High-Resolution CT of the Lung
3rd Edition

Chapter 8
Airways Diseases
High-resolution computed tomography (HRCT) has revolutionized our understanding of diseases affecting the airways. HRCT not only allows direct, noninvasive visualization of structural changes involving both large, and medium-sized bronchi [1,2,3,4,5,6,7,8], but also allows a previously unattainable insight into airway physiology [9,10,11,12,13,14,15,16,17]. Furthermore, it is now possible to directly visualize a number of findings indicative of small airways disease using HRCT [18,19,20,21,22]. In this chapter, we review the HRCT diagnosis of large airway abnormalities specifically related to bronchiectasis and small airway abnormalities and bronchiolitis.
Bronchiectasis
Bronchiectasis is defined as localized, irreversible dilatation of the bronchial tree. Bronchiectasis has been associated with a wide variety of causes (Table 8-1), the most frequent of which is acute, chronic, or recurrent infection [23,24,25]. In a review of 123 patients who had documented bronchiectasis, an antecedent potentially causative event, usually pneumonia, could be identified in 70% of cases [26]. In up to 40% of cases of bronchiectasis, however, an etiology cannot be established.
TABLE 8-1. Bronchiectasis–associated conditions and possible mechanisms
Condition Mechanisms
Infection (bacteria, mycobacteria, fungus, virus) Impaired mucociliary clearance, disruption of respiratory epithelium, microbial toxins, host-mediated inflammation
Immunodeficiency states [including acquired immunodeficiency syndrome (AIDS)] Genetic or acquired predisposition to recurrent infection, associated with lymphocytic interstitial pneumonia in AIDS
Bronchial obstruction (tumor, foreign body, congenital abnormalities) Impaired mucociliary clearance, recurrent infection
Alpha-1-antitrypsin deficiency Proteinase-antiproteinase imbalance
Cystic fibrosis Abnormal airway epithelial chloride transport, impaired mucus clearance, recurrent infection
Dyskinetic cilia syndrome (Kartagener’s syndrome) Genetic defect, absent or dyskinetic ciliary beating, impaired mucus clearance, recurrent infection
Young’s syndrome (obstructive azoospermia) Abnormal mucociliary clearance
Yellow nail-lymphedema syndrome Unknown, lymphatic hypoplasia and sometimes immune deficiency, predisposition to recurrent infection?
Williams-Campbell syndrome Congenital deficiency of bronchial cartilage, obstruction, impaired mucus clearance, recurrent infection
Tracheobronchomegaly (Mounier-Kuhn syndrome) Congenital deficiency of membranous and cartilaginous parts of tracheal and bronchial walls, impaired mucus clearance, recurrent infection
Marfan syndrome Unknown, genetic tissue defect, structural bronchial defect?
Asthma Airway inflammation, mucous plugging
Allergic bronchopulmonary aspergillosis Type I and Type III immune responses to fungus in airway lumen, mucous plugging
Bronchiolitis obliterans (e.g., postinfectious, lung transplant) Bronchial wall inflammation, epithelial damage, recurrent infection in some cases
Aspiration, toxic fume inhalation Inflammation
Systemic diseases (e.g., collagen-vascular diseases, inflammatory bowel disease, amyloidosis, endometriosis, sarcoidosis) Various, including inflammation, infection, fibrosis
Chronic fibrosis Traction bronchiectasis
Modified from Davis AL, Salzman SH. Bronchiectasis. In: Cherniack NS, ed. Chronic obstructive pulmonary disease. Philadelphia: WB Saunders, 1991:316-338.
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Bronchiectasis can result from chronic or severe bacterial infection, especially with necrotizing infections such as Staphylococcus, Klebsiella, or Bordetella pertussis [25]. Granulomatous infections, including those caused by Mycobacterium tuberculosis [27], atypical mycobacteria, especially Mycobacterium avium complex (MAC) [28,29,30], and fungal organisms such as histoplasmosis are also associated with bronchiectasis. Furthermore, bronchiectasis is often present in patients who have bronchiolitis obliterans (BO) or the Swyer-James syndrome resulting from viral infection.
Bronchiectasis is commonly identified in patients infected with human immunodeficiency virus (HIV) [31]. A number of mechanisms have been proposed to account for accelerated bronchial wall destruction occurring in patients who have acquired immunodeficiency syndrome (AIDS), including recurrent infections, BO, and lymphocytic interstitial pneumonitis (LIP) [32,33]. King et al. [34] have shown that bronchial dilatation is common in HIV-positive patients, being seen in 36% of cases, and is associated with elevated levels of neutrophils in bronchoalveolar lavage fluid. Neutrophil elastase is associated with airway destruction in patients who have alpha-1-antitrypsin deficiency, and similarly may be an early mediator of bronchial wall destruction, even in asymptomatic HIV-positive patients.
Bronchiectasis may occur in association with a variety of genetic abnormalities, especially those with abnormal mucociliary clearance, immune deficiency, or structural abnormalities of the bronchus or bronchial wall (Table 8-1) [35]. In addition to cystic fibrosis (CF), causes of bronchiectasis having a genetic basis include alpha-1-antitrypsin deficiency; the dyskinetic cilia syndrome; Young’s syndrome; Williams-Campbell syndrome (congenital deficiency of the bronchial cartilage); Mounier-Kuhn syndrome (congenital tracheobronchomegaly); immunodeficiency syndromes, including Bruton’s hypogammaglobulinemia, immunoglobulin (Ig) A, and combined IgA-IgG subclass deficiencies; and the yellow nail syndrome (yellow nails, lymphedema, and pleural effusions). Chronic or recurrent infection is common in these conditions.
Noninfectious diseases that result in airway inflammation and mucous plugging can also result in bronchiectasis. These
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include allergic bronchopulmonary aspergillosis and, to a lesser extent, asthma [36,37,38]. Bronchiectasis may also occur in patients who have BO, regardless of its cause but including chronic rejection after heart-lung or lung transplantation [39,40,41,42,43,44,45] or bone marrow transplantation, most often as a result of rejection or chronic graft-versus-host disease (GVHD) [46].
FIG. 8-1. Cystic bronchiectasis with bronchographic correlation. A: HRCT through the right upper lobe shows numerous thin-walled cysts (straight arrows). Note that despite their thin walls, many of these cysts lie adjacent to vessels and a few are obviously branching (curved arrow). Rarely, bronchiectasis can result in thin-walled cysts that nonetheless maintain a characteristic anatomic configuration. B: Coned-down radiograph after limited bronchography, performed through a centrally positioned bronchoscope, confirms presence of extensive cystic bronchiectasis. (From McGuinness G, Naidich DP, Leitman BS, et al. Bronchiectasis: CT evaluation. AJR Am J Roentgenol 1993;160:253-259, with permission.)
Although the incidence of bronchiectasis is generally cited as decreasing in the United States, the true incidence of bronchiectasis has probably been underestimated [47]. In part, this may reflect decreased awareness in recent years of the protean manifestations of bronchiectasis, especially in an older population [23,26]. It should also be noted that documentation has traditionally relied on bronchography, which is rarely performed in current medical practice.
In general, a clinical diagnosis of bronchiectasis is possible only in the most severely affected patients, and differentiation from chronic bronchitis may be problematic even in this setting [48]. Most patients present with purulent sputum production and recurrent pulmonary infections [23,24,26]. Hemoptysis also is frequent, occurring in up to 50% of cases, and may be the only clinical finding [24,49,50]. Bronchitis, bronchiolitis, or emphysema frequently accompanies bronchiectasis and may cause obstructive abnormalities on pulmonary function tests.
Radiographic and Bronchographic Findings
The radiographic manifestations of bronchiectasis have been well described [51]. These include a loss of definition of vascular markings in affected lung segments, presumably secondary to peribronchial fibrosis and volume loss; evidence of bronchial wall thickening; and, in more severely affected cases, the presence of discrete cysts occasionally containing air-fluid levels. It should be emphasized that most of these findings are nonspecific; a definitive radiographic diagnosis of bronchiectasis is generally considered difficult to make, except in the most advanced cases [48].
Woodring has suggested that a greater degree of accuracy may be achieved in the radiographic diagnosis of bronchiectasis by the use of additional radiographic criteria [52]. Most important of these is the assessment of bronchial dilatation, either by comparing the diameters of end-on bronchi in normal and abnormal areas of the lung or by direct measurement of bronchoarterial ratios in the same locations. Using these criteria, Woodring was able to accurately diagnosis bronchiectasis in 38 patients who had either bronchographic or HRCT evidence of bronchiectasis. Specifically, bronchial dilatation was found to be present in 100% of cases, volume loss in 97%, bronchial wall thickening in 92%, a signet ring sign (abnormal bronchoarterial ratio) in 79%, compensatory hyperinflation in 45%, and discrete cysts in 42%. Also, radiographs identified 235 of 255 (92%) bronchiectatic lung segments [52]. Although there is no doubt that an accurate diagnosis of bronchiectasis may be made by using specific criteria, especially when films are closely correlated with clinical history, plain radiographs will likely remain of greatest value in those patients who have severe disease.
Bronchographic findings indicative of bronchiectasis include proximal or distal bronchial dilatation, or both; pruning or lack of normal tapering of peripheral airways; and luminal filling defects (Fig. 8-1). Although traditionally considered the gold standard, the reliability of bronchography in
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the diagnosis of bronchiectasis has been questioned. Currie et al. [48], in a study of 27 patients who had chronic sputum production evaluated bronchographically, showed that there was significant interobserver variability when studies were interpreted by two well-trained bronchographers. Agreement was reached in only 19 of 27 patients (70%) and 94 of 448 bronchopulmonary segments (21%). Bronchiectasis was identified in two additional patients (7%) by only one radiologist. These findings suggest that bronchography may be more limited in its utility than previously thought and should not be considered an absolute standard for diagnosis.
TABLE 8-2. HRCT findings in bronchiectasis
Direct signs
 Bronchial dilatationa,b
  Internal diameter > adjacent pulmonary arterya,b
 Contour abnormalitiesa,b
   Signet ring sign (vertically oriented bronchi)
   Tram tracks (horizontally oriented bronchi)
   String of pearls (horizontally oriented bronchi)
   Cluster of cysts (especially in atelectatic lung)
 Lack of tapering greater than 2 cm distal to bifurcationb
 Visibility of peripheral airwaysa,b
   Within 1 cm of the costal pleuraa,b
   Touching the mediastinal pleuraa,b
Indirect signs
 Bronchial wall thickeninga,b
   Greater than 0.5 × diameter of an adjacent pulmonary artery (vertically oriented bronchi)b
 Fluid- or mucus-filled bronchia,b
   Tubular or Y-shaped structuresa,b
   Branching or rounded opacities in cross sectiona,b
   Air-fluid levelsb
 Mosaic perfusiona
 Centrilobular nodules or tree-in-buda
 Atelectasis/consolidationa
 Air-trapping on expiratory scansa
a Most common findings.
b Findings most helpful in differential diagnosis.
Computed Tomography and High-Resolution Computed Tomography Findings of Bronchiectasis
Bronchiectasis results in characteristic abnormalities, both direct and indirect, identifiable on HRCT (Table 8-2) [35,53]. Direct findings of bronchiectasis include bronchial dilatation [often described as cylindrical (Fig. 8-2), varicose (Fig. 8-3), or cystic (Figs. 8-3, 8-4, 8-6, and 8-7) depending on its appearance], lack of normal bronchial tapering, and visibility of airways in the peripheral lung zones (Fig. 8-6). Indirect signs include bronchial wall thickening and irregularity (Figs. 8-2, 8-3, and 8-9), as well as the presence of mucoid impaction of the bronchial lumen (Figs. 8-10 and 8-11), bronchiolectasis, and tree-in-bud (TIB) (Figs. 8-16 and 8-17). Ancillary signs have also been described and include mosaic perfusion visible on inspiratory scans (Fig. 8-18), focal air-trapping identifiable on expiration scans (Fig. 8-18), tracheomegaly (Fig. 8-41), bronchial artery enlargement, and emphysema. A combination of these findings enables an accurate diagnosis in a large percentage of cases (Table 8-2).
FIG. 8-2. Cylindrical bronchiectasis with bronchial dilatation and wall thickening. Target-reconstructed HRCT through the right lower lobe in a patient who has mild cylindrical bronchiectasis, obtained at full inspiration. Dilated bronchi have a signet ring appearance when sectioned vertically (straight arrow) and a tram track appearance when sectioned horizontally (curved arrow). Bronchial walls in the lower lobe are considerably thicker than in the middle lobe.
Bronchial Dilatation
Because bronchiectasis is defined by the presence of bronchial dilatation, recognition of increased bronchial diameter is key to the CT diagnosis of this abnormality. Various sophisticated methods for measuring airway dimensions have been proposed. These include the use of digital image analysis programs, requiring operator-dependent definition of a “seed point” at the lumen-wall interface to obtain isocontour lines of the bronchial lumen [14], and automated thresholding to detect airway lumen area [54]. Whereas these approaches may allow precise quantitative assessment of airways and may prove particularly valuable in physiologic
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studies, subjective visual criteria for establishing the presence of bronchial dilatation are most often used in the interpretation of scans [4,38,55,56,57,58].
FIG. 8-3. Section through the middle lung fields in a patient who has varicose bronchiectasis in the left upper lobe (straight arrows). Note that there is also evidence of cystic bronchiectasis with a few air-fluid levels in the lower lobes (curved arrows).
For the purposes of the interpretation of HRCT, bronchial dilatation may be diagnosed using a comparison of bronchial size to that of adjacent pulmonary artery branches (i.e., the bronchoarterial ratio), by detecting a lack of bronchial tapering, and by identifying airways in the peripheral lung.
Bronchoarterial Ratio
In most cases, bronchiectasis is considered to be present when the internal diameter of a bronchus is greater than the diameter of the adjacent pulmonary artery branch–that is, the bronchoarterial ratio is greater than 1 (Figs. 8-2, 8-3 and 8-4) [53]. The accuracy of this finding in diagnosing bronchiectasis has been validated in a number of studies comparing CT to
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bronchography in patients who have bronchiectasis [59,60,61,62]. In patients who have bronchiectasis, the bronchial diameter is often much larger than the pulmonary artery diameter (i.e., greater than 1.5 times the artery diameter), a finding that not only reflects the presence of bronchial dilatation but also demonstrates some reduction in pulmonary artery size as a consequence of decreased lung perfusion in affected lung regions [56]. The association of a dilated bronchus with a much smaller adjacent pulmonary artery branch has been termed the signet ring sign (see Figs. 3-135 and 3-137; Figs. 8-2, 8-3 and 8-4). This sign is valuable in recognizing bronchiectasis and in distinguishing it from other cystic lung lesions.
FIG. 8-4. Cystic bronchiectasis. A, B: Sequential target-reconstructed HRCT sections through the middle and right lower lobe. Markedly dilated airways are apparent diffusely, some obviously branching (straight arrows, A). Numerous signet rings are identifiable as well (curved open arrow, A). Note the cluster of cysts appearing within the collapsed middle lobe (arrow, B). A number of fluid-filled airways can be identified peripherally that are clearly centrilobular in distribution (open arrows, B); these represent dilated terminal bronchioles. (From Naidich DP. High-resolution computed tomography of cystic lung disease. Semin Roentgenol 1991;26:151-174, with permission.)
FIG. 8-5. Bronchial dilatation associated with asthma. HRCT section through the upper lobes in an asthmatic shows evidence of proximal bronchial dilatation, especially on the right (arrows), with bronchi being larger than adjacent vessels. This finding should be interpreted with caution in an asthmatic, as it may be reversible.
Although an increased bronchoarterial ratio is typical of bronchiectasis, it should be kept in mind that a bronchoarterial ratio of more than 1 need not always indicate the presence of bronchiectasis [4,38,56]. There are a number of instances in which airways may appear dilated in the absence of wall destruction, although this dilatation is usually minimal; this has been reported in asthmatic patients [36,38,63], in patients living at high altitudes [38,56], and in a small percentage of normals [64] (Fig. 8-5). For example, in an HRCT evaluation of 14 normal subjects [65], although the bronchoarterial ratio averaged 0.65 ± 0.16, 7% of interpretations showed some evidence of bronchial dilatation. Kim et al. [56] found that nine of 17 (53%) normal subjects living at an altitude of 1,600 meters had evidence of at least one bronchus equal to or larger in size than the adjacent pulmonary artery. These authors also found that two of 16 (12.5%) individuals living at sea level showed evidence of at least one abnormally dilated airway. Similarly, Lynch et al. [38] compared the internal diameters of lobular, segmental, subsegmental, and smaller bronchi to those of adjacent pulmonary artery branches in 27 normal subjects living in Denver. The authors found that 37 of 142 (26%) bronchi evaluated and 59% of individuals had increased bronchoarterial ratios. Evaluation of the distribution of these abnormal airways has failed to identify any significant difference in the likelihood of abnormal bronchoarterial ratios in airways either by lobe or anteroposterior location within the lungs [56]. A similar lack of variation by segments, lobes, or lungs has been reported by Kim et al. [58].
It must be emphasized that bronchiectasis should not be diagnosed on the basis of an increased bronchoarterial ratio alone unless it is significant; in a study by Lynch et al. [38] of normal subjects and patients who had asthma, although bronchoarterial ratios of greater than 1 were frequently seen, in none of these was the bronchoarterial ratio greater than 1.5 [66]. Also, bronchial wall thickening is almost always seen in association with bronchial dilatation in patients who have bronchiectasis, as are irregularities in bronchial diameter and lack of bronchial tapering. In the normal subjects studied by Lynch et al. [38] who demonstrated an increased bronchoarterial ratio, bronchial wall thickening was relatively uncommon, and it is unlikely that any of the subjects in this study would have been diagnosed on clinical HRCT studies as having true bronchiectasis.
The definition of an abnormal bronchoarterial ratio varies widely among reported series [4,53,55,57,58,65,67], a fact that limits their comparison. In addition to variations in size criteria for considering a bronchus to be dilated (ranging from one to two times the diameter of the adjacent pulmonary artery) and the use of internal or external bronchial diameters for comparison to pulmonary artery diameter, important differences may also be attributable to the use of either visual inspection or objective measurements of bronchial and arterial dimensions. As emphasized by Kim et al. [56], visual inspection alone may lead to an overestimation of bronchoarterial ratios due to a subtle optical illusion, in which the diameter of hollow circles appears larger than solid circles despite their being identical in size. Considerable variation in bronchoarterial ratio may also be seen in normals. In a study by Kim et al. [58], the arterobronchus ratio, defined as the outer diameter of the pulmonary artery divided by the outer diameter of its accompanying bronchus measured at the subsegmental level, averaged 0.98 ± 0.14 but ranged from 0.53 to 1.39.
Despite variability in normal bronchial size and the methods by which bronchial diameter has been assessed, several studies have shown that measurements of bronchial diameter may be reliably made from HRCT [68,69]. Desai et al. [68] evaluated both inter- and intraobserver variation in CT measurements of bronchial wall circumference in 61 subsegmental bronchi and found the reproducibility of these measurements to be sufficiently clinically useful in demonstrating the progression of bronchiectasis. As emphasized by Diederich et al. [57], visual inspection remains the mainstay for assessing bronchial dilatation, as obtaining objective measurements (with or without the use of calipers) is time consuming and often clinically impractical. In this regard, use of visual inspection has been shown to
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have acceptable interobserver variability. Using visual inspection only, Diederich et al. [57] found close agreement among three readers both in the detection (κ = 0.78) and assessment of the severity (κ = 0.68) of bronchiectasis.
FIG. 8-6. Cystic bronchiectasis. A, B: Sections through the carina and lower lobes, respectively, show evidence of extensive cystic bronchiectasis. Bronchi are considerably larger than adjacent pulmonary artery branches (i.e., the bronchoarterial ratio is increased). In A, bronchi oriented in the plane of scan show a distinct lack of tapering. Note that despite marked dilatation, there is little evidence of bronchial wall thickening. In the left lower lobe, the cysts appear grouped together, giving the appearance of a cluster of grapes. In this region, the airway walls appear thickened, likely due to the presence of minimal consolidation in the posterior basilar segment. Note also the finding of a few bullae, most marked in the lingula but identifiable along the medial border of the left lower lobe as well.
A potential limitation of the use of bronchoarterial ratios is the necessity of identifying both airways and accompanying arteries. This may not always be possible in patients who have coexisting parenchymal consolidation [4]. Kang et al. was unable to determine the bronchoarterial ratios in three cases in a study of 47 resected lobes with documented bronchiectasis due to the presence of parenchymal consolidation [4].
Lack of Bronchial Tapering
Lack of bronchial tapering has come to be recognized as an important finding in the diagnosis of bronchiectasis, and subtle cylindrical bronchiectasis in particular (Table 8-2) (Fig. 8-6). It has been suggested that for this finding to be present, the diameter of an airway should remain unchanged for at least 2 cm distal to a branching point [56]. First emphasized by Lynch et al. [38] as a necessary finding for diagnosis, lack of bronchial tapering has been reported by some to be the most sensitive means for diagnosing bronchiectasis. Kang et al. [4], for example, in an assessment of 47 lobes with pathologically proved bronchiectasis, found lack of tapering of bronchial lumina in 37 cases (79%) as compared with increased bronchoarterial ratios seen in only 28 cases (60%). In another study [64], lack of tapering of bronchi was seen in 10% of HRCT interpretations in healthy subjects, compared with 95% of reviews in patients who had bronchiectasis. It should be emphasized that the accurate detection of this finding is difficult in the absence of contiguous HRCT sections, especially for vertically or obliquely oriented airways. The value of this sign is doubtful when HRCT scans are obtained
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at spaced intervals in a noncontiguous fashion. As discussed in this book, this has clear implications for optimizing scan technique in patients who have suspected airways disease.
FIG. 8-7. A, B: Cystic bronchiectasis largely limited to the right middle lobe in a patient who has a history of tuberculosis.
Visualization of Peripheral Airways
Another frequently cited manifestation of bronchiectasis is the visibility of airways in the lung periphery (Table 8-2) [4,64]. The smallest airways normally visible using HRCT techniques have a diameter of approximately 2 mm and a wall thickness of 0.2 to 0.3 mm [70]; in normal subjects, airways in the peripheral 2 cm of lung are uncommonly seen because their walls are too thin [71]. Peribronchial fibrosis and bronchial wall thickening in patients who have bronchiectasis, in combination with dilatation of the bronchial lumen, allow the visualization of small airways in the lung periphery, and this finding can be very helpful in diagnosing the presence of an airway abnormality. In a study by Kang et al. [4], bronchi visualized within 1 cm of pleura were seen in 21 of 47 (45%) bronchiectatic lobes.
