Published online before print February 12, 2008, 10.1148/radiol.2471070369
(Radiology 2008;247:251-259.)
© RSNA, 2008
Nonspecific Interstitial Pneumonia and Idiopathic Pulmonary Fibrosis: Changes in Pattern and Distribution of Disease over Time1
C. Isabela S. Silva, MD, PhD,
Nestor L. Müller, MD, PhD,
David M. Hansell, MD,
Kyung S. Lee, MD,
Andrew G. Nicholson, MD, and
Athol U. Wells, MD
1 From the Department of Radiology, Vancouver General Hospital, University of British Columbia, 3350-950 W 10th Ave, Vancouver, BC, Canada V5Z 4E3 (C.I.S.S., N.L.M.); Department of Radiology (D.M.H.), Department of Pathology (A.G.N.), and Interstitial Lung Disease Unit (A.U.W.), Royal Brompton Hospital, London, England; and Department of Radiology and the Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (K.S.L.). Received February 22, 2007; revision requested May 8; revision received June 12; accepted July 18; final version accepted September 11.
Address correspondence to C.I.S.S. (e-mail: isabela.silva{at}vch.ca).
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ABSTRACT
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Purpose: To retrospectively assess the change in disease pattern of nonspecific interstitial pneumonia (NSIP) and idiopathic pulmonary fibrosis (IPF) findings seen at thin-section computed tomography (CT) at long-term follow-up and to compare the same with initial findings at CT.
Materials and Methods: The study included 48 patients (28 men, 20 women; mean age, 57.5 years) with biopsy-proved NSIP (n = 23) or IPF (n = 25) who underwent CT at initial diagnosis and at follow-up 34–155 months later. The CT scans were randomized and reviewed by two independent thoracic radiologists for pattern and distribution of ground-glass opacity (GGO), reticulation, traction bronchiectasis and bronchiolectasis, and honeycombing. Statistical analysis was performed by using nonparametric methods and univariate logistic regression.
Results: Follow-up CT in patients with NSIP showed marked decrease in the extent of GGO, increase in reticulation, and a greater likelihood of peripheral distribution (all P < .05). At presentation, the CT findings were interpreted as suggestive of NSIP in 18 of 23 patients with NSIP and indeterminate or suggestive of IPF in five. In five (28%) of 18 patients with initial findings suggestive of NSIP, the follow-up CT scans were interpreted as more suggestive of IPF. No CT features seen at presentation allowed distinction between patients with NSIP that maintained an NSIP pattern at follow-up and those that progressed to an IPF pattern.
Conclusion: At follow-up CT, 28% of patients with initial CT findings suggestive of NSIP progressed to findings suggestive of IPF. Similar initial CT findings for NSIP may have different imaging outcomes.
© RSNA, 2008
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INTRODUCTION
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The idiopathic interstitial pneumonias are a group of interstitial lung diseases characterized by varying patterns of inflammation and fibrosis (1). The two most common forms are idiopathic pulmonary fibrosis (IPF), characterized by a histologic pattern of usual interstitial pneumonia (UIP), accounting for up to 65% of patients, and nonspecific interstitial pneumonia (NSIP), which accounts for 4%–36% of patients (2). On average, the outcome is substantially better in NSIP than in IPF (2). However, the 5- and 10-year mortality in fibrotic NSIP has been substantial in some series (3,4). It appears that a sizeable minority of NSIP patients follow an IPF-like disease course, with progression despite treatment and a similar mortality to that seen in IPF patients (5). It has been suggested that in some patients, NSIP may represent an early stage of UIP or, alternatively, that an NSIP pattern seen at biopsy may simply be indicative of relatively inactive UIP (2,6). However, Katzenstein et al (7) compared lung biopsy and subsequent explant tissues in 20 patients with idiopathic interstitial pneumonias and found no explant showing UIP that was preceded by biopsy findings of NSIP.
The important role of thin-section computed tomography (CT) in the evaluation of idiopathic interstitial pneumonias is well known (1,8). The characteristic CT features of IPF consist of a reticular pattern, traction bronchiectasis, and honeycombing that involves mainly the peripheral lung regions and the lung bases (8). In approximately one-half of patients with IPF, a confident diagnosis can be made on the basis of clinical and thin-section CT findings, precluding the need to obtain a surgical biopsy (9). However, in the remaining 50% of patients the thin-section CT findings may mimic those of other interstitial lung diseases, particularly NSIP. The most common thin-section CT manifestation of NSIP consists of symmetric bilateral areas of ground-glass opacity (GGO) with superimposed fine reticular opacities, often with traction bronchiectasis and bronchiolectasis but with no or only mild honeycombing (10–14). Therefore, the findings of NSIP, particularly fibrotic NSIP, may resemble those of IPF (10,11,14).
