Patrones Tomograficos Epid PDF

CHAPTER
High-Resolution Computed
Tomography of Interstitial
and Occupational Lung
Disease
David M. Hansell, Zelena A. Aziz and Nestor L. Mller
High-resolution computed tomography patterns of interstitial
lung disease
Idiopathic interstitial pneumonias
Sarcoidosis
Hypersensitivity pneumonitis
Langerhans cell histiocytosis
Lymphangioleiomyomatosis
Connective tissue diseases
Systemic vasculitides
Drug-induced lung disease
Occupational lung disease
The pulmonary interstitium is the network of connective tissue
fibres that supports the lung. It includes the alveolar walls, inter-
lobular septa and the peribronchovascular interstitium. The term
interstitial lung disease (ILD) is used to refer to a group of disor-
ders that mainly affects these supporting structures. Although the
majority of these disorders also involve the airspaces, the predomi-
nant abnormality is thickening of the interstitium which may be
due to the accumulation of fluid, cells, or fibrous tissue.
The chest radiograph remains part of the initial assessment of
ILD, but the radiographic pattern is often non-specific, observer
variation is considerable
1
and it is relatively insensitive to early
ILD
24
. High-resolution computed tomography (HRCT) has
revolutionized the imaging of ILD as it enables early detection of
disease, allows a histospecific diagnosis to be made in certain cases,
and provides insight into disease reversibility and prognosis.
HIGH-RESOLUTION COMPUTED TOMOGRAPHY
PATTERNS OF DIFFUSE LUNG DISEASE
Diffuse abnormalities of the lung on HRCT may be broadly
classified into one of the following four patterns: (A) reticular
or linear; (B) nodular; (C) ground-glass opacity through to
consolidation; and (D) areas of decreased lung attenuation.
Reticular pattern
A reticular pattern on CT almost always represents sig-
nificant ILD. Morphologically, a reticular pattern may be
caused by thickened interlobular or intralobular septa or
honeycomb (fibrotic) destruction. Numerous thickened
interlobular septa indicate an extensive interstitial abnor-
mality and causes include infiltration by fibrosis (interstitial
fibrosis), abnormal cells (lymphangitis carcinomatosa), or
fluid (pulmonary oedema). Although thickened interlobu-
lar septa can be a consequence of infiltration by fibrosis,
this feature is not a frequent finding in idiopathic pulmo-
nary fibrosis (IPF). Interlobular septal thickening is usu-
ally described as smooth (seen in pulmonary oedema and
alveolar proteinosis) or irregular (lymphangitic spread of
tumour), but the distinction is not always easily made. Sar-
coidosis causes nodular septal thickening although this pat-
tern is not usually the dominant feature
5
.
Intralobular septal thickening manifests as a fine reticu-
lar pattern on HRCT and is seen in all ILDs but most
commonly in IPF. Often, the intralobular septal thicken-
ing may be so fine that HRCT does not demonstrate dis-
crete intralobular opacities but a generalized increase in
lung density (ground-glass opacification). Severe pulmonary
fibrosis usually results in a coarse reticular pattern made up
of interlacing irregular linear opacities. The reticular pat-
tern of end-stage fibrotic (honeycomb) lung is character-
ized by cystic airspaces surrounded by irregular walls. The
distortion of normal lung morphology by extensive fibrosis
results in irregular dilatation of segmental and subsegmen-
tal airways (traction bronchiectasis/bronchiolectasis); in
the periphery of the lung, it can be difficult to distinguish
dilated airways from true honeycomb change.
19
Ch19-F0163.indd 351 6/28/07 3:37:29 PM
SECTION 2 THE CHEST AND CARDIOVASCULAR SYSTEM 352
Nodular pattern
A nodular pattern is a feature of both interstitial and airspace
disease. The distribution and density of nodules can help narrow
what can be a lengthy differential diagnosis. Nodules within
the lung interstitium, especially those related to the lymphatic
vessels, are seen in the interlobular septa, subpleural and peri-
bronchovascular regions; a distribution seen most commonly
in sarcoidosis but also in lymphangitis carcinomatosa. Cen-
trilobular nodules are seen in several conditions (Table 19.1).
In particular, distinguishing between subacute hypersensitivity
pneumonitis and respiratory bronchiolitisinterstitial lung dis-
ease (RBILD) can be difficult, because both cause relatively
low density, poorly defined centrilobular nodules which may
look identical on HRCT. A random distribution of very small
well-defined nodules is seen in patients with haematogenous
spread of tuberculosis, pulmonary metastases, pneumoconiosis
and rarely in pulmonary sarcoidosis.
Ground-glass pattern
A ground-glass pattern on HRCT is defined as a generalized
increase in opacity that does not obscure pulmonary vessels. At
a microscopic level, the changes responsible for ground-glass
opacity are complex and include partial filling of the airspaces,
considerable thickening of the interstitium, or a combina-
tion of the two. Ultimately though, the pattern of ground-
glass opacity on HRCT results from displacement of air from
the lungs. Many conditions result in the non-specific pattern
of ground-glass opacity but the most common causes include
subacute hypersensitivity pneumonitis, acute respiratory dis-
tress syndrome (ARDS), acute interstitial pneumonia (AIP),
non-specific interstitial pneumonia (NSIP) and diffuse pneu-
monias, particularly Pneumocystis jirovecii (carinii) pneumonia in
patients with acquired immune deficiency syndrome (AIDS).
The definite identification of dilated airways within areas of
ground glass is usually an indication of fine fibrosis and thus
usually indicates irreversible disease. The caveat is that, in cer-
tain entities (e.g. organizing pneumonia), dilated airways that
are present within areas of ground glass in the acute setting
may completely resolve following successful treatment.
Mosaic attenuation pattern
The term mosaic attenuation pattern refers to regional attenu-
ation differences demonstrated on HRCT. The attenuation of a
given area of lung depends on the amount of blood, parenchymal
tissue and air in that area, and thus the sign of a mosaic attenu-
ation pattern is non-specific. It is the dominant abnormality in
three completely different types of diffuse pulmonary disease:
small airways disease, occlusive vascular disease and infiltrative
lung disease. In the first two processes, the decreased attenuation
(black) lung is abnormal; in infiltrative lung disease it is the
grey lung that is abnormal. In a study of 70 patients in whom
a mosaic attenuation pattern was the dominant abnormality,
Worthy et al showed that small airways disease and infiltrative
lung disease were correctly identified but the mosaic attenua-
tion pattern caused by occlusive vascular disease was frequently
misinterpreted
6
. Bronchial abnormalities and the presence of
air trapping on expiratory CT are the most useful discrimina-
tory features in identifying small airways disease as the cause
of mosaic attenuation. However, the phenomenon of hypoxic
bronchodilatation in chronic occlusive vascular disease
7
, and the
demonstration that air trapping is seen on expiration in acute
pulmonary embolism
8
complicates the interpretation. Never-
theless, the differentiation between the three basic causes of a
mosaic attenuation pattern is usually easily made when clinical
and physiological information is taken into account.
IDIOPATHIC INTERSTITIAL PNEUMONIAS
The term idiopathic interstitial pneumonia (IIP) is applied to
a group of disorders with no known cause, and with more or
less distinct histological and radiological appearances. Over the
years, there have been additions and subtractions to the clas-
sification, but in 2001 an American Thoracic Society (ATS)/
European Respiratory Society (ERS) consensus panel consist-
ing of clinicians, radiologists and pathologists sought to clarify
the nomenclature by combining the histopathological pattern
seen on lung biopsy with clinical and radiological features
9
.
The current classification of IIPs is outlined in Table 19.2.
Current guidelines recommend a multidisciplinary approach
to the diagnosis of the IIPs and a recent study has demon-
strated that dynamic interaction between clinicians, radiolo-
gists and pathologists improves interobserver agreement and
diagnostic confidence
10
.
Usual interstitial pneumonia/idiopathic
pulmonary brosis
Usual interstitial pneumonia (UIP) is the most common his-
topathological pattern in patients with the clinical presenta-
tion of cryptogenic fibrosing alveolitis (CFA)/IPF. Under the
new classification, the term IPF is exclusively reserved for
patients with the idiopathic clinical syndrome associated with
the morphological pattern of UIP. Other causes of a UIP-
type pattern on histology include chronic hypersensitivity
pneumonitis, asbestosis, connective tissue disease and rarely
drugs. The pathological features of UIP are the presence
of fibroblastic foci, normal areas, dense fibrosis and honey-
combing; the crucial finding is of areas of fibrosis at different
stages of maturity. The number of fibroblastic foci on lung
biopsy is an important predictor of survival
11
. Classic chest
radiographic features include bilateral asymmetric peripheral
reticular opacities most profuse at the lung bases associated
with lung volume loss, although in the presence of coexist-
ing emphysema, lung volumes may be preserved or increased.
The characteristic and virtually pathognomonic appearance
of IPF on HRCT is of a predominantly subpleural bibasal
Table 19.1 CONDITIONS CHARACTERIZED BY PROFUSE
CENTRILOBULAR NODULES IN HRCT
Subacute hypersensitivity pneumonitis
Respiratory bronchiolitisinterstitial lung disease
Diffuse panbronchiolitis
Endobronchial spread of tuberculosis or bacterial pneumonia
Cryptogenic organizing pneumonia (unusual pattern)
Ch19-F0163.indd 352 6/28/07 3:37:30 PM
CHAPTER 19 HIGH-RESOLUTION COMPUTED TOMOGRAPHY OF INTERSTITIAL AND OCCUPATIONAL LUNG DISEASE 353
reticular pattern within which there are areas of honeycomb
destruction (Fig. 19.1)
12
. As the disease progresses, it often
appears to creep around the periphery of the lung to involve
the anterior aspects of the upper lobes (Fig. 19.2); the find-
ing of upper lobe irregularities (reticulation) is an important
discriminator between UIP and other conditions with similar
clinical presentations
13
. In the study by Hunninghake et al, the
presence of both honeycombing and upper lobe irregularities
increased the specificity for UIP from 69% (honeycombing
alone) to 81%
13
. The presence of ground-glass opacification
is not a dominant feature and when present, there is usually
obvious traction bronchiectasis and bronchiolectasis. Medias-
tinal lymphadenopathy (up to 2 cm) unrelated to infection or
malignancy is a frequent accompaniment
14
.
