Pipavath et al.

Radiologic and Pathologic Features of Bronchiolitis

C h e s t I m a g i n g Pe r s p e c t i v e

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Radiologic and Pathologic Features of Bronchiolitis

Sudhakar J. Pipavath1,2 David A. Lynch3 Carlyne Cool3 Kevin K. Brown4 John D. Newell4
Pipavath SJ, Lynch DA, Cool C, Brown KK, Newell JD OBJECTIVE. The purpose of this article is to describe and illustrate the clinical, pathologic, and imaging features of the inflammatory and fibrotic forms of bronchiolitis. The CT features presented in this article represent the typical features associated with each entity. CONCLUSION. Direct signs of bronchiolitis include centrilobular nodules and tree-in-bud pattern. Indirect signs include mosaic attenuation and air trapping. Although classic examples of each entity exist, there can be substantial overlap in the appearances, and distinguishing among these entities is not always possible. When high-resolution CT features overlap, clinical details will usually help to narrow the differential diagnosis. nderstanding the imaging features of small airways diseases requires an appreciation of the histopathologic findings of these disorders. The purpose of this article is to describe and illustrate the clinical, pathologic, and imaging features of inflammatory and fibrotic forms of bronchiolitis (Table 1).

Received September 10, 2004; accepted after revision December 17, 2004.
1Department

of Radiology, University of Washington,

Seattle, WA.
2Present address: Teleradiology Solutions, Bangalore,

KA, India.
3Department

of Radiology, University of Colorado Health Sciences Center, 4200 E Ninth Ave., Box A030, Denver, CO 80262. Address correspondence to D. A. Lynch (david.lynch@uchsc.edu).

4National Jewish Medical and Research Center,

Denver, CO. AJR 2005; 185:354363 0361803X/05/1852354 American Roentgen Ray Society

CT Signs of Small Airways Disease Direct Signs Bronchioles are usually not directly visible on CT. However, when there is increased soft tissue in or around the bronchioles, they can become visible at the center of the secondary pulmonary lobule [1]. Thickening of the bronchiolar wall by inflammatory cells results in centrilobular nodules and V- or Y-shaped branching linear opacities that represent the tree-in-bud pattern [2] (Fig. 1). Inflammatory cellular infiltration in the peribronchiolar alveoli, typically seen in respiratory bronchiolitis or hypersensitivity pneumonitis, results in poorly defined centrilobular nodules that often have an attenuation less than that of soft tissue (Fig. 2). Bronchiolectasis is a less common direct sign of bronchiolitis and is found most commonly in chronic forms of bronchiolitis. The dilated bronchioles are identifiable close to the pleural surface (Fig. 3). Indirect Signs Air trapping is an indirect sign of obstructive small airways disease and may be iden-

tified by the presence of mosaic attenuation on inspiratory CT that is accentuated with expiratory imaging (Fig. 4). Air trapping is easily detected when focal because it produces mosaic attenuation, but it may be difficult to detect when it is diffuse. Because air trapping often becomes apparent only on expiratory imaging, this technique is an essential part of the CT evaluation for bronchiolitis [3]. In patients with bronchiolitis obliterans, the extent of air trapping on expiratory CT provides the best correlation with indexes of physiologic impairment [4]. Interpretation of expiratory CT is complicated by the knowledge that the prevalence of air trapping in healthy individuals is substantial. In a study by Mastora et al. [5], isolated lobules of air trapping were found in 31 (53%) of 59 nonsmoking healthy subjects, whereas larger (segmental or lobar) areas of air trapping were found in five (8%). A more recent study by Tanaka et al. [6] indicates that extensive air trapping may be found in a minority of healthy subjects. These articles suggest that the CT finding of air trapping may sometimes be normal and should be ignored in the absence of physiologic evidence of airway obstruction. Inflammatory Bronchiolitis Infectious Bronchiolitis Infectious bronchiolitis is characterized histologically by a pattern of acute bronchiolar injury, with epithelial necrosis and inflammation of the bronchiolar walls and intraluminal

