Proceedings of the American Thoracic Society Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Misumi, S.
Right arrow Articles by Lynch, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Misumi, S.
Right arrow Articles by Lynch, D. A.
The Proceedings of the American Thoracic Society 3:307-314 (2006)
© 2006 The American Thoracic Society

Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia

Imaging Diagnosis, Spectrum of Abnormalities, and Temporal Progression

Shigeki Misumi and David A. Lynch

Department of Radiology, National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to David A. Lynch, M.D., Department of Radiology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: lynchd{at}njc.org

ABSTRACT

The role of high-resolution computed tomography in the diagnosis of interstitial lung disease is increasing as our understanding of its diagnostic accuracy improves. The characteristic findings on high-resolution computed tomography of usual interstitial pneumonia (UIP) are reticular abnormality and honeycombing with basal predominance. Honeycombing is a strong predictor of UIP and also is an important predictor of mortality. Because UIP carries the most adverse prognosis among the subtypes of idiopathic interstitial pneumonia, it is important to be able to differentiate this entity from nonspecific interstitial pneumonia and desquamative interstitial pneumonia from UIP, because these patients may show similar clinical presentations. A confident computed tomography diagnosis of UIP, in association with typical clinical features, will allow the clinician to avoid an unnecessary surgical biopsy.

Key Words: high-resolution computed tomography • idiopathic interstitial pneumonia • idiopathic pulmonary fibrosis • nonspecific interstitial pneumonia • usual interstitial pneumonia

IMAGING FINDINGS OF USUAL INTERSTITIAL PNEUMONIA/IDIOPATHIC PULMONARY FIBROSIS

The typical finding on chest radiographs of patients with idiopathic pulmonary fibrosis (IPF) is peripheral reticular opacity with predominance at the lung bases (Figure 1). Honeycombing and lower lobe volume loss may also be seen. Virtually all patients with IPF have an abnormal chest radiograph at the time of presentation, and radiographic abnormalities are often visible retrospectively for several years before the diagnosis of IPF. In individuals with presymptomatic radiographic abnormalities, high-resolution computed tomography (HRCT) could lead to early diagnosis of IPF. However, because this type of abnormality often remains unchanged for years, it is unclear how many patients with radiographic abnormalities will actually go on to develop symptomatic IPF.


Figure 1
Figure 1
View larger version (269K):
[in this window]
[in a new window]
  		Figure 1. (A and B) Chest radiograph of a 72-yr-old woman with usual interstitial pneumonia (UIP), showing reticular and ground-glass opacities in both lungs with basal predominance. Lung volumes are slightly decreased in both lower lobes.

 
On HRCT images (Figure 2), usual interstitial pneumonia (UIP) is characterized by the presence of reticular opacities, often associated with traction bronchiectasis. Architectural distortion suggestive of lung fibrosis is also frequently recognized. Ground-glass attenuation, if present, is less extensive than reticular abnormality. When ground-glass attenuation is seen in other conditions, such as nonspecific interstitial pneumonia (NSIP) or desquamative interstitial pneumonia (DIP), it is often indicative of a reversible process; however, in patients with IPF it is usually irreversible, and progresses to lung fibrosis. In advanced stages of IPF, honeycombing and lower lung volume loss are usually prominent (1–4).


Figure 2
View larger version (113K):
[in this window]
[in a new window]
  		Figure 2. Typical computed tomography (CT) features of UIP in a 72-yr-old woman. CT through the lower lungs shows subpleural honeycombing (black arrows) and reticular abnormality (arrowhead). Bronchial dilation (white arrows) is due to traction bronchiectasis.

 
Because reticular abnormality and honeycombing are the salient features of UIP, it is important to have a clear understanding of what these terms describe. "Reticular abnormality" refers to a fine network of lines, which should be distinguished from coarser linear scarring occurring as a sequel of previous pneumonia or infarction. Interlobular septal thickening or intralobular lines may be seen as a component of reticular abnormality, but the lobular architecture is usually so distorted that these are impossible to recognize. Honeycombing is recognized by the presence of one or more rows of clustered cysts, almost always subpleural in location, and usually less than 5 mm in diameter. The subpleural clustering and relative small size of these cysts distinguish them from those of cystic lung disease (Figure 2).