Table 19.2 HISTOLOGICAL AND CLINICAL CLASSIFICATION OF THE IDIOPATHIC INTERSTITIAL PNEUMONIAS
Clinicoradiologicalpathological criteria Histological pattern HRCT features
Idiopathic pulmonary fibrosis Usual interstitial pneumonia Reticular opacities
Honeycombing
Areas of ground-glass opacity associated with traction
bronchiectasis
Non-specific interstitial pneumonia Non-specific interstitial pneumonia Areas of ground-glass opacity traction bronchiectasis
Honeycombing minimal
Cryptogenic organizing pneumonia Organizing pneumonia Peripheral or peribronchial consolidation
Areas of ground-glass opacity
Perilobular pattern (increasingly recognized)
Acute interstitial pneumonia Diffuse alveolar damage Consolidation (dependent lung)
Areas of ground-glass opacity
Traction bronchiectasis (organizing phase)
Respiratory bronchiolitisinterstitial lung RBILD Poorly defined centrilobular nodules
disease (RBILD) Areas of ground-glass opacity
Bronchial wall thickening
Limited emphysema
Desquamative interstitial pneumonia (DIP) DIP Areas of ground-glass opacity
Features of interstitial fibrosis
Lymphoid interstitial pneumonia (LIP) LIP Areas of ground-glass opacity
Centrilobular nodules
Thickened interlobular septa
Thin-walled discrete cysts
Figure 19.1 Usual interstitial pneumonia. HRCT abnormalities predo-
minate in the posterior, subpleural regions of the lower lobes and comprise
honeycombing and traction bronchiectasis within the abnormal lung.
Figure 19.2 Usual interstitial pneumonia. In the upper lobes
anteriorly there are peripheral irregular lines with areas of honeycombing.
Ch19-F0163.indd 353 6/28/07 3:37:30 PM
Studies have demonstrated that when a confident diagnosis of
IPF is made on HRCT, the diagnosis is invariably correct
15,16
, and
it has been suggested that a confident diagnosis of IPF made by
experienced observers should obviate biopsy
16
. HRCT also has a
role in predicting survival. A study by Flaherty et al suggested that
patients with histological UIP who had definite or probable UIP
by HRCT criteria had a worse prognosis than those who had
interdeterminate HRCT findings
17
.
The rapid development of a diffuse increase in the attenu-
ation of lung parenchyma in patients with IPF should raise
the possibility of an opportunistic infection (such as PCP), an
accelerated phase of the disease (Fig. 19.3)
18
, or concurrent
pulmonary oedema. Other complications include lung can-
cer
19
and pulmonary tuberculosis (Fig. 19.4); the latter usually
has atypical appearances on CT due to the presence of under-
lying lung fibrosis
20
.
Non-specic interstitial pneumonia
NSIP is characterized by varying degrees of interstitial inflam-
mation and fibrosis without the specific features that allow
a diagnosis of UIP or desquamative interstitial pneumonia
(DIP)
21
. While NSIP may have significant fibrosis, it is usually
of uniform temporality (in comparison to UIP), and fibro-
blastic foci and honeycombing, if present, are scanty. Although
the clinical features of NSIP resemble those of UIP, progno-
sis is considerably better
22,23
. Non-idiopathic NSIP is most
often found on lung biopsy in patients with connective tissue
disease and may be the pattern identified in some cases of
drug-induced lung disease and hypersensitivity pneumonitis.
On HRCT, NSIP is characterized by a predominant pat-
tern of ground-glass opacification in a predominantly basal
and subpleural distribution with or without associated distor-
tion of airways (Fig. 19.5). A reticular pattern is common but
honeycombing is sparse or absent
24
. In general, NSIP may be
distinguished from UIP on CT by a more prominent compo-
nent of ground-glass attenuation and a finer reticular pattern
in the absence of honeycombing
25
. However, the variability of
CT appearances reflects the heterogeneity of the pathological
processes encompassed by NSIP and a confident diagnosis of
NSIP based on CT alone is less readily made than in cases
of UIP. Consolidation is reportedly a highly variable feature
(098%
24,25
) and this discrepancy probably reflects the fact
that some patients with non-idiopathic NSIP have significant
amounts of histological organizing pneumonia, making clas-
sification of individual cases difficult.
Cryptogenic organizing pneumonia
A component of organizing pneumonia is identifiable in a
variety of different contexts, including infection
26
, malig-
nancy
27
, drug-related lung injury
28
and in association with
connective tissue disease
29
. However, in 1983, Davison et
al
30
described a clinicopathological entity of isolated orga-
nizing pneumonia in patients without an identifiable associ-
Figure 19.4 Tuberculosis on a background of usual interstitial
pneumonia. Biopsy of the area of consolidation in the right lower lobe
confirmed tuberculosis.
Figure 19.3 Usual interstitial pneumonia. HRCT performed (A) before
and (B) after clinical deterioration in a patient with biopsy proven usual
interstitial pneumonia. HRCT obtained during the accelerated phase of
the disease demonstrates a generalized increase in lung attenuation and
progression of both the reticular and honeycomb patterns.
Ch19-F0163.indd 354 6/28/07 3:37:32 PM
ated disease. In 1985, Epler et al
31
described the same entity
and used the term bronchiolitis obliterans organizing pneu-
monia (BOOP). The ATS/ERS Consensus statement
9
rec-
ommends that the term cryptogenic organizing pneumonia
(COP) be used because it avoids confusion with airway
diseases such as constrictive obliterative bronchiolitis. On a
chest radiograph the most frequent feature of COP is patchy,
often subpleural and basal, areas of consolidation with pres-
ervation of lung volumes. The areas of airspace consolida-
tion have a propensity to progress and change location over
time. On HRCT, consolidation corresponding to areas of
organizing pneumonia is the cardinal feature found more
frequently in the lower zones, with either a subpleural or a
peribronchial distribution (Fig. 19.6)
32,33
; the peribronchial
distribution is typically seen in patients with poly myositis
or dermatomyositis. Ground-glass opacification, subpleural
linear opacities and a distinctive perilobular pattern (Fig.
19.7)
34
are also commonly encountered. The histopatho-
logical appearance of organizing pneumonia is a uniform
temporal appearance of mild interstitial chronic inflamma-
tion associated with an intra luminal organizing fibrosis in
distal airspaces. The lung architecture is generally well pre-
served. A complete response to a long (23 months) course
of high-dose steroid treatment is the general rule, although
in a minority of patients the process progresses with the
incorporation of the organizing pneumonia into the alveo-
lar walls as mature fibrosis
35
.
Respiratory bronchiolitisinterstitial lung disease
and desquamative interstitial pneumonia
These two entities are considered together because of their
strong association with cigarette smoking. All cigarette smokers
have, to some degree, inflammation around their small airways
(respiratory bronchiolitis) but this is clinically unimportant
and not considered further here. Patients generally present with
an insiduous onset of dyspnoea and cough. The chest radio-
graph is relatively insensitive for the detection of RBILD and
DIP and a normal chest radiograph has been reported in up to
20% of patients with RBILD
36
and 25% in DIP
37
. On HRCT,
the features of RBILD include areas of patchy ground-glass
opacification (resulting from macrophage accumulation within
alveolar spaces and alveolar ducts) and poorly defined low atten-
uation centrilobular nodules (Fig. 19.8). In addition, upper lobe
centrilobular emphysema, usually of very limited extent and
areas of air trapping, reflecting that the bronchiolitic element of
this entity may be present
38
. Some patients show thickening of
the interlobular septa and features of interstitial fibrosis, but this
is unusual
36
. Ground-glass opacification is also the dominant
feature seen in DIP (Fig. 19.9). The distribution is typically
Figure 19.5 Non-specific interstitial pneumonia. The predominant
abnormality is patchy, bilateral ground-glass opacification, mild
reticulation and traction bronchiectasis. There is no frank honeycombing
destruction.
Figure 19.6 Cryptogenic organizing pneumonia. HRCT through
the upper lobes demonstrates areas of consolidation in a subpleural
and peribronchial distribution in association with areas of ground-glass
opacification (left upper lobe).
Figure 19.7 Biopsy proven organizing pneumonia. There are poorly
defined arcade-like and polygonal opacities (the perilobular pattern) in
the subpleural and posterior regions of both lungs. The opacities resemble
ill-defined thickened interlobular septa.
Ch19-F0163.indd 355 6/28/07 3:37:34 PM
lower zone, peripheral and may be patchy
39
. In some patients
there are HRCT features of established fibrosis (in the form
of architectural distortion with dilatation of some bronchi),
usually of limited extent. The majority of patients with DIP
or RBILD have a relatively stable clinical course. Smoking
cessation is an important part of the management of patients
but the influence of smoking on the clinical course of these
patients has not been fully delineated; some patients have per-
sistent abnormalities on HRCT even with smoking cessation
and corticosteroid therapy. Because of the significant overlap
between the clinical, imaging and histological features of DIP
and RBILD and to a lesser extent between these two patterns
and Langerhans cell histiocytosis (LCH) and interstitial fibrosis,
the global term smoking related-interstitial lung disease (SR-
ILD) has been proposed to encompass DIP, RBILD, LCH and
interstitial fibrosis (Fig. 19.10)
36,40,41
.
Acute interstitial pneumonia
Acute interstitial pneumonia (AIP) can be regarded as an idio-
pathic form of the ARDS and is histologically (and clinically)
distinct from the other interstitial pneumonias. The histo-
logical pattern seen in AIP is that of diffuse alveolar damage
(DAD), which is also found in infection, connective tissue dis-
ease, drug toxicity, toxic inhalation, uraemia and sepsis. DAD
has an acute exudative phase and a subsequent organizing and
fibrotic phase. Lung biopsy shows diffuse involvement with
temporal homogeneity, which may imply lung injury due to
a single event
42
. The chest radiograph shows bilateral patchy
airspace opacification
43
. HRCT demonstrates a combination
of ground-glass opacification, consolidation, bronchial dilata-
tion and architectural distortion
44
. Ground-glass opacification
on HRCT is found in all three phases of AIP, but coexistent
traction bronchiectasis probably reflects the incorporation of
established fibrosis in the proliferative and fibrotic phases
45
.
Follow-up CT studies in survivors demonstrate clearing of the
ground-glass attenuation and consolidation, leaving reticular
opacities consistent with residual fibrosis. Anterior non-
dependent fibrotic damage in survivors secondary to baro-
trauma has also been reported
46
.
Lymphoid interstitial pneumonia
The term lymphoid interstitial pneumonia (LIP) was pro-
posed by Liebow and Carrington
47
to describe a disease entity
characterized by a widespread interstitial lymphoid infiltrate
Figure 19.9 Several areas of non-specific ground-glass opacification in
the right middle lobe and both lower lobes.
Figure 19.8 Respiratory bronchiolitisinterstitial lung disease. HRCT shows (A) subtle areas of ground-glass opacification and (B) ill-defined
centrilobular nodules.
Ch19-F0163.indd 356 6/28/07 3:37:36 PM
of the lung, resembling lymphoma but with a clinical course
more akin to a chronic interstitial pneumonia. Although in
the past LIP has been considered by some to be a pulmonary
lymphoproliferative disorder, evolution to frank lymphoprolif-
erative disease is rare and thus LIP remains within the group of
interstitial pneumonias
9
. Classically, LIP occurs in association
with autoimmune diseases, most often Sjgrens syndrome.
Other diseases associated with LIP include dysproteinaemias,
autologous bone marrow transplantation and viral, mycobac-
terial and human immunodeficiency virus (HIV) infections.
Intrathoracic Castlemans disease is frequently associated with
LIP
48
. The incidence of LIP is approximately two-fold greater
in women and symptoms of progressive cough and dyspnoea
usually predominate. Common HRCT findings are nodules
of varying sizes (which may be ill-defined), areas of ground-
glass opacification, thickened bronchovascular bundles, inter-
lobular septal thickening and thin-walled cysts (130 mm) (Fig.