Distinction between IPF and NSIP is important because NSIP has a considerably better prognosis than IPF (1). To our knowledge, there is limited information regarding the change in pattern and distribution of thin-section CT findings of NSIP at long term follow-up (15–19). Given the presence of a subgroup of NSIP patients with inexorably progressive disease (5), we hypothesized that at least some patients with histologic diagnoses of NSIP at surgical biopsy may progress from an NSIP pattern to a UIP pattern at follow-up CT. Thus, the purpose of our study was to retrospectively assess the change in disease pattern of NSIP and IPF findings seen at thin-section CT at long-term follow-up and to compare the same with initial findings at CT.
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MATERIALS AND METHODS
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Patients
Approval for this study was obtained from the institutional clinical research ethics board of the three hospitals participating in the study. Informed consent was waived.
Patient selection was made by a review of the medical records of all patients who had received a histologic diagnosis of NSIP or UIP on the basis of surgical lung biopsy at one of three large teaching hospitals between 1993 and 2005. Only those patients with a final clinical diagnosis of idiopathic UIP (IPF) and idiopathic NSIP, who underwent thin-section CT at the time of initial diagnosis and underwent follow-up CT a minimum of 3 years later, were included. Patients with coexistent pneumonia and cardiac failure at the initial or follow-up studies were excluded. The patient group (n = 48) consisted of 23 patients with NSIP and 25 patients with IPF (28 men, 20 women; age range, 32–78 years; mean, 57.5 years ± 9.3 [standard deviation]). The proportions of male to female patients were statistically different in NSIP and IPF; there was a larger proportion of men in IPF (20 of 25, 80%) than in NSIP (eight of 23, 35%) (P 
.005, 
2 analysis). There was no significant (P 
.10, Student t test) difference in age between the NSIP and IPF groups (mean, 55.7 years ± 10.5 and 59.1 years ± 8.1, respectively).
The interval between the initial and follow-up CT scans ranged from 34–155 months (median, 61 months) in the NSIP patients and 34–131 months (median 66 months) in the IPF patients. All patients underwent treatment with corticosteroids, with or without immunosuppressive agents, between the initial and follow-up CT scans. The dose and duration of treatment was determined by the clinical conditions and varied between the three institutions participating in the study.
Histologic Diagnosis
In all patients, the histologic diagnoses of UIP and NSIP were made by consensus agreement between at least two pathologists (6–21 years experience in lung pathology) by using the combined American Thoracic Society and European Respiratory Society Consensus Classification criteria (1). The histologic diagnosis of UIP was made given the presence of temporal heterogeneity with nonuniform and variable interstitial changes, including intermingled zones of established interstitial fibrosis, inflammation, fibroblastic foci, honeycomb change, and normal lung coexisting in variable proportions (1). The diagnosis of NSIP was made on the basis of the presence of temporally uniform interstitial inflammation and/or fibrosis, with subdivision into cellular (n = 4), mixed (n = 10), and fibrotic (n = 9) types according to current diagnostic criteria (1).
CT Scanning Protocol
Several CT scanners were used for this study: Two scanners were from one manufacturer (HiSpeed Advantage and LightSpeed 16; GE Healthcare, Milwaukee, Wis), three multidetector scanners were from another manufacturer (Somatom [Volume Zoom] 4-section and Sensation 16- and 64-section; Siemens Medical Solutions, Erlangen, Germany), and one electron beam scanner was from a third manufacturer (C-150L; Imatron, San Francisco, Calif). The images were obtained by using 1- or 2-mm collimation at 10-mm intervals or volumetrically on multidetector CT scanners with 0.6- or 1-mm collimation and 1-mm reconstruction. The scans were obtained with the patient in supine position at full inspiration and were reconstructed by using a high-spatial-frequency algorithm. All images were viewed at window settings optimized for assessment of lung parenchyma (width, 1000–1500 HU; level, –600 to –700 HU). Hardcopy images were available for 19 patients. In the remaining 29 patients, the images were reviewed on a dedicated picture archiving and communication system workstation (CS 5000, AGFA; Mortsel, Belgium).