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Radiologic and Pathologic Features of Bronchiolitis TABLE 1: CT Classification of Bronchiolitis

Type of Bronchiolitis Inflammatory Infectious Acute or chronic infection (viral, Mycoplasma organisms, mycobacterial) Infiltration of bronchiolar wall Centrilobular nodules, tree-in- Hypersensitivity pneumonitis with inflammatory cells bud pattern Bronchiolar and peribronchiolar lymphoplasmacytic infiltration Accumulation of pigmented macrophages in and around respiratory bronchioles Poorly defined centrilobular Respiratory bronchiolitis nodules, mosaic attenuation, ground-glass attenuation Centrilobular nodules, ground-glass opacity Hypersensitivity pneumonitis Cause or Associated Condition Histologic Features CT Features Imaging Differential Diagnosis

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Hypersensitivity pneumonitis Organic or inorganic inhaled agents

Respiratory bronchiolitis

Cigarette smoking

Follicular and lymphocytic

Sjgrens syndrome, rheumatoid arthritis, immunodeficiency Idiopathic

Lymphoid cell accumulation in Tree-in-bud pattern, nodules, and around bronchioles cysts Transmural infiltration of bronchiolar wall by inflammatory cells Inflammatory or fibrotic bronchiolitis (or both) Tree-in-bud pattern, bronchiolectasis, bronchiectasis Tree-in-bud pattern, air trapping, bronchiolectasis Mosaic attenuation, bronchiectasis, air trapping on expiratory CT

Cellular bronchiolitis, panbronchiolitis Cellular bronchiolitis, follicular bronchiolitis, other causes of bronchiectasis Other causes of bronchiolitis

Panbronchiolitis

Bronchiectasis Fibrotic Constrictive

Cystic fibrosis, previous infection

Narrowing or obliteration of Postinfectious, toxic fumes, transplantation, cryptogenic, bronchiolar lumen by progressive fibrosis collagen vascular diseases, drugs

Asthma, panlobular, emphysema, neuroendocrine hyperplasia

Fig. 135-year-old man with cellular bronchiolitis secondary to Mycoplasma infection. Highresolution CT image through left mid lung shows multiple poorly defined centrilobular nodules, many of which connect to branching linear structures (arrows), tree-in-bud pattern.

Fig. 257-year-old cigarette smoker with respiratory bronchiolitis. High-resolution CT image shows diffuse fine poorly defined centrilobular nodules (arrows) with more patchy ground-glass opacity posteriorly.

exudates [1] (Fig. 5). Lymphoplasmacytic bronchiolar wall infiltrates with neutrophil-rich intraluminal exudates are seen. Edema and fibrosis also may be present in the bronchiolar walls. Extensive injury to the respiratory mucosa, causing loss of cilia and ciliated cells, can be observed in the ultrastructure. Acute infections caused by viruses or Mycoplasma organisms are associated with this

type of bronchiolitis. In children, infectious bronchiolitis is clinically more severe than in adults; most cases are secondary to viral infection, most commonly a respiratory syncytial virus [7]. In adults, cellular bronchiolitis is less common and may be secondary to either a viral or a bacterial infection [811] (Fig. 1). More chronic infections, particularly tuberculosis [12] and atypical mycobacterial

infection [13], also show evidence of cellular bronchiolitis (Fig. 6). In the immunocompromised patient, infection with Aspergillus fumigatus may produce this appearance. On high-resolution CT of the chest in patients with infectious cellular bronchiolitis, the intense bronchiolar mural inflammation of cellular bronchiolitis results in centrilobular nodules that are usually associated with