19.11)
49,50
. Airspace disease, large nodules and pleural effusions
are rare in these patients. The cysts in LIP are usually discrete,
are not found in clusters and are found deep within the lung
parenchyma
49
. The cysts have been postulated to result from
the lymphocytic infiltrate compressing bronchioles, causing
stenosis or obstruction and subsequent postobstructive bron-
chiolar ectasia.
SARCOIDOSIS
Sarcoidosis is a multisystem granulomatous disorder of
unknown aetiology. As a consequence, the diagnosis of this
syndrome is defined by the presence of characteristic clini-
cal and radiological data along with histological evidence of
noncaseating granuloma. Granulomas in the lung have a char-
acteristic distribution along the lymphatics in the broncho-
vascular sheath and, to a lesser extent, in the interlobular septa
and subpleural lung regions. Sarcoidosis is a disease of young
adults, with a peak incidence in the second to fourth decades.
The hilar and mediastinal nodes and the lungs are affected
clinically much more commonly than any other organ or
system. They are followed in decreasing order of frequency
by the skin (26%), peripheral lymph nodes (22%), eyes (15%),
spleen (6%), central nervous system (4%), parotid glands (4%)
and bones (3%)
51
.
Pulmonary involvement accounts for most of the morbid-
ity and mortality associated with sarcoidosis. Sarcoidosis is
traditionally staged according to its appearance on the chest
radiograph: stage I, lymphadenopathy; stage II, lymphadenopa-
thy with parenchymal opacity; stage III, parenchymal opac-
ity alone
52
. Low stages at presentation are reported to have a
Figure 19.10 Smoking related-interstitial lung disease. Images of the (A) upper and (B) lower lobes of a 42 year old man with a 25-pack year smoking
history and dyspnoea. The combination of a fine reticular pattern representing fibrosis and ground-glass opacification on a background of emphysema suggests a
diagnosis of smoking related-interstitial lung disease.
Figure 19.11 Lymphocytic interstitial pneumonitis. There is a
background of ground-glass opacification and a few thin-walled cystic
airspaces (the pathogenesis of these cysts is unclear).
Ch19-F0163.indd 357 6/28/07 3:37:38 PM
better prognosis than high stages, although the precision and
clinical usefulness of such staging is questionable.
Lymphadenopathy
Sarcoidosis is characterized by bilateral, symmetrical hilar and
paratracheal lymphadenopathy. Some degree of lymphade-
nopathy is evident on a chest radiograph in about 7080%
of patients at some time during the course of the condition.
Hilar lymph node enlargement ranges from the barely detect-
able to the massive and gives the hila a lobulated and usually
well-demarcated outline. Occasionally hilar lymphadenopathy
appears to be asymmetrical or, in 15% of cases, may even
be strictly unilateral although this is distinctly unusual
53,54
.
Marked asymmetry that is confirmed by CT is sufficiently
unusual to bring the diagnosis into question. Clinically sig-
nificant compression of adjacent airways, arteries and veins is
extremely unusual, even though lymph node enlargement is
often massive.
Paratracheal lymphadenopathy may be bilateral or uni-
lateral and in the latter instance is usually right sided. The
most common manifestation of left-sided lymphadenopathy
is enlargement of the aortopulmonary window nodesa
common and characteristic feature on the chest radiograph.
Other mediastinal nodes (anterior prevascular, posterior and
subcarinal) are often not identified as being enlarged on the
chest radiograph but on CT are seen to be affected in about
half of patients
55
. In 90% of patients with lymphadenopathy,
nodal enlargement is maximal on the first radiograph and
usually disappears within 612 months. In about 5%, how-
ever, large nodes persist more or less indefinitely and these
can be a source of confusion. Recurrence of lymphadenopa-
thy is exceedingly rare. The lymph nodes may calcify, some-
times in a characteristic eggshell fashion. This latter feature
is shared by only a few conditions (Table 19.3). Although
lymph node calcification is seen on the radiograph in 5%
or less of patients with sarcoidosis, it may be evident on
CT in up to 40% of patients with long-standing disease
56
.
The calcification is of variable intensity but may be rela-
tively light, and the affected lymph nodes are usually small in
volume and evenly distributed throughout the mediastinum
and hila (very different from calcified nodes due to tuber-
culous infection which usually follow a drainage path)
57
.
About 40% of patients presenting with nodal enlargement
will develop parenchymal opacities, usually within a year,
and of these about one-third will go on to have persistent
(fibrotic) shadowing. Nodal enlargement does not develop
after parenchymal opacities have appeared.
Parenchymal changes
Parenchymal changes probably occur histologically in all
patients but are only detected on the chest radiograph in
5070% of cases. Characteristically, parenchymal abnormalities
appear as the nodal enlargement is subsiding (in lymphoma
such abnormalities tend to progress in unison). The most com-
mon radiographic pattern, seen in 7590% of patients with
parenchymal opacities, is of rounded or irregular nodules 2
4 mm in diameter, which are usually moderately well defined.
Smaller or larger opacities are not uncommon, though they
rarely exceed 5 mm. Very small aggregated opacities sometimes
give a ground-glass appearance. All zones tend to be affected
but there is usually a mid and upper zonal predominance. The
second most common pattern, seen in 1020% of patients with
parenchymal opacity, is patchy airspace consolidation. Opaci-
ties sometimes contain air bronchograms and have ill-defined
margins that commonly break up into a nodular pattern. They
tend to involve predominantly the peribronchovascular regions
of the middle and upper lungs zones, although they may be dif-
fuse or, occasionally, have a subpleural predominance.
The parenchymal opacities described above will clear com-
pletely in about two-thirds of cases and progress to fibrosis in
one-third. Permanent fibrotic shadowing is unusually coarse
with a mid and upper zone predominance. The radiographic
pattern consists of coarse linear opacities with evidence of
volume loss and ring shadowing caused by bullae or traction
bronchiectasis. Occasionally a conglomerate opacity develops
resembling progressive massive fibrosis. Cor pulmonale, bullous
disease with or without mycetoma formation, and pneumo-
thorax are all recognized complications of this fibrotic stage.
High-resolution computed tomography features
Parenchymal opacities are well demonstrated on HRCT (Fig.
19.12)
5,58
and HRCT appearances have a high sensitivity and
specificity for the diagnosis. The most consistent pulmonary
parenchymal abnormality is the presence of nodular opacities
(15 mm) distributed in a perilymphatic fashion, predomi-
nantly along the bronchovascular bundles and subpleurally
and, to a lesser extent, along inter lobular septa. Other find-
ings include irregular and beaded interfaces, larger ill-defined
nodules with/without an air bronchogram, patchy ground-
glass opacities and occasional interlobular septal thickening. In
advanced disease there is evidence of fibrosis, predominantly
in the perihilar regions of the middle and upper lung zones
(Fig. 19.13). Air trapping is a common HRCT feature of sar-
coidosis and its presence shows a good correlation with indi-
ces of small airways disease on pulmonary function tests
59
. The
combination of a peribronchovascular, subpleural distribution,
small well-defined nodules, fibrosis and a mid and upper zone
distribution has been highlighted as the features most helpful
in making a diagnosis of sarcoidosis. In a very small number of
cases, sarcoidosis has been shown to mimic IPF with intralob-
ular septal thickening and ground-glass opacity seen predomi-
nantly in the basal subpleural regions of the lung
60
. Despite
the better delineation of parenchymal disease on HRCT, it
is not recommended as part of the initial diagnostic work-up
in patients with suspected sarcoidosis; its greatest use being
Table 19.3 CAUSES OF EGGSHELL NODAL CALCIFICATION
Sarcoidosis
Silicosis
Histoplasmosis
Lymphoma (postirradiation)
Blastomycosis
Amyloidosis
Ch19-F0163.indd 358 6/28/07 3:37:40 PM
in patients who present with an atypical chest radiograph
61
.
Previous HRCT studies have shown that areas of parenchy-
mal consolidation and ground-glass opacity are usually revers-
ible, whereas little resolution is identified following treatment
in patients with reticulation and architectural distortion
56,62
.
Despite this distinction between reversible and irreversible
disease on HRCT, studies comparing HRCT assessment of
disease activity to clinical, scintigraphic and bronchoscopic
findings have yielded contradictory results
63,64
. Hence, HRCT
is not generally used to guide prognosis in patients with sar-
coidosis.
Other thoracic ndings
Pleural thickering and effusions
Pleural thickening and effusions are unusual manifestations of
sarcoidosis and do not occur in isolation. Effusions, though
commonly unilateral, may be bilateral and are usually small.
They are seen most often in the context of established disease
and are subacute, lasting weeks or months. The prevalence of
effusions is about 2%.
Bronchial stenosis and airflow obstruction
Mild large airway narrowing may be due to nodal compres-
sion, but significant lesions are usually due to intrinsic mural
sarcoidosis. Stenoses may be single or multiple and particularly
affect larger airways to segmental level
65
. Such stenoses are very
rare but can cause significant airflow obstruction or atelecta-
sis, particularly in the middle lobe. However, the functional
severity of airflow obstruction seems to be largely determined
by the extent of a reticular pattern, representing established
fibrosis, on HRCT
66
.
HYPERSENSITIVITY PNEUMONITIS
Hypersensitivity pneumonitis, also known as extrinsic allergic
alveolitis, is an immunologically mediated lung disease charac-
terized by an inflammatory reaction to specific antigens con-
tained in a variety of organic dusts
67
. Common causes include
avian proteins (e.g. bird breeders lung) and thermophilic bacte-
ria present in mouldy hay (farmers lung), mouldy grain (grain
handlers lung), or heated water reservoirs (humidifier or air
conditioner lung). A more comprehensive list is given in Table
19.4. These antigens reach the alveoli where they provoke an
immunological reaction that includes both type III (immune
complex response) and type IV (cell-mediated) mechanisms.
The cell-mediated response results in a delayed hypersensitiv-
ity reaction and the presence of granulomatous inflammation
within the pulmonary interstitium. Interestingly, several stud-
ies have shown that cigarette smoking has a suppressive effect
that interferes with the immunopathological process that ulti-
mately leads to hypersensitivity pneumonitis
68,69
.
The clinical features of hypersensitivity pneumonitis are char-
acteristic. Approximately 6 h after exposure the patient develops
fever, chills, dyspnoea and cough. There is no eosinophilia, and
Figure 19.12 Sarcoidosis. Typical HRCT features are (A) nodular opacities which (B) may become confluent, and (C) interlobular septal thickening.
Figure 19.13 Fibrotic sarcoidosis. There are areas of conglomerate
fibrosis in a perihilar distribution with associated bronchial distortion and
volume loss. The appearances superficially mimic progressive massive
fibrosis seen in the pneumoconioses.
Ch19-F0163.indd 359 6/28/07 3:37:41 PM
wheeze is not a prominent feature. The radiological findings
are influenced by the stage of the disease. A chest radiograph
taken during the acute episode can be normal
70
, but typical
radiographic findings include diffuse ground-glass opacifica-
tion and a fine nodular or reticulonodular pattern; these two
features become more prominent in the subacute phase
71
.
