354 AJR:185, August 2005

AJR 2005; 185:354–363

0361–803X/05/1852–354

© American Roentgen Ray Society

Pipavath et al.Radiologic and Pathologic Features of Bronchiolitis

C h e s t I m ag i n g • Pe r s p e c t i ve

Radiologic and Pathologic Features of Bronchiolitis

Sudhakar J. Pipavath1,2

David A. Lynch3

Carlyne Cool3Kevin K. Brown4

John D. Newell4

Pipavath SJ, Lynch DA, Cool C, Brown KK, Newell JD

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.

OBJECTIVE. The purpose of this article is to describe and illustrate the clinical, patho-logic, and imaging features of the inflammatory and fibrotic forms of bronchiolitis. The CT fea-tures presented in this article represent the typical features associated with each entity.

CONCLUSION. Direct signs of bronchiolitis include centrilobular nodules andtree-in-bud pattern. Indirect signs include mosaic attenuation and air trapping. Although classicexamples of each entity exist, there can be substantial overlap in the appearances, and distin-guishing among these entities is not always possible. When high-resolution CT features over-lap, clinical details will usually help to narrow the differential diagnosis.

nderstanding the imaging featuresof small airways diseases requiresan appreciation of the histopatho-logic findings of these disorders.

The purpose of this article is to describe andillustrate the clinical, pathologic, and imagingfeatures of inflammatory and fibrotic formsof bronchiolitis (Table 1).

CT Signs of Small Airways DiseaseDirect Signs

Bronchioles are usually not directly visibleon CT. However, when there is increased softtissue in or around the bronchioles, they canbecome visible at the center of the secondarypulmonary lobule [1]. Thickening of thebronchiolar wall by inflammatory cells re-sults in centrilobular nodules and V- orY-shaped branching linear opacities that rep-resent the tree-in-bud pattern [2] (Fig. 1).Inflammatory cellular infiltration in theperibronchiolar alveoli, typically seen inrespiratory bronchiolitis or hypersensitivitypneumonitis, results in poorly defined centri-lobular nodules that often have an attenuationless than that of soft tissue (Fig. 2).

Bronchiolectasis is a less common directsign of bronchiolitis and is found most com-monly in chronic forms of bronchiolitis. Thedilated bronchioles are identifiable close tothe pleural surface (Fig. 3).

Indirect SignsAir trapping is an indirect sign of obstruc-

tive small airways disease and may be iden-

tified by the presence of mosaic attenuationon inspiratory CT that is accentuated withexpiratory imaging (Fig. 4). Air trapping iseasily detected when focal because it pro-duces mosaic attenuation, but it may be dif-ficult to detect when it is diffuse. Because airtrapping often becomes apparent only on ex-piratory imaging, this technique is an essen-tial part of the CT evaluation for bronchioli-tis [3]. In patients with bronchiolitisobliterans, the extent of air trapping on expi-ratory CT provides the best correlation withindexes of physiologic impairment [4].

Interpretation of expiratory CT is compli-cated by the knowledge that the prevalence ofair trapping in healthy individuals is substan-tial. In a study by Mastora et al. [5], isolatedlobules of air trapping were found in 31(53%) of 59 nonsmoking healthy subjects,whereas larger (segmental or lobar) areas ofair trapping were found in five (8%). A morerecent study by Tanaka et al. [6] indicates thatextensive air trapping may be found in a mi-nority of healthy subjects. These articles sug-gest that the CT finding of air trapping maysometimes be normal and should be ignoredin the absence of physiologic evidence of air-way obstruction.

Inflammatory BronchiolitisInfectious Bronchiolitis

Infectious bronchiolitis is characterized his-tologically by a pattern of acute bronchiolar in-jury, with epithelial necrosis and inflammationof the bronchiolar walls and intraluminal

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exudates [1] (Fig. 5). Lymphoplasmacyticbronchiolar wall infiltrates with neutrophil-richintraluminal exudates are seen. Edema and fi-brosis also may be present in the bronchiolarwalls. Extensive injury to the respiratory mu-cosa, causing loss of cilia and ciliated cells, canbe observed in the ultrastructure.