Image Evaluation
The thin-section CT scans (initial and follow-up) were randomized and reviewed by two independent fellowship-trained thoracic radiologists (N.L.M. and C.I.S.S., with 22 and 4 years experience, respectively) without knowledge of clinical information or histologic diagnosis. The readers were aware that only patients with NSIP and IPF were included in the study, but did not know the diagnosis or whether it was the initial or follow-up CT. The CT findings were interpreted on the basis of the recommendations of the nomenclature committee of the Fleischner Society (20).
Simple dichotomous presence variables were assessed at CT. GGO was defined as an area of hazy increased attenuation without obscuration of underlying vascular markings. Intralobular reticular opacity was considered to be present when interlacing line shadows were seen in secondary pulmonary lobules. Traction bronchiectasis and bronchiolectasis were defined as irregular bronchial and bronchiolar dilatation in areas with parenchymal abnormality. Honeycombing was considered to be present when clustered cystic air spaces with well-defined and thick walls were seen.
The anatomic distribution was classified as peribronchovascular (a predominance of abnormalities along the bronchi and vessels), peripheral (a predominance of abnormalities in the outer one-third of the lung or along the interlobar fissures), or random (no peribronchovascular or peripheral predominance). Zonal predominance of abnormalities was assessed as being upper, lower, or random. Upper lung zone predominance was considered present when disease extent was greatest above the level of the tracheal carina; lower zone predominance was considered present when disease extent was greatest below this level. Relative sparing of the lung immediately adjacent to the pleura in the dorsal regions of the lower lobes (relative subpleural sparing), presence of fibrosis in upper lobes, and basal and peripheral predominance of fibrosis were also assessed. Subpleural refers to the region immediately adjacent to the costal pleura (ie, located 1 cm from the pleura), whereas peripheral refers to the outer one-third of the lung.
Observations made by using semiquantitative scores include the extents of GGO, consolidation, reticulation, and honeycombing, each scored as grade 0, absent; grade 1, involving 1%–4% of the lung parenchyma; grade 2, involving 5%–25% of the lung parenchyma; grade 3, involving 26%–50% of the lung parenchyma; or grade 4, involving more than 50% of the lung parenchyma. Honeycombing cysts were categorized as grade 0, absent; grade 1, 1–5 mm; or grade 2, larger than 5 mm.
The size of honeycomb cysts was determined given the largest visualized cyst. The predominant CT pattern, which was classified as grade 0, predominantly inflammatory (if the extent of ground-glass attenuation and/or consolidation was greater than the extent of reticulation and/or honeycombing); grade 1; equivalent fibrotic and inflammatory; or grade 2, predominantly fibrotic (if the extent of reticulation and/or honeycombing was greater than the extent of ground-glass attenuation and/or consolidation). The observations of the two radiologists were summed for the purposes of analysis; a nine-point scale (score of 0–8) was used for extents of GGO, consolidation, reticulation, and honeycombing and a five-point scale (score of 0–4) was used for the size of honeycomb cysts and the predominance of the reticular pattern.
Following the initial assessment of the thin-section CT images, each radiologist made a first-choice diagnosis of NSIP or IPF for each patient and graded the degree of confidence in this diagnosis as being definite (high) or probable (low), according to specific diagnostic criteria (Table 1). When the CT findings did not match any of the criteria, the first-choice diagnosis was considered as indeterminate. Disagreements on presence variables and on the likely thin-section CT diagnosis were resolved by consensus review of divergent scores.
Statistical Analysis
Results are given as means and standard deviations or medians and ranges (for nonnormally distributed variables). Interobserver variation in CT findings was quantified by using the unweighted kappa coefficient (
) of agreement for presence variables and the weighted kappa coefficient (w) of agreement (quadratic weighting) for variables scored by using semiquantitative scales. The interobserver agreement was classified as follows: poor, = 0–0.20; fair, = 0.21–0.40; moderate, = 0.41–0.60; good, = 0.61–0.80; and excellent, = 0.81–1.00 (21).