Between acute attacks the radiograph may return to normal
and the fluctuating nature of changes on serial radiographs is
highly suggestive of the diagnosis. In chronic hypersensitiv-
ity pneumonitis, fibrosis with upper lobe retraction, reticu-
lar opacity, volume loss and honeycombing may be seen. On
HRCT, the nodules of hypersensitivity pneumonitis are typi-
cally poorly defined, < 5 mm in diameter
72
, centrilobular
70
and seen throughout the lung, although a mid to lower lung
zone predominance has been variably reported (Fig. 19.14)
73
.
Ground-glass opacity is most common in the acute phase but
may also be a feature of subacute and chronic hypersensitiv-
ity pneumonitis, especially if there is ongoing exposure
74
. A
mosaic attenuation pattern is common in hypersensitivity
pneumonitis; the presence of lobular areas of decreased vascu-
larity that show air trapping on expiratory HRCT, reflecting
the coexisting bronchiolitis caused by antigen deposition in
the small airways (Fig. 19.15)
75
. The combination on HRCT
of features of infiltrative (ill-defined nodules and ground-glass
opacity) and small airways disease may be remarkably similar
to that seen in patients with RBILD; however, the distinc-
tion can usually be made with knowledge of the smoking his-
tory. Lymph node enlargement (smaller than 20 mm) has been
described in both acute and subacute hypersensitivity pneu-
monitis
14
, and the presence of thin-walled lung cysts is also an
occasional feature in subacute hypersensitivity pneumonitis.
Cysts range in size from 3 to 25 mm and resemble those seen
in lymphocytic interstitial pneumonia
76
, although their patho-
genesis remains uncertain. Emphysema is a reported sequela of
farmers lung and a study has demonstrated that in hypersensi-
Figure 19.15 Hypersensitivity pneumonitis. (A) Inspiratory image
shows patchy density differences reflecting both the interstitial infiltrate
of subacute hypersensitivity pneumonitis and coexisting small airways
disease. (B) End-expiratory image enhances the density differences
revealing several secondary pulmonary lobules of decreased attenuation.
Table 19.4 MAJOR CAUSES OF HYPERSENSITIVITY
PNEUMONITIS
Agent Source Disease
Aspergillus Mouldy hay Farmer's lung
Thermophilic actinomyces Compost Mushroom worker's
lung
Trichosporum asahii Tatami mats Japanese summer-type
hypersensitivity
pneumonitis
Isocyanates Paint sprays, plastics Isocyanate hypersensi-
tivity pneumonitis
Mycobacterium avium Hot tubs Hot tub lung
complex
Unknown Metal working fluids Metal worker's lung
Bird proteins Bird feathers, Bird fancier's lung
excrement
Figure 19.14 Subacute extrinsic allergic alveolitis. HRCT shows
numerous poorly defined, relatively low attenuation nodules.
Ch19-F0163.indd 360 6/28/07 3:37:43 PM
tivity due to farmers lung, emphysema was a more prominent
feature than honeycombing/fibrosis (even in never smokers)
and was seen in approximately one-third of patients
74
. This is
in comparison to pigeon breeders disease, where lung fibrosis
is the major complication. The chronic stage of hypersensitiv-
ity pneumonitis is characterized by fibrosis, although evidence
of active disease is often present. Radiological findings include
intralobular and interlobular interstitial thickening, traction
bronchiectasis and honeycomb destruction (Fig. 19.16)
77
. In
some cases, there is a mid zone predominance, but the fibrotic
appearance may be seen in the upper or lower lobes
73
. Patients
with hypersensitivity pneumonitis may exhibit histological
and imaging features of NSIP
78,79
or UIP
80,81
, and thus should
be considered as a differential diagnosis when either IPF or
NSIP is being considered on HRCT appearances. Imaging
features that favour hypersensitivity pneumonitis over IPF
include an upper or mid zone predominance, the presence of
ground-glass opacity and air trapping
81
.
LANGERHANS CELL HISTIOCYTOSIS
Langerhans cell histiocytosis (LCH), formerly known as pul-
monary histiocytosis X or eosinophilic granuloma of the lung,
is a granulomatous disorder characterized histologically by the
presence of large histiocytes containing rod- or racket-shaped
organelles (Langerhans cells)
67
. The male-to-female ratio is
about 4:1, and the vast majority of adult patients are cigarette
smokers. In the earliest stages, patients are often asymptomatic.
Others present with dyspnoea, cough, constitutional symptoms
or a spontaneous pneumothorax. Pulmonary involvement is
widespread, bilateral and usually symmetrical. At presentation,
usually because of dyspnoea or a pneumothorax, the chest
radiograph is abnormal. Typical appearances are of reticulo-
nodular shadowing in the mid and upper zones of the lungs
that are of normal or increased volume
82
. The nodules vary
in size from micronodular to approximately 1 cm in diameter
and, although histopathological examination will often dem-
onstrate cavitation
83
, this feature is often difficult to appreciate
on chest radiography.
The classical appearances of LCH on HRCT are nodules
(ranging in size from a few millimetres to 2 cm), several of
which show cavitation (this feature often clinches the diag-
nosis) and have bizarre shapes (Fig. 19.17). At this stage of the
disease, there are no obvious features of fibrosis. The distribu-
tion of disease is a useful diagnostic pointer and the typical
sparing of the extreme lung bases and anterior tips of the right
middle lobe and lingula is preserved even in end-stage dis-
ease
84
. The typical nodules of LCH
85
tend to show a predict-
able progression through the following stages: cavitation of the
nodules, thin-walled cystic lesions, and finally emphysematous
and fibro bullous destruction
86
.
Figure 19.16 Chronic hypersensitivity pneumonitis. The reticular
pattern with distortion of the lung parenchyma indicates established
fibrosis in this case of chronic hypersensitivity pneumonitis.
Figure 19.17 Langerhans cell histiocytosis. (A) Shows the characteristic combination of thin-walled cysts and poorly defined nodules, some of
which are just beginning to cavitate. (B) Image from a patient with more advanced disease. There are numerous irregularly-shaped cysts bilaterally and a
pneumothorax on the right.
Ch19-F0163.indd 361 6/28/07 3:37:44 PM
LYMPHANGIOLEIOMYOMATOSIS
Lymphangioleiomyomatosis (LAM) is a disease characterized
histologically by two key features: cysts and proliferation of
atypical smooth muscle cells (LAM cells) of the pulmonary
interstitium, particularly in the bronchioles, pulmonary vessels
and lymphatics
67
. LAM is a rare disease seen almost exclusively
in women, the vast majority of cases being diagnosed during
childbearing age. Similar pulmonary abnormalities can be seen
in approximately 1% of patients with tuberous sclerosis.
The most commonly described radiographic manifestation
of LAM is a pattern of generalized, symmetrical, reticular, or
reticulonodular opacities with normal or increased lung vol-
umes
87,88
. Pleural effusions occur in 1040% of patients
8991
(these may be unilateral or bilateral) and pneumothoraces in
approximately 50% of cases. The effusions are chylous and result
from involvement of the thoracic duct by the leiomyomatous
tissue. The CT manifestations of LAM are distinctive, charac-
terized by numerous thin-walled cysts randomly distributed
throughout the lungs with no zonal predilection
92
(Fig.19.18).
Imaging features that help distinguish LAM from LCH include
a more diffuse distribution of cysts typically with no sparing
of the bases, more regularly shaped cysts and normal interven-
ing lung parenchyma. Occasionally HRCT may demonstrate
interlobular septal thickening
88
(attributed to dilatation of lym-
phatic channels secondary to obstruction of pleuropulmonary
lymphatics) or patchy areas of ground-glass attenuation (pre-
sumably the result of pulmonary haemorrhage)
89
.
CONNECTIVE TISSUE DISEASES
The connective tissue diseases form a heterogeneous group of
chronic inflammatory and immunologically mediated disor-
ders, all of which affect the lung and pleura to a variable extent
and in various ways. Although the lung is a particularly vulner-
able target organ, the frequency of pleuropulmonary involve-
ment varies widely within the spectrum of disease and also
in each disease separately, depending upon whether imaging,
physiological, or histological criteria are used to judge involve-
ment. Although the radiographic and HRCT appearances are
not specific for any of the collagen vascular disorders, they fre-
quently provide good corroborative evidence in substantiating
what is often a difficult clinical diagnosis.
Rheumatoid disease
Rheumatoid arthritis (RA) is a connective tissue disease char-
acterized by a symmetrical inflammatory arthritis. The major-
ity of patients have extra-articular disorders, thus the term
rheumatoid disease is commonly used to emphasize the sys-
temic nature of the disorder. RA is associated with a broad
spectrum of pleural and pulmonary manifestations. Most, but
not all, patients with pleuropulmonary disease have other
clinical evidence of RA. In a significant minority of patients
with rheumatoid disease, pleuropulmonary disease antedates
the development of arthritis and in general, pleuropulmonary
involvement is not related to the severity of the arthritis.
The most frequently encountered manifestations of rheuma-
toid disease in the chest are listed in Table 19.5. Pleural involve-
ment, either manifesting as effusions or thickening, is common.
Pleural effusions can be unilateral or bilateral, are usually small
or moderate in size, and the majority resolve spontaneously
93
.
Figure 19.18 Lymphangioleiomyomatosis. (A) There is a profusion of thin-walled cystic airspaces scattered evenly throughout the lungs. The cysts
are relatively uniform in size. (B) In a more advanced case of LAM, note the small left-sided pleural effusion.
Table 19.5 INTRATHORACIC MANIFESTATIONS OF
RHEUMATOID DISEASE
Pleural effusion or thickening
Interstitial fibrosis (most frequently usual interstitial pneumonia type)
Constrictive obliterative bronchiolitis
Bronchiectasis
Organizing pneumonia
Follicular bronchiolitis
Drug-induced lung disease (methotrexate)
Necrobiotic nodules/Caplan's syndrome
Ch19-F0163.indd 362 6/28/07 3:37:46 PM
ILD in RA is more common in men with seropositive disease.
The most common histopathological pattern in RA-associated
ILD is UIP with HRCT features that are indistinguishable from
idiopathic cases; namely reticular opacities with honeycomb-
ing predominantly in the subpleural regions of the lung (Fig.
19.19)
94
. It is thought that the prognosis for RAILD is better
than for idiopathic cases; Flaherty et al have demonstrated that
patients with a connective tissue disease-associated UIP pattern
had fewer fibroblastic foci and better survival when compared
with patients with the idiopathic type
95
. NSIP is also seen but
is less prevalent than in the other connective tissue diseases such
as systemic sclerosis. Other pulmonary abnormalities seen in
RA include follicular bronchiolitis, bronchiectasis (in up to
30% of cases) (Fig. 19.20)
96,97
, obliterative bronchiolitis (this
can occur in patients who are on penicillamine, gold or no
treatment)
98
, methotrexate-induced pneumonitis and organiz-
ing pneumonia
94
.