CT–pathologic correlation of the features of UIP has been described (1, 4, 5). Reticular abnormality and honeycombing on CT correlate with fibrosis and honeycombing, respectively, on histopathologic examination. When ground-glass attenuation is associated with reticular lines or traction bronchiectasis, it usually indicates histologic fibrosis, whereas isolated ground-glass attenuation may indicate interstitial inflammation, airspace filling, or patchy fibrosis (6). However, because no systematic radiologic–pathologic correlative study has been performed since the publication of the American Thoracic Society/ European Respiratory Society classification (1), some of the cases included in the earlier works cited here may have represented NSIP rather than UIP.

Quantitative CT Evaluation
Despite the accuracy of CT in the diagnosis of IPF, several studies have identified substantial interobserver variation in characterization and visual quantification of diffuse lung disease. For this reason, there is increasing interest in quantitative evaluation of the digital data provided by CT. The simplest form of CT image analysis uses mean lung attenuation, which reflects the relative proportions of air and soft tissue in a given image pixel. Skewness and kurtosis are other properties of the CT density histogram that reflect the amount of soft tissue in the lung. These parameters correlate with the severity of physiologic impairment in patients with diffuse lung fibrosis (7, 8). In a serial study of patients with lung fibrosis, we have found that these parameters typically progress over 12 mo (our unpublished data). More sophisticated image analysis techniques used in IPF have included fractal analysis (9) and the adaptive multiple feature method (10).

Positron Emission Tomography
In general, the lungs of patients with IPF appear to show increased uptake of [18F]fluorodeoxyglucose on positron emission tomography (Figure 3) (11, 12). It was found with a series of seven patients with UIP that uptake was increased in all but one patient, who had advanced honeycombing (12). In one patient with mixed NSIP and UIP, initial increased uptake decreased after treatment with corticosteroids, and subsequently increased when the patient underwent clinical deterioration. The degree of uptake may therefore reflect clinically active disease.


Figure 3
Figure 3
Figure 3
Figure 3
View larger version (339K):
[in this window]
[in a new window]
  		Figure 3. Lung cancer in a 64-yr-old man with UIP. (A and B) Chest CT images show a large left upper lobe mass, with subpleural reticular and honeycomb abnormality in the lower lobes strongly suggestive of UIP. (C) Anterior view (positron emission tomography acquisition) shows high metabolic activity in the left upper lobe lung cancer, with uptake in multiple right hilar and mediastinal nodes suggesting metastases. (D) Axial positron emission tomography image through the lower lungs, at a level corresponding to (B), shows increased activity in the posterior subpleural regions (arrows), corresponding to the areas of fibrosis.

 
DIFFERENTIAL DIAGNOSIS

Because UIP may have a clinical presentation indistinguishable from those of NSIP and DIP, it is important to understand the CT findings that can be used to discriminate between these entities.

Differentiation between UIP and DIP is usually straightforward. Although the basal and peripheral distribution of abnormality is similar in DIP and UIP, the pattern of abnormality is different. In patients with DIP, HRCT shows ground-glass attenuation in all cases, because of spatially homogeneous accumulation of intraalveolar macrophages and alveolar septal thickening (13). Reticular abnormality, traction bronchiectasis, and honeycombing, if present, are relatively sparse, but cysts may be seen (Figure 4) (14, 15).


Figure 4
View larger version (87K):
[in this window]
[in a new window]
  		Figure 4. Desquamative interstitial pneumonia (DIP) in a 52-yr-old man. CT through the mid-lungs shows subpleural predominant ground-glass attenuation containing numerous thin-walled cysts. There is some associated fine reticulation.

 
The CT features of NSIP may overlap with those of UIP in some cases. Like UIP, the abnormality of NSIP usually predominates in the middle and lower lungs. However, NSIP is less likely than UIP to have a subpleural distribution; indeed, the presence of subpleural sparing strongly favors NSIP (Figure 5). Ground-glass attenuation is a frequent feature of NSIP, and it is found in 76 to 100% of cases (16–24). Reticular opacity is found in 46 to 93% of cases, the prevalence of honeycombing has ranged from 0 to 30% in different series, while the prevalence of consolidation has ranged even more widely, from 16 to 80% of cases. In the most recent article regarding NSIP, Johkoh and coworkers (19) reported that ground-glass attenuation was found in 100%, consolidation in 98%, reticular abnormality in 87%, and honeycombing in 27% of cases. They also found that the extent of reticular abnormality and traction bronchiectasis correlated with increasing amounts of fibrosis on histology. Honeycombing was seen mainly in patients with purely fibrotic NSIP. The most likely reason for the wide variability in descriptions of the CT appearances of NSIP is the heterogeneity of histologic diagnostic criteria for NSIP at different sites, because pathologists have been slow to agree on the features that distinguish NSIP from UIP, organizing pneumonia, and DIP, and most articles have used only one pathologist to establish the diagnosis, without determining interobserver or intraobserver variability. In a study by Flaherty and coworkers three expert pathologists agreed on histologic diagnoses of NSIP or UIP in only 67% of cases (16), and a study by Nicholson and coworkers found that the {kappa} coefficient of agreement between two pathologists for distinguishing UIP from fibrotic NSIP was only 0.26 (25). The study by Flaherty and coworkers, of 109 patients who had biopsies of multiple lobes, showed that discordant diagnoses of UIP and NSIP were obtained from different lobes in 28 (26%) (16). The difficulty of differentiating between these entities is compounded by the fact that UIP and NSIP may coexist in the same lung.