Comparisons between baseline and follow-up thin-section CT findings positive for NSIP and IPF were made by using 2 statistics or a two-tailed Fisher exact test (when the smallest of the four expected numbers was less than five). Interrelationships between CT variables were examined by using the Spearman rank correlation coefficient (
). The Wilcoxon rank sum test was used for unpaired group comparisons of semiquantitative scales and the Wilcoxon signed rank test for paired comparisons of data. The predictive value of baseline CT features in NSIP patients against evolution to an IPF-like appearance were assessed by means of univariate logistic regression. A P value of less than .05 was considered to indicate a significant difference.
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RESULTS
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Thin-Section CT Findings
There was moderate to excellent interobserver agreement in the interpretation of simple dichotomous presence variables ( = 0.56–1.00) and good to excellent agreement for continuous semicategorical variables (w = 0.73–1.00). There was excellent interobserver agreement (w = 0.90) on the likely CT diagnosis of NSIP or IPF. Given the lack of major disagreement between the two radiologists, analyses of the extents of individual patterns were made by using summed scores.
Comparison between NSIP and IPF Findings at Initial CT
NSIP patients were characterized by a lower prevalence of honeycombing (five of 23, 22%) (P = .01) and peripheral predominance of fibrosis (16 of 23, 70%) (P = .01), higher prevalence of relative subpleural sparing (10 of 23, 43%) (P < .005), and a random distribution of disease (13 of 23, 57%) (P < .005) as compared with IPF patients (14 of 25, 56%; 24 of 25, 96%; two of 25, 8%; and three of 25, 12%, respectively) (Figs 1, 2; Table 2). NSIP was also characterized by greater extent of GGO (P = .002), lower extent of honeycombing (P = .02), smaller size of honeycomb cysts (P = .01), and a lower percentage of patients with predominant reticular pattern (P = .01) (Table 3). Variables that were almost invariably positive (presence of reticulation, presence of GGO, traction bronchiectasis and bronchiolectasis, upper lobe fibrosis, basal predominance of fibrosis, and lower lobe predominance of disease) or negative (presence of consolidation) were not evaluated further.
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Figure 1a: Transverse thin-section lung CT scans of characteristic NSIP findings in 40-year-old woman. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show bilateral GGO and minimal reticulation. Note relative subpleural sparing (arrowheads) immediately adjacent to pleura in dorsal regions of lower lobes and traction bronchiectasis and bronchiolectasis. (c, d) Follow-up scans 45 months later show increase in extent of reticulation and traction bronchiectasis and bronchiolectasis. Minimal subpleural honeycombing has developed (arrows) and relative subpleural sparing is still apparent (arrowheads). All scans were interpreted as being consistent with NSIP.
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Figure 1b: Transverse thin-section lung CT scans of characteristic NSIP findings in 40-year-old woman. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show bilateral GGO and minimal reticulation. Note relative subpleural sparing (arrowheads) immediately adjacent to pleura in dorsal regions of lower lobes and traction bronchiectasis and bronchiolectasis. (c, d) Follow-up scans 45 months later show increase in extent of reticulation and traction bronchiectasis and bronchiolectasis. Minimal subpleural honeycombing has developed (arrows) and relative subpleural sparing is still apparent (arrowheads). All scans were interpreted as being consistent with NSIP.
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Figure 1c: Transverse thin-section lung CT scans of characteristic NSIP findings in 40-year-old woman. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show bilateral GGO and minimal reticulation. Note relative subpleural sparing (arrowheads) immediately adjacent to pleura in dorsal regions of lower lobes and traction bronchiectasis and bronchiolectasis. (c, d) Follow-up scans 45 months later show increase in extent of reticulation and traction bronchiectasis and bronchiolectasis. Minimal subpleural honeycombing has developed (arrows) and relative subpleural sparing is still apparent (arrowheads). All scans were interpreted as being consistent with NSIP.
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Figure 1d: Transverse thin-section lung CT scans of characteristic NSIP findings in 40-year-old woman. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show bilateral GGO and minimal reticulation. Note relative subpleural sparing (arrowheads) immediately adjacent to pleura in dorsal regions of lower lobes and traction bronchiectasis and bronchiolectasis. (c, d) Follow-up scans 45 months later show increase in extent of reticulation and traction bronchiectasis and bronchiolectasis. Minimal subpleural honeycombing has developed (arrows) and relative subpleural sparing is still apparent (arrowheads). All scans were interpreted as being consistent with NSIP.
