Dr. Collins is an Associate Professor of Radiology and
Medicine, University of Wisconsin Hospital and Clinics,
Clinical Science Center, Madison, WI; Dr. Stern is a Professor
of Radiology and Medicine, Director of Thoracic Imaging, and
Director for Faculty Development, Harborview Medical Center,
University of Washington, Seattle, WA; and Dr. Franquet is an
Associate Professor of Radiology and Director of Thoracic
Imaging, Hospital de Sant Pau, Barcelona, Spain.
This article will define bronchiolar anatomy, present an optimal
method for computed tomography (CT) scanning of the chest when
bronchiolar disease is suspected, describe the direct and indirect
CT findings of bronchiolar disease, and review the main causes of
The division of the trachea gives rise to the left and right
mainstem bronchi, which further divide into lobar and segmental
bronchi. Segmental bronchi divide, and after 6 to 20 divisions they
no longer contain cartilage in their walls and are referred to as
bronchioles. The bronchioles divide, and the last of the purely
conducting airways is referred to as the terminal bronchiole.
Beyond the terminal bronchioles lie the acini, the gas exchange
units of the lung. The central bronchi down to the segmental level
can be identified routinely with 10-mm collimation CT sections, and
8th order branching airways can be seen with thin sections.
The secondary pulmonary lobule refers to the smallest unit of
lung structure marginated by connective tissue septa, and it is
easily visible on the surface of the lung. The size of secondary
pulmonary lobules varies from about 1 to 2.5 cm in diameter in most
locations, and each is supplied by a central small bronchiole
(<1 mm in diameter) and a pulmonary artery. The lobules are
marginated by connective tissue interlobular septa that contain
pulmonary vein and lymphatic branches (figure 1).
Because visibility on CT is limited to bronchi >2 mm in
diameter, normal lobular bronchioles cannot be seen on CT scans.
However, centrilobular arteries and diseased bronchioles can be
easily resolved using the high-resolution CT (HRCT) technique.
CT patterns of bronchiolar disease
When bronchiolar disease is suspected, CT scanning should be
performed using thin collimation (1.0 to 1.5 mm), image
reconstruction with a high-spatial frequency "sharp" algorithm
(i.e., "bone" algorithm), short scan time (1 to 2 seconds), and
increased kVp (120 to 140) and mA (140 to 240) technique. Thicker
sections do not characterize the bronchiolar disease as well.
Windowing may need to be customized, although in general, window
width between 1200 and 2000 and level between -500 to -750 is
recommended for viewing pleuro-parenchymal disease. Scanning should
include the entire lungs, at 1.0-cm intervals during full
inspiration. Expiratory scanning should be performed at the same
levels, or every 2 to 3 cm throughout the lungs. The presence of
air trapping on expiratory scanning may be the only finding of
bronchiolar disease, and, therefore, scans obtained during
expiration are especially important when the inspiratory scans are
Direct CT findings of bronchiolar disease include bronchiolar
wall thickening, bronchiolar dilatation, and luminal impaction
Bronchiolar impaction with pus, mucus, granulomas, inflammatory
exudate, or fibrotic material all have similar appearances, and
manifest as 2- to 4-mm nodular and linear branching centrilobular
opacities on CT. Usually, abnormal bronchioles can be distinguished
from normal centrilobular vessels by their more irregular
appearance, a lack of tapering, or a knobby or bulbous appearance
at the tips of small branches.
The "tree-in-bud" pattern represents a form of bronchiolar
impaction. The term "tree-in-bud" dates back to the bronchogram
descriptions of normal respiratory bronchioles by Twining and
and Reid and Simon
(figure 3), and has been popularized by Im et al
to describe the CT appearance of the endobronchial spread of
. This pattern is analogous to the "finger-in-glove" appearance of
bronchial impaction, but on a much smaller scale. Because of its
similar appearance to the metal "jack" used in the childhood game
played with a rubber ball, the "tree-in-bud" pattern has also been
described as resembling "jacks."
Indirect or secondary CT signs of bronchiolar disease include
subsegmental atelectasis and air trapping. Air trapping appears as
focal or diffuse areas of decreased lung attenuation, often forming
a "mosaic" pattern of lung attenuation, which is best seen (or only
seen) on expiratory scanning. Lung parenchyma normally increases in
CT attenuation as lung volume is reduced during expiration. This
change can be recognized on CT as an increase in lung opacity.
Normally, the lungs of people without bronchiolar disease can show
occasional lobular-sized areas of focal lucency on expiratory CT
scans; in these regions, the lung does not increase normally in
attenuation, probably due to physiologic air trapping.
This is limited to a small proportion of lung volume, and when more
than a few secondary pulmonary lobules are involved, pathologic air
trapping should be considered.
