Expert Review of Respiratory Medicine

ISSN: 1747-6348 (Print) 1747-6356 (Online) Journal homepage: https://www.tandfonline.com/loi/ierx20

The place of high-resolution computed

tomography imaging in the investigation of
interstitial lung disease

Florence Jeny, Pierre-Yves Brillet, Young-Wouk Kim, Olivia Freynet, Hilario

Nunes & Dominique Valeyre

To cite this article: Florence Jeny, Pierre-Yves Brillet, Young-Wouk Kim, Olivia Freynet, Hilario
Nunes & Dominique Valeyre (2019) The place of high-resolution computed tomography imaging in
the investigation of interstitial lung disease, Expert Review of Respiratory Medicine, 13:1, 79-94,
DOI: 10.1080/17476348.2019.1556639

To link to this article: https://doi.org/10.1080/17476348.2019.1556639

Accepted author version posted online: 05

Dec 2018.
Published online: 12 Dec 2018.

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EXPERT REVIEW OF RESPIRATORY MEDICINE
2019, VOL. 13, NO. 1, 79–94
https://doi.org/10.1080/17476348.2019.1556639

REVIEW

The place of high-resolution computed tomography imaging in the investigation of

interstitial lung disease
Florence Jenya,b, Pierre-Yves Brilletb,c, Young-Wouk Kimc, Olivia Freynetb, Hilario Nunesa,b and Dominique Valeyrea,b
a
Université Paris 13, EA2363 “Hypoxie & Poumon”, Sorbonne-Paris-Cité, Bobigny, France; bService de pneumologie, hôpital Avicenne, Bobigny,
France; cService de radiologie, hôpital Avicenne, Bobigny, France

ABSTRACT ARTICLE HISTORY

Introduction: High-resolution computed tomography (HRCT) has revolutionized the diagnosis, prog- Received 21 May 2018
nosis and in some cases the prediction of therapeutic response in interstitial lung disease (ILD). HRCT Accepted 4 December 2018
represents an essential second step to a patient’s clinical history, before considering any other KEYWORDS
investigation, including lung biopsy. Automated quantification;
Areas covered: This review describes the current place of HRCT in the diagnosis, prognosis and high-resolution computed
monitoring of ILD. It also lists some perspectives for the near future. tomography; interstitial lung
Expert commentary: Since the 1980s, HRCT and its interpretation have improved, the diagnosis value disease
of patterns, and the integration of bio-clinical elements to HRCT have been better standardized. The
interobserver agreement has been investigated, allowing a better use of some limits in the interpreta-
tion of various signs. It not only takes into account one particular predominant sign, but the combina-
tion of patterns and the distribution of findings. Thanks to HRCT, the range of diagnoses and their
probability are more accurately identified. The contribution of HRCT has been optimized during the
multidisciplinary discussion that a difficult diagnosis calls for. HRCT quantification of the extent of
diffuse lung disease becomes possible and is linked to prognosis. In the future, artificial intelligence may
significantly modify the practice of radiology.

1. Introduction ‘computed tomography (CT),’ ‘imaging’ ‘diagnosis,’ ‘prognosis’

Chronic interstitial Lung Diseases (ILD) are multiple, with differ-
ent therapeutic and prognosis issues. The superiority of chest
high-resolution computed tomography (HRCT) over conven-
tional radiography has considerably improved the diagnosis of
ILD, which was previously often centered mainly on surgical
lung histopathological findings. Now, thanks to HRCT, in addi-
tion to clinical findings, the diagnosis of idiopathic pulmonary
fibrosis (IPF), respiratory bronchiolitis-related interstitial lung
disease (RB-ILD), pulmonary Langerhans cell histiocytosis
(PLCH), and of some other diseases can be made without
surgery in a significant proportion of patients. Methods of read-
ing and analyzing HRCT have progressed and are better stan-
dardized. Radiologists, thanks to HRCT, have become key actors,
alongside clinicians and pathologists, in multidisciplinary dis-
cussion (MDD). HRCT also allows a quantification of the extent
of lung disease, helping predict prognosis of the disease and to
monitor its evolution. In this review we discuss the place of
HRCT in chronic ILD for the diagnosis investigation and in MDD,
if required, for ILD’s prognostic and severity factors identifica-
tion, prediction of therapeutic response, and its monitoring.
2. Methods
We have used PubMed and MeSH software for original articles
and reviews about ‘the place of HRCT imaging in ILD,’ pub-
lished in English, with the following combining terms:
‘serial CT,’ ‘monitoring,’ ‘follow-up’ ‘ILD,’ ‘lung fibrosis,’ ‘idio-
pathic interstitial pneumonia (IIP)’ ‘idiopathic pulmonary fibro-
sis (IPF),’ ‘connective tissue associated interstitial lung disease
(CTD-ILD),’ ‘sarcoidosis,’ ‘hypersensitivity pneumonitis (HP),’
and ‘occupational ILD.’ We have selected articles published
in the last 10 years but without excluding earlier ones, espe-
cially if they were highly cited articles or if they reported
unique or high-quality clinical trials.
3. Technical issues, and interpretation pitfalls
3.1. Acquisition
The interpretation of lung parenchyma requires optimal HRCT
protocols and techniques. Acquisition should be performed
without contrast agent (which can simulate ground glass opa-
cities (GGO)), with infra-millimetric section images (0.5–1 mm)
reconstructed at ≤2 cm intervals [1].
HRCT images should be obtained at full inspiration and with-
out respiratory motion [1]. Concerning radiation, modern HRCT
and protocols have resulted in substantial reduction in dose
delivery without lost reliability. With noncontiguous CT there is
a loss of information, notably for serial CT. Acceptable CT scans
can be obtained with a reduced dose technique by using auto-
matic tube current modulation, optimization of tube potential
beam shaping filters or dynamic z-axis collimators [2,3]. In a
study by Pontana et al, in 55 patients with systemic sclerosis

CONTACT Florence Jeny florence.jeny-ext@aphp.fr Service de pneumologie, hôpital Avicenne, 125 rue de Stalingrad, Bobigny 93009, France
© 2018 Informa UK Limited, trading as Taylor & Francis Group
80 F. JENY ET AL.
related ILD (Ssc-ILD) [4] reconstruction algorithms, such as itera-
tive algorithms, reduced the dose by 60%, without lowering the
quality of the detection of subtle interstitial abnormalities com-
pared to standard dose CT images. However, low dose CT is not
recommended for ILD diagnosis process.
A complementary sequential technique, providing 10–20
images after a full inspiration is useful for patients having
difficulty holding apnea [5]. Noncontiguous acquisition is
also used to reduce radiation exposure in young patients, or
during expiratory or prone position sequences [2].
Expiratory acquisition can be performed in case of mosaic
attenuation pattern to search air trapping due to small air-
ways obstruction. A prone position acquisition can eliminate
gravity dependent atelectasis in the posterior basal segments
of the lung, which may simulate early signs of an infiltrative
disease [6]; it also improved overall interobserver agreement
of usual interstitial pneumonia (UIP) classification [7].
The administration of a contrast agent is not recommended
in routine but is convenient when identifying a lymphadeno-
pathy as well as in patients with vascular complications,
including pulmonary hypertension; when acute exacerbation
is suspected it is useful to rule out a pulmonary embolism.
3.2. Reconstruction
Multidetector helical CT techniques are used to obtain a volu-
metric image of the entire thorax and other axis images (e.g.
frontal, sagittal). It helps to determine topography, and screen all
associated patterns. For the Fleischner Society, volumetric acquisi-
tion is to be preferred to noncontiguous imaging [3]. Also, post-
processing techniques such as maximum intensity projection
(MIP) and minimum intensity projection (MinIP) are very conveni-
ent. MIP allows the study of micronodules distribution and can
differentiate mosaic attenuation from mosaic perfusion thanks to
the study of vessel size [8]. MinIP makes possible the detection of
low-density structures in a given volume and is the optimal tool
for detection, localization, and quantification of GGO and linear
attenuation patterns [8]. Notably, it helps to differentiate honey-
combing from bronchiectasis, especially in cine mode that shows
the running of bronchus and bronchioles directly [9].
3.3. Visualization
Analysis of GGO needs perfect lighting conditions and strong
adjustment on the diagnostic screens. Bone windows help in
detecting calcifications in the different thoracic organs.
Recently, diffuse pulmonary ossification (defined by 10 or
more dense nodules) has been shown to be common and
significantly more present in patients with IPF (28%) than in
those with other fibrosing ILDs (8%) [10].
4. Place of HRCT in ILD diagnosis
4.1. Superiority of HRCT over radiography and practical
consequences
With the introduction of CT in the early of the 1980s, many
studies compared its diagnosis accuracy in ILDs to chest radio-
graphy [11]. Even if chest radiography is helpful in detecting
ILDs, due to its cost, low irradiation dose, and availability, this
test can be normal in 10–40% of patients with biopsy proven
ILDs [12,13], and can also lead to a false positive diagnosis
because of superimposed images. Mathieson et al. [14] com-
pared the accuracy of chest radiography to CT in the prediction
of specific diagnosis in 118 patients with ILDs. A confident
diagnostic was achieved in 23% for radiography versus 49%
for CT. Similar results were found by Grenier et al. especially in
patients presenting pulmonary PLCH or sarcoidosis. Also,
authors evidenced a better interobserver agreement for CT
than for chest radiography [15]. The diagnosis of silicosis [14],
lymphangitic carcinomatosis [14] UIP [14,16], alveolar lipopro-
teinosis [16], HP [16], and pulmonary lymphangioleiomyomato-
sis [16] benefited from the superiority of CT over radiography.
Interestingly, as CT is usually performed after gathering clinical
and radiographic findings, the extra contribution of CT on top
of clinical and radiographic findings have been evidenced in
1994 by Grenier et al. [17]. The confidence level for specific
diagnoses with HRCT was illustrated by Aziz et al. who demon-
strated that the need for surgical lung biopsy in patients diag-
nosed with idiopathic fibrosis, decreased from 26.8% to 11.2%
after obtaining HRCT results [18]. HRCT is also helpful in guiding
biopsy [19] in several disease such as sarcoidosis [20], and may
be an important diagnostic criterion for the inclusion of
patients in treatment trials, particularly in IPF trials [21,22].
4.2. Role in incidental diagnostic of ILDs
ILDs may be unintentionally discovered on HRCT, during
cancer screening or on lower lung sections during abdom-
inal HRCT for example. Recently, several studies have been
conducted on Interstitial Lung Abnormalities (ILA) defined
by the presence of specific densities on HRCT commonly
associated with ILDs or pulmonary fibrosis that have been
identified in research participants without a clinical diagno-
sis of ILD [23,24]. In lung cancer screening populations, the
prevalence of ILA cases reported was 9.7%–22.8% [25–27] or
7% in a cohort from the Framingham Heart Study [24].
Patients with ILA are more likely to present respiratory
symptoms, physiologic decrements, and an increased risk
of death [24,28]; ILA progression is also associated with
greater forced vital capacity (FVC) decline and risk of
death [29]. ILA shares similarities with IPF. ILA’s prevalence
increases with age, smoking status, and has been associated
with the MUC5B promoter polymorphism [24]. Importantly,
biopsy of subpleural areas of some ILAs’ patients corre-
sponded to UIP or other histopathologic findings that are
present in UIP [30], suggesting that screening some ILAs
might be a way to detect early forms of IPF. However,
because of the heterogeneity of ILA, it is essential to
define it accurately and by consensus [31]. Subclinical ILDs
were also evaluated quantitatively on HRCT by High
Attenuation Areas (HAA) [32] defined by the percentage of
lung voxels between −600 and −250 Hounsfield Units (HU).
Interestingly, HAA was associated with biomarkers of inflam-
mation and extracellular matrix remodeling, reduced lung
function, higher risk of death [32] and occupational or
pollution exposures [33,34].
 EXPERT REVIEW OF RESPIRATORY MEDICINE 81

