Noninfectious Inflammatory Lung Disease: Imaging Considerations and Clues to Differential Diagnosis

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1 Cardiopulmonary Imaging Review Nemec et al. Noninfectious Inflammatory Lung Disease Cardiopulmonary Imaging Review Stefan Franz Nemec 1 Ronald L. Eisenberg Alexander A. Bankier Nemec SF, Eisenberg RL, Bankier AA Keywords: CT, differential diagnosis, noninfectious inflammatory lung disease, DOI: /AJR Received August 6, 2012; accepted without revision September 17, A. A. Bankier is a consultant for Spiration (Olympus Medical Systems) and has received authorship honoraria from Elsevier. 1 All authors: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA Address correspondence to R. L. Eisenberg (rleisenb@bidmc.harvard.edu). CME/SAM This article is available for CME/SAM credit. AJR 2013; 201: X/13/ American Roentgen Ray Society Noninfectious Inflammatory Lung Disease: Imaging Considerations and Clues to Differential Diagnosis OBJECTIVE. Noninfectious inflammatory lung diseases represent a spectrum of idiopathic and secondary conditions that may involve the airspaces, vasculature, or interstitium. The most important clinical and pathologic characteristics are reviewed, emphasizing CT findings and potential clues to differential diagnosis. CONCLUSION. Noninfectious inflammatory lung diseases translate into various CT appearances that are important in making the correct diagnosis. N oninfectious inflammatory lung diseases are a clinically, radiologically, and histopathologically heterogeneous group of acute and chronic conditions [1 3]. These disorders may affect the airspaces, pulmonary vasculature, pulmonary interstitium, or a combination of these three anatomic compartments [1 3]. They can be isolated to the lung or involve multiple organs. Noninfectious inflammatory lung diseases may be idiopathic or may represent a secondary reaction to autoimmune diseases, infection, environmental exposures, or drugs [1 3]. Overall, our understanding of the pathophysiologic mechanisms of these diseases is still limited [1 3]. Imaging plays a pivotal role in detecting and characterizing noninfectious inflammatory lung diseases. Therefore, radiologists must be aware of the imaging findings seen in these diseases and have an understanding of their underlying clinical manifestations and pathologic causes [1 3]. This article is a comprehensive description of the imaging, pathologic, and clinical features of noninfectious inflammatory lung diseases and provides a practical framework for the diagnostic approach to this group of diseases. The structure of this article follows the anatomic components predominantly affected by noninfectious inflammatory lung diseases the airspaces, vasculature, and interstitium (Fig. 1 and Tables 1 3). Given the often nonspecific manifestation of these diseases on chest radiographs, the imaging part of this article is mainly focused on CT. Airspace-Predominant Diseases Noninfectious inflammatory airspace diseases primarily affect structures distal to the respiratory bronchioles, resulting in changes that may be acute (most often reversible) or chronic (often irreversible) [3, 4] (Table 1). Simultaneous involvement of the interstitium is common [3, 4]. The airspace-predominant types of noninfectious inflammatory lung disease are either idiopathic or secondary to collagen vascular diseases, infection, or drugs [3 5]. Hypersensitivity pneumonitis, although a noninfectious inflammation, is a well-recognized disease primarily caused by organic or inorganic dust exposure and will not be discussed in detail in this article [6]. Eosinophilic Pneumonia Acute eosinophilic pneumonia Acute eosinophilic pneumonia is a relatively rare disease characterized by the accumulation of eosinophils in the lungs [7, 8]. It may be idiopathic or secondary to fungal infections, vaccinations, and drugs (minocycline, fludarabine, progesterone) or to environmental exposures such as dust inhalation, tear gas, or gasoline [9]. Patients usually present with dyspnea, hypoxemia, and fever [7, 8]. If untreated, acute eosinophilic pneumonia may result in acute respiratory failure [7, 8]. Bronchoalveolar lavage typically shows a high percentage of eosinophils, whereas the peripheral blood eosinophil level is frequently normal [7, 8]. Most patients have a good prognosis, with prompt and complete response to corticosteroids [7, 8]. 278 AJR:201, August 2013

2 Noninfectious Inflammatory Lung Disease TABLE 1: Airspace-Predominant Diseases: Summary of Clinical and Radiologic Findings Disease Key Clinical Key Features Spectrum of Radiologic Findings Key Radiologic Findings Acute eosinophilic pneumonia Chronic eosinophilic pneumonia Organizing pneumonia Langerhans cell histiocytosis RB-ILD DIP Eosinophil level on BAL, dyspnea, fever, acute respiratory failure in severe cases Eosinophil level on BAL, dyspnea, cough, fever, common with asthma Mild dyspnea, cough, fever over several weeks Young smoker, progressive dyspnea, cough, fatigue Heavy cigarette smoker, mild dyspnea, cough Heavy cigarette smoker, mild dyspnea, cough Histologically, acute eosinophilic pneumonia is characterized by eosinophilic infiltration of the alveoli and, to a lesser extent, of the interstitium; severe cases may show diffuse alveolar damage [8, 10]. There is no distinct zonal predominance [11, 12]. Chest radiographs show nonspecific bilateral consolidations and reticular opacities [11, 12]. On CT, ground-glass opacities, centrilobular nodules, and consolidations likely reflect the combination of alveolar eosinophilic infiltration and diffuse alveolar damage, whereas interlobular septal thickening and thickening of the bronchovascular bundles probably represent interstitial eosinophilic infiltration [11, 12] (Fig. 2). Pleural effusions may develop owing to eosinophilic infiltration of the pleura [11, 12] (Fig. 2). The differential diagnosis of acute eosinophilic pneumonia includes other diseases manifesting as a combination of alveolar and interstitial opacities, sometimes with pleural effusions. These entities include pulmonary edema, acute interstitial pneumonia (AIP), and infectious pneumonia [12]. However, the imaging findings in pulmonary edema and late-stage AIP have a lower lung predominance, whereas pneumonia, unless multifocal, is often limited to a single lobe. Thus, the bilateral and multifocal appearance of eosinophilic pneumonia without zonal predominance is an important diagnostic clue [11, 12]. GGOs, consolidations, thickening of interlobular septa and bronchovascular bundles, pleural effusions Upper lung predominance, nonsegmental peripheral bandlike airspace opacities, subpleural fibrosis in advanced disease Lower lung predominance; typical appearance is peripheral unilateral or bilateral airspace opacities with air bronchograms and subpleural sparing; atypical appearance is perilobular pattern, GGOs with reversedhalo sign, masses, migration on follow-up Noncavitating and cavitating peribronchiolar nodules, cystic lesions, recurrent pneumothoraces Upper lung predominance, centrilobular nodules and GGOs, accompanying centrilobular emphysema and bronchial