Rheumatoid (necrobiotic) pulmonary nodules are an uncom-
mon feature of the disease. They are usually associated with the
presence of subcutaneous nodules, and like them may wax and
wane. They may be single or multiple, vary in size from a few
millimetres to several centimetres, are well circumscribed and
may cavitate
99
. They are usually asymptomatic and may occur in
association with pulmonary fibrosis and pleural changes. Radio-
logically identical nodules, characteristically appearing rapidly
and in crops, may occur in patients with rheumatoid arthri-
tis who have been exposed to silica. Radiographic findings of
pneumoconiosis may be present but usually are not a prominent
feature
100
. This phenomenon was originally described in Welsh
coalminers (Caplans syndrome). These nodules contain dust
particles and are quite different from necrobiotic nodules on
histological examination. Follicular bronchiolitis (discussed
here because of its frequent association with rheumatoid disease)
is part of the spectrum of lymphoproliferative disease and is
characterized histologically by a diffuse peribronchiolar pro-
liferation of hyperplastic lymphoid follicles and mild, if any,
alveolar interstitial inflammation
101
. Clinically the patients
usually present during young adulthood or middle age with
insidious dyspnoea
102
. Most cases of follicular bronchiolitis
are associated with connective tissue disease, especially RA,
Sjgrens syndrome and scleroderma, but it is also seen in asso-
ciation with immuno deficiency syndromes including AIDS,
pulmonary infections, or ill-defined hypersensitivity reactions.
The cardinal features of follicular bronchiolitis on HRCT
consist of centrilobular nodules measuring 112 mm in diam-
eter, variably associated with peribronchial nodules and patchy
areas of ground-glass opacity
103
. Nodules and ground-glass
opacities are generally bilateral and diffuse in distribution.
Mild bronchial dilatation with wall thickening and a tree-in-
bud pattern are less frequent findings
104
.
Sjgrens syndrome
Sjgrens syndrome (SjS) is a chronic autoimmune inflam-
matory disease characterized by a triad of clinical features:
dry mouth (xerostomia), dry eyes (keratoconjunctivitis
sicca) and arthritis
105
. SjS can occur alone as primary SjS or
in association with other autoimmune diseasessecondary
SjS. A recent study evaluating the radiological and patho-
logical manifestations of lung diseases associated with pri-
mary SjS found that NSIP was the most common entity;
other pathologies included bronchiolitis, lymphoma, amy-
loid and atelectasis
106
. HRCT studies have demonstrated
LIP in patients with Sjgrens syndrome
107,108
; the imaging
findings of which are described under the section on the
IIPs. The association of LIP and amyloidosis (manifesting on
HRCT as multiple irregular nodules) in patients with SjS
is recognized (Fig. 19.21)
107
, but as these patients are also
at increased risk of pulmonary lymphoma
108
, the finding of
LIP on HRCT in conjunction with multiple nodules in a
patient with SjS should at least prompt the consideration of
a neoplastic process.
Figure 19.20 Rheumatoid arthritis. HRCT demonstrates both mild
cylindrical bronchiectasis and constrictive obliterative bronchiolitis
(reflected by areas of low attenuation in which there is a reduction in the
number of vessels present) in this patient with rheumatoid arthritis.
Figure 19.19 Rheumatoid arthritis with a usual interstitial pneumonia
(UIP)-type pattern. In this case the HRCT appearances of peripheral reticular
abnormality and honeycombing are indistinguishable from that of UIP.
Ch19-F0163.indd 363 6/28/07 3:37:48 PM
Progressive systemic sclerosis (scleroderma)
Progressive systemic sclerosis (SSc) is a collagen vascular dis-
ease characterized by the deposition of excessive extracellu-
lar matrix with vascular occlusion involving several organs. It
commonly affects the skin (scleroderma), peripheral vascula-
ture, kidneys, oesophagus and lungs. As with systemic lupus
erythematosus, SSc occurs more frequently in women. Cuta-
neous features dominate the clinical picture, at least in the
early stages, although the prognosis is usually determined by
involvement of the heart, lungs and kidneys. ILD is common
in patients with SSc and causes considerable morbidity and
mortality. The interstitium and pulmonary vasculature are the
predominant sites that are affected
109,110
. The HRCT findings
of interstitial fibrosis in SSc include peripheral reticular opaci-
ties, ground-glass attenuation associated with traction bron-
chiectasis and occasionally honeycomb destruction
111,100
. At
microscopy, NSIP is increasingly regarded as the more preva-
lent histological pattern in patients with SSc
112,113
, and indeed
CT studies have confirmed that patients with SSc typically
have HRCT features more akin to idiopathic NSIP with a
less coarse fibrosis when compared with IPF and a greater
proportion of ground-glass opacification (Fig. 19.22)
114
. A
UIP pattern is thought to occur in 510% of cases
113
. Pleural
disease is much less common in SSc than in other connective
tissue diseases; pleural thickening being seen on HRCT in
approximately 10% of patients
115
. As in other diffuse fibros-
ing lung diseases, enlarged mediastinal lymph nodes (which
histologically show reactive hyperplasia) are a frequent finding
on CT
116
.
Polymyositis/dermatomyositis
Polymyositis (PM) is an idiopathic autoimmune inflamma-
tory myopathy that results in proximal muscle weakness
117
.
Dermatomyositis (DM) is similar except that it is accompa-
nied by a skin rash. Pulmonary complications of PM/DM are
important determinants of the clinical course with aspiration
pneumonia being the most important pulmonary disease due
to its prevalence as well as its associated morbidity and mortal-
ity
118
. Respiratory muscle weakness and a poor cough reflex
are responsible for the high prevalence of recurrent aspiration.
ILD in PM/DM was first described in 1956
119
and occurs
in an estimated 547% of patients. Initial clinical presentation
is with cough, dyspnoea and fever, prior to musculoskeletal
manifestations of arthralgia, myalgia and weakness in 30%, with
simultaneous occurrence in only 20%
120
. NSIP is thought to
Figure 19.21 Sjgrens syndromelymphoid interstitial pneumonia
and amyloid. There are numerous thin-walled cysts in association with
multiple irregular solid nodules, some of which are heavily calcified.
Histopathological examination showed marked thickening of the
interstitium with an infiltrate of small, mature lymphocytes and plasma
cells. Multiple deposits of amyloid were seen throughout the specimen
and there was no evidence of malignancy.
Figure 19.22 Scleroderma. (A,B) Two patients with scleroderma showing ground-glass opacification in association with traction bronchiectasis and a
fine reticular pattern. The pattern of fibrosis is closest to that of non-specific interstitial pneumonia. Note the dilated oesophagus in both examples.
Ch19-F0163.indd 364 6/28/07 3:37:50 PM
be the most common histological pattern seen in PM/DM
120
.
The ILD can be acute and aggressive, similar to AIP, with some
series reporting up to 10.5% mortality
29,121
, or more slowly
progressive. In some, the lung disease is responsive to steroids
and immunosuppression
121
. At presentation, the most common
HRCT features of PM/DM are linear opacities with a lower
lung predominance, ground-glass opacities, irregular interfaces
and areas of consolidation (Fig. 19.23). Parenchymal micro-
nodules and honeycombing are less frequently observed
29
.
Histologically, organizing pneumonia is the correlate of
consolidation and ground-glass opacification seen on HRCT.
DAD is demonstrated in some cases and is associated with
widespread involvement, dense dependent consolidation
and extensive diffuse ground-glass opacification. Organizing
pneumonia in PM/DM can also be admixed with interstitial
fibrosis with a predominance of reticular elements and archi-
tectural distortion, traction bronchiectasis and honeycombing,
and this overlap entity is associated with a poor prognosis
122
.
When comparing patients with PM/DM ILD as a whole, the
3-year survival is 74.7% and 5-year survival 60.4%
120
, which is
better than in IPF, but not significantly different from patients
with idiopathic NSIP.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a chronic multisystem
disease of unknown origin characterized by the presence of
autoantobodies against various cell nuclear antigens
123
. SLE is
associated with widespread inflammatory changes in the con-
nective tissues, vessels and serosal surfaces. Pleuropulmonary
disease will occur in more than half of patients with SLE at
some point during the course of their illness
124
. Although pleu-
ritis is the most common manifestation of SLE, diverse thoracic
manifestations which range from diaphragmatic dysfunction
(shrinking lung syndrome) to life-threatening pneumonitis or
pulmonary haemorrhage are encountered. A list of the other
pulmonary complications may be found in Table 19.6.
Pleural effusions are the most common radiographic abnor-
mality. They are frequently bilateral, usually only small in
volume and, unlike those in rheumatoid disease, are often asso-
ciated with pleuritic pain. Thick horizontal band shadows at
the lung bases due to linear atelectasis may be secondary to the
pleurisy or, more likely, restricted diaphragmatic movement.
Pulmonary consolidation in patients with SLE may cause
diagnostic difficulty as it may be a consequence of infection
(the incidence of respiratory tract infection in patients with
SLE is high due to the immunological abnormalities, immu-
nosuppression from steroids and respiratory muscle weak-
ness), pulmonary oedema, lupus pneumonitis, or pulmonary
haemorrhage. Pulmonary oedema may be secondary to renal
Table 19.6 INTRATHORACIC MANIFESTATIONS OF
SYSTEMIC LUPUS ERYTHEMATOSUS
Pleural effusion
Segmental or subsegmental collapse
Lupus pneumonitis
Pulmonary infection
Pulmonary oedema
Diaphragmatic dysfunction
Interstitial fibrosis (rare)
Pericardial effusion
Pulmonary vascular disease
Pulmonary arterial hypertension
Vasculitis/capillaritis
Pulmonary embolism
Pulmonary veno-occlusive disease
Figure 19.23 Polymyositis/dermatomyositis. HRCT features include (A) reticular opacities and (B) areas of ground-glass opacification. The
appearances of (B) are compatible with organizing pneumonia being incorporated as fibrosis.
Ch19-F0163.indd 365 6/28/07 3:37:52 PM
disease or cardiac failure. Acute lupus pneumonitis is a well-
recognized but rare manifestation of the disease that is char-
acterized by fever, severe hypoxaemia and diffuse pulmonary
infiltrates
125
. Radiological features are typically patchy consoli-
dation and focal atelectasis seen predominantly in the lower
lung zones with concomitant pleural effusions. Histological
findings are not diagnostic but include alveolar wall damage,
inflammatory cell infiltration and haemorrhage
125
.
Compared with many other collagen vascular diseases, SLE
is not commonly associated with chronic diffuse ILD. When
present, reported HRCT findings include irregular linear and
bandlike opacities (in part atelectasis), ground-glass opacities
and interlobular septal thickening. Honeycombing which
can resemble IPF is extremely rare
100
. Loss of lung volume is
sometimes a prominent feature and is secondary to a myopa-
thy of the diaphragmatic muscle. Diffuse alveolar haemorrhage
is a rare but dramatic complication of SLE
126
, which manifests
radiologically as widespread ground-glass opacity and con-
solidation. SLE is associated with increased risk of malignancy,
with lymphoma being the most common
124
.
