The idiopathic interstitial pneumonias: understanding key radiological features

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1 Clinical Radiology 65 (2010) 823e831 Contents lists available at ScienceDirect Clinical Radiology journal homepage: Pictorial Review The idiopathic interstitial pneumonias: understanding key radiological features S. Dixon, R. Benamore * Department of Radiology, The Churchill Hospital, Old Road, Oxford OX3 7LJ, UK article information Article history: Received 10 December 2009 Received in revised form 18 March 2010 Accepted 22 March 2010 Many radiologists find it challenging to distinguish between the different interstitial idiopathic pneumonias (IIPs). The British Thoracic Society guidelines on interstitial lung disease (2008) recommend the formation of multidisciplinary meetings, with diagnoses made by combined radiological, pathological, and clinical findings. This review focuses on understanding typical and atypical radiological features on high-resolution computed tomography between the different IIPs, to help the radiologist determine when a confident diagnosis can be made and how to deal with uncertainty. Ó 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Introduction The term idiopathic interstitial pneumonia (IIP) refers to a group of acute and chronic diffuse parenchymal lung disorders of unknown aetiology that often share similar features. The current accepted classification is based on histological criteria; each histological pattern is associated with characteristic high-resolution computed tomography (HRCT) imaging features 1e3 (Table 1). IIPs are divided into idiopathic pulmonary fibrosiseusual interstitial pneumonia (IPF-UIP) or IIPs other than IPF-UIP: nonspecific interstitial pneumonia (NSIP); cryptogenic organising pneumonia (COP), acute interstitial pneumonia (AIP); respiratory bronchiolitis interstitial lung disease (RBILD); desquamative interstitial pneumonia (DIP); and lymphocytic interstitial pneumonia (LIP). The British Thoracic Society (BTS) classification [adapted from the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines, ] delineates the roles of the pathologist, radiologist and clinician in diagnosing * Guarantor and correspondent: R. Benamore, Department of Radiology, The Churchill Hospital, Old Road, Oxford OX3 7LJ, UK. Tel.: þ address: Rachel.Benamore@orh.nhs.uk (R. Benamore). these conditions. It stresses the importance of distinguishing UIP from other IIPs, as UIP is associated with a poorer prognosis. HRCT is now the recommended imaging mode of choice. To make an accurate radiological diagnosis, it is important to use standardised terms with a pattern-based approach. 4 There is considerable overlap among the IIPs and although classification is based on histological criteria, there is considerable interobserver disagreement between pathologists in the diagnosis of interstitial pneumonias. Therefore, histopathology should not necessarily be considered the reference standard and the diagnosis, even though extremely challenging within a multidisciplinary team setting, can only be achieved by means of agreement with stringent correlation of the clinical, imaging, and pathological findings. 1,2 In this article, we illustrate the main radiological HRCT patterns of IIPs to help the radiologist to make a confident diagnosis or differential. Idiopathic pulmonary fibrosis-usual interstitial pneumonia IPF-UIP is the most common IIP. UIP is the pathological pattern of lung injury seen in IPF patients, characterised by temporal and spatial heterogeneity (the identification of /$ e see front matter Ó 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi: /j.crad