wall thickening Upper lung predominance, diffuse GGOs, bronchial wall thickening, mild fibrosis with reticular opacities and small cysts Bilateral multifocal GGOs and consolidations, no zonal predominance Upper lung predominance, peripheral bandlike airspace opacities Lower lung predominance, peripheral airspace opacities with air bronchograms and subpleural sparing, migration of changes Peribronchiolar cavitating nodules and cystic lesions Upper lung predominance, centrilobular nodules, GGOs Upper lung predominance, diffuse GGOs, mild fibrosis Note BAL = bronchoalveolar lavage, GGOs = ground-glass opacities, RB-ILD = respiratory bronchiolitis associated interstitial lung disease, DIP = desquamative interstitial pneumonia. Chronic eosinophilic pneumonia Chronic eosinophilic pneumonia is a distinct clinical and pathologic entity that is not necessarily the consequence of acute eosinophilic pneumonia and is frequently associated with asthma [10, 13]. It may be idiopathic or secondary to drugs (nonsteroidal antiinflammatory agents, salicylates, minocycline, cotrimoxazole, fludarabine, progesterone) or to fungal or parasitic infections [9]. Most patients are middle-aged women who present with dyspnea, cough, malaise, and fever [10, 13]. There is typically a high percentage of eosinophils in the bronchoalveolar lavage but only moderate blood eosinophilia [10, 13]. Patients usually respond well to corticosteroid therapy and have a good prognosis, but most require long-term treatment to prevent relapse [10, 13]. Histology shows an accumulation of eosinophils and lymphocytes in the alveoli and interstitium. Unlike acute eosinophilic pneumonia, chronic eosinophilic pneumonia tends to show fibrosis at the alveolar level [10]. The upper lungs are predominantly involved [14]. Chest radiographs show bilateral peripheral consolidations that spare the central lung zones, producing a pattern that has been described as the photographic negative shadow of pulmonary edema [13]. CT shows nonsegmental peripheral airspace consolidations, which resemble bandlike opacities parallel to the pleura and may represent the chronic alveolar accumulation of eosinophils [14, 15] (Fig. 3). Signs of fibrosis are seen in advanced disease [16]. The differential diagnosis of chronic eosinophilic pneumonia includes other conditions with peripheral airspace opacities, such as organizing pneumonia and Churg-Strauss syndrome [15, 17]. Organizing pneumonia, however, has a lower lung predominance and spares the subpleural areas, and Churg- Strauss syndrome tends to have a random distribution [15, 17]. Thus, a striking peripheral distribution of airspace opacities in the upper lungs is the imaging clue in chronic eosinophilic pneumonia [13 15]. Organizing Pneumonia Organizing pneumonia is a nonspecific response to pulmonary injury [5, 18]. When idiopathic, it is known as cryptogenic organizing pneumonia [5, 18]. The term organizing pneumonia is preferred if the disease occurs secondary to collagen vascular disease, infection, various drugs (e.g., amiodarone, nitrofurantoin, interferon), or organ transplantation [5, 18]. Many patients are middleaged adults who present with at least several weeks of mild dyspnea, cough, and fever [5, 18]. Most recover completely after aggressive corticosteroid therapy, but relapses can occur after treatment is stopped [18]. Histologically, organizing pneumonia refers to the organization of exudate into inflam- AJR:201, August

3 Nemec et al. TABLE 2: Vascular-Predominant Diseases: Summary of Clinical and Radiologic Findings Disease Key Clinical Features Spectrum of Radiologic Findings Key Radiologic Findings Thickening of wall of aorta and its branches, stenoses Acute phase findings are high attenuation of vessel wall on unenhanced CT, vessel wall thickening and delayed wall enhancement, increased attenuation of mediastinal fat, vessel stenosis or occlusion with infarctions and mosaic perfusion; chronic fibrotic phase findings are vessel wall calcifications and arterial stenoses Takayasu arteritis Young women; arteritis of aorta and its branches; retinopathy; stenosis of carotid, renal, and subclavian arteries; pulmonary vasculitis Multiple noncavitating or cavitating nodules, consolidations, subglottic tracheal stenosis Multiple noncavitating or cavitating nodules, random or peribronchovascular distribution, consolidations with ground-glass halo, subglottic tracheal stenosis, bronchiectasis, pleural effusions Granulomatosis with polyangiitis a ANCA associated, rhinosinusitis, glomerulonephritis, pulmonary vasculitis GGOs, consolidations, centrilobular nodules, random distribution GGOs, consolidations, centrilobular nodules, bronchial wall thickening, random or peripheral distribution Churg-Strauss syndrome ANCA associated, pulmonary eosinophilia, asthma, polyneuropathy, pulmonary vasculitis, alveolar hemorrhage Perihilar predominance, bilateral GGOs with interlobular septal thickening, consolidations Perihilar predominance, bilateral GGOs with interlobular septal thickening ( crazy paving ), consolidations with GGO halo, pleural effusions Microscopic polyangiitis ANCA associated, rapidly progressive, glomerulonephritis, pulmonary vasculitis, alveolar hemorrhage Pulmonary artery pseudoaneurysms Fusiform or saccular pulmonary artery pseudoaneurysms, GGOs and consolidations (parenchymal hemorrhage), subpleural infarctions and mosaic perfusion, pleural effusions, ulcerative tracheal stenosis, fibrosing mediastinitis Behçet disease Young men of Middle East or Far East descent, oral and genital ulcers, uveitis, venous thrombotic disease, pulmonary vasculitis Note ANCA = antineutrophil cytoplasmic antibody, GGOs = ground-glass opacities. a References [103, 104]. matory debris and the subsequent formation of granulation tissue in the alveolar ducts and alveoli [5, 18]. Because this fibroinflammatory process may translate into various radiologic appearances, the diagnosis should always be confirmed by biopsy [18]. Chest radiographs may show nonspecific multifocal consolidations but without pleural effusions [19]. On CT, organizing pneumonia may manifest typical or atypical findings, which mimic various other lung diseases [5]. Typical organizing pneumonia appears as unilateral or bilateral airspace consolidations with air bronchograms, which tend to occur in a peripheral distribution with subpleural sparing and primarily involve the lower lobes (Fig. 4). Areas of abnormality range from a few centimeters to an entire lobe [5, 15, 20]. Atypical CT appearances include ground-glass areas with surrounding dense opacity ( atoll or reversed-halo sign) and a perilobular pattern along the interlobular septa [5, 21, 22] (Fig. 5). Another atypical presentation of organizing pneumonia is single or multiple masslike lesions, which may mimic lung cancer and may be FDG-avid on PET/CT (reflecting acute inflammation) [5] (Fig. 6). On follow-up CT, both typical and atypical changes of organizing pneumonia may migrate or decrease in size even without treatment [5, 18]. The differential diagnosis of organizing pneumonia includes other conditions with airspace opacities, such as chronic eosinophilic