Kim et al. have further assessed the value of this sign in the diagnosis of bronchiectasis [64], pointing out that although normal bronchi are not visible within 1 cm of the costal pleural surfaces, bronchi may be seen within 1 cm of the mediastinal pleural surfaces in normal subjects; visible bronchi were identified within 1 cm of the mediastinal pleura in 40% of normal subjects [64]. These authors found that visible bronchi within 1 cm of the pleural surface or bronchi touching the mediastinal pleural surfaces were visible in 81% and 53%, respectively, of HRCT interpretations in patients who had clinical or pathologic evidence of cylindrical bronchiectasis (Figs. 8-4A, 8-6, and 8-7).
Bronchial Wall Thickening
Although bronchial wall thickening is a nonspecific finding, it is usually present in patients who have bronchiectasis (Table 8-2) (Figs. 8-3, 8-4, and 8-7, 8-8 and 8-9). Generally accepted criteria for determining abnormal bronchial wall thickening have yet to be established.
Airways divide by asymmetric dichotomous branching, with approximately 23 generations of branches from the trachea to the alveoli. Anatomically, second- to fourth-generation segmental airways have mean diameters of between 5 and 8 mm, corresponding to a wall thickness of approximately 1.5 mm; sixth- to eighth-generation airways have mean diameters measuring between 1.5 and 3 mm with walls of approximately 0.3 mm; and eleventh- to thirteenth-generation airways have diameters measuring 0.7 to 1 mm, with walls of 0.1 to 0.15 mm [72]. The wall thickness of conducting airways distal to the segmental level is approximately proportional to their diameter. In general, the thickness of the wall of a bronchus or bronchiole smaller than 5 mm in diameter should measure from one-sixth to one-tenth of its diameter [73]; however, precise measurement of the wall thickness of small bronchi or bronchioles is difficult, as wall thickness approximates pixel size [70].
Precise definitions of bronchial wall thickening have been proposed by several investigators, relying on the visual assessment or measurement of the ratio between bronchial wall thickness and the diameter of adjacent pulmonary arteries or nearby normal airways (Fig. 8-9) [57,67,74,75]. Proposed techniques include determining the ratio of airway wall thickness to the outer airway diameter, as well as the percentage wall area defined as (wall area/total airway area) × 100. Using these parameters, Awadh et al. have shown that there is a
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clearly definable gradient in bronchial wall thickness between normal subjects and asthmatic patients of varying severity [76]. The relationship between wall thickness and bronchial diameter has also been assessed by Kim et al. [58], using the bronchial lumen ratio (BLR). At the subsegmental level, the BLR, defined as the inner diameter of the bronchus divided by its outer diameter, was measured at the subsegmental level on a display console. Considerable variation in the BLR was found, averaging 0.66 ± 0.06 with a range of 0.51 to 0.86 [58]. It has also been suggested that bronchial wall thickening may be diagnosed if the airway wall is at least 0.5 times the width of an adjacent vertically oriented pulmonary artery (Table 8-2).
FIG. 8-8. Cystic bronchiectasis. A, B: Sections through the carina and mid lungs, respectively, show isolated foci of cystic bronchiectasis. Bronchi are dilated and thick-walled. Note that some of these clearly communicate with proximal airways (arrows in A and B); others have clearly defined air-fluid levels (asterisk in B).
Identification of thickened bronchial walls for the purposes of interpretation of clinical scans remains largely subjective (Fig. 8-9) [4,36]. Because bronchiectasis and bronchial wall thickening are often multifocal rather than diffuse and uniform, a comparison of one lung region to another can be helpful in making this diagnosis. It must be emphasized that using consistent window settings is very important in the diagnosis of bronchial wall thickening; bronchial walls can vary significantly in apparent thickness with different CT window settings (see Chapter 1).
Although estimates of airway wall thickening are subjective, it has been shown that visual assessment of wall thickening may be reliable when sequential scans are assessed. Using a visual estimation of wall thickness, Diederich et al. [57] found acceptable levels of agreement among three readers as to the presence or absence of bronchial wall thickening
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(κ = 0.64). It should be emphasized, however, that interobserver agreement in itself might be a misleading statistic in assessing the validity of HRCT measurements. Bankier et al. [77], in a study of normal and abnormal airways evaluated by three independent observers before and after a training period, showed that although interobserver variability improved significantly on second readings, training had no effect on sensitivity. Sensitivity in detecting abnormal bronchi was 46% before and 44% after training, and specificity measured 71% and 72%, respectively [77]. Although these results are disappointing, it should be emphasized that the airway abnormalities evaluated in this study were extremely subtle, with abnormal segmental and subsegmental wall thickness measuring 1.77 mm and 0.95 mm, respectively, as compared with normal segmental and subsegmental airways measuring 1.14 mm and 0.46 mm. Furthermore, individual airways were assessed individually on targeted reconstructed images only. Nonetheless, a statistically significant difference (p = .001) between measured wall thickness of normal and pathologic bronchi was found [77].
FIG. 8-9. Bronchial wall thickening. HRCT section through the lung bases shows evidence of subtle bronchial wall thickening. Although this is usually diagnosed by visual inspection, it has been suggested that bronchial wall thickening should not be diagnosed until the airway wall is at least one-half the width of an adjacent vertically oriented pulmonary artery. By this criterion, the airway walls in the present example should not be considered abnormal in the absence of careful clinical correlation.
Mucoid Impaction
The presence of mucus- or fluid-filled bronchi may be helpful in confirming a diagnosis of bronchiectasis (Table 8-2). The HRCT appearance of fluid- (Fig. 8-8) or mucus-filled airways is dependent both on their size and orientation relative to the scan plane. Larger mucus-filled airways result in abnormal lobular or branching structures when they lie in the same plane as the CT scan (Figs. 8-10, 8-11, 8-12, 8-13, 8-14, and 8-15). Although these may be confused with abnormally dilated vessels, in most cases, the recognition of dilated, fluid-filled airways is simplified by the identification of other areas of bronchiectasis in which the bronchi are air-filled; these are usually present if carefully sought (Figs. 8-10A and 8-11). In problematic cases, a distinction between larger fluid-filled bronchi and dilated blood vessels is easily made by rescanning patients after the bolus injection of intravenous contrast medium (Fig. 8-13). Alternatively, with the introduction of newer-generation scanners, it is now possible to obtain high quality multiplanar and maximum-intensity projection images in a variety of imaging planes as a means for further evaluation (Figs. 8-14 and 8-15).
Although commonly associated with bronchiectasis and infection, dilated mucus-filled airways in the central lung can also result from congenital bronchial abnormalities, such as bronchopulmonary sequestration or bronchial atresia (Fig. 8-15) [78,79,80,81,82,83].
It should also be emphasized that the finding of dilated mucus-filled airways, especially when central or predominantly segmental or lobular in distribution, should alert one to the possibility of central endobronchial obstruction, resulting either from tumor or foreign body aspiration. As previously discussed, the use of intravenous contrast media in this setting may allow differentiation between central tumor and fluid-filled peripheral airways.
As is discussed in greater detail in the section on Bronchiolitis, mucus- or pus-filled small airways in the lung periphery are usually identifiable either as branching structures within the center of secondary lobules, aptly described as having a tree-in-bud (TIB) appearance [27,84] or as ill-defined centrilobular nodules (Table 8-2) [70,85,84,85,86,87,88] (Figs. 8-4, 8-11, 8-16, and 8-17). These are frequently identified in association with bronchiectasis and usually indicate infection. For example, in patients who have diffuse panbronchiolitis (DPB) [89], bronchiolectasis results in small, ring-shaped, round, or branching opacities in the peripheral lung. These opacities correspond to abnormalities of distal airways, including terminal and respiratory bronchioles [86,87,88].
FIG. 8-10. Mucoid impaction. A: Section through the lower lobes shows typical appearance of mucoid impaction, appearing as a tubular branching density (asterisk) associated with adjacent air-filled dilated airways. B: Section through the lower lobes in a different patient than A shows typical findings of mucoid impaction with linear branching densities throughout the left lower lobe. A focal area of ill-defined consolidation is also present in the medial tip of the middle lobe. C: Section at the same level as in B, after a course of antibiotic therapy and postural drainage. After clearing of retained secretions, cystic bronchiectasis is now easily identified.
FIG. 8-11. Varicose bronchiectasis in allergic bronchopulmonary aspergillosis. A: HRCT at the level of the middle lobe bronchus in a patient who has proven allergic bronchopulmonary aspergillosis. The proximal portion of the superior segmental bronchus of the right lower lobe is dilated and has a distinctly beaded appearance (curved arrow). Varicose bronchiectasis can only be diagnosed when involved bronchi course horizontally within the plane of the CT section. The rounded opacity on the left (straight arrow) is the result of mucoid impaction within a vertically coursing bronchus. B: HRCT in the same patient just below the carina. At this level, the predominant finding is mucoid impaction, recognizable as lobulated linear or branching densities extending toward the lung periphery (arrows).
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Mosaic Perfusion and Air-Trapping
Over the past several years it has become increasingly apparent that in most cases, patients who have bronchiectasis also show evidence of small airway pathology. Kang et al., for example, in their study of 47 resected lobes with documented bronchiectasis, found pathologic evidence of bronchiolitis in 85% [4]. These included six lobes with obliterative bronchiolitis, 18 with inflammatory or suppurative bronchiolitis, and 16 with both obliterative and inflammatory bronchiolitis. HRCT findings consistent with bronchiolitis were identified in 30 of 47 (75%) lobes, including a pattern of mosaic perfusion (n = 21) (Fig. 8-18); bronchiolectasis (n = 17); and centrilobular nodular or branching opacities, or both (i.e., TIB) (n = 10) (Figs. 8-4 and 8-16) [4].
In particular, the findings of mosaic perfusion on inspiratory scans and focal air-trapping on expiratory scans may prove of special interest in the early diagnosis of bronchiolitis associated with large airways disease (Table 8-2) (Figs. 8-18 and 8-19). In one study of 70 patients [90] who had HRCT evidence of bronchiectasis visible in 52% of lobes evaluated, areas of decreased attenuation (i.e., mosaic perfusion) were visible on inspiratory scans in 20% of lobes, and on expiration (air-trapping) in 34%. Although areas of decreased attenuation on expiratory scans were more prevalent in lobes with severe (59%) or localized (28%) bronchiectasis, in 17% of lobes, air-trapping was identified in the absence of associated bronchiectasis. This has led to speculation that evidence of bronchiolar disease may in fact precede and even lead to the development of bronchiectasis [7,90,91].
FIG. 8-12. Bronchiectasis with mucoid impaction. Target-reconstructed HRCT through the right upper lobe. mucus-filled airways can be recognized as lobulated linear or branching structures when they course horizontally in the plane of the section (curved arrows) or as discrete nodular opacities when they course vertically (straight arrow).
FIG. 8-13. Mucoid impaction–contrast enhancement. A: Section through the left upper lobe spur shows central mucoid impaction, with some distortion of the adjacent superior segmental bronchus identified. There is no evidence of peripheral air-trapping on this inspiratory scan. B: Section at the same level as in A after a bolus of intravenous contrast material shows no evidence of enhancement, confirming the diagnosis of mucoid impaction. Despite the absence of an apparent central tumor, this appearance is consistent with a focal endobronchial lesion. Bronchoscopically confirmed small central carcinoid tumor.
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In this same study [90], the presence of decreased attenuation on expiratory scans was also associated with mucoid impaction. This finding was seen in 73% of lobes with large mucous plugs and in 58% of those with centrilobular mucous plugs. These same authors noted a correlation (r = 0.40; p <.001) between the total extent and severity of bronchiectasis and the extent of decreased attenuation shown on expiratory CT. Not surprisingly, in 55 patients who had pulmonary function tests, the extent of expiratory attenuation abnormalities proved inversely related to measures of airway obstruction, such as forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FVC) [90].
Associated Bronchial Artery Hypertrophy
Normal bronchial arteries extend along the central airways to a level a few generations proximal to the terminal bronchioles and are the main blood supply for the bronchi. Arising directly from the proximal descending thoracic aorta, these typically measure less than 2 mm and, in addition to supplying the central airways, supply blood to the esophagus and mediastinal lymph nodes. Enlarged bronchial arteries can be identified pathologically in most cases of bronchiectasis and, when severe, usually account for the occurrence of hemoptysis in these patients. With HRCT, it has proved possible to identify both normal and abnormal
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bronchial arteries in select cases, especially after a bolus of intravenous contrast [92,93].
Song et al. were able to demonstrate good correlation between non-contrast enhanced HRCT images and corresponding CT angiograms for demonstrating hypertrophied bronchial arteries in patients who had bronchiectasis [94]. Specifically, these authors showed that the finding of tubular or nodular areas of soft-tissue attenuation, distinct from blood vessels within the mediastinum and adjacent to the central airways, correctly predicted bronchial artery hypertrophy in 88% and 53% of cases, respectively. Although the diagnosis of bronchiectasis rarely is dependent on demonstrating bronchial artery hypertrophy, identification of focal bronchial wall abnormalities due to enlarged bronchial arteries is important before attempted bronchoscopy, as inadvertent biopsy may lead to significant hemorrhage [94].
Classification of Bronchiectasis
Traditionally, bronchiectasis has been classified into three types, depending on the severity of bronchial dilatation. These three types are cylindrical, varicose, and cystic [95]. Although a distinction between these three types of bronchiectasis is sometimes helpful in diagnosis and correlates with the severity of the anatomic and functional abnormality [67], their differentiation is generally less important clinically than is a determination of the extent and distribution of the airways disease. Evaluating the
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extent of bronchiectasis is particularly important, as surgery is only rarely performed in patients who have involvement of multiple lung segments [23,24,96].
FIG. 8-14. Mucoid impaction–value of retrospective reconstructions. A, B: Select axial images through the upper and lower lobes, respectively, acquired in a single breath-hold period on a multidetector-row CT scanner using 1-mm detectors, show evidence of central mucoid impaction in both upper lobes (arrows in A) and both lower lobes (arrows in B). Fig. 8-2. Multiplanar coronal reconstruction through the posterior aspect of the lower lobes shows to better advantage the appearance of branching densities in both lower lobes (curved arrow). D: Maximum intensity projection image in the coronal plane using five adjacent 1-mm sections also shows the extent of mucoid impaction in the lower lobes and right upper lobe to better advantage (asterisks).
In CT scoring systems for bronchiectasis [67], the severity of bronchiectasis, in part, is related to its diameter relative to adjacent pulmonary artery branches, as less than two times the artery diameter, from two to three times the artery diameter, or more than three times the artery diameter. Although these three measurements of bronchial size have no specific relationship to the type of bronchiectasis defined pathologically,
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they may be reasonable clinical correlates with the terms cylindrical, varicose, and cystic, respectively.
Cylindrical Bronchiectasis
Mild or cylindrical bronchiectasis is diagnosed if the dilated bronchi are of relatively uniform caliber and have roughly parallel walls (Fig. 8-2). The appearance of cylindrical bronchiectasis varies depending on whether the abnormal bronchi have a horizontal or vertical course relative to the scan plane. When horizontal, bronchi are visualized along their length and are recognizable as branching tram tracks that fail to taper as they extend peripherally and are visible more peripherally than is normal. When cylindrically dilated bronchi are oriented in a vertical direction, they are scanned in cross section and appear as thick-walled, circular lucencies.
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In most cases, dilated bronchi seen in cross section can easily be distinguished from emphysematous blebs or other causes of lung cysts by identifying the signet ring sign and the continuity of the dilated bronchus on adjacent scans.
FIG. 8-15. Complex congenital disease–bronchial atresia and bronchogenic cyst. A: Axial section through the upper lobes, acquired in a single breath-hold period on a multidetector-row CT scanner using 1-mm collimation, shows classic appearance of mucoid-impacted airways in the left upper lobe (asterisks), associated with peripheral decreased lung attenuation. B, C: Volumetric rendering in the coronal plane and maximum intensity projection image in the sagittal plane, respectively, confirm the presence of extensive mucoid impaction restricted to the left upper lobe associated with peripheral air-trapping, findings characteristic of bronchial atresia. Fig. 8-15. Continued D: Axial section obtained without intravenous contrast media shows a high attenuation bronchogenic cyst insinuated between the descending thoracic aorta and the left main pulmonary artery (asterisk). Combinations of congenital airway anomalies should not be considered rare.
Varicose Bronchiectasis
With increasingly severe abnormalities of the bronchial wall, bronchi may assume a beaded configuration referred to as varicose bronchiectasis. This diagnosis can be made consistently only when the involved bronchi course horizontally in the plane of scan (Figs. 8-3, 8-11, and 8-16). Varicose bronchiectasis is much less frequent than cylindrical bronchiectasis.
Cystic Bronchiectasis
With severe or cystic bronchiectasis, involved airways are cystic or saccular in appearance and may extend to the pleural surface (Figs. 8-4 and 8-6, 8-7 and 8-8). On HRCT, cystic bronchiectasis may be associated with the presence of (i) air-fluid
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levels caused by retained secretions in the dependent portions of the dilated bronchi (Fig. 8-8), (ii) a string of cysts, caused by sectioning irregularly dilated bronchi along their length, or (iii) a cluster of cysts (Figs. 8-7 and 8-20), caused by multiple dilated bronchi lying adjacent to each other. Clusters of cysts are most frequently seen in atelectatic lobes (Fig. 8-20), presumably as a result of chronic infection such as commonly occurs in patients who have pulmonary tuberculosis. In general, the dilated airways in patients who have cystic bronchiectasis are thick-walled; however, cystic bronchiectasis may also appear thin-walled (Fig. 8-6). Recognition of some combination of dilated bronchi, air-fluid levels, and strings or clusters of cysts should be diagnostic of cystic bronchiectasis [97].
FIG. 8-16. A-C: Varicose bronchiectasis associated with chronic airway infection by Haemophilus influenzae. Irregularly dilated and thick-walled bronchi are typical of varicose bronchiectasis. Ill-defined branching structures (tree-in-bud) and small centrilobular nodules (arrows, B and C) are also visible. Continued
FIG. 8-17. Bronchiectasis associated with endobronchial spread of mycobacteria. A: Target-reconstructed HRCT section through the right upper lobe in a patient who has documented active cavitary tuberculosis. Note the presence of a focal cluster of small nodules anterior to the cavity, and adjacent to peripheral pulmonary artery branch (arrow). This has been called a tree-in-bud appearance and results from mucus or infected material within small peripheral airways. This finding is associated with endobronchial spread of infection. B: Target-reconstructed HRCT image through the right lung in a different patient shows marked volume loss and varicose bronchiectasis throughout the middle lobe (straight arrow). In addition, note the presence of mucous plugging with a tree-in-bud appearance in the right lower lobe (curved arrows). In the appropriate clinical setting, this constellation of findings should suggest the possibility of mycobacterial infection, specifically Mycobacterium avium complex, which was subsequently documented.
FIG. 8-18. Bronchiolitis obliterans and bronchiectasis. A, B: Sections through the lower lobes in inspiration (INSP) and expiration, respectively. Moderately severe bronchiectasis is present in the right lower lobe, resulting in mild bronchial dilatation and wall thickening. Whereas mosaic attenuation is apparent on the inspiratory scan, air-trapping is more definitively identified on the expiration scan. Areas of low density in regions of bronchiectasis have been shown to be due to bronchiolitis obliterans, which may in fact precede the development of bronchiectasis.
Assessment of Bronchiectasis Extent and Severity
It has been shown that CT classification of the type of bronchiectasis may be useful as an index of disease severity. As documented by Lynch et al. [98] in a study of 261 patients who had symptomatic and functionally significant bronchiectasis, excluding patients who had cystic fibrosis (CF), allergic bronchopulmonary aspergillosis (ABPA), or fungal or mycobacterial infections, there was significant correlation between the severity and extent of bronchiectasis with FEV1 and FVC. Furthermore, those who had cystic bronchiectasis were more likely to have purulent sputum, especially due to Pseudomonas, than patients who had cylindrical or varicose bronchiectasis.
FIG. 8-19. Mosaic perfusion in bronchiectasis and bronchiolitis: assessment with minimum-intensity projection images. A: HRCT section through the midlungs shows evidence of mild bronchial dilatation and subtle mosaic perfusion in this patient who has known obliterative bronchiolitis. B: Corresponding minimum-intensity projection image using five contiguous 1-mm sections shows to better advantage the extent of mosaic perfusion (arrows).
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Although visual estimates of disease severity and extent are commonly used, it is apparent that a more accurate approach to disease assessment requires some degree of quantification. Given the importance that has traditionally been placed on the radiographic and clinical scoring of abnormalities in patients who have CF, it is not surprising that CT scoring systems have been most carefully evaluated in this population. Bhalla et al., in the most widely cited method, used nine separate variables, including the extent of mucous plugging, peribronchial thickening, generations of bronchial divisions involved, number of bullae, and the presence of emphysema to calculate a global CT score [74]. Based on this approach, these authors found CT to be a valuable tool for objectively evaluating the extent and severity of bronchiectasis in patients who have CF.
Subsequent modifications of this system have been proposed by a number of authors [55,67,99,100,101,102,103]. Although similar in scope, there are important differences among these approaches. These include differences in the definition of bronchial dilatation and bronchial wall thickening and the extent of bronchiectasis. For example, although Bhalla et al. [74] assessed segments in their scoring system, Smith et al. [55] assessed lobes using a five-point scale based on the visual assessment of the number of abnormal bronchi (as less than 25%, 25 to 49%, 50 to 74%, or greater than 75%). Although this approach has the benefit of relative simplicity, its adequacy has been questioned by Diederich et al. [57], who reported only moderate interobserver agreement among three readers (κ = 0.58) for assessing disease severity.
FIG. 8-20. Cystic bronchiectasis. A, B: Target-reconstructed HRCT images through the right lower lung field show the characteristic appearance of a cluster-of-grapes sign. This sign typically results when bronchiectasis occurs in atelectatic lung. Note that in this case both the middle lobe (arrow, A) and the right lower lobe (straight arrow, B) are collapsed, causing marked displacement of the oblique fissure (curved arrows, A, B).
