiologic indices of vital capacity, DLCO, and DLCO/VA (expressed as percentage predicted) in patients with the bronchiolitis CT pattern tended to show less impairment than they did in patients with the other CT patterns. There was no significant difference in physiologic indices among patients with the usual interstitial pneumonia, nonspecific interstitial pneumonia, and organizing pneumonia CT patterns. With regard to the correlation between the extent of CT findings and pulmonary function test results, significant correlations were observed between GGO and FEV 1 /FVC ratio, between reticulation and vital capacity (expressed as percentage predicted) or the FEV 1 /FVC ratio, and between bronchiectasis and FEV 1 /FVC ratio (Table 4). DISCUSSION Since the introduction of the concept of nonspecific interstitial pneumonia by Katzenstein and Fiorelli (42) in 1994, it has been known that nonspecific interstitial pneumonia is frequently associated with collagenous vascular disease. In their article, these authors found collagenous vascular disease in 16% of patients with nonspecific interstitial pneumonia. In a review of pathologic findings in 40 patients with rheumatoid arthritis who underwent open-lung biopsy, Yousem et al (20) found cellular interstitial pneumonia as a primary or secondary lesion, which seemed identical to nonspecific interstitial pneumonia, in 10 patients. In our study, the nonspecific interstitial pneumonia CT pattern was observed in 19 (30%) patients, whereas the histologic finding of nonspecific interstitial pneumonia was identified in 10 (59%) of the 17 patients in whom biopsy findings were available. Our study findings, therefore, confirm the high prevalence of nonspecific interstitial pneumonia as a histologic and CT finding in rheumatoid disease. The common CT findings of nonspecific interstitial pneumonia are bilateral areas of GGO, with a predominant distribution in the peripheral or subpleural area in the lower zone of the lung (22 25,29,30), and associated reticular abnormalities. These findings are thought to occur in at least 80% of patients (23). Honeycombing is not frequently seen and is sparse when present. In the current study, areas of GGO were more extensive with the nonspecific interstitial pneumonia CT pattern than they were with the usual interstitial pneumonia CT pattern. In our study, the finding of honeycombing was more frequently observed than it was in the previous reports of Remy-Jardin et al (4) and Akira et al (6) (Table 5), which raises the possibility that some patients may have had mixed usual interstitial pneumonia and nonspecific interstitial pneumonia patterns. GGO, reticulation, traction bronchiectasis, and architectural distortion were all 88 Radiology July 2004 Tanaka et al

9 TABLE 4 Correlation between CT Findings and Pulmonary Function Test Results Radiology Pulmonary Function Test* Consolidation GGO Reticulation Bronchovascular Bundle Thickening Honeycombing Nodules Bronchiectasis Vital capacity (n 43) FEV 1 /FVC ratio (n 42) Total lung capacity (n 27) Residual volume (n 27) Maximum expiratory flow at 25% of vital capacity (n 18) NA DLCO (n 29) DLCO/VA (n 29) Note. Numbers are correlation coefficients for correlation between pulmonary function test result and CT finding. * Unless otherwise specified, values used to calculate correlation coefficients were expressed as percentage predicted. FEV 1 /FVC ratio was expressed as a percentage. P.05. NA not applicable. TABLE 5 Comparison of CT Findings in Current and Previous Studies of Patients with Rheumatoid Arthritis Finding more frequently observed than they were in either of the previous studies (Table 5). The higher prevalence of these findings in the current study may be caused by referral bias, since many of the patients in our series were seen at an interstitial lung disease clinic. Remy-Jardin et al (4) and Akira et al (6) stressed that bronchial and bronchiolar changes, which included bronchiectasis, centrilobular nodules, or the tree-in-bud pattern, were the most prevalent lung lesions in patients with rheumatoid arthritis. In the current study, centrilobular micronodules were observed in 23 (37%) of 63 patients, but bronchiectasis and the