Acute infections caused by viruses or My-coplasma organisms are associated with this

type of bronchiolitis. In children, infectiousbronchiolitis is clinically more severe than inadults; most cases are secondary to viral in-fection, most commonly a respiratory syncy-tial virus [7]. In adults, cellular bronchiolitisis less common and may be secondary to ei-ther a viral or a bacterial infection [8–11](Fig. 1). More chronic infections, particularlytuberculosis [12] and atypical mycobacterial

infection [13], also show evidence of cellularbronchiolitis (Fig. 6). In the immunocompro-mised patient, infection with Aspergillus fu-migatus may produce this appearance.

On high-resolution CT of the chest in pa-tients with infectious cellular bronchiolitis,the intense bronchiolar mural inflammationof cellular bronchiolitis results in centrilob-ular nodules that are usually associated with

TABLE 1: CT Classification of Bronchiolitis

Type of BronchiolitisCause or

Associated Condition Histologic Features CT Features Imaging Differential Diagnosis

Inflammatory

Infectious Acute or chronic infection (viral, Mycoplasma organisms, mycobacterial)

Infiltration of bronchiolar wall with inflammatory cells

Centrilobular nodules, tree-in-bud pattern

Hypersensitivity pneumonitis

Hypersensitivity pneumonitis Organic or inorganic inhaled agents

Bronchiolar and peribronchiolar lymphoplasmacytic infiltration

Poorly defined centrilobular nodules, mosaic attenuation, ground-glass attenuation

Respiratory bronchiolitis

Respiratory bronchiolitis Cigarette smoking Accumulation of pigmented macrophages in and around respiratory bronchioles

Centrilobular nodules, ground-glass opacity

Hypersensitivity pneumonitis

Follicular and lymphocytic Sjögren’s syndrome, rheumatoid arthritis, immunodeficiency

Lymphoid cell accumulation in and around bronchioles

Tree-in-bud pattern, nodules, cysts

Cellular bronchiolitis, panbronchiolitis

Panbronchiolitis Idiopathic Transmural infiltration of bronchiolar wall by inflammatory cells

Tree-in-bud pattern, bronchiolectasis, bronchiectasis

Cellular bronchiolitis, follicular bronchiolitis, other causes of bronchiectasis

Bronchiectasis Cystic fibrosis, previous infection

Inflammatory or fibrotic bronchiolitis (or both)

Tree-in-bud pattern, air trapping, bronchiolectasis

Other causes of bronchiolitis

Fibrotic

Constrictive Postinfectious, toxic fumes, transplantation, cryptogenic, collagen vascular diseases, drugs

Narrowing or obliteration of bronchiolar lumen by progressive fibrosis

Mosaic attenuation, bronchiectasis, air trapping on expiratory CT

Asthma, panlobular, emphysema, neuroendocrine hyperplasia

Fig. 1—35-year-old man with cellular bronchiolitis secondary to Myco-plasma infection. High-resolution CT image through left mid lung shows multiple poorly defined centrilobular nodules, many of which connect to branching lin-ear structures (arrows), tree-in-bud pattern.

Fig. 2—57-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.

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the tree-in-bud pattern (Fig. 1). Consolida-tion or ground-glass attenuation may also bepresent [9].

Hypersensitivity PneumonitisAlthough cellular bronchiolitis is a common

manifestation of hypersensitivity pneumonitis[1] (Fig. 7), the centrilobular nodules of hyper-sensitivity pneumonitis differ from those ofinfectious cellular bronchiolitis in that theyare usually diffuse, poorly defined, and of

ground-glass attenuation rather than soft-tissueattenuation (Fig. 8). The tree-in-bud pattern isuncommon, but areas of mosaic attenuationdue to air trapping are frequent [14, 15].

Respiratory Bronchiolitis and Respiratory Bronchiolitis–Associated Interstitial Lung Disease

Respiratory bronchiolitis and respiratorybronchiolitis–associated interstitial lung dis-ease are characterized by occurrence in pa-tients who smoke and, more rarely, in thosewith collagen vascular diseases and mineraldust–induced diseases. On histology, submu-cosal inflammation and fibrosis of the respi-ratory bronchioles consisting of fibroticmural thickening and mononuclear cell infil-tration are noted. Pigmented macrophages arepresent in the bronchiolar lumen; alveolarducts; and, to a lesser extent, the alveolarspaces (Fig. 9).