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Other differences among scoring systems include the methods of describing the axial extent of disease. Some investigators assess the number of generations of airways involved [74,102,103], whereas others use descriptive schema based on the identification of abnormal airways either in the peripheral half or one-third of the lung [67,99,100] or describe the overall extent of disease as assessed regionally by lobe and zone [101]. More recent scoring systems have also emphasized the inclusion of centrilobular nodules and mosaic perfusion as additional signs of airways disease [99,100,102,103].
These differences notwithstanding, most reports have documented good correlation between HRCT assessment of bronchiectasis extent and severity of disease when compared with more traditional radiographic, clinical, or functional evaluations [55,74,100,102,103]. For example, Smith et al. [55] found correlations between the extent of bronchiectasis and both dyspnea and FEV1. In patients who had CF, Shah et al. [100] found that HRCT severity scores in symptomatic and asymptomatic patients correlated with FVC (r = 0.44; p = .01) and FEV1 (r = 0.34; p = .04), whereas severity of bronchiectasis correlated with FVC (r = 0.50; p = .004) and FEV1 (r = 0.40; p = .02). In symptomatic patients, improvement in HRCT score correlated with changes in FEV1/FVC (r = 0.39; p = .049). In a study by Roberts et al. [91], the extent and severity of bronchiectasis and the severity of bronchial wall thickening correlated strongly with the severity of airflow obstruction. The severity of bronchial dilatation was negatively associated with airflow obstruction.
Nonetheless, given the lack of general clinical acceptance for the use of CT scoring systems to quantitatively assess and monitor patients, especially those who have chronic diseases such as CF, the need for a standardized scoring system is apparent not only for accurate assessment of response to therapy, but also to ensure valid comparisons between studies of differing populations. Such a system derived from existing published reports is proposed in Table 8-3.
Technical Considerations in the High-Resolution Computed Tomography Diagnosis of Airways Disease
Given the range and subtlety of abnormalities that can be identified in patients who have airways disease, it is apparent that an accurate diagnosis requires meticulous attention to both scan technique and scan protocols. These techniques are discussed in more detail in Chapter 1.
Scan Technique
A number of technical factors need to be considered in assessing airway pathology. As discussed in Chapter 1, these include slice thickness, slice spacing, field of view (FOV), and reconstruction algorithm. Using an FOV of 13 cm × 13 cm provides the maximum spatial resolution, with resulting pixels measuring approximately 0.25 mm × 0.25 mm [104]. If 1-mm collimation is used, voxel size is 0.25 mm × 0.25 mm × 1.00 mm, equal to 0.06 mm3 [105]. Although a small FOV is rarely used in routine clinical imaging, the ability to obtain target-reconstructed images through select areas may enhance visualization of fine parenchymal detail and be of value in select cases with airways disease.
Most important for accurate airway evaluation is the use of appropriate window levels and windows, especially in those cases for which quantitative information is sought (see Fig. 1-13). As first shown by Webb and coworkers using phantoms composed of lucite cylinders, an optimal window level for assessing the airway lumen and walls is -450 Hounsfield units (HU) [106]. A similar conclusion has been reached by McNamara et al., also by using a reference phantom [105,107]. In distinction, others have suggested that window
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width is as important as or more important than window level in airway measurements. Bankier et al. [108], using inflation-fixed lungs to evaluate the effect of window width and levels on bronchial wall thickness confirmed by planimetry, concluded that an optimal window width should vary between 1,000 and 1,400 HU, whereas window levels could vary as much as between -250 and -700 HU. In our experience, for practical purposes, these windows and levels are adequate for routine visual assessment (see Fig. 1-13).
TABLE 8-3. HRCT bronchiectasis scoring systema
  Score
Category 0 1 2 3
Severity        
Bronchiectasisb,d Normal <2× 2-3× >3×
Bronchial wall thickeningb,d,f Normal <0.5× or <10 mm 0.5-1× or 10-15 mm >1× or >15 mm
Mosaic perfusionh Normal 1-5 segments 6-9 segments >9 segments
Sacculations/abscessese Normal 1-5 segments 6-9 segments >9 segments
Extent        
Bronchiectasise Normal 1-5 segments 6-9 segments >9 segments
Axial distributiong Normal Centralc Peripheralc Mixed
Mucous plugging/centrilobular nodulesh Normal 1-5 segments 6-9 segments >9 segments
Optional        
Severity of emphysemae Normal 1-5 segments >5 segments  
Severity of bullaee Normal Unilateral (<4) Bilateral (<4) >4
Severity of consolidation/atelectasisa Normal 1-3 segments 4-6 segments >7 segments
 a Total score: without options, from 0 to 21; with options, from 0 to 29.
 b Compared to the diameter of an adjacent pulmonary artery.
 c Peripheral defined as the outer 50% of the lung parenchyma in axial section.
 d From Reiff DB, Wells AU, Carr DH, et al. CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types. AJR Am J Roentgenol 1995;165:261.
 e From Bhalla M, Turcios N, Aponte V, et al. Cystic fibrosis: scoring system with thin-section CT. Radiology 1991;179:783.
 f From Shah RM, Sexauer W, Ostrum BJ, et al. High-resolution CT in the acute exacerbation of cystic fibrosis: evaluation of acute findings, reversibility of those findings, and clinical correlation. AJR Am J Roentgenol 1997;169:375.
 g From Cartier Y, Kavanagh PV, Johkoh T, et al. Bronchiectasis: accuracy of high-resolution CT in the differentiation of specific diseases. AJR Am J Roentgenol 1999;173:47.
 h From Helbich TH, Heinz-Peer G, Eichler I, et al. Evolution of CT findings in patients with cystic fibrosis. AJR Am J Roentgenol 1999;173:81.
Scan Protocols
Following the report of Grenier et al., the use of HRCT sections acquired every 10 mm in deep inspiration has become standard for diagnosing bronchiectasis [109]. Using this protocol, Grenier et al. [109] have found a very high accuracy for HRCT in diagnosing bronchiectasis as compared to bronchography. Subsequent reports have further confirmed the value of these techniques for establishing the diagnosis of bronchiectasis [62,110].
Based on the results of these studies and several others, the following technique is recommended for patients who have suspected bronchiectasis (see Chapter 1). In patients in whom there are no specific clinical or radiographic signs to help localize disease, 1- to 1.5-mm high-resolution images should be obtained every 10 mm from the lung apices to bases. Despite the lack of contiguous scanning, this technique allows adequate assessment of the bronchial tree in nearly all cases. Although the routine use of thick sections is not indicated, in select cases, especially those in whom mild cylindrical bronchiectasis is suspected, selected thick sections within a limited range of interest may be of value [38].
This approach can be modified to reflect varying clinical presentations. For example, in patients presenting with hemoptysis, it is usually necessary to rule out occult central endobronchial lesions in addition to detecting bronchiectasis. This is best accomplished by obtaining 1- to 1.5-mm-thick sections every 10 mm through the upper- and lower-lung zones, and contiguous 3- to 5-mm-thick sections from the carina to the level of the inferior pulmonary veins [50]. Using this protocol, in a retrospective study of 59 patients evaluated both by CT and fiberoptic bronchoscopy, CT proved abnormal in all cases in which fiberoptic bronchoscopy depicted focal airway pathology [50]. Alternatively, when available, helical or spiral scanning can be substituted for the routine 5-mm axial images through the central airways. These have
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the advantage of eliminating misregistration artifacts as well as allowing high quality three-dimensional or multiplanar reconstructions to be performed.
FIG. 8-21. Cystic fibrosis evaluation with low-dose CT. HRCT section through the midlung in a patient who has diffuse bronchiectasis due to cystic fibrosis. Note that central bronchi are involved to a greater degree than peripheral bronchi. Although cylindrical bronchiectasis predominates, small cystic lucencies are also present, reflecting cystic bronchiectasis or abscess cavities. This 2-second scan was performed using 120 kV(p) and 20 mA. In select patients for whom repeated follow-up CT scans may be indicated, high-quality images can be obtained using a low-dose technique. (Courtesy of Minnie Bhalla, M.D., Massachusetts General Hospital, Boston, Massachusetts.)
Additional scan techniques have also been advocated. As suggested by Remy-Jardin et al. [111], visualization of bronchiectatic segments may be enhanced by use of 20-degree cranial angulation of the CT gantry (see Fig. 1-19). Although unnecessary in most patients, this technique may be of value in equivocal cases, especially for those airways that normally course obliquely, such as the middle lobe and lingular bronchi.
The use of low-dose HRCT techniques for performing routine follow-up scans in patients who have severe chronic disease has also been suggested [74,112]. Bhalla et al. [74], evaluating scans obtained using both 70 and 20 mA, showed that high-quality HRCT images of bronchiectatic airways could be obtained in patients who had CF (Fig. 8-21).
The introduction of spiral CT scanning has led to a reconsideration of optimal scan protocols in patients who have airways disease. In a study by van der Bruggen-Bogaarts et al. [113], spiral CT was found to have a high sensitivity (91%) and specificity (99%) in the diagnosis of bronchiectasis detected using HRCT. In this study, 30 patients and 177 lobes were evaluated with spiral CT (slice thickness, 5 mm; pitch, 1; reconstructed at 2 mm) and HRCT (1.5 mm, 10 mm scan spacing). At HRCT, 14 patients showed signs of bronchiectasis in 32 lobes: Spiral CT confirmed the presence in 29 lobes. In one lobe, spiral CT was falsely positive. In a study by Lucidarme et al. [6] of 50 consecutive patients who had suspected bronchiectasis, 1.5-mm HRCT sections obtained at 10-mm intervals were compared to a single 24-second volumetric acquisition using 3-mm collimation. These authors found volumetric data acquisition to be more accurate than routine HRCT for the identification of bronchiectasis. Although helical CT failed to identify bronchiectasis in seven segments in which the disease was diagnosed with HRCT, in four cases a diagnosis of subsegmental cylindrical bronchiectasis was made only with helical CT. In comparison, there were no patients in whom a diagnosis of bronchiectasis was established by HRCT alone.
Spiral CT shows greatest promise in the diagnosis of subtle cylindrical bronchiectasis. Evaluation of the finding of lack of bronchial tapering is difficult using noncontiguous 1-mm sections, effectively reducing the value of this sign to those bronchi that course within the plane of the CT scan. As documented by Giron et al. [110], in a study of 54 patients who had bronchographic evidence of bronchiectasis, obtaining 1-mm sections every 10 mm, three cases were missed and all had mild cylindrical bronchiectasis.
The introduction of multidetector-row spiral CT scanners promises to greatly improve our ability to diagnose airway pathology (see Fig. 1-23; Figs. 8-14, 8-15, and 8-22). The ability to scan the entire thorax in a single breath hold, using 1- to 1.25-mm detector width, and enabling sections of varying thickness to be prospectively and retrospectively reconstructed at any level, is of great value in the diagnosis of airways disease. As indicated in Chapter 1, this technique may fundamentally change the manner in which HRCT is obtained, at least in some patients. The use of reconstruction techniques such as maximum- and minimum-intensity projection images and precise internal and external volumetric renderings of the airways (see Fig. 1-23; Figs. 8-14, 8-15, 8-19, and 8-22) is of potential value. Although many of these techniques are best suited to evaluating small airways disease, potential applications also extend to the larger airways. Of particular interest is the potential to generate CT bronchograms (Fig. 8-22) [8,114].
Given these options, it is apparent that choice of scan technique depends on the type of scanner available, as well as available postprocessing capabilities. It is also likely that specific protocols will continue to evolve with continued clinical experience. Our current recommendation for single-detector scanners calls for an initial series of 1-mm routine axial sections acquired every 10 mm. This may be supplemented with volumetric acquisition of 3-mm sections through the central airways with a pitch of 1.6 to 2, reconstructed every 2 mm [6,115]. Based on our initial experience, a range of potential scan techniques may be applicable to multidetector-row scanners. Using either 1-mm or 1.25-mm detector widths, we reconstruct 3- to 5-mm sections every 2 to 4 mm, as well as contiguous
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1- to 1.25-mm sections or 1- to 1.25-mm sections every 10 mm.
FIG. 8-22. CT bronchography. A-D: Sequential axial images through the left lower lobe obtained with a multidetector-row scanner, using 1-mm detectors acquired in a single breath-hold using cardiac gating, show focal filling defects consistent with retained secretions (arrows). E: External surface rendering of these same airways creating a CT bronchogram: Note the presence of focal airway narrowing corresponding to the same foci identified in A through D (arrows). (Courtesy of Dr. Bernhard Geiger, Siemens Medical Research Inc., Princeton, New Jersey.)
HRCT may also be used to evaluate the presence of air-trapping in patients who have suspected bronchiectasis (see Figs. 3-148, 3-149, 3-150, 3-151, 3-152 and 3-153; Fig. 8-18) [11,17,90,91,116,117]. This may be accomplished by repeatedly acquiring scans at one preselected level during a forced expiration or as two separate acquisitions, first in deep inspiration, followed by scans obtained through the same region in expiration (see Chapters 1 and 2) [9,10,14,90,115,118,119]. This technique of paired inspiratory and expiratory images may be obtained using HRCT or spiral volumetric techniques. It should be emphasized that although a variety of strategies for acquiring expiratory scans have been proposed, including 1-mm images obtained at three levels (aortic arch, tracheal carina, and above the diaphragm) are usually sufficient to identify significant air-trapping, even when inspiratory scans are normal [117].
Regardless of the expiratory scan technique used, the resulting images allow the identification of focal areas of air-trapping, as well as changes in the appearance of the airways themselves. In a study of 100 patients who had bronchiectasis having both inspiratory and expiratory scans [91], the extent of decreased attenuation (i.e., air-trapping) on the
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expiratory CT scan correlated strongly with the severity of airflow obstruction; the closest relationship (r = -0.55; p = .00005) was seen between decreased FEV1.
TABLE 8-4. Pitfalls in the HRCT diagnosis of bronchiectasis
Technical factorsaa
 Respiratory and/or cardiac motion artifactsaa
 Inappropriate collimation (sections greater than 3 mm)
 Inappropriate window settings (e.g., window width less than 1,000 HU)
Reversible bronchiectasisaa
 Lung consolidation/pneumonia
 Atelectasis
Pseudobronchiectasis
 (e.g., Langerhans histiocytosis; cavitary metastases; Pneumocystis carinii pneumonia)
Traction bronchiectasisa
Increased bronchoarterial ratio in normals, asthmatics, or at high altitudeaa
 a aMost common findings.
It is worth noting that in select cases, minimum-intensity projection images may be more sensitive than routine images for detecting subtle regions of air-trapping on expiratory scans (Fig. 8-19) [120,121,122].
Pitfalls in the Diagnosis of Bronchiectasis
Several potential pitfalls in the diagnosis of bronchiectasis should be avoided (Table 8-4) [1]. Of particular concern are those due to respiratory and cardiac motion artifacts (Fig. 8-23). Transmitted cardiac motion artifacts frequently obscure detail in the left lower lobe and may lead to an erroneous diagnosis of subtle bronchiectasis [123]. Respiratory motion artifacts also cause ghosting that can very closely mimic the appearance of tram tracks. As previously discussed in the section Bronchial Wall Thickening, and in Chapter 1, the appearance of bronchial wall thickening is dependent on the use of appropriate window widths and levels [108]. Furthermore, on expiratory scans, bronchi can appear thicker-walled and narrower than on inspiratory scans.
Bronchiectasis is especially difficult to diagnose in patients who have concurrent parenchymal consolidation or atelectasis, as CT often discloses dilated peripheral airways that will revert to normal after resolution of the lung disease, so-called reversible bronchiectasis (Fig. 8-24) [124]. In such cases, follow-up scans are recommended, pending radiographic resolution. Another potential pitfall related to lung consolidation is the fact that consolidation may obscure vascular anatomy, rendering interpretation of bronchoarterial ratios difficult or impossible [4]. Of course, as emphasized throughout this textbook, visualization of small structures within the lung requires a high-resolution technique. This is especially true when assessing smaller airways (Fig. 8-25).
FIG. 8-23. Pseudobronchiectasis. HRCT section through the lung bases in a normal patient. In this case, transmitted cardiac pulsations have caused characteristic stellate artifacts in the left lower lobe that superficially mimic the appearance of bronchiectasis (arrows). Note the normal appearance of the lung on the right side by comparison.
A number of cystic lung diseases may also be difficult to differentiate from bronchiectasis (Figs. 8-26 and 8-27). Included in this grouping are cavitary nodules in patients who have either widespread bronchoalveolar cell carcinoma or cavitary metastases. Rarely, cystic lesions in patients who have Pneumocystis carinii pneumonia (PCP) may superficially simulate bronchiectasis: In these cases, it should be recognized that cystic changes usually occur within areas of ground-glass opacity, simplifying differential diagnosis. In patients who have Langerhans cell histiocytosis, bizarre-shaped cysts are often seen, especially in the upper lobes. As these may appear to branch, their appearance may be suggestive of bronchiectasis, so-called pseudobronchiectasis (Figs. 8-26A and 8-27). In fact, pathologically, some of these cystic abnormalities indeed represent abnormally dilatated bronchi, presumably the result of peribronchiolar inflammation.
Bronchiectasis may occur as a component of fibrotic lung diseases or may be seen after radiation therapy. Regardless of the underlying etiology, the result is so-called traction bronchiectasis (Figs. 8-28 and 8-29). This is easily identified, as peripheral bronchi appear irregularly thick-walled or corkscrewed and are invariably found in association with either diffuse reticular changes or honeycombing [125]. Traction bronchiectasis does not represent primary airways disease and is unassociated with symptoms [125].
Utility of High-Resolution Computed Tomography for the Diagnosis of Bronchiectasis
In our experience, most patients studied using HRCT have clinically suspected disease and subtle abnormalities identified on routine radiographs. Symptomatic patients who have
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entirely normal radiographs are the exception. In a prospective study comparing chest radiographs and HRCT [126], a normal chest radiograph was found to almost always exclude significant bronchiectasis. In this study, 37 patients had a normal radiograph, and 32 of these had a normal HRCT. The other five had mild cylindrical bronchiectasis. In distinction, in the 47 patients who had an abnormal radiograph, 36 had signs of bronchiectasis at HRCT and 11 had a normal HRCT. Thus, in this study, the sensitivity of chest radiography for detecting bronchiectasis diagnosed by HRCT was 88% and the specificity was 74%.
FIG. 8-24. Reversible bronchiectasis. A, B: HRCT section shows marked narrowing of the right lower lobe bronchus (arrow), with an associated mass in the right hilum (asterisk) and apparent bronchiectasis in the right lower lobe, respectively. These findings were interpreted as secondary to a partially obstructing proximal tumor. At bronchoscopy, the right lower lobe bronchus proved to be obstructed by aspirated foreign material (cellulose) without tumor. Nodal enlargement proved to be reactive hyperplasia. C: HRCT section at the same level as B, obtained 3 months later, shows minimal residual dilatation of the airways. These findings indicate that care should be exercised in diagnosing the presence and severity of bronchiectasis in the presence either of obstruction, atelectasis, or active parenchymal inflammation.
FIG. 8-25. Bronchiectasis: value of HRCT. A, B: Corresponding 7- and 1-mm axial images, respectively, obtained through the same level of the lower lobes in a patient who has moderately severe cylindrical bronchiectasis in both the middle and right lower lobes, clearly demonstrate the superiority of HRCT for identifying dilated airways (arrows).
Although its use was initially controversial, HRCT has emerged as the imaging modality of choice for evaluating bronchiectasis; HRCT has all but eliminated the use of bronchography.
Studies assessing the CT diagnosis of bronchiectasis using 10-mm-thick collimation provided low sensitivities, ranging between 60% and 80%, with specificities between 90% and 100% [59,60,61,127,127,129,130]. It quickly became apparent, however, that a significant improvement in diagnostic sensitivity could be achieved by the use of high-resolution 1- and 1.5-mm sections.
Grenier et al. [109], using 1.5-mm-thick sections obtained every 10 mm, retrospectively compared CT and bronchography in 44 lungs in 36 patients and found that CT confirmed the diagnosis of bronchiectasis with a sensitivity of 97% and a specificity of 93%. Young et al. [62] also assessed the reliability of HRCT in the assessment of bronchiectasis as compared to bronchography in 259 segmental bronchi from 70 lobes of 27 lungs. HRCT was positive in 87 of 89 segmental bronchi shown to have bronchiectasis
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(sensitivity, 98%). HRCT was negative in 169 of 170 segmental bronchi without bronchiectasis at bronchography (specificity, 99%). Similar results have been reported by Giron et al. [110].
FIG. 8-26. Pitfalls in the diagnosis of bronchiectasis: diffuse cystic lung disease. A: Langerhans cell histiocytosis. Section through the middle lungs shows scattered, thick-walled cystic lesions. Although some appear to be branching (straight arrow), others are unrelated to any accompanying artery (curved arrows), whereas others appear to have feeding vessels (open arrow). Note also the presence of few ill-defined subpleural nodules. This constellation of findings is characteristic of Langerhans cell histiocytosis. Although most of these cystic lesions represent cavitating nodules, some likely actually represent abnormally dilated airways. B: Cystic Pneumocystis carinii pneumonia. Section through the middle lungs shows scattered thin- and thick-walled cysts, some with an apparent branching configuration (small arrow). Many of these cysts are unrelated to adjacent arteries, whereas others are clearly subpleural (large arrow), accounting in this case for the presence of a small anterior pneumothorax on the left side. C: Metastatic adenocarcinoma: 1-mm section in a patient who has adenocarcinoma metastatic to the airways. The bronchi are dilated diffusely and thick-walled (straight arrow), without central obstruction. Solid lobular densities (curved arrow) represent impacted bronchi.
It should be emphasized that despite the excellent sensitivity of HRCT, bronchiectasis may be focal and exceedingly subtle on HRCT scans. Cylindrical bronchiectasis, in particular, can be missed on HRCT, especially if care is not taken to obtain images in deep inspiration [109,110,131]. Giron et al. [110], in a study of 54 patients who had bronchographic evidence of bronchiectasis, found that they missed three cases, all with mild cylindrical bronchiectasis, using 1-mm-thick slices obtained every 10 mm.
