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Pulmonary aspergillosis
M.L. Chabi a,, A. Goracci b, N. Roche c, A. Paugam d,
A. Lupo e, M.P. Revel f
a
Service de radiologie polyvalente et oncologique, groupe hospitalier de la Piti-Salptrire
Charles-Foix, APHP, 83, boulevard de lHpital, 75651 Paris cedex 13, France
b
Dpartement dimagerie mdicale, service de radiologie, IRCCS Istituto Clinico Humanitas,
Via Manzoni 56, 20089 Rozzano, Italy
c
Service de pneumologie, hpital dinstruction des armes du Val-de-Grce, 74, boulevard de
Port-Royal, 75230 Paris cedex 05, France
d
Service de parasitologie-mycologie-mdecine tropicale, hpital Cochin, 27, rue du
Faubourg-Saint-Jacques, 75679 Paris cedex 14, France
e
Service danatomie et de cytologie pathologiques, hpital Cochin, 27, rue du
Faubourg-Saint-Jacques, 75679 Paris cedex 14, France
f
Service de radiologie A, hpital Cochin, 27, rue du Faubourg-Saint-Jacques, 75679 Paris
cedex 14, France
KEYWORDS Abstract Aspergillosis is a mycotic disease usually caused by Aspergillus fumigatus, a sapro-
Aspergillosis; phytic and ubiquitous airborne fungus. Aspergillus-related lung diseases are traditionally
Lung infections; classied into four different forms, whose occurrence depends on the immunologic status of the
Computed host and the existence of an underlying lung disease. Allergic broncho-pulmonary aspergillo-
tomography sis (ABPA) affects patients with asthma or cystic brosis. Saprophytic infection (aspergilloma)
occurs in patients with abnormal airways (chronic obstructive pulmonary disease, bronchiec-
tasis, cystic brosis) or chronic lung cavities. Chronic necrotizing aspergillosis (semi-invasive
form) is described in patients with chronic lung pathology or mild immunodeciency. Invasive
aspergillosis (angio-invasive or broncho-invasive forms) occurs in severely immuno-compromised
patients. Knowledge of the various radiological patterns for each form, as well as the corre-
sponding associated immune disorders and/or underlying lung diseases, helps early recognition
and accurate diagnosis.
2015 ditions franc aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
Abbreviations: A. fumigatus, Aspergillus fumigatus; ABPA, allergic broncho-pulmonary aspergillosis; COPD, chronic obstructive pul-
monary disease; CF, cystic brosis; HRCT, high-resolution computed tomography; CAN, chronic necrotizing aspergillosis; BAL, bronchoalveolar
lavage.
Corresponding author.
http://dx.doi.org/10.1016/j.diii.2015.01.005
2211-5684/ 2015 ditions franc
aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Chabi ML, et al. Pulmonary aspergillosis. Diagnostic and Interventional Imaging (2015),
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Figure 1. A 30-year-old asthmatic man with productive cough and dyspnea. Axial (a) and coronal (b, c) CT images show bilateral subseg-
mental bronchectasis lled with mucus (arrows). These images are called nger-in-glove opacities and are consistent with ABPA diagnosis.
On mediastinal windowing (d), mucus plugs are hyperdense (102 HU); e: coronal CT image after treatment. Mucus plugging has disappeared
whereas bronchectasis persist (head arrow).
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Figure 3. Coronal (a) and sagittal (b) CT images showing pathognomonic aspergilloma: mass within a lung cavity surrounded by air, which
is called the air crescent sign. Aspergilloma cannot be diagnosed on chest X ray (c), because the air crescent sign is not visible.
Figure 4. a: tuberculosis sequelae in pulmonary apices on chest X ray; b and c: CT images demonstrate a fungus ball within a pulmonary
cavity in the left lower lung apex, which is pathognomonic for aspergilloma. Chest X ray only demonstrates bilateral opacities with retraction
of both lung apices.