2 824 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e831 Table 1 Table adapted from American Thoracic Society/European Respiratory Society guidelines 1 demonstrating the relationship between the histopathological and the corresponding clinicaleradiologicalepathological diagnoses for idiopathic interstitial pneumonias. Histological features Clinicaleradiologicalepathological diagnosis Usual interstitial pneumonia Idiopathic pulmonary fibrosis Nonspecific interstitial Nonspecific interstitial pneumonia pneumonia Organising pneumonia Cryptogenic organising pneumonia Diffuse alveolar damage Acute interstitial pneumonia Respiratory bronchiolitis Respiratory bronchiolitis interstitial lung disease Desquamative interstitial Desquamative interstitial pneumonia pneumonia Lymphoid interstitial pneumonia Lymphoid interstitial pneumonia interstitial inflammation and fibrosis of different stages by fibroblast foci, mature fibrosis, and honeycombing). This distinguishes it from other IIPs that are temporally uniform (i.e., changes appear to have occurred over a single, relatively narrow time span). 5,6 UIP is seen in patients with connective tissue diseases and asbestosis, 7e10 and it is important to exclude underlying causes of a UIP pattern as these patients often have a better prognosis than those with IPF. 7 Typical HRCT features The main aim of HRCT is to separate patients with typical features of IPF-UIP from the other IIPs. If the typical features are present, radiologists can make a confident diagnosis of UIP in greater than 90% when compared to surgical lung biopsy as the reference standard, justifying non-invasive diagnosis. 1,11e17 The typical features are reticulation, honeycombing and traction bronchiectasis, with basal and subpleural predominance. In the early stages there may only be irregularity seen at the pleuraeparenchymal border at the lung bases, whilst extensive honeycombing is characteristic in end-stage disease 1,2,5,12,18 (Fig. 1). Honeycombing is the strongest indicator of UIP on CT (with a 90% positive predictive value, PPV), occurring in 70e80% of cases. Pathologically, honeycombing represents destroyed and fibrotic lung tissue, with cystic air spaces (from a few millimetres to several centimetres) with thick fibrous walls, indicating end-stages of the disease. This correlates on HRCT with clustered cystic air spaces of varying sizes with well-defined walls in a subpleural, predominantly lower zone location. 3 Its presence may infer a poorer survival. If UIP is seen with honeycombing the median survival is 2.1 years, whilst UIP without honeycombing has a median survival of 5.8 years. 1,11e16 Atypical HRCT features Ground-glass opacification (GGO) or nodules are not typical features. 1,5,12,14,15,17,19,20 If present, they can increase in extent or progress to fibrosis despite treatment. 21 If GGO is seen as a predominant feature, another diagnosis should Figure 1 HRCT images demonstrating the typical features of UIP; reticulation (thin arrows), honeycombing (thick arrows), and traction bronchiectasis (arrowheads) in a basal, subpleural predominance. (a) In the early stages there may only be irregularity/reticulation seen at the pleuraeparenchymal border, whilst (b) honeycombing is characteristic in end-stage disease. The lungs are generally of reduced volume. be considered. However, it is necessary to recognise that GGO can be commonly seen in UIP, where it is usually associated with dilated airways in keeping with established fine fibrosis. Difficulty arises when a reticular pattern and GGO coexist; in this instance it is important to recognise which is the dominant feature. If a reticular pattern is the dominant pattern and the GGO occurs in the same area, then it is most likely UIP with micro-honeycombing. If there are no reticular changes or traction bronchiectasis then the diagnosis is less likely to be UIP. 22 Although GGO is not a typical feature in UIP, it is characteristic of accelerated UIP, when consolidation may also be seen. This is an acute idiopathic deterioration of a patient with known IPF, which generally presents with a short history of worsening dyspnoea, only occasionally associated with systemic symptoms. 23,24 The GGO and/or consolidation may be diffuse or peripheral, and must be distinguished from infections that have similar appearances on CT (e.g., Pneumocystis jiroveci).