Differentiation of Causes of Bronchiectasis
Although an underlying cause of bronchiectasis is identified in less than 40% to 70% of cases, specific HRCT findings in a number of disease entities have been described. The reliability of CT for distinguishing between these is still debated
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[67,101,132]. Reiff et al. [67] evaluated the HRCT scans of 168 patients who had chronic purulent sputum production suspected of having bronchiectasis. With the exception of a predominant lower lobe distribution in patients who had syndromes of impaired mucociliary clearance, these authors found no significant difference in lobar distribution between cases of idiopathic bronchiectasis and those with a known etiology. Although central bronchiectasis was more common in patients who had ABPA, the sensitivity of this finding as a diagnostic feature proved to be only 37% [67]. Similarly, although the extent and severity of disease were more pronounced in patients who had both ABPA and CF, these features were of only limited value in individual cases [67].
FIG. 8-27. Pseudobronchiectasis in Langerhans cell histiocytosis. Target-reconstructed HRCT image through the right middle lung of a patient who has Langerhans cell histiocytosis shows multiple, variably sized cystic lesions, some with bizarre or branching appearances (arrow).
Lee et al. [132], in a similar study of CT scans in 108 patients who had bronchiectasis from a variety of causes, found that a correct first-choice diagnosis was made by three experienced observers in only 45% of cases; more problematic still, a high confidence level was reached in only 9%, and of these, a correct diagnosis was made in only 35%. Furthermore, interobserver agreement was poor (mean, K= 0.20) leading these investigators to conclude that CT was of little value in diagnosing specific etiologies of bronchiectasis. It should be emphasized that CT scans were interpreted in the absence of clinical data [132].
Cartier et al. [101] reported slightly better results in a retrospective study of 82 consecutive patients who had bronchiectasis with documented etiologies. These authors noted that a correct diagnosis was reached by two independent observers in 61% of cases, including a correct diagnosis in 68% of cases of CF, 67% of cases with tuberculosis, and 56% of cases of ABPA [101]. Specifically, in this study, a bilateral upper lobe distribution was most commonly seen in patients who had CF and ABPA, whereas unilateral upper lobe distribution was most common in patients who had tuberculosis, and a lower lobe distribution was most often seen in patients after childhood viral infections.
It should be emphasized that the value of HRCT is considerably enhanced when more focused clinical issues are addressed. Ward et al. [63], for example, assessing the accuracy of HRCT in the diagnosis of ABPA in asthmatic patients, found that a combination of bronchiectasis in more than three
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lobes, centrilobular nodules, and mucoid impaction could be identified in 95%, 93%, and 67% of cases, respectively, in patients who had ABPA. By comparison, these same findings were present in only 29%, 28%, and 4% of asthmatic controls, leading these investigators to conclude that HRCT is of clinical value in identifying asthmatic patients who have ABPA [63].
FIG. 8-28. Traction bronchiectasis in interstitial fibrosis. A: Section through the lower lobes in a patient who has histologically documented usual interstitial pneumonia (UIP) shows architectural distortion and honeycombing predominantly affecting the peripheral and inferior portions of the lower lobes. Dilated irregular bronchi are apparent bilaterally (arrows), associated with peribronchial increased soft tissue, findings characteristic of traction bronchiectasis due to peribronchial cicatrization. Continued B: Section through the lung bases at nearly the same level as in A, in a different patient also with histologically proven UIP. Despite the lack of honeycombing, there are marked reticular markings and a suggestion of diffuse ground-glass opacity. Note that the airways are dilated and mildly corkscrewed and fail to taper peripherally. This appearance is consistent with extensive and irreversible parenchymal fibrosis with resultant traction bronchiectasis.
FIG. 8-29. Traction bronchiectasis in interstitial fibrosis. HRCT section through the lower lobes shows evidence of diffuse parenchymal consolidation and ground-glass opacity associated with numerous dilated, tortuous airways both centrally (curved arrow) and peripherally (straight arrows). An autopsy performed shortly after this study revealed extensive pulmonary fibrosis and traction bronchiectasis without significant inflammation.
Diseases Associated with Bronchiectasis
The HRCT appearances of a number of diseases associated with bronchiectasis have been described. In many of these, such as hypogammaglobulinemia [133], HRCT findings are unremarkable as described previously. On the other hand, a few conditions associated with bronchiectasis have been reported to have distinctive HRCT appearances that can aid in their diagnosis or are sufficiently common to warrant detailed description. The most important of these are CF, ABPA, and nontuberculous mycobacterial infection. Bronchiectasis in association with lung nodules is characteristic of nontuberculous mycobacterial infection resulting from MAC (Fig. 8-30) and is described in detail in Chapter 5. It should also be recognized that bronchiectasis is a common feature of diseases usually regarded to predominantly involve small airways, such as BO and panbronchiolitis. These are described in detail later in this chapter.
Cystic Fibrosis
CF is the most common cause of pulmonary insufficiency in the first three decades of life [134,135]. It results from an autosomal-recessive genetic defect in the structure of the
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cystic fibrosis transmembrane regulator protein, which leads to abnormal chloride transport across epithelial membranes. The mechanisms by which this leads to lung disease are not entirely understood, but an abnormally low water content of airway mucus is at least partially responsible, resulting in decreased mucus clearance, mucous plugging of airways, and an increased incidence of bacterial airway infection. Bronchial wall inflammation progressing to secondary bronchiectasis is universal in patients who have long-standing disease and is commonly visible on chest radiographs [136].
FIG. 8-30. Atypical mycobacterial infection. Section through the middle lungs in a patient who has documented Mycobacterium avium infection shows extensive bronchiectasis primarily involving the middle lobe, and, to a lesser degree, the lingula, with near-complete sparing of the lower lobes. Scattered small centrilobular nodules are also apparent. This distribution of disease is characteristic of this infection, especially in elderly women.
Plain radiographs can be diagnostic in patients who have CF, showing increased lung volumes, accentuated linear opacities in the central or upper lung regions due to bronchial wall thickening or bronchiectasis, central bronchiectasis, and mucoid impaction [136]. However, plain film findings in patients who have early or mild disease may be quite subtle. Hyperinflation, which can represent an early finding, reflects the presence of obstruction of small airways by mucus; thickening of the wall of the right upper lobe bronchus, best seen on the lateral radiograph, can also be an early sign of disease [137]. In adult CF patients and patients who have chronic disease, abnormalities can include cystic regions in the upper lobes, representing cystic bronchiectasis, healed abscess cavities, or bullae; atelectasis, findings of pulmonary hypertension, or cor pulmonale; pneumothorax; and pleural effusion [138]. In the large majority of patients who have an established diagnosis of CF, clinical findings and chest radiographs are sufficient for clinical management. On the other hand, it should be recognized that patients who have CF can have a significant exacerbation of their symptoms with little visible radiographic change [139].
High-Resolution Computed Tomography Findings
HRCT findings in patients who have CF have been well described (Figs. 8-31, 8-32, 8-33, 8-34 and 8-35) [74,99,100,102,103,135,140,141,142]. Bronchiectasis is present in all patients who have advanced CF who are studied using HRCT (Table 8-5) [74,99,100,102,103,135,140,141]. Proximal or perihilar bronchi are always involved when bronchiectasis is present, and bronchiectasis is limited to these central bronchi in approximately one-third of the cases, a finding that is referred to as central bronchiectasis (Figs. 8-34 and 8-35). Both the central and peripheral bronchi are abnormal in approximately two-thirds of patients [74,140]. All lobes are typically involved, although early in the disease abnormalities are often predominantly upper lobe in distribution, and a right upper lobe predominance may be present in some patients (Fig. 8-32) [74,99,100,102,103,135,140,141,142].
Cylindrical bronchiectasis is the most frequent pattern seen; it was visible in 94% of lobes in one study of patients who had severe disease [140]. Thirty-four percent of lobes in this study showed cystic bronchiectasis, whereas varicose bronchiectasis was seen in 11%. In another report, cystic lesions representing cystic bronchiectasis or abscess cavities were present in eight of 14 (57%) patients (Fig. 8-21) [74].
Bronchial wall thickening, peribronchial interstitial thickening, or both are also commonly present in patients who have CF (Figs. 8-31, 8-32, 8-33, 8-34 and 8-35) [99,102,103,143]. The thickening is generally more evident than bronchial dilatation in patients who have early disease and may be seen independent of bronchiectasis [74,142]. Thickening of the wall of proximal right upper lobe bronchi was the earliest abnormal feature visible on HRCT in one study of patients who had mild CF [74,142].
Mucous plugging is also common, reported in between one-quarter and one-half of cases [99,102,103], and may be visible in all lobes [74,141]. Collapse or consolidation can be seen in as many as 80% of cases (Figs. 8-31 and 8-33) [74,99,143]. Volume loss was visible in 20% of lobes in patients who had advanced disease [140].
FIG. 8-31. Cystic fibrosis. A, B: HRCT at two levels shows extensive bronchial wall thickening (large white arrows); bronchiectasis, which is most evident anteriorly in the middle lobe and lingula; and mucous impaction in both large (small white arrows) and small (small black arrows) airways resulting in a tree-in-bud appearance. Lingular atelectasis is also present. (A from Webb WR. High-resolution computed tomography of obstructive lung disease. Radiol Clin North Am 1994;32:745-757, with permission.)
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Branching or nodular centrilobular opacities (i.e., tree-in-bud) which reflect the presence of bronchiolar dilatation with associated mucous impaction, infection, or peribronchiolar inflammation, can be an early sign of disease (Figs. 8-31 and 8-32) [141]. Focal areas of decreased lung opacity, representing air-trapping or mosaic perfusion, are common (Figs. 8-33, 8-34, 8-35). These can be seen to correspond to pulmonary lobules or subsegments and may appear to surround dilated, thick-walled, or mucous-plugged bronchi [141] in as many as two-thirds of patients [102]. Air-trapping can often be seen on expiratory scans (Fig. 8-35) [140].
FIG. 8-32. Cystic fibrosis with early abnormalities in a boy with a normal sweat chloride test. A: HRCT at the level of the middle and lower lobes shows bronchial wall thickening (open arrow), bronchiectasis with mucous impaction (large arrow), and small airway impaction with a tree-in-bud appearance (small arrows). B: At a slightly higher level, a region of the middle lobe (arrows) shows extensive bronchiolar impaction with a characteristic tree-in-bud appearance. This region also appears relatively lucent compared to surrounding lung as a result of mosaic perfusion.
FIG. 8-33. Cystic fibrosis. Atelectasis of the left lung is associated with extensive bronchiectasis. Bronchial wall thickening and bronchiectasis are visible on the right. A region of relatively increased attenuation (arrows) anteriorly reflects mosaic perfusion. Note that bronchiectasis is not visible in this region, and vessels appear larger than in lucent lung regions. (From Webb WR. High-resolution computed tomography of obstructive lung disease. Radiol Clin North Am 1994;32:745-757, with permission.)
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Lung volumes may appear increased on CT, although this diagnosis is rather subjective and may be better assessed on chest radiographs [140]. Cystic or bullous lung lesions can also be visible and typically predominate in the subpleural regions of the upper lobes [74,140]. Hilar or mediastinal lymph node enlargement and pleural abnormalities can also be seen, largely reflecting chronic infection. Pulmonary artery dilatation resulting from pulmonary hypertension can also be seen in patients who have long-standing disease.
Utility of High-Resolution Computed Tomography
HRCT can demonstrate morphologic abnormalities in patients who have early CF who are asymptomatic, have normal pulmonary function, have normal chest radiographs, or a combination of these. In a study of 38 patients who had mild CF with normal pulmonary function [142], chest radiographs were normal in 17 (45%), showed mild bronchial wall thickening in 17, and showed mild bronchiectasis in four (10%). On HRCT in this group, features of bronchiectasis were present in 77% of all patients and in 65% of those with normal chest radiographs; only three patients had a normal HRCT [142]. In another study of HRCT findings in 12 largely asymptomatic pediatric patients who had early CF, chest radiographs were normal in seven, whereas HRCT was normal in only two. HRCT findings not visible on radiographs included bronchial wall thickening, bronchiectasis, centrilobular small airway abnormalities, and lobular or segmental inhomogeneities representing mosaic perfusion or air-trapping [141].
In patients who have more advanced disease, HRCT can also show abnormalities not visible on chest radiographs. In a study of 14 patients who had CF [74], HRCT was found to be superior to chest radiographs in detecting bronchiectasis and mucous plugging. Of a total of 162 segments assessed, bronchiectasis was detected in 124 segments using HRCT, whereas only 71 segments were considered to show this finding on chest radiographs. Mucous plugs were detected on HRCT in 38 segments, whereas they were seen on radiographs in only four segments. In a study by Hansell et al. [140], bronchiectasis was considered to be present on HRCT in 124 of 126 lobes; on chest radiographs, only 84 of 102 lung zones were considered to show this finding. Chest radiographs also underestimated the extent of bronchiectasis. Bronchiectasis was considered to be both central and peripheral in only 31% of lung zones on chest radiographs, whereas a diffuse distribution was seen in 59% of lobes using HRCT.
Despite numerous reports detailing the range of abnormalities identified in patients who have CF, few if any of these find
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ings are specific. Reiff et al., in an assessment of 168 patients who had suspected bronchiectasis from a variety of etiologies, found that patients who had adult CF tended to have more widespread involvement than idiopathic bronchiectasis (p <.01) [67]. In patients who have early disease, abnormalities are often predominantly upper lobe in distribution, with a right upper lobe predominance. Despite these findings, as reported by Lee et al. and Cartier et al., a specific diagnosis of adult CF was made in only 38% and 68% of cases, respectively [101,132].
TABLE 8-5. HRCT findings in adult cystic fibrosis
Bronchiectasisa,b
 Central bronchi and upper lobes involved in all casesa,b
 Sometimes severe (varicose and cystic) and widespread (5-6 lobes)b
Bronchial wall thickeninga,b
 Central and upper lobe distributiona,b
 Right upper lobe first involvedb
Mucous plugginga,b
Branching or linear centrilobular opacities (tree-in-bud)a,b
Large lung volumesa,b
Areas of atelectasisa
Mosaic perfusiona
Air-trapping on expirationa
  a Most common findings.
  b bFindings most helpful in differential diagnosis.
FIG. 8-34. A, B: Cystic fibrosis in an adult. HRCT scans through the upper lung zones show central bronchiectasis and inhomogeneous opacity due to mosaic perfusion. Note the presence of decreased vessel size and abnormal bronchi in the relatively lucent lung regions. A cyst is visible in the posterior right lung.
The routine clinical evaluation of CF makes use of clinical and radiograph-based scoring systems. Several authors have also suggested the use of an HRCT scoring system [74,99,144]; these are described in detail above. It is hypothesized that such a scoring system may facilitate the objective evaluation of existing and newly developed therapeutic regimens [74]. One scoring system [74], based on an assessment of the degree and extent of bronchiectasis, bronchial wall thickening, mucous plugging, atelectasis, emphysema, and other findings, showed a statistically significant correlation to the percent ratios of FEV1/FVC (r = 0.69; p = .006) [74]. In another study based on assessment of bronchiectasis and mucous plugging [144], CT scores correlated highly with clinical (r = 0.88; p <.0001) and radiographic (r = 0.93; p <.0001) scores and several pulmonary function tests. The best correlation was with bronchiectasis.
Several reports have shown that CT offers a reliable alternative to routine radiographic and clinical methods for monitoring disease status and progression, as well as assessing
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response to treatment [74,103,144,145]. These studies consistently document close correlation between HRCT findings and clinical and pulmonary functional evaluation of these patients.
HRCT may be used to closely monitor potentially reversible morphologic changes as a means for monitoring disease progression and treatment therapy. Shah et al., using a modification of the scoring system proposed by Bhalla et al. [74], reported findings in 19 symptomatic patients who had adult CF evaluated initially and after 2 weeks of therapy, compared to a control group of eight asymptomatic CF patients [100]. Reversible findings included air-fluid levels in bronchiectatic cavities, centrilobular nodules, mucous plugging, and peribronchial thickening. Significantly, whereas severity of bronchiectasis was found to correlate with FVC (p = .004) and FEV1 (p = .02), no correlation was identified between pulmonary function test (PFT) parameters and either mucous
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plugging or centrilobular nodules, suggesting that PFTs were an insensitive means for identifying potentially reversible and hence treatable disease [100].
FIG. 8-35. A-D: Cystic fibrosis in an adult patient who has bronchiectasis, mosaic perfusion, and air-trapping on an expiratory scan. HRCT scans through the upper (A), middle (B), and lower (C) lung zones show multiple thick-walled and dilated bronchi. Bronchiectasis is most evident in the central lung regions, a finding typical of cystic fibrosis and termed central bronchiectasis. On the inspiratory scans (A-C), the lung appears inhomogeneous in opacity, with decreased vessel size and abnormal bronchi visible in the lucent lung regions. This is typical of mosaic perfusion secondary to air-trapping. An expiratory scan (D), obtained at the same level as C, shows air-trapping in lucent lung regions.
In a related study, Helbich et al. [103] evaluated serial CT studies obtained at various time intervals of up to 48 months in 107 patients to determine both the evolution of findings and optimal time intervals for sequential CT evaluation. These authors found that 6 to 18 months of follow-up were valuable for identifying potentially reversible morphologic changes, in particular, the presence of mucous plugging. In distinction, bronchiectasis and mosaic perfusion progressed at a significantly slower rate, rendering them less useful as a means for monitoring therapeutic interventions. Of particular interest was the finding that although CT correlated significantly with PFTs and clinical scores, these same parameters by comparison with CT were relatively insensitive means for identifying either improvement or disease progression [103]. Whereas mucous plugging could be identified in 25% of patients reexamined by CT within 18 months, for example, only minor changes could be identified by PFTs.
These findings lend support to the notion that HRCT should be incorporated into follow-up regimens of patients who have CF. In distinction, it has been reported that CT may play only a limited role in the preoperative assessment of patients who have CF before lung transplantation [146]. In a retrospective review of 26 patients who had CF who subsequently underwent bilateral lung transplantation, in no case was an unsuspected malignancy identified [146]. Of particular surgical interest, CT proved of little value in predicting the presence of pleural adhesions, a potential concern before transplantation.
Asthma
Asthma is characterized by airway inflammation, largely reversible airway obstruction, and hyperreactivity of the airways to various stimuli [66,147]. Pathologically, patients who have asthma show bronchial wall thickening, caused by inflammation and edema, and excess mucus production, which can result in mucous plugging [148]. Bronchiectasis may be seen in some patients who have long-standing asthma.
Radiographic findings associated with asthma include increased lung volume, increased lung lucency, mild bronchial wall thickening, and mild prominence of hilar vasculature due to transient pulmonary hypertension [149,150,151,152]. Bronchial wall thickening is visible in approximately half of patients [38,152]. Bronchiectasis is not usually recognized, but small mucous plugs can sometimes be seen. Associated complications of asthma, although uncommon, include pneumonia, atelectasis, pneumomediastinum, and pneumothorax [151]. Radiographic abnormalities are generally more common and more severe in children with asthma [150,151].
Plain radiographs are uncommonly used to make a diagnosis of asthma; radiographs are often normal, and visible abnormalities in this disease are usually nonspecific [66,150]. The usefulness of radiography in patients who have an established diagnosis of asthma who experience an acute attack is also limited. A correlation between the severity of radiographic findings and the severity or reversibility of an asthma attack is generally poor [149,150,151], and radiographs provide significant information that alters treatment in 5% or fewer of patients who have acute asthma [153,154]. Although it is difficult to generalize regarding the role of radiographs in adults and children with acute asthma, chest films are often used to exclude the presence of associated pneumonia or other complications when significant symptoms, appropriate clinical or laboratory findings, or both, are suggestive [149,150,151,153].
High-Resolution Computed Tomography Findings
HRCT is uncommonly indicated in the routine assessment of patients who have asthma, but it is sometimes used when complications, particularly ABPA, are suspected [36], and in documenting the presence of emphysema in smokers with asthma [155,156]. ABPA is associated with more severe bronchiectasis than that typically seen in patients who have uncomplicated asthma.
HRCT findings in patients who have uncomplicated asthma include mild bronchial dilatation. Mild bronchial dilatation has been reported in from 15% to 77% of patients who have uncomplicated asthma (Fig. 8-5) [36,38,65,152,157]. In a study by Lynch et al. [38], bronchi were defined as dilated if their internal diameters exceeded those of accompanying pulmonary arteries. Using this criteria, 77% of asthmatic patients and 153 (36%) of 429 bronchi assessed in asthmatic patients were considered dilated (Fig. 8-5). In a study by Grenier et al., bronchiectasis was found in 28.5% of the asthmatic subjects, primarily involving subsegmental and distal bronchi. As noted by Lynch and others [38,66], bronchial dilatation in asthmatic patients may partially reflect reduction in pulmonary artery diameter, due to changes in blood volume or local hypoxia, or may be physiologic; Lynch suggests caution in diagnosing mild bronchiectasis in this patient population [66].
Experimental studies in dogs [14] and asthmatic subjects [13,158] have measured bronchial luminal diameter using HRCT before and during a histamine or methacholine-induced episode of bronchospasm. These studies have found a significant reduction in the luminal diameter of small bronchi in association with acute asthma. Also, a significant decrease in lung attenuation due to air-trapping was seen in association with induced bronchospasm in these subjects [13].
Bronchial wall thickening, mucoid impaction, and centrilobular bronchiolar abnormalities such as tree-in-bud, patchy areas of lucency, and regional air-trapping on expiratory scans may also be identified on HRCT in patients who have uncomplicated asthma. Bronchial wall thickening has been reported in from 16% to 92% of patients [38,65,152,157], and there appears to be some tendency for the degree of bronchial wall thickening to correlate with the severity of disease [65,76].
Mucoid impaction has been reported in as many as 21% of cases [152]; this abnormality may clear after treatment. Branching or nodular centrilobular opacities have been
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reported to be present in as many as 10% to 21% of patients, sometimes manifested as tree-in-bud. These likely reflect bronchiolar wall thickening or inflammation, with or without mucoid impaction. However, this finding is absent or tends to be inconspicuous in most patients who have asthma.
TABLE 8-6. HRCT findings in allergic broncho-pulmonary aspergillosis
Central bronchiectasisa,b
 Typically severe and widespreada
Mucous plugginga
High-density mucusa,b
Linear or branching centrilobular opacities (tree-in-bud)
Atelectasis
Peripheral consolidation or diffuse ground-glass opacity
Mosaic perfusiona
Air-trapping on expirationaa
 a Most common findings.
 b Findings most helpful in differential diagnosis.