tree-in-bud sign were less frequent than they were in the patients in the study of Akira et al (Table 5). The reason for the lower frequency of Remy-Jardin et al (n 77)* Akira et al Current Study (n 29) (n 63) Consolidation 5 (7) 10 (34) 22 (35) GGO 11 (14) 19 (66) 57 (90) Reticulation 14 (18) 21 (72) 62 (98) Honeycombing 8 (10) 10 (34) 38 (60) All nodules 17 (22) 13 (45) 31 (49) Centrilobular nodules 6 (8) 9 (31) 23 (37) Emphysema 4 (5) 2 (7) 15 (24) Bronchiectasis or bronchiolectasis 23 (30) 15 (52) 14 (22) Traction bronchiectasis NA 13 (45) 47 (75) Tree-in-bud sign 6 (8) 9 (31) 6 (10) Mosaic perfusion NA 2 (7) 15 (24) Air trapping NA NA 10/23 (43) Architectural distortion 5 (7) NA 39 (62) Pulmonary artery enlargement 7 (10) NA 26/57 (46) Lymph node enlargement 7 (10) NA 12/61 (20) Pleural effusion or thickening 12 (16) NA 18 (29) Note. Data are numbers of patients. Data in parentheses are percentages. Percentages were rounded to whole numbers. NA not applicable. * Reference 4. Reference 6. the tree-in-bud pattern in our study is unknown, but it may be related to differing criteria for distinguishing between centrilobular nodules and the tree-in-bud pattern. The lower frequency of bronchiectasis in the patients in our study was probably because the group with bronchiectasis in the study of Akira et al clearly included 13 patients with traction bronchiectasis, as well as two with pure bronchiectasis. As found in our study, the characteristic CT findings of usual interstitial pneumonia include the reticular pattern and honeycombing with subpleural or peripheral distribution and lower lung zone predominance (22 25). Traction bronchiectasis and architectural distortion are also frequent findings. There was considerable overlap in the frequency of individual CT findings in patients with nonspecific interstitial pneumonia and usual interstitial pneumonia CT patterns in our study. Frequent and characteristic findings in both groups included GGO and reticulation. Honeycombing was also seen in 53% of patients with the nonspecific interstitial pneumonia CT pattern in the current study. The only effective differential point seemed to be the distribution and extent of GGO; GGO was seen more diffusely and extensively in patients with histologically proved nonspecific interstitial pneumonia than they were in patients with usual interstitial pneumonia. There were two discrepant cases, however, in which patients were classified as having the usual interstitial pneumonia CT pattern, but at pathologic analysis of the specimens the cases proved to be nonspecific interstitial pneumonia. There have been several other reports that showed a difficulty in discrimination between some cases of usual interstitial pneumonia and those of nonspecific interstitial pneumonia at CT because of overlapping findings (30,43). It is speculated that the biopsy-proved cases with the usual interstitial pneumonia CT pattern might have been selected for biopsy because of confusing or overlapping CT findings. Patients with CT features typical of usual interstitial pneumonia rarely undergo surgical biopsy. The discrepancy between the CT pattern and pathologic diagnosis may reflect the difficulty in discrimination between usual interstitial pneumonia and fibrotic nonspecific interstitial pneumonia both on CT images and in pathologic specimens (14,22,24, 29,43). MacDonald et al (30) stressed the difficulty in correct diagnosis of usual intersti- Volume 232 Number 1 Rheumatoid Arthritis related Lung Diseases at CT 89

10 tial pneumonia and nonspecific interstitial pneumonia because of considerable overlap in thin-section CT appearances. They reported that a misdiagnosis of usual interstitial pneumonia in patients with biopsyproved nonspecific interstitial pneumonia was associated with coarse fibrosis (honeycombing). Although the frequency of honeycombing in patients with nonspecific interstitial pneumonia has been reported as relatively rare, CT images obtained in patients with it can show honeycombing. This finding was relatively frequent in the current study. The finding of histologic desquamative interstitial pneumonia in one patient with the nonspecific interstitial pneumonia CT pattern is not