"Bronchiolitis" is a term used to describe a spectrum of
inflammatory disorders affecting small bronchioles. These disorders
show great heterogeneity in regard to cause, clinical features, and
histopathologic changes. Myers and Colby
classified these conditions into 8 types: 1) constrictive
bronchiolitis; 2) cryptogenic organizing pneumonia; 3) infectious
bronchiolitis; 4) adult bronchiolitis; 5) respiratory
bronchiolitis; 6) mineral dust airways disease; 7) diffuse
panbronchiolitis; and 8) follicular bronchiolitis. The causes of
bronchiolitis are similar to the causes of bronchiectasis, as most
of the causes of bronchiectasis can also involve the bronchioles,
leading to bronchiolectasis and other direct CT signs of
bronchiolar disease. Causes of bronchiolectasis include infection,
aspiration of gastric or other irritant substances, impaired host
defenses/immunologic deficiencies, cigarette smoking, and
Endobronchial spread of infectious organisms can result in
centrilobular nodules and linear branching opacities on CT and is
the most common cause of the "tree-in-bud" pattern.
Bacterial organisms are the most common cause of a bronchiolar
pattern of disease on CT (figures 4 through 6), and viral,
parasitic, mycobacterial (figures 7 and 8), and fungal organisms
are the less common causes.
The term "tree-in-bud" is commonly associated with endobronchial
, though this pattern is not pathognomonic for tuberculosis. The
"tree-in-bud" appearance is characteristic of active and likely
contagious tuberculosis, especially when associated with adjacent
cavitary nodules in the lungs (figure 9). The presence of multiple
cavitary lesions on CT in the absence of the "tree-in-bud" pattern,
however, makes the diagnosis of active and potentially contagious
tuberculosis much less likely. In addition to the "tree-in-bud"
pattern, CT findings that can be seen with tuberculosis include air
space consolidation, cavitation, small, well-defined nodules
indicative of miliary or hematogenous spread of infection, pleural
effusion, and lymph node enlargement with central necrosis.
Reactivation tuberculosis has a propensity for predominantly
involving the posterior segments of the upper lobes and the
superior segments of the lower lobes. Histologically, the terminal
tufts of the "tree-in-bud" pattern represent lesions in the
bronchioles and alveolar ducts, whereas the stalk represents a
lesion affecting the last-order bronchus in the secondary pulmonary
Non-tuberculous mycobacterial infections can appear similar to
tuberculosis, or can manifest in a "nonclassical" way on CT. This
nonclassical nontuberculous mycobacterial infection is typically
produced by infection with
The typical patients are women in their 70s who lack predisposing
conditions. This phenomenon has been termed the "Lady Windermere
It has been hypothesized that habitual voluntary suppression of
cough may lead to the development of nonspecific inflammatory
processes in poorly draining lung regions, upon which the
mycobacterial organisms grafted. Computed tomography shows patchy
bronchiectasis and other direct signs of bronchiolar disease,
commonly in the middle lobe and lingula (figure 10).
involvement of the airways may take the form of colonization, as in
allergic bronchopulmonary aspergillosis (ABPA), or, in the
immunosuppressed patient, as an invasive bronchitis and
tracheobronchitis. Allergic bronchopulmonary aspergillosis is an
immunologic hyperimmune response to airway colonization with
, usually seen in patients with asthma. The fungus proliferates in
the proximal bronchi, acting as an antigenic stimulus for the
production of IgE and IgG antibodies. The inflammatory reaction
causes mucoid impaction in the central airways, which leads to
damage of the bronchial wall and subsequent bronchiectasis. The CT
findings include central bronchiectasis with an upper-lobe
predominance and mucoid impaction.
This mucoid impaction can extend into the bronchioles, resulting in
a "tree-in-bud" pattern on CT (figure 11).
Predominant airway involvement is seen in 14% to 34% of cases of
invasive aspergillosis. The CT findings include peribronchial areas
of consolidation, centrilobular nodules, and the "tree-in-bud"
Histologically, the peribronchial areas represent bronchopneumonia
and the nodules represent bronchiolitis caused by
, often with fungal hyphae found in the airway lumen.
Bronchiolar changes can be seen on CT after aspiration of
infected oral secretions, other irritant material, or inert
material (i.e., barium). With barium aspiration, the nodular and
linear branching opacities seen on CT are composed of
Aspiration can occur during periods of altered consciousness or in
persons with neuromuscular disorders. The clinical features of a
large amount of aspirated gastric contents are abrupt in onset and
consist of cough, wheezing, cyanosis, dyspnea, and tachypnea.
Initially, pathologic changes consist of a chemical
tracheobronchitis and pneumonia. Secondary bacterial infection is
common, however, and the clinical course may be further complicated
by acute respiratory distress syndrome. The severity of the
pulmonary changes depends on the volume of fluid aspirated and the
pH of the aspirate.