Figure 5
View larger version (105K):
[in this window]
[in a new window]
  		Figure 5. Nonspecific interstitial pneumonia (NSIP) in a 53-yr-old man. CT through the lower lungs shows moderately extensive bilateral reticular and ground-glass abnormality with basal predominance. The abnormality shows slight peribronchovascular predominance, particularly in the right lower lobe. Traction bronchiectasis is more marked on the right than on the left. Honeycombing is absent.

 
Several studies have evaluated the ability to differentiate between UIP and NSIP by HRCT. In a study by McDonald and coworkers of 21 patients with NSIP and 32 patients with UIP, the sensitivity, specificity, and accuracy of a CT diagnosis of NSIP were 70, 63, and 66%, respectively (21). UIP was falsely diagnosed in 21 (33%) of 64 readings of patients with fibrotic NSIP. Conversely, NSIP was diagnosed in 48 (38%) of 128 readings in patients with histologic UIP. In a study by Elliot and coworkers of 29 patients with NSIP and 24 with UIP (22), a predominant pattern of ground-glass attenuation and/or reticular opacity, with minimal to no honeycombing, was demonstrated in 57 (98%) of 58 readings in patients with NSIP, and in 21 (43%) of 48 readings of patients with UIP. Conversely, the presence of honeycombing as a predominant feature had a specificity of 98% and positive predictive value of 96% for UIP. The positive predictive value of a confident diagnosis of NSIP was 77%, and the positive predictive value of a confident diagnosis of UIP was 91%. Using similar criteria, Tsubamoto and coworkers achieved a correct diagnosis with a high level of confidence in 61% of cases of NSIP (23). Bna and coworkers suggested that the presence of ground-glass abnormality (unassociated with reticular abnormality), involving more than 15% of the lung, was a significant predictor of the presence of NSIP rather than UIP (24). Not surprisingly, fibrotic NSIP appears to be more difficult to distinguish from UIP than cellular NSIP.

The above studies suggest that it is possible to confidently identify UIP when substantial honeycombing is present, but a substantial minority of patients with UIP have CT findings similar to those of NSIP, and can be distinguished only by biopsy. Jeong and coworkers found that patients who have UIP without honeycombing on CT have a mortality rate similar to those with NSIP, and significantly lower than those with UIP and honeycombing (26). Although Flaherty and coworkers reached similar conclusions, they found that the predictive value of honeycombing on CT was less strong than that of the histologic diagnosis of UIP (17). As indicated above, pathologists show substantial variation in differentiating between UIP and NSIP, so the "gold standard" for this diagnosis is not established, and the most accurate assessment requires correlation of CT and biopsy.

Several clinical conditions may be associated with the histologic pattern of UIP, and must therefore be considered in the differential diagnosis of UIP on CT. In addition to IPF, these include collagen vascular disease, chronic hypersensitivity pneumonitis, asbestosis, and familial IPF.

The CT pattern of UIP related to collagen vascular disease (Figure 6) is similar to that found in idiopathic UIP, although the fibrotic pattern may be less coarse (27). In many patients, clues to the diagnosis may be gleaned from ancillary findings such as esophageal dilation, pulmonary arterial enlargement, or pleural or pericardial thickening or fluid.


Figure 6
View larger version (123K):
[in this window]
[in a new window]
  		Figure 6. UIP pattern in a 48-yr-old woman with scleroderma. CT through the lower lungs shows extensive, subpleural predominant honeycombing with some associated fine reticular pattern and architectural distortion. These findings are undistinguishable from idiopathic pulmonary fibrosis (IPF). Note the mild esophageal dilation.