pneumonia, aspiration, and infectious pneumonia [5, 15]. However, chronic eosinophilic pneumonia has an upper lung predominance without peripheral sparing, aspiration is located in the dependent lung, and infectious pneumonia is randomly distributed and is often accompanied by pleural effusion [15]. Thus, peripheral multifocal airspace opacities with subpleural sparing and lower lung predominance are important imaging clues suggesting organizing pneumonia [5, 15, 20]. Langerhans Cell Histiocytosis Langerhans cell histiocytosis (LCH) represents a spectrum of rare diseases characterized by monoclonal proliferation and infiltration of organs by Langerhans cells [23, 24]. Pulmonary disease, which occurs almost exclusively in smokers, may be isolated to the lung or may be associated with involvement of bone, skin, pituitary gland, liver, lymph nodes, or thyroid [23, 24]. Patients tend to be years old without sex predominance [24] and present with cough, dyspnea, and fatigue [24]. Most stabilize or improve with smoking cessation and corticosteroid therapy. However, lung transplantation may be considered in a subgroup of patients who have progressive disease and severe respiratory impairment [23, 24]. Histologically, this granulomatous disease is characterized by bronchiolocentric nodules that contain Langerhans cells and may cavitate [23, 24]. Over time, the nodules are replaced by fibrous tissue that may cause scarring with cystic airspace enlargement [23 26]. The imaging findings of LCH tend to be more pronounced in the upper lungs [24, 27]. The earliest radiographic manifestation is a micronodular pattern [24, 27]. As the disease progresses, reticulonodular and cystic changes predominate [24, 27]. The typical CT findings include nodules or cysts or both [24 27]. Both well- and illdefined nodules (1 10 mm), many of which undergo cavitation, develop around the peribronchiolar structures and reflect Langerhans cell granulomas [25 27] (Fig. 7A). Cystic lesions (1 3 cm) may result from paracicatricial cystic airspace enlargement and from cavitating nodules [23 26] (Fig. 7B). The rupture of cystic lesions may cause recurrent pneumothoraces [24, 26]. 280 AJR:201, August 2013

4 Noninfectious Inflammatory Lung Disease TABLE 3: Interstitial-Predominant Diseases: Summary of Clinical and Radiologic Findings Disease Key Clinical Features Spectrum of Radiologic Findings Key Radiologic Findings Usual interstitial pneumonia NSIP Sarcoidosis Lymphoid interstitial pneumonia Rapidly progressive dyspnea and cough, no corticosteroid response Progressive dyspnea, cough, response to corticosteroids Young adults, malaise, mild fever, dyspnea Autoimmune disorder or immunodeficiency Note GGOs = ground-glass opacities, NSIP = nonspecific interstitial pneumonia. The differential diagnosis of LCH includes other conditions with micronodules, such as sarcoidosis, silicosis, and tuberculosis [24]. However, LCH typically shows both noncavitating and cavitating nodules and cystic changes and is strongly associated with smoking but lacks an occupational or infectious clinical history [24 27]. Apicobasal gradient with basilar predominance, prominent honeycombing, traction bronchiectasis and architectural distortion, GGOs, volume loss Lower lung subpleural predominance; early cellular NSIP findings are bilateral GGOs, centrilobular nodules, and fine reticulation; early fibrotic NSIP findings are reticulation, traction bronchiectasis, and mild honeycombing; advanced disease findings are architectural distortion, coarse reticulation, and honeycombing Hilar and mediastinal lymphadenopathy with possible calcifications; typical appearance is micronodules with peribronchovascular and interlobular distribution, upper lung predominance; atypical appearance is airspace nodules, GGOs, or consolidations; progressive massive fibrosis is seen in advanced disease GGOs combined with thin-walled perivascular cysts, thickening of bronchovascular bundles and interlobular septa, mild fibrosis Respiratory Bronchiolitis Associated Interstitial Lung Disease and Desquamative Interstitial Pneumonia Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) is strongly associated with cigarette smoking [28 30]. RB- ILD and desquamative interstitial pneumonia (DIP) represent a pathologic continuum, with RB-ILD at the mild end and DIP at the severe end of the spectrum [28 31]. However, DIP has also been reported in nonsmokers secondary to infection or dust exposure [29, 32]. Most patients are middle-aged adults who present with mild dyspnea and cough [29, 30]. The prognosis of RB-ILD is good, with the morphologic changes regressing completely with smoking cessation and corticosteroid therapy [30]. DIP has a less favorable prognosis because of the associated fibrosis [30]. Histologically, RB-ILD is as an accumulation of pigmented macrophages in the respiratory bronchioles [28, 29, 32]. This macrophage accumulation is more severe in DIP and can be combined with mild interstitial fibrosis [28, 29, 31, 32]. Chest radiographs are often normal in RB-ILD [32]. CT shows upper lung predominant centrilobular nodules, which sometimes coalesce into larger groundglass opacities [28, 32] (Fig. 8). Because RB- ILD is a smoking-related disease, bronchial wall thickening and centrilobular emphysema may also be seen [28, 32]. In DIP, the severity and extent of ground-glass opacities increase [28, 33]. Additional reticular opacities and small cysts may indicate mild fibrosis [28, 33] (Fig. 9). The differential diagnosis of RD-ILD and DIP includes other conditions with centrilobular nodules and ground-glass opacities, such as subacute hypersensitivity pneumonitis [6] (Fig. 10). The latter disease, however, is caused by inhalation of organic dusts or chemical antigens and has a more widespread distribution than RB-ILD [6]. The imaging clue to the diagnosis of RB-ILD is upper lung predominance of centrilobular nodules in a heavy smoker [28, 32]. Vascular-Predominant Diseases Noninfectious pulmonary vasculitis is characterized by inflammation of the walls of arteries and veins of any size [2]. It may be idiopathic or secondary to collagen vascular disease, particularly systemic lupus erythematosus, or may be drug induced or associated with smoking crack cocaine [2, 34 36] (Figs. 11 and 12 and Table 2). Complications of pulmonary vasculitis include vascular stenoses, thromboses, and aneurysm formation [2]. Parenchymal sequelae include pulmonary infarction and diffuse alveolar hemorrhage [2, 37]. Prominent honeycombing, basilar predominance Fibrosis with GGOs, architectural distortion, lower lung predominance Lymphadenopathy, peribronchovascular micronodules, upper lung predominance GGOs combined with thin-walled cysts Takayasu Arteritis Takayasu arteritis is a rare large-vessel vasculitis that involves the aorta and its branches and the coronary and pulmonary arteries [2, 38 40]. The disease causes stenosis, occlusion, or aneurysm formation [2, 38 40]. Although the pathophysiology is not fully known, there is certainly an autoimmune component [38, 40]. Most patients are women between 20 and 30 years old [38] who present with malaise, fever, and