3 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e Rarely, IPF-UIP presents with upper zone predominance and/or a peribronchovascular distribution, 25e27 but alternative diagnoses, such as chronic hypersensitivity pneumonitis (HP), should be strongly considered. Consolidation is a very unusual feature of UIP. Mediastinal adenopathy can be seen in two-thirds of patients. 28 When atypical features are present, the pathological diagnosis is UIP in approximately 50% of cases 22 ; however, a biopsy is often required to confirm the diagnosis. Differential diagnosis The main differentials of UIP are NSIP, asbestosis, connective tissue diseases, and chronic HP. The cardinal feature distinguishing UIP from NSIP is GGO, which is a more predominant feature in NSIP. 29 It is harder to quantify the exact proportion of GGO on CT, therefore, recognising the degree of honeycombing is now recommended to help distinguish UIP from NSIP. 1,30 The differentiation of UIP and asbestosis is extremely difficult. No one CT feature can distinguish between them. Biopsy is not advocated 31 as the presence of a UIP pattern of fibrosis and asbestos bodies histologically does not necessarily always indicate asbestosis. 8,32 Bronchoalveolar lavage may have a role, but occupational history is the main key to diagnosis, as well as the presence of pleural plaques. In the absence of pleural plaques, to aid differentiation, subpleural dot-like or branching opacites, curvilinear lines, and bandlike opacities are significantly more common in patients with asbestosis, whereas honeycombing, visible bronchioles, and bronchiolectasis within consolidation are significantly more common in patients with IPF 33 Bronchiolar obstruction in the subpleural region may be more prominent in asbestosis, whereas bronchiolar dilatation may be more prominent in IPF. 33 IPF-UIP may co-exist with emphysema. There is usually upper zone paraseptal (>90%) emphysema and lower zone fibrosis. Emphysema is distinguished from honeycombing by the lack of well-defined walls and the presence of internal centrilobular structures. 34,35 The lung volumes are usually preserved and associated with pulmonary arterial hypertension in approximately 50%. If, however, the fibrosis and emphysema coexist in the same part of the lung, it can mimic cystic lung disease. 32,34e36 Nonspecific interstitial pneumonia NSIP was first recognised in the late 1990s, 5 and is now accepted as a distinct clinical entity. 37 Pathologically, there is temporal homogeneity of inflammation and fibrosis with the absence of honeycombing and fibrotic foci. 38 There are two recognised types of NSIP: fibrotic NSIP and cellular NSIP. Fibrotic NSIP is a combination of fibrosis and inflammation and is much more common than pure cellular NSIP. Cellular NSIP, although rare, has a better prognosis than fibrotic NSIP. 10 In contrast to UIP, which is usually idiopathic, 39 NSIP is often associated with collagen vascular disease (with known major involvement in scleroderma, 40 polymyositis, dermatomyositis, or Sjogrens syndrome) and is a frequent pattern in drug-induced pneumonitis. Therefore, a histopathological diagnosis of NSIP should prompt a search for an underlying cause. Immunosuppression with oral corticosteroids and immunosuppressive agents is the treatment of choice. Typical HRCT features NSIP is often difficult to diagnose with confidence on HRCT, as the features are more variable than UIP. 41,42 If the typical features are present and diagnosed correctly, the PPV for the diagnosis of NSIP is approximately 67%. 29 GGO is found in 75e100% of cases. It is usually bilateral, symmetrical and subpleural in two-thirds of patients and has lower zone predominance in over 50%. Reticulation and irregular linear opacities are present in 50e85%, of which up to 50% are peribronchovascular in nature. The appearance of traction bronchiectasis is variable, ranging from 35e95% (Fig. 2). There may be associated volume loss, especially in fibrotic NSIP. Honeycombing is not a major feature of NSIP but occurs in 25e30%; it is associated with finer fibrosis that is temporally homogeneous whereas fibrosis in UIP is temporally heterogeneous. 29,43 Atypical features and differential diagnosis Consolidation, centrilobular nodules and pleural effusions are rare. 11,41,42 There is an overlap in the imaging between NSIP and UIP in up to 25%. In 32% of cases NSIP presents with less generalised GGO, a coarser pattern of fibrosis than expected and does not conform to its usual subpleural location, appearing indistinguishable from UIP. These cases require a biopsy to help differentiate NSIP and UIP. If the two diseases co-exist pathologically, HRCT and histology need to be reviewed together. 13,29,42,44,45 However, even with an atypical distribution of GGO (i.e., apical or non-subpleural), in the absence of honeycombing, the diagnosis favours NSIP over UIP. 11,46 Subtle early NSIP can be mistaken for dependent change, with subpleural GGO only at the lung bases. If in doubt, a prone scan will help clarification. NSIP can co-exist with organising pneumonia (14%), and HP (20%), 42 and in this circumstance, responds better to treatment with steroids. Other differentials are chronic HP and DIP. Cryptogenic organising pneumonia COP, previously known as bronchiolitis obliteranseorganising pneumonia (BOOP) is a patchy organising pneumonia caused by bronchiolar obstruction by plugs of loose organising connective tissue that may wax and wane. 1,47,48 Typical HRCT features The main finding of COP is consolidation, seen in 90% and is usually multifocal and bilateral. Unilateral COP can also occur. In 50%, consolidation is subpleural or peribronchovascular. It has a lower zone predominance, but can affect any lobe. 49 Dilated airways are often seen on HRCT with air bronchograms mimicking acute pneumonia (Fig. 3).