Focal or diffuse hyperlucency has been observed on inspiratory scans in from 18% to 31% of cases [38,157,159], undoubtedly due to air-trapping and mosaic perfusion. Expiratory CT can show evidence of patchy air-trapping in asthmatic patients (see Figs. 3-149 and 3-151) [160]. In a study by Park et al. [65], air-trapping involving more than a segment was seen in 50% of asthmatic patients. In some patients, air-trapping may be seen in the absence of morphologic abnormalities visible on inspiratory scans [117,161].
Allergic Bronchopulmonary Aspergillosis
ABPA reflects a hypersensitivity reaction to Aspergillus species and is characteristically associated with eosinophilia; symptoms of asthma, such as wheezing and findings of central or proximal bronchiectasis, usually associated with mucoid impaction; atelectasis; and sometimes consolidation similar to that seen in patients who have eosinophilic pneumonia. It occurs in asthmatics, but ABPA has also been noted to occur in between 2% and 10% of patients who have CF [162,163].
FIG. 8-36. Allergic bronchopulmonary aspergillosis (ABPA) with early changes. A, B: Sequential target-reconstructed HRCT images through the right upper lobe bronchus in a patient who has ABPA. The proximal portions of the anterior and posterior segmental bronchi are mildly dilated and have a distinctly beaded, irregular, and varicose appearance (arrows, A). Branches of the apical segmental bronchus are also dilated (arrow, B). Central bronchiectasis is typical of ABPA.
ABPA results from both type I and type III (IgE and IgG) immunologic responses to the endobronchial growth of fungal (Aspergillus) species. The immune reactions result in central bronchiectasis, which is usually varicose or cystic in appearance, and the formation of mucous plugs, which contain fungus and inflammatory cells. The acronym ARTEPICS has been proposed as an aid for remembering the primary criteria for ABPA, which include A for asthma, R for radiologic evidence of pulmonary disease, T for positive skin test for Aspergillus fumigatus, E for eosinophilia, P for precipitating antibodies to A. fumigatus, I for elevated IgE, C for central bronchiectasis, and S for elevated A. fumigatus serum-specific IgE and IgG [162]. A diagnosis of ABPA is nearly certain when six of these eight criteria are fulfilled. Secondary criteria include the presence of A. fumigatus in sputum, a history of expectoration of mucous plugs, and delayed cutaneous reactivity to Aspergillus antigen [162].
It has been suggested that disease progression be divided into five separate phases. These include: (i) an acute phase, which usually leads to (ii) resolution, during which time pulmonary infiltrates clear and serum IgE declines; resolution is followed by (iii) remission, when all diagnostic criteria recur, evolving to (iv) a phase of dependence on corticosteroids and, finally, leading in some cases to (v) diffuse pulmonary fibrosis [162].
High-Resolution Computed Tomography Findings
HRCT findings in patients who have ABPA have been well described (Table 8-6) (Fig. 8-11 and Figs. 8-36, 8-37, 8-38 and 8-39) [36,37,63,66,67,101,132,164,165,166,167,168,169]. A characteristic finding of
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central bronchiectasis can be identified in nearly all cases. As documented by Panchal et al. in their study of 23 patients who had ABPA, central bronchiectasis could be identified in 85% of lobes and 52% of lung segments using 4- and 8-mm-thick sections [169]. Central bronchiectasis typically occurred in association with bronchial occlusion due to mucous plugging; air-fluid levels in dilated, cystic airways; and bronchial wall thickening.
FIG. 8-37. Allergic bronchopulmonary aspergillosis with central bronchiectasis. Irregular, thick-walled, and mildly dilated bronchi (arrows) are visible in both lungs.
In addition to widespread and severe central bronchiectasis, a number of ancillary findings have been reported to
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occur in patients who have ABPA. As noted by Webb et al., disease involving the small airways is often present resulting in either a tree-in-bud appearance due to mucus-filled bronchioles or mosaic perfusion, and air-trapping due to bronchiolar obstruction (Figs. 8-11 and 8-39) [161].
FIG. 8-38. A-C: Allergic bronchopulmonary aspergillosis with mild central bronchiectasis. Thick-walled and dilated bronchi are visible diffusely, but with an upper lobe predominance. Mild inhomogeneity of lung attenuation reflects mosaic perfusion.
The finding of aspergillomas in ectatic airways in patients who have ABPA has also been reported [170]. Additional parenchymal abnormalities, including consolidation, collapse, cavitation, and bullae, may be identified, especially in the upper lobes in as many as 43% of cases [169]. An identical
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percentage of cases also had evidence of pleural abnormalities, especially focal pleural thickening. Masslike foci of eosinophilic pneumonia may also be seen in ABPA patients who have acute exacerbations [171,172].
FIG. 8-39. Allergic bronchopulmonary aspergillosis with extensive bronchiectasis. A: HRCT scan through the upper lobes shows bilateral cystic bronchiectasis. mucous-plugged bronchi (white arrows) are visible and ill-defined foci of parenchymal consolidation are also present (black arrow). B: HRCT near the lung bases shows extensive bronchiectasis. In some regions, dilated bronchioles (arrow) are visible in the lung periphery. Lung attenuation is inhomogeneous as a result of mosaic perfusion.
Of particular interest is the finding of high-attenuation mucoid impaction (Fig. 8-40) [173,174]. First described in association with chronic fungal sinusitis, high-density mucus presumably represents the presence of calcium ions, metallic ions, or both, within viscous mucus [175]. The prevalence of this finding has been noted to be as high as 28% in one series, and when present should be considered characteristic [174].
ABPA should be distinguished from both angioinvasive and airway-invasive aspergillosis [176]. These latter entities occur almost exclusively in severely immunosuppressed individuals–for example, after bone marrow or renal transplantation or in patients who have leukemia. By definition, the airway-invasive form of the disease is associated with the presence of organisms deep to the airway basement membrane. In distinction to the angioinvasive form of disease, airway-invasive aspergillosis may occur clinically even when the degree of immunosuppression is mild. Radiologically, airway-invasive aspergillosis most often manifests as patchy areas of parenchymal consolidation. On HRCT scans, the majority of patients have been reported to have a distinct peribronchial or peribronchiolar distribution of disease, ranging from patchy areas of con
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solidation to poorly defined centrilobular nodules [176]. In one study, sequential CT studies showed that airway-invasive aspergillosis resulted in bronchiectasis in cases without prior airway dilatation [176].
FIG. 8-40. Allergic bronchopulmonary aspergillosis (ABPA): high-density mucoid impaction. Noncontrast-enhanced CT section through the upper lung shows atelectasis of the right upper lobe. Within are numerous high-density foci representing dilated airways. This finding is characteristic of long-standing ABPA and presumably represents the presence of calcium, metallic, or both, types of ions within viscous mucus.
Utility of High-Resolution Computed Tomography
Although ABPA is classically associated with central bronchiectasis, this finding in itself is nonspecific and insensitive [67,132]. For example, Reiff et al. [67], in a study of 168 patients who had chronic sputum production [67], patients who had ABPA were significantly more likely than patients who had other diseases to have central bronchiectasis (p <.005), and bronchiectasis was more likely to be varicose or cylindrical morphologically (p <.01); however, the sensitivity of central bronchiectasis in this same study proved to only be 37% in diagnosing ABPA. Similarly, in a retrospective study of 82 consecutive patients who had bronchiectasis with known etiologies, Cartier et al. found that in only five (56%) of nine cases was a diagnosis of ABPA specifically suggested [101].
CT may be valuable in the early identification of lung damage in patients who have ABPA and thus help in planning treatment [164,165]. HRCT is more sensitive than plain radiographs in detecting abnormalities associated with ABPA [166]. In one study, narrow-section (3-mm) CT and plain chest radiography were compared in ten patients who had ABPA [164]. Bronchiectasis was reported in 31 of 60 lobes on CT scans but was visible in only 15 lobes on plain chest radiographs; CT was also more sensitive in detecting central bronchiectasis. In another study, CT with 8-mm collimation was compared to bronchography in two pediatric patients who had ABPA [165]; CT was able to identify 24 of 27 segments that showed central bronchiectasis.
As previously mentioned, whereas ABPA occurs exclusively in asthmatics, this diagnosis may be difficult to make in a general population of asthmatics on clinical grounds alone; many of the features of asthma and ABPA overlap. In addition to the finding of bronchiectasis, these include serum precipitins to A. fumigatus in up to 10% of asthmatics, a positive skin test to Aspergillus in up to 25% of asthmatics, and elevated IgE levels and eosinophilia. In a study by Neeld et al. [36], the HRCT findings in patients who had ABPA were compared to those in patients who had uncomplicated asthma. Bronchial dilatation was seen in 41% of lobes in the patients who had ABPA as compared to 15% of lobes in the patients who had asthma.
In the most extensive evaluation to date, Ward et al. retrospectively assessed the accuracy of CT in the diagnosis of ABPA in asthmatic patients [63]. Comparing the CT findings in 44 patients who had documented ABPA with 36 asthmatic controls, these authors noted a clear distinction in the frequency of a number of CT findings in patients who had ABPA, including the following: bronchiectasis in 95% of cases, versus 29% of asthmatics; centrilobular nodules in 93% of cases, versus 28% of asthmatics; and mucoid impaction in 67% of cases, versus 4% of asthmatics. Furthermore, as noted by others, patients who had ABPA consistently had more severe and extensive disease compared with asthmatics, especially when present in three or more lobes [63]. It should be noted that the prevalence of bronchiectasis in this study far exceeds that reported in most other studies. In comparison to patients who have CF who often have diffuse cylindrical bronchiectasis, those with ABPA more typically show bronchiectasis that is cystic in appearance [140].
Tracheobronchomegaly
Also referred to as Mounier-Kuhn syndrome, the term tracheobronchomegaly is used to describe a heterogeneous group of patients who have marked dilatation of the trachea and mainstem bronchi, frequently in association with tracheal diverticulosis, recurrent lower respiratory tract infections, and bronchiectasis [177,178,179]. The etiology of this disorder is controversial. Findings in favor of a congenital etiology include histopathologic evidence of deficiency of tracheobronchial muscle fibers and absence of the myenteric plexus, as well as an association with other congenital or connective tissue disorders, including ankylosing spondylitis, Marfan’s syndrome, CF, Ehlers-Danlos syndrome, and cutis laxa in children [180,181]. In distinction, findings in favor of an acquired etiology include the fact that tracheobronchomegaly most often is diagnosed in men in their third and fourth decades without an antecedent history of respiratory tract infection, often in association with chronic cigarette smoking [180,181]. An association between tracheomegaly and diffuse pulmonary fibrosis has also been reported, presumably the result of increased traction on the tracheal wall due to increased elastic recoil pressure in both lungs [180,181].
CT findings in patients who have tracheobronchomegaly have been described (Fig. 8-41) [182,183,184]. Using a tracheal diameter of greater than 3 cm and measured 2 cm above the aortic arch, and diameters of 2.4 and 2.3 cm for the right and left main bronchi, respectively, the diagnosis of tracheobronchomegaly is relatively straightforward [182]. Additional findings include tracheal scalloping, diverticulae, or both, diverticulae being especially common along the posterior tracheal wall. Also common is the finding of a marked tracheal flaccidity, identifiable as a marked decrease in the diameter of the trachea on expiration, even to the point of airway occlusion, indicative of tracheomalacia [10].
The importance of tracheomegaly lies in its association with distal airway inflammation. In a study of 75 consecutive patients referred for CT evaluation of possible bronchiectasis, Roditi and Weir [180] found that overall, 12% of their patients proved to have dilated tracheas, including seven (17%) of 42 patients who had CT evidence of bronchiectasis as well as three (6%) of 32 without. These data suggest that tracheomegaly may play a causative role in the development of bronchiectasis as a result of a predisposition to infection resulting from abnormal mucous clearance in patients who have inefficient cough and stagnant mucus.
FIG. 8-41. Tracheobronchomegaly with bronchiectasis. Section through the carina shows massive enlargement of both the right and left main bronchi, associated with thin-walled cystic bronchiectasis bilaterally. Bronchiectasis frequently can be identified in patients with tracheobronchomegaly.
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Williams-Campbell Syndrome
Williams-Campbell syndrome is a rare type of cystic bronchiectasis that is due to defective cartilage in the fourth- to sixth-order bronchi. HRCT can show areas of central cystic bronchiectasis with distal regions of abnormal lucency, probably related to air-trapping or bronchiolitis. These findings are useful in differentiating Williams-Campbell syndrome from other causes of cystic bronchiectasis (Fig. 8-42) [185]. Ballooning of central bronchi on inspiration and collapse on expiration have also been reported [186].
Alpha-1-Antitrypsin Deficiency
In addition to emphysema, bronchiectasis is also frequently identified in patients who have alpha-1-antitrypsin deficiency. King et al., in a study of 14 patients who had alpha-1-antitrypsin deficiency, found evidence of bronchiectasis in six (43%) [187]. This correlates well with the fact that approximately 50% of patients who have this deficiency manifest symptoms of airways disease, in particular chronic sputum production. Surprisingly, a frequent association between bronchiectasis and other forms of emphysema has not been well documented [187].
FIG. 8-42. A-C: Williams-Campbell syndrome with bronchiectasis in a patient who had left lung transplantation. Histologic evaluation of the resected lung revealed deficient cartilage in central bronchi. HRCT at three levels shows marked dilatation of bronchi within central lung regions. Peripheral lung appears lucent, particularly when compared to the normal left lung transplant. This lucency reflects air-trapping and mosaic perfusion. Continued
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Bronchiectasis Associated with Systemic Diseases
Bronchiectasis may be an important finding in a number of major systemic diseases. Of particular interest is the association between bronchiectasis and both rheumatologic diseases and inflammatory bowel disease.
Collagen-Vascular Disease
Rheumatoid arthritis (RA) may be associated with a variety of parenchymal abnormalities, including pulmonary fibrosis, bronchiolitis obliterans organizing pneumonia (BOOP), respiratory tract infections (including tuberculosis), and necrobiotic nodules. Airways disease, including both bronchiectasis and bronchiolectasis, is often overlooked as an association with RA [188]. Although airways disease was previously reported to occur in 5% to 10% of patients who have RA, since the introduction of HRCT, it has been estimated that bronchiectasis occurs in up to 35% of all patients who have this disease [189,190,191,192]. McDonagh et al., for example, in an evaluation of 20 patients who had clinical and radiologic evidence of RA, found that bronchiectasis could be identified in six patients, including two previously
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thought to have diffuse interstitial lung disease, on the basis of chest radiographs [190]. In this same study, bronchiectasis was also identified in four of 20 asymptomatic control patients who had documented RA and normal chest radiographs. In a study of 38 patients who had documented RA reported by Remy-Jardin et al., there was evidence of either bronchiectasis or bronchiolectasis in 23 (30%) including 8% of asymptomatic patients, with additional features suggestive of small airways disease in another six patients [189]. These findings included linear or branching centrilobular opacities, or both, believed by these authors to represent BO [189]. Whereas this included seven patients who had traction bronchiectasis in areas of honeycombing, in the remaining 16 patients bronchiectasis was seen in the absence of CT evidence of lung fibrosis.
More recently, it has been shown that in a select population of RA patients who have normal radiographs, the prevalence of airways disease may be considerably higher than previously thought. In a study of 50 RA patients who did not have radiographic evidence of lung disease, Perez et al. [192] reported findings of both direct and indirect bronchial and/or bronchiolar disease in 35 (70%), including air-trapping on expiratory scans in 32%, cylindrical bronchiectasis in 30%, mosaic attenuation on inspiratory scans in 20%, and centrilobular nodules in 6%. Importantly, HRCT depicted features of small airways disease in 20 of 33 patients who had normal pulmonary function tests.
It has long been observed that airway obstruction is especially common in patients who have RA [193], leading to speculation by some to a possible etiologic relationship between bronchiectasis and RA. It has been suggested, for example, that chronic bacterial infections may trigger an immune reaction in genetically predisposed individuals, leading to autoimmune disease [188]. In this regard, it has been observed that bronchiectasis may precede the development of RA by several decades. However, in distinction, it has also been suggested that steroid therapy or related treatment, especially with immunosuppressive therapy itself, may lead to an increased incidence of respiratory infections. It has also been suggested that the association between RA and bronchiectasis may reflect a shared genetic predisposition, although this remains controversial [191]. More recently, it has been suggested that airway obstruction in RA patients is only secondarily related to bronchiectasis and in fact primarily reflects the presence of BO [189,194].
Regardless of the precise role played by bronchiectasis in the etiology of RA, it has been shown that although there is no evidence to suggest that patients who have coexisting bronchiectasis have more severe RA, these individuals appear to have decreased survival. Swinson et al. [195], in a case-control study of the 5-year survival of 32 patients who had both RA and bronchiectasis matched for age, gender, and disease duration with 32 patients who had RA alone, and an additional 31 patients who had bronchiectasis alone, found that patients who had both RA and bronchiectasis were 7.3 times as likely to die than the general population, five times more likely to die than patients who had RA alone, and 2.4 times more likely to die than patients who had bronchiectasis alone.
Similar to the unexpectedly high incidence of bronchiectasis in patients who have RA, it has been shown that bronchiectasis may be identified in up to 20% of patients who have systemic lupus erythematosus (SLE) [196]. Banker et al., in a prospective study of 45 patients who had documented SLE and normal radiographs, found abnormal CT findings in 38%, including bronchial wall thickening in 20% and bronchial dilatation in another 18% [197]; bronchiectasis has usually not been considered a manifestation of SLE [188]. A similarly unexpected high prevalence of airway pathology has also been noted in patients who have primary Sjögren’s syndrome [198].
Ulcerative Colitis
A wide range of airway abnormalities has been identified in patients who have ulcerative colitis. In addition to BOOP and diffuse interstitial lung disease, these include subglottic stenosis, chronic bronchitis, and chronic suppurative inflammation of both large and small airways [188]. Similar to what is seen in patients who have RA, chronic suppurative airways disease may precede, coexist with, or follow, the development of inflammatory bowel disease. Of particular interest is the fact that, unlike other causes of bronchiectasis, chronic suppurative airways disease associated with ulcerative colitis frequently responds to treatment with inhaled steroids [188].
Human Immunodeficiency Virus- and Acquired Immunodeficiency Syndrome-Related Airways Disease
A number of reports have documented an increase in the prevalence of airway-related infections in HIV-positive/AIDS patients [31,34,199,200,201,202]. Paralleling a marked decrease in the incidence of PCP due to routine prophylaxis, lower respiratory tract infections, including bacterial pneumonia and bronchitis, have superseded PCP as the most common infections in the lungs of AIDS patients [203,204,205]. Wallace et al., for example, in a study of more than 1,000 HIV-positive patients who did not have an AIDS-defining illness, found a significantly higher incidence of acute bronchitis compared to HIV-negative subjects [205]. Most commonly, they result from organisms such as Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus viridans, or Streptococcus pneumoniae, and in fact a wide range of infectious agents has been described affecting the airways, including both mycobacterial and fungal infections [199].
First reported by Holmes et al. [201], and later confirmed by McGuinness et al. [31], an accelerated form of bronchiectasis appears to occur in HIV-positive patients. Although the etiology is unclear, it is likely that bronchiectasis results from recurrent bacterial infections affecting airways, possibly made more susceptible due to the
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direct effects of HIV infection on the pulmonary immune system. A correlation has also been shown between airway dilatation identified by CT and the presence of elevated levels of neutrophils on bronchoalveolar lavage (BAL). In a study comparing BAL findings in 50 HIV-positive subjects with 11 HIV-negative individuals, King et al. showed that patients who had bronchial dilatation on CT had significantly higher BAL neutrophil counts (p = .014) as well as significantly lower diffusing capacity (p = .003) [34]. As noted by these authors, neutrophils are an important mediator of pulmonary damage, possibly due to the action of human neutrophil elastase.
FIG. 8-43. Acquired immunodeficiency syndrome (AIDS)-associated bronchiectasis: 1.5-mm axial image in a 32-year-old AIDS patient who has productive cough and left lower lobe infiltrate. Evidence of focal rounded and tubular densities in the posteriobasilar segment of the left lower lobe (arrow) is consistent with mucoid impaction in the absence of parenchymal consolidation. At bronchoscopy, the bronchial mucosa was inflamed, and the lumen was packed with inflammatory material and hyphae, identified as Aspergillus.
AIDS-related airways disease is manifested by a variety of HRCT abnormalities, a fact that reflects the number of organisms that may be involved. Findings include bronchial wall thickening, bronchiectasis, bronchial or bronchiolar impaction with tree-in-bud, endoluminal masses or nodules, and consolidation [199]. A lower lobe predominance is typical. The common finding of air-trapping in HIV-positive patients has also been stressed [206], suggesting that small airways disease may be a significant contributor to pulmonary function decline and may precede more obvious findings of airways disease. Gelman et al. [206] evaluated the HRCT scans of 59 subjects using inspiratory and expiratory HRCT, 48 of whom were HIV-positive and 11 of whom were HIV-negative. Expiratory CT revealed focal air-trapping in 33 subjects, 30 of whom were HIV-positive and three of whom were HIV-negative (p = .0338). The mean values of FEV1, forced mid-expiratory flow, and diffusion capacity were significantly lower for subjects with focal air-trapping than for those with normal findings on CT (p = .001, p = .021, and p = .003, respectively).
It should also be noted that although less common than bacterial or viral infections, the airways may also be the site of fungal infections, especially due to Aspergillus (Fig. 8-43). Typically occurring late in the course of HIV infection, and usually in association with other risk factors, including corticosteroid use and granulocytopenia, approximately 10% of all reported cases of aspergillosis in AIDS patients will affect the airways [199]. Whereas several distinct subtypes of aspergillosis of the airways have been described, including necrotizing acute tracheobronchitis, obstructing bronchial aspergillosis, and chronic cavitary parenchymal aspergillosis, it is likely that these represent a single spectrum of fungal disease potentially affecting the airways [207,208,209].
On one end of the spectrum is obstructing bronchial aspergillosis. Representing a stage before frank tissue invasion, obstructing bronchial aspergillosis typically presents acutely with fever, dyspnea, and progressive cough associated with the expectoration of fungal casts and is characterized on CT by the presence of mucoid impaction typically involving the lower lobe airways [209]. It has been suggested that this form of disease is unique to AIDS patients. Rarely, aspergillosis primarily affects the small airways again in the absence of bronchial inflammation. Described in only two patients who had AIDS, this form of infection has been termed chronic cavitary parenchymal aspergillosis and results in necrotic debris and fungi filling respiratory bronchioles with extension into adjacent alveolar spaces in the absence of bronchial invasion [210]. In distinction, necrotizing tracheobronchial aspergillosis (also referred to as diffuse, ulcerative, and pseudomembranous tracheobronchitis) is associated with frank tissue invasion resulting on CT in a range of abnormalities, from subtle focal irregularity and nodularity of airway walls to airway obstruction with or without accompanying parenchymal infiltrates.