weight loss and commonly with retinopathy [38, 40]. Pulmonary artery stenosis leads to dyspnea [38], carotid artery stenosis results in strokelike symptoms, subclavian artery stenosis causes limb claudication, and renal artery stenosis leads to arterial hypertension [38, 40]. Corticosteroids induce a remission of disease in 50% of patients, with the other 50% responding well to methotrexate [38]. Nevertheless, surgical or endovascular procedures are often required to treat the consequences of vascular stenoses [38, 40]. Histologically, acute Takayasu arteritis is characterized by inflammation of the vasa vasorum of the adventitia, lymphocytic infiltration of the media, and thickening of the intima [38, 40]. In the chronic stage, fibrosis of all vessel layers can result in luminal narrowing or aneurysm formation [38, 40]. CT angiography is well suited to detect and characterize Takayasu arteritis [2, 39, 41]. In the acute stage, on unenhanced CT images, high attenuation of the aortic or pulmonary artery wall and the adjacent mediastinal fat ( stranding ) indicates active inflammation [2, 39] (Fig. 13). Arterial phase enhanced CT images show circumferential wall thickening due to inflammation [2, 39]. Studies obtained minutes after contrast injection may show delayed arterial wall enhance- AJR:201, August

5 Nemec et al. ment [2, 39]. On MRI, Takayasu arteritis shows thickening and delayed enhancement of the arterial wall [41]. There is increased FDG uptake on PET/CT [41]. Rarefaction of segmental or subsegmental arteries and mosaic perfusion, reflecting regional hypoperfusion, result from vessel stenosis and are well shown by CT [42] (Fig. 13). In the fibrotic stage, CT can show calcifications of all layers of the vessel wall, reflecting the transmural nature of the disease [39]. The differential diagnosis of Takayasu arteritis includes other rare vasculitides, such as Behçet disease, giant cell arteritis, and polyarteritis nodosa [2]. Infectious conditions, such as syphilis, that may cause a vasculitis are also included in the differential diagnosis [2]. Therefore, the diagnosis of Takayasu arteritis involving the aorta and its branches, typically in a young female, is based on a combination of clinical and radiologic findings [2, 39, 41]. Granulomatosis With Polyangiitis Granulomatosis with polyangiitis is an antineutrophil cytoplasmic antibody (ANCA) associated systemic disorder characterized by vasculitis of small and medium-sized vessels [43, 44]. Upper respiratory tract involvement with rhinosinusitis occurs in virtually all patients and may lead to cartilage destruction and saddle nose deformity [44 46]. Lung involvement develops in 60 85% of patients, and glomerulonephritis occurs in up to 70% [44]. The eyes, ears, nervous system, skin, joints, and heart also may be affected [44, 46]. Most patients are middle-aged adults [44, 45] who present with nasal obstruction, stridor, hemoptysis, dyspnea, fever, and chest pain [44 46]. In most patients, cyclophosphamide or methotrexate and glucocorticoids can induce remission, but further maintenance therapy is essential because of high relapse rates [44, 45]. Renal, pulmonary, and cardiac involvement are associated with increased mortality [44]. The major histologic abnormality is a necrotizing granulomatous vasculitis that involves arteries, veins, capillaries, airways, and pleura [43]. Pulmonary nodules and masses occur in up to 70% of patients and are the most common radiographic findings [45, 47]. CT typically shows multiple noncavitating or cavitating nodules or masses that may be up to several centimeters in size and have a random, peribronchovascular, or subpleural distribution [45 48] (Fig. 14A). Nodules and masses indicate active inflammation, whereas cavitation reflects necrosis resulting from ischemia caused by vasculitis [48]. Another common CT finding is a consolidation with groundglass halo, likely reflecting a combination of inflammation, alveolar hemorrhage, and superimposed infection [45 48] (Fig. 14B). On follow-up CT of treated patients, most nodules and ground-glass opacities have disappeared, virtually without scarring [49]. Residual fibrosis usually follows the occurrence of masses and consolidations [49]. In addition to parenchymal changes, inflammation can affect the tracheobronchial tree [45 47]. CT may show circumferential, smooth, or nodular wall thickening of the subglottic trachea resulting in stenosis, bronchial wall thickening, and bronchiectasis [45 47]. In addition, pleural effusions result from pleural inflammation or fluid overload from concurrent renal disease [45]. The differential diagnosis of granulomatosis with polyangiitis includes other cavitating conditions of the lungs, such as upper lung predominant tuberculosis, peripheral lower lung predominant metastasis and septic embolism, and fungal infection that typically occurs in immunocompromised patients [45]. Thus, cavitating lesions with either random or peribronchovascular distribution especially when combined with rhinosinusitis and glomerulonephritis should suggest granulomatosis with polyangiitis [2, 45]. The term Wegener granulomatosis, referring to Dr. Friedrich Wegener, should be abandoned because of his controversial role during the Nazi regime [50]. The alternative name for Wegener s granulomatosis is granulomatosis with polyangiitis [51]. Churg-Strauss Syndrome Churg-Strauss syndrome is an ANCA associated disorder that may affect virtually any organ [52]. It is characterized by eosinophilic tissue infiltration and vasculitis of small or medium-sized vessels [52]. Pulmonary involvement is very common, and asthma is almost invariably present [52, 53]. Interacting immunogenetic mechanisms, cytokines, and chemokines may be causative agents [52]. The role of the antiasthma drug montelukast as a cause of disease is controversial [52]. Most patients present with asthmalike symptoms, allergic sinusitis, fever, and weight loss [52, 53]. Polyneuropathy may be also present [52 54]. Steroid therapy, alone or in combination with immunosuppressive drugs, is associated with a good prognosis in Churg-Strauss syndrome [52, 53]. The asthma component, however, is rarely affected by this therapy [52]. Histologically, eosinophilic infiltrates form granulomas in blood-vessel walls, resulting in necrotizing vasculitis of arterioles, venules, and capillaries [52, 54]. The most common radiographic findings are nonspecific bilateral consolidations and small nodular or diffuse reticular opacities without any obvious zonal predominance [53, 54]. The main CT findings are consolidations or ground-glass opacities that are randomly or peripherally distributed and likely represent eosinophilic alveolar infiltration and diffuse alveolar hemorrhage [17, 53, 54] (Fig. 15). Other manifestations are centrilobular nodules, reflecting eosinophilic accumulation, and bronchial wall thickening caused by eosinophilic infiltration of the airways [17, 53, 54]. The differential diagnosis of Churg-Strauss syndrome includes other eosinophilic conditions, such as chronic eosinophilic pneumonia [2]. However, unlike the peripheral upper lobe predominance of the