On high-resolution CT of patients with res-piratory bronchiolitis, ill-defined centrilobu-lar nodules, similar to those seen in hypersen-sitivity pneumonitis, are seen (Fig. 2). Smallpatches of ground-glass opacity may also bepresent. These abnormalities may predomi-nate in the upper lobes.

Although most patients with respiratorybronchiolitis are asymptomatic, some mayhave an extensive enough abnormality tocause severe symptoms and impairment oflung function and gas exchange: These casesare diagnosed as respiratory bronchiolitis–as-sociated interstitial lung disease. In these in-dividuals, patchy areas of ground-glass opac-ity and air trapping are usually present(Fig. 10). Although respiratory bronchiolitisand respiratory bronchiolitis–associated in-

terstitial lung disease share some histologicfeatures, respiratory bronchiolitis–associatedinterstitial lung disease is classified as an id-iopathic interstitial pneumonia.

If a patient with respiratory bronchiolitis–as-sociated interstitial lung disease stops smoking,lung abnormalities may stop progressing ormay begin to regress [16]. If patients continueto smoke, emphysema may develop in the ar-eas of respiratory bronchiolitis [17].

The imaging differential diagnosis of res-piratory bronchiolitis and respiratory bron-chiolitis–associated interstitial lung diseaseincludes desquamative interstitial pneumo-nia, nonspecific interstitial pneumonia, andhypersensitivity pneumonitis. Respiratorybronchiolitis–associated interstitial lung dis-ease differs from desquamative interstitialpneumonia in that the ground-glass opacityof respiratory bronchiolitis–associated inter-stitial lung disease is patchier and poorly de-fined. Centrilobular nodules are less com-mon in desquamative interstitial pneumonia.There is probably a continuum of smok-ing-related lung diseases from respiratorybronchiolitis to respiratory bronchiolitis–as-sociated interstitial lung disease to desqua-mative interstitial pneumonia [18]. Nonspe-cific interstitial pneumonia differs fromrespiratory bronchiolitis–associated intersti-tial lung disease in that the ground-glassopacity is usually more diffuse and is com-monly associated with a reticular abnormal-ity. Similarly, the centrilobular nodules andground-glass opacity found in patients withhypersensitivity pneumonitis are usuallymore diffuse than those seen in cases ofrespiratory bronchiolitis. In addition, most

Fig. 3—50-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.

A B

Fig. 4—30-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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Fig. 5—Photomicrograph of lung specimen in patient with bronchiolitis shows histo-pathologic features of cellular bronchiolitis. Note partial bronchiolar wall destruction with infiltration of neutrophils (arrow). (H and E, × 200)

A B

Fig. 6—62-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. 7—Patient 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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patients with hypersensitivity pneumonitisare nonsmokers.

Follicular BronchiolitisFollicular bronchiolitis is characterized by

lymphoid hyperplasia of bronchus-associatedlymphoid tissue (BALT). On histology, it ischaracterized by the presence of hyperplasticlymphoid follicles with reactive germinal cen-ters distributed along the bronchioles and, to alesser extent, the bronchi (Fig. 11). The lym-

phocytes are polyclonal on immunohis-tochemistry. The differential diagnosis on his-tology includes BALT–associated lymphomaand lymphocytic interstitial pneumonitis.Lymphoma is differentiated by the presence oflymphoepithelial lesions and monoclonality oflymphocytes. Lymphocytic interstitial pneu-monitis is differentiated by its diffuse involve-ment of the interstitium. Most cases of follicu-lar bronchiolitis are associated with collagenvascular diseases, particularly rheumatoid ar-

thritis and Sjögren’s syndrome. Other associa-tions, such as immunodeficiency or hypersen-sitivity reaction, are less frequent.