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Figure 2a: Transverse thin-section lung CT scans show characteristic UIP findings in 53-year-old woman. Initial scans at levels of (a) right upper lobe bronchus and (b) lower zones show reticular pattern and traction bronchiectasis involving mainly peripheral lung regions and bases. Note mild honeycombing (arrowheads) and minimal GGO. (c, d) Follow-up scans 67 months later show progression of reticulation and honeycombing in predominantly peripheral and basal distribution. All scans were interpreted as being consistent with UIP.
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Figure 2b: Transverse thin-section lung CT scans show characteristic UIP findings in 53-year-old woman. Initial scans at levels of (a) right upper lobe bronchus and (b) lower zones show reticular pattern and traction bronchiectasis involving mainly peripheral lung regions and bases. Note mild honeycombing (arrowheads) and minimal GGO. (c, d) Follow-up scans 67 months later show progression of reticulation and honeycombing in predominantly peripheral and basal distribution. All scans were interpreted as being consistent with UIP.
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Figure 2c: Transverse thin-section lung CT scans show characteristic UIP findings in 53-year-old woman. Initial scans at levels of (a) right upper lobe bronchus and (b) lower zones show reticular pattern and traction bronchiectasis involving mainly peripheral lung regions and bases. Note mild honeycombing (arrowheads) and minimal GGO. (c, d) Follow-up scans 67 months later show progression of reticulation and honeycombing in predominantly peripheral and basal distribution. All scans were interpreted as being consistent with UIP.
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Figure 2d: Transverse thin-section lung CT scans show characteristic UIP findings in 53-year-old woman. Initial scans at levels of (a) right upper lobe bronchus and (b) lower zones show reticular pattern and traction bronchiectasis involving mainly peripheral lung regions and bases. Note mild honeycombing (arrowheads) and minimal GGO. (c, d) Follow-up scans 67 months later show progression of reticulation and honeycombing in predominantly peripheral and basal distribution. All scans were interpreted as being consistent with UIP.
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Interrelationships between Selected Thin-Section CT Patterns at Baseline
In the combined patient population and separately in the IPF and NSIP patient subsets, the extent of reticulation was not linked to either the extent of GGO or of honeycombing. By contrast, there was a strong negative relationship ( = –0.69, P < .001) between the extent of GGO and that of honeycombing, which remained significant in both diseases when analyzed separately (IPF, = –0.71, P < .001; NSIP, = –0.54, P < .01).
Comparison between NSIP and IPF Findings at Follow-up CT
Variables that differed significantly between the two diseases at baseline were compared at follow-up thin-section CT. Group differences that remained significant were the higher prevalence of relative subpleural sparing in NSIP (nine of 23, 39%) than in IPF (0%) (P < .001) patients, the greater prevalence (23 of 25, 92%) (P = .03) and extent (P = .01) of honeycombing in IPF than in NSIP patients, and the larger size of honeycomb cysts in IPF patients (P = .02). The extent of honeycombing increased between the initial and follow-up scans in NSIP (P = .005) and IPF (P < .001) groups (Figs 1, 2). In contrast, baseline differences in the extent of GGO were absent at follow-up, reflecting a marked decrease in the extent of GGO in NSIP between the baseline and follow-up scans (P < .001), as compared with a minor reduction in the extent of GGO in IPF (P = .05) (Fig 3). The prevalence of a random distribution of disease in NSIP was also absent at follow-up; as seen in a subset of NSIP patients, disease was random in distribution at baseline but became more peripheral at follow-up. Similarly, baseline differences in scores for the predominance of a reticular pattern were absent at follow-up.
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Figure 3a: Transverse thin-section lung CT of characteristic NSIP findings at level of inferior pulmonary vein of right lung in 41-year-old man. (a) Initial scan shows extensive GGO and minimal reticulation. Note relative subpleural sparing (arrowheads) and mild traction bronchiectasis. (b) Follow-up scan 67 months later shows decrease in extent of GGO and increase in extent of reticulation. Relative subpleural sparing persists (arrowheads) and traction bronchiectasis is more evident. All scans were interpreted as being consistent with NSIP.
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Figure 3b: Transverse thin-section lung CT of characteristic NSIP findings at level of inferior pulmonary vein of right lung in 41-year-old man. (a) Initial scan shows extensive GGO and minimal reticulation. Note relative subpleural sparing (arrowheads) and mild traction bronchiectasis. (b) Follow-up scan 67 months later shows decrease in extent of GGO and increase in extent of reticulation. Relative subpleural sparing persists (arrowheads) and traction bronchiectasis is more evident. All scans were interpreted as being consistent with NSIP.