consolidations in chronic eosinophilic pneumonia, the distribution of consolidations in Churg-Strauss syndrome is random and without any zonal predominance [17, 53, 54]. Microscopic Polyangiitis Microscopic polyangiitis is an ANCA-associated systemic inflammation of small vessels that lacks a granulomatous component and eosinophilia [2, 55]. Its pathogenesis is based on an interaction of environmental and genetic factors [55]. Microscopic polyangiitis is the most common cause of the pulmonaryrenal syndrome, which is characterized by combined glomerulonephritis and diffuse alveolar hemorrhage [55]. However, it may also involve the nervous system, skin, musculoskeletal system, heart, eyes, and intestines [55, 56]. Patients are usually older than 50 years [55] and present with a prodromal phase of fever and weight loss that is followed by rapidly progressive glomerulonephritis [55, 56]. Patients with pulmonary hemorrhage may have hemoptysis [37, 55]. Although a remission often can be achieved with cyclophosphamide and glucocorticoids, the overall prognosis is variable, with relapse and end-stage renal failure as frequent complications [55, 56]. On histology, necrotizing vasculitis most often affects venules, arterioles, and capillaries [37]. Pulmonary capillaritis manifests as interstitial neutrophilic infiltration and causes necrosis of the alveolar and capillary walls, which results in diffuse alveolar hemorrhage [37]. Chest radiographs show patchy, bilateral airspace opacities predominantly in the perihilar areas [2, 35]. The most common CT features are bilateral perihilar ground-glass 282 AJR:201, August 2013

6 Noninfectious Inflammatory Lung Disease opacities and consolidations that reflect diffuse alveolar hemorrhage [2, 35]. A groundglass halo around the consolidations indicates their hemorrhagic nature [35, 57]. The combination of interlobular septal thickening and ground-glass opacities (crazy-paving appearance) indicates interstitial and airspace involvement by capillaritis and hemorrhage [35, 58]. Pleural effusions likely result from accompanying renal failure [35]. The differential diagnosis of microscopic polyangiitis includes other conditions associated with the pulmonary-renal syndrome [2]. These conditions include Goodpasture syndrome and systemic lupus erythematosus, both of which may be associated with alveolar hemorrhage and thus resemble the imaging appearance of microscopic polyangiitis [2] (Fig. 16). Therefore, the diagnosis of microscopic polyangiitis is not based on imaging alone but must incorporate clinical and laboratory parameters [2, 55]. Behçet Disease Behçet disease is a systemic vasculitis affecting vessels of any size that usually occurs in young men of Mediterranean, Middle East, or Far East descent [2, 59]. Immune-mediated mechanisms and inflammatory mediators, as well as genetic factors and infectious agents, may play a causative role [59]. The typical clinical findings are oral and genital ulcers and uveitis [59]. Venous thrombotic disease is a predominant feature, whereas arterial involvement is substantially less frequent [59, 60]. Pulmonary involvement, occurring in up to 18% of cases, typically causes pulmonary artery aneurysms that may result in pulmonary infarction or hemorrhage [61]. Patients present with dyspnea, chest pain, cough, and hemoptysis [61]. Although aneurysms may decrease in size or may even disappear after cyclophosphamide and methylprednisolone therapy, rupture remains a major cause of mortality [60, 62]. Histologically, vasculitis shows inflammation of the vasa vasorum of the tunica media that causes destruction of the elastic fibers [59], which may result in a pseudoaneurysm with mural thrombus formation [59]. On chest radiographs, pulmonary artery aneurysms may manifest as hilar enlargement or nodular opacities [63, 64]. CT angiography typically shows multiple fusiform or saccular pseudoaneurysms of the main or lower lobe pulmonary arteries [64 66]. Complications include aneurysm rupture with hemorrhage, resulting in groundglass opacities and consolidations, and thrombotic occlusion of pulmonary vessels causing either subpleural infarctions or mosaic perfusion [64 66]. Pleural effusions occur secondary to pulmonary infarction or vasculitis of the pleura [66]. At times, CT may show ulcerative changes of the proximal airways [66]. Finally, Behçet disease is a rare cause of fibrosing mediastinitis, which is characterized by diffuse soft-tissue encasement of vascular and airway structures [66]. The differential diagnosis of Behçet disease includes other conditions resulting in pulmonary artery aneurysms, such as iatrogenic trauma, infection, congenital heart disease, neoplasms, and connective tissue disease [63]. However, the combination of pulmonary artery aneurysms, ulcers, and venous thrombotic disease in a man of appropriate geographic descent indicates Behçet disease [59]. Pulmonary artery aneurysms and venous thrombotic disease occurring without ulcers is known as Hughes-Stovin syndrome (incomplete Behçet disease) [67]. Acute Interstitial Pneumonia AIP is a fulminant permeability edema with diffuse alveolar damage [1, 68]. It may be idiopathic or secondary [1]. AIP is the morphologic reflection of the clinical entity known as acute respiratory distress syndrome (ARDS) [1]. AIP may be caused by exposure to chemical agents or infectious pathogens or by systemic diseases such as sepsis [69], can occur in patients of any age, and has no sex predilection [1, 70]. Patients rapidly develop respiratory failure requiring mechanical ventilatory assistance, which itself may cause pulmonary damage [71]. The mortality rate of AIP of 15 70% is substantially influenced by coexisting medical conditions such as sepsis [72, 73]. Histologically, AIP shows permeability edema with diffuse alveolar damage that occurs in three partly overlapping stages exudative, proliferative, and fibrotic [1, 68, 74]. In the exudative stage, the rapid spread of interstitial edema to the alveoli is associated with hemorrhage and hyaline membrane formation [1, 68]. In the proliferative stage, there is organization of the fibrinous exudate, whereas scarring and cysts develop in the fibrotic stage [1, 68]. If the patient survives, the changes may progress to honeycomb fibrosis [1, 68]. On chest radiographs, the earliest changes (within the first hours) of AIP are usually not detected. Subsequently, there are bilateral coalescent airspace opacities with sparing of the costophrenic angles and no or only minimal pleural effusion [69] (Fig. 17A). As the disease progresses, extensive consolidations with central air bronchograms develop, particularly in the lower lung, an appearance commonly termed white lung [69] (Fig. 18). Cardiomegaly, vessel enlargement, and pleural effusions are typically absent [69]. Because of its higher sensitivity, CT usually shows symmetric, bilateral ground-glass opacities with sparing of the costophrenic angles in the early exudative phase of disease [70, 74]. As the disease progresses, the distribution of consolidations follows a gravitational gradient and increases in severity from the ventral to the dorsal lung