Ankylosing spondylitis
Ankylosing spondylitis is a chronic inflammatory disease that
affects mainly the axial skeleton, particularly the costovertebral,
apophyseal and sacroiliac joints
127
. The majority of patients
with ankylosing spondylitis have airway and interstitial abnor-
malities evident on HRCT, but these are usually mild and
seldom evident on the chest radiograph
128
. Apical fibrosis,
evident on chest radiography, is seen in approximately 1% of
patients
100
. The upper lobe fibrosis causes upward retraction
of the hila, and is often associated with bullous formation and
apical pleural thickening. The changes are usually bilateral but
may be unilateral, especially initially, and are indistinguishable
from tuberculosis. Occasionally pulmonary changes may ante-
date the spondylitis. Ankylosing spondylitis is one of a number
of causes (albeit a very rare one) of upper lobe fibrosis (Table
19.7). As with tuberculosis, mycetomas may form within the
upper lobe cavities. The HRCT findings of ankylosing spon-
dylitis include apical fibrosis, mild peripheral interstitial fibro-
sis, parenchymal bands, bronchiectasis and bullae
128,129
.
SYSTEMIC VASCULITIDES
A number of disorders are characterized histologically by a
systemic vasculitis in which the primary pathogenetic mecha-
nism is the deposition of immune complexes in the walls of
blood vessels. The systemic vasculitides that most commonly
affect the lung are Wegeners granulomatosis, ChurgStrauss
syndrome and Behets disease. Only ChurgStrauss syndrome
and Wegeners granulomatosis will be covered in this section.
Wegeners granulomatosis
Wegeners granulomatosis is a multisystem disease with variable
clinical expression. It is characterized histologically by necrotiz-
ing granulomatous inflammation of the upper and lower respi-
ratory tracts, the lungs being involved in approximately 90% of
cases; focal necrotizing glomerulonephritis; and a small vessel
vasculitis affecting arteries, capillaries and veins
130
. The majority
of patients present with symptoms referable to the nose, para-
nasal sinuses, or chest; in some patients, the disease manifests
solely in the respiratory tract and is known as limited (nonrenal)
Wegeners granulomatosis
131
. Chest symptoms include cough,
dyspnoea, pleuritic chest pain and haemoptysis. Multiple nod-
ules or masses are the most common imaging finding in Wegen-
ers granulomatosis, being seen in approximately 70% of cases
132
.
Nodules range in size from a few millimetres to 10 cm, are fre-
quently multiple, and increase in size and number as the disease
progresses. Nodules are bilateral in 75% of cases, have no predi-
lection for any lung zone, and usually show cavitation at about
2 cm in size
133
. HRCT may demonstrate nodules not apparent
on radiography and is superior in demonstrating the presence
of cavitation. Airspace consolidation and ground-glass opacities
also may occur with or without the presence of nodules. Several
patterns of consolidation have been described: (A) peripheral
wedge-shaped lesions abutting the pleura mimicking pulmo-
nary infarcts
134
; (B) a peribronchial distribution of consolida-
tion
135
; and (C) a region of focal consolidation with or without
cavitation (Fig. 19.24). Diffuse bilateral areas of ground-glass
opacification are often a consequence of pulmonary haemor-
rhage
132
, but may also be related to necrotizing granulomatous
inflammation similar to that associated with nodules. Rarely,
Wegeners granulomatosis may present as a fibrosing lung disease
(closest to a UIP-type pattern) on HRCT
136
. Histopathologists
have also described bronchocentric granulomatosis
137
and orga-
nizing pneumonia
138
in patients with Wegeners granulomatosis,
all of whom also demonstrated typical features of necrotizing
vasculitis. Unilateral or bilateral pleural effusions are present in
about 10% of patients and hilar or mediastinal lymphadenopa-
thy has also been reported. Airway involvement is common in
Wegeners granulomatosis which may lead to subglottic, tracheal
or bronchial narrowing (the latter resulting in segmental or
lobar atelectasis). Mild bronchiectasis is an additional feature in
Wegeners granulomatosis occurring in up to 40% of cases
134
.
ChurgStrauss syndrome
ChurgStrauss syndrome is an antineutrophil cytoplasmic anti-
body (ANCA)-associated systemic vasculitis affecting small
arteries and veins. It is characterized histologically by the pres-
ence of necrotizing vasculitis and extravascular granulomatous
inflammation rich in eosinophils, and clinically by the presence
of asthma, fever and blood eosinophilia
130
. While the vascu-
litis affects both arteries and veins, predominant small vessel
involvement is rarely encountered, and it is therefore not sur-
Table 19.7 CAUSES OF BILATERAL UPPER LOBE FIBROSIS
Tuberculosis (including atypical mycobacterial infections)
Sarcoidosis
Histoplasmosis
Allergic bronchopulmonary aspergillosis
Chronic extrinsic allergic alveolitis
Ankylosing spondylitis
Progressive massive fibrosis (distinctive mass-like opacities)
Ch19-F0163.indd 366 6/28/07 3:37:54 PM
prising that diffuse pulmonary haemorrhage is an uncommon
manifestation of ChurgStrauss syndrome. HRCT appearances
largely reflect the eosinophilic infiltrate and are largely non-
specific. HRCT features include ground-glass opacities, areas
of airspace consolidation, centrilobular nodules (some of which
may display cavitation) and airways abnormalities attributable to
asthma (Fig. 19.25)
139
. Histologically the airspace disease is due
to eosinophilic infiltrate or foci of organizing pneumonia
139
.
Interlobular septal thickening may be seen as a result of inter-
stitial pulmonary oedema secondary to cardiac involvement.
However, a significant proportion (up to 25%) of patients with
ChurgStrauss syndrome have few or no imaging abnormali-
ties and imaging is often of little help in making this somewhat
elusive diagnosis. Even when HRCT abnormalities exist they
are not specific and the diagnostic accuracy for ChurgStrauss
syndrome was less than 50% in one study
140
.
DRUG-INDUCED LUNG DISEASE
The lung is less commonly the site of drug-induced dis-
ease than other organs such as the skin and gastrointestinal
tract. Nevertheless, approximately 350 drugs can cause injury
to the lungs, and the list of drugs and patterns of involve-
ment continues to increase. Respiratory disease secondary to
drugs may be the result of the pharmacological action of the
drug in normal or excessive dosage, or caused by an allergic
or idiosyncratic reaction. The radiological manifestations of
drug-induced ILD, although heterogeneous and non-specific,
Figure 19.24 Wegeners granulomatosis. Images through the (A) mid and (B) upper zones in a patient with Wegeners granulomatosis. Thick-walled
cavitating mass in the left upper lobe (A). Note also the focal narrowing of the mid intrathoracic trachea (B) reflecting focal involvement by Wegeners
granulomatosis.
Figure 19.25 ChurgStrauss
syndrome. Spectrum of HRCT
features: (A) areas of ground-glass
opacification, (B) small cavitating
nodules,
Continued
Ch19-F0163.indd 367 6/28/07 3:37:54 PM
enable many alternative diagnoses to be excluded. There is no
specific radiological pattern of parenchymal change associated
with drug-induced lung disease and in the early stages of dis-
ease, patients with symptoms secondary to drug reaction may
have a normal chest radiograph. Furthermore, data based on
a small number of cases suggest that the different histological
patterns of drug reaction are not always reflected by distinctive
HRCT findings
141
. Despite these limitations, it is reasonable
to understand the radiological manifestations of drug-induced
lung disease via an appreciation of the underlying histological
patterns of drug-induced disease
142
. The most common his-
tological manifestations can be classified into DAD, chronic
interstitial pneumonia (a vague term used by histopathologists
which incorporates drug-induced lung disease with histologi-
cal features that resemble either NSIP or less commonly UIP),
hypersensitivity pneumonitis, organizing pneumonia and
eosinophilic pneumonia
142
. Most drugs typically cause more
than one type of histological pattern. Table 19.8 lists the drugs
associated with the different histological patterns.
Diffuse alveolar damage
Chemotherapeutic drugs such as busulphan, cyclophosphamide,
carmustine (BCNU) and bleomycin constitute the largest group
of drugs associated with this pattern of lung toxicity
141
. DAD
usually develops a few weeks or months after initiating therapy
and disease onset is heralded by progressive dyspnoea. The cor-
responding radiological features, not surprisingly, are similar to
those found in ARDS with bilateral patchy or homogeneous
Figure 19.25, Contd (C) thickened
interlobular septa, and (D) an area of
airspace opacification, likely to be a
peripheral infarct.
Table 19.8 HISTOLOGICAL PATTERN OF DRUG-INDUCED LUNG DISEASE
Diffuse Non-specific
alveolar Diffuse alveolar interstitial Organizing Eosinophilic
damage haemorrhage pneumonia pneumonia pneumonia
Amiodarone Amphotericin B Amiodarone Amiodarone Ampicillin
Bleomycin Cyclophosphamide Carmustine Carbamazepine Captopril
Methotrexate Nitrofurantoin Busulphan Interferon Chlorpropamide
Nitrofurantoin Amiodarone Methotrexate Methotrexate Ethambutol
Carmustine Anticoagulants Nitrofurantoin Sotalol Indomethacin
Busulphan Penicillamine Melphalan Nitrofurantion Mesalazone
Sulphasalazine Streptokinase Phenytoin Minocycline Naproxen
Vinblastine Haloperidol Simvastatin Phenytoin Tetracycline
Ranitidine
Propranolol
Ch19-F0163.indd 368 6/28/07 3:37:57 PM
airspace consolidation involving mainly the middle and lower
lung zones. HRCT demonstrates extensive bilateral ground-
glass opacities and dependent areas of airspace consolidation
(Fig. 19.26)
143
. In most circumstances there are no histologi-
cal features that allow separation of drug toxicity from other
potential causes of DAD and the diagnosis of drug-induced
lung disease requires vigorous exclusion of other potential aeti-
ologies, most importantly opportunistic infection.
Non-specic interstitial pneumonia
Drugs reported to cause an NSIP-type pattern include amio-
darone, busulphan, carmustine, methotrexate, phenytoin and
simvastatin
142
. Descriptions of HRCT findings are available
for a limited number of agents, but demonstrate the same
range of abnormalities described in patients with the idio-
pathic form of NSIP (Fig. 19.27)
143,144
. With disease progres-
sion, there may be evidence of fibrosis with development of
a reticular pattern and traction bronchiectasis. The fibrosis is
patchy in distribution and predominantly peribronchovascular,
a pattern most commonly seen in patients receiving nitrofu-
rantoin. In some cases, however, HRCT features suggestive of
irreversible fibrosis may show complete resolution on cessation
of nitrofurantoin
145
. NSIP is the most common manifestation
of amiodarone-induced lung disease
146
. HRCT features that
have been described with amiodarone-induced lung disease
include ground-glass opacities in association with fine intra-
lobular reticulation seen predominantly in a peripheral distri-
bution. Foci of consolidation have also been described
147
, and
are likely to represent areas of organizing pneumonia.
