CASE CONFERENCES

Thoracic Radiology
Section Editors: Juliana Bueno, M.D., Jonathan Chung, M.D., and Stephen Hobbs, M.D.

Combined Pulmonary Fibrosis and Emphysema

Eric W. Pepin1, Nupur Verma1, Hiren J. Mehta2, and Tan-Lucien Mohammed1
1
Department of Radiology, and 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida College of Medicine,
Gainesville, Florida
ORCID ID: 0000-0001-7331-747X (H.J.M.).

Case Vignette

A 62-year-old man with 45 pack-year

history of cigarette smoking and known
emphysema presents with 3 months of
worsening dyspnea, now with symptoms at
rest, and reports increased use of home
supplemental oxygen. Chest radiograph is
shown (Figure 1), which prompted
computed tomographic (CT) imaging,
shown in Figure 2.

Figure 2. High-resolution computed tomography imaging of the thorax at apex (A) showing
centrilobular and paraseptal emphysema (asterisks); at the level of the carina (B) again showing
emphysema (asterisk) and now with subpleural reticulation and cyst formation, indicating interstitial
fibrosis (arrow); and at the base (C) showing more subpleural interstitial fibrosis with the characteristic
“honeycombing” pattern (arrow).

Figure 1. Anteroposterior chest radiograph Questions 3. What are characteristic pulmonary

showing coarsened lower-lobe–predominant function test results in patients with this
interstitial markings (asterisks) with decreased 1. Name two radiograph abnormalities in entity?
upper lung markings (arrows). Paucity of upper Figure 1 that may contribute to the patient’s 4. What treatment options are available to
lung markings is typical of the architectural dyspnea. this patient?
destruction caused by emphysema. There are
many potential etiologies of increased basilar 2. Given the combination of findings seen on
interstitial markings and additional imaging is CT imaging (Figure 2), what is the most
needed to further characterize this appearance. likely diagnosis? [Continue onto next page for answers]

(Received in original form June 18, 2017; accepted in final form September 22, 2017 )
Correspondence and requests for reprints should be addressed to Tan-Lucien Mohammed, M.D., University of Florida COM, Room G347, Box 100374,
Gainesville, FL 32610. E-mail: pepine@radiology.ufl.edu.
Ann Am Thorac Soc Vol 15, No 1, pp 110–112, Jan 2018
Copyright © 2018 by the American Thoracic Society
DOI: 10.1513/AnnalsATS.201706-473CC
Internet address: www.atsjournals.org

110 AnnalsATS Volume 15 Number 1 | January 2018

 CASE CONFERENCES

Discussion disruptive of the elastin–antielastin

balance (e.g., alpha-1 antitrypsin deficiency)
In patients with known emphysema who and thus affects the upper and lower lung
present with worsening dyspnea, chest zones. In all three subtypes, fibrotic changes
radiographs provide an initial assessment are not typical and should prompt further
of the pulmonary architecture. In our etiological investigation.
patient, the addition of bibasilar interstitial The coexistence of pulmonary fibrosis
markings to the established appearance and emphysema was first noted in 1990, but
of emphysema raises concern for a it was not hypothesized to be a distinct
superimposed process. Although this entity until further characterization 15 years
finding is nonspecific, it can be seen in later. Combined pulmonary fibrosis and
emphysema has been observed to occur Figure 3. High-resolution computed tomography
atypical infection, pulmonary edema, imaging near the level of the carina showing
infiltrative processes involving the almost exclusively in men with a history of
emphysematous changes (asterisks) and thick-
lymphatic system, and with parenchymal tobacco smoking. Typically, these patients
walled cystic lesions (arrows), which have
fibrosis. Clinical decision-making informed present with dyspnea on exertion and been hypothesized to be characteristic of
by history and physical examination without underlying connective tissue combined pulmonary fibrosis and emphysema.
would direct further investigation, which disease. One review by Papiris and The thick-walled cystic lesions demonstrate wall
may include microbiological studies, colleagues reported smoking histories thickness in excess of 1 mm and overall diameter
echocardiogram, routine blood analysis, ranging from 5 to 73 pack-years. greater than 1 cm. This is in contrast to the thin
Emphysema can be fully characterized walls of emphysematous changes and the smaller
and additional thoracic imaging. cyst size typical of honeycombing as seen in usual
In our patient, the classic appearance of on noncontrast enhanced computed
tomographic imaging of the chest and, given interstitial pneumonia.
lower-lung honeycombing on computed
the relation to smoking, is limited to
tomographic imaging confirms end-stage
paraseptal and centrilobular subtypes. Patients with combined pulmonary
fibrosis as the etiology of the increased
However, some cases can demonstrate fibrosis and emphysema have characteristic
interstitial markings seen on chest
severe confluent emphysema with pulmonary function tests showing mean
radiograph. The computed tomographic
destruction of the entire secondary values of forced vital capacity and total
imaging further characterizes the patient’s
pulmonary lobule, similar to the panlobular lung capacity usually within relatively
emphysema as centrilobular and paraseptal.
pattern. Upward of 90% of cases normal range, whereas diffusing capacity
This combination of emphysema and
demonstrate the presence of paraseptal of the lung for carbon monoxide is severely
fibrosis describes the distinct diagnosis
emphysema. Typically, fibrosis and diminished. Compared with patients with
of combined pulmonary fibrosis and honeycombing are diagnosed with high- only idiopathic pulmonary fibrosis, patients
emphysema. resolution computed tomographic imaging; with combined pulmonary fibrosis and
The American Thoracic Society has however, as thin computed tomographic emphysema have increased total lung
defined emphysema as “abnormal imaging slices become standardized, this capacity and reduced diffusing capacity
permanent enlargement of the airspaces diagnosis can be made on standard-protocol of the lung for carbon monoxide. Patients
distal to the terminal bronchiole, noncontrast computed tomographic with combined pulmonary fibrosis and
accompanied by destruction of their walls, imaging, with prone imaging reserved for emphysema are at increased risk of primary
and without obvious fibrosis.” This clarifying subpleural involvement. Thick- pulmonary malignancy compared with
destruction is hypothesized to occur via walled cystic lesions, defined as being greater similar patients having chronic obstructive
neutrophil-mediated disruption of the than 1 cm in diameter with a wall thickness pulmonary disease alone; they also have a
elastin–antielastin balance in the lung greater than 1 mm, have been proposed to worse prognosis. The overall prognosis
parenchyma. This process is believed to be the characteristic computed tomographic of combined pulmonary fibrosis and
be driven by chemokines released by imaging finding of combined pulmonary emphysema has been linked to the presence
macrophages as they respond to inhaled fibrosis and emphysema by Inomata and of pulmonary hypertension at the time
particulates (e.g., tobacco smoke), resulting colleagues, as these were seen in 73% of of diagnosis, with those patients having
in acquired emphysema having an upper patients with combined pulmonary fibrosis a shorter mean survival by 1 year. As many
lung predominance. At the histologic and emphysema and not seen in patients as half of patients with newly diagnosed
level, this is manifest as destruction of with idiopathic pulmonary fibrosis or disease have pulmonary hypertension on
the secondary pulmonary lobule with chronic obstructive pulmonary disease echocardiography at the time of combined
threefold classification. Centrilobular (Figure 3). Over time, patients with pulmonary fibrosis and emphysema
emphysema is characterized as destruction combined pulmonary fibrosis and diagnosis, a higher proportion than patients
about the respiratory bronchiole leading to emphysema demonstrate more rapid with idiopathic pulmonary fibrosis or
the acinus. Paraseptal emphysema is expansion of emphysematous lung than chronic obstructive pulmonary disease.
destruction more distally in the acinus patients with chronic obstructive Combined pulmonary fibrosis and
with damage to the alveoli. Last, panlobular pulmonary disease alone, and more rapid emphysema is a grave diagnosis with
emphysema encompasses the proximal lung destruction than patients with treatment largely being supportive care, in
and distal portions of the acinus, most chronic obstructive pulmonary disease or line with standard chronic obstructive
commonly seen in genetic disorders idiopathic pulmonary fibrosis. pulmonary disease and idiopathic