areas with the patient in the supine position [70, 74] (Fig. 17B); with the patient in the prone position, this gradient can be reversed [75]. The change from supine to prone position in patients with ARDS is sometimes used to reventilate previously atelectatic areas of dorsal lung [75]. The consolidations may reflect alveolar exudate in the exudative phase, granulation tissue during the proliferative phase, or fibrosis in the fibrotic phase [1, 74]. In the late fibrotic phase, CT shows cysts and traction bronchiectasis as well as consolidations that tend to be replaced by ground-glass opacities [70, 74]. Subsequently, CT may show progression of fibrotic changes to honeycombing and architectural distortion, notably in the nondependent lung [76]. This distribution may be explained by a protective effect of atelectasis on the dependent lung during the acute phase, which attenuates injury caused by mechanical ventilation [76]. The differential diagnosis of AIP includes other diseases with ground-glass opacities and consolidations. These entities include lower lung predominant hydrostatic edema, randomly distributed acute eosinophilic pneumonia, and infectious pneumonia that is often limited to a single lobe [1, 69]. Thus, in a patient with fulminant respiratory failure, airspace opacities, predominantly in the dependent lungs strongly suggest AIP as the diagnosis [69, 70, 74]. Interstitial-Predominant Diseases Noninfectious inflammatory interstitial diseases comprise a heterogeneous group of chronic conditions that are characterized by varying patterns of inflammation and interstitial fibrosis [1, 77] (Table 3). They may affect all interstitial spaces peripheral, peribronchovascular, intralobular and then proceed to involve the vessels and airspaces [1, 78]. Interstitial disease may be idiopathic or secondary to collagen vascular disease or a drug-related condition [1, 77]. Consequently, establishing the diagnosis of an AJR:201, August

7 Nemec et al. idiopathic disease requires that potential underlying causes be clinically excluded [1]. Silicosis, although an interstitial inflammatory condition, has a distinct occupational background and therefore will not be covered in detail. Usual Interstitial Pneumonia Usual interstitial pneumonia (UIP), a fibrotic disease characterized by scattered fibroblastic foci, is the morphologic reflection of the clinical entity known as idiopathic pulmonary fibrosis [1, 79]. UIP may also occur secondary to systemic sclerosis, rheumatoid arthritis, Sjögren syndrome, or drug toxicity [1, 34, 79, 80]. Patients are typically older than 60 years and present with rapidly progressive dyspnea and cough [79]. In the absence of any current effective treatment, lung transplantation may be the only therapeutic option [79]. The median survival is years in cases of idiopathic UIP, but can be longer in secondary disease [79, 80]. In the past, UIP was conceptually associated with inflammation [79]. More recent concepts suggest that alveolar microinjuries cause fibroblast activation, which leads to exaggerated extracellular matrix formation and eventually results in fibrotic lung destruction [79]. The major histologic features are peripheral fibrosis with honeycombing, architectural destruction, and scattered fibroblastic foci [1, 79, 81]. There is heterogeneous lung involvement, with frequent changes between normal and diseased lung [1, 81]. Chest radiographs may appear normal initially [82]. In advanced disease, there are low lung volumes with subpleural reticular opacities that increase from the lung apices to the bases [82]. CT confirms this apicobasal gradient and shows subpleural reticular opacities with extensive honeycombing, traction bronchiectasis, and architectural distortion [81 84] (Fig. 19). Ground-glass opacities may reflect the inflammatory component or represent microscopic fibrosis [81] (Fig. 19). The differential diagnosis of UIP includes other fibrotic diseases, such as chronic hypersensitivity pneumonitis, asbestosis, and nonspecific interstitial pneumonia (NSIP) [85]. Unlike UIP, chronic hypersensitivity pneumonitis has an upper lung predominance; asbestosis is commonly associated with pleural plaques [85]. NSIP predominantly shows ground-glass opacities, whereas basilar honeycombing is the major feature in UIP [83 85]. Nonspecific Interstitial Pneumonia NSIP has a distinct histologic fibrotic pattern and can be classified into cellular (inflammatory) and fibrotic subtypes [1, 86 88]. NSIP may be idiopathic or secondary to connective tissue diseases (systemic sclerosis, rheumatoid arthritis) or drug exposure (bleomycin, methotrexate) [34, 89]. Patients are often middle-aged adults who present with worsening dyspnea, fatigue, and weight loss [1, 86]. The clinical presentation is milder and of longer duration than in UIP [1, 86]. Most patients with NSIP stabilize when treated with a combination of corticosteroids and cytotoxic drugs, and the 5-year survival rate is approximately 80% [1, 86, 88]. Furthermore, cellular NSIP has a better prognosis than the fibrotic subtype of the disease [90]. On histology, NSIP is a spatially and temporally uniform process [1, 87]. Cellular NSIP has prominent alveolar wall inflammation, which can be differentiated from the interstitial fibrosis seen in the fibrotic subtype [1, 87, 88]. Mixed patterns of cellular and fibrotic NSIP may also occur [1, 87]. In early NSIP, chest radiographs may appear normal. As the disease progresses, bilateral nonspecific hazy opacities are the most frequent finding [87, 91] and the lung volume decreases [86, 88]. In early cellular NSIP, CT typically shows bilateral symmetric ground-glass opacities, centrilobular nodules, and mild reticulation, all of which have a subpleural predominance [83, 91, 92] (Fig. 20). These findings most prominently affect the lower lung, although the apicobasal gradient is less pronounced than in UIP [1, 86, 91, 92] (Fig. 20B). In early fibrotic NSIP, CT shows traction bronchiectasis, fine reticular opacities, and mild honeycombing [89] (Fig. 21). In advanced disease, both subtypes of NSIP may progress to more widespread fibrotic lung destruction with architectural distortion, coarse reticulation, and honeycombing [93]. The differential diagnosis of NSIP includes other fibrotic conditions [1, 86]. UIP can be differentiated from fibrotic NSIP by its characteristic basilar honeycombing [84]. The ground-glass opacities of DIP and hypersensitivity pneumonitis have an upper lung predominance [28, 85]. Thus, a fibrotic disease that primarily affects the lower lungs with ground-glass opacities and architectural distortion, but no prominent honeycombing, should suggest NSIP [83, 89, 91, 92]. Sarcoidosis Sarcoidosis is a systemic, noninfectious granulomatous disorder [94, 95]. An association with genetic and immunologic factors, as well an environmental agents, has been suggested [94]. The thorax, eyes, and skin are most commonly involved [94, 95]. Most patients are years old and present with malaise, weakness, mild dyspnea, cough, or fever [94 96]. Pulmonary sarcoidosis has a good prognosis, with spontaneous remission in approximately one third