Hypersensitivity pneumonitis
Several drugs have been associated with a pattern of lung toxicity
with radiological and histopathological features indistinguishable
from hypersensitivity pneumonitis
144
, although in general, this
pattern is an uncommon manifestation of drug-induced lung
disease. Methotrexate is the best known offender; similar changes
have been attributed to cyclophosphamide, fluoxetine, nitrofu-
rantoin and amitriptyline. The radiological and HRCT findings
are similar to those seen in hypersensitivity pneumonitis sec-
ondary to the inhalation of organic dust and consist of bilateral
ground-glass opacities (Fig. 19.28) and/or small, poorly defined
centrilobular nodular opacities
141,144
. HRCT and lung biopsies
in methotrexate toxicity show features more characteristic of
NSIP in the majority of patients with a pattern resembling hyper-
sensitivity pneumonitis seen in only a few patients
142
.
Organizing pneumonia
An organizing pneumonia-like reaction has been reported most
frequently in association with methotrexate, cyclophosphamide,
gold, nitrofurantoin, amiodarone, bleomycin and busulphan
141
.
The chest radiograph shows patchy bilateral areas of consolida-
tion, masses or nodules, which may be asymmetric or symmet-
ric. HRCT may demonstrate patchy asymmetrical ground-glass
opacity and areas of consolidation which often have a predomi-
nantly peripheral or peribronchiolar distribution (Fig. 19.29)
144
.
Figure 19.26 Diffuse alveolar damage secondary to amiodarone.
There is extensive bilateral ground-glass opacification and airspace
consolidation. Note also the bilateral pleural effusions.
Figure 19.27 Non-specific interstitial pneumonia secondary to
bleomycin. The dominant abnormality is ground-glass opacification
in association with a fine reticular pattern. The pattern of fibrosis most
closely resembles non-specific interstitial pneumonia.
Figure 19.28 Hypersensitivity pneumonitis secondary to sertraline.
HRCT shows extensive bilateral ground-glass opacification and lobular
areas of air trapping (arrows).
Ch19-F0163.indd 369 6/28/07 3:37:58 PM
Figure 19.29 Organizing pneumonia secondary to (A,B) nitrofurantoin and (C) amiodarone. The HRCT features of ground-glass opacification and
consolidation (A,C) and a perilobular pattern (B) are in keeping with organizing pneumonia. The areas of consolidation in (C) are both peribronchial and
perilobular in distribution.
Table 19.9 EXAMPLES OF OCCUPATIONAL EXPOSURES THAT
CAUSE LUNG PATHOLOGY
Occupational lung
disease Pathology Radiology
Flock worker's lung Lymphocytic Ground-glass
bronchiolitis opacities with
centrilobular nodules
181
Flavour worker's lung Obliterative Mosaic attenuation
(flavouring agents used bronchiolitis pattern, air trapping,
in microwave popcorn) bronchial wall
thickening
182
Berylliosis Noncaseating Nodules with a similar
granulomas distribution to
(indistinguishable sarcoidosis, ground-glass
from sarcoidosis) opacities, thickened
accompanied by interlobular septa,
mononuclear cell reticular opacities and
infiltrates and honeycombing
interstitial fibrosis (rare)
183,184
. Mediastinal
adenopathy is less com-
mon than in sarcoidosis.
Conglomerate masses are
seen in advanced disease
Hard metal Giant cell interstitial Ground-glass attenuation
pneumoconiosis pneumonia and consolidation. Cysts
(alloys of tungsten and reticular
carbide and cobalt, abnormality may also
titanium and occur
185
tantalum)
Eosinophilic pneumonia
Eosinophilic pneumonia is characterized histologically by
the accumulation of eosinophils in the alveolar airspaces and
infiltration of the adjacent interstitial space by eosinophils and
variable numbers of lymphocytes and plasma cells. Periph-
eral blood eosinophilia is present in around 40% of patients.
Eosinophilic pneumonia secondary to drug reaction is seen
most commonly in association with methotrexate, sulphasala-
zine, para-aminosalicylic acid, nitrofurantoin and non-steroidal
anti-inflammatory drugs. Chest radiography and HRCT show
bilateral airspace consolidation, which tends to involve mainly
the peripheral lung regions and the upper lobes
141,143
.
The diagnosis of drug-induced disease will be missed unless
specifically sought as a cause of unexplained diffuse pulmonary
shadowing in patients at known risk with clinical symptoms of
lung disease. It is particularly important, though often difficult, to
differentiate between drug-induced disease, infections (particu-
larly of the opportunistic variety) and metastatic malignancy in
patients who are susceptible to a combination of these processes.
OCCUPATIONAL LUNG DISEASE
Diseases of the lung caused by workplace and environmental
exposures are common throughout both developed and devel-
oping worlds, and as industrial techniques continue to evolve,
new occupational diseases will be recognized.
The following section highlights the imaging features of
the main pneumoconiosessilicosis, coal workers pneumo-
coniosis and asbestos-related pulmonary disease. Table 19.9
summarizes some of the other main occupational lung dis-
eases. Hypersensitivity pneumonitis is covered in the preced-
ing section on ILD. Work-related asthma is one of the most
frequently reported occupational lung diseases in a number
of industrialized countries
148
but as these patients are not fre-
quently imaged (and the contribution of imaging is negligi-
ble), this topic is not further discussed.
The International Labour Ofce Classication
The International Labour Office (ILO) International Classi-
fication of Radiographs for the Pneumoconioses is a system
used for the recording of chest radiographic abnormalities
related to the inhalation of dusts. Its intent was to improve
health workers health surveillance by facilitating interna-
tional comparisons of pneumoconiosis statistics and research
reports
149
. Thus, it was designed primarily for population epi-
demiology, rather than for individual diagnosis. In the ILO
system, the size, shape and profusion of opacities on radio-
graphs are classified in a detailed manner by trained observers
using a set of standard radiographs. Rounded or nodular opac-
ities are graded as p (< 1.5 mm diameter), q (1.53 mm), or r
(310 mm). Irregular opacities are classified as s, t, or u, using
the same size criteria. Large opacities (> 10 mm) are graded
as A, B and C based on the combined dimensions of all large
opacities present. The classification also scores the extent and
thickness of plaques, pleural thickening, fissural thickening and
Ch19-F0163.indd 370 6/28/07 3:38:00 PM
calcified nodules. Profusion of the opacities is classified into
four categories (03); category 0 indicating that there is no
excess of small opacities above normal. The use of two profu-
sion categories is useful when appearances lie between those of
the standard radiographs. Thus, 1/0 indicates that appearances
most closely resemble category 1, but that the reader has also
considered category 0. Despite acknowledged limitations and
problems with the ILO classification (interobserver variabil-
ity, the presence of background opacities that are unrelated to
dust exposure, the relative insensitivity of the chest radiograph
to early disease, and the misuse of the classification in legal
settlements for compensation), it remains a useful shorthand
whose meaning is widely understood for population studies.
HRCT classification systems for the pneumoconioses have
been developed
150
, but it is too early to gauge whether such a
classification will be widely accepted and adopted.
Silicosis/coal workers pneumoconiosis
Silicon dioxide or silica is the most abundant mineral on earth
and is formed from the elements silicon and oxygen under
conditions of increased heat and pressure. Any occupation that
disturbs the earths crust or exposes the worker to the use
or processing of silica-containing rock or sand has potential
risks. Mining, tunnelling through rock, quarrying, stone cut-
ting and foundry work, amongst others, are potentially haz-
ardous occupations. Coal workers pneumo coniosis (CWP) is
a consequence of the inhalation of coal dust. Both coalmine
dust and silica predispose workers to chronic bronchitis, sim-
ple pneumoconiosis, emphysema, complicated pneumoconiosis
(progressive massive fibrosis [PMF]), lung cancer (in excess of
that expected from smoking alone) and mycobacterial pulmo-
nary infectionthe risk for tuberculosis is increased three-fold
in patients with chronic silicosis
151
. As coal also contains a vari-
able proportion of quartz, it has often been difficult to separate
the pulmonary effects of coal dust from that of silica; in general,
coal of high rank (high carbon content), such as anthracite, is
associated with a higher incidence of CWP.
Silica causes three distinct clinical patterns of lung disease
(Table 19.10) which are related to both level and duration of
exposure. The earliest radiographic changes of silicosis and
CWP are nearly identical. Typical appearances are a profusion
of small (13 mm) round nodules distributed in the posterior
aspects of the upper two-thirds of the lung
152
. Radiologically, the
only difference between simple CWP and simple silicosis is that
the nodules in CWP are often smaller (typically p, rather than
q opacities, according to the ILO classification). With advanc-
ing disease, the nodules increase in size and number to involve
all lung zones. The nodules are sometimes calcified. Hilar and
mediastinal lymph node enlargement with calcification of the
eggshell type is not uncommon and may be seen on the chest
radiograph or CT. On CT, the micronodules are sharply defined
and distributed throughout the lungs but are frequently most
numerous in the upper lung zones. The nodules may be centri-
lobular or subpleural in location; the subpleural micronodules
may become confluent, forming a pseudo-plaque
153
.
PMF refers to the coalescence of large nodules and is much
more common in silicosis than in CWP. On the chest radio-
graph, PMF is seen as mass-like opacities, typically in the
posterior upper lobes and associated with contraction of the
upper lobes and hilar elevation. Sequential evaluation of these
masses often demonstrates migration towards the hila, leaving
a peripheral rim of cicatricial emphysema. The outer margins
of PMF often parallel the contour of the adjacent chest wall.
CT confirms the architectural distortion associated with PMF
(Fig. 19.30). Large lesions (> 5 cm) often show irregular low
attenuation regions on CT indicative of necrosis. Frank cavita-
tion is a less frequent finding and when present should always
raise the suspicion of tuberculosis (conventional or atypical).
Unilateral or asymmetric PMF may be distinguished from
lung cancer by the presence of lobar volume loss and periph-
eral emphysema.
Acute silicoproteinosis develops after exposure to high con-
centrations of crystalline silica. The dominant feature is the
presence of an alveolar proteinaceous exudate, similar to that
found in pulmonary alveolar proteinosis, hence the term acute
silicoproteinosis. The chest radiograph demonstrates widespread
alveolar opacity with an upper and mid zone dominance. Air
Figure 19.30 Progressive massive fibrosis in coalworkers
pneumoconiosis. Mass-like opacities are seen bilaterally in the upper
lobes in association with multiple small nodules and calcified mediastinal
lymphadenopathy.
Table 19.10 PATTERNS OF DISEASE CAUSED BY SILICA
EXPOSURE
Clinical pattern Duration and level of exposure
Acute silcoproteinosis Occurs in response to a massive inhalation
of silica (e.g. in sandblasting) usually within a
few weeks to 45 years after exposure
Accelerated silicosis Develops less than 10 years after first inhala-
tion of high concentrations of silica. Its more
rapid development than in simple silicosis
indicates that the worker is at great risk for
the development of progressive massive
fibrosis
Chronic simple silicosis The most common manifestation usually
developing after 1050 years of low level
silica exposure
Ch19-F0163.indd 371 6/28/07 3:38:01 PM
bronchograms may be seen initially and hilar and mediastinal
adenopathy also occur.