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At follow-up, there was no difference between the predominant CT pattern scores for IPF (median, 4; range, 0–4) and NSIP (median, 4; range, 0–4) (P = .67). Across the 48 patients, the grade did not change in 19 (NSIP, n = 8; IPF, n = 11), it became relatively more inflammatory in three (all IPF), but became relatively more fibrotic in 26 (NSIP, n = 15; IPF, n = 11). Change in pattern score differed between NSIP (median, 2; range, 0–4) and IPF (median, 0; range, –2 to 4) (P = .05). On paired testing, the pattern score at follow-up (median, 4; range, 0–4) was strikingly more fibrotic than at initial CT (median, 2; range, 0–4) (P < .001). For NSIP, this trend was strikingly significant (P < .001). For IPF, this trend was weak (P = .03).
Diagnostic Thin-Section CT Features at Baseline and at Follow-up
At presentation, thin-section CT findings seen in IPF patients were interpreted as suggestive of IPF in 11 (44%) of 25 patients (definite IPF, n = 6; probable IPF, n = 5), indeterminate in five (20%) patients, and suggestive of NSIP in nine (36%) patients (definite NSIP, n = 8; probable NSIP, n = 1) by consensus reading by the two thoracic radiologists. Thin-section CT findings seen in NSIP patients were suggestive of NSIP in 18 (78%) of 23 (definite NSIP, n = 16; probable NSIP, n = 2), indeterminate in three (13%), and suggestive of IPF in two (9%) (definite IPF, n = 1; probable IPF, n = 1) patients.
Of 23 NSIP patients, two were interpreted as suggestive of IPF and three as indeterminate at baseline CT; six patients were interpreted as suggestive of IPF and five as indeterminate at follow-up CT. Overall, 18 of these patient findings were interpreted as suggestive of NSIP at baseline CT and 12 at follow-up CT. Five (28%) of 18 patients with initial CT findings suggestive of NSIP developed findings interpreted as suggestive of IPF (Fig 4) and one as indeterminate at follow-up CT. On univariate logistic regression, no individual thin-section CT feature at baseline was found to distinguish between these two subgroups. The patients that progressed from an NSIP pattern to a UIP pattern had mixed (n = 2) or fibrotic (n = 3) NSIP at lung biopsy; none of these patients had cellular NSIP.
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Figure 4a: Transverse thin-section lung CT in 61-year-old man with biopsy-proved NSIP. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show GGO in lower lobe predominance, minimal traction bronchiectasis, and mild reticulation and were interpreted as being characteristic of NSIP. (c, d) Follow-up scans 83 months later show increase in extension of reticulation, worsening of the traction bronchiectasis, and development of honeycombing. Note reduction in extent of GGO. Follow-up scan was interpreted as suggestive of IPF.
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Figure 4b: Transverse thin-section lung CT in 61-year-old man with biopsy-proved NSIP. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show GGO in lower lobe predominance, minimal traction bronchiectasis, and mild reticulation and were interpreted as being characteristic of NSIP. (c, d) Follow-up scans 83 months later show increase in extension of reticulation, worsening of the traction bronchiectasis, and development of honeycombing. Note reduction in extent of GGO. Follow-up scan was interpreted as suggestive of IPF.
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Figure 4c: Transverse thin-section lung CT in 61-year-old man with biopsy-proved NSIP. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show GGO in lower lobe predominance, minimal traction bronchiectasis, and mild reticulation and were interpreted as being characteristic of NSIP. (c, d) Follow-up scans 83 months later show increase in extension of reticulation, worsening of the traction bronchiectasis, and development of honeycombing. Note reduction in extent of GGO. Follow-up scan was interpreted as suggestive of IPF.
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Figure 4d: Transverse thin-section lung CT in 61-year-old man with biopsy-proved NSIP. Initial scans at levels of (a) bronchus intermedius and (b) lower zones show GGO in lower lobe predominance, minimal traction bronchiectasis, and mild reticulation and were interpreted as being characteristic of NSIP. (c, d) Follow-up scans 83 months later show increase in extension of reticulation, worsening of the traction bronchiectasis, and development of honeycombing. Note reduction in extent of GGO. Follow-up scan was interpreted as suggestive of IPF.
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The intervals between scans did not vary significantly with changes in CT findings, either across the whole cohort or in either disease subset (all P > .1).