surprising, as both conditions are characterized at CT by a predominance of GGO. Differentiation between nonspecific interstitial pneumonia and desquamative interstitial pneumonia, however, is usually not critical because the prognosis of both conditions is similar. Organizing pneumonia shows bilateral areas of airspace consolidation with or without areas of GGO, with a subpleural or peribronchial distribution at CT in the majority of cases (22 28,44). Centrilobular nodules, branching structures, and multiple large nodules have been reported. The current study also showed similar findings. Types of bronchiolitis commonly seen in rheumatoid arthritis are bronchiolitis obliterans and follicular bronchiolitis. The common thin-section CT abnormalities of bronchiolitis obliterans consist of patchy areas of air trapping, bronchial dilatation, and centrilobular nodules with branching linear structures (36 38). Follicular bronchiolitis is characterized by centrilobular micronodules and branching structures at thin-section CT (14). In the current study, it is not clear which histologic pattern was present in 11 patients with the bronchiolitis CT pattern because only one patient underwent surgical biopsy. In the current study, patients with the usual interstitial pneumonia, nonspecific interstitial pneumonia, and organizing pneumonia CT patterns showed some evidence of airway disease, such as centrilobular micronodules, mosaic perfusion, and air trapping. Conversely, evidence of interstitial disease, such as GGO and reticulation, was seen in patients with the bronchiolitis CT pattern. Also, eight patients with the usual interstitial pneumonia and six patients with the bronchiolitis CT patterns had associated airspace consolidation, a finding that suggested organizing pneumonia. These results show that several kinds of pathologic conditions can coexist in one patient with rheumatoid arthritis. Yousem et al (20) also reported a wide variety of pathologic findings and a multiplicity of lesions in individual cases. In our study, multiple conditions coexisted in several specimens in the limited number of patients with biopsyproved cases. The multiplicity of CT patterns in patients with rheumatoid arthritis and other collagenous vascular diseases might help differentiate these patients from those with idiopathic diffuse lung disease. In these patients, CT may be of substantial value in identification of the dominant pattern of abnormality. Enlargement of the pulmonary artery was a rather frequent finding in the current study. This result is different from findings in previous studies that showed that pulmonary hypertension is rare (2,11). Among 26 patients with pulmonary hypertension, however, 10 patients had the nonspecific interstitial pneumonia CT pattern, 13 patients had the usual interstitial pneumonia CT pattern, and one patient had the organizing pneumonia CT pattern. The cause of pulmonary hypertension in these patients might have been interstitial lung disease. Only two patients showed pulmonary hypertension without evidence of interstitial pneumonia, such as honeycombing. Furthermore, pulmonary hypertension is not a rare feature in patients with rheumatoid arthritis. In regard to the correlation between pulmonary function test results and the extent of CT findings, the extent of reticulation was correlated with vital capacity (expressed as percentage predicted), which suggests that this is a valid reflection of the amount of restrictive physiologic impairment. Conversely, the extent of bronchiectasis was correlated with the FEV 1 /FVC ratio, which suggests that this reflects airflow impairment. Although rheumatoid arthritis is less common in men than in women, several study results indicate that pulmonary complications are more common in men (1,2). Our study findings indicated an overall predominance of women, which was mainly due to a predominance of women among the patients with the nonspecific interstitial pneumonia and bronchiolitis CT patterns. The reason for the female predominance in those with the nonspecific interstitial pneumonia CT pattern is unclear. Shadick et al (19) reported that severe bronchiectasis predominantly occurs in female patients, and