Studies have shown that silica workers have an increased
risk of IPF
154,155
, although epidemiological data are currently
insufficient firmly to establish an aetiological link between
exposure to silica and IPF-like diseases
156
. In addition, there
has been a long-recognized association of silicosis with con-
nective tissue disease (CTD)
157
. Among the CTDs, the associa-
tion of silicosis and rheumatoid arthritis (Caplans syndrome)
is more common than systemic sclerosis (Erasmus syndrome).
In the development of CTD, it appears that exposure to very
fine silica dust (silica flour) is necessary; this exposure may be
experienced by dental technicians and workers exposed to
fine scouring powders
158
.
Asbestos-related disease
Asbestos is the generic term for a group of fibrous silicates
that share the property of heat resistance. They are classified
into two groups: the serpentines and the amphiboles. The only
serpentine asbestos used commercially is chrysolite, which
accounts for more than 90% of the asbestos used in the USA.
The pathological hallmark of asbestos exposure is the asbestos
body consisting of an asbestos fibre usually 25 m in width.
These bodies can be identified in tissue sections in interstitial
fibrous tissue and intra-alveolar macrophages in broncho-alve-
olar lavage (BAL) fluid. The effects of asbestos on the lung are
diverse and clinical manifestations of these abnormalities typi-
cally do not appear until 20 years or more after initial expo-
sure, apart from asbestos-related pleural effusions which may
be present as early as 5 years post exposure.
Benign pleural effusions
The exact prevalence of benign pleural effusions is unknown,
as many are subclinical. The effusions are typically haemor-
rhagic exudates of mixed cellularity and usually do not contain
asbestos bodies. Their diagnosis is therefore reliant largely on
the exclusion of other causes of effusions in an asbestos-exposed
patient. The development of effusions is thought to be exposure
dependent
159
. The effusions are often small, may be persistent or
recurrent and may be simultaneously or sequentially bilateral
160
.
Diffuse pleural thickening is the usual consequence.
Pleural plaques
The most common manifestation of asbestos exposure is pleural
plaques which macroscopically are discrete foci of pearly white
fibrous tissue, usually 25-mm thick. They involve the parietal
pleural almost exclusively and on the chest radiograph are clas-
sically distributed along the posterolateral chest wall between
the 7th and 10th ribs, lateral chest wall between the 6th and 9th
ribs, the dome of the diaphragm and the mediastinal pleura
161
.
CT also demonstrates anterior and paravertebral plaques that
are not well demonstrated on chest radiography. Calcification is
reported in 1015% of cases
161
. At histological examination, the
plaques are relatively acellular, with a basket-weave appearance
of collagen bundles. Asbestos fibres (usually chrysolite) are often
seen, but asbestos bodies are usually absent. CT is undoubt-
edly more sensitive for the detection of pleural plaques. Only
5080% of cases of documented pleural thickening are detected
by chest radiography
162,163
; on chest radiography pleural plaques
were most commonly missed in the paravertebral and posterior
regions of the costal pleural
164
. Studies have suggested that pleu-
ral plaques are not associated with significantly impaired lung
function
165,166
.
Diffuse pleural thickening
The frequency of diffuse pleural thickening increases with
time from first exposure and is thought to be dose related.
It results from thickening and fibrosis of the visceral pleura,
which leads to fusion with the parietal pleura and may be
caused by extension of interstitial fibrosis to the visceral pleura,
consistent with the pleural migration of asbestos fibres. Diffuse
pleural thickening superimposed on circumscribed plaques
has been observed, often after a pleural effusion. Histologically,
there is a similarity between pleural thickening and plaques,
except that fusion of the pleural layers is suggestive of more
intense inflammation. It has been shown that workers with dif-
fuse pleural thickening have a significant reduction in forced
vital capacity (FVC) and gas transfer (DL
CO
)
167
. CT is more
sensitive and specific than chest radiography in the detection
of diffuse pleural thickening
168
and is better at the distinction
between mild pleural disease and extrapleural fat
169
. Although
oblique views can enhance detection of pleural abnormalities
in cases in which HRCT is unavailable, they may also fail to
distinguish plaques from extrapleural fat
170
.
Round atelectasis
Round atelectasis, also known as folded lung, is a form of
parenchymal collapse that occurs most commonly in the
peripheral lung in the dorsal regions of the lower lobes. Patho-
logical examination shows pleural fibrosis overlying the abnor-
mal parenchyma as well as invaginations of fibrotic pleura into
the region of collapse. The appearance suggests that retraction
of collagen in the pleura as it matures is the cause of the col-
lapse.
Because of the pathogenetic association with fibrosis, the
areas of atelectasis are always seen adjacent to the visceral
pleura. A characteristic finding is the presence of crowding
of bronchi and blood vessels that extend from the border of
the mass to the hilum (comet tail sign)
171
. In most cases, the
collapsed lung has a rounded or oval shape; however, wedge-
and irregularly-shaped masses can also occur (Fig. 19.31). Vol-
ume loss of the affected lobe is invariably present and often
associated with hyperlucency of the adjacent lung
172
. Serial
examinations show a relatively stable appearance, and the dif-
ferentiation from a lung neoplasm is usually straightforward
on CT.
Asbestosis
Asbestosis is defined as pulmonary parenchymal fibrosis second-
ary to inhalation of asbestos fibres. The lag between exposure
and onset of symptoms is usually 20 years or longer. Histologi-
cally, fibrosis is first seen in the interstitium of respiratory bronchi-
oles, particularly in the lower lobes adjacent to the visceral pleura.
With advancing disease, the fibrous tissue extends into the adja-
cent alveolar septa, eventually involving the entire lobule
173
. In the
Ch19-F0163.indd 372 6/28/07 3:38:02 PM
Figure 19.31 Atelectasis. Two examples of rounded atelectasis in association with (A) pleural thickening and (B) a pleural effusion. In both cases, there
is evidence of lobar volume loss as evidenced by displacement of fissures. The most common location of rounded atelectasis is in the lower lobes.
Figure 19.32 Asbestosis. (A) HRCT features of early asbestosis include subpleural lines (arrowheads) and fine reticulation (arrows). These subtle
abnormalities persisted on prone sections. (B) In more advanced disease, a coarse reticular pattern with honeycombing, often indistinguishable from
usual interstitial pneumonia on HRCT, is seen. Note the calcified pleural plaques in both examples.
most severe cases there is diffuse interstitial fibrosis associated with
parenchymal remodelling and honeycombing. Asbestos bodies are
almost always identifiable microscopically in the fibrous tissue or
macrophages in residual airspaces. Early CT changes indicative of
asbestosis are the presence of subpleural curvilinear lines and dots,
pleural-based nodular irregularities, parenchymal bands and septal
lines
164
. The fine reticulation eventually progresses to a coarse linear
pattern with honeycombing (Fig. 19.32). These abnormalities are
usually most severe in the subpleural regions of the lower lobes.
HRCTpathological correlation studies have shown that subpleu-
ral dots and branching structures correspond to peribronchiolar
fibrosis
174
. The sensitivity of HRCT over the chest radiograph for
the identification of early fibrosis in asbestos-exposed individuals is
well established
175,176
; however, sensitivity is not 100% and a histo-
pathological diagnosis of asbestosis can be present in patients with
normal or near-normal HRCTs
177
. The diagnosis of asbestosis has
significant implications for the patient in terms of prognosis, work
ability and the possibility of receiving legal compensation. Although
both the chest radiograph and HRCT can confirm previous expo-
sure, the diagnosis of asbestosis is largely inferential and based on
Ch19-F0163.indd 373 6/28/07 3:38:02 PM
demonstrating a compatible structural lesion, an appropriate expo-
sure history with a suitable latency, and the exclusion of other plau-
sible conditions. One of the problems in interpreting the presence
of interstitial fibrosis, whether on chest radiography or HRCT, is
the fact that asbestos-exposed individuals are as likely as the rest of
the population to develop other causes of fibrosis such as IPF
178
.
Distinguishing asbestosis from IPF is also desirable, as asbestosis is
associated with a much slower rate of progression and hence better
prognosis. Discrimination between the two by HRCT appearances
is by no means straightforward and is usually impossible. It has been
suggested that subpleural dot-like or branching opacities are sig-
nificantly more common in patients with asbestosis, whereas hon-
eycombing, traction bronchiectasis with areas of confluent fibrosis
and a mosaic perfusion pattern resulting from air trapping are more
common in patients with IPF
179
. Additionally, pleural disease may
be a discriminator: in Akira et als study, pleural disease was found
in 83% (66/80) of patients with asbestosis but only in 4% (3/80)
of patients with IPF
179
. Copley et al found no statistically signifi-
cant differences in the coarseness of fibrosis between individuals
with asbestosis and a cohort of individuals with biopsy-proven UIP,
although the CT findings of asbestosis were strikingly different
from NSIP; the quality of fibrosis was coarser, there was a lower
proportion of ground-glass opacification, and a higher likelihood
of a basal and subpleural distribution
180
.
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SUGGESTED FURTHER READING
Books/book chapters
Hansell D M, Armstrong P, Lynch D A, McAdams H P (eds) 2005
Basic HRCT patterns of lung disease. Drug- and radiation-induced
Ch19-F0163.indd 377 6/28/07 3:38:07 PM
diseases of the lung. Idiopathic interstitial pneumonias and
immunologic diseases of the lung. Miscellaneous diffuse lung
diseases. In: Hansell DM (ed) Imaging of Diseases of the Chest, 4th
edn. Philadelphia, Elsevier Mosby, pp 143181, 485533, 535629,
631709
Franquet T 2005 High resolution computed tomography of the lungs.
In: Wells A U, Denton C P (eds) Handbook of systemic autoimmune
diseases, vol 2. Elsevier BV
Lynch D A, Newell J D, Lee J S (eds) 1999 Imaging of diffuse lung disease.
Elsevier, Ontario
Schwarz M I, King Jr T E (eds) 2003 Interstitial lung disease, 4th edn. BC
Decker Inc, Ontario
Webb W R, Mller N L, Naidich D P (eds) 2001 High-resolution CT of the
lung, 3rd edn. Lippincott-Raven, Philadelphia
Reviews/papers
Akira M 2002 High-resolution CT in the imaging of occupational and
environmental disease. Radiol Clin North Am 40: 4359
American Thoracic Society/European Respiratory Society 2002 International
Multidisciplinary Consensus Classication of the Idiopathic Interstitial
Pneumonias. Am J Respir Crit Care Med 165: 277304
Cleverley JR, Screaton NJ, Hiorns MP et al 2002 Drug-induced lung disease:
high-resolution CT and histological ndings. Clin Radiol 57: 292299
Kim J S, Lynch D A 2002 Imaging of non-malignant occupational lung
disease. J Thoracic Imaging 17: 238260
Lynch D A, Travis W D, Mller N L et al 2005 Idiopathic interstitial
pneumonias: CT features. Radiology 236: 1021
Myers J L, Limper A H, Swensen S J 2003 Drug-induced lung disease: A
pragmatic classication incorporating HRCT appearances. Semin Respir
Crit Care Med 24: 445453
Ch19-F0163.indd 378 6/28/07 3:38:08 PM

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