4 826 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e831 Figure 3 HRCT images demonstrating proven COP. Consolidation (short arrows) occurs in 90%. It is multifocal with a peribronchovascular (a) and subpleural (b)(dotted arrows) distribution in 50%. Within the consolidation dilated airways are often seen (arrowheads). Coarse linear opacities are often seen, predominantly within the lower zones (white arrows) (b). GGO is a prominent pattern in 60%. Linear opacities occur in isolation or in association with multifocal areas of consolidation in COP (Fig. 3b). Nodules, usually less than 10 mm are seen in 30e50%. Lung volumes are usually preserved in 75%. If the typical features of COP are present the radiological accuracy for correct diagnosis is 60e79%. 14,50 Atypical HRCT features and differential diagnoses Figure 2 Histologically proven NSIP. HRCT images demonstrating (a) GGO in a typical bilateral, symmetrical, predominantly subpleural, and lower zone predominance (arrowheads). GGO may be the only finding in one-third of cases. (b) Reticulation/irregular linear opacities (thin arrows) occur in 50e85%. Traction bronchiectasis occurs in 35e95% (thick arrows). (c) CT with lung windows showing GGO can be peribronchovascular in up to 50% (dotted arrows) and can be indistinguishable from organising pneumonia. Pleural effusions are very rare. Pleural thickening occurs in 33% and parenchymal bands in 25%. In approximately 15% of cases COP presents as multiple masses, which need to be differentiated from infection and neoplasms, particularly lymphoma (Fig. 4a). COP rarely presents as the reversed halo sign, 51 which is also seen in South American blastomycosis and lymphomatoid granulomatosis 52,53 (Fig. 4b). COP may demonstrate a perilobular distribution resembling interlobular septal thickening. 51,54,55 The differential diagnosis for multifocal consolidation includes bronchoalveolar cell carcinoma, lymphoma, sarcoid, vasculitis, eosinophilic pneumonia, connective

5 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e and the extent usually correlates with disease duration. It is often in a geographic pattern, with lobular sparing. Consolidation occurs in 90% of patients with early AIP, but is not as common as GGO, and mostly occurs posteriorly. In 85% of cases there is a degree of bronchial dilatation with interlobular septal thickening (Fig. 5). There is associated parenchymal distortion but honeycombing is not a feature acutely, being more common in the later stages. 48 Pleural effusions occur in 33%. 50,57 Most patients are ventilated in the early stages of the disease. In the later stages, consolidation is replaced by GGO, representing fibroblast proliferation histologically. There is cyst formation with increased areas of lucency. At this stage parenchymal distortion becomes more obvious, especially within the non-dependent regions of the lung. This is best explained by the protective effect of the consolidation within the dependent portions of the lungs against barotrauma of mechanical ventilation. 58 Differential diagnoses The main differential is acute respiratory distress syndrome (ARDS). AIP and ARDS are commonly indistinguishable, although AIP is often more symmetrical and lower zone predominant. 57,59 Other considerations are infection [such as Pneumocystis pneumonia (PCP)], pulmonary oedema, and pulmonary haemorrhage dependent upon clinical features. Figure 4 CT with lung windows demonstrating biopsy-proven COP. (a) COP presenting as multiple masses. Note the air bronchograms within the masses. (b) HRCT demonstrating the reverse halo sign (arrows), which is areas of GGO surrounded by crescent and ringshaped consolidation. tissue diseases (poly/dermatomyositis), drug-induced diseases, and infection. If GGO is a predominant feature, NSIP must be excluded. If the disease is subpleural in distribution then eosinophilic pneumonia and vasculitis should be excluded. Mediastinal lymphadenopathy is less commonly seen in COP than the other IIPs, with an overall prevalence of 38% compared to 66% in IPF, 81% in NSIP, and 71% in RBILD/DIP. 28 If clinical and radiographic features are uncertain, a lung biopsy is required. COP presenting as consolidation or nodules has a better prognosis than if presenting predominantly as linear opacities, as these may not resolve with treatment. 56 Respiratory bronchiolitis interstitial lung disease Respiratory bronchiolitis (RB) is a histopathological diagnosis found in almost all smokers. The term RBILD is reserved for clinically symptomatic smokers with imaging/ histological findings of RB. 48,60 It usually occurs in the fourth/fifth decade, with a male predominance (2:1). Histologically, there is macrophage accumulation and chronic inflammation in the respiratory bronchioles, which manifests as centrilobular nodules on HRCT (Fig. 6). GGO is typically multifocal and upper zone predominant; it is due Acute interstitial pneumonia AIP is a distinct histological entity characterised by diffuse alveolar damage of unknown aetiology. 1 HRCT features The HRCT features of AIP depend on whether it presents in an early or late stage of the disease process. In both stages it has lower zone predominance in 40%. GGO is invariable Figure 5 CT with lung windows demonstrating histologically proven AIP in a young women post-partum. There is lower zone predominance with consolidation and GGO with lobular sparing (arrow).