our study results suggest that this female predominance also extends to bronchiolitis. There were several limitations of this study. The sample size of this study might be too small to allow confident detection of some correlations in the Results section, because we studied all available patients who met the eligibility criteria for rheumatoid arthritis, and a power analysis was not performed. Because pathologic confirmation was not available in all 63 patients, it is unclear whether the classification that was based on CT findings really reflects the pathologic classification. In particular, it is likely that some cases of usual interstitial pneumonia and nonspecific interstitial pneumonia were misclassified. However, it is not practical in clinical medicine to determine the diagnosis in all patients by means of surgical biopsy, especially in those patients who have typical clinical and thin-section CT features of usual interstitial pneumonia. A further limitation was that a precise correlation between radiologic findings and pathologic findings was not possible because the site of biopsy was not identified. Because of the retrospective nature of this study, clinical information, pulmonary function test results, or expiratory CT scans were not available in all patients. More patients with air trapping would have been detected if expiratory CT scans were obtained in all patients. In conclusion, GGO or reticulation was the most common CT finding in 63 patients with rheumatoid arthritis related lung disease, and a classification that was based on CT features was largely successful for prediction of the histologic diagnosis; however, a multiplicity of CT patterns is commonly seen in patients with rheumatoid arthritis. Acknowledgments: The authors thank Martin E. Wallace, HTBS, National Jewish Center for Immunology and Respiratory Medicine, for his assistance in collecting pathologic specimens, Mario Lujan, Department of Radiology at the National Jewish Center for Immunology and Respiratory Medicine, for his assistance in collecting CT scans, and Noriaki Harada, MD, PhD, for his assistance in statistical data analysis. References 1. Anaya JM, Diethelm L, Ortiz LA, et al. Pulmonary involvement in rheumatoid arthritis. Semin Arthritis Rheum 1995; 24: Shannon TM, Gale ME. Noncardiac manifestations of rheumatoid arthritis in the thorax. J Thorac Imaging 1992; 7: Tanoue LT. Pulmonary manifestations of rheumatoid arthritis. Clin Chest Med 1998; 19: Remy-Jardin M, Remy J, Cortet B, Mauri F, Delcambre B. Lung changes in rheuma- 90 Radiology July 2004 Tanaka et al

11 toid arthritis: CT findings. Radiology 1994; 193: Steinberg DL, Webb WR. CT appearances of rheumatoid lung disease. J Comput Assist Tomogr 1984; 8: Akira M, Sakatani M, Hara H. Thin-section CT findings in rheumatoid arthritisassociated lung disease: CT patterns and their courses. J Comput Assist Tomogr 1999; 23: Fujii M, Adachi S, Shimizu T, Hirota S, Sako M, Kono M. Interstitial lung disease in rheumatoid arthritis: assessment with high-resolution computed tomography. J Thorac Imaging 1993; 8: McDonagh J, Greaves M, Wright AR, Heycock C, Owen JP, Kelly C. High-resolution computed tomography of the lungs in patients with rheumatoid arthritis and interstitial lung disease. Br J Rheumatol 1994; 33: Fewins HE, McGowan I, Whitehouse GH, Williams J, Mallya R. High definition computed tomography in rheumatoid arthritis associated pulmonary disease. Br J Rheumatol 1991; 30: Cervantes-Perez P, Toro-Perez AH, Rodriguez-Jurado P. Pulmonary involvement in rheumatoid arthritis. JAMA 1980; 243: Balagopal VP, de Costa P, Greenstone MA. Fatal pulmonary hypertension and rheumatoid vasculitis. Eur Respir J 1995; 8: Hayakawa H, Sato A, Imokawa S, Toyosima M, Chida K, Iwata M. Bronchiolar disease in rheumatoid arthritis. Am J Respir Crit Care Med 1996; 154: Geddes DM, Webley M, Emerson PA. Airways obstruction in rheumatoid arthritis. Ann Rheum Dis 1979; 38: Howling SJ, Hansell DM, Wells AU, Nicholson AG, Flint JD, Müller NL. Follicular bronchiolitis: thin-section CT and histologic findings. Radiology 1999; 212: Begin R, Masse S, Cantin A, Menard HA, Bureau MA. Airway disease in a subset of nonsmoking rheumatoid patients: characterization of the disease and evidence for an autoimmune pathogenesis. Am J Med 1982; 72: Herzog CA, Miller RR, Hoidal JR. Bronchiolitis and rheumatoid arthritis. Am Rev Respir Dis 1981; 124: Perez T, Remy-Jardin M, Cortet B. Airways involvement in rheumatoid arthritis: clinical, functional, and HRCT findings. Am J Respir Crit Care Med 1998; 157: Vergnenegre A, Pugnere N, Antonini MT, et al. Airway obstruction and rheumatoid arthritis. Eur Respir J 1997; 10: Shadick NA, Fanta CH, Weinblatt ME, O Donnell W, Coblyn JS. Bronchiectasis: a late feature of severe rheumatoid arthritis. Medicine (Baltimore) 1994; 73: Yousem SA, Colby TV, Carrington CB. Lung biopsy in rheumatoid arthritis. Am Rev Respir Dis 1985; 131: Silman AJ. The 1987 revised American Rheumatism Association criteria for rheumatoid arthritis. Br J Rheumatol 1988; 27: American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June Am J Respir Crit Care Med 2002; 165: Lynch DA. High-resolution CT of idiopathic interstitial pneumonias. Radiol Clin North Am 2001; 39: Reynolds JH, Hansell DM. The interstitial pneumonias: understanding the acronyms. Clin Radiol 2000; 55: Müller NL, Colby TV. Idiopathic interstitial pneumonias: high-resolution CT and histologic findings. RadioGraphics 1997; 17: Epler GR. Heterogeneity of bronchiolitis obliterans organizing pneumonia. Curr Opin Pulm Med 1998; 4: Lee KS, Kullnig P, Hartman TE, Müller NL. Cryptogenic organizing pneumonia: CT findings in 43 patients. AJR Am J Roentgenol 1994; 162: Preidler KW, Szolar DM, Moelleken S, Tripp R, Schreyer H. Distribution pattern of computed tomography findings in patients with bronchiolitis obliterans organizing pneumonia. Invest Radiol 1996; 31: Kim TS, Lee KS, Chung MP, et al. Nonspecific interstitial pneumonia with fibrosis: high-resolution CT and pathologic findings. AJR Am J Roentgenol 1998; 171: MacDonald SL, Rubens MB, Hansell DM, et al. Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparative appearances at and diagnostic accuracy of thin-section CT. Radiology 2001; 221: Johkoh T, Müller NL, Pickford HA, et al. Lymphocytic interstitial pneumonia: thinsection CT findings in 22 patients. Radiology 1999; 212: Ichikado K, Johkoh T, Ikezoe J, et al. Acute interstitial pneumonia: high-resolution CT findings correlated with pathology. AJR Am J Roentgenol 1997; 168: Johkoh T, Müller NL, Taniguchi H, et al. Acute interstitial pneumonia: thin-section CT findings in 36 patients. Radiology 1999; 211: Primack SL, Hartman TE, Ikezoe J, Akira M, Sakatani M, Müller NL. Acute interstitial pneumonia: radiographic and CT findings in nine patients. Radiology 1993; 188: Akira M, Hamada H, Sakatani M, Kobayashi C, Nishioka M, Yamamoto S. CT findings during phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis. AJR Am J Roentgenol 1997; 168: Hwang JH, Kim TS, Lee KS, et al. Bronchiolitis in adults: pathology and imaging. J Comput Assist Tomogr 1997; 21: Lau DM, Siegel MJ, Hidebolt CF, Cohen AH. Bronchiolitis obliterans syndrome: thin-section CT diagnosis of obstructive changes in infants and young children after lung transplantation. Radiology 1998; 208: Worthy SA, Park CS, Kim JS, Müller NL. Bronchiolitis obliterans after lung transplantation: high-resolution CT findings in 15 patients. AJR Am J Roentgenol 1997; 169: Kuriyama K, Gamsu G, Stern RG, Cann CE, Herfkens RJ, Brundage BH. CT-determined pulmonary artery diameters in predicting pulmonary hypertension. Invest Radiol 1984; 19: Glazer GM, Gross BH, Quint LE, Francis IR, Bookstein FL, Orringer MB. Normal mediastinal lymph nodes: number and size according to the American Thoracic Society mapping. AJR Am J Roentgenol 1985; 144: Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society. Am Rev Respir Dis 1991; 144: Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis: histologic features and clinical significance. Am J Surg Pathol 1994; 18: Johkoh T, Müller NL, Cartier Y, et al. Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients. Radiology 1999; 211: Nishimura K, Itoh H. High-resolution computed tomographic features of bronchiolitis obliterans organizing pneumonia. Chest 1992; 102:26S 31S. Volume 232 Number 1 Rheumatoid Arthritis related Lung Diseases at CT 91