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DISCUSSION
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To our knowledge, our study is the first to compare the CT findings of NSIP and IPF at long-term follow-up (34–155 months). The most striking finding at follow-up was that the differences between the two diseases do diminish because the findings in a proportion of patients with NSIP come to resemble those of IPF. At follow-up CT, there is a decrease in the extent of GGO, increase in the extent of reticulation and honeycombing in NSIP, development of cysts, and increase in honeycombing and reticulation. Although the extent of reticulation and honeycombing of NSIP remain less severe than those of IPF, both diseases increase fibrotic elements in the same direction, but this has a more radical influence on NSIP scores as these were less IPF-like from the start.
Overall, among patients with NSIP, 18 had initial abnormalities suggestive of NSIP at thin-section CT. At follow-up, the pattern remained as NSIP in 12 of these 18 patients but evolved to an indeterminate pattern in one patient and a pattern resembling IPF in the remaining five. No individual thin-section CT at baseline was found to distinguish between these two subgroups.
The results of our study suggest that there are two separate NSIP subgroups, with one subgroup representing NSIP progressing to a pattern that resembles IPF and one subgroup that maintains the overall features of NSIP even with progression of fibrosis. This observation is concordant with the findings of Latsi et al (5) in a study of serial pulmonary function change against mortality in IPF and idiopathic NSIP. In that study, a minority of NSIP patients exhibited early deterioration despite treatment, and this was predictive of an IPF-like course to a fatal outcome (5). However, in our study there was no appreciable difference in the pattern, extent, or distribution of findings between patients with NSIP that maintained an NSIP pattern at follow-up and those that changed to a pattern resembling IPF.
Our study shows that at initial presentation NSIP is characterized by greater extent of GGO, predominance of ground-glass attenuation rather than reticulation, absent or relatively mild honeycombing, and greater likelihood of random distribution of findings as compared with IPF. These results are similar to those of previous studies (10–12,14). On the basis of anecdotal experience, it was recently suggested that relative subpleural sparing may help distinguish NSIP from IPF (2). This was confirmed in our study, which showed relative sparing of the lung immediately adjacent to the pleura in the dorsal lung regions of the lower lobes in 10 (43%) of 23 patients with NSIP compared with two (8%) of 25 patients with IPF.
Our study had limitations. It was retrospective, included a small number of patients who underwent CT with different scanners, and had a small interval between the initial and follow-up CT examinations. Because lung biopsy is seldom obtained from patients with characteristic thin-section CT findings positive for IPF, the study is biased toward patients with atypical IPF findings. The study did not compare the CT with the clinical or functional findings at diagnosis or follow-up and did not assess the effect of therapy. The study included a small number of patients with NSIP who had follow-up CT. Although five (28%) of 18 patients with initial findings suggestive of NSIP had follow-up CT scans that were more suggestive of IPF, this may not be representative of the entire NSIP population owing to potential bias in patient selection.
Furthermore, although initial thin-section CT findings characteristic of NSIP progressed to a pattern of UIP, this change in pattern does not necessarily reflect a change in histologic pattern of NSIP to UIP. All five patients who progressed from an NSIP to a UIP pattern had mixed or fibrotic NSIP at biopsy; none of the four NSIP patients with a cellular pattern at biopsy progressed to an IPF pattern at CT. Prospective studies in a larger number of patients with close correlation between the CT, clinical, and histologic findings will be required to further assess the possibility that in some patients NSIP may progress to UIP.
In summary, at presentation, NSIP is characterized by the predominance of GGO, lack of honeycombing, presence of relative subpleural sparing, and low prevalence of peripheral distribution of disease, findings which allow distinction from IPF in the majority of patients. At 3 years or longer follow-up, 28% of patients with initial CT findings suggestive of NSIP progress to findings suggestive of IPF. Given the results of our study, there are no CT features seen at presentation that allow distinction between patients with NSIP that maintain an NSIP pattern at follow-up and those that progress to an IPF pattern; in other words, similar initial CT findings positive for NSIP may have different outcomes.
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ADVANCE IN KNOWLEDGE
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- Our study shows that at 3 years or longer follow-up, 28% of patients with initial CT findings suggestive of nonspecific interstitial pneumonia (NSIP) progress to findings suggestive of idiopathic pulmonary fibrosis (IPF).