 
The distinction of IPF from chronic hypersensitivity pneumonitis is important because the management of these disorders is different. CT features that should lead to suspicion of chronic hypersensitivity pneumonitis (Figure 7) include predominance of disease in the upper or middle zones of the lung, widespread ground-glass attenuation, and the presence of poorly defined micronodules or areas of mosaic attenuation or air trapping. Patients with hypersensitivity pneumonitis are less likely than those with UIP to show honeycombing (28). However, if honeycombing is present, it is associated with an adverse prognosis.


Figure 7
Figure 7
View larger version (225K):
[in this window]
[in a new window]
  		Figure 7. UIP pattern in a 75-yr-old woman with chronic hypersensitivity pneumonitis. (A) CT image through the upper lungs shows reticular abnormality in the upper lobes, with a few poorly defined micronodules associated with traction bronchiectasis and architectural distortion. (B) CT through the lower lobes shows subpleural reticular abnormality with focal honeycombing. Although the subpleural honeycombing is compatible with UIP, the upper lobe predominance and micronodules are inconsistent with IPF, and suggest chronic hypersensitivity pneumonitis.

 
Patients with asbestosis may also present with a histologic and CT pattern of UIP, but the presence of pleural disease usually provides a clue to this diagnosis (Figure 8). When the CT scans of patients with asbestosis are compared with those of patients with IPF, patients with asbestosis have a higher prevalence of parenchymal bands, centrilobular nodules, and subpleural curvilinear lines, whereas the prevalence of traction bronchiolectasis and honeycombing is lower (29, 30). Copley and coworkers have shown that asbestosis presents a coarser pattern of fibrosis on CT than that found in UIP or NSIP (31).


Figure 8
View larger version (142K):
[in this window]
[in a new window]
  		Figure 8. UIP pattern related to asbestosis in a 77-yr-old man. CT through the lower lungs shows multiple calcified and noncalcified pleural plaques, and subpleural reticular abnormality and honeycombing. The parenchymal fibrotic bands (arrows) and subpleural curvilinear lines (arrowhead) are common in asbestosis but uncommon in IPF.

 
About 5% of cases of lung fibrosis have a family history of fibrosis in a family member (32). The histologic appearance of familial lung fibrosis varies, but most cases show either UIP or NSIP pattern (33). The CT spectrum is correspondingly varied. Although some cases of familial UIP look identical to sporadic UIP, a lack of basal predominance may be a clue to a familial etiology (Figure 9).


Figure 9
Figure 9
View larger version (262K):
[in this window]
[in a new window]
  		Figure 9. (A and B) Familial lung fibrosis in a 63-yr-old man. Reticular abnormality and ground-glass attenuation, with subpleural irregularity and traction bronchiectasis, are diffusely present on CT. Although these findings could be due to NSIP or UIP, the diffuse distribution, lack of subpleural predominance, and fine irregular reticular pattern are atypical, and raise the possibility of familial fibrosis.

 
ACCURACY OF HRCT IN DIAGNOSIS OF UIP

Multiple studies have documented that the accuracy of a confident diagnosis of UIP, made on CT by an experienced observer, exceeds 90%. However, between one-third and one-half of patients with histologic UIP will fail to receive a confident CT diagnosis of UIP, and will therefore require biopsy (34, 35). Hunninghake and coworkers (4), in a prospective CT evaluation of 91 patients (54 cases with UIP, 37 cases without UIP), concluded that lower lung honeycombing and upper lung irregular lines were the only independent predictors and, using only these two factors, a diagnosis of UIP could be established with a sensitivity of 74%, a specificity of 81%, and a positive predictive value of 85%. Although upper lobe irregular lines were an independent predictive feature of UIP in this article, this finding has not been reproduced in other studies, and was most likely an artifact resulting from the types of cases that ended up in the non-IPF group in that study, which included a large number of cases of respiratory bronchiolitis and hypersensitivity pneumonitis, and relatively few cases of NSIP. Other studies have consistently found that honeycombing is the best discriminator between UIP and other conditions, particularly chronic hypersensitivity pneumonitis and NSIP (22, 28). In a study of 168 patients with IIP, Flaherty and coworkers showed that the presence of honeycombing on HRCT indicated the presence of histologic UIP with a sensitivity of 90% and a specificity of 86% (36). Table 1 shows the relative prevalence of CT features in fibrotic lung conditions, and Table 2 indicates the relative diagnostic importance of these features.