4.3. Current place of HRCT in the diagnosis of ILDs
When ILDs are suspected, radiologists should follow certain
guidelines to achieve a diagnosis, or at least propose a gamut
of diagnosis hypotheses (Figure 1): (i) the different technical
issues should be checked in order to obtain the optimal chest
HRCT and avoid interpretation pitfalls (see supra), (ii) then the
radiologists should identify the elementary lung lesions, their
distribution and search for extrapulmonary associated features
(e.g. pleural, mediastinal, esophageal, cardiac, or extra-thoracic
abnormalities), (iii) the radiologist should therefore individua-
lize either a diagnosis or a pattern allowing hypotheses with
different degrees of confidence [1,3,35]; this step being illu-
strated in IPF, for which the CT presentation has been recently
reclassified into four radiological patterns [36]: UIP, probable
UIP, indeterminate, and alternate diagnosis, (iv) eventually,
these radiological findings are confronted to epidemiological
characteristics (age, gender, familial history, smoking, occupa-
tional, and environmental exposures), clinical history and
examination (particularly the presence of extrapulmonary
involvement suggesting connective tissue disease, sarcoidosis
or any other specific condition), blood and often broncho-
alveolar lavage (BAL), biological data and histopathological
data if available and a conclusion may warrant, if necessary,
a MDD.
4.3.1. Elementary lesions and their distribution in the lung
The elementary lesions are (Table 1): nodular, linear, increased
pulmonary attenuation (GGO, consolidations), reduced pul-
monary attenuation (cyst, cyst like lesion…). The presence of
fibrosis is defined by the presence of one of the following
features: honeycombing, traction bronchiectasis, or existence
of volume loss, related to reticular abnormalities. The distribu-
tion must be studied according to three axes: cranio-caudal,
anteroposterior and axial (peripheral or central), and according
to secondary pulmonary lobule, the lesions may be centrolob-
ular, centroperilobular, pan lobular or of aleatory distribution
[6]. Lesions may or may not be symmetrical. Associated fea-
tures should be searched at the bronchial or bronchiolar,
pleural, vascular, or lymph node level. It is particularly impor-
tant to identify certain features, for their diagnostic and prog-
nostic values. Traction bronchiectasis are indicative of lung
fibrosis and are associated with poor prognosis. A more cen-
tral distribution of lesions suggests diseases like sarcoidosis,
while more peripheral lesions are seen in UIP (Figure 2). In
conclusion, the predominant lesion must be evidenced and/or

Figure 1. Algorithm representing the current place of HRCT in the diagnosis of ILD.
Abbreviations: LAM: Lymphangioleiomyomatosis; PHCL: Pulmonary Langherans Cell Histiocytosis; ILD: Interstitial Lung disease; HRCT: High resolution computed tomography; IPF: idiopathic
Pulmonary Fibrosis, UIP: usual interstitial pneumonia; NSIP: non specific interstitial pneumonia; HP: hypersensitivity pneumonitis, MDD multidisciplinary discussion, OP organizing
pneumonia, PPFE: pleuroparenchymal fibrosis Elastosis. *Regarding age sex smoking status **confirmation with a compatible radio clinical presentation, biological or non surgical cyto-
histopathology sample. *** The answer to that questions will integrate imaging with the demographical, clinical, biological and BAL findings and evolution trend of the disease if known.§
occupational disease, hypersensitivity pneumonitis, drug-induced lung disease, systemic autoimmune disease or other systemic disease (sarcoidosis, immune-system dysregulation), genetic
syndromes with familial ILD, lung cancer or pulmonary edema. # diagnosis of non fibrosing ILD are numerous, will depend of the MDD, and if necessary from the surgical biopsy. + with the
result or not of the surgical lung biopsy
82 F. JENY ET AL.

Table 1. Pulmonary parenchymal elementary lesions according to [6].

Nodular lesions Focal areas of increased attenuation, usually with discrete borders, with diameter of
- <3 mm: micronodules
- ≤3 cm: nodules
- >3 cm: mass
For anatomic distributions: centrilobular, lymphatic, random or cluster*.
Linear opacities - Reticular pattern: collection of innumerable small linear opacities that, by summation, produce an appearance resembling a net
- Interlobular septal thickening: highlight the margin of secondary pulmonary lobules. Extension from and perpendicular to the
pleural
- Intra-lobular lines: fine linear opacities in a lobule. When numerous, they may appear as a fine reticular pattern
- Parenchymal band: linear opacity, usually 1–3 mm thick and up to 5 cm long that usually extends to the visceral pleura
- Subpleural curvilinear line: thin curvilinear opacity, 1–3 mm in thickness, lying less than 1 cm from and parallel to the pleural
surface
Increased pulmonary The increased lung attenuation pattern develops when the density of the lung parenchyma increases
attenuation
- Ground-glass opacity: hazy increased opacity of lung, with preservation of bronchial and vascular margins
- Consolidation: homogeneous increase in pulmonary parenchymal attenuation that obscures the margins of vessels and airway
walls
Decrease pulmonary The decreased lung attenuation pattern develops when the density of the lung parenchyma decreases.
attenuation
- Cyst: round parenchymal low-attenuating area with a well-defined interface with normal lung.
- Honeycombing: subpleural regions of clustered cysts, usually stacked together in 1 or more layers.
- Emphysema: focal areas or regions of low attenuation, usually without visible walls. Bulla: rounded focal lucency or area of
decreased attenuation, 1 cm or more in diameter, bounded by a thin wall
- Mosaic attenuation pattern: This pattern appears as patchwork of regions of differing attenuation that may represent) patchy
interstitial disease, obliterative small- airways disease, or occlusive vascular disease.
* rounded or long clusters of multiple small nodules in the pulmonary parenchyma that are close to each other but not confluent.

Figure 2. HRCT images illustrating the different type of traction bronchiectasis: (a) Usual interstitial pneumonia pattern in patient with IPF, with bilateral peripheral
honeycombing reticulation and distal traction bronchiectasis. (b) Fibrotic sarcoidosis, with posterior retraction of the hilum, bronchial distortions mainly central in
the upper zones. (c) Patient with idiopathic non specific interstitial pneumonia with ground-glass opacification associated to proximal traction bronchiectasis.

a pattern must be recognized regarding both pulmonary and
extra-pulmonary abnormalities.
4.3.2. Scenarios according to HRCT diagnosis performance
When hypotheses have been considered, the radiologists
should follow the principle of ‘keeping it simple’ and consider
the most frequent diagnoses in ILDs: lung cancer, left ventricu-
lar failure pulmonary edema, IPF and sarcoidosis. Radiologists
are confronted to two situations (i) HRCT suggests a diagnosis
with a high probability in a compatible clinical context, and
therefore a confirmation of this diagnosis is needed, (ii) HRCT
does not allow consideration of a specific disease and the
context appears essential for managing the diagnosis process.
(i) HRCT suggests a diagnosis with a high level of prob-
ability: this diagnosis makes investigations important for
definitely confirming it: a surgical lung biopsy is not
warranted. Also, HRCT can help in guiding non surgical