The CT findings can include areas of consolidation, small irregular
shadows, and small nodular and linear branching opacities (figure
12). The distribution of the abnormalities is generally perihilar
or bibasilar, although this can vary depending on the patient's
position during the time of aspiration. The abnormal opacities can
even be entirely unilateral.
Impaired host defenses/immunologic deficiencies
Cystic fibrosis is a genetic disorder affecting the upper and
lower respiratory tracts, pancreas, liver, gallbladder, intestines,
and genital tract. An abnormally low water content of airway mucus
is at least partially responsible for decreased mucous clearance,
mucus plugging of small and large airways, and an increased
incidence of bacterial airway infection. Bronchial wall
inflammation progressing to bronchiectasis and bronchiolectasis is
eventually seen on CT, in addition to nodular and tubular areas of
mucus plugging, bronchial/bronchiolar wall thickening, and areas of
lung collapse or consolidation. The "tree-in-bud" pattern is seen
with extensive mucus plugging of bronchioles or airway spread of
infected organisms (figure 13).
Dyskinetic cilia syndromes are inherited disorders of ciliary
structure and function. They can be characterized by
bronchiectasis, situs inversus, sinusitis (the triad defining
Kartagener's syndrome), and infertility. Abnormal ciliary motion in
the respiratory tract results in recurrent bronchial infections and
subsequent bronchiectasis, bronchiolectasis, air trapping, and the
"tree-in-bud" pattern on CT. Numerous other genetic abnormalities
affecting mucociliary clearance, immune deficiency, or structural
abnormalities of the bronchus or bronchial wall can result in
Respiratory bronchiolitis is a clinicopathologic syndrome that
is seen in current heavy cigarette smokers. Pathologic findings
consist of an excess of pigmented macrophages in respiratory
bronchioles and adjacent alveolar ducts and alveoli, a membranous
and respiratory mononuclear bronchiolitis, fibrous scarring
extending outward from airways into alveolar walls, and an abnormal
airway epithelium. CT findings include centrilobular nodules
(figure 14), ground-glass opacities, and intralobular and
interlobular septal thickening.
Diffuse panbronchiolitis is a disorder characterized by chronic
sinusitis and bronchial inflammation, and is found most commonly in
patients with Japanese, Chinese, or Korean heritage. In a late
stage, the disorder is characterized by repeated bacterial
infections, resulting in bronchiectasis and bronchiolectasis. The
histologic findings involve the respiratory bronchioles, and
include dense peribronchial and intraluminal infiltrate of acute
and chronic inflammatory cells, particularly mononuclear cells,
with hyperplasia of lymphoid follicles. High-resolution CT scans
can be quite striking, showing diffuse centrilobular nodules, thin,
branching linear opacities, thickened bronchiolar walls, and air
trapping (figure 15).
Follicular bronchiolitis is a condition most commonly described
in patients with rheumatoid arthritis and Sjögren's syndrome, and
represents a form of lymphoid hyperplasia characterized by
coalescent germinal centers distributed along airways.
The hyperplastic lymphoid follicles narrow airways by external
compression. Findings on CT include small nodular opacities in a
Asthma is characterized by reversible airway narrowing from
bronchoconstriction, edema of the airway wall, and mucus
hypersecretion. Computed tomography shows nonspecific findings
consisting of some or all of the following: bronchial/bronchiolar
wall thickening, bronchiolar dilatation, air trapping, atelectasis,
and centrilobular nodules (figure 16).
Bronchiolitis obliterans is characterized histologically by
plugs of granulation tissue that fill and obstruct the
centrilobular terminal or respiratory bronchioles and by a variable
intraluminal and peribronchiolar inflammatory response. Although
often idiopathic, bronchiolitis obliterans is associated with viral
infection of the airways, toxic fume inhalation, collagen vascular
diseases, complication of drug therapy, chronic graft-versus-host
disease following bone marrow transplantation, or chronic rejection
in patients with lung transplantation. Computed tomography findings
can include bronchiectasis/ bronchiolectasis, bronchial/bronchiolar
wall dilatation, centrilobular nodular and linear branching
opacities, and often severe air trapping (figure 17).
When bronchiolar disease is suspected, HRCT should be performed,
in both inspiration and expiration. Direct computed tomography (CT)
signs of bronchiolar disease include bronchiolar wall thickening,
bronchiolar dilatation, and bronchiolar luminal impaction. Indirect
signs include subsegmental atelectasis, and air trapping. The term
"tree-in-bud" is used to describe a severe form of bronchiolar
disease with mucoid impaction of dilated bronchioles. The most
common cause of the CT "tree-in-bud" pattern is infectious
bronchiolitis. A specific infectious organism is not implied when
this pattern is seen, although the presence of adjacent cavitary
lesions on CT suggests tuberculosis.