View this table:
[in this window]
[in a new window]
  		TABLE 1. PREVALENCE OF IMAGING FEATURES IN FIBROTIC LUNG DISEASES

 

View this table:
[in this window]
[in a new window]
  		TABLE 2. FEATURES HELPFUL IN MAKING CONFIDENT COMPUTED TOMOGRAPHY DIAGNOSIS OF FIBROTIC LUNG DISEASES

 
TEMPORAL COURSE OF IPF ON CT

Several studies have evaluated sequential changes in IPF (3, 37, 38). Comparison of serial scans in patients with IPF is dependent on identifying comparable scan levels, by matching anatomic features such as vessels and bronchi. In untreated patients scanned at intervals of greater than 6 mo, the extent of IPF usually increases progressively (Figure 10). In patients who are treated, some areas of ground-glass attenuation progress to reticular abnormality and honeycombing, but some areas regress. Reticular abnormality usually progresses to honeycombing (38). Areas of honeycombing increase inexorably in extent, and the size of the honeycomb cysts also increases (3). The appropriate interval for detecting change in patients with IPF would appear to be about 1 yr, although some patients may show clear evidence of change in 3 to 4 mo. Of course, sequential scanning is indicated only if it will change management.


Figure 10
Figure 10
View larger version (274K):
[in this window]
[in a new window]
  		Figure 10. (A and B) Serial CT studies in a 72-yr-old woman with UIP. On the initial CT scan (A), subpleural predominant honeycombing and reticular abnormality are characteristic of UIP. (B) Follow-up study performed 10 mo later shows an increase in the extent of honeycombing, reticular abnormality, and ground-glass attenuation. Areas of ground-glass attenuation have evolved into reticular abnormality, reticular abnormality has become coarser, and the honeycomb cysts have enlarged.

 
As discussed above, it is clear that the presence of honeycombing on CT is an important prognostic determinant in patients with IPF. For patients with a histologic diagnosis of UIP who have honeycombing on CT, the relative risk of death is 3.72, compared with those without honeycombing (median survival, 2.08 and 5.76 yr, respectively) (39). In addition, the extent of reticular abnormality and honeycombing on HRCT is an important independent predictor of mortality (40).

Although the clinical course of IPF is generally characterized by slow progression, acute exacerbations may occur. The incidence of acute exacerbation is unknown. Acute deterioration is usually associated with multifocal, diffuse, and peripheral ground-glass opacities and consolidation superimposed on underlying reticular opacities or honeycombing (Figure 11). The presence of honeycombing in these patients serves to distinguish acute exacerbation of IPF from acute interstitial pneumonia. Differential diagnosis of these findings should always include infection.


Figure 11
Figure 11
View larger version (310K):
[in this window]
[in a new window]
  		Figure 11. (A and B) Acute exacerbation of IPF, in a 57-yr-old man with recent myocardial infarction. CT images through (A) mid-lungs and (B) lower lungs show widespread ground-glass abnormality superimposed on background changes of IPF. Differential diagnosis would include infection, particularly with Pneumocystis. Edema is unlikely because of the absence of venous engorgement or fissural thickening.

 
Most, although not all, studies have shown that IPF is associated with an increased risk of lung cancer (Figure 3) (41–43). CT descriptions of lung cancer associated with IPF have varied (44–46). However, many of these lung cancers appear as well-defined lobulated lesions within or adjacent to areas of lung fibrosis (46). In a study by Kishi and coworkers, 5 of 30 such lung cancers were not visible on chest radiograph (46). Evaluation of CT scans in patients with IPF should include careful scrutiny for potentially malignant nodules.

CONCLUSIONS

The most important role of CT in patients with IIP is to identify patients with a typical UIP pattern, who do not need surgical biopsy if the clinical features are typical of IPF. The radiologic UIP pattern may also be seen in patients with collagen vascular disease, drug toxicity, chronic hypersensitivity pneumonitis, asbestosis, familial idiopathic pulmonary fibrosis, and Hermansky-Pudlak syndrome. A UIP pattern can be identified with confidence on HRCT when honeycombing, traction bronchiectasis, bronchiolectasis, and lower lobe volume loss are prominent. UIP is unlikely when HRCT shows ground-glass attenuation, decreased attenuation, mosaic attenuation, and centrilobular nodules, or when there is upper lobe predominance of abnormality. A confident CT diagnosis of UIP can be made in 50 to 75% of cases of histologically proven UIP, and is associated with a poorer prognosis. In all cases, the CT features must be interpreted in conjunction with a complete clinical evaluation.