Figure 5. a: axial CT image showing a broncho-pleural stula complicating left upper lobe resection; b: CT scan performed 1 year later
shows thickening of the cavity walls; c: two years later, a fungus ball with air crescent sign is demonstrated. All chronic lung cavities can
be colonized by Aspergillus and develop aspergilloma. The rst sign of the saprophytic infection is usually a thickening of the cavity walls.
the main complication. Aspergillomas remain stable in the Chronic necrotizing aspergillosis (former
majority of cases, but can also decrease in size or even spon- semi-invasive form)
taneously resolve in about 10% of cases. Aspergillomas more
rarely show size increase [10]. Chronic necrotizing aspergillosis (CNA) is a rare and
Other causes of air crescent sign include angio- poorly understood form of aspergillosis, which can
invasive and chronic necrotizing aspergillosis. In these cases, mimic other chronic pulmonary infections (tuberculosis,
there are no pre-existing cavities; radiological manifesta- histoplasmosis. . .). Its recognition and diagnosis are often
tions appear within a few days in the angio-invasive forms delayed.
and within several weeks or months in the chronic necrotiz- CNA is a locally invasive disease that occurs in patients
ing forms [11] (Fig. 6). with chronic lung pathology [12] or mild immunodeciency
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Figure 6. Air crescent sign. Axial CT images of 3 different patients, showing a lung parenchyma opacity surrounded by an air crescent
sign. This feature is not specic of saprophytic infection (aspergilloma; a), it can be seen in semi-invasive aspergillosis (chronic necrotizing
aspergillosis; b) and in invasive aspergillosis (c). In the latter two cases (b and c), there was not any pre-existing lung cavity; the focal area
of necrosis is due to fungal invasion.
such as long-standing steroid therapy, diabetes, renal fail- Invasive aspergillosis: angio-invasive and
ure, COPD. . . airway-invasive forms
Radiologically, CNA is characterized by pulmonary
consolidations, usually involving the upper lobes, with Invasive pulmonary aspergillosis is an aggressive disease due
bronchiectasis. The consolidation progresses with time to to the invasion of the bronchial wall and the accompany-
cavitation over weeks to months [12,13]. ing arterioles by the hyphae. This form primarily occurs in
As indicated earlier, a fungal ball with air crescent severely immuno-compromised patients, especially patients
sign may develop in CNA as a secondary phenomenon due with neutropenia due to allogenic bone marrow transplan-
to the parenchymal destruction by the fungus [11] (Fig. 7). tation or chemotherapy for acute leukemia [15], but also
In 2003, Denning et al. proposed diagnostic criteria for patients who received solid-organ transplantation, espe-
CNA [14] (Boxed text). cially lung transplantation [16].
The most important risk factor is neutropenia. The risk of
invasive aspergillosis is strongly correlated with the duration
and degree of neutropenia [11].
Symptoms are non-specic and usually mimic bron-
Boxed text: Dennings criteria [14] for chronic
chopneumonia, but also include pleuritic chest pain and
necrotizing aspergillosis.
Chronic pulmonary or systemic symptoms (duration haemoptysis [11].
Invasive aspergillosis is a diagnostic and therapeutic chal-
3 months) compatible with CPA, including at least 1
lenge due to the high morbidity and mortality.
of the following symptoms: weight loss, productive
There are two sub-categories of invasive aspergillosis,
cough, or haemoptysis.
Cavitary pulmonary lesion with evidence of the airway-invasive form and the angio-invasive form.
The airway-invasive form accounts for 15 to 30% of
paracavitary inltrates, new cavity formation,
invasive aspergillosis, and is dened by the presence of
or expansion of cavity size over time.
Either positive result of serum Aspergillus precipitins Aspergillus deep to the basal membrane of the bronchi [17].
Radiologically, it can mimic bronchiolitis with patchy cen-
test or isolation of Aspergillus spp. from pulmonary
trilobular nodules with tree-in-bud appearance, similar to
or pleural cavity.
Elevated levels of inammatory markers (C- those seen in endobronchial spread of tuberculosis. A bron-
chopneumonia presentation is common, with conuence of
reactive protein, plasma viscosity, or erythrocyte
peribronchial consolidations, similar to bacterial bronchop-
sedimentation rate).
Exclusion of other pulmonary pathogens, by results neumonia [8,17] (Fig. 8).