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Pipavath et al. ground-glass attenuation rather than soft-tissue attenuation (Fig. 8). The tree-in-bud pattern is uncommon, but areas of mosaic attenuation due to air trapping are frequent [14, 15]. Respiratory Bronchiolitis and Respiratory BronchiolitisAssociated Interstitial Lung Disease Respiratory bronchiolitis and respiratory bronchiolitisassociated interstitial lung disease are characterized by occurrence in patients who smoke and, more rarely, in those with collagen vascular diseases and mineral dustinduced diseases. On histology, submucosal inflammation and fibrosis of the respiratory bronchioles consisting of fibrotic mural thickening and mononuclear cell infiltration are noted. Pigmented macrophages are present in the bronchiolar lumen; alveolar ducts; and, to a lesser extent, the alveolar spaces (Fig. 9). On high-resolution CT of patients with respiratory bronchiolitis, ill-defined centrilobular nodules, similar to those seen in hypersensitivity pneumonitis, are seen (Fig. 2). Small patches of ground-glass opacity may also be present. These abnormalities may predominate in the upper lobes. Although most patients with respiratory bronchiolitis are asymptomatic, some may have an extensive enough abnormality to cause severe symptoms and impairment of lung function and gas exchange: These cases are diagnosed as respiratory bronchiolitisassociated interstitial lung disease. In these individuals, patchy areas of ground-glass opacity and air trapping are usually present (Fig. 10). Although respiratory bronchiolitis and respiratory bronchiolitisassociated interstitial lung disease share some histologic features, respiratory bronchiolitisassociated interstitial lung disease is classified as an idiopathic interstitial pneumonia. If a patient with respiratory bronchiolitisassociated interstitial lung disease stops smoking, lung abnormalities may stop progressing or may begin to regress [16]. If patients continue to smoke, emphysema may develop in the areas of respiratory bronchiolitis [17]. The imaging differential diagnosis of respiratory bronchiolitis and respiratory bronchiolitisassociated interstitial lung disease includes desquamative interstitial pneumonia, nonspecific interstitial pneumonia, and hypersensitivity pneumonitis. Respiratory bronchiolitisassociated interstitial lung disease differs from desquamative interstitial pneumonia in that the ground-glass opacity of respiratory bronchiolitisassociated interstitial lung disease is patchier and poorly defined. Centrilobular nodules are less common in desquamative interstitial pneumonia. There is probably a continuum of smoking-related lung diseases from respiratory bronchiolitis to respiratory bronchiolitisassociated interstitial lung disease to desquamative interstitial pneumonia [18]. Nonspecific interstitial pneumonia differs from respiratory bronchiolitisassociated interstitial lung disease in that the ground-glass opacity is usually more diffuse and is commonly associated with a reticular abnormality. Similarly, the centrilobular nodules and ground-glass opacity found in patients with hypersensitivity pneumonitis are usually more diffuse than those seen in cases of respiratory bronchiolitis. In addition, most

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Fig. 350-year-old American woman of Asian origin with panbronchiolitis. High-resolution CT image of chest shows centrilobular nodules with tree-in-bud pattern (arrowheads), bronchiolectasis (arrow), and cylindric bronchiectasis.

the tree-in-bud pattern (Fig. 1). Consolidation or ground-glass attenuation may also be present [9]. Hypersensitivity Pneumonitis Although cellular bronchiolitis is a common manifestation of hypersensitivity pneumonitis [1] (Fig. 7), the centrilobular nodules of hypersensitivity pneumonitis differ from those of infectious cellular bronchiolitis in that they are usually diffuse, poorly defined, and of

A
Fig. 430-year-old man with postinfectious constrictive bronchiolitis and history of Mycoplasma pneumonia. A, High-resolution CT image of chest shows multiple patchy areas of low attenuation in both lungs. Also note mild bronchial wall thickening and cylindric bronchiectasis. B, Expiratory high-resolution CT image shows accentuation of areas of decreased attenuation, confirming presence of air trapping.