FOOTNOTES

Conflict of Interest Statement: S.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.A.L. has been a consultant to Intermune, Inc., Encysive, Inc., and Actelion, Inc. regarding the use of HRCT in multicenter studies of lung fibrosis.

(Received in original form February 14, 2006; accepted in final form March 6, 2006)

REFERENCES

  1. American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165:277–304.[Free Full Text]
  2. Collins CD, Wells AU, Hansell DM, Morgan RA, MacSweeney JE, du Bois RM, Rubens MB. Observer variation in pattern type and extent of disease in fibrosing alveolitis on thin section computed tomography and chest radiography. Clin Radiol 1994;49:236–240.[CrossRef][Medline]
  3. Akira M, Sakatani M, Ueda E. Idiopathic pulmonary fibrosis: progression of honeycombing at thin-section CT. Radiology 1993;189:687–691.[Abstract/Free Full Text]
  4. Hunninghake GW, Lynch DA, Galvin JR, Gross BH, Müller N, Schwartz DA, King TE Jr, Lynch JP III, Hegele R, Waldron J, et al. Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia. Chest 2003;124:1215–1223.[Abstract/Free Full Text]
  5. Nishimura K, Kitaichi M, Izumi T, Nagai S, Kanaoka M, Itoh H. Usual interstitial pneumonia: histologic correlation with high-resolution CT. Radiology 1992;182:337–342.[Abstract/Free Full Text]
  6. Remy-Jardin M, Giraud F, Remy J, Copin MC, Gosselin B, Duhamel A. Importance of ground-glass attenuation in chronic diffuse infiltrative lung disease: pathologic–CT correlation. Radiology 1993;189:693–698.[Abstract/Free Full Text]
  7. Hartley PG, Galvin JR, Hunninghake GW, Merchant JA, Yagla SJ, Speakman SB, Schwartz DA. High-resolution CT-derived measures of lung density are valid indexes of interstitial lung disease. J Appl Physiol 1994;76:271–277.[Abstract/Free Full Text]
  8. Best AC, Lynch AM, Bozic CM, Miller D, Grunwald GK, Lynch DA. Quantitative CT indexes in idiopathic pulmonary fibrosis: relationship with physiologic impairment. Radiology 2003;228:407–414.[Abstract/Free Full Text]
  9. Rodriguez LH, Vargas PF, Raff U, Lynch DA, Rojas GM, Moxley DM, Newell JD. Automated discrimination and quantification of idiopathic pulmonary fibrosis from normal lung parenchyma using generalized fractal dimensions in high-resolution computed tomography images. Acad Radiol 1995;2:10–18.[CrossRef][Medline]
  10. Uppaluri R, Hoffman EA, Sonka M, Hunninghake GW, McLennan G. Interstitial lung disease: a quantitative study using the adaptive multiple feature method. Am J Respir Crit Care Med 1999;159:519–525.[Abstract/Free Full Text]
  11. Lyburn ID, Lowe JE, Wong WL. Idiopathic pulmonary fibrosis on F-18 FDG positron emission tomography. Clin Nucl Med 2005;30:27.[Medline]
  12. Meissner HH, Soo Hoo GW, Khonsary SA, Mandelkern M, Brown CV, Santiago SM. Idiopathic pulmonary fibrosis: evaluation with positron emission tomography. Respiration 2006;73:197–202.[Medline]
  13. Hartman TE, Primack SL, Swensen SJ, Hansell D, McGuinness G, Muller NL. Desquamative interstitial pneumonia: thin-section CT findings in 22 patients. Radiology 1993;187:787–790.[Abstract/Free Full Text]
  14. Akira M, Yamamoto S, Hara H, Sakatani M, Ueda E. Serial computed tomographic evaluation in desquamative interstitial pneumonia. Thorax 1997;52:333–337.[Abstract]
  15. Koyama M, Johkoh T, Honda O, Tsubamoto M, Kozuka T, Tomiyama N, Hamada S, Nakamura H, Akira M, Ichikado K, et al. Chronic cystic lung disease: diagnostic accuracy of high-resolution CT in 92 patients. AJR Am J Roentgenol 2003;180:827–835.[Abstract/Free Full Text]
  16. Flaherty KR, Travis WD, Colby TV, Toews GB, Kazerooni EA, Gross BH, Jain A, Strawderman RL, Flint A, Lynch JP, et al. Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001;164:1722–1727.[Abstract/Free Full Text]
  17. Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch JP III, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;168:543–548.[Abstract/Free Full Text]