6 828 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e831 accumulation and alveolar septal thickening. It has a homogeneous pattern on CT with a basal peripheral predominance. Its main feature is GGO. Reticulation and cysts may be seen. 38,41 Like RBILD it is part of the smokingrelated ILD spectrum. It primarily affects smokers in their fourth/fifth decade so centrilobular emphysema often coexists. There is a male predominance (2:1). 61,64e66 In general the clinical prognosis is good with a 70% 10-year survival. 1 The GGO has a lower zone predominance in 75%, with a peripheral distribution in over half of cases, a patchy distribution in a quarter, and a diffuse/uniform pattern in 18% (Fig. 7). Small cystic spaces may be seen within the GGO. The GGO may remain stable or improve with treatment. 21,67 Progression to reticulation and honeycombing with architectural distortion is uncommon (<20%), and usually improves with treatment. 65 Differential diagnoses Pathologically, DIP generally shows diffuse rather than bronchocentric lung involvement. 60 Acute or sub-acute HP can appear similar to DIP, but as in RBILD, smoking history and allergen exposure are important 20 ; infections such as PCP may mimic DIP. Lymphocytic interstitial pneumonia Figure 6 HRCT images demonstrating RBILD. There is subtle multifocal ground glass attenuation, some of which is centrilobular in distribution (arrows) within the upper zones on inspiration (a). There is accentuation of the mosaic pattern on expiration (b) confirming air-trapping. to the accumulation of macrophages within the air spaces. There is bronchial wall thickening with centrilobular emphysema and air trapping (Fig. 6). Reticulation may occur, but is not a major feature. If present, there is no associated honeycombing or traction bronchial dilatation. The features seen on HRCT may regress or show improvement after the patient stops smoking with or without additional treatment with steroids. 61 LIP is a rare disorder, characterised pathologically by polyclonal lymphocyte aggregates that accumulate diffusely in the interstitium. 68 It is usually associated with an underlying disease, mainly connective tissue diseases (especially Sjögren s) or in patients with immunodeficiency. Therefore, it is important to exclude an underlying cause in all patients. 1 Typical HRCT findings are GGO with a diffuse distribution in two-thirds of patients, thin-walled perivascular/subpleural cysts in two-thirds of patients, and reticulation in 50%. Nodules typically follow the lymphatics, therefore, are Differential diagnoses There are three main differentials: (1) HP, which is often associated with a history of allergen exposure, but there is a decreased incidence of HP in smokers compared with nonsmokers 62,63 ; (2) DIP, where the GGO is more extensive but centrilobular nodules are uncommon. The differentiation between DIP and RBILD can be indistinguishable by CT 60 and may be referred to as a spectrum of smoking-related ILD ;(3) NSIP, which usually has a lower zone predominance when compared with the mid to upper zone predominance in RBILD. Desquamative interstitial pneumonia DIP is an extremely rare interstitial pneumonia. It is a diffuse process with intra-alveolar macrophage Figure 7 HRCT image demonstrating histologically proven DIP. Image shows GGO, which is in a patchy and diffuse distribution (seen in 18% of cases), but in over 50% there is predominantly a peripheral distribution.