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Radiologic and Pathologic Features of Bronchiolitis

Fig. 5Photomicrograph of lung specimen in patient with bronchiolitis shows histopathologic features of cellular bronchiolitis. Note partial bronchiolar wall destruction with infiltration of neutrophils (arrow). (H and E, 200)

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Fig. 662-year-old woman with Mycobacterium avium-intercellulare infection and cellular bronchiolitis pattern. A and B, CT images show tree-in-bud pattern (arrow, A; arrowheads, B) consistent with cellular bronchiolitis. Associated bronchiectasis and collapse of right middle lobe and lingula are important clues to diagnosis of atypical mycobacterial infection.

Fig. 7Patient with hypersensitivity pneumonitis. Histopathologic image of lung shows poorly formed peribronchiolar granuloma (arrow) with chronic interstitial inflammation. (H and E, 400)

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Pipavath et al.
Fig. 855-year-old man with cellular bronchiolitis secondary to subacute hypersensitivity pneumonitis. A and B, High-resolution CT images through right mid lung show diffuse ill-defined centrilobular nodules with patchy areas of low attenuation (arrows, A), probably representing air trapping.

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Fig. 1040-year-old female cigarette smoker with respiratory bronchiolitisassociated interstitial lung disease. Highresolution CT image through right mid lung shows patchy groundglass opacity with centrilobular nodules (arrow).

Fig. 9Patient with respiratory bronchiolitis. Histopathologic image of lung shows multiple brown-pigmented macrophages (arrows) within bronchiolar and alveolar space lumen. (H and E, 400)

patients with hypersensitivity pneumonitis are nonsmokers. Follicular Bronchiolitis Follicular bronchiolitis is characterized by lymphoid hyperplasia of bronchus-associated lymphoid tissue (BALT). On histology, it is characterized by the presence of hyperplastic lymphoid follicles with reactive germinal centers distributed along the bronchioles and, to a lesser extent, the bronchi (Fig. 11). The lym-

phocytes are polyclonal on immunohistochemistry. The differential diagnosis on histology includes BALTassociated lymphoma and lymphocytic interstitial pneumonitis. Lymphoma is differentiated by the presence of lymphoepithelial lesions and monoclonality of lymphocytes. Lymphocytic interstitial pneumonitis is differentiated by its diffuse involvement of the interstitium. Most cases of follicular bronchiolitis are associated with collagen vascular diseases, particularly rheumatoid ar-

thritis and Sjgrens syndrome. Other associations, such as immunodeficiency or hypersensitivity reaction, are less frequent. On high-resolution CT of the chest in patients with follicular bronchiolitis, centrilobular and peribronchial nodules are characteristically present, with most being around 3 mm in size, but ranging from 1 to 12 mm [19]. Tree-in-bud pattern may be present (Fig. 12). Areas of ground-glass opacity and rarely bronchial dilatation and interlobular

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Radiologic and Pathologic Features of Bronchiolitis

Fig. 1237-year-old woman with rheumatoid arthritis and follicular bronchiolitis. High-resolution CT image shows tree-in-bud pattern (arrowhead) with a few larger nodules and occasional discrete small thin-walled cysts (arrow).

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Fig. 11Patient with follicular bronchiolitis. Photomicrograph of lung biopsy specimen shows lymphoid follicle (arrow) with germinal center formation in bronchiolar wall. (H and E, 200)

Fig. 13Photomicrograph of lung specimen of 67-year-old Asian woman with panbronchiolitis shows severe transmural inflammation of bronchiole. (H and E, 200)

Fig. 14Patient with bronchiolitis obliterans. Photomicrograph of lung specimen shows abundant yellow-staining fibrous tissue within elastic lamina of bronchiole, partially obliterating bronchiolar lumen. (pentachrome, 200)

septal thickening may also be seen. In contrast to its appearance in cases of follicular bronchiolitis, ground-glass opacity is the predominant feature of lymphocytic interstitial pneumonitis. Thin-walled cysts (Fig. 12) may be seen either in lymphocytic interstitial pneumonitis or in follicular bronchiolitis and are thought to be due to check-valve obstruction of small bronchioles by lymphatic tissue [20].