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IMPLICATION FOR PATIENT CARE
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- The results of this study indicate that there are no CT features at presentation that allow distinction between patients with NSIP that maintain an NSIP pattern from those that progress to an IPF pattern at follow-up.
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FOOTNOTES
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Abbreviations: GGO = ground-glass opacity • IPF = idiopathic pulmonary fibrosis • NSIP = nonspecific interstitial pneumonia • UIP = usual interstitial pneumonia
Author contributions: Guarantors of integrity of entire study, C.I.S.S., N.L.M.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, C.I.S.S., N.L.M., K.S.L., A.U.W.; clinical studies, C.I.S.S., N.L.M., D.M.H., K.S.L., A.G.N.; statistical analysis, C.I.S.S., N.L.M., A.U.W.; and manuscript editing, all authors
Authors stated no financial relationship to disclose.
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References
|
|---|
- 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 2001. Am J Respir Crit Care Med 2002;165(2):277–304. [Published correction appears in Am J Respir Crit Care Med 2002;166(3):426.][Free Full Text]
- Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc 2006;3(4):285–292.[Abstract/Free Full Text]
- 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(6):2213–2217.[Abstract/Free Full Text]
- Travis WD, Matsui K, Moss J, Ferrans VJ. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns. Am J Surg Pathol 2000;24(1):19–33.[CrossRef][Medline]
- Latsi PI, du Bois RM, Nicholson AG, et al. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med 2003;168(5):531–537.[Abstract/Free Full Text]
- Nicholson AG, Wells AU. Nonspecific interstitial pneumonia: nobody said it's perfect. Am J Respir Crit Care Med 2001;164(9):1553–1554.[Free Full Text]
- Katzenstein AL, Zisman DA, Litzky LA, Nguyen BT, Kotloff RM. Usual interstitial pneumonia: histologic study of biopsy and explant specimens. Am J Surg Pathol 2002;26(12):1567–1577.[CrossRef][Medline]
- Lynch DA, Travis WD, Muller NL, et al. Idiopathic interstitial pneumonias: CT features. Radiology 2005;236(1):10–21.[Abstract/Free Full Text]
- Hunninghake GW, Zimmerman MB, Schwartz DA, et al. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001;164(2):193–196.[Abstract/Free Full Text]
- 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(3):600–605.[Abstract/Free Full Text]
- Hartman TE, Swensen SJ, Hansell DM, et al. Nonspecific interstitial pneumonia: variable appearance at high-resolution chest CT. Radiology 2000;217(3):701–705. [Published correction appears in Radiology 2001;218(2):606.][Abstract/Free Full Text]
- Screaton NJ, Hiorns MP, Lee KS, et al. Serial high resolution CT in non-specific interstitial pneumonia: prognostic value of the initial pattern. Clin Radiol 2005;60(1):96–104.[CrossRef][Medline]
- 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(6):1645–1650.[Abstract/Free Full Text]
- Elliot TL, Lynch DA, Newell JD Jr, et al. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr 2005;29(3):339–345.[CrossRef][Medline]
- Flaherty KR, Mumford JA, Murray S, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;168(5):543–548.[Abstract/Free Full Text]
- Kim EY, Lee KS, Chung MP, Kwon OJ, Kim TS, Hwang JH. Nonspecific interstitial pneumonia with fibrosis: serial high-resolution CT findings with functional correlation. AJR Am J Roentgenol 1999;173(4):949–953.[Abstract/Free Full Text]
- Nishiyama O, Kondoh Y, Taniguchi H, et al. Serial high resolution CT findings in nonspecific interstitial pneumonia/fibrosis. J Comput Assist Tomogr 2000;24(1):41–46.[CrossRef][Medline]
- Akira M, Inoue G, Yamamoto S, Sakatani M. Non-specific interstitial pneumonia: findings on sequential CT scans of nine patients. Thorax 2000;55(10):854–859.[Abstract/Free Full Text]
- Jeong YJ, Lee KS, Muller NL, et al. Usual interstitial pneumonia and non-specific interstitial pneumonia: serial thin-section CT findings correlated with pulmonary function. Korean J Radiol 2005;6(3):143–152.[Medline]
- Austin JH, Müller NL, Friedman PJ, et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 1996;200(2):327–331.[Free Full Text]
- Brennan P, Silman A. Statistical methods for assessing observer variability in clinical measures. BMJ 1992;304(6840):1491–1494.[Free Full Text]
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ABSTRACT
INTRODUCTION