  18. Hartman TE, Swensen SJ, Hansell DM, Colby TV, Myers JL, Tazelaar HD, Nicholson AG, Wells AU, Ryu JH, Midthun DE, et al. Nonspecific interstitial pneumonia: variable appearance at high-resolution chest CT. Radiology 2000;217:701–705.[Abstract/Free Full Text]
  19. Johkoh T, Muller NL, Colby TV, Ichikado K, Taniguchi H, Kondoh Y, Fujimoto K, Kinoshita M, Arakawa H, Yamada H, et al. Nonspecific interstitial pneumonia: correlation between thin-section CT findings and pathologic subgroups in 55 patients. Radiology 2002;225:199–204.[Abstract/Free Full Text]
  20. Kim TS, Lee KS, Chung MP, Han J, Park JS, Hwang JH, Kwon OJ, Rhee CH. Nonspecific interstitial pneumonia with fibrosis: high resolution CT and pathologic findings. AJR Am J Roentgenol 1998;171:1645–1650.[Abstract/Free Full Text]
  21. MacDonald SL, Rubens MB, Hansell DM, Copley SJ, Desai SR, du Bois RM, Nicholson AG, Colby TV, Wells AU. Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparative appearances and diagnostic accuracy of high-resolution computed tomography. Radiology 2001;221:600–605.[Abstract/Free Full Text]
  22. Elliot TL, Lynch DA, Newell JD Jr, Cool C, Tuder R, Markopoulou K, Veve R, Brown KK. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr 2005;29:339–345.[CrossRef][Medline]
  23. Tsubamoto M, Muller NL, Johkoh T, Ichikado K, Taniguchi H, Kondoh Y, Fujimoto K, Arakawa H, Koyama M, Kozuka T, et al. Pathologic subgroups of nonspecific interstitial pneumonia: differential diagnosis from other idiopathic interstitial pneumonias on high-resolution computed tomography. J Comput Assist Tomogr 2005;29:793–800.[CrossRef][Medline]
  24. Bna C, Zompatori M, Poletti V, Spaggiari E, Chetta A, Calabro E, Ormitti F, Berti E, Cancellieri A, Chilosi M. Differential diagnosis between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) assessed by high-resolution computed tomography (HRCT). Radiol Med (Torino) 2005;109:472–487.
  25. Nicholson AG, Colby TV, du Bois RM, Hansell DM, Wells AU. The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 2000;162:2213–2217.[Abstract/Free Full Text]
  26. Jeong YJ, Lee KS, Muller NL, Chung MP, Chung MJ, Han J, Colby TV, Kim S. Usual interstitial pneumonia and non-specific interstitial pneumonia: serial thin-section CT findings correlated with pulmonary function. Korean J Radiol 2005;6:143–152.[Medline]
  27. Desai SR, Veeraraghavan S, Hansell DM, Nikolakopolou A, Goh NS, Nicholson AG, Colby TV, Denton CP, Black CM, du Bois RM, et al. CT features of lung disease in patients with systemic sclerosis: comparison with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Radiology 2004;232:560–567.[Abstract/Free Full Text]
  28. Lynch D, Newell J, Logan P, King T, Muller N. Can CT distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis? AJR Am J Roentgenol 1995;165:807–811.[Abstract/Free Full Text]
  29. al Jarad N, Strickland B, Pearson MC, Rubens MB, Rudd RM. High resolution computed tomographic assessment of asbestosis and cryptogenic fibrosing alveolitis: a comparative study. Thorax 1992;47:645–650.[Abstract/Free Full Text]
  30. Akira M, Yamamoto S, Inoue Y, Sakatani M. High-resolution CT of asbestosis and idiopathic pulmonary fibrosis. AJR Am J Roentgenol 2003;181:163–169.[Abstract/Free Full Text]
  31. Copley SJ, Wells AU, Sivakumaran P, Rubens MB, Lee YC, Desai SR, MacDonald SL, Thompson RI, Colby TV, Nicholson AG, et al. Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT features. Radiology 2003;229:731–736.[Abstract/Free Full Text]
  32. Hodgson U, Laitinen T, Tukiainen P. Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland. Thorax 2002;57:338–342.[Abstract/Free Full Text]
  33. Marshall RP, Puddicombe A, Cookson WO, Laurent GJ. Adult familial cryptogenic fibrosing alveolitis in the United Kingdom. Thorax 2000;55:143–146.[Abstract/Free Full Text]