Bronchiolitis
Bronchiolitis is a nonspecific term used to describe inflammation of the small airways. Although a number of classifications have been proposed to encompass the wide spectrum of clinicopathologic conditions associated with bronchiolar inflammation, none has gained widespread acceptance [211]. At least partially, this is because there is all too frequently little correspondence between histologic findings and specific diseases. For example, patients who have RA may develop BO, BOOP, follicular bronchiolitis, or panbronchiolitis. Perhaps most confusing is the fact that even within the narrower confines of histologic and etiologic or clinical classifications, there is still little agreement concerning appropriate terminology.
TABLE 8-7. Bronchiolar disease: pathologic classification
Cellular bronchiolitis
Common
 Infectious bronchiolitis
 Hypersensitivity pneumonitis
Rare
 Follicular bronchiolitis
 Panbronchiolitis
Respiratory bronchiolitis
Common
 Respiratory bronchiolitis
 Respiratory bronchiolitis-interstitial lung disease
Rare
 Desquamative interstitial pneumonia
Constrictive bronchiolitis
Common
 Secondary (i.e., associated with infection, drugs,
  collagen-vascular disease, transplantation)
Rare
 Idiopathic
Bronchiolitis obliterans with intraluminal polyps
Common
 Idiopathic
 Secondary (i.e., associated with infection, drugs,
  collagen-vascular disease, transplantation)
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Pathologic Classification of Bronchiolitis
Histologically, bronchiolitis may be classified in different ways, but several entities are consistently recognized by different authors [21,212]. These include cellular bronchiolitis, respiratory bronchiolitis, constrictive bronchiolitis, and bronchiolitis obliterans with intraluminal polyps (Table 8-7). In some classifications, respiratory bronchiolitis is classified with cellular bronchiolitis, and constrictive bronchiolitis and BO with intraluminal polyps are considered subtypes of BO.
Cellular Bronchiolitis
Included in the category of cellular bronchiolitis is a diverse set of diseases characterized in common by the presence of inflammatory cellular infiltrates involving both the bronchiolar lumen and wall and some degree of fibrosis. Further characterized as acute or chronic, and by the predominant cell type, this classification most commonly includes (i) infectious bronchiolitis (bacterial, viral, mycoplasma, and fungal), (ii) follicular bronchiolitis in collagen-vascular diseases, (iii) panbronchiolitis, (iv) aspiration bronchiolitis, (v) bronchiolitis associated with hypersensitivity pneumonitis, and (vi) asthma. Nonspecific cellular bronchiolitis is also frequently identified in patients who have bronchiectasis and chronic obstructive pulmonary disease.
Respiratory Bronchiolitis
Respiratory bronchiolitis is part of a spectrum of smoking-related diseases of the airways and lungs, characterized by the accumulation of pigmented macrophages within respiratory bronchioles and alveoli. This spectrum includes respiratory bronchiolitis (RB), respiratory bronchiolitis-interstitial lung disease (RB-ILD), and desquamative interstitial pneumonitis (DIP), also known as alveolar macrophage pneumonia [213,214,215,216,217]. Although RB is typically identified as an incidental finding in asymptomatic smokers, it has been recognized that some smokers present with both signs and symptoms of diffuse interstitial lung disease, so-called RB-ILD. Histologically, these patients are considered to have an exaggerated form of RB with evidence of inflammation and fibrosis away from respiratory bronchioles and into adjacent alveolar septa. In distinction, patients who have DIP have more diffuse involvement with a greater likelihood of developing parenchymal fibrosis and progressive lung disease. It has been suggested that RB, RB-ILD, and DIP be further classified as one of a larger group of smoking-related diseases, aptly termed smoking-related interstitial lung diseases, that also includes centrilobular emphysema and Langerhans cell histiocytosis [216]. Support for this classification stems from a possible association between respiratory bronchiolitis and the development of centrilobular emphysema [216,217].
Constrictive Bronchiolitis (Bronchiolitis Obliterans)
Constrictive bronchiolitis is defined histologically by the presence of concentric fibrosis predominantly between the bronchiolar epithelium and the muscularis mucosa, resulting in marked narrowing or obliteration of bronchioles, or both, in the absence of intraluminal granulation tissue polyps or surrounding parenchymal inflammation. Clinically, constrictive bronchiolitis is associated with marked airflow obstruction that usually is not responsive to steroid therapy [218,219]. Radiographically, little if any abnormality apart from hyperinflation is apparent. This pathologic entity is associated with the clinical syndrome often referred to as BO. It may result from a variety of diseases or conditions, described below in detail.
Bronchiolitis Obliterans with Intraluminal Polyps
BO with intraluminal polyps, also known as BOOP or cryptogenic organizing pneumonia (COP), is defined by the presence of granulation tissue polyps within respiratory bronchioles and alveolar ducts (Masson bodies) associated with patchy organizing pneumonia [220,221,222]. Because in the majority of cases the predominant histologic abnormality is the presence of organizing pneumonia, the terms BOOP and COP are usually used to describe this entity.
Two distinct patterns of intraluminal fibrosis or Masson bodies have been described [223]. Type 1 Masson bodies are
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those that show abundant myxoid matrix, sparse fibrosis, and little or no fibrin and presumably represent immature mesenchymal cells. In distinction, Type 2 Masson bodies contain fibrin and have histochemical properties of myofibroblasts. This distinction may be of importance, as in at least one study patients who had Type 1 disease showed good response to steroid therapy, whereas those who had Type 2 disease generally failed to respond to treatment [223].
TABLE 8-8. Bronchiolar disease: etiologic classification
Common
 Infection (bacteria, fungi, mycoplasma, viruses, parasites)
 Smoking
 Immunologic disease
 Organ transplantation
 Connective tissue disease
 Hypersensitivity pneumonitis
 Irradiation
 Chronic aspiration
Rare
 Inhalational disease (gases, fumes, dusts)
 Drugs and chemicals, including Sauropus androgynus ingestion
 Neuroendocrine cell hyperplasia
 Wegener’s granulomatosis
 Ulcerative colitis
 Acute and chronic eosinophilic pneumonia
Although the majority of cases of BOOP are idiopathic, similar findings may be seen in association with a variety of clinical conditions. As described by Katzenstein [219], BOOP may be classified into three separate categories. In the first, BOOP is the primary cause of respiratory illness. This includes idiopathic BOOP as well as BOOP resulting from RA, toxic inhalants, drug toxicity, and collagen-vascular diseases; prior infection, both viral and bacterial; and acute radiation pneumonitis [219,224]. In the second category are cases in which BOOP is found as a nonspecific reaction along the periphery of unrelated pathologic processes, including neoplasms, infectious granulomas, vasculitis, and even infarcts. Finally, BOOP may also be identified as a minor component of other diseases, including hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and Langerhans cell histiocytosis, among others [219]. It is for this reason that the finding of features consistent with BOOP on transbronchial biopsy is of only limited value in the absence of detailed clinical and radiologic correlation (Fig. 8-52 and 8-53) [219].
Reflecting not only the presence of intraluminal polyps, but also more extensive inflammatory changes involving alveolar ducts and alveoli, BOOP characteristically results in predominantly restrictive lung disease manifested radiographically as ill-defined areas of parenchymal consolidation [211,218,219,225]. BOOP is described in Chapter 6.
Clinical and Etiologic Classification of Bronchiolitis
It is also possible to classify bronchiolitis by known etiology or clinical association (Table 8-8). Etiologies of bronchiolitis include (i) diverse infections, including viruses, bacteria, mycoplasma, fungi, and parasites; (ii) inhalation of fumes, gases, and dusts, including cigarette smoke and asbestos; (iii) inhalation of organic material with hypersensitivity pneumonitis; (iv) exposure to a wide variety of drugs and chemicals (e.g., amiodarone, paraquat, and Sauropus androgynus); (v) a wide range of immunologic diseases, including connective tissue diseases; and (vi) as a complication of bone marrow, heart-lung, or lung transplantation. Bronchiolitis is also commonly identified in a number of miscellaneous conditions that affect the lung including vasculitides, eosinophilic lung syndromes, inflammatory bowel diseases, and chronic aspiration [226]. BO has also been described in patients who have neuroendocrine cell hyperplasia [227].
Computed Tomography Classification of Bronchiolitis
It is not an exaggeration to say that the introduction of HRCT has revolutionized our ability to diagnose small airways disease [3,18,19,27,85,88,89,161,228,229,230,231,232,233,234,235,236,237]. Reflecting the lack of reliable plain radiologic or physiologic methods for diagnosing small airways disease, bronchiolitis is uncommonly diagnosed or even suspected clinically. As a consequence, small airways pathology has usually required histologic confirmation. However, HRCT findings are frequently suggestive, if not diagnostic, of small airways disease. In our experience, CT findings are frequently the first indication of the presence of small airways pathology. Equally important, HRCT provides the most reliable assessment of both the extent and severity of disease, and provides a reliable, noninvasive method for assessing response to therapy without the need for repeated histologic evaluation.
Anatomic Considerations
Airways distal to those containing identifiable cartilage in their walls are termed bronchioles. Terminal bronchioles are the last purely conductive airways, varying in length from 0.8 to 2.5 mm, and are usually found between the sixth and twenty-third airway generations. Respiratory bronchioles lie distal to terminal bronchioles and are defined as airways in which the ciliated epithelial lining is interrupted by alveoli [148,238]. Along with alveolar ducts and sacs, respiratory bronchioles comprise the gas-exchanging unit of the lung. A number of different cell types can be identified in normal bronchioles. These include special columnar secretory stem cells, known as Clara cells, as well as neuroendocrine or Kulchitsky cells. In distinction, mucus-secreting goblet cells and bronchus-associated lymphoid tissue are only rarely identified in nonsmokers.
Along with their accompanying pulmonary artery branches, bronchioles lie within the center of secondary pulmonary lobules. Normally, individual airways can only be identified
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when their walls are larger than 300 microns, corresponding to bronchi between 1.5 and 2 mm in size. As a consequence, normal bronchioles with luminal diameters of approximately 0.6 mm cannot be identified on HRCT.
Although the term small airways disease is usually used synonymously with bronchiolar disease, this term as originally defined was used to describe inflammatory changes in peripheral airways in smokers resulting in moderate to severe airflow obstruction [239]. Subsequently defined by Macklem and colleagues [240] to indicate an idiopathic syndrome of chronic airflow obstruction in patients having no evidence of underlying emphysema or chronic bronchitis, this concept of small airways disease is essentially physiologic and is associated with abnormalities involving airways between 2 and 3 mm in diameter. The distinction between anatomic and physiologic definitions is significant, as small airways contribute only approximately 10% of total airway resistance. As a consequence, numerous small airways can be damaged before conventional measurements of lung function, in particular measurements of airway resistance, become abnormal.
Although normal intralobular bronchioles cannot usually be identified, direct and indirect signs of bronchiolar disease have been described [18,19,161]. Direct signs result from the presence of bronchiolar secretions, peribronchiolar inflammation, or, less commonly, bronchiolar wall thickening. Characteristically, these result in either branching or Y-shaped linear densities (Figs. 8-17 and 8-44), or poorly defined centrilobular nodules (Fig. 8-45). Less commonly, bronchiolar inflammation results in the finding of small centrilobular lucencies due to bronchiolectasis [3,70,85,89].
Indirect signs have also been described, the most important of which are the findings of mosaic perfusion on inspiratory scans and areas of lucency and air-trapping, either focal or global, on scans obtained at end expiration [116,161,241,242].
Using a combination of HRCT findings, it is possible to classify bronchiolitis into one of four basic HRCT patterns based on the predominant abnormality (Table 8-9). These include (i) bronchiolar diseases associated with a tree-in-bud appearance, (ii) bronchiolar diseases associated with poorly-defined centrilobular opacities, (iii) bronchiolar diseases associated with areas of decreased lung attenuation, and (iv) bronchiolar diseases associated with focal or diffuse ground-glass opacity, consolidation, or both. Use of this classification in conjunction with clinical findings frequently allows precise diagnoses even in the absence of histologic correlation.
Bronchiolar Diseases Associated with a Tree-in-Bud Pattern
The hallmark of this group of diseases is the finding of dilated, mucus-filled bronchioles resulting in a pattern of centrilobular nodular, branching, or Y-shaped densities that has been aptly referred to as simulating a TIB appearance or the children’s toy jacks (Figs. 8-17, 8-31, 8-32, 8-44, and 8-46 through 8-48) [84,85,86]. A TIB appearance is most typical of cellular bronchiolitis. In our experience this appearance is almost always the result of acute or chronic infection (Table 8-9). The differential diagnosis of TIB is discussed in greater detail in Chapter 3.
Aquino et al. [84] found that a TIB pattern could be identified on HRCT in 25% of patients who had bronchiectasis (including patients who had CF and ABPA) and 17% of patients who had acute infectious bronchitis or pneumonia. On the other hand, this pattern was not identified in any of 141 HRCT studies in patients who had noninfectious airways diseases, including emphysema, RB, constrictive bronchiolitis, BOOP, and hypersensitivity pneumonitis, among others.
Infectious Bronchiolitis
The finding of a TIB pattern is nearly always due to acute infectious bronchiolitis, regardless of the underlying disease (Figs. 8-17 and 8-47A). As documented by Im et al. [27], in patients who had tuberculosis, the TIB pattern correlates pathologically with the presence of secretions within dilated terminal and respiratory bronchioles (Fig. 8-44). These are characteristically centrilobular in distribution and are most easily identified in the lung periphery. Ill-defined buds associated with the branching airway reflect the presence of peribronchiolar granulomas, a finding especially common in patients who have chronic infection due to MAC (Fig. 8-30) [84] or peribronchiolar inflammation. Poorly defined centrilobular nodules or rosettes of nodules are almost always visible in patients who have TIB; these may be seen if images show distended centrilobular bronchioles in cross section. In our experience, however, these are always ancillary to the main finding of linear or branching densities. Additional findings include areas of ground-glass opacity, consolidation, or both. With healing, a distinctive pattern of branching or V-shaped densities associated with secondary lobular emphysema may be identified, presumably the result of bronchial, bronchiolar, or both types of obstruction.
Infectious bronchiolitis is usually reversible and is most often caused by Mycoplasma pneumoniae, Haemophilus influenzae, and Chlamydia species and viral infections, especially respiratory syncytial virus. Infectious bronchiolitis is common in infants and children and is being increasingly diagnosed in adults, especially those who have atypical mycobacterial infections or other causes of chronic airways disease [28,29], AIDS [34,199], or a combination of both. Although histologic examination typically shows necrosis of respiratory epithelium with a mixed cellular infiltrate usually in association with accompanying pneumonitis, it is, in fact, rarely necessary to obtain biopsies in these patients. In our experience, HRCT findings in conjunction with clinical findings are usually sufficient to allow presumptive therapy with antibiotics, pending the results of sputum culture.
It should be emphasized that an appearance similar to that of TIB has also been reported in association with noninfectious etiologies. Numerous reports, for example, have documented linear or branching centrilobular densities in patients
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who had RA or Sjögren’s syndrome [189,192,198,243]. Although usually attributed to either follicular bronchiolitis [244,245,246] or BO, many of the patients have coexisting productive cough and other clinical signs indicative of possible infection. In this regard, Hayakawa et al. correlated HRCT findings with histologic findings identified on open lung biopsy in 14 RA patients who had documented bronchiolitis [247]. Whereas linear or branching centrilobular nodules could be identified in five of seven patients who had follicular bronchiolitis and three of seven who had BO, as noted by the authors, 73% of patients had chronic sinusitis, and 93% of patients had chronic cough with sputum. Furthermore, bacterial cultures were positive in 50% and 71% of patients who had follicular bronchiolitis and BO, respectively.
FIG. 8-44. Fig. 8-44. Infectious bronchiolitis: Chlamydia pneumonia. A: A 5-mm section through the middle lung shows a central endobronchial lesion partially obstructing the distal left main stem bronchus (open arrow). Throughout the superior segment of the left lower lobe are ill-defined nodules clustered around peripheral vessels, an appearance aptly described as resembling tree-in-bud. These fail to reach the pleural surface, a finding characteristic of centrilobular, as opposed to perilymphatic, distribution. Centrilobular nodules with a tree-in-bud appearance are diagnostic of infectious bronchiolitis, in this case resulting from a central carcinoid tumor. B: Histologic section obtained in A after lobectomy shows inspissated infected secretions within bronchioles.
Panbronchiolitis
In Asia, especially in Japan, a form of diffuse panbronchiolitis termed DPB is common (Figs. 8-63 and 8-65) [89]. DPB has been defined as a clinicopathologic entity, characterized by symptoms of chronic cough, sputum, and dyspnea; associated with abnormal PFTs, usually indicating mild to moderate airway obstruction and radiographic evidence of ill-defined nodular infiltrates typically basilar in distribution [248]. Histologically, DPB is characterized by chronic inflammation with mononuclear cell proliferation and foamy macrophages predominantly involving the walls of respiratory bronchioles, adjacent alveolar ducts, and alveoli, constituting the so-called unit lesion of panbronchiolitis [248]. Inclusion of this entity in the
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category of infectious etiologies of bronchiolitis is justified, as nearly all patients develop superinfection with Pseudomonas. On HRCT, a characteristic diffuse TIB pattern is invariably seen, predominantly affecting the lung bases, that has been shown to disappear after treatment with erythromycin (Fig. 8-64) [249]. Despite initial improvement, DPB is usually considered a progressive disease, with 5- and 10-year survival rates reported to be in the range of 60% and 30%, respectively [248]. DPB is described in further detail below.
FIG. 8-45. Centrilobular nodules–hypersensitivity pneumonitis. A: Target-reconstructed HRCT image through the left middle lung shows typical appearance of centrilobular nodules. Although some of these seem to branch, the vast majority is best described as poorly defined ground-glass opacity nodules without evidence of branching. Diffuse distribution is characteristic of subacute hypersensitivity pneumonitis. B: Open lung biopsy in a different patient than in A also with hypersensitivity pneumonitis shows foam cells in the interstitium (arrow). C: Different section from the same patient as B shows an ill-defined, noncaseating granuloma (arrows). These histologic features are characteristic of hypersensitivity pneumonitis.
Bronchiolar Diseases Associated with Poorly Defined Centrilobular Nodules
The hallmark of this group of diseases is the finding of ill-defined centrilobular nodules without associated TIB or branching densities (Table 8-9). As indicated by Gruden et al. [85,86], although the finding of ill-defined centrilobular nodules in patients who have bronchiolar disease usually results from peribronchiolar inflammation or fibrosis, in the absence of airway impaction with secretions, a similar CT appearance may also be the result of perilymphatic or perivascular disease. Not surprisingly, this pattern is associated with a wide range of pathologic entities (see Chapter 3). Diseases associated with primarily peribronchiolar abnormalities include RB and RB-ILD, hypersensitivity pneumonitis, follicular bronchiolitis, pneumoconioses (e.g., asbestosis, silicosis, and coal worker’s pneumoconiosis), Langerhans cell histiocytosis, and, rarely, BOOP.
Despite the large number of diseases included in this category, in most cases, differential diagnosis is simplified by detailed clinical correlation, including careful occupational and environmental exposure histories. A few entities are sufficiently characteristic to warrant special attention.
Respiratory Bronchiolitis
RB is a smoking-related disease of the airways and lungs characterized by the accumulation of pigmented macrophages within respiratory bronchioles and alveoli [213,214,215,216]. RB is typically identified as an incidental finding in asymptomatic smokers; if symptoms are associated, this disease is termed RB-ILD.
HRCT findings in RB and RB-ILD have been described, and are discussed in detail in Chapter 6 (Fig. 8-49). In most patients who have documented RB, the lungs appear either normal or show evidence of poorly defined, predominantly middle and upper lobe centrilobular ground-glass opacities, with or without accompanying areas of diffuse ground-glass opacity [235]. Findings in the few reported series published to date in patients who had RB-ILD have proven more variable. First reported in five patients by Holt et al., findings ranged from normal lungs to either ill-defined centrilobular and/or diffuse ground-glass opacity, or bibasilar areas of atelectasis and/or scarring [250]. In another study of eight patients evaluated by HRCT reported by Moon et al., five of the eight had evidence of both areas of ground-glass opacity and mild reticulation, whereas one case showed evidence of only diffuse ground-glass opacity. In all, six cases were interpreted as consistent with either RB-ILD or DIP. Interestingly, in two cases there was also evidence of diffuse centrilobular emphysema [216].
Hypersensitivity Pneumonitis
Hypersensitivity pneumonitis is associated with a chronic, nonspecific, predominantly interstitial lymphocytic pneumonitis that early in its course is primarily distributed around respiratory bronchioles with relative sparing of intervening lung [219]. This pattern may persist even later in the course of disease. Additionally, in nearly two-thirds of cases, there is also evidence of nonnecrotizing granulomas, again typically localized to the peribronchiolar interstitium. Foci of BOOP may also be identified in some cases, with characteristic findings of intraluminal fibrous plugs.
Together, these findings result in a pattern of diffuse, poorly defined centrilobular nodular opacities, especially in the subacute phase of disease (Figs. 8-45 and 8-50) [251,252,253,254,255,256,257]. These nodules are typically uniform in distribution. On occasion, their proliferation is so widespread as to result in diffuse ground-glass opacity. Close inspection, however, invariably discloses
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the presence of innumerable centrilobular ground-glass nodules accounting for this appearance. Findings in hypersensitivity pneumonitis are described in greater detail in Chapter 6.
TABLE 8-9. Bronchiolar disease: HRCT classification by predominant abnormality
Bronchiolar diseases with tree-in-bud pattern
Common
 Mycobacterium tuberculosis
 Atypical mycobacterial infections (Mycobacterium avium complex)
 Bacterial infections [e.g., cystic fibrosis; HIV(+)/acquired immunodeficiency syndrome (AIDS) patients]
Uncommon
 Viral and fungal infections, (e.g., cytomegalovirus, Pneumocystis carinii pneumonia)
 Asiatic panbronchiolitis
 Collagen-vascular diseases (follicular bronchiolitis or infection)
 Asthma
 Allergic bronchopulmonary aspergillosis
Bronchiolar diseases with poorly defined centrilobular nodules
Common
 Subacute hypersensitivity pneumonitis
 Respiratory bronchiolitis with interstitial lung disease
Uncommon
 Lymphocytic interstitial pneumonitis in AIDS patients
 Follicular bronchiolitis
 Mineral dust-induced bronchiolitis
 Collagen-vascular diseases
 Sarcoidosis
Bronchiolar disease associated with decreased lung attenuation
Common
 Constrictive bronchiolitis after lung and/or bone marrow transplantation
 Postinfectious (e.g., Swyer-James syndrome)
 Toxic fume inhalation (e.g., smoke inhalation)
Uncommon
 Idiopathic
 Associated with collagen-vascular diseases
 Consumption of Sauropus androgynus
 Constrictive bronchiolitis associated with neuroendocrine hyperplasia
 Sarcoidosis
Bronchiolar disease associated with ground-glass opacity and/or consolidation
Common
 Idiopathic bronchiolitis obliterans organizing pneumonia (BOOP)
 BOOP associated with toxic fume inhalation
 Collagen-vascular diseases
 Prior infection
 Radiation therapy
Uncommon
 BOOP associated with unrelated pathologic processes (e.g., neoplasm, infectious granulomas, and vasculitides)
 BOOP as a component of other diseases (e.g., hypersensitivity pneumonitis, Langerhans cell histiocytosis)
Adapted from Müller NL, Miller RR. Diseases of the bronchioles: CT and histopathologic findings. Radiology 1995;196:3.
Another feature described in these patients is the finding of focal air-trapping, frequently restricted to secondary pulmonary lobules. Whereas this may be the result of inhomogeneous distribution of inhaled causative agents resulting in sparing of individual pulmonary lobules, it has alternatively been speculated that air-trapping may represent associated obliterative bronchiolitis [117,257].
FIG. 8-46. Infectious bronchiolitis. Target-reconstructed HRCT section through the right lower lobe shows innumerable centrilobular linear and branching structures consistent with the clinical diagnosis of infection. Note that these densities do not extend to the pleural surface. Follow-up confirmed complete resolution after antibiotic therapy.
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Follicular Bronchiolitis
Follicular bronchiolitis represents nonspecific lymphoid hyperplasia of the bronchus-associated lymphoid tissue. Histologically, follicular bronchiolitis is characterized by the finding of hyperplastic lymphoid follicles with reactive germinal centers, typically characteristically distributed along bronchioles, and, to a lesser extent, bronchi. Extension into the lung interstitium with resulting pulmonary infiltrates is generally not considered a feature of follicular bronchiolitis [258]. Most cases are associated with underlying disorders, most often collagen-vascular diseases, in particular RA [189,245,247] and Sjögren’s syndrome, immunodeficiency disorders, and hypersensitivity reactions [259]. In children, the disease typically occurs in the first 6 to 8 weeks of life, results in respiratory distress and fever, and is usually unresponsive to either bronchodilator therapy or steroids [258].
CT findings in adult patients who have follicular bronchiolitis have been described in a few small series [189,244,260]. Cardinal features include bilateral centrilobular, peribronchial, or both types of ground-glass opacity nodules measuring 3 to 12 mm in diameter, corresponding histologically with bronchial and peribronchial lymphoid infiltration (see Fig. 5-14). Areas of ground-glass opacity may also be identified, but never in isolation. In the majority of cases, although characteristic, definitive diagnosis requires histologic confirmation. Interestingly, CT findings in one report of individuals with RA and documented follic
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ular bronchiolitis showed that in all cases in which both branching and poorly defined centrilobular nodules were evident, the disease was either stabilized or reversed after treatment with erythromycin, reinforcing the notion that a TIB pattern likely reflects underlying infection [247].
FIG. 8-47. Infectious bronchiolitis: endobronchial tuberculosis (TB). A: Enlargement of a section through the middle lobe in a patient who has documented cavitary TB. Note the typical appearance of a tree-in-bud pattern, resulting from endobronchial spread of TB. B: A 1-mm section through the right middle lung in a patient who has long-standing chronic TB, resulting in complete atelectasis of the left lung. Small, well-defined nodules are identified adjacent to peripheral branching vessels, around which a distinct zone of hyperlucency can be identified. This appearance correlates with healed endobronchial spread of TB with focal emphysema resulting from prior bronchial and bronchiolar obstruction. (Reprinted from Naidich DP, Webb WR, Müller NL, et al. Computed tomography and magnetic resonance imaging of the thorax, 3rd ed. Philadelphia: Lippincott-Raven, 1999.)
FIG. 8-48. Infectious bronchiolitis: use of maximum-intensity projection images. A: A 1-mm axial image through the lower chest shows well-defined nodular densities in the right lower lobe associated with mosaic attenuation. This appearance is nonspecific. Architectural distortion is apparent in the left base. B: Corresponding maximum intensity projection image using five contiguous 1-mm sections shows to better advantage that the nodules in the right lower lobe have a tree-in-bud configuration characteristic of infectious bronchiolitis (arrows, B).
Similar CT findings have been identified in patients who have lymphocytic interstitial pneumonitis (LIP), especially in HIV-positive and AIDS patients (Fig. 8-51) [33]. Characterized by an interstitial infiltrate of mature lymphocytes, LIP is part of the spectrum of hyperplasia of bronchus-associated lymphoid tissue that also includes follicular bronchiolitis. Although characterized by more diffuse interstitial involvement, histologic differentiation between follicular bronchiolitis and LIP may be difficult, raising the possibility that the poorly defined centrilobular nodules identified on CT in most cases of LIP diagnosed by transbronchial biopsy actually represent follicular bronchiolitis.
Bronchiolitis Obliterans Organizing Pneumonia
BOOP is characterized histologically by the presence of granulation tissue polyps within respiratory bronchioles and alveolar ducts associated with patchy organizing pneumonia [220,221,222]. Ill-defined centrilobular nodules reflecting bronchiolitis and focal organizing pneumonia may be seen. BOOP more often results in patchy consolidation.
Bronchiolar Diseases Associated with Decreased Lung Attenuation
In this category are patients who have BO (i.e., constrictive bronchiolitis or obliterative bronchiolitis). BO is defined histologically by the presence of concentric fibrosis involving the submucosal and peribronchial tissues of terminal and
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respiratory bronchioles exclusively, with resulting bronchial narrowing or obliteration (Fig. 8-54F). This process is typically nonuniform and, as the surrounding parenchyma is normal, may be difficult to identify even on open lung biopsy. Clinically, whereas these patients may be relatively asymptomatic, in most cases there is progressive airways obstruction, resulting in severe respiratory compromise that is usually unresponsive to steroid therapy.
Conditions associated with constrictive bronchiolitis include heart-lung or lung transplantations, chronic allograft rejection, allogeneic bone marrow transplantation with chronic graft-versus-host disease, and collagen-vascular diseases, especially RA [211]. Also known as the Swyer-James syndrome, BO frequently occurs as the sequela of childhood respiratory tract infections, most often viral [261]; similar findings may also be seen in children after infection with mycoplasma. Constrictive bronchiolitis is only rarely idiopathic. Obliterative bronchiolitis has also been linked to consumption of S. androgynus [242,262], a small, lowland shrub found in Asia consumed in the form of an uncooked juice as a means of weight reduction, especially in Taiwan. An HRCT pattern of mosaic perfusion has also been reported in association with neuroendocrine hyperplasia in patients who had carcinoid tumorlets [227,263].
BO is characterized by patchy areas of decreased attenuation due to mosaic perfusion and air-trapping on expiratory scans. Ancillary findings include bronchial wall thickening, bronchiectasis, atelectasis, and mucous plugging. The HRCT appearance of BO is described in detail below.
FIG. 8-49. Respiratory bronchiolitis-interstitial lung disease (RB-ILD). A-C: Sections through the upper, middle, and lower lungs show diffuse centrilobular ground-glass opacity nodules without evidence of significant bronchial dilatation (arrows, B). Mild bronchial wall thickening is identified in the lower lobes, accentuated by the use of narrow windows to target centrilobular changes. Note the absence of reticular densities, architectural distortion, or tubular or branching structures. This appearance is consistent with the diagnosis of RB-ILD in a known cigarette smoker with mildly obstructive pulmonary function test results. Continued
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Bronchiolar Diseases Associated with Focal Ground-Glass Opacity, Consolidation, or Both
This pattern of presentation is characteristic of BOOP [211,218]. BOOP is characterized histologically by the presence of granulation tissue polyps within respiratory bronchioles and alveolar ducts (Masson bodies) associated with patchy organizing pneumonia [220,221,222].
Clinically, patients who have idiopathic BOOP usually present with a 1- to 3-month history of nonproductive cough, low-grade fever, and increasing shortness of breath [220,221,222,264,265]. A variety of radiographic patterns have been described [266]. Most often radiographs show patchy, nonsegmental, unilateral, or bilateral foci of airspace consolidation [221,222,264,265]; however, in a smaller number of cases, focal nodules as well as irregular, predominantly basilar reticular densities have been described. Honeycombing is rare. Whereas the majority of patients who have ill-defined areas of patchy airspace consolidation respond to treatment with corticosteroids, the response in patients who have interstitial infiltrates has been noted to be worse [266].
Several studies have reviewed the CT and HRCT findings in patients who have BOOP; these are described in detail in Chapter 6 (see Figs. 3-76 and 3-77; Fig. 8-52 and 8-53)
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[229,267,268]. The most common abnormality consists of patchy bilateral consolidation, seen in approximately 80% of cases, which frequently has a predominantly peribronchial and subpleural distribution (Figs. 8-52 and 8-53). Bronchial wall thickening and dilatation are commonly present in the areas with consolidation. Although small (1- to 10-mm), ill-defined, predominately peribronchial or peribronchiolar nodules are seen in 30% to 50% of cases, the finding of a TIB pattern is distinctly unusual [3,84].
FIG. 8-50. A, B: Sections through the carina and lower lobes, respectively, show innumerable ill-defined centrilobular ground-glass opacity nodules, characteristic of subacute hypersensitivity pneumonitis. Note the absence of linear or branching structures, suggestive of infectious bronchiolitis. There is evidence of mild and probably physiologic airway dilatation. Note that there are also foci of relative sparing associated with air-trapping (arrows, B), likely due to inhomogeneous distribution of inhaled agents. Continued
Areas of ground-glass opacity may be seen in up to 60% of immunocompetent patients who have BOOP, but they are seldom the predominant abnormality in these patients. These are seen more commonly in immunocompromised patients who have BOOP and may be the predominant or only abnormality seen in these patients [267]. Small nodules are also seen more commonly in immunocompromised patients; nodules 1 to 10 mm in diameter were observed in 6 of 11 (55%) immunocompromised patients as compared to seven of 32 (22%) immunocompetent patients who had idiopathic BOOP reported by Lee et al. [267].
In a minority of cases, BOOP may present as multiple, large (1- to 5-cm) nodules or masses. In a report by Akira
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et al. [269], 12 of 50 (20%) patients who had BOOP presented with multiple nodules or masses as the predominant finding. Of a total of 60 lesions, 88% proved to have irregular margins, 45% were associated with air bronchograms, and 38% had pleural tags. The finding of an irregular masslike area of consolidation adjacent to pleural surfaces, in particular, proved suggestive. Similar findings have been reported by Bouchardy et al., who also found nodular or masslike opacities to be a frequent finding, occurring in 5 of 12 (42%) patients [229].
FIG. 8-51. Lymphoproliferative disorders in acquired immunodeficiency syndrome (AIDS). A: A 44-year-old mildly dyspneic woman with AIDS contracted from a blood transfusion. Her CD4 cell count was 123 cells per mm3. A 1.5-mm section shows innumerable centrilobular nodules 2 to 4 mm in diameter. These nodules are poorly marginated and of a hazy, ground-glass attenuation. At biopsy, poorly formed granulomas secondary to lymphocytic interstitial pneumonitis were identified. B: Denser nodules in the same size range are seen on the 1.5-mm sections in a 36-year-old man who has atypical lymphoproliferative disorder. Nodules are identified throughout the interstitium; the peribronchovascular distribution results in nodular vascular margins (arrows).
FIG. 8-52. Bronchiolitis obliterans organizing pneumonia (BOOP). A: Pulmonary artery radiograph shows bilateral, patchy, and poorly defined areas of parenchymal consolidation. B, C: Sections through the lung bases on inspiration and expiration, respectively, show evidence of bilateral, slightly nodular areas of parenchymal consolidation with a distinctly lower lobe and peribronchovascular distribution (asterisks, B, C). In addition, there is evidence of air-trapping most pronounced in the middle lobe on expiration. This combination of findings is nonspecific: differential diagnosis includes, among others, chronic eosinophilic pneumonia. Open lung biopsy confirmed the diagnosis of idiopathic BOOP. Continued
FIG. 8-53. A: Bronchiolitis obliterans organizing pneumonia (BOOP). Most commonly bibasilar and peribronchial in distribution, BOOP is frequently associated with mild bronchial wall thickening. BOOP may also appear predominantly unilateral, lobar, or even nodular. These findings are nonspecific: Identical findings may be seen, especially in patients with eosinophilic pneumonia. However, in distinction to diseases resulting in interstitial fibrosis, evidence of reticulation, architectural distortion, or traction bronchiectasis is unusual. B: BOOP in a 27-year-old man with polymyositis. HRCT demonstrates peribronchial and subpleural areas of consolidation and ill-defined nodular opacities involving mainly the lower lobes.
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Diseases Associated with Bronchiolitis
Bronchiolitis may be associated with a number of diseases (Table 8-8), including those described above in the section Bronchiectasis. In several diseases, the predominant abnormality is bronchiolitis. These are discussed in detail below.
Bronchiolitis Obliterans (Constrictive Bronchiolitis)
BO (constrictive bronchiolitis) represents a nonspecific reaction that may be caused by a variety of insults. It is characterized by concentric fibrosis involving the submucosal and peribronchial tissues of terminal and respiratory bronchioles, with resulting bronchiolar narrowing or obliteration of the bronchiolar lumen. BO may be classified by etiology [211,219], as (i) postinfectious BO, due to bacterial, mycoplasmal, or viral (especially respiratory syncytial virus, adenovirus, influenza, parainfluenza, and cytomegalovirus) infection, or as a sequela of PCP, HIV viral infection, or both in AIDS patients [218,261,270,271,272,273,274]; (ii) toxic fume BO, resulting from exposure to gases such as nitrogen dioxide (silo-filler’s lung), sulfur dioxide, ammonia, chlorine, phosgene, and ozone [218,270,275,276,277,278] (Fig. 8-54); (iii) idiopathic [279,280]; (iv) BO associated with connective tissue diseases, particularly RA and polymyositis [218,236,281,282,283,284]; (v) BO associated with drug therapy (e.g., penicillamine or gold) [218]; and (vi) BO as a complication of lung or bone marrow transplantation [39,40,44,45,46,285,286,287,288,289]. Obliterative bronchiolitis has also been linked to consumption of S. androgynus [242,262], a small, lowland shrub found in Asia, consumed in the form of an uncooked juice as a means of weight reduction, especially in Taiwan. BO has also been reported in association with neuroendocrine hyperplasia, especially in patients who have carcinoid tumors [227,263]. In may also be present in children surviving bronchopulmonary dysplasia [290].
The radiologic manifestations of the various forms of BO were described by Gosink et al. [270] and have been reviewed by McLoud [291]. The chest radiograph in BO is often normal. In some patients, mild hyperinflation, subtle peripheral attenuation of the vascular markings [292], and evidence of central airway dilatation may be seen [19,39,41,42].
High-Resolution Computed Tomography Findings
The HRCT appearance of BO has been described in a number of studies (Table 8-10) [18,20,39,43,87,141,230,234,242,293,294], and characteristic abnormalities have been reported in patients who have both idiopathic and secondary BO [18,230,234,294]. HRCT findings are similar regardless of the cause of disease (Fig. 8-54).
The most obvious HRCT finding is often that of focal, sharply defined areas of decreased lung attenuation associated with vessels of decreased caliber (Fig. 8-54A and C). These changes represent a combination of air-trapping and oligemia, typically occurring in the absence of parenchymal consolidation, and termed mosaic perfusion [230]. Bronchiectasis, both central and peripheral, may be present as well (Fig. 8-54A) [42]. Rarely, 2- to 4-mm centrilobular branching opacities, representing inspissated secretions within distal airways or ill-defined centrilobular opacities, may be the predominant finding [85,234], but recognizable small airway abnormalities are usually inconspicuous in patients who have BO.
Air-trapping is commonly visible on expiratory HRCT in patients who have BO (Fig. 8-54 B, D, and E). In fact, the presence of air-trapping on expiratory scans may be the only abnormal HRCT finding in patients who have BO (Fig. 8-55) [117]. In a study by Arakawa and Webb of 45 patients who had air-trapping found on routine expiratory HRCT scans [117], nine patients had normal inspiratory HRCT findings; five of these nine patients had BO.
Abnormal findings are far more evident on HRCT than on chest radiographs in patients who have BO. For example, in one study of patients who had BO [294], chest radiographs were normal in one-third of patients and showed mild hyperinflation and vascular attenuation in the remaining two-thirds. CT, on the other hand, showed widespread and conspicuous abnormalities in lung attenuation in nearly 90% of the patients.
Postinfectious Bronchiolitis Obliterans and the Swyer-James Syndrome
Chang et al. [261] assessed the long-term clinical, imaging, and pulmonary function sequelae of postinfectious BO in 19 children. Clinical follow-up averaging 6.8 years revealed a high incidence of continuing problems, largely relating to asthma and bronchiectasis. Fixed airway obstruction was the most common pulmonary function abnormality. Chest radiographs showed five patterns: (i) unilateral hyperlucency of increased volume, (ii) complete collapse of the affected lobe, (iii) unilateral hyperlucency of a small or normal-sized lung, (iv) bilateral hyperlucent lungs and a mixed pattern of persistent collapse, and (v) hyperlucency and peribronchial thickening.
Lynch et al. [141] reported the HRCT findings of post-infectious BO in six children. The most striking finding in these patients was the presence of focal areas of decreased lung opacity, which usually had sharp margins. These areas of decreased opacity corresponded to segments or lobules, and the pulmonary vessels within these areas appeared to be reduced in size. Four of these six had bronchiectasis visible on HRCT (Fig. 8-56), and in all four the abnormal bronchi were in areas of lung showing decreased opacity. It is likely that the areas of decreased opacity represent regions of lung that are poorly ventilated and perfused. Areas of increased lung opacity containing vessels that were normal or large in size were also seen in this series; these areas of increased opacity reflect well-perfused areas of lung or mosaic perfusion.
FIG. 8-54. Inspiratory and expiratory HRCT in a young woman with bronchiolitis obliterans resulting from smoke inhalation. A: Inspiratory scan shows mild bronchiectasis bilaterally, associated with a distinct pattern of mosaic perfusion, manifested by sharply marginated areas of inhomogeneous lung opacity. B: A postexpiratory scan at the same level shows an accentuation of the mosaic appearance as a result of air-trapping. C: Targeted view of the right lower lobe on inspiration shows findings of mosaic perfusion with reduced vessel size in lucent lung regions. D: Postexpiratory scan at this level shows air-trapping. E: This appearance is further accentuated on a dynamic expiratory scan. F: Histologic section from an open-lung biopsy in a different patient shows typical histologic findings of constrictive bronchiolitis, with concentric fibrosis and narrowing of a bronchiole in the absence of associated parenchymal disease.
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Zhang et al. [295] performed a prospective study to define the HRCT features of 31 pediatric patients who had postinfectious BO. All patients had chest radiographs and lung perfusion scans, and 27 of the 31 patients had HRCT of the lung. The most common abnormal features shown on CT included bronchial wall thickening (100%), bronchiectasis (85%, graded as moderate or severe in 30%), and areas of increased and decreased attenuation (82%), likely due to mosaic perfusion secondary to air-trapping. Perfusion defects on radionuclide imaging were found in all patients. Lobular, segmental, or subsegmental atelectasis was also common, being seen in 70% of cases.
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In this study [295], HRCT showed a higher sensitivity than chest radiography in detecting pulmonary abnormalities. Although bronchial wall thickening was seen on radiographs in all cases showing this finding on HRCT, areas of decreased opacity were seen in only 59% of HRCT-positive cases, and bronchiectasis was seen in only 35%.
BO is a major component of Swyer-James or MacLeod syndrome [296,297]. In patients who have Swyer-James syndrome, BO is the result of lower respiratory tract infection, usually viral, occurring in infancy or early childhood. Damage to the terminal and respiratory bronchioles leads to incomplete development of their alveolar buds. The radiographic hallmark of this syndrome is unilateral hyperlucent lung with reduced lung volume on inspiration and air-trapping on expiration (Figs. 8-56 and 8-57). Although previously necessitating confirmation either by bronchography (to demonstrate extensive bronchiecta
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sis), or arteriography (to demonstrate a small central pulmonary artery and decreased peripheral vascularity), these procedures have been all but obviated by HRCT.
TABLE 8-10. HRCT findings in bronchiolitis obliterans (constrictive bronchiolitis)
Mosaic perfusion, usually patchy in distributiona,b
Bronchiectasisaa
Air-trapping on expiration, usually patchy in distributionaa
Air-trapping on expiration with normal inspiratory scansa,b
Areas of consolidation or increased lung opacity
Reticulonodular opacities (rare)
Tree-in-bud (rare)
  a Most common findings.
  b Findings most helpful in differential diagnosis.
Marti-Bonmati et al. [293] described the CT findings in nine patients who had Swyer-James syndrome. On CT, the affected lung showed decreased opacity in eight patients (Figs. 8-56 and 8-57); in the one remaining patient, the affected lung was very small but of normal attenuation. Lung volume on the affected site was reduced in six patients and normal in three; one patient showed normal lung opacity on chest radiographs but decreased opacity on CT. In all patients, the size of the affected lung did not change on CT scans obtained during inspiration and expiration.
All nine patients had CT findings of bronchiectasis [293]. In each, cylindrical bronchiectasis was present, but two also had cystic bronchiectasis and three had varicose bronchiectasis. The lower lobes were affected in eight patients, the middle lobes or lingula in seven patients, and the upper lobes in three patients. Parenchymal abnormalities were present in eight patients.