As with respiratory bronchiolitis, there is probably a continuum of abnormality ranging from the peribronchiolar pattern of follicular bronchiolitis and the more diffuse pattern of lymphoid interstitial pneumonia. Follicular bronchiolitis may share the imaging features of other causes of bronchiolitis, but the presence of an underlying condition such as Sjgrens syndrome or immunodeficiency should lead to a suspicion of this diagnosis.

Diffuse Panbronchiolitis Diffuse panbronchiolitis [21] is a unique entity of unknown cause that is seen mainly in Asia, especially Japan and Korea. Some cases have been reported in white patients [22], and the condition may be underdiagnosed in the United States. It typically affects middle-aged men and has no relationship to smoking. It has been associated with the human leukocyte antigengenotype Bw54 in more than 60% of the

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Pipavath et al.
Fig. 1555-year-old woman with rheumatoid arthritis and bronchiolitis obliterans. Expiratory high-resolution CT image through left upper lobe shows patchy areas of air trapping. Note right upper lobe tracheal bronchus (arrow).

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Fig. 1610-year-old girl with Swyer-James syndrome. A, Inspiratory high-resolution CT image through lower lungs shows asymmetric decrease in lung attenuation in lingula, associated with decreased size of pulmonary vessels and cylindric bronchiectasis. There is mild patchy decrease in attenuation in anterior right lung. B, Expiratory high-resolution CT image confirms extensive asymmetric air trapping.

cases. Progressive cough, dyspnea, and severe pansinusitis (30%) are seen. Long-term lowdose erythromycin is the recommended treatment with initial responses in 85% of patients, although the long-term prognosis is variable. On histology, transmural inflammatory nodules are composed of mononuclear cells centered on the respiratory bronchioles (Fig. 13). Foamy macrophages are present in the interstitium around the bronchioles and within the alveoli. Neutrophilia on bronchoalveolar lavage analysis with or without intraluminal exudates may be present. On high-resolution CT, centrilobular opacities with branching lines (tree-in-bud pattern), bronchiolectasis, and bronchiectasis are noted (Fig. 3). Basal and peripheral lung predominance may be noted. Areas of decreased lung attenuation due to air trapping and large

lung volumes are rare features. Cystic fibrosis, hypogammaglobulinemia, ciliary dysmotility, and atypical mycobacterial infection can mimic diffuse panbronchiolitis on high-resolution CT. Bronchiectasis Signs of inflammatory and fibrotic bronchiolitis are frequently seen in patients with bronchiectasis of any cause, including cystic fibrosis, immune deficiency, and previous infection, presumably because the pathologic process involving the bronchi has also involved the small airways. Fibrotic Bronchiolitis Constrictive Bronchiolitis (Bronchiolitis Obliterans) Constrictive bronchiolitis is defined histologically as concentric luminal narrowing of

the membranous and respiratory bronchioles secondary to submucosal and peribronchiolar inflammation and fibrosis without any intraluminal granulation tissue or polyps (Fig. 14). Constrictive bronchiolitis can be cryptogenic; postinfectious (mostly secondary to prior viral or Mycoplasma infection); or secondary to noxious fume inhalation, graft-versus-host disease, lung transplantation, rheumatoid arthritis, inflammatory bowel disease, and penicillamine therapy [23] (Appendix 1). The histology varies according to the cause; however, all of these cases show a basic group of findings that justify the diagnosis of constrictive bronchiolitis. In patients who have undergone lung or heartlung transplantation, bronchiolitis obliterans represents chronic rejection and is characterized by submucosal and intraepithelial lymphocytic and histiocytic infiltrates.