On high-resolution CT of the chest in pa-tients with follicular bronchiolitis, centrilob-ular and peribronchial nodules are character-istically present, with most being around3 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 andrarely bronchial dilatation and interlobular

A B

Fig. 8—55-year-old man with cellular bronchiolitis sec-ondary 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.

Fig. 10—40-year-oldfemale cigarette smokerwith respiratory bronchi-olitis–associated inter-stitial lung disease. High-resolution CT imagethrough right mid lungshows patchy ground-glass opacity with centri-lobular nodules (arrow).

Fig. 9—Patient with respiratory bronchiolitis. Histopathologic image of lung showsmultiple brown-pigmented macrophages (arrows) within bronchiolar and alveolarspace lumen. (H and E, × 400)

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septal thickening may also be seen. In con-trast to its appearance in cases of follicularbronchiolitis, ground-glass opacity is thepredominant feature of lymphocytic intersti-tial pneumonitis. Thin-walled cysts (Fig. 12)may be seen either in lymphocytic intersti-tial pneumonitis or in follicular bronchiolitisand are thought to be due to check-valve ob-struction of small bronchioles by lymphatictissue [20].

As with respiratory bronchiolitis, there isprobably a continuum of abnormality rangingfrom the peribronchiolar pattern of follicularbronchiolitis and the more diffuse pattern oflymphoid interstitial pneumonia. Follicularbronchiolitis may share the imaging features ofother causes of bronchiolitis, but the presenceof an underlying condition such as Sjögren’ssyndrome or immunodeficiency should lead toa suspicion of this diagnosis.

Diffuse PanbronchiolitisDiffuse panbronchiolitis [21] is a unique en-

tity of unknown cause that is seen mainly inAsia, especially Japan and Korea. Some caseshave been reported in white patients [22], andthe condition may be underdiagnosed in theUnited States. It typically affects middle-agedmen and has no relationship to smoking. It hasbeen associated with the human leukocyte an-tigen–genotype Bw54 in more than 60% of the

Fig. 12—37-year-old woman with rheumatoid arthritis and follicular bronchiolitis. High-reso-lution CT image shows tree-in-bud pattern (arrowhead) with a few larger nodules and occa-sional discrete small thin-walled cysts (arrow).

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

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

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

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cases. Progressive cough, dyspnea, and severepansinusitis (30%) are seen. Long-term low-dose erythromycin is the recommended treat-ment with initial responses in 85% of patients,although the long-term prognosis is variable.

On histology, transmural inflammatorynodules are composed of mononuclear cellscentered on the respiratory bronchioles (Fig. 13).Foamy macrophages are present in the inter-stitium around the bronchioles and within thealveoli. Neutrophilia on bronchoalveolar lav-age analysis with or without intraluminal ex-udates may be present.

On high-resolution CT, centrilobular opac-ities with branching lines (tree-in-bud pat-tern), bronchiolectasis, and bronchiectasis arenoted (Fig. 3). Basal and peripheral lung pre-dominance may be noted. Areas of decreasedlung attenuation due to air trapping and large

lung volumes are rare features. Cystic fibro-sis, hypogammaglobulinemia, ciliary dysmo-tility, and atypical mycobacterial infectioncan mimic diffuse panbronchiolitis onhigh-resolution CT.

BronchiectasisSigns of inflammatory and fibrotic bron-

chiolitis are frequently seen in patients withbronchiectasis of any cause, including cysticfibrosis, immune deficiency, and previous in-fection, presumably because the pathologicprocess involving the bronchi has also in-volved the small airways.

Fibrotic BronchiolitisConstrictive Bronchiolitis (Bronchiolitis Obliterans)

Constrictive bronchiolitis is defined histo-logically as concentric luminal narrowing of

the membranous and respiratory bronchiolessecondary to submucosal and peribronchiolarinflammation and fibrosis without any intralu-minal granulation tissue or polyps (Fig. 14).Constrictive bronchiolitis can be cryptogenic;postinfectious (mostly secondary to prior viralor Mycoplasma infection); or secondary to nox-ious fume inhalation, graft-versus-host disease,lung transplantation, rheumatoid arthritis, in-flammatory bowel disease, and penicillaminetherapy [23] (Appendix 1). The histology var-ies according to the cause; however, all of thesecases show a basic group of findings that jus-tify the diagnosis of constrictive bronchiolitis.In patients who have undergone lung orheart–lung transplantation, bronchiolitis oblit-erans represents chronic rejection and is char-acterized by submucosal and intraepitheliallymphocytic and histiocytic infiltrates.