biopsy, and per-bronchoscopic sampling in order to
confirm the disease and to exclude definitely other
causes, such neoplastic or infectious diseases.
A diagnosis of lymphangioleiomyomatosis [37] can be estab-
lished in a young to middle-aged females presenting with wor-
sening dyspnoea and/or pneumothorax/chylothorax without
features suggestive of other cystic lung disease; numerous, bilat-
eral, uniform, round, thin-walled cysts are found in a diffuse
distribution on chest HRCT (Figure 3) associated with lymphan-
gioleiomyomas or renal angiomyolipomas. Another example is
the lipoid pneumonia for which negative densities with values
between −150 and −30HU inside areas of consolidation are
highly suggestive of intrapulmonary fat, and consistent with
the diagnosis, especially when associated with a history of expo-
sure to oil [38]. Pulmonary alveolar microlithiasis can be diag-
nosed definitely thanks to HRCT in patients with a familial
context, in the presence of dense homogenous parenchymal
opacification in bone window, and a ‘crazy paving’ pattern with
calcifications along the interlobular septa is pathognomonic [39].
Another similar situation is the presence of a “UIP pattern” which
allows, in an appropriate clinical setting, and in absence of any
cause and systemic manifestations, a diagnosis of IPF [1].
Eventually, the diagnosis of RB-ILD can be obtained with HRCT
in smokers without exposure to organic antigenic air contami-
nants [40].
In sarcoidosis, diffuse micronodules with a typical perilym-
phatic distribution, upper lobe predominance and/or bilateral
symmetrical hilar lymphnode enlargement predicts with a con-
fidence >95% the diagnosis of sarcoidosis in 80% of patients
[17,41,42]. In the rare cases where predominant elementary
lesions are unusually predominant like GGO or multiple con-
solidations, the presence, in the background, of typical perilym-
phatic micronodules, usually visible at close examination or
linked to a typical lymphadenopathy, allow, in most cases, a
high probability diagnosis of sarcoidosis (Figure 4), as shown in
two studies based on logical data analysis [43,44]. The presence
of posterior retraction of the hila (Figure 2), marked perihilar
bronchovascular distortion, and bilateral calcified hilar and
mediastinal lymphnodes, also makes the fibrotic form of this
Figure 3. HRCT image of a middle aged woman with lymphangioleiomyoma-
tosis presenting with numerous, bilateral, uniform, round, thin-walled cysts with
a diffuse distribution.
EXPERT REVIEW OF RESPIRATORY MEDICINE 83
disease in patients without exposure to silica virtually quasi-
pathognomonic [11].
HRCT findings are also often highly suggestive in PLCH.
Nodules are seen in early stages and tend to evolve into cavities
with disease progression while cysts are seen in later stages
[45]. Cysts are usually thin-walled, ranging in size from 1 to
20 mm, and may coalesce to form irregular or bizarre shapes.
Abnormalities are predominantly located in the upper and
middle lung fields with lung bases relatively spared [46]. HRCT
has significantly reduced the need for surgical lung biopsy,
particularly when combinations of nodular and cystic changes
are present in an appropriate clinical setting (young adult
smoker) [46]. Bronchoscopy with transbronchial lung biopsy
lead to diagnosis in about 30% of cases; it allows the exclusion
of other diagnoses that mimic PLCH [47]. Pulmonary lymphan-
gitic carcinomatosis [48], pulmonary alveolar lipoproteinosis
(Figure 5) [49] and subacute hypersensitivity pneumonitis [50]
may also be very typical on HRCT.
Recently, two studies have evaluated the performance of
HRCT in order to have a diagnosis among multiple possible
chronic diffuse ILDs presenting with predominant GGO pat-
tern or with chronic multifocal consolidation patterns by using
logical analysis of data (LAD) [43,44]. LAD is a mathematical
method based on techniques of optimization and logic. This
big data technique allows the identification, from a large set of
data, of the informative combinations of attributes which
provides the grounds for diagnosis. These two papers have
demonstrated that the diagnostic performance of HRCT was
high, including the identification of new specific patterns.
Moreover, the specificity of the diagnoses was increased by
adding very little clinical data.
(ii) HRCT does not permit a specific diagnosis: When radi-
ological signs or patterns are not specific to any disease
or are compatible with several diseases, it is necessary
to integrate imaging with the demographical, clinical,
biological, and BAL findings, as well as the evolution
trend of the disease if known. A MDD associating a
pulmonologist, a radiologist, and a pathologist is held
to determine whether a pulmonary biopsy is required
or, if not, whether a diagnosis based on disease beha-
vior can be made, or if a provisional diagnosis is chosen.
This process is done in order to eliminate or confirm
differential diagnoses and, in case of cause not found, to
classify the disease according to the statement of
Idiopathic interstitial pneumonias established in 2002
[51], revised in 2013 by the ATS/ERS [40]. This diagnosis
process [11], should be centered around the important
question: ‘Is it an idiopathic pulmonary fibrosis or not ?’,
since it is one of the most frequent [52] and the most
severe ILD that calls for treatment with anti-fibrotic
drugs [1,36].
4.4. How integrate HRCT in multidisciplinary discussion
4.4.1. Multidisciplinary discussion
Before the joint statement of ATS/ERS [51], the gold standard
for the diagnosis of ILD was lung histopathology. The revised
84 F. JENY ET AL.
Figure 4. HRCT images showing a typical pattern of sarcoidosis associating bilateral consolidations in the upper zones (a) typical perilymphatic micronodules (c) and
mediastino hilar calcified lymphadenopathies (b,d).
Figure 5. HRCT image of a patient with auto-immune pulmonary alveolar
proteinosis showing a « crazy paving » pattern defined by the association of
reticulations superimposed on ground glass opacifications and a geographic
distribution (juxtaposition of healthy and sick zones).
statement [40] recommended the adoption of a ‘dynamic
integrated approach’ using MDD with pulmonologists, radiol-
ogists and pathologists after lung biopsy [40]. Now, a confi-
dent diagnosis can be retained for IPF in a compatible clinical
setting and a typical UIP pattern at HRCT. In the absence of a
UIP pattern, a surgical lung biopsy is usually recommended
when reasonably feasible, but It should be pointed out that a
definite pathological diagnosis of IPF, once considered the
gold standard, could be overridden by an incompatible radi-
ological presentation [53]. Histopathologists modified their
diagnosis in almost 20% of cases when clinical and HRCT
data were provided [54] and more recently MDD has changed
the original histological diagnoses in 30% of cases [55].
Histopathological diagnosis of ILD couldn’t remain the gold
standard, firstly because of the morbimortality related to sur-
gical lung biopsy [56] and secondly because it did not guar-
antee a diagnosis. In the study of Nicholson et al. diagnoses
made with 100% confidence were achieved for only 39% and
the interobserver variation between pathologists was conse-
quent [57]. Recently, Mäkelaä et al. showed that even in the
well-defined cohort of IPF patients according to the ATS/ERS
from 2011 statement, a high level of interobserver variability
between pathologists persisted highlighting the importance
of MDD and perhaps a need for reassessment of the histolo-
gical criteria [58]. MDD provided a definite diagnosis for 80.5%
of presented cases in a retrospective study with 938
patients [59]. The impact of MDD was evaluated in the inter-
national study by Walsh et al. [60] with seven expert multi-
disciplinary teams (MDT) consisting of at least one clinician,
one radiologist, and one pathologist; the study demonstrated
high levels of inter-MDT agreement for a diagnosis of IPF
(κ = 0.60) and for the diagnostic likelihood of IPF (κ = 0.71).
Furthermore, MDT made the diagnosis of IPF with high con-
fidence more frequently than clinicians or radiologists alone
[60]. Inter-MDT agreement for a diagnosis of (CTD)-related ILD
was also good (κ = 0.64) but was poor for idiopathic nonspe-
cific idiopathic pneumonia (NSIP) and HP, suggesting the
urgent need for improving criteria and thus interobserver
agreement. Recently, two reviews proposed different algo-
rithms helping the diagnosis of chronic HP, integrating both
clinical and HRCT data [61,62]. Also, in an international
Modified Delphi survey, three items received 100% endorse-
ment by the experts as important: (1) history of environmental

exposure, (2) air trapping-mosaic attenuation on HRCT and (3)
case discussion in MDT meeting [63].
The impact of HRCT on clinical or histopathological diag-
nosis has been reported in several studies. Using a Bayesian
model, Grenier et al. showed that a correct ILD diagnosis was
achieved for 36% with CT alone, and for 27–29% with clinical
data alone. This increased when radiography was added to
clinical data to 53–54% and with integration of clinical, X-ray
and CT data, to 61–80% [17].
Aziz et al. have reported the effect of HRCT data on clinical
diagnosis in 168 patients with suspected ILD. In that study, the
clinician’s first-choice diagnosis changed in 51% of cases, and
diagnostic confidence improved once CT data were known by
them [18].
4.4.2. Role of MDD when HRCT does not allow a specific
diagnosis