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Radiologic and Pathologic Features of Bronchiolitis lobular, segmental, or lobar or present as larger areas of confluent decreased lung attenuation that are accentuated on expiratory imaging. Areas of low attenuation may be associated with a reduction in the size of the pulmonary vessels. Obtaining expiratory high-resolution CT scans increases the likelihood of identifying areas of air trapping that are not apparent on inspiratory scans. Most patients with bronchiolitis obliterans show central and peripheral bronchiectasis in addition to mosaic attenuation. The cause of the bronchiectasis associated with bronchiolitis obliterans remains unclear, but it seems most likely to be due to concomitant injury to the large airways by the cause of the small airways disease. Postinfectious Bronchiolitis Most cases of postinfectious constrictive bronchiolitis are secondary to an infection with adenovirus type 7 during childhood or infancy, but constrictive bronchiolitis may also develop with measles, pertussis, tuberculosis, and Mycoplasma infection [7] (Fig. 1). Alveolar maturation occurs in children by the age of 8 years. If bronchiolitis occurs before this age, it affects the division of alveoli, with a resultant decrease in the number of alveoli and pulmonary vessels. Patients with postinfectious bronchiolitis usually have a patchy distribution of bronchiolitis and air trapping that results in a dramatic pattern of mosaic attenuation. Those with Swyer-James syndrome, which is also called Macleods syndrome, have predominant involvement of one lobe or one lung [25] (Fig. 16). These patients have focal areas of decreased lung opacity with sharp margins, reduced-size pulmonary vessels, bronchial wall thickening, and bronchiectasis. Toxic Fume Exposure Reactive airways dysfunction syndrome appears to be more common than bronchiolitis as a sequel of toxic fume exposure [26] and is usually not associated with any CT manifestations. Silo fillers lung is a classic cause of constrictive bronchiolitis, although its incidence may have decreased with aggressive corticosteroid treatment [27]. Other toxic fume exposures may also cause bronchiolitis [28]. Most recently, work-related inhalation of flavoring agents (used in making popcorn) has been found to result in a clinical presentation and imaging pattern typical of constrictive bronchiolitis [29] (Fig. 17). Transplant-Related Bronchiolitis Constrictive bronchiolitis remains the most common form of chronic rejection in patients with lung transplants, occurring in up to 50% of patients. Because it is not appropriate to surgically biopsy the transplanted lung to make this diagnosis in transplant recipients, the diagnosis of bronchiolitis obliterans

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Fig. 17Constrictive bronchiolitis pattern in worker, in a microwave popcorn-flavoring factory, who had severe obstructive lung disease. CT image shows diffuse decrease in lung attenuation, with mild cylindric bronchiectasis.

In patients with constrictive bronchiolitis, because the amount of abnormal soft tissue in and around the bronchioles is relatively small, direct CT signs of bronchiolitis are usually absent. Mosaic attenuation, air trapping, and bronchial dilation are the most common findings [24] (Figs. 4 and 15). Air trapping can be

Fig. 18Constrictive bronchiolitis pattern in 41-year-old male double lung transplant recipient with bronchiolitis obliterans syndrome. CT image shows bilateral diffuse cylindric bronchiectasis, with diffuse decrease in vascularity, and decrease in lung attenuation.

Fig. 19Constrictive bronchiolitis pattern in patient with pulmonary neuroendocrine cell hyperplasia. High-resolution CT image shows mosaic attenuation, which is more marked on right than on left.