In rare cases, the fungal infection is entirely or pre-
of appropriate cultures and serological tests, that
dominantly conned to the tracheobronchial tree. Acute
are associated with similar disease presentation,
Aspergillus tracheobronchitis usually occurs in lung trans-
including mycobacteria and endemic fungi
plantation recipients [16]. Radiologically, it may appear as
(especially Coccidioides immitis and Histoplasma
tracheal or bronchial irregular wall thickening, with occa-
capsulatum).
No overt immunocompromising conditions (e.g., sionally high attenuation aspect due to ability of Aspergillus
to x calcium. Atelectasis or endobronchial masses have
HIV infection, leukemia, and chronic granulomatous
even been described. However, most of the time, there are
disease).
no detectable radiological abnormalities [8,18].
Please cite this article in press as: Chabi ML, et al. Pulmonary aspergillosis. Diagnostic and Interventional Imaging (2015),
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Figure 7. Chronic necrotizing aspergillosis; a and b: axial CT images showing a right upper lobe consolidation with bronchectasis; c and
d: correspond to CT images of the same patient 5 months (c) and 7 months (d) latter. Progressive cavitation of the initial consolidation is
seen; e and f: are chest radiographs corresponding to CT scans images c and d. They show a progressive cavitation of the right upper lobe.
Comparison with the rst available chest X ray is crucial, to detect the progressive cavitation because changes occur slowly, which is the
source of delayed diagnosis.
The angio-invasive form is histologically characterized consolidation, similar to those seen in pulmonary infarcts
by the invasion and occlusion of small to medium-size complicating pulmonary embolism, correspond to haemor-
pulmonary arteries by fungal hyphae [8]. Typical CT nd- rhagic infarcts.
ings [8,17] consist in larges nodules surrounded by ground Differential diagnoses of halo sign in neu-
glass attenuation, which is called the halo sign. Nod- tropenic patients include infections due to Candida,
ules are due to coagulation necrosis, whereas the halo Herpes simplex and cytomegalovirus, Wegener gran-
of ground glass is due to surrounding alveolar haemorr- ulomatosis, haemorrhagic metastases and Kaposi
hage [19] (Fig. 9). Other ndings are pleura-based areas of sarcoma.
Figure 8. Broncho-invasive aspergillosis in a 50-year-old man with allogenic bone marrow transplantation. Axial CT images (a, b) showing
bilateral lobular consolidation with centrilobular nodules in the left lower lobe (b). These features are non-specic of fungal infection and
could also be due to bacterial bronchopneumonia.
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Pulmonary aspergillosis 7
Figure 10. a: axial CT image in a leukemia patient showing a right upper lobe nodule surrounded by mild ground glass attenuation; b and
c: axial and coronal CT images acquired 3 weeks later showing an air crescent sign surrounding a focal opacity. This feature is similar to
aspergilloma but is relevant to a necrotic lung fragment in an angio-invasive form of aspergillosis.
Please cite this article in press as: Chabi ML, et al. Pulmonary aspergillosis. Diagnostic and Interventional Imaging (2015),
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8 M.L. Chabi et al.
Further, as for serum, Aspergillus antigens (galactoman- brosis state of the art: Cystic Fibrosis Foundation Consensus
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[21]. [7] Knutsen AP, Slavin RG. Allergic bronchopulmonary aspergillo-
sis in asthma and cystic brosis. Clin Dev Immunol
2011;2011:843763.
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[15] Bommart S, Bourdin A, Makinson A, Durand G, Micheau
Disclosure of interest A, Monnin-Bares V, et al. Infectious chest complications
in haematological malignancies. Diagn Interv Imaging
2013;94(2):193201.
The authors declare that they have no conicts of interest
[16] Hemmert C, Ohana M, Jeung MY, Labani A, Dhar A, Kessler R,
concerning this article. et al. Imaging of lung transplant complications. Diagn Interv
Imaging 2014;95(4):399409.
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Please cite this article in press as: Chabi ML, et al. Pulmonary aspergillosis. Diagnostic and Interventional Imaging (2015),
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