Fig. 15—55-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).

A B

Fig. 16—10-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.

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In patients with constrictive bronchiolitis,because the amount of abnormal soft tissue inand around the bronchioles is relatively small,direct CT signs of bronchiolitis are usually ab-sent. Mosaic attenuation, air trapping, andbronchial dilation are the most common find-ings [24] (Figs. 4 and 15). Air trapping can be

lobular, segmental, or lobar or present as largerareas of confluent decreased lung attenuationthat are accentuated on expiratory imaging.Areas of low attenuation may be associatedwith a reduction in the size of the pulmonaryvessels. Obtaining expiratory high-resolutionCT scans increases the likelihood of identify-ing areas of air trapping that are not apparenton inspiratory scans. Most patients with bron-chiolitis obliterans show central and peripheralbronchiectasis in addition to mosaic attenua-tion. The cause of the bronchiectasis associ-ated with bronchiolitis obliterans remains un-clear, but it seems most likely to be due toconcomitant injury to the large airways by thecause of the small airways disease.

Postinfectious BronchiolitisMost cases of postinfectious constrictive

bronchiolitis are secondary to an infection withadenovirus type 7 during childhood or infancy,but constrictive bronchiolitis may also developwith measles, pertussis, tuberculosis, and My-coplasma infection [7] (Fig. 1). Alveolar mat-uration occurs in children by the age of 8 years.If bronchiolitis occurs before this age, it affectsthe division of alveoli, with a resultant de-crease in the number of alveoli and pulmonaryvessels. Patients with postinfectious bronchi-olitis usually have a patchy distribution ofbronchiolitis and air trapping that results in adramatic pattern of mosaic attenuation. Those

with Swyer-James syndrome, which is alsocalled Macleod’s syndrome, have predomi-nant involvement of one lobe or one lung [25](Fig. 16). These patients have focal areas ofdecreased lung opacity with sharp margins, re-duced-size pulmonary vessels, bronchial wallthickening, and bronchiectasis.

Toxic Fume ExposureReactive airways dysfunction syndrome

appears to be more common than bronchioli-tis as a sequel of toxic fume exposure [26] andis usually not associated with any CT mani-festations. Silo filler’s lung is a classic causeof constrictive bronchiolitis, although its inci-dence may have decreased with aggressivecorticosteroid treatment [27]. Other toxicfume exposures may also cause bronchiolitis[28]. Most recently, work-related inhalationof flavoring agents (used in making popcorn)has been found to result in a clinical presenta-tion and imaging pattern typical of constric-tive bronchiolitis [29] (Fig. 17).

Transplant-Related BronchiolitisConstrictive bronchiolitis remains the most

common form of chronic rejection in patientswith lung transplants, occurring in up to 50%of patients. Because it is not appropriate tosurgically biopsy the transplanted lung tomake this diagnosis in transplant recipients,the diagnosis of bronchiolitis obliterans

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

Fig. 18—Constrictive 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. 19—Constrictive 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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syndrome in these patients is based on reduc-tion in the forced expiratory flow volume in1 sec (FEV1) to less than 80% of the post-transplantation baseline value, provided thatother causes such as infection, rejection,anastomotic stenosis, or disease recurrencehave been excluded [30]. Risk factors for thedevelopment of the syndrome include acuterejection, lymphocytic bronchiolitis, andprobably also medication noncompliance andcytomegalovirus infection.