of patients and remission under corticosteroid treatment in another third [95]. In up to 30%, however, the disease progresses despite treatment [95]. The key histologic abnormality in sarcoidosis is noncaseating granulomas, which are collections of macrophages and epithelioid cells encircled by lymphocytes [94 96]. These granulomas are found in thoracic lymph nodes and in all interstitial spaces (peripheral, peribronchovascular, interlobular) [78, 95]. On chest radiographs, sarcoidosis manifests as bilateral hilar and mediastinal lymphadenopathy and reticulonodular opacities with an upper lung predominance [95 97] (Fig. 22). On the basis of radiographic findings, sarcoidosis has been classified into the following five stages [95]: stage 0, normal chest radiograph in histologically confirmed disease; stage I, bilateral hilar lymphadenopathy; stage II, lymphadenopathy and pulmonary opacities; stage III, pulmonary opacities only; and stage IV, pulmonary fibrosis. However, these stages do not necessarily reflect consecutive phases of disease and have limited prognostic value [95]. CT is more sensitive in detecting hilar and mediastinal lymphadenopathy than radiography. CT also may show amorphous, punctuate, or eggshell calcification, which may develop later in the course of disease [96]. In addition, CT is highly sensitive for visualizing the typical interstitial disease of sarcoidosis, which appears as small nodules (1 5 mm) in a peribronchovascular distribution [96, 98, 99] (Fig. 23A). Nodules in the interlobular septa can result in the beaded septum sign [78] (Fig. 23B). In advanced disease, coalescent nodules may form masses causing progressive massive fibrosis with architectural distortion and honeycombing [98, 100]. Sarcoidosis also has a spectrum of atypical CT manifestations including ground-glass opacities, an alveolar pattern of airspace nodules, consolidations, cysts, and cavitations [96] (Fig. 23C). At times, large nodules may be surrounded by tiny satellite nodules, an appearance known as the sarcoid galaxy sign [96] (Fig. 23D). Finally, CT may show nodular bronchiolar wall thickening and bronchomalacia with mosaic attenuation, indicating granulomatous airway involvement [96, 101]. 284 AJR:201, August 2013

8 Noninfectious Inflammatory Lung Disease The differential diagnosis of sarcoidosis includes other micronodular diseases such as silicosis, berylliosis, military tuberculosis, and LCH [96]. However, silicosis and berylliosis are associated with a distinct occupational history. Miliary tuberculosis is a severe infectious disease that frequently occurs in immunocompromised patients. Unlike sarcoidosis, LCH typically shows cavitating nodules and cystic changes and is associated with a smoking history [24]. Thus, upper lung predominant interstitial micronodules combined with lymphadenopathy in a patient with no clinical history characteristic of another condition in this category are suggestive of sarcoidosis [96, 98, 99]. Lymphoid Interstitial Pneumonia Lymphoid interstitial pneumonia (LIP) is a rare inflammatory pulmonary reaction that is secondary to autoimmune disorders, particularly Sjögren syndrome, and to immunodeficiency [1, 102, 103]. Idiopathic LIP is exceedingly rare [1, 102]. Patients with LIP present with slowly progressive dyspnea, cough, and fever [102]. Corticosteroid therapy often results in clinical improvement, although the course of LIP may vary from resolution without treatment to respiratory failure despite treatment [102]. LIP is characterized histologically by lymphoid cell infiltration that expands the interlobular and alveolar septa [102, 104, 105]. Peribronchiolar lymphoid follicles, alveolar accumulation of inflammatory cells, and cystic lesions are also seen; fibrosis may occur in advanced disease [102, 104, 105]. Chest radiographs show nonspecific bilateral reticular, reticulonodular, or alveolar opacities that may be distributed diffusely or have a lower lung predominance [103]. The major CT finding is a combination of ground-glass opacities and cystic lesions [104, 105] (Fig. 24). Ground-glass opacities likely reflect lymphoid cell accumulation, whereas thin-walled perivascular cysts may result from postobstructive bronchiolar ectasia caused by peribronchiolar lymphocytic infiltrates [104, 105]. Additional CT findings are thickening of bronchovascular bundles and interlobular septa, which are likely caused by perilymphatic interstitial infiltration [104]. Bronchiectasis, architectural distortion, and mild honeycombing can be seen with coexisting fibrosis [104]. Lymphadenopathy is common [104]. The differential diagnosis of LIP includes diseases characterized by either ground-glass opacities (NSIP) or multiple cystic lesions (LCH, lymphangioleiomyomatosis). However, none of these diseases presents with the unique combination of ground-glass opacities and cysts that is characteristic of LIP [104, 105]. 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11 Nemec et al. Noninfectious Inflammatory Lung Diseases Fig. 1 Noninfectious inflammatory lung diseases represent a spectrum of idiopathic and secondary conditions that may involve the airspaces, vasculature, or interstitium. ANCA = antineutrophil cytoplasmic antibody, RB-ILD = respiratory bronchiolitis associated interstitial lung disease. Airspace predominant Vascular predominant Interstitial predominant Eosinophilic pneumonia Acute Chronic Organizing pneumonia Langerhans cell histiocytosis RB ILD and desquamative interstitial pneumonia Hypersensitivity pneumonitis Acute Chronic Takayasu arteritis ANCA associated vasculitis Granulomatosis with polyangiitis Churg Strauss syndrome Microscopic polyangiitis Behçet disease Acute interstitial pneumonia Vasculitis associated with collagen vascular diseases Drug induced vasculitis Fig. 2 Acute eosinophilic pneumonia in 85-year-old man with acute respiratory failure and high percentage of eosinophils on bronchoalveolar lavage. Transverse CT image of chest shows bilateral ground-glass opacities (open arrows) and consolidations (white arrow) in upper lung and pleural effusions (black arrows). Fibrotic disease Usual interstitial pneumonia Nonspecific interstitial pneumonia Sarcoidosis Lymphoid interstitial pneumonia Pneumoconiosis Silicosis Berylliosis A Fig. 3 Chronic eosinophilic pneumonia in 85-year-old woman with asthmatic complaint and high percentage of eosinophils on bronchoalveolar lavage. Transverse CT image of chest shows peripheral subpleural bandlike airspace opacities (arrows) in upper lung. B Fig. 4 Cryptogenic organizing pneumonia. A, 60-year-old man who presented with cough and mild dyspnea over weeks. Transverse CT image of chest shows bilateral peripheral consolidations (arrows) with air bronchograms in lower lobes that partially spare subpleural regions. B, 70-year-old man who presented with cough and mild dyspnea over weeks. Transverse CT image of chest shows multifocal peripheral consolidations (solid arrows) in lower lung that partially spare subpleural regions (open arrow) and are more prominent on right. 288 AJR:201, August 2013