7 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e Malignant transformation is unusual. HRCT may suggest the diagnosis of LIP, but it is extremely difficult to diagnose confidently, and almost always requires surgical lung biopsy. Other conditions that may mimic LIP are sarcoid, HP, and Langerhan s cell histiocytosis (LCH). 70 In LCH the nodules are ill-defined, rarely subpleural, and the cysts are characteristically bizarre shaped with thick walls, sparing the lung bases, whilst in LIP the cysts are thin-walled and randomly distributed. 69 Conclusion The IIPs pose a diagnostic challenge. HRCT is indicated in virtually all patients with suspected IIP, and in order to make a confident diagnosis, one should be aware of key radiological features. Specific entities, such as a UIP pattern of pulmonary fibrosis and typical COP, can often be diagnosed with confidence by the radiologist. The diagnoses of the other IIPs require a multidisciplinary approach. In general, honeycombing, reticulation, and traction bronchiectasis are characteristic of UIP, whilst GGO suggests NSIP or DIP. Consolidation is seen in COP and AIP, whilst cysts are a feature of DIP or LIP. References Figure 8 HRCT images displaying the typical features of histologically proven LIP. (a) GGO is invariable (occurs in a diffuse distribution two thirds) with centrilobular nodules (arrows), although as nodules occur in the distribution of the lymphatics they can also occur in subpleural and peribronchovascular locations. (b) Thin-walled perivascular cysts occur in two-thirds of cases (arrowheads). (c) Diffuse nodular GGO with atypical features of nodular consolidation (white arrowheads) and traction bronchiectasis (white arrows). seen in a centrilobular (100%), subpleural (86%), and perichronchovascular distribution 69 (Fig. 8). Unlike other IIPs, lymphadenopathy is common, being seen in two-thirds. Atypical features include perivascular honeycombing, larger nodules, and consolidation. 41,50 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;165:277e British Thoracic Society Guideline. Interstitial lung disease guideline: the British thoracic society in collaboration with the thoracic society of Australia and New Zealand and the Irish thoracic society. Thorax 2008;63:v1ev Leibow A. Definition and classification of interstitial pneumonias in human pathology. Prog Respir Res 1975;8:1e Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008;246:679e Katzenstein AA, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med 1998;157:1301e Verbeken EK. Classifying interstitial lung diseases in a fractal lung: a morphologists view anno Domini Eur Respir J 2001;18:107e Park JH, Kim DS, Park I-N, et al. Prognosis of fibrotic interstitial pneumonia. Idiopathic versus collagen vascular of fibrotic interstitial pneumonia. Idiopathic versus collagen vascular disease-related subtypes. Am J Resp Crit Care Med 2007;175:705e Copley SJ, Wells AU, Sivakumaran P, et al. Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT features. Radiology 2003;229:731e6. 9. Goh NSL. Connective tissue disease and the lung. Clin Pulmon Med 2009;16:309e Kim EJ, Collard HR, King TE. Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern. Chest 2009;136:1397e Tafti SF, Mokri B, Mohammadi F, et al. Comparison of clinicoradiologic manifestation of nonspecific interstitial pneumonia and usual interstitial pneumonia/iodpathic pulmonary fibrosis: a report from NRITLD. Ann Thorac Med 2008;3:140e Misumi A, Lynch DA. Idiopathic pulmonary fibrosis/usual intersititial pneumonia imaging diagnosis, spectrum of abnormalities, and temporal progression. Proc Am Thorac Soc. 2006;3:307e Flaherty KR, Thwaite EL, Kazerooni EA, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax 2003;58:143e8.

8 830 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e Swensen SJ, Aughenbaugh GL, Myers JL. Diffuse lung disease: diagnostic accuracy of CT in patients undergoing surgical biopsy of the lung. Radiology 1997;205:229e 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;164:193e Hunninghake GW, Lynch DA, Galvin JR, et al. Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia. Chest 2003;124:1215e Raghu G, Mageto YN, Lockhart D, et al. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease. Chest 1999;116:1168e Akira M, Sakatani M, Ueda E. Idiopathic pulmonary fibrosis: progression of honeycombing at thin-section CT. Radiology 1993;189:687e Elliot TL, Lynch DA, Newell JD, et al. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr 2005;29:339e Lynch DA, Newell JD, Logan PM, et al. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis? AJR Am J Roentgenol 1995;165:807e Hartman TE, Primac SL, Kang EY, et al. Disease progression in usual interstitial pneumonia compared with desquamative interstitial pneumonia: assessment with serial CT. Chest 1996;110:378e Raghu G, Nicholson AG, Lynch D. The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias. Eur Respir Rev 2008;17:108e Ambrosini V, Cancellieri A, Chilosi M, et al. Acute exacerbation of idiopathic pulmonary fibrosis: report of a series. Eur Respir J 2003;22:821e Akira M, Hamada H, Sakatani M, et al. CT findings during phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis. AJR Am J Roentgenol 1997;168:79e Osamu N, Hiroyuki T, Yasuhiro K, et al. Familial idiopathic pulmonary fibrosis: serial high-resolution computed tomography findings in 9 patients. J Comput Assist Tomogr 2004;28:443e Silva IS, Muller NL, Lynch DA, et al. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology 2008;246:288e Sumikawa H, Johkoh T, Colby TV, et al. Computed tomography findings in pathological usual interstitial pneumonia. Relationship to survival. Am J Respir Crit Care Med 2008;177:433e Souza CA, Müller NL, Lee KS, et al. Idiopathic interstitial pneumonias: prevalence of mediastinal lymph node enlargement in 206 patients. AJR Am J Roentgenol 2006;186:995e MacDonald SLS, 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;221:600e American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med 2000;161:646e American Thoracic Society. Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Respir Crit Care Med 2004;170:691e Yamamoto S. Histopathological features of pulmonary asbestosis with particular emphasis on the comparison with those of usual interstitial pneumonia. Osaka City Med J 1997;43:225e Akira M, Yamamoto S, Inoue Y, et al. High-resolution CT of asbestosis and idiopathic pulmonary fibrosis. AJR Am J Roentgenol 2003;181:163e Doherty MJ, Pearson MG, O Grady EA, et al. Cryptogenic fibrosing alveolitis with preserved lung volumes. Thorax 1997;52:998e Wells AU, King AD, Rubens MB, et al. Lone cryptogenic fibrosing alveolitis: a functionalemorphologic correlation based on extent of disease on thin-section computed tomography. Am J Respir Crit Care Med 1997;155:1367e Cottin V, Nunes H, Brillet P-Y, et al. Combined pulmonary fibrosis and emphysema: a distinct under-recognized entity. Eur Respir J 2005;26:586e Travis WD, Matsui K, Moss J, et al. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol 2000;24:19e Visscher DW, Myers JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc 2006;3:322e Kinder BW, Collard HR, Koth L, et al. Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease? Am J Respir Crit Care Med 2007;176:691e Goldin JG, Lynch DA, Strollo DC, et al. High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest 2008;134:358e Johkoh T, Muller NL, Cartier Y, et al. Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section HRCT in 129 patients. Radiology 1999;211:555e Hartman TE, Swensen SJ, Hansell DM, et al. Nonspecific interstitial pneumonia: variable appearance at high resolution chest CT. Radiology 2000;217:701e Shin KM, Lee KS, Chung MP, et al. Prognostic determinants among clinical, thin-section CT, and histopathologic findings for fibrotic idiopathic interstitial pneumonias: tertiary hospital study. Radiology 2008;249:328e Flaherty KR, Travis WD, Colby TV, et al. Histopathologic variability in usual and nonspecific interstitial pneumonia. Am J Respir Crit Care Med 2001;164:1722e Vogelmeier C. IPF or NSIP? That is the question. Ed. Eur Respir J 2003;22:191e Rubinowitz AN, Moon M, Homer RA. 34-year-old man presenting with gradual onset of shortness of breath and interstitial lung disease. Chest 2008;133:1041e McAdams HP, Rosado-de-Christenson ML, WEhunt WD, et al. The alphabet soup revisited: the chronic interstitial pneumonias in the 1990s. RadioGraphics 1996;16:1009e Lynch DA, Travis WD, Müller NL, et al. Idiopathic interstitial pneumonia: CT features. Radiology 2005;236:10e Lee KS, Kullnig P, Hartman TE, et al. Cryptogenic organising pneumonia: CT findings in 43 patients. AJR Am J Roentgenol 1994;162:543e Johkoh T, Muller NL, Pickford HA, et al. Lymphocytic interstitial pneumonia: thin-section CT findings in 22 patients. Radiology 1999;212:567e Kim SJ, Lee KS, Ryu YH, et al. Reversed halo sign on high-resolution CT of cryptogenic organising pneumonia: diagnostic implications. AJR Am J Roentgenol 2003;180:1251e Gasparetto EL, Escuissato DL, Davaus T, et al. Reversed halo sign in pulmonary paracoccidioidomycosis. AJR Am J Roentgenol 2005;184:1932e Benamore RE, Weisbrod GL, Hwang DM. Reverse halo sign in lymphomatoid granulomatosis. Br J Radiol 2007;80:e162ee Akira M, Yamamoto S, Sakatani M. Bronchiolitis obliterans organising pneumonia manifesting as multiple large nodules or masses. AJR Am J Roentgenol 1998;170:291e Ujita M, Renzoni EA, Veeraraghavan S, et al. Organising pneumonia: perilobular pattern at thin-section CT. Radiology 2004;232:757e Lee JS, Lynch DA, Sharma S, et al. Organising pneumonia: implication of high-resolution computed tomography features. J Comput Assist Tomogr 2003;27:260e Primack SL, Hartman TE, Ikezoe J, et al. Acute interstitial pneumonia: radiographic and CT findings in nine patients. Radiology 1993;188:817e Desai SR, Wells AU, Rubens MB, et al. Acute respiratory distress syndrome: CT abnormalities at long-term follow-up. Radiology 1999;210:29e Tomiyama N, Muller NL, Johkoh T, et al. Acute respiratory distress syndrome and acute interstitial pneumonia: comparison of thin-section CT findings. J Comput Assist Tomogr 2001;25:28e Heyneman LE, Ward S, Lynch DA, et al. Respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative interstitial pneumonia: different entities or part of the spectrum of the same disease process? AJR Am J Roentgenol 1999;173:1617e22.

9 S. Dixon, R. Benamore / Clinical Radiology 65 (2010) 823e Attili AK, Kazerooni EA, Gross BH, et al. Smoking-related interstitial lung disease: radiologiceclinicalepathologic correlation. RadioGraphics 2008;28:1383e Blanchet M-R, Israel-Assayag E, Cormier Y. Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro. Am J Respir Crit Care Med 2004;169:903e Hansell DM, Wells AU, Padley SPG, et al. Hypersensitivity pneumonitis: correlation of individual HRCT patterns with functional abnormalities. Radiology 1996;199:123e Koyama M, Johkoh T, Honda O, et al. Chronic cystic lung disease: diagnostic accuracy of high-resolution CT in 92 patients. AJR Am J Roentgenol 2003;180:827e Akira M, Yamamoto S, Hara H, et al. Serial computed tomographic evaluation in desquamative interstitial pneumonia. Thorax 1997;42:333e Ryu JH, Myers JL, Capizzi SA, et al. Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease. Chest 2005;127:178e Hartman TE, Primack SL, Swensen SJ, et al. Desquamative interstitial pneumonia: thin section CT findings in 92 patients. AJR Am J Roentgenol 1993;187:787e Cha S-I, Fessler MB, Cool CD, et al. Lymphoid interstitial pneumonia: clinical features, associations and prognosis. Eur Respir J 2006;28:364e Raoof S, Amchentev A, Vlahos I, et al. Multinodular disease. Chest 2006;129:805e Webb RW. Thin-section CT of the secondary pulmonary lobule: anatomy and the imageethe 2004 Fleischner lecture. Radiology 2006;239:322e38.