Case Conferences: Thoracic Radiology 111

 CASE CONFERENCES

pulmonary fibrosis treatments. These are basilar predominant subpleural cysts transplantation is the only curative
patients need to be evaluated for lung and reticular markings representing fibrosis treatment.
transplantation, as this is the only curative and honeycombing. Given the constellation
intervention. of these findings, a diagnosis of combined
pulmonary fibrosis and emphysema is Follow-Up
made.
Answers
3. What are characteristic pulmonary Our patient was observed to have
1. Name two radiograph abnormalities in function test results in patients with this a progressive decline in his capacity
Figure 1 that may contribute to the patient’s entity? for diffusing carbon monoxide, less
dyspnea. than 35% when last assessed
Patients with combined pulmonary fibrosis pretransplant. He completed pre–lung
Decreased upper lung markings are and emphysema have mean values of forced transplant evaluation and underwent
suggestive of emphysema in this long-time vital capacity and total lung capacity usually successful bilateral lung transplantation.
smoker. Prominent bibasilar interstitial within relatively normal range, whereas Histopathologic analysis of the
markings raise concern for a superimposed diffusing capacity of the lung for carbon explanted lungs confirmed the
parenchymal process, such as pulmonary monoxide is severely diminished. diagnosis showing severe paraseptal and
edema or other chronic process like fibrosis, centrilobular emphysema with extensive
4. What treatment options are available to
which should prompt further workup. anthracotic pigment deposition in the
this patient?
2. Given the combination of findings seen on apices and significant interstitial
Patients with combined pulmonary fibrosis fibrosis with microcystic formation
CT imaging (Figure 2), what is the most
and emphysema require supplemental and scattered fibroblastic foci in the
likely diagnosis?
oxygen and derive some benefit from lower lobes. n
The CT imaging shows moderate mainstays of chronic obstructive pulmonary
centrilobular emphysema as well as mild disease, including bronchodilators and Author disclosures are available with the text
paraseptal emphysema. Furthermore, there inhaled steroids. Ultimately, lung of this article at www.atsjournals.org.

Recommended Reading
Inomata M, Ikushima S, Awano N, Kondoh K, Satake K, Masuo M, et al. Papiris SA, Triantafillidou C, Manali ED, Kolilekas L, Baou K, Kagouridis K,
An autopsy study of combined pulmonary fibrosis and emphysema: et al. Combined pulmonary fibrosis and emphysema. Expert Rev
correlations among clinical, radiological, and pathological features. Respir Med 2013;7:19–31, quiz 32.
BMC Pulm Med 2014;14:104. Standards for the diagnosis and care of patients with chronic
Matsuoka S, Yamashiro T, Matsushita S, Fujikawa A, Kotoku A, Yagihashi K, et obstructive pulmonary disease (COPD) and asthma. This official
al. Morphological disease progression of combined pulmonary fibrosis statement of the American Thoracic Society was adopted by the
and emphysema: comparison with emphysema alone and pulmonary ATS Board of Directors, November 1986. Am Rev Respir Dis 1987;
fibrosis alone. J Comput Assist Tomogr 2015;39:153–159. 136:225–244.

112 AnnalsATS Volume 15 Number 1 | January 2018