  34. Hunninghake GW, Zimmerman MB, Schwartz DA, King TE Jr, Lynch J, Hegele R, Waldron J, Colby T, Muller N, Lynch D, et al. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001;164:193–196.[Abstract/Free Full Text]
  35. Swensen S, Aughenbaugh G, Myers J. Diffuse lung disease: diagnostic accuracy of CT in patients undergoing surgical biopsy of the lung. Radiology 1997;205:229–234.[Abstract/Free Full Text]
  36. Flaherty KR, Toews GB, Travis WD, Colby TV, Kazerooni EA, Gross BH, Jain A, Strawderman RL III, Paine R, Flint A, et al. Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J 2002;19:275–283.[Abstract/Free Full Text]
  37. Wells AU, Rubens MB, du Bois RM, Hansell DM. Serial CT in fibrosing alveolitis: prognostic significance of the initial pattern. AJR Am J Roentgenol 1993;161:1159–1165.[Abstract/Free Full Text]
  38. Terriff B, Kwan S, Chan-Yeung M, Muller N. Fibrosing alveolitis: chest radiography and CT as predictors of clinical and functional impairment at followup in 26 patients. Radiology 1992;184:445–449.[Abstract/Free Full Text]
  39. Flaherty KR, Thwaite EL, Kazerooni EA, Gross BH, Toews GB, Colby TV, Travis WD, Mumford JA, Murray S, Flint A, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax 2003;58:143–148.[Abstract/Free Full Text]
  40. Lynch DA, David Godwin J, Safrin S, Starko KM, Hormel P, Brown KK, Raghu G, King TE Jr, Bradford WZ, Schwartz DA, et al.; Idiopathic Pulmonary Fibrosis Study Group. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med 2005;172:488–493.[Abstract/Free Full Text]
  41. Ma Y, Seneviratne CK, Koss M. Idiopathic pulmonary fibrosis and malignancy. Curr Opin Pulm Med 2001;7:278–282.[CrossRef][Medline]
  42. Samet JM. Does idiopathic pulmonary fibrosis increase lung cancer risk? Am J Respir Crit Care Med 2000;161:1–2.[Free Full Text]
  43. Daniels CE, Jett JR. Does interstitial lung disease predispose to lung cancer? Curr Opin Pulm Med 2005;11:431–437.[CrossRef][Medline]
  44. Park J, Kim DS, Shim TS, Lim CM, Koh Y, Lee SD, Kim WS, Kim WD, Lee JS, Song KS. Lung cancer in patients with idiopathic pulmonary fibrosis. Eur Respir J 2001;17:1216–1219.[Abstract/Free Full Text]
  45. Lee HJ, Im JG, Ahn JM, Yeon KM. Lung cancer in patients with idiopathic pulmonary fibrosis: CT findings. J Comput Assist Tomogr 1996;20:979–982.[CrossRef][Medline]
  46. Kishi K, Homma S, Kurosaki A, Motoi N, Yoshimura K. High-resolution computed tomography findings of lung cancer associated with idiopathic pulmonary fibrosis. J Comput Assist Tomogr 2006;30:95–99.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Eur Respir JHome page
L. Thiberville, M. Salaun, S. Lachkar, S. Dominique, S. Moreno-Swirc, C. Vever-Bizet, and G. Bourg-Heckly
Human in vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy
Eur. Respir. J., May 1, 2009; 33(5): 974 - 985.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
M. Akira, Y. Inoue, M. Kitaichi, S. Yamamoto, T. Arai, and K. Toyokawa
Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia with and without Concurrent Emphysema: Thin-Section CT Findings
Radiology, April 1, 2009; 251(1): 271 - 279.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
D. M. Hansell, A. A. Bankier, H. MacMahon, T. C. McLoud, N. L. Muller, and J. Remy
Fleischner Society: Glossary of Terms for Thoracic Imaging
Radiology, March 1, 2008; 246(3): 697 - 722.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
D. S. Kim, H. R. Collard, and T. E. King Jr.
Classification and natural history of the idiopathic interstitial pneumonias.
Proceedings of the ATS, January 1, 2006; 3(4): 285 - 292.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Misumi, S.
Right arrow Articles by Lynch, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Misumi, S.
Right arrow Articles by Lynch, D. A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS