AJR 2004; 183:817-824
© American Roentgen Ray Society
Asthma and Associated Conditions: High-Resolution CT and Pathologic Findings
C. Isabela S. Silva1,
Thomas V. Colby2 and
Nestor L. Müller1,3
1 Department of Radiology, Vancouver General Hospital, 899 W 12th Ave.,
Vancouver, BC V5Z 1M9, Canada.
2 Department of Pathology, Mayo Clinic, 13400 E Shea Blvd., Scottsdale, AZ
85259.
3 Department of Radiology, University of British Columbia, 3350-950 W 10th Ave.,
Vancouver, BC V5Z 4E3, Canada.
Received September 8, 2003;
accepted after revision January 30, 2004.
Address correspondence to N. L. Müller
(nmuller{at}vanhosp.bc.ca).
Asthma is an inflammatory disease of the lungs characterized by increased
airway reactivity to various stimuli and by airflow obstruction that is at
least partially reversible. High-resolution CT manifestations of asthma
include thickening of the bronchial wall, narrowing of the bronchial lumen,
areas of decreased attenuation and vascularity on inspiratory CT scans, and
air trapping on expiratory CT scans
[13].
Other findings that are seen with increased frequency in patients with asthma
are bronchiectasis and emphysema
[1,
2]. Asthma is associated with
several complications including atelectasis, pneumonia, mucoid impaction,
allergic bronchopulmonary aspergillosis (ABPA), bronchocentric granulomatosis,
eosinophilic lung disease, and Churg-Strauss syndrome.
The aim of this pictorial essay is to illustrate the high-resolution CT
manifestations of asthma and associated conditions and to compare the CT
findings with the pathologic findings.
High-Resolution CT and Histologic Manifestations of Asthma
Bronchial Abnormalities
Histologically, asthma is characterized by the presence of chronic
inflammation of the airways that involves mainly the mediumsized and small
bronchi [4]. The bronchi are
thickened by the combination of edema and an increase in the amount of smooth
muscle and in the size of the mucous glands
(Fig. 1). These histologic
changes are manifested on high-resolution CT by the presence of bronchial wall
thickening and narrowing of the bronchial lumen
(Fig. 2).

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Fig. 1. Photomicrograph of autopsy specimen obtained in 10-year-old boy with
fatal asthmaticus reveals bronchus with luminal mucus plug
(asterisks), thinning of surface mucosa (arrowheads), and
submembranous fibrosis (so-called basement membrane thickening) (vertical
straight arrows), muscle hypertrophy (horizontal straight
arrow), and inflammatory infiltrate (curved arrows) that is rich
in eosinophils. (H and E, low magnification)
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Fig. 2. High-resolution CT scan obtained in 72-year-old woman with chronic
asthma shows bronchial wall thickening (large arrows) with associated
narrowing of bronchial lumen. Also noted are subtle areas of decreased
attenuation and vascularity (small arrows), which are more clearly
seen in Figures 3A and
3B.
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Fig. 3A. 52-year-old man with asthma and bronchiectasis. High-resolution MDCT
scan shows bilateral bronchiectasis (straight arrows) and areas of
decreased attenuation and vascularity (curved arrows). Note that
bronchi are dilated but are not thick-walled.
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Fig. 3B. 52-year-old man with asthma and bronchiectasis. Coronal reformatted
image shows ectatic bronchi and areas of decreased attenuation and vascularity
in lower lobes (arrows) and normal upper lobes.
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The prevalence of bronchial thickening on high-resolution CT in patients
with asthma reported by various authors ranges from 44% to 92%
[13].
The wide variability in prevalence is presumably related to the subjective
nature of the assessment and different patient populations. Park et al.
[3] identified bronchial wall
thickening in 17 (44%) of 39 asthmatic patients compared with only 4% of
healthy control subjects. Bronchial wall thickening was more prevalent among
patients with severe air-flow obstruction (83% of patients with forced
expiratory volume in 1 sec [FEV1] that was < 60% of predicted
volume) than in patients with mild obstruction (35% of patients with
FEV1
60%). Park et al. assessed the degree of bronchial
narrowing by objectively measuring the ratio between the short-axis internal
bronchial diameter and the short-axis diameter of the accompanying pulmonary
artery. Asthmatic patients with an FEV1 of less than 60% of
predicted volume had a lower bronchoarterialdiameter ratio (mean ± SD,
0.48 ± 0.11) than patients with mild airway obstruction (0.60 ±
0.18) or healthy subjects (0.65 ± 0.16) (p < 0.01)
[3].
In patients with asthma, most of the bronchi have normal or decreased
internal diameters; however, in approximately 3040% of adult patients
with uncomplicated asthma, one or more bronchi are dilated
[2,
3] (Figs.
3A and
3B). The presence of
bronchiectasis does not correlate with the severity of airflow obstruction in
these patients [2,
4]. The bronchiectasis seen in
patients with uncomplicated asthma typically is cylindrical, and the
bronchoarterial-diameter ratio is less than 1.5
[1,
5].
Bronchiolar Abnormalities
Histologic bronchiolar abnormalities seen in asthma include bronchiolar
wall thickening, mucus stasis in bronchioles, and constrictive bronchiolitis
(Figs. 4A and
4B). Between clinical episodes,
the bronchioles may be (nearly) normal when viewed in tissue collected for
other reasons from asthmatic patients (Colby TV, personal observation). The
high-resolution CT manifestations include areas of decreased attenuation and
vascularity, air trapping, and small centrilobular opacities (Figs.
3A,
3B and
5A,
5B).

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Fig. 4A. Bronchiolar abnormalities in two patients with asthma.
Photomicrograph of histopathologic specimen obtained in 10-year-old boy with
fatal asthmaticus shows small bronchiole (outside diameter, 0.5 mm from
adventitia to adventitia) with muscle hypertrophy (short straight
arrow), submucosal and submembranous fibrosis (long straight
arrows), and inflammatory infiltrate (curved arrows) rich in
eosinophils. Goblet cell metaplasia (more typically seen in bronchi of
patients with asthma) is prominent and seen as pale swollen cells
(arrowheads) replacing much of columnar ciliated epithelium. Extent
of submembranous and submucosal fibrosis (structural remodeling) is indicative
of presence of mild constrictive bronchiolitis histologically. (H and E,
intermediate magnification)
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Fig. 4B. Bronchiolar abnormalities in two patients with asthma.
Photomicrograph of histopathologic specimen obtained in 48-year-old woman with
long history of asthma shows bronchiole with submucosal thickening that was
caused by fibrous tissue (arrows) and resulted in luminal narrowing.
These findings are characteristic of mild constrictive bronchiolitis.
(Trichrome stain, intermediate magnification)
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Fig. 5B. 45-year-old woman with asthma and air trapping. High-resolution CT
scan obtained at maximal expiration shows bilateral areas of air trapping with
associated decrease (arrows) in vascularity. Presence of parenchymal
abnormalities due to airway obstruction is much more readily seen on
expiratory scan. Note invagination of posterior tracheal wall, which aids in
identifying this as expiratory scan.
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Areas of decreased attenuation and vascularity are seen on high-resolution
CT scans obtained at end-inspiration in approximately 20% of patients with
asthma
[13].
A more common finding on CT scans obtained after maximal expiration is the
presence of air trapping. In the study by Park et al.
[3], air trapping involving a
total volume equivalent to one pulmonary segment or more was seen in 50% of
asthmatic patients compared with 14% of healthy subjects (p <
0.001).
Prominent centrilobular structures or small centrilobular opacities have
been reported in 1020% of patients with asthma
[1,
2]. These presumably reflect
the presence of mucus stasis in bronchioles or peribronchiolar
inflammation.
Parenchymal Abnormalities
Parenchymal abnormalities in asthma include hyperinflation, emphysema, and,
rarely, cysts. Hyperinflation is a common finding radiographically in patients
with severe asthma, but emphysema is quite uncommon. Lynch et al.
[1] found evidence of emphysema
in nine (19%) of 48 asthmatic patients compared with zero of 27 healthy
control subjects. However, only two of the asthmatic patients with emphysema
had never smoked. The diagnosis of emphysema in these patients was based on
the presence of areas of abnormally low attenuation consistent with emphysema
on high-resolution CT of the chest
[1]. Histologically, emphysema
is uncommon in asthmatic nonsmokers; it is usually mild and secondary to
cicatricial peribronchial fibrosis
[4]. Rarely cystic changes may
result from overinflating distal to chronic inflammatory bronchiolitis (Figs.
6A and
6B).

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Fig. 6A. 27-year-old woman with asthma and cystic changes. Patient had never
smoked. Photomicrograph of histopathologic specimen shows strand of residual
alveolar tissue (curved arrow) remaining in cyst arising adjacent to
bronchiole (straight arrow). (H and E, low magnification)
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Fig. 6B. 27-year-old woman with asthma and cystic changes. Patient had never
smoked. CT scan (5-mm collimation) shows bilateral small localized rounded
areas of low attenuation (arrows) with well-defined smooth walls
consistent with cysts, raising concerns of possible lymphangioleiomyomatosis.
However, no evidence of lymphangioleiomyomatosis was found at surgical
biopsy.
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High-Resolution CT and Histologic Manifestations of Associated Conditions
ABPA
ABPA is a clinical syndrome characterized by hypersensitivity reaction to
endobronchial growth of Aspergillus fumigatus. The histologic
findings, which vary from case to case, may include mucoid impaction of
bronchi with the typical mucous plugs (allergic mucin) (Figs.
7A and
7B), bronchocentric
granulomatosis, bronchiectasis, and eosinophilic pneumonia
[4]. These patients also
typically have positive results on skin tests and markedly elevated serum
levels of immunoglobulin E (IgE) levels. Bronchocentric granulomatosis often
occurs in patients with ABPA. It is characterized by a pattern of necrotizing
granulomatous inflammation that destroys the walls of small bronchi and
bronchioles [4].

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Fig. 7A. Histopathologic specimens of allergic bronchopulmonary aspergillosis
(ABPA) obtained in 33-year-old woman with history of asthma. Diagnosis of ABPA
was based on findings of this biopsy. Photomicrograph shows sections of mucus
plug with typical features of allergic mucin with layering of mucus and cell
debris (arrows). (H and E, intermediate magnification)
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Fig. 7B. Histopathologic specimens of allergic bronchopulmonary aspergillosis
(ABPA) obtained in 33-year-old woman with history of asthma. Diagnosis of ABPA
was based on findings of this biopsy. Photomicrograph obtained with higher
magnification than A shows that cell debris consists of degenerated
eosinophils with associated Charcot-Leyden crystals (arrows). (H and
E, high magnification)
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The high-resolution CT manifestations of ABPA include homogeneous tubular,
finger-in-glove, or branching endobronchial opacities and bronchiectasis
involving mainly the segmental and subsegmental bronchi of the upper lobes
(Figs. 8A,
8B,
9A,
9B,
10A,
10B, and
10C). In approximately 30% of
patients with ABPA, the impacted mucus exhibits attenuation greater than that
of soft tissue, consistent with calcification. The mucus plugging can extend
into bronchioles resulting in centrilobular nodular opacities
[4] (Figs.
10A,
10B, and
10C).

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Fig. 8B. 73-year-old woman with allergic bronchopulmonary aspergillosis.
High-resolution CT scan obtained at slightly higher level than A shows
that mucoid impaction is present in several small bronchi.
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Fig. 10A. 56-year-old man with allergic bronchopulmonary aspergillosis.
High-resolution MDCT scan obtained through upper lobes shows severe bilateral
bronchiectasis and marked bronchial wall thickening. Also noted is mucoid
impaction (arrows).
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Fig. 10B. 56-year-old man with allergic bronchopulmonary aspergillosis.
High-resolution MDCT scan obtained at level of lower lobe bronchi shows
central bronchiectasis, areas of decreased attenuation and vascularity, and
mucoid impaction (arrows).
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Fig. 10C. 56-year-old man with allergic bronchopulmonary aspergillosis.
Sagittal reformatted image of right lung shows equal severity of upper and
lower lobe bronchiectasis and extensive areas of decrease attenuation and
vascularity. Also noted are a few small centrilobular nodules
(arrows).
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Ward et al. [6] compared the
high-resolution CT findings in 44 asthmatic patients with ABPA and 38
asthmatic patients without ABPA. Abnormalities seen more commonly in patients
with ABPA included bronchiectasis, centrilobular nodules, and mucoid impaction
(p < 0.01). Bronchiectasis was present in 95% of patients with
ABPA; centrilobular nodules, in 93%; and mucoid impaction, in 67%. By
comparison, bronchiectasis was detected in 29% of the asthmatic control group;
centrilobular nodules, in 28%; and mucoid impaction, in 4%
[6]. Mitchell et al.
[5] compared the
high-resolution CT scans obtained in 19 patients with documented ABPA with
scans obtained in 18 asthmatic control subjects. Seventeen patients (89%) with
ABPA had central cystic or varicose bronchiectasis typically involving several
lobes. By comparison, only three asthmatic patients (17%) had bronchiectasis,
and it was exclusively cylindrical in nature
[5].
Chronic Eosinophilic Pneumonia
Chronic eosinophilic pneumonia is a condition characterized histologically
by the presence of intraalveolar eosinophils, macrophages, an amorphous
proteinaceous exudate, and organizing pneumonia
(Fig. 11). The organizing
pneumonia can be associated with intraluminal organization in bronchioles
(bronchiolitis obliterans with organizing pneumonia). The patients present
clinically with fever, night sweats, cough, and dyspnea. Most patients have
peripheral eosinophilia. Approximately 50% of patients are asthmatics; women
are affected twice as frequently as men. The characteristic radiologic
manifestations consist of bilateral areas of consolidation mainly affecting
the peripheral regions of the middle and upper lung zones (Figs.
12A and
12B). The predominantly
peripheral distribution of the consolidation is evident on radiography in
approximately 65% of patients and on high-resolution CT in 95% of patients
[7].

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Fig. 11. Histopathologic specimen obtained in 50-year-old man shows foci of
eosinophilic pneumonia with air-space fibrin (straight arrows) and
numerous eosinophils (curved arrow) in air spaces. Also noted are
increased alveolar macrophages and mild mononuclear cell infiltrate. (H and E,
intermediate magnification)
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Fig. 12A. 75-year-old woman with chronic eosinophilic pneumonia.
High-resolution CT scan obtained at level of main bronchi shows extensive
consolidation in right upper lobe and small localized areas of ground-glass
attenuation and consolidation in left upper lobe.
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Churg-Strauss Syndrome
Churg-Strauss syndrome is a multisystem disorder characterized by the
combination of allergy, peripheral blood eosinophilia, and systemic vasculitis
(Figs. 13A and
13B). Almost all patients with
Churg-Strauss syndrome are asthmatics, and most present with peripheral
neuropathy, typically mononeuritis multiplex. The histologic findings consist
of a necrotizing vasculitis of mediumto small-sized blood vessels associated
with eosinophilic infiltration around the vessels and adjacent tissues. Common
sites of involvement include the lungs, heart, kidneys, and skin.

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Fig. 13A. Histopathologic findings of Churg-Strauss syndrome in two patients.
Photomicrograph of pathologic specimen obtained in 67-year-old woman shows
vasculitis (arrow) involving small vessel at its branch point.
Transmural inflammatory infiltrate was mixed in composition, with histiocytes,
lymphocytes, and numerous eosinophils that are just barely discernible. (H and
E, intermediate magnification)
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Fig. 13B. Histopathologic findings of Churg-Strauss syndrome in two patients.
Photomicrograph of pathologic specimen obtained in 50-year-old man shows areas
of consolidation and early necrosis (arrows) that primarily
represented degenerating eosinophils. Inflammatory interstitial and air-space
infiltrate is mixed in composition, and resulting consolidation obscures
underlying architecture of lung. (H and E, intermediate magnification)
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The most common high-resolution CT findings consist of patchy nonsegmental
bilateral areas of consolidation or ground-glass opacities that often have a
predominately peripheral distribution characteristic of chronic eosinophilic
pneumonia [8]
(Fig. 14). Less common
manifestations include multiple solid or cavitated 1- to 3-cm-diameter
pulmonary nodules, small centrilobular nodules, and interlobular septal
thickening (Figs. 15A and
15B). The interlobular septal
thickening may result from pulmonary eosinophilic infiltration or the presence
of pulmonary edema due to cardiac involvement. Histologically, the infiltrates
and nodules in ChurgStrauss syndrome show varying degrees of inflammatory
consolidation, rich in eosinophils (including eosinophilic pneumonia),
granulomatous reaction, vasculitis, and necrosis. Necrosis may be punctate and
surrounded by giant cells (the Churg-Strauss granuloma) or much more extensive
and predominantly composed of necrotic eosinophils.

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Fig. 14. 52-year-old man with Churg-Strauss syndrome. High-resolution CT scan
obtained at level of aortic arch shows bilateral focal areas of peripheral
consolidation. Appearance is identical to that of chronic eosinophilic
pneumonia or bronchiolitis obliterans with organizing pneumonia.
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Fig. 15A. 68-year-old woman with Churg-Strauss syndrome. High-resolution MDCT
scan obtained at level of upper lobes shows extensive bilateral septal
thickening. Also noted are bronchial wall thickening (arrows), small
peripheral ground-glass opacities, and a small right pleural effusion.
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Fig. 15B. 68-year-old woman with Churg-Strauss syndrome. Sagittal reformatted
image of right lung shows septal thickening predominately in upper lobe
(white arrows) and in dorsal regions of lower lobe. Also noted is
extensive bronchial wall thickening (black arrows).
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