Novel clinical scoring system to identify patients with
pneumothorax with suspicion for Birt–Hogg–Dubé syndrome
Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo;
Pneumothorax Research Center and Division of Thoracic Surgery, Nissan Tamagawa Hospital, Tokyo;
The Study Group for
Pneumothorax and Cystic Lung Diseases, Tokyo, Japan
Background and objective: Birt–Hogg–Dubé syndrome
(BHDS) is a rare hereditary disease that presents with
multiple lung cysts and pneumothorax (PTX). Although
some reports propose that ﬁndings from chest com-
puted tomography enable one to distinguish BHDS from
primary spontaneous pneumothorax (PSP), it is still
unclear whether clinical features are useful for identify-
ing patients with suspicion of BHDS from those
Methods: We retrospectively reviewed the medical
records of patients with PTX who underwent video-
assisted thoracoscopic surgery at Nissan Tamagawa
Hospital from January 2012 to December 2015.
Results: We identiﬁed a total of 1141 patients with PTX,
including 54 with BHDS and 517 with PSP. Among
them, logistic regression analysis segregated ﬁve fea-
tures that were signiﬁcantly associated with BHDS:
familial history of PTX, past history of bilateral PTX,
age at the ﬁrst episode of PTX (≥25 years old (y.o.)),
body mass index (≥18.5) and gender (female). We
assigned scores of 3, 3, 2, 2 and 1 to the ﬁve features,
respectively, to establish a system with a calculated
score from 0 to 11. The cut-off value of a calculated
score ≥ 4 yielded the highest sensitivity of 93% and
speciﬁcity of 86%. Receiver operating characteristic
(ROC) analysis showed the area under the curve reﬂect-
ing an accuracy of this diagnostic test as 0.953.
Conclusion: BHDS has several clinical features distinct
from PSP. Our scoring system consists of only ﬁve clini-
cal variables that are easily evaluated and efﬁciently
separate BHDS patients from those who have PTX with-
out relying on an imaging study. Further prospective
study is needed to conﬁrm our ﬁndings.
Birt–Hogg–Dubé syndrome, scoring system, spon-
taneous pneumothorax, total pleural covering.
AIC, Akaike information criterion; AUC, area
under the curve; BHDS, Birt–Hogg–Dubé syndrome; CT,
computed tomography; PSP, primary spontaneous
pneumothorax; PTX, pneumothorax; ROC, receiver operating
characteristic; VATS, video-assisted thoracoscopic surgery.
Birt–Hogg–Dubé syndrome (BHDS), a hereditary geno-
dermatosis, was ﬁrst described in 1975 and 1977.
Subsequent studies revealed that the candidate gene
for BHDS was located on chromosome 17p11.2. This
subsequently named FLCN gene is composed of
14 exons and encodes a protein called folliculin.
indications of this syndrome are recognized as multiple
lung cysts with recurrent pneumothorax (PTX), ﬁbro-
folliculomas of the skin and renal tumours. Among
these clinical features, lung manifestations are the ear-
liest to occur, usually at 20–30 years of age, whereas
skin and renal manifestations do not appear until the
In particular, PTX presents with sudden-
onset shortness of breath and/or chest pain; therefore,
patients with BHDS are often referred to outpatient or
emergency departments, as PTX is the ﬁrst presenta-
tion of the disease. Accordingly, pulmonologists and
thoracic surgeons have a complex role if they are to
establish the earliest possible diagnosis of BHDS,
thereby beneﬁtting patients by initiating periodic
screenings for renal neoplasia.
Primary spontaneous pneumothorax (PSP), the most
common type of PTX, is a spontaneously occurring air
leakage into the pleural space. The disease usually
Correspondence: Hiroki Ebana, Division of Respiratory
Medicine, Juntendo University Faculty of Medicine and
Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo
113-8421, Japan. Email: email@example.com
Received 10 May 2017; invited to revise 20 June and
6 August 2017; revised 19 July and 9 August 2017; accepted
13 August 2017 (Associate Editor: Ioannis Kalomenidis).
SUMMARY AT A GLANCE
The novel scoring system described here readily dis-
tinguishes Birt–Hogg–Dubé syndrome (BHDS) from
primary spontaneous pneumothorax (PTX) by
applying ﬁve clinical variables that are easily evalu-
ated, are highly sensitive and have strong speciﬁcity.
This system provides pulmonologists and thoracic
surgeons a tool to avoid overlooking BHDS among
the patients with PTX in daily clinical practice.
© 2017 Asian Paciﬁc Society of Respirology Respirology (2018) 23, 414–418