CT findings in patients with bronchiolitisobliterans syndrome include bronchial dila-tion, bronchial wall thickening, mosaic perfu-sion, and air trapping on expiratory images(Fig. 18). Of these findings, expiratory air trap-ping appears to be the most sensitive indicator.In one study, expiratory air trapping achieveda sensitivity and specificity of 87.5% for thedetection of bronchiolitis obliterans syndrome[31]; in another study [32], the sensitivity of airtrapping for histopathologically proven bron-chiolitis obliterans was 74%, with a specificityof 67%. Although the presence of air trappingmay sometimes precede the development ofspirometric criteria for bronchiolitis obliteranssyndrome, its sensitivity is not sufficientlygreat to justify the routine use of CT for the de-tection of bronchiolitis obliterans. The bron-chial dilation found in patients with posttrans-plantation bronchiolitis obliterans usually haslower lung predominance [33].

Constrictive bronchiolitis is seen as a man-ifestation of graft-versus-host disease in 10%of people who have received allogeneic bonemarrow transplants. Imaging findings in pa-tients with this form of bronchiolitis are iden-tical to those found with bronchiolitis obliter-ans after lung transplantation [34, 35].

Cryptogenic Bronchiolitis ObliteransCryptogenic bronchiolitis obliterans is an

uncommon entity that is most common in olderwomen and is characterized by airway obstruc-tion that progresses to respiratory failure.

Imaging findings—The imaging findingsin this entity are similar to those of patientswith other forms of constrictive bronchioli-tis—mosaic attenuation, air trapping, and cy-lindrical bronchiectasis [4, 36, 37]. A similarentity is found in patients with rheumatoid ar-thritis (Fig. 15).

Differential diagnosis—The progressiveairway obstruction of cryptogenic bronchioli-tis obliterans must be differentiated from re-fractory asthma. Although most cases ofasthma can be distinguished from bronchioli-tis obliterans by the presence of reversible

rather than irreversible airflow obstruction,some cases of severe asthma show a lack ofreversibility even with aggressive treatment.When we compared the CT findings in pa-tients with refractory asthma with those of pa-tients with cryptogenic bronchiolitis obliter-ans, we found that a mosaic pattern of lungattenuation was the most reliable distinguish-ing feature, being found in one (3%) of 30 pa-tients with asthma and in seven (50%) of 14patients with bronchiolitis obliterans [37].Bronchial dilation and vascular attenuationare also less common in patients with asthma[38]. Distinction between bronchiolitis oblit-erans and panlobular emphysema is facili-tated by the recognition of parenchymal de-struction, vascular distortion, and linear scarsor thickened septa at the lung bases in mostpatients with panlobular emphysema due toα1-antitrypsin deficiency [38].

Neuroendocrine hyperplasia, a rare entity,can cause a pattern of mosaic attenuationidentical to that of bronchiolitis obliterans,but it is usually associated with small scat-tered pulmonary nodules [39, 40] (Fig. 19).

Bronchiolitis Obliterans with Organizing Pneumonia

According to the recent consensus state-ment from the American Thoracic Society andEuropean Respiratory Society [41], bronchi-olitis obliterans with organizing pneumonia isconsidered to be an idiopathic interstitial pneu-monia (cryptogenic organizing pneumonia)rather than a small airways disease because itsradiologic, clinical, and physiologic featuresare more similar to those of a restrictive paren-chymal process than a small airways disease.For this reason, this entity will not be discussedfurther in this article.

SummaryBronchiolitis may be classified into in-

flammatory and fibrotic subtypes. Directsigns of bronchiolitis include centrilobularnodules and tree-in-bud pattern. Indirectsigns include mosaic attenuation and air trap-ping. High-resolution CT findings correlatewith the histology of different forms of bron-chiolitis. The CT features presented in this ar-ticle represent the typical features associatedwith each entity. Although classic examplesof each entity exist, there can be substantialoverlap in the appearances, and distinguish-ing among these entities is not always possi-ble. When high-resolution CT features over-lap, clinical details will usually help tonarrow the differential diagnosis.

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APPENDIX 1: Causes of Constrictive Bronchiolitis

IdiopathicCryptogenic bronchiolitis obliterans

Collagen vascular diseaseRheumatoid arthritis

Postinfectious causesVirusMycoplasma infection

Inhalation injuryNoxious fumes (e.g., chlorine, nitrogen dioxide)“Flavor worker’s” lung

TransplantationLungBone marrow

DrugPenicillamine

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