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Pipavath et al. syndrome in these patients is based on reduction in the forced expiratory flow volume in 1 sec (FEV1) to less than 80% of the posttransplantation baseline value, provided that other causes such as infection, rejection, anastomotic stenosis, or disease recurrence have been excluded [30]. Risk factors for the development of the syndrome include acute rejection, lymphocytic bronchiolitis, and probably also medication noncompliance and cytomegalovirus infection. CT findings in patients with bronchiolitis obliterans syndrome include bronchial dilation, bronchial wall thickening, mosaic perfusion, and air trapping on expiratory images (Fig. 18). Of these findings, expiratory air trapping appears to be the most sensitive indicator. In one study, expiratory air trapping achieved a sensitivity and specificity of 87.5% for the detection of bronchiolitis obliterans syndrome [31]; in another study [32], the sensitivity of air trapping for histopathologically proven bronchiolitis obliterans was 74%, with a specificity of 67%. Although the presence of air trapping may sometimes precede the development of spirometric criteria for bronchiolitis obliterans syndrome, its sensitivity is not sufficiently great to justify the routine use of CT for the detection of bronchiolitis obliterans. The bronchial dilation found in patients with posttransplantation bronchiolitis obliterans usually has lower lung predominance [33]. Constrictive bronchiolitis is seen as a manifestation of graft-versus-host disease in 10% of people who have received allogeneic bone marrow transplants. Imaging findings in patients with this form of bronchiolitis are identical to those found with bronchiolitis obliterans after lung transplantation [34, 35]. Cryptogenic Bronchiolitis Obliterans Cryptogenic bronchiolitis obliterans is an uncommon entity that is most common in older women and is characterized by airway obstruction that progresses to respiratory failure. Imaging findingsThe imaging findings in this entity are similar to those of patients with other forms of constrictive bronchiolitismosaic attenuation, air trapping, and cylindrical bronchiectasis [4, 36, 37]. A similar entity is found in patients with rheumatoid arthritis (Fig. 15). Differential diagnosisThe progressive airway obstruction of cryptogenic bronchiolitis obliterans must be differentiated from refractory asthma. Although most cases of asthma can be distinguished from bronchiolitis obliterans by the presence of reversible rather than irreversible airflow obstruction, some cases of severe asthma show a lack of reversibility even with aggressive treatment. When we compared the CT findings in patients with refractory asthma with those of patients with cryptogenic bronchiolitis obliterans, we found that a mosaic pattern of lung attenuation was the most reliable distinguishing feature, being found in one (3%) of 30 patients with asthma and in seven (50%) of 14 patients with bronchiolitis obliterans [37]. Bronchial dilation and vascular attenuation are also less common in patients with asthma [38]. Distinction between bronchiolitis obliterans and panlobular emphysema is facilitated by the recognition of parenchymal destruction, vascular distortion, and linear scars or thickened septa at the lung bases in most patients with panlobular emphysema due to 1-antitrypsin deficiency [38]. Neuroendocrine hyperplasia, a rare entity, can cause a pattern of mosaic attenuation identical to that of bronchiolitis obliterans, but it is usually associated with small scattered pulmonary nodules [39, 40] (Fig. 19). Bronchiolitis Obliterans with Organizing Pneumonia According to the recent consensus statement from the American Thoracic Society and European Respiratory Society [41], bronchiolitis obliterans with organizing pneumonia is considered to be an idiopathic interstitial pneumonia (cryptogenic organizing pneumonia) rather than a small airways disease because its radiologic, clinical, and physiologic features are more similar to those of a restrictive parenchymal process than a small airways disease. For this reason, this entity will not be discussed further in this article. Summary Bronchiolitis may be classified into inflammatory and fibrotic subtypes. Direct signs of bronchiolitis include centrilobular nodules and tree-in-bud pattern. Indirect signs include mosaic attenuation and air trapping. High-resolution CT findings correlate with the histology of different forms of bronchiolitis. The CT features presented in this article represent the typical features associated with each entity. Although classic examples of each entity exist, there can be substantial overlap in the appearances, and distinguishing among these entities is not always possible. When high-resolution CT features overlap, clinical details will usually help to narrow the differential diagnosis. References
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APPENDIX 1: Causes of Constrictive Bronchiolitis Idiopathic Cryptogenic bronchiolitis obliterans Collagen vascular disease Rheumatoid arthritis Postinfectious causes Virus Mycoplasma infection Inhalation injury Noxious fumes (e.g., chlorine, nitrogen dioxide) Flavor workers lung Transplantation Lung Bone marrow Drug Penicillamine

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