First, with the clinical, biological, evolution data and when
available cyto-histopathological elements, the practitioner
will search or eliminate known causes of ILDs. These elements
can also direct toward a specific entity among IIPs (e.g. age
<55, being female and a nonsmoker is more in favor of NSIP
than IPF). With previous HRCTs, when available, the radiologist
may date the beginning of the disease, and characterize its
progression and speed. Importantly, a prior HRCT can provide
clues to the diagnosis: for example, consolidation migrating
over time suggests an organizing pneumonia in the absence
of eosinophilia. Development of honeycombing over time can
be misleading since it can occur in both IPF patients with a
possible UIP on CT [64] or NSIP patients [65]. It is also inter-
esting to investigate HRCT evolution when a corticosteroid
treatment has been initiated, a resolution or improvement
reinforcing the probability of an NSIP rather than an IPF, or
the initiation of a treatment with diuretics if a pulmonary
edema is considered. Micronodules on HRCT in smoking
related disease such as RB-ILD may improve after smoking
cessation [66]; after antigen removal, GGO or centrilobular
nodules can also disappear in HP [67].
The known cases of ILD are occupational disease, HP, drug
induced lung disease, systemic connective_tissue disease,
humoral immune dysregulated condition like, amyloidosis for
example, genetic syndromes with familial ILD, lung cancer, or
pulmonary edema. Some clues, in addition to the bio-clinical
Figure 6. HRCT images of a patient with non specific interstitial pneumonia (NSIP) due to connective tissue disease (CTD). In this case of typical HRCT pattern of
NSIP, the esophageal dilatation suggests the diagnosis of CTD.
EXPERT REVIEW OF RESPIRATORY MEDICINE 85
data, can be found on HRCT, in asbestosis subpleural dots,
subpleural lines seen less than 5 mm from the inner chest wall,
pleural plaques, calcifications and bands for instance; parench-
ymal bands and rounded atelectasis help to differentiate
asbestosis from other ILD and, particularly UIP [68,69]. CTD-
ILD can be suggested by the presence on HRCT of pleural
effusion, esophageal dilation (Figure 6), or pericardial abnorm-
ality [70]. In a recent study the presence of one of the follow-
ing signs suggested a connective disease with a UIP pattern:
the anterior upper lobe sign (fibrosis within the upper lobes
predominates in their anterior part); exuberant honeycombing
(greater than 70% of the fibrosis); the straight-edge sign (iso-
lation of fibrosis to the lung bases without substantial exten-
sion along the lateral margins of the lungs on coronal images)
[71]. Also, an airway remodeling with air trapping can be
associated in the particular case of rheumatoid arthritis with
anti cyclic citrillinated peptide antibody [72].
The radiological presentation of familial pulmonary fibrosis
may differ from that of sporadic IPF, with a diffuse ILD in the
craniocaudal axis without basal predominance despite a pre-
dominantly peripheral distribution in the axial dimension as
seen in IPF [73].
If no cause has been found, three questions should be asked
according to Walsh et al. [11]: ‘(i) Is there a predominantly fibros-
ing lung disease? (ii) If it is fibrotic, is this a classic UIP pattern? (iii)
If it is not classic UIP pattern, what are the alternative diagnoses?’.
An International Working Group Perspective recently proposed a
standardized ontological framework for the classification of fibro-
tic ILD, using the terms of confident diagnosis that meets guide-
line criteria or is ≥ 90% confident, a provisional diagnosis with
high (70–89%) and low confidence diagnosis (51–69%) and
unclassified when the diagnosis has a confidence <50% [35].
(i) Fibrosis will be identified by the presence of one of
several of these items: honeycombing, traction bronch-
iectasis, or existence of volume loss, related to reticular
abnormalities.
(ii) In 2011, UIP criteria have been clearly identified by the ATS
ERS statement on fibrosis [1], with three patterns: UIP,
possible UIP, and inconsistent UIP. This classification
makes the diagnosis of IPF easier, and avoids surgical
lung biopsy when the pattern is classical. However, even
if the specificity is good (when there is a typical pattern),
86 F. JENY ET AL.
reported for 94–100% [3], sensitivity is low, at 43–78%, as
some patients present no honeycombing or atypical signs
[3]. Moreover, interobserver agreement was moderate to
poor for the current ATS/ERS CT criteria, and especially for
the recognition of honeycombing [74,75]. In a recent post
hoc subgroup analysis of IPF clinical trial, patients with
honeycombing on HRCT and/or confirmation of UIP by
biopsy versus patients with neither, the response to ninte-
danib was similar [76]. In another post hoc study, an HRCT
pattern of possible UIP was associated for 94% to a con-
cordant histopathology [77]. However, patients with col-
lagen vascular disease and occupational lung diseases
were excluded in that study. Nevertheless adding clinical
(age >60, being male, history of smoking) and radiological
features (total traction bronchiectasis score) to possible UIP
patterns on HRCT increases the value of HRCT in diagnos-
ing IPF [78]. Salisbury et al. showed in a multivariable
model adjusted for age and gender that extensive reticular
densities (OR 2.93) predicted IPF, while increasing GGO
predicted a diagnosis other than IPF [79]. Diagnostic cri-
teria of ‘probable UIP’ have been proposed allowing to
reduce the need for lung biopsy [71,80,81].
According to Yagihashi et al. [82] the term ‘inconsistent
with UIP’ is misleading since they showed that 73% of
patients with a final diagnosis of IPF had HRCT findings
‘inconsistent with UIP,’ but demonstrated a definite histo-
pathological UIP. Similar results were found in other stu-
dies [80,83]. Eventually, a substantial minority (>7%) of
cases could not be confidently categorized according to
current guidelines for IPF because of the diffuse axial (i.e.
no peripheral or central distribution) or zonal distribution
(i.e. no upper or mid or lower predominance) [84]. For
Table 2. Diagnostic categories of UIP in HRCT adapted from [36].
Typical UIP CT pattern Probable UIP CT pattern
Subpleural and basal Subpleural and basal
predominant; distribution is often predominant; distribution is often
heterogeneous* heterogeneous
Honeycombing with or without Reticular pattern with peripheral
peripheral traction traction bronchiectasis or
bronchiectasis or bronchiolectasis
bronchiolectasis† May have mild GGO
UIP = usual interstitial pneumonia. IPF = idiopathic pulmonary fibrosis CT = computed tomography; CTD = connective tissue disease; GGO = ground-glass opacities;
RA = rheumatoid arthritis;
*Variants of distribution: occasionally diffuse, may be asymmetrical.
†Superimposed CT features: mild GGO, reticular pattern, pulmonary ossification.
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society.
these different reasons, the Fleischner society and the
ATS/ERS/JRS/ALAT proposed to change the HRCT classifi-
cation of cases in 4 categories: UIP, probable UIP, indeter-
minate, or alternative diagnosis [3,36] (Table 2).
(iii) If it is not a UIP, despite fibrosis on HRCT, the following
diagnoses should be suggested: nonspecific interstitial
pneumonia (NSIP), fibrosing variant of organizing pneu-
monia, chronic HP and, more rarely, chronic fibrotic sar-
coidosis, or pleuroparenchymal fibroelastosis (PPFE).
In NSIP compared to UIP (Figure 2), HRCT presentation is
characterized by no or mild reticulation, extensive GGO, mini-
mal traction bronchiectasis (but when present surrounded by
GGO), relative subpleural sparing, minimal honeycombing,
peribronchovascular predominance, more uniform pattern
compared to UIP [85]. Using new technology, a computer-
aided differential diagnosis (CADD) system was able to distin-
guishes between UIP and NSIP on HRCT [86].
HP should be researched since a prospective study on 46
patients diagnosed with IPF found that almost half of them
were subsequently diagnosed with chronic HP, and most of
the patients had been exposed to occult avian antigens
[87]. In HP there is in two thirds of cases an upper-lung or
mid-lung distribution of fibrosis. Centrolobular nodules, and
mosaic attenuation or air trapping particularly when present
in a nonfibrotic area of the lung, are suggestive of HP.
Mosaic attenuation is also frequently seen in patients with
IPF but within areas of advanced fibrosis in the lower
lobes [88].
Fibrosing variant of organizing pneumonia may occur after
a long disease course, and the consolidations may only be
evidenced on previous CT through scan review. The typical
CT pattern indeterminate CT features most consistent with non-IPF
for UIP diagnosis. Alternative diagnosis
Subpleural and basal Findings suggestive of another diagnosis,
predominant including
Subtle reticulation; may
have mild ● Predominant distribution
GGO or distortion (‘early o Peribronchovascular
UIP pattern’) o Perilymphatic
CT features and/or o Upper or mid-lung
distribution of ● CT features
lung fibrosis that do not o Cysts
suggest o Marked mosaic attenuation
any specific etiology o Predominant GGO
(“truly o Profuse micronodules
indeterminate for UIP”) o Centrilobular nodules
o Nodules
o Consolidation
● Other
o Pleural plaques (consider asbestosis)
o Dilated esophagus (consider CTD)
o Distal clavicular erosions (consider RA)
o Extensive lymph node enlargement (consider
other etiologies)
o Pleural effusions, pleural thickening (consider
CTD/drugs)

Figure 7. HRCT image of a patient with organizing pneumonia. In this case, the
reverse halo sign (so call atoll sign), defined by central ground glasses opacities
surrounded by a denser consolidation of crescentic or ring shape is highly
suggestive of the diagnosis.
features of organizing pneumonia [89] include bilateral patchy
areas of consolidation with subpleural and lower zone predo-
minance. Consolidative areas or nodules are distributed along
the bronchovascular bundles or along subpleural areas. Rarely
the so-called reverse halo or atoll sign is present (Figure 7). In
longitudinal studies on organizing pneumonia, the evolution
to fibrosis may be similar to fibrotic NSIP [89,90]
Lung fibrosis in sarcoidosis is characterized by different
main patterns: bronchial distortions mainly central (Figure 2),
or peripheral honeycombing both predominantly in the upper
and/or middle lung regions, whereas linear opacities are dif-
fuse [91]. Atypical forms have been described with basal hon-
eycombing, and UIP pattern [92].
HRCT features for PPFE are bilateral, irregular pleuropar-
enchymal thickening in the upper and mid lungs, with a
platithorax, and often pneumomediastinum or pneumothorax.
It has been reported an association with UIP HRCT and histo-
pathological pattern in a subset of patients with PPFE [93,94].
5. Role in determining prognosis
HRCT can be sometimes predictive of the disease outcome,
either spontaneous or under treatment in different ways, but
can’t be used as tool for daily use in this matter. HRCT allows: (1)
the evaluation of disease activity and the evidence of potentially
reversible features, (2) the identification of HRCT pattern (e.g.
UIP vs. NSIP) which correlates to histopathological data and can
predict irreversible features, (3) to measure, using tools (semi
and quantitative) the extent of lung infiltration and notably of
fibrosis, and (4) the detection of pulmonary hypertension.
5.1. Evaluation of lesion reversibility
Reversible lesions in HRCT normally correlate with inflammatory
lesions on a histopathological level. They are supposed to
respond to treatment, and help assess the prognosis of the
disease. However, conflicting results have been reported con-
cerning the predictive value of some lesions. As a matter of
EXPERT REVIEW OF RESPIRATORY MEDICINE 87
facts, some of these supposed ‘reversible’ features such as GGO
or consolidation, may reflect either inflammatory patterns or
first step fibrosis especially in sarcoidosis [95–99] or NSIP
[100,101]. Recently in sarcoidosis, a score assessing the pre-
sence nodularity, GGO, interlobular septal thickening, and con-
solidation was found to predict FVC response to treatment at
1 year and was highly reproducible between radiologists [102].
Early studies on HP reported that GGO change, micronodules,
and focal air trapping all regressed following exposure cessation,
whereas reticular or honeycomb patterns did not [67].
5.2. Patterns and prognosis
Flaherty et al. observed that in presence of a biopsy-proven
UIP, a typical UIP pattern on HRCT was associated with higher
mortality than with an atypical UIP or fibrotic NSIP pattern on
HRCT [103]. On the basis of HRCT results, the prognosis of
definite UIP pattern was significantly worse than possible UIP,
indeterminate findings (either UIP or NSIP), or NSIP [85].
HRCT UIP patterns (definite or possible) in the setting of
rheumatoid arthritis related lung disease or of Ssc-ILD have also
been associated with increased mortality versus NSIP [104] or
inconsistent UIP patterns [105]. For patients with connective
tissue disease and biopsy proven UIP, there are survival differ-
ences between those with UIP pattern and those without typical
features of UIP on HRCT [106].
IPF prognosis seems to be more impacted by traction
bronchiectasis and fibrosis scores [107], than by the different
pattern with a debated literature [108,109].
5.3. Extent of the disease
5.3.1. Fibrosis
The prognostic impact of specific lesions has been studied,
especially for those indicating fibrosis and particularly in
patients with IPF. The evaluation of fibrosis is based on
extent evaluation of the respective fibrotic features (i.e. reti-
culation, honeycombing or traction bronchiectasis) and uses
visual or semi quantitative tools or, more recently, automated
quantitative tools. Histo-radiological correlation studies
showed that fibroblastic foci, the number of which predicts
mortality [110,111], were significantly associated with reticu-
lation, honeycombing and, particularly, traction bronchiecta-
sis in chronic HP or IPF [111,112]. Several studies have
demonstrated the predictive value on mortality of the extent
of fibrosis and its components measured by semiquantitative
visual analysis (e.g. visual fibrosis score). The extent of fibrosis
predicted mortality in IPF [113,114], chronic HP [115,116],
NSIP [113], rheumatoid arthritis-related ILD [117],
unclassifiable ILD [118], Ssc-ILD [119,120] and in sarcoido-
sis [121]. A visual score of fibrosis threshold of 20% has
been reported to be a valuable prognostic factor in several
studies [117,121–123], and, for instance a fibrosis score >20%
increased the risk of mortality ninefold in bivariate cox
regression analysis in rheumatoid related ILD [121].
Specific assessment of lesions showed that traction bronch-
iectasis had a strong predictive value [106,115,124–126].
Reticulations [116] and honeycombing [114,124] are also
88 F. JENY ET AL.
predictive but the interobserver agreement to assess honey-
combing is only moderate [75].
5.3.2. Extension of others features
In cryptogenic organizing pneumonia, the extent of consolida-
tion was an independent factor predictive of incomplete reso-
lution, and 74% of unresolved cases were similar to fibrotic
NSIP [90]. In chronic HP mosaic attenuation by air trapping
predicted survival [127].
5.3.3. Automated quantification
Fibrosis assessment has used automated tools for a few years
[21], with parameters derived from analysis of image density
histograms (mean lung attenuation, skewness, and kurtosis
[128] or with more sophisticated approaches based on the ana-
lysis of image texture [62,129–131].The published results showed
the interest of these approaches, with sometimes better results
than those obtained by the radiologist [132]. Analysis of the
texture predicted disease progression [133] or mortality. A com-
puter algorithm, CALIPER (Computer-Aided Lung Informatics for
Pathology Evaluation and Rating), developed at the Biomedical
Imaging Resource, Mayo Clinic, Rochester, MN, USA, was com-
pared with conventional CT and pulmonary function measures in
IPF. Using the software’s CT-derived parameters, in particular
with evaluation of honeycombing or pulmonary vessel volume,
were more accurate to predict poor outcome than traditional
visual CT scores [134]. Recently, the authors showed that derived
features, particularly vessel-related structure (VRS) scores, were
among the strongest predictors of survival and FVC decline in a
multicentric study and their use reduced the requisite sample
size of an IPF drug trial by 26% [22]. This study outlined the need
to understand the complexities of the pulmonary vasculature in
IPF [135].
Comparable results were obtained by other American [131],
Korean [136], and Japanese groups. In the future, new artificial
intelligence approaches based on ‘deep learning’ are expected
to overcome some of the limitations of ‘texture’-based techni-
ques. There is free and open-source software that has per-
mitted to obtain the analysis of attenuation histograms, such
as OsiriX or Horos. This software is able to calculate quantita-
tive indexes related to pulmonary function and prognosis in
Ssc-ILD [137].
5.4. Role in detection of pulmonary hypertension
HRCT may be a tool to predict pulmonary hypertension, and thus
predict mortality in IPF by measuring the ratio of the diameters
of the pulmonary artery to the aorta’s (PA/Ao) [111,138], or with
integration of this ratio to other variables (% predicted
DLCO <50%, PA/Ao ratio ≥0.9 PaO2 < 80 Torr with an AUC of
0.757) [139]. This score was interesting since other studies demon-
strated that PA/Ao ratio alone was ineffective to predict pulmonary
hypertension [140,141].
5.5. Comparison and integration with the pulmonary
function tests
Walsh et al. showed that HRCT abnormalities such as the
extent of traction bronchiectasis predicted mortality with
more accuracy than pulmonary function in chronic HP [115].
Also, the progression of fibrosis scoring in serial HRCT may
help identify patients with a poor prognosis in IPF, especially
for those without marked changes in %FVC [142].
The Composite physiologic index (CPI) was derived from a
quantitative radiographic scoring of pulmonary fibrosis [143]
with a stepwise regression to generate an equation with lung
function variables reflecting the extent of pulmonary fibrosis
on HRCT. The CPI was predictive of mortality in or IPF [143], or
unclassifiable disease [126]. In sarcoidosis: fibrosis extent
>20% on CT and pulmonary hypertension are two strong
factors of mortality [121,122], until the value of CPI is still
debated [121,122,144]. An integrated clinico-radiological sta-
ging system including the extension of fibrosis on HRCT, PA/
Ao diameter measured on CT and CPI was successfully more
predictive of mortality in pulmonary sarcoidosis than any
individual variable alone [122]. In Ssc-ILD, Goh et al. demon-
strated that a simple algorithm integrated fibrosis and FVC
with a threshold of 20% and 70%, respectively, and was pre-
dictive of mortality [119]. In a retrospective analysis the addi-
tion of CT extent scores to the GAP (gender age physiology)
model increased the accuracy of mortality prediction. A CT-
GAP score (with DLCO substituted by a CT fibrosis
extent score) had comparable accuracy with the original GAP
model [145].This may be a useful alternative model in situa-
tions where CT scoring is more reliable and available than
DLCO measurement [145].
6. Role in monitoring the disease
Longitudinal HRCT data has provided significant information.
In addition to increase the accuracy of initial diagnosis (see
diagnosis and MDD) and prognosis assessment [142], HRCT
may identify progression, detect new processes in patients
with acute worsening symptoms; and other abnormalities or
complications, such as lung cancer [21,146].
6.1. Assess the progression
Regular use of CT follow-up is still debated in routine practice
and is not recommended for patients who have a clinically
stable disease [21]. Except for rare cases, repeated CTs are not
recommended due to the risk of radiation for young people
despite improved technology that reduces radiation levels,
cost, and a lack of evidence supporting it. The monitoring of
pulmonary infiltration evolution has low sensitivity, less than
symptoms and pulmonary function tests. According to
Zappala et al. serial chest radiography and serial spirometry
were tested to investigate pulmonary disease outcome in
sarcoidosis, serial CT being the morphologic reference [147].
FVC was the most reliable tool with a good agreement,
whereas the agreement was only moderate with chest radio-
graphy [147]. These findings justify the use of FVC as the
primary end-point in monitoring sarcoidosis. In this study,
isolated or disproportionate declines in gas transfer were fre-
quent and had no morphologic substrate on serial HRCT scan,
gas transfer measurement being more likely a consequence of

Figure 8. HRCT images and images obtained after segmentation based on deep learning (a): native HRCT image, (b) manual segmentation of fibrotic areas (pink and
purple) by the radiologist (c): same segmentation obtained with machine learning algorithm (convolutional neural network), showing very similar results. (Courtesy
of S. Tarando and C. Fetita; ARTEMIS department, Telecom SudParis, Institut Mines-Telecom, CNRS UMR 8145 – UMR 5157, Evry, France).
vascular involvement, perhaps useful for detecting an even-
tual pulmonary hypertension.
However, serial CT can be used to assess on a routine basis
the progression of ILD in selected patients [21]. CT can be
useful when there is (i) discordant evolution between symp-
toms and pulmonary function tests (PFT) or chest X ray, (ii)
when patients are unable to perform a PFT, or (iii) when PFT
don’t reflect the progression of the disease (e.g. patients
with IPF and emphysema greater than or equal to 15%
where the FVC measurement doesn’t reflect progression of
the disease) [148] (iv) or to evaluate early ILD without impaired
lung function. In prospective report for early diagnosis of Ssc-
ILD, 62% of patients had a significant ILD sometimes with
fibrosis on HRCT, but with normal FVC values [149]. Findings
on HRCT have also been used as independent endpoints in
clinical drug trials, and the quantification of lung imaging may
provide an objective endpoint.
6.2. Role of HRCT with acute new or worsening
dyspnoea
Another important role of HRCT in monitoring ILD is when
patients present new or worsening symptoms. HRCT may help
in detecting new abnormalities, suggestive of infectious dis-
ease, notably in patients with immunosuppressive treatment,
or pulmonary embolism, for instance, in sarcoidosis [150], or
pneumothorax, which can occur in 20% of patients with
IPF [151].
HRCT manifestations also belong to the diagnostic criteria of
acute exacerbation in IPF [152] with new bilateral GGO/consoli-
dation not fully explained by cardiac failure or fluid overload.
6.3. Role in detecting complications
Eventually, HRCT can detect complication in ILDs, such as
lung cancer in patients with IPF the incidence of which is
increased compared to general population with a rate ratio
of 5 [153]. In the majority of cases, a squamous cell carci-
noma is developing in the peripheral lung adjacent to UIP
[154]. In asbestosis or other occupational respiratory dis-
ease, serial chest CTs are also used to detect lung cancer
[155]. In sarcoidosis, comorbidities such as chronic pulmon-
ary aspergillosis can be diagnosed with highly suggestive
imaging in CT [144].
EXPERT REVIEW OF RESPIRATORY MEDICINE 89
7. Expert commentary
Despite continuous improvements, diagnostic of ILD at HRCT
remains a challenge for radiologists and most diagnoses
should be discussed during MDD. However, it is sometimes
complicated to organize MDD in every hospital and to dis-
cuss every case, due to time restraints. Therefore, the role of
MDD could be lessened in patients with CT images, based
on a diagnosis with a high degree of confidence. Even
though MDD are important to establish a diagnosis in
most patients, some cases remain difficult to classify [156].
Indeed, causes of uncertainty with image interpretation are
numerous, including decision-making in case of pattern
overlap [157], lack of consensually accepted definition of
typical CT patterns (which is on debate for hypersensitivity
pneumonitis [61]), ambiguity of some CT features included
in the definition of typical patterns (which is the case for
honeycombing no longer considered as the keystone of the
diagnosis of UIP), or the lack of specificity of CT images in
case of early abnormalities [31].
8. Five-year view
Tomorrow, radiologists will dispose of new computer-aided
diagnosis systems [158]. The interest of such tools has been
demonstrated in IPF, where automatic quantification of fibro-
sis did better than the radiologist to predict survival [132].
Data mining techniques can mimic the reasoning of a radiol-
ogist and give the most probable diagnosis based on the
presence of CT features in combination with the description
of the extent and location of abnormalities [43] Nowadays,
artificial intelligence, especially approaches based on deep
learning, is declared a revolution [159] (Figure 8). These tech-
niques could improve understanding of the pathophysiology
of diseases or provide models of progression [160].
Key issues
● Investigating lung parenchyma, requests optimal HRCT pro-
tocols and methods of acquisition.
● Thanks to HRCT, the range of diagnoses and their prob-
ability are more accurately identified. For difficult diagnoses
requiring a multidisciplinary discussion, radiologists, with
HRCT, are able to optimize the contribution of imaging.
● HRCT can predict the disease outcome: by evaluation of
disease activity and evidencing potentially reversible or
90 F. JENY ET AL.
irreversible features; by measuring the extent of lung infil-
tration and notably of fibrosis; by detecting pulmonary
hypertension.
● The integration of HRCT findings with pulmonary function
test results might help predict ILD’s prognosis.
● Longitudinal HRCT data provides significant information. In
addition to increasing the accuracy of initial diagnosis and
prognosis assessment, longitudinal HRCT may unveil pro-
gression, detect new processes in patients with acute wor-
sening symptoms, and other abnormalities or
complications, such as lung cancer.
● In the coming years, artificial intelligence might significantly
modify radiological practice.
Funding
This manuscript was not funded.
Declaration of interest
No potential conflict of interest was reported by the authors.
Reviewers Disclosure
Peer reviewers on this manuscript have no relevant financial relationships
or otherwise to disclose.
References
Papers of special note have been highlighted as either of interest (•) or of
considerable interest (••) to readers.
1. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT
statement: idiopathic pulmonary fibrosis: evidence-based guide-
lines for diagnosis and management. Am J Respir Crit Care Med.
2011;183:788–824.
2. Moser JB, Sheard SL, Edyvean S, et al. Radiation dose-reduction
strategies in thoracic CT. Clin Radiol. 2017;72:407–420.
3. Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for
idiopathic pulmonary fibrosis: a Fleischner society white paper.
Lancet Respir Med. 2018;6:138–153.
•• This review provides an updated approach to the diagnosis of
idiopathic pulmonary fibrosis, based on a systematic search
of the medical literature and the expert opinion of members of
the thoracic radiology Fleischner Society.
4. Pontana F, Billard A-S, Duhamel A, et al. Effect of iterative recon-
struction on the detection of systemic sclerosis-related interstitial
lung disease: clinical experience in 55 patients. Radiology.
2016;279:297–305.
5. Bankier AA, O’Donnell CR, Boiselle PM. Quality initiatives. Respiratory
instructions for CT examinations of the lungs: a hands-on guide.
Radiogr Rev Publ Radiol Soc N Am Inc. 2008;28:919–931.
6. Hansell DM, Bankier AA, MacMahon H, et al. Fleischner society:
glossary of terms for thoracic imaging. Radiology. 2008;246:697–722.
7. Kim M, Lee SM, Song J-W, et al. Added value of prone CT in the
assessment of honeycombing and classification of usual interstitial
pneumonia pattern. Eur J Radiol. 2017;91:66–70.
8. Beigelman-Aubry C, Hill C, Guibal A, et al. Multi-detector row
CT and postprocessing techniques in the assessment of diffuse
lung disease. Radiogr Rev Publ Radiol Soc N Am Inc.
2005;25:1639–1652.
9. Johkoh T, Sakai F, Noma S, et al. Honeycombing on CT; its defini-
tion, pathologic correlation, and future direction of its diagnosis.
Eur J Radiol. 2014;83:27–31.
10. Egashira R, Jacob J, Kokosi MA, et al. Diffuse pulmonary ossification
in fibrosing interstitial lung diseases: prevalence and associations.
Radiology. 2017;284:255–263.
11. Walsh SLF, Hansell DM. High-resolution CT of interstitial lung dis-
ease: a continuous evolution. Semin Respir Crit Care Med.
2014;35:129–144.
12. Epler GR, McLoud TC, Gaensler EA, et al. Normal chest roentgen-
ograms in chronic diffuse infiltrative lung disease. N Engl J Med.
1978;298:934–939.
13. Padley SP, Hansell DM, Flower CD, et al. Comparative accuracy of
high resolution computed tomography and chest radiography in
the diagnosis of chronic diffuse infiltrative lung disease. Clin Radiol.
1991;44:222–226.
14. Mathieson JR, Mayo JR, Staples CA, et al. Chronic diffuse infiltrative
lung disease: comparison of diagnostic accuracy of CT and chest
radiography. Radiology. 1989;171:111–116.
15. Grenier P, Valeyre D, Cluzel P, et al. Chronic diffuse interstitial lung
disease: diagnostic value of chest radiography and high-resolution
CT. Radiology. 1991;179:123–132.
16. Nishimura K, Izumi T, Kitaichi M, et al. The diagnostic accuracy of
high-resolution computed tomography in diffuse infiltrative lung
diseases. Chest. 1993;104:1149–1155.
17. Grenier P, Chevret S, Beigelman C, et al. Chronic diffuse infiltrative
lung disease: determination of the diagnostic value of clinical data,
chest radiography, and CT and Bayesian analysis. Radiology.
1994;191:383–390.
18. Aziz ZA, Wells AU, Bateman ED, et al. Interstitial lung disease:
effects of thin-section CT on clinical decision making. Radiology.
2006;238:725–733.
19. Raj R, Raparia K, Lynch DA, et al. Surgical lung biopsy for interstitial
lung diseases. Chest. 2017;151:1131–1140.
20. Boer SDE, Milne DG, Zeng I, et al. Does CT scanning predict the
likelihood of a positive transbronchial biopsy in sarcoidosis?
Thorax. 2009;64:436–439.
21. Hansell DM, Goldin JG, King TE, et al. CT staging and monitoring of
fibrotic interstitial lung diseases in clinical practice and treatment
trials: a position paper from the Fleischner society. Lancet Respir
Med. 2015;3:483–496.
22. Jacob J, Bartholmai BJ, Rajagopalan S, et al. Predicting outcomes in
idiopathic pulmonary fibrosis using automated CT analysis. Am J
Respir Crit Care Med. 2018.
23. Washko GR, Hunninghake GM, Fernandez IE, et al. Lung volumes
and emphysema in smokers with interstitial lung abnormalities. N
Engl J Med. 2011;364:897–906.
24. Hunninghake GM, Hatabu H, Okajima Y, et al. MUC5B promoter
polymorphism and interstitial lung abnormalities. N Engl J Med.
2013;368:2192–2200.
25. Hoyer N, Wille MMW, Thomsen LH, et al. Interstitial lung abnorm-
alities are associated with increased mortality in smokers. Respir
Med. 2018;136:77–82.
26. Sverzellati N, Guerci L, Randi G, et al. Interstitial lung diseases in a
lung cancer screening trial. Eur Respir J. 2011;38:392–400.
27. Jin GY, Lynch D, Chawla A, et al. Interstitial lung abnormalities in a
CT lung cancer screening population: prevalence and progression
rate. Radiology. 2013;268:563–571.
28. Putman RK, Hatabu H, Araki T, et al. Association between interstitial
lung abnormalities and all-cause mortality. JAMA. 2016;315:672–681.
29. Araki T, Putman RK, Hatabu H, et al. Development and progression
of interstitial lung abnormalities in the framingham heart study.
Am J Respir Crit Care Med. 2016;194:1514–1522.
30. Miller ER, Putman RK, Vivero M, et al. Histopathology of interstitial
lung abnormalities in the context of lung nodule resections. Am J
Respir Crit Care Med. 2018;197:955–958.
31. Wells AU, Kokosi MA. Subclinical interstitial lung abnormalities:
toward the early detection of idiopathic pulmonary fibrosis? Am J
Respir Crit Care Med. 2016;194:1445–1446.
32. Podolanczuk AJ, Oelsner EC, Barr RG, et al. High attenuation areas
on chest computed tomography in community-dwelling adults: the
MESA study. Eur Respir J. 2016;48:1442–1452.

33. Sack CS, Doney BC, Podolanczuk AJ, et al. Occupational exposures
and subclinical interstitial lung disease. The MESA (Multi-Ethnic
Study of Atherosclerosis) air and lung studies. Am J Respir Crit
Care Med. 2017;196:1031–1039.
34. Sack C, Vedal S, Sheppard L, et al. Air pollution and subclinical
interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis
(MESA) air-lung study. Eur Respir J. 2017;50.
35. Ryerson CJ, Corte TJ, Lee JS, et al. A standardized diagnostic ontol-
ogy for fibrotic interstitial lung disease. An international working
group perspective. Am J Respir Crit Care Med. 2017;196:1249–1254.
36. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic
pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice
guideline. Am J Respir Crit Care Med. 2018;198:e44–e68.
37. Gupta N, Finlay GA, Kotloff RM, et al. Lymphangioleiomyomatosis
diagnosis and management: high-resolution chest computed
tomography, transbronchial lung biopsy, and pleural disease man-
agement. Am J Respir Crit Care Med. 2017;196:1337–1348.
38. Marchiori E, Zanetti G, Mano CM, et al. Exogenous lipoid pneu-
monia. Clinical and radiological manifestations. Respir Med.
2011;105:659–666.
39. Castellana G, Castellana G, Gentile M, et al. Pulmonary alveolar
microlithiasis: review of the 1022 cases reported worldwide. Eur
Respir Rev Off J Eur Respir Soc. 2015;24:607–620.
40. Travis WD, Costabel U, Hansell DM, et al. An official American
thoracic society/European respiratory society statement: update
of the international multidisciplinary classification of the idio-
pathic interstitial pneumonias. Am J Respir Crit Care Med.
2013;188:733–748.
• This statement proposed an update of the international multi-
disciplinary classification of the idiopathic interstitial
pneumonias.
41. Spagnolo P, Rossi G, Trisolini R, et al. Pulmonary sarcoidosis. Lancet
Respir Med. 2018;6:389–402.
42. Müller NL, Kullnig P, Miller RR. The CT findings of pulmonary
sarcoidosis: analysis of 25 patients. AJR Am J Roentgenol.
1989;152:1179–1182.
43. Martin SG, Kronek L-P, Valeyre D, et al. High-resolution computed
tomography to differentiate chronic diffuse interstitial lung dis-
eases with predominant ground-glass pattern using logical analysis
of data. Eur Radiol. 2010;20:1297–1310.
44. De Margerie-Mellon C, Dion G, Darlay J, et al. High-resolution
computed tomography to differentiate chronic diffuse infiltrative
lung diseases with chronic multifocal consolidation patterns using
logical analysis of data. Sarcoidosis Vasc Diffuse Lung Dis Off J
WASOG. 2016;33:355–371.
45. Brauner MW, Grenier P, Tijani K, et al. Pulmonary Langerhans cell
histiocytosis: evolution of lesions on CT scans. Radiology.
1997;204:497–502.
46. Vassallo R, Harari S, Tazi A. Current understanding and manage-
ment of pulmonary Langerhans cell histiocytosis. Thorax.
2017;72:937–945.
47. Gupta N, Vassallo R, Wikenheiser-Brokamp KA, et al. Diffuse cystic
lung disease. Part I Am J Respir Crit Care Med. 2015;191:1354–1366.
48. Munk PL, Müller NL, Miller RR, et al. Pulmonary lymphangitic carci-
nomatosis: CT and pathologic findings. Radiology. 1988;166:705–
709.
49. Ishii H, Trapnell BC, Tazawa R, et al. Comparative study of high-
resolution CT findings between autoimmune and secondary pul-
monary alveolar proteinosis. Chest. 2009;136:1348–1355.
50. Dias OM, Baldi BG, Pennati F, et al. Computed tomography in
hypersensitivity pneumonitis: main findings, differential diagnosis
and pitfalls. Expert Rev Respir Med. 2018;12:5–13.
51. American Thoracic Society, European Respiratory Society. American
Thoracic Society/European Respiratory Society International
Multidisciplinary Consensus Classification Of The Idiopathic
Interstitial Pneumonias. This joint statement of the American
Thoracic Society (ATS), and the European Respiratory Society
(ERS) was adopted by the ATS board of directors, June 2001 and
by the ERS executive committee, June 2001. Am J Respir Crit Care
Med. 2002;165:277–304.
EXPERT REVIEW OF RESPIRATORY MEDICINE 91
52. Duchemann B, Annesi-Maesano I, Jacobe de Naurois C, et al.
Prevalence and incidence of interstitial lung diseases in a multi-
ethnic county of greater Paris. Eur Respir J. 2017;50.
53. Homer R, Lederer DJ. Diagnosing idiopathic pulmonary fibrosis
without a lung biopsy: honeycombing not required. Thorax.
2017;72:391–392.
54. Flaherty KR, King TE, Raghu G, et al. Idiopathic interstitial pneumo-
nia: what is the effect of a multidisciplinary approach to diagnosis?
Am J Respir Crit Care Med. 2004;170:904–910.
55. Burge PS, Reynolds J, Trotter S, et al. Histologist’s original opinion
compared with multidisciplinary team in determining diagnosis in
interstitial lung disease. Thorax. 2017;72:280–281.
56. Hutchinson JP, McKeever TM, Fogarty AW, et al. Surgical lung
biopsy for the diagnosis of interstitial lung disease in England:
1997–2008. Eur Respir J. 2016;48:1453–1461.
57. Nicholson AG, Addis BJ, Bharucha H, et al. Inter-observer variation
between pathologists in diffuse parenchymal lung disease. Thorax.
2004;59:500–505.
58. Mäkelä K, Hodgson U, Piilonen A, et al. Analysis of the histologic
features associated with interobserver variation in idiopathic pul-
monary fibrosis. Am J Surg Pathol. 2018;42:672–678.
59. De Sadeleer LJ, Meert C, Yserbyt J, et al. Diagnostic ability of a
dynamic multidisciplinary discussion in interstitial lung diseases: a
retrospective observational study of 938 cases. Chest.
2018;153:1416–1423.
60. Walsh SLF, Wells AU, Desai SR, et al. Multicentre evaluation of
multidisciplinary team meeting agreement on diagnosis in diffuse
parenchymal lung disease: a case-cohort study. Lancet Respir Med.
2016;4:557–565.
•• This multicenter study evaluated the intermultidisciplinary
team agreement for the diagnosis of diffuse parenchymal
lung disease.
61. Vasakova M, Morell F, Walsh S, et al. Hypersensitivity pneumonitis:
perspectives in diagnosis and management. Am J Respir Crit Care
Med. 2017;196:680–689.
62. Salisbury ML, Myers JL, Belloli EA, et al. Diagnosis and treatment of
fibrotic hypersensitivity pneumonia. Where we stand and where
we need to go. Am J Respir Crit Care Med. 2017;196:690–699.
63. Morisset J, Johannson KA, Jones KD, et al. Identification of diag-
nostic criteria for chronic hypersensitivity pneumonitis: an interna-
tional modified delphi survey. Am J Respir Crit Care Med. 2017.
DOI:10.1164/rccm.201710-1986OC
64. Yamauchi H, Bando M, Baba T, et al. Clinical course and changes in
high-resolution computed tomography findings in patients with
idiopathic pulmonary fibrosis without honeycombing. PloS One.
2016;11:e0166168.
65. Silva CIS, Müller NL, Hansell DM, et al. Nonspecific interstitial pneu-
monia and idiopathic pulmonary fibrosis: changes in pattern and
distribution of disease over time. Radiology. 2008;247:251–259.
66. Nakanishi M, Demura Y, Mizuno S, et al. Changes in HRCT find-
ings in patients with respiratory bronchiolitis-associated intersti-
tial lung disease after smoking cessation. Eur Respir J.
2007;29:453–461.
67. Remy-Jardin M, Remy J, Wallaert B, et al. Subacute and chronic bird
breeder hypersensitivity pneumonitis: sequential evaluation with
CT and correlation with lung function tests and bronchoalveolar
lavage. Radiology. 1993;189:111–118.
68. Akira M, Morinaga K. The comparison of high-resolution computed
tomography findings in asbestosis and idiopathic pulmonary fibro-
sis. Am J Ind Med. 2016;59:301–306.
69. Arakawa H, Kishimoto T, Ashizawa K, et al. Asbestosis and other
pulmonary fibrosis in asbestos-exposed workers: high-resolution
CT features with pathological correlations. Eur Radiol.
2016;26:1485–1492.
70. Hwang J-H, Misumi S, Sahin H, et al. Computed tomographic
features of idiopathic fibrosing interstitial pneumonia: comparison
with pulmonary fibrosis related to collagen vascular disease. J
Comput Assist Tomogr. 2009;33:410–415.
71. Chung JH, Cox CW, Montner SM, et al. CT features of the usual
interstitial pneumonia pattern: differentiating connective tissue
92 F. JENY ET AL.
disease-associated interstitial lung disease from idiopathic pulmon-
ary fibrosis. AJR Am J Roentgenol. 2018;210:307–313.
72. Park WH, Kim SS, Shim SC, et al. Visual assessment of chest com-
puted tomography findings in anti-cyclic citrullinated peptide anti-
body positive rheumatoid arthritis: is it associated with airway
abnormalities? Lung. 2016;194:97–105.
73. Lee HY, Seo JB, Steele MP, et al. High-resolution CT scan findings in
familial interstitial pneumonia do not conform to those of idio-
pathic interstitial pneumonia. Chest. 2012;142:1577–1583.
74. Walsh SLF, Calandriello L, Sverzellati N, et al. Interobserver agree-
ment for the ATS/ERS/JRS/ALAT criteria for a UIP pattern on CT.
Thorax. 2016;71:45–51.
75. Watadani T, Sakai F, Johkoh T, et al. Interobserver variability in the
CT assessment of honeycombing in the lungs. Radiology.
2013;266:936–944.
• This study showed that interobserver agreement was only
moderate in the CT assessment of honeycombing.
Disagreement was largely caused by conditions that mimic
honeycombing.
76. Raghu G, Wells AU, Nicholson AG, et al. Effect of nintedanib in
subgroups of idiopathic pulmonary fibrosis by diagnostic criteria.
Am J Respir Crit Care Med. 2017;195:78–85.
77. Raghu G, Lynch D, Godwin JD, et al. Diagnosis of idiopathic pul-
monary fibrosis with high-resolution CT in patients with little or no
radiological evidence of honeycombing: secondary analysis of a
randomised, controlled trial. Lancet Respir Med. 2014;2:277–284.
78. Brownell R, Moua T, Henry TS, et al. The use of pretest probability
increases the value of high-resolution CT in diagnosing usual inter-
stitial pneumonia. Thorax. 2017;72:424–429.
79. Salisbury ML, Xia M, Murray S, et al. Predictors of idiopathic pul-
monary fibrosis in absence of radiologic honeycombing: a cross
sectional analysis in ILD patients undergoing lung tissue sampling.
Respir Med. 2016;118:88–95.
80. Chung JH, Chawla A, Peljto AL, et al. CT scan findings of probable
usual interstitial pneumonitis have a high predictive value for
histologic usual interstitial pneumonitis. Chest. 2015;147:450–459.
81. Gruden JF, Panse PM, Gotway MB, et al. Diagnosis of usual inter-
stitial pneumonitis in the absence of honeycombing: evaluation of
specific CT criteria with clinical follow-up in 38 patients. AJR Am J
Roentgenol. 2016;206:472–480.
82. Yagihashi K, Huckleberry J, Colby TV, et al. Radiologic-pathologic
discordance in biopsy-proven usual interstitial pneumonia. Eur
Respir J. 2016;47:1189–1197.
83. Sverzellati N, Wells AU, Tomassetti S, et al. Biopsy-proved idiopathic
pulmonary fibrosis: spectrum of nondiagnostic thin-section CT
diagnoses. Radiology. 2010;254:957–964.
84. Chung JH, Oldham JM, Montner SM, et al. CT-pathologic correla-
tion of major types of pulmonary fibrosis: insights for revisions
to current guidelines. AJR Am J Roentgenol. 2018;210:1034–
1041.
85. Sumikawa H, Johkoh T, Fujimoto K, et al. Pathologically proved
nonspecific interstitial pneumonia: CT pattern analysis as compared
with usual interstitial pneumonia CT pattern. Radiology.
2014;272:549–556.
86. Jun S, Park B, Seo JB, et al. Development of a computer-aided
differential diagnosis system to distinguish between usual intersti-
tial pneumonia and non-specific interstitial pneumonia using tex-
ture- and shape-based hierarchical classifiers on HRCT images. J
Digit Imaging. 2018;31:235–244.
87. Morell F, Villar A, Montero M-Á, et al. Chronic hypersensitivity
pneumonitis in patients diagnosed with idiopathic pulmonary
fibrosis: a prospective case-cohort study. Lancet Respir Med.
2013;1:685–694.
88. Silva CIS, Müller NL, Lynch DA, et al. Chronic hypersensitivity pneu-
monitis: differentiation from idiopathic pulmonary fibrosis and
nonspecific interstitial pneumonia by using thin-section CT.
Radiology. 2008;246:288–297.
89. Lee JW, Lee KS, Lee HY, et al. Cryptogenic organizing pneumonia:
serial high-resolution CT findings in 22 patients. AJR Am J
Roentgenol. 2010;195:916–922.
90. Chung MP, Nam BD, Lee KS, et al. Serial chest CT in cryptogenic
organizing pneumonia: evolutional changes and prognostic deter-
minants. Respirol Carlton Vic. 2018;23:325–330.
91. Abehsera M, Valeyre D, Grenier P, et al. Sarcoidosis with pul-
monary fibrosis: CT patterns and correlation with pulmonary
function. AJR Am J Roentgenol. 2000;174:1751–1757.
• This study identified CT patterns of pulmonary fibrosis in
patients with sarcoidosis and correlated these patterns with
pulmonary function tests.
92. Cozzi D, Bargagli E, Calabrò AG, et al. Atypical HRCT manifestations
of pulmonary sarcoidosis. Radiol Med (Torino). 2018;123:174–184.
93. Reddy TL, Tominaga M, Hansell DM, et al. Pleuroparenchymal
fibroelastosis: a spectrum of histopathological and imaging pheno-
types. Eur Respir J. 2012;40:377–385.
94. Nunes H, Jeny F, Bouvry D, et al. Pleuroparenchymal fibroelastosis
associated with telomerase reverse transcriptase mutations. Eur
Respir J. 2017;49.
95. Remy-Jardin M, Giraud F, Remy J, et al. Pulmonary sarcoidosis:
role of CT in the evaluation of disease activity and functional
impairment and in prognosis assessment. Radiology.
1994;191:675–680.
96. Murdoch J, Müller NL. Pulmonary sarcoidosis: changes on follow-up
CT examination. AJR Am J Roentgenol. 1992;159:473–477.
97. Akira M, Kozuka T, Inoue Y, et al. Long-term follow-up CT scan
evaluation in patients with pulmonary sarcoidosis. Chest.
2005;127:185–191.
98. Brauner MW, Lenoir S, Grenier P, et al. Pulmonary sarcoidosis: CT
assessment of lesion reversibility. Radiology. 1992;182:349–354.
99. Remy-Jardin M, Giraud F, Remy J, et al. Importance of ground-
glass attenuation in chronic diffuse infiltrative lung disease:
pathologic-CT correlation. Radiology. 1993;189:693–698.
100. Sumikawa H, Johkoh T, Ichikado K, et al. Nonspecific interstitial
pneumonia: histologic correlation with high-resolution CT in 29
patients. Eur J Radiol. 2009;70:35–40.
101. Park IN, Jegal Y, Kim DS, et al. Clinical course and lung function
change of idiopathic nonspecific interstitial pneumonia. Eur Respir
J. 2009;33:68–76.
102. Benamore R, Kendrick YR, Repapi E, et al. CTAS: a CT score to
quantify disease activity in pulmonary sarcoidosis. Thorax.
2016;71:1161–1163.
103. Flaherty KR, Thwaite EL, Kazerooni EA, et al. Radiological versus
histological diagnosis in UIP and NSIP: survival implications. Thorax.
2003;58:143–148.
104. Yunt ZX, Chung JH, Hobbs S, et al. High resolution computed
tomography pattern of usual interstitial pneumonia in rheumatoid
arthritis-associated interstitial lung disease: relationship to survival.
Respir Med. 2017;126:100–104.
105. Okamoto M, Fujimoto K, Sadohara J, et al. A retrospective cohort
study of outcome in systemic sclerosis-associated interstitial lung
disease. Respir Investig. 2016;54:445–453.
106. Walsh SLF, Sverzellati N, Devaraj A, et al. Connective tissue disease
related fibrotic lung disease: high resolution computed tomo-
graphic and pulmonary function indices as prognostic determi-
nants. Thorax. 2014;69:216–222.
107. Sumikawa H, Johkoh T, Colby TV, et al. Computed tomography
findings in pathological usual interstitial pneumonia: relation-
ship to survival. Am J Respir Crit Care Med. 2008;177:433–439.
108. Le Rouzic O, Bendaoud S, Chenivesse C, et al. Prognostic value of
the initial chest high-resolution CT pattern in idiopathic pulmonary
fibrosis. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG.
2016;32:353–359.
109. Salisbury ML, Tolle LB, Xia M, et al. Possible UIP pattern on high-
resolution computed tomography is associated with better survi-
val than definite UIP in IPF patients. Respir Med. 2017;131:229–
235.
110. King TE, Schwarz MI, Brown K, et al. Idiopathic pulmonary fibrosis:
relationship between histopathologic features and mortality. Am J
Respir Crit Care Med. 2001;164:1025–1032.
111. Chiba S, Tsuchiya K, Akashi T, et al. Chronic hypersensitivity pneu-
monitis with a usual interstitial pneumonia-like pattern: correlation

between histopathologic and clinical findings. Chest.
2016;149:1473–1481.
112. Walsh SLF, Wells AU, Sverzellati N, et al. Relationship between
fibroblastic foci profusion and high resolution CT morphology in
fibrotic lung disease. BMC Med. 2015;13:241.
113. Shin KM, Lee KS, Chung MP, et al. Prognostic determinants among
clinical, thin-section CT, and histopathologic findings for fibrotic
idiopathic interstitial pneumonias: tertiary hospital study.
Radiology. 2008;249:328–337.
114. Lynch DA, Godwin JD, Safrin S, et al. High-resolution computed
tomography in idiopathic pulmonary fibrosis: diagnosis and prog-
nosis. Am J Respir Crit Care Med. 2005;172:488–493.
115. Walsh SLF, Sverzellati N, Devaraj A, et al. Chronic hypersensitivity
pneumonitis: high resolution computed tomography patterns and
pulmonary function indices as prognostic determinants. Eur Radiol.
2012;22:1672–1679.
116. Mooney JJ, Elicker BM, Urbania TH, et al. Radiographic fibrosis score
predicts survival in hypersensitivity pneumonitis. Chest.
2013;144:586–592.
117. Ito Y, Arita M, Kumagai S, et al. Radiological fibrosis score is
strongly associated with worse survival in rheumatoid arthritis-
related interstitial lung disease. Mod Rheumatol. 2018;1–7.
118. Nakamura Y, Sugino K, Kitani M, et al. Clinico-radio-pathological
characteristics of unclassifiable idiopathic interstitial pneumonias.
Respir Investig. 2018;56:40–47.
119. Goh NSL, Desai SR, Veeraraghavan S, et al. Interstitial lung disease
in systemic sclerosis: a simple staging system. Am J Respir Crit Care
Med. 2008;177:1248–1254.
120. Takei R, Arita M, Kumagai S, et al. Radiographic fibrosis score
predicts survival in systemic sclerosis-associated interstitial lung
disease. Respirol Carlton Vic. 2018;23:385–391.
121. Kirkil G, Lower EE, Baughman RP. Predictors of Mortality in pul-
monary sarcoidosis. Chest. 2018;153:105–113.
122. Walsh SL, Wells AU, Sverzellati N, et al. An integrated clinicoradio-
logical staging system for pulmonary sarcoidosis: a case-cohort
study. Lancet Respir Med. 2014;2:123–130.
• This study provided by a simple staging system integrating the
pulmonary function and two HRCT variables to predict prog-
nosis in pulmonary sarcoidosis.
123. Moore OA, Goh N, Corte T, et al. Extent of disease on high-resolu-
tion computed tomography lung is a predictor of decline and
mortality in systemic sclerosis-related interstitial lung disease.
Rheumatol Oxf Engl. 2013;52:155–160.
124. Edey AJ, Devaraj AA, Barker RP, et al. Fibrotic idiopathic interstitial
pneumonias: HRCT findings that predict mortality. Eur Radiol.
2011;21:1586–1593.
125. Nurmi HM, Kettunen H-P, Suoranta S-K, et al. Several high-resolu-
tion computed tomography findings associate with survival and
clinical features in rheumatoid arthritis-associated interstitial lung
disease. Respir Med. 2018;134:24–30.
126. Jacob J, Bartholmai BJ, Rajagopalan S, et al. Unclassifiable-intersti-
tial lung disease: outcome prediction using CT and functional
indices. Respir Med. 2017;130:43–51.
127. Chung JH, Zhan X, Cao M, et al. Presence of air trapping and
mosaic attenuation on chest computed tomography predicts sur-
vival in chronic hypersensitivity pneumonitis. Ann Am Thorac Soc.
2017;14:1533–1538.
128. Best AC, Meng J, Lynch AM, et al. Idiopathic pulmonary fibrosis:
physiologic tests, quantitative CT indexes, and CT visual scores as
predictors of mortality. Radiology. 2008;246:935–940.
129. Jacob J, Bartholmai BJ, Rajagopalan S, et al. Automated quantita-
tive computed tomography versus visual computed tomography
scoring in idiopathic pulmonary fibrosis: validation against pul-
monary function. J Thorac Imaging. 2016;31:304–311.
130. Bartholmai BJ, Raghunath S, Karwoski RA, et al. Quantitative com-
puted tomography imaging of interstitial lung diseases. J Thorac
Imaging. 2013;28:298–307.
131. Humphries SM, Yagihashi K, Huckleberry J, et al. Idiopathic pul-
monary fibrosis: data-driven textural analysis of extent of fibrosis at
baseline and 15-month follow-up. Radiology. 2017;285:270–278.
EXPERT REVIEW OF RESPIRATORY MEDICINE 93
132. Sverzellati N, Brillet P-Y. When deep blue first defeated kas-
parov: is a machine stronger than a radiologist at predicting
prognosis in idiopathic pulmonary fibrosis? Eur Respir J.
2017;49.
133. Salisbury ML, Lynch DA, van Beek EJR, et al. Idiopathic pulmonary
fibrosis: the association between the adaptive multiple features
method and fibrosis outcomes. Am J Respir Crit Care Med.
2017;195:921–929.
134. Jacob J, Bartholmai BJ, Rajagopalan S, et al. Mortality prediction in
idiopathic pulmonary fibrosis: evaluation of computer-based CT
analysis with conventional severity measures. Eur Respir J.
2017;49.
135. Jacob J, Nicholson AG, Wells AU, et al. Impact of pulmonary vas-
cular volume on mortality in IPF: is it time to reconsider the role of
vasculature in disease pathogenesis and progression? Eur Respir J.
2017;49.
136. Yoon RG, Seo JB, Kim N, et al. Quantitative assessment of change in
regional disease patterns on serial HRCT of fibrotic interstitial
pneumonia with texture-based automated quantification system.
Eur Radiol. 2013;23:692–701.
137. Ariani A, Silva M, Seletti V, et al. Quantitative chest computed
tomography is associated with two prediction models of mortality
in interstitial lung disease related to systemic sclerosis. Rheumatol
Oxf Engl. 2017;56:922–927.
138. Yagi M, Taniguchi H, Kondoh Y, et al. CT-determined pulmonary
artery to aorta ratio as a predictor of elevated pulmonary artery
pressure and survival in idiopathic pulmonary fibrosis. Respirol
Carlton Vic. 2017;22:1393–1399.
139. Furukawa T, Kondoh Y, Taniguchi H, et al. A scoring system to
predict the elevation of mean pulmonary arterial pressure in
idiopathic pulmonary fibrosis. Eur Respir J. 2018;51.
140. Alkukhun L, Wang X-F, Ahmed MK, et al. Non-invasive screening for
pulmonary hypertension in idiopathic pulmonary fibrosis. Respir
Med. 2016;117:65–72.
141. Zisman DA, Karlamangla AS, Ross DJ, et al. High-resolution chest
CT findings do not predict the presence of pulmonary hyperten-
sion in advanced idiopathic pulmonary fibrosis. Chest.
2007;132:773–779.
142. Oda K, Ishimoto H, Yatera K, et al. High-resolution CT scoring
system-based grading scale predicts the clinical outcomes in
patients with idiopathic pulmonary fibrosis. Respir Res.
2014;15:10.
143. Wells AU, Desai SR, Rubens MB, et al. Idiopathic pulmonary fibrosis:
a composite physiologic index derived from disease extent
observed by computed tomography. Am J Respir Crit Care Med.
2003;167:962–969.
144. Uzunhan Y, Nunes H, Jeny F, et al. Chronic pulmonary aspergillosis
complicating sarcoidosis. Eur Respir J. 2017;49.
145. Ley B, Elicker BM, Hartman TE, et al. Idiopathic pulmonary fibrosis:
CT and risk of death. Radiology. 2014;273:570–579.
146. ElickerBM, Kallianos KG, Henry TS. The role of high-resolution
computed tomography in the follow-up of diffuse lung disease:
number 2 in the series “radiology” edited by Nicola Sverzellati
and Sujal Desai. Eur Respir Rev Off J Eur Respir Soc. 2017;26
147. Zappala CJ, Desai SR, Copley SJ, et al. Accuracy of individual vari-
ables in the monitoring of long-term change in pulmonary sarcoi-
dosis as judged by serial high-resolution CT scan data. Chest.
2014;145:101–107.
• This article described the disease-monitoring strategies of
serial pulmonary function tests and chest radiography com-
pared against morphologic change on HRCT.
148. Cottin V, Hansell DM, Sverzellati N, et al. Effect of emphysema
extent on serial lung function in patients with idiopathic pul-
monary fibrosis. Am J Respir Crit Care Med. 2017;196:1162–
1171.
149. Suliman YA, Dobrota R, Huscher D, et al. Brief report: pulmon-
ary function tests: high rate of false-negative results in the
early detection and screening of scleroderma-related interstitial
lung disease. Arthritis Rheumatol Hoboken NJ. 2015;67:3256–
3261.
94 F. JENY ET AL.
150. Ungprasert P, Crowson CS, Matteson EL. Association of sarcoidosis
with increased risk of VTE: a population-based study, 1976 to 2013.
Chest. 2017;151:425–430.
151. Nishimoto K, Fujisawa T, Yoshimura K, et al. The prognostic
significance of pneumothorax in patients with idiopathic pul-
monary fibrosis. Respirol Carlton Vic. 2018;23:519–525.
152. Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of
idiopathic pulmonary fibrosis. An international working group
report. Am J Respir Crit Care Med. 2016;194:265–275.
153. Le Jeune I, Gribbin J, West J, et al. The incidence of cancer in patients
with idiopathic pulmonary fibrosis and sarcoidosis in the UK. Respir Med.
2007;101:2534–2540.
154. Kato E, Takayanagi N, Takaku Y, et al. Incidence and predictive
factors of lung cancer in patients with idiopathic pulmonary fibro-
sis. ERJ Open Res. 2018;4.
155. Weissman DN. Role of chest computed tomography in prevention
of occupational respiratory disease: review of recent literature.
Semin Respir Crit Care Med. 2015;36:433–448.
156. Cottin V, Wells A. Unclassified or unclassifiable interstitial lung
disease: confusing or helpful disease category? Eur Respir J.
2013;42:576–579.
157. Walsh SLF, Hansell DM. Diffuse interstitial lung disease: overlaps
and uncertainties. Eur Radiol. 2010;20:1859–1867.
158. Tarando SR, Fetita C, Faccinetto A, et al. Increasing CAD system
efficacy for lung texture analysis using a convolutional network. SPIE
Med Imaging. 2016;97850Q – 9785–10. DOI:10.1117/12.2217752
159. Litjens G, Kooi T, Bejnordi BE, et al. A survey on deep learning in
medical image analysis. Med Image Anal. 2017;42:60–88.
160. Blum A, Zins M. Radiology: is its future bright? Diagn Interv
Imaging. 2017;98:369–371.