12 Noninfectious Inflammatory Lung Disease Fig. 5 Reversed-halo sign ( atoll sign) in cryptogenic organizing pneumonia. Coronal CT image of 36-year-old woman who presented with cough shows several round areas of ground-glass attenuation surrounded by denser opacity (arrows) in lower lung. A Fig. 6 Cryptogenic organizing pneumonia in 64-year-old man with chronic cough. A, Transverse CT image of chest shows isolated spiculated mass (arrow) with pleural contact in right upper lobe. B, Transverse PET/CT image of chest shows avid tracer accumulation in mass (arrow) reflecting its inflammatory activity. Biopsy ruled out malignancy and confirmed organizing pneumonia. A Fig. 7 Spectrum of appearances of Langerhans cell histiocytosis in different patients. A, 55-year-old female smoker with moderate dyspnea. Transverse CT image of chest shows multiple ill-defined peribronchiolar nodules (white arrows) and cystic lesions (black arrow) in upper lobes. B, 67-year-old male smoker with severe dyspnea. Transverse CT image of chest shows diffuse innumerable microcystic changes that have caused destruction of normal parenchyma but virtually no nodules. B B Fig. 8 Respiratory bronchiolitis associated interstitial lung disease in 60-year-old male heavy smoker with chronic cough. Transverse CT image of chest shows slight ground-glass opacities as well as fine centrilobular nodules (thin arrows) and bronchial wall thickening (thick arrow) in left upper lobe. AJR:201, August

13 Nemec et al. Fig. 9 Desquamative interstitial pneumonia in 51-year-old female heavy smoker with chronic cough. Transverse CT image of chest shows bilateral diffuse groundglass opacities as well as subpleural fibrotic changes (solid arrows) and traction bronchiectasis (open arrow) with bronchial wall irregularities. Fig. 11 Vasculitis with diffuse alveolar hemorrhage secondary to collagen vascular disease in 27-year-old man with hemoptysis. Transverse CT image of chest shows multifocal airspace opacities (arrows) with bilateral perivascular distribution, without consolidations or pleural effusions. Fig. 10 Hypersensitivity pneumonitis (subacute stage) due to recurrent dust exposure in 40-year-old woman with mild dyspnea. Transverse CT image of chest shows diffuse bilateral ground-glass opacities that cause geographic pattern of mosaic attenuation in upper lung but no consolidation or distinct fibrosis. Fig. 12 Vasculitis with diffuse alveolar hemorrhage secondary to crack cocaine smoking in 52-year-old man with dyspnea and hemoptysis. Transverse CT image of chest shows combination of bilateral airspace opacities and interstitial changes. Fig. 13 Takayasu arteritis in 25-year-old woman with malaise and fever. Transverse CT image of chest shows vessel thickening of wall of descending aorta (black arrow) as well as mural changes and lumen narrowing of segmental left upper lobe pulmonary artery (white arrow). 290 AJR:201, August 2013

14 Noninfectious Inflammatory Lung Disease Fig. 15 Churg-Strauss syndrome in 56-year-old woman with asthmatic symptoms, sinusitis, and fever. Transverse CT image of chest shows faint bilateral airspace opacities with random distribution (arrows). A Fig. 14 Granulomatosis with polyangiitis. A, 59-year-old woman with cough, rhinosinusitis, and glomerulonephritis. Transverse CT image of chest shows multiple ill-defined nodular lesions (arrows), some of which are situated adjacent to pulmonary vessels. B, 26-year-old man with hemoptysis. Transverse CT image of chest shows bilateral consolidations (arrows), some with ground-glass halo, along segmental pulmonary arteries. A Fig. 16 Goodpasture syndrome in 18-year-old man with dyspnea and glomerulonephritis. Transverse CT image of chest shows diffuse bilateral airspace nodules indicating diffuse alveolar hemorrhage but no consolidations or pleural effusions. B Fig. 17 Idiopathic acute interstitial pneumonia in 50-year-old woman with acute respiratory distress. A, Anteroposterior chest radiograph shows diffuse bilateral airspace opacities with sparing of lung bases. Note normal size of heart and absence of pleural effusions. B, Transverse CT image of chest obtained 5 days after A shows severe bilateral ground-glass opacities and consolidations predominantly located in dependent lung. B AJR:201, August

15 Nemec et al. Fig. 18 Acute interstitial pneumonia secondary to sepsis in 50-year-old woman with acute respiratory distress. Anteroposterior chest radiograph shows bilateral extensive airspace opacities with air bronchograms (white arrows) that predominantly involve lower lungs ( white lung appearance) (black arrows). A Fig. 19 Idiopathic usual interstitial pneumonia in 79-year-old man with progressively severe dyspnea over 12 months. A, Transverse CT image of chest shows subpleural reticular changes with prominent honeycombing (arrows) and ground-glass opacities at lung base. B, Coronal CT image of chest shows obvious apicobasilar gradient of fibrotic changes (arrows), which primarily involve lower lung. A Fig. 20 Cellular subtype of nonspecific interstitial pneumonia in 77-year-old man with progressive, moderate dyspnea over months. A and B, Transverse (A) and coronal (B) CT images of chest show lower lung predominant subpleural ground-glass attenuation with very fine reticular opacities (arrows) but no consolidation or honeycombing. B B 292 AJR:201, August 2013

16 Noninfectious Inflammatory Lung Disease Fig. 21 Fibrotic subtype of nonspecific interstitial pneumonia in 65-year-old woman with progressive dyspnea. Transverse CT image of chest shows bilateral diffuse ground-glass opacities and subpleural reticular opacities with traction bronchiectasis (arrows) in lower lung. A Fig. 22 Sarcoidosis in 25-year-old man with malaise and fever over several weeks. Posteroanterior chest radiograph shows bilateral hilar enlargement (arrows) due to lymphadenopathy but virtually no abnormality in lung parenchyma. Fig. 23 Sarcoidosis. Spectrum of pulmonary findings are shown in different patients, all of whom presented with mild dyspnea, malaise, and slight fever. A, 45-year-old man. Transverse CT image of chest shows innumerable micronodules with peribronchovascular distribution. B, 35-year-old woman. Transverse CT image of chest shows micronodules along interlobular septa (beaded septum sign) (arrows). (Fig. 23 continues on next page) B AJR:201, August

17 Nemec et al. Fig. 23 (continued) Sarcoidosis. Spectrum of pulmonary findings are shown in different patients, all of whom presented with mild dyspnea, malaise, and slight fever. C, 60-year-old woman. Transverse CT image of chest shows bilateral large masslike consolidations (arrows) but no micronodules. D, 40-year-old man. Transverse CT image of chest shows coalescence of small nodules resembling galaxy of stars ( galaxy sign) (arrows). FOR YOUR INFORMATION Fig. 24 Lymphocytic interstitial pneumonia secondary to Sjögren syndrome in 44-year-old woman with mild dyspnea. Transverse CT image of chest shows diffuse ground-glass opacities and multiple small perivascular cysts (arrows) in both lungs. This article is available for CME/SAM credit. To access the exam for this article, follow the prompts associated with the online version of the article. C D 294 AJR:201, August 2013