FIG. 8-55. Bronchiolitis obliterans (constrictive bronchiolitis) with air-trapping on expiratory HRCT. A: HRCT at full inspiration shows minimal lung inhomogeneity as a result of bronchiolitis obliterans. No bronchiectasis is visible, and the chest radiograph was normal. B: On a postexpiratory HRCT, marked lung inhomogeneity is visible as a result of air-trapping.
FIG. 8-56. Bronchiolitis obliterans (constrictive bronchiolitis) in the Swyer-James syndrome. On HRCT, the lungs appear asymmetric, with marked volume loss on the left. The left lung appears relatively lucent, with diminished vascular markings and extensive cystic bronchiectasis. These findings are characteristic of the Swyer-James syndrome. CT scans through the left hilum (not shown) confirmed the presence of a hypoplastic left pulmonary artery. Currently asymptomatic, this patient recalled a history of childhood pneumonia.
Idiopathic Bronchiolitis Obliterans
Idiopathic BO usually affects middle-aged women and has a relentless downhill course despite steroid therapy. A more benign course has been described in a limited number of patients who have more stable disease, suggesting a wider range of clinical presentations than previously appreciated [280].
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Sweatman et al. [294] described the CT findings in 15 patients who had idiopathic BO. The chest radiograph was normal in five patients and showed mild hyperinflation and vascular attenuation in the remaining ten. CT showed widespread abnormalities in 13 of the 15 patients (87%), consisting of patchy irregular areas of high and low attenuation in variable proportions (Fig. 8-58). These changes were accentuated on expiration.
FIG. 8-57. Air-trapping in the Swyer-James syndrome. A: Section through the midlung fields in deep inspiration in an asymptomatic patient shows homogeneous decreased lung density in the left lower lobe in the absence of endobronchial obstruction or evidence of bronchiectasis. B: Section at the same level as (A) in expiration confirms that there is air-trapping in the left lower lobe. In this case, the patient recalled having had a severe childhood pneumonia.
Bronchiolitis Obliterans Associated with Rheumatoid Arthritis
The pulmonary manifestations of RA include bronchiolar diseases such as follicular bronchiolitis and BO [247]. BO is an uncommon manifestation, being seen in one of 29 patients suspected of having lung disease studied by Akira et al. [243]. The HRCT and expiratory CT findings of two patients who had RA and BO have been reported by Aquino et al. [194]. Both had been treated using penicillamine and gold. Plain film findings were limited to large lung volumes, but HRCT showed similar findings in both patients, with evidence of bronchiectasis and regional lung inhomogeneities (mosaic perfusion) (Fig. 8-59). In both, dynamic expiratory CT showed air-trapping on expiratory scans. Among 77 patients who had RA studied by Remy-Jardin et al. using HRCT, four of 16 with bronchiectasis were considered to have BO based on PFTs [189].
Bronchiolitis Obliterans Associated with Heart-Lung or Lung Transplantation
BO is the major long-term complication of lung transplantation, occurring in 25% to 50% of transplant recipients, and its presence or absence usually determines long-term sur
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vival [298,299,300,301]. It rarely develops in the first 3 months after transplantation, and instead usually occurs at the end of or after the first postoperative year [302]. The prompt diagnosis of BO is important, as appropriate immunosuppressive treatment may be helpful in the maintenance of lung function [303]. Of patients developing BO, between 25% and 40% die as a direct result.
FIG. 8-58. Bronchiolitis obliterans (constrictive bronchiolitis). HRCT sections through the right upper (A) and lower (B) lobes, in a young woman presenting with progressive dyspnea. Pulmonary function tests disclosed severe obstructive lung disease. Corresponding chest radiograph (not shown) was interpreted as normal. HRCT sections obtained in deep inspiration show geographic areas of low attenuation interspersed with areas of relatively increased opacity. Dilated thick-walled bronchi are easily identified throughout the lower lobes, middle lobe, and lingula. This constellation of clinical and CT findings is characteristic of patients with idiopathic constrictive bronchiolitis (cryptogenic bronchiolitis obliterans). This patient is currently awaiting lung transplantation.
Although most likely due to immunologically mediated injury of the pulmonary endothelial and bronchial epithelial cells, other etiologies have been implicated, including vascular insufficiency and infection. The primary risk factor for posttransplantation constrictive bronchiolitis appears to be the frequency and severity of acute cellular rejection that nearly always occurs in patients in the early postoperative setting [304]. Histologically, BO reflects chronic rejection and is characterized by submucosal and intraepithelial lymphocytic and histiocytic infiltrates primarily affecting the distal small airways, associated with dense submucosal eosinophilic scar tissue. Intraluminal fibrous plaques also occur, leading to either partial or complete bronchiolar obstruction [289].
FIG. 8-59. Bronchiolitis obliterans (constrictive bronchiolitis) in a patient who has rheumatoid arthritis treated with penicillamine. HRCT at two levels (A, B) shows bronchiectasis and patchy lung opacity as a result of air-trapping. (B from Webb WR. High-resolution computed tomography of obstructive lung disease. Radiol Clin North Am 1994;32:745-757, with permission.)
FIG. 8-60. Bronchiolitis obliterans (constrictive bronchiolitis) after heart-lung transplantation. Note that there is moderate dilatation of the central bronchi bilaterally (arrows). This may be an early finding in patients with bronchiolitis obliterans. (Case courtesy of Denise Aberle, M.D., University of California, Los Angeles, UCLA Medical Center.)
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Clinically, the earliest manifestation of chronic rejection is nonproductive cough, which may progress to a cough productive of purulent but sterile sputum. Later, the course is dominated by increasingly severe dyspnea. Pulmonary function tests show progressive obstruction. In accordance with definitions proposed by the International Society of Heart Lung Transplantation, the term bronchiolitis obliterans is reserved for patients having a biopsy diagnosis [305]. However, because a histologic diagnosis of BO may be difficult to make, particularly by transbronchial biopsy, the term bronchiolitis obliterans syndrome (BOS) has been proposed to describe a clinical constellation of findings consistent with this diagnosis [304]. BOS is used to refer to patients who have a progressive deterioration of graft function secondary to airways disease, but not explained by other factors such as infection, acute rejection, or anastomotic complications [305]. Using criteria established by the International Society of Heart Lung Transplantation, the diagnosis of BOS is established by a decrease in FEV1 by 20% or more from previous baseline PFT studies obtained at least one month previously [305]. A decrease in FEF25-75% to less than 70% of predicted has also been suggested as a more sensitive criterion in patients who have undergone a bilateral lung transplantation [232,289,298,299,306]. However, in patients who have undergone a single lung transplant for emphysema, FEF25-75% is usually abnormal regardless of graft function, and this criterion is difficult to apply.
Radiographic findings in transplant patients who have BO are often nonspecific. In most, chronic rejection is associated with a normal-appearing radiograph, or an appearance suggestive of CF with mild to extensive bronchiectasis. Skeens et al. [39] described the radiologic findings in 11 patients who had BO after heart-lung transplantation. In all patients, the chest radiographs showed parenchymal abnormalities consisting of reticulonodular, nodular, or airspace opacities. Radiographic evidence of central bronchiectasis was present in 9 of the 11 patients. Chest CT scans performed in two patients confirmed the radiographic findings of bronchiectasis.
HRCT findings in patients who have BO after lung transplantation include both central and peripheral bronchiectasis (Fig. 8-60); focal lucencies, presumably the result of air-trapping and mosaic perfusion; and localized parenchymal consolidation [39,40,41,42,43,44,307,308]. Bronchiectasis is commonly reported in these series but should be considered a relatively late finding of BO in patients who had undergone transplantation; the sensitivity of this finding in the detection of early disease is limited. In a study by Worthy et al. [309], 80% of patients who had proven BO after lung transplantation showed bronchial dilatation, whereas 27% were believed to have bronchial wall thickening; in a control group of normal patients, bronchial wall dilatation was felt to be present in 22%. Lentz et al. [42] found a close correlation between the percentage of bronchi in the lower lobes that appeared dilated on HRCT and PFT findings of airway obstruction. They concluded that dilatation of lower lobe bronchi is a good indicator of BO in this population, and that the percentage of dilated bronchi generally increases with increasing pulmonary dysfunction [42].
The relatively low sensitivity of the HRCT finding of bronchiectasis, however, has been emphasized by others [310]. In a study by Leung et al. [311] in patients who had an established diagnosis of BO, bronchiectasis was visible on HRCT in 4 of 11 (36%) patients who had BO and two of ten (20%) patients who did not have BO. In this study, the sensitivity, specificity, and accuracy of bronchiectasis in making the diagnosis of BO were 36%, 80%, and 57%, respectively. Others have suggested that this finding may predict the development of BO. In a study by Loubeyre et al. [308], bronchiectasis visible on HRCT was found to be a predictor of the development of clinical BO with a sensitivity of 14%, a specificity of 77%,
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a positive predictive value of 25%, and a negative predictive value of 63%. Bronchiectasis appeared concomitantly with symptoms of BO in 8 of 12 (67%) patients.
Hruban et al. [43] reported the HRCT findings seen in seven lung specimens obtained from patients who received a heart-lung transplant. The lungs were fixed using a method that allows direct one-to-one pathologic-radiologic correlation. They examined two lungs from patients who had clinical, pathologic, and HRCT evidence of chronic rejection; both lungs showed severe BO associated with bronchiectasis and peribronchial fibrosis.
Mosaic perfusion due to BO and abnormal lung ventilation is commonly seen in patients who have obliterative bronchiolitis, but the accuracy of this finding in predicting the presence of BO is limited, particularly in patients who have early disease [310]. In a study by Worthy et al. [309], mosaic perfusion was visible in 40% of patients who had proven BO after lung transplantation and in 22% of controls. In the study by Leung et al. of patients who had known disease [311], the presence of mosaic perfusion was present in 7 of 11 (64%) patients who had BO, and one of ten (10%) patients who did not have BO (p <.05). In this study, the sensitivity, specificity, and accuracy of mosaic perfusion for diagnosing BO were 64%, 90%, and 70%, respectively.
The presence of air-trapping on expiratory HRCT may be of the most value in making the diagnosis of BO [309,311], but the accuracy of this finding may be limited in patients who have early disease [310]. In the study by Worthy et al. [309], air-trapping, diagnosed on expiratory scans if a total area of more than one segment appeared abnormal, was seen in four of five (80%) patients who had biopsy-proven BO and expiratory scans, and in none of three patients who had a negative biopsy. In a study by Leung et al. [311], air-trapping was found in ten of 11 patients who had biopsy-diagnosed BO, compared to two of ten patients who did not have biopsy-diagnosed BO or PFT abnormalities. Thus, air-trapping was found to have a sensitivity of 91%, a specificity of 80%, and accuracy of 86% for diagnosing BO. However, the patients who had BO in this study had established disease; the mean time from lung transplantation to CT in their study was 4.8 years, and the mean duration of a known diagnosis of BO was 1.3 years.
In a study by Lee et al. [310], HRCT including expiratory scans was reviewed in consecutive normal lung transplant patients and patients first diagnosed as having BO or BOS (i.e., early disease). The frequency of significant air-trapping in patients who had BO or BOS was significantly higher than in patients who had a normal biopsy and PFTs. However, the sensitivity of significant air-trapping on expiratory CT was only 74%; its specificity was 67%, and its accuracy was 71%.
The role of repeated HRCT scans in monitoring the development of BOS after lung transplantation has also been assessed by Ikonen et al. [312]. In a study of 13 lung transplant recipients who underwent a total of 126 HRCT scans during a mean follow-up period of 23 months, 8 of the 13 patients developed BOS. The authors demonstrated that the HRCT findings occurred concurrently with the development of BOS. Making use of a combination of abnormalities for diagnosis, the overall sensitivity of HRCT for the diagnosis of BO was 93% and the specificity was 92% [312].
The HRCT appearance of posttransplantation BOS has been reviewed by Lau et al. [313] in six infants and young children with BOS (age range, 2 months to 5.5 years) and in 15 control patients who did not have obstructive airways disease (age range, 2 months to 7 years). HRCT scans were obtained during quiet sleep at a median of 24 months (range, 6 to 36 months) after transplantation. The HRCT findings in the six patients who had clinically proven BOS were mosaic perfusion in five (83%), bronchial dilation in three (50%), and bronchial wall thickening in one (17%). Of the 15 control patients who had normal PFT results, six (40%) were believed to have findings of mosaic perfusion, whereas none had bronchial dilatation or bronchial wall thickening. Mucous plugging was not seen in either group. Only the association of bronchial dilatation with BOS was significant (p = .02).
Bronchiolitis Obliterans Associated with Bone Marrow Transplantation
BO is one of several pulmonary complications of bone marrow transplantation, occurring in approximately 10% of patients [46,314,315,316]. Other complications include infection (bacterial, viral, and fungal–in particular, invasive aspergillosis); pulmonary edema; drug and radiation toxicity; and metastatic tumor. A syndrome of diffuse pulmonary hemorrhage has also been described, occurring within the first two weeks after bone marrow transplantation [317]. Determining the cause of pulmonary disease in these patients is frequently problematic, as biopsies are usually contraindicated due to severe thrombocytopenia.
BO is usually identified in patients after allogeneic transplants, presumably the result of chronic graft-versus-host disease (GVHD) (Figs. 8-61 and 8-62) [45,46,218,285,318]. Histologically, BO (constrictive bronchiolitis) is the predominant abnormality, characterized both by neutrophilic and lymphocytic peribronchiolar inflammation. Importantly, histologic evidence of BOOP/COP (or proliferative bronchiolitis) with extension into alveolar ducts and alveoli is distinctly unusual as a cause of airway obstruction in this population [46]. Typically, these patients also have evidence of GVHD involving the skin, liver, and gastrointestinal tract. Patients also frequently have evidence of chronic sinusitis. In fact, bronchiolitis has also been identified in patients after autologous bone marrow transplants, leaving the true etiology of bronchiolitis unexplained [46].
Clinically, patients may present with cough, wheezing, or dyspnea between 1 and 10 months after transplantation [46]. Alternatively, evidence of airways obstruction may be present physiologically in otherwise asymptomatic patients. In either setting, the key to diagnosing bronchiolitis in these patients are serial PFTs. The hallmark of this disease is a decrease in the FEV1/FVC ratio of less than 70% predicted, often in association with an increased residual volume. In
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most institutions, in distinction to patients who have lung or heart-lung transplantations, pulmonary function testing is considered diagnostic even in the absence of histologic verification. BAL is indicated only in those patients who can tolerate this procedure, in whom concomitant infection is suspected. Despite aggressive therapy with steroids, bronchodilators, or azathioprine, nearly 50% of patients die from progressive respiratory insufficiency.
FIG. 8-61. Bronchiolitis obliterans in a bone marrow transplant patient. Extensive bronchiectasis is associated with patchy areas of mosaic perfusion.
In the absence of infection, radiographs typically are normal or show only mild hyperinflation, similar to changes identified in other conditions associated with constrictive bronchiolitis. HRCT shows typical findings of BO, with evidence of bronchiectasis, mosaic perfusion, and air-trapping. In an early stage, ill-defined peribronchiolar, centrilobular opacities have been identified [85]. In a study by Ooi et al. [319], HRCT was performed in nine patients who had moderately severe irreversible airflow obstruction and a clinical diagnosis of BOS (persistent lung function deterioration, with FEV1 of less than 80% of baseline values) after bone marrow transplantation. Two patients had normal HRCT scans. In the remaining seven patients, 7 of 11 HRCT scans were abnormal, with nonspecific findings of bronchial dilatation (one patient), consolidation (two patients), areas of decreased opacity (four patients), and vascular attenuation (four patients).
It should be emphasized that constrictive bronchiolitis represents only one of a wide range of potential pulmonary abnormalities that can occur after bone marrow transplantation [316]. Not surprisingly, the range of CT findings that can be identified primarily reflects the patient’s clinical status. Graham et al. [45], in a broad-based study of 18 patients who had 21 episodes of intrathoracic complications after allogeneic bone marrow transplantation, showed that CT disclosed diagnostically relevant findings not apparent on chest radiographs in more than 50% of cases. These included a ground-glass pattern in five patients who had early pneumonia; a peripheral distribution of abnormalities, including bronchiectasis, in four patients who had BO, eosinophilic lung disease, or both; and cavitating lesions or hemorrhagic infarcts in one case each of PCP and invasive aspergillosis, respectively [45]. In comparison, a much narrower range of findings has been described when only febrile patients are evaluated. In this setting, CT has been advocated as a noninvasive means for diagnosing invasive fungal infections. Mori et al. [320], in a retrospective study of 33 febrile bone marrow transplant recipients, documented 21 episodes of fungal infection. In 20 of 21 of these cases, CT showed nodules most of which proved either cavitary, poorly defined, or had associated characteristic halo signs. In distinction, in nine patients who had bacteremia, CT failed to disclose any abnormalities, suggesting that the source of infection was outside the lungs.
FIG. 8-62. Bronchiolitis obliterans in a bone marrow transplant patient. A: Targeted image of the left lower lobe shows mild bronchiectasis with the signet ring sign (arrows). B: Dynamic low-dose expiratory scan shows patchy air-trapping.
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Diffuse Panbronchiolitis
DPB is a unique syndrome described almost exclusively in Asia, especially in Japan and Korea [88,89,218,321,322,323]. This entity typically affects middle-aged men. Patients present with the subacute development of airways obstruction, and in nearly three-fourths of patients, there is associated sinusitis. The disease is progressive, marked by frequent episodes of superimposed infection, typically with Pseudomonas aeruginosa. In nearly 20% of cases, death occurs within 5 years of the onset of the disease, with another 30% dying within ten years. Current therapy requires long-term low-dose administration of erythromycin.
Histologically, characteristic findings of this disease include centrilobular peribronchiolar infiltrates of acute and chronic inflammatory cells, principally at the level of the respiratory bronchioles, associated with bronchiolar dilatation and intraluminal inflammatory exudates (Fig. 8-63). A striking accumulation of interstitial foam cells and lymphoid hyperplasia is also commonly seen. This combination of findings has been referred to as the unit lesion of panbronchiolitis and is considered unique to this syndrome [218]. Although the disease characteristically involves respiratory bronchioles, terminal bronchioles may be involved. In a minority of cases, there is also evidence of peripheral bronchiectasis. Chest radiographs in patients who have DPB are nonspecific and usually show small nodular shadows throughout both lungs and, often, increased lung volumes.
High-Resolution Computed Tomography Findings
HRCT findings in patients who have DPB have been extensively described (Table 8-11) [88,89,248,249,321,322]. As initially shown by Akira et al. [89], the most important findings, in order of severity, are poorly defined centrilobular
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nodules, centrilobular branching opacities or TIB, and branching thick-walled centrilobular lucencies (see Fig. 3-75; Fig. 8-64). As confirmed by Nishimura et al. [88], these findings correspond to, respectively, peribronchiolar inflammation and fibrosis, dilated bronchioles with inflammatory wall thickening and intraluminal secretions, and dilated, air-filled bronchioles (Fig. 8-65) [88]. The finding of small, peripheral peribronchiolar nodules is particularly characteristic, resulting in a TIB appearance.
FIG. 8-63. Diffuse panbronchiolitis. Open lung biopsy specimen shows centrilobular peribronchiolar infiltrates of acute and chronic inflammatory cells (solid arrows), principally at the level of the respiratory bronchioles, associated with bronchiolar dilatation (open arrows). (From Gruden JF, Webb WR, Warnock M. Centrilobular opacities in the lung on high-resolution CT: diagnostic considerations and pathologic correlation. AJR Am J Roentgenol 1994;162:569-574, with permission.)
TABLE 8-11. HRCT findings in diffuse panbronchiolitis
Centrilobular branching opacities, tree-in-buda,b
Bronchiolectasisa,b
Bronchiectasisaa,b
Diffuse distribution/basilar predominanceaa
Large lung volumes
Mosaic perfusion
Air-trapping on expirationaa
  a Most common findings.
  b Findings most helpful in differential diagnosis.
In addition to these findings, patients who have DPB usually show evidence of air-trapping with large lung volumes and decreased attenuation of peripheral lung parenchyma [88]. As documented by Murata et al. [322], in a study comparing positron emission tomography and CT in seven patients who had DPB, CT attenuation values were considerably lower in the periphery of the lung as compared with the central portions, a finding indicative of extensive peripheral air-trapping. Such stratified distribution of ventilatory impairment may be considered characteristic of diffuse bronchiolar narrowing.
Utility of High-Resolution Computed Tomography
Although the course of this disease is typically monitored clinically, HRCT may play a role in select cases. As documented by Akira et al. [321], in a study of 19 patients randomly assigned either to therapy with low-dose erythromycin or to follow-up without treatment, centrilobular nodular and branched opacities decreased in number and size in treated patients, suggesting a positive response to therapy. In distinction, among untreated patients, similar densities observed initially were found to have progressed with resultant dilatation of the proximal airways. Similar results have been shown by Ichikawa et al. [249]. These findings suggest a potential role for HRCT for monitoring as well as for predicting the outcome of therapy.
It should be noted that the finding of nodular or branching centrilobular opacities may be seen in a number of different diseases in which bronchiolar abnormalities are present [70,85]. Linear or branching centrilobular opacities result from bronchiolar dilatation with intraluminal accumulation of mucus, fluid, or pus. As noted previously, this has been termed the TIB appearance and can be identified in patients who have CF [141]; endobronchial spread of tuberculosis [27] or nontuberculous mycobacteria; lobular pneumonia or bronchopneumonia, including those with PCP or cytomegalovirus pneumonia; bronchiectasis of any cause; and other airways diseases that result in the accumulation of mucus or pus in small bronchi. The differential diagnosis of centrilobular opacities is described in detail in Chapter 3.
FIG. 8-64. Diffuse panbronchiolitis. HRCT at two levels shows findings of poorly defined centrilobular nodules in the lung periphery, centrilobular branching opacities or tree-in-bud, and bronchiectasis. (Courtesy of Shin-Ho Kook, M.D., Koryo General Hospital, Seoul, Korea.)
FIG. 8-65. Diffuse panbronchiolitis. A: Radiograph of a 1-mm slice of lung obtained from a patient who has panbronchiolitis. A dilated air-filled bronchiole (arrows) is visible in the lung periphery, extending to within 5 mm of the pleural surface. B: Photomicrograph shows a dilated bronchiole (arrows) in the subpleural lung filled with secretions. (From Nishimura K, Kitaichi M, Isum T, et al. Diffuse panbronchiolitis: correlation of high-resolution CT and pathologic findings. Radiology 1992;184:779-785, with permission.)
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