Pneumothorax

Pneumothorax
Classification and Etiology

Nai-Chien Huan, MBBS, MRCPa, Calvin Sidhu, MBBS, FRACPb,c,
Rajesh Thomas, MBBS, PhD, FRACPc,d,*
KEYWORDS
Pneumothorax Smoking Primary pneumothorax Secondary pneumothorax
Diffuse cystic lung disease
KEY POINTS
Pneumothorax can develop because of diverse etiologies; in many cases, no specific cause may be
identified.
Tension pneumothorax is a pathophysiologic, not a radiologic, diagnosis.
Patients with primary spontaneous pneumothorax may have lung abnormalities that are not
apparent on chest radiographs. Tobacco smoking is the most important risk factor.
Chronic obstructive pulmonary disease is the most common underlying lung disorder associated
with secondary spontaneous pneumothorax.Recurrent pneumothorax is common in diffuse cystic
lung diseases.
The exact pathogenetic mechanisms of spontaneous pneumothorax development are unknown.
An interplay between lung-related abnormalities and environmental factors is likely in most cases.
INTRODUCTION knowledge and understanding of underlying risks

and pathophysiologic mechanisms that lead to
Pneumothorax is a common clinical problem development of pneumothorax.
worldwide.1 Pneumothorax is defined as presence
of air in the pleural cavity. It can develop second-
ary to diverse etiologies including traumatic, in- HISTORICAL PERSPECTIVE
flammatory, infective, malignant, genetic, and Pneumothorax has been long recognized since the
hormonal causes; in many cases, the lung appears days of Hippocrates (circa 460–370 BC). Ancient
normal and there may be no recognizable underly- Greek physicians would listen to a “succussion
ing lung abnormality. The severity of clinical man- splash,” elicited by vigorously shaking the pa-
ifestations in a patient with pneumothorax ranges tient’s chest, to diagnose the presence of a hydro-
from asymptomatic to life-threatening, and may pneumothorax. The native Americans had learned
be disproportionate to pneumothorax size. In this that a single arrow into the chest of a North Amer-
review, we provide an overview of the historical ican bison could quickly incapacitate it during
perspective, epidemiology, classification, and eti- hunting. Unlike most mammals, the bison has a
ology of pneumothorax. We also explore current single pleural cavity because of an incomplete
chestmed.theclinics.com
Funding: R. Thomas has received career research fellowship funding from National Health and Medical
Research Council, Australia and Cancer Council Western Australia, Australia.
Declaration of interest: The authors have nothing to disclose.
a
Department of Pulmonology, Serdang Hospital, Kajang, Malaysia; b Edith Cowan University, Perth, Australia;
c
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia; d School of Medicine,
University of Western Australia, Perth, Australia
* Corresponding author.
E-mail address: rajesh.thomas@health.wa.gov.au
Clin Chest Med 42 (2021) 711–727

https://doi.org/10.1016/j.ccm.2021.08.007
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712 Huan et al
mediastinum, making it vulnerable to bilateral ten- incidence rate of 0.042% (0.050% in males vs
sion pneumothoraces following a penetrating 0.018% in females).10 Although asymptomatic,
injury in one hemithorax (Fig. 1). 50% of these affected students had moderate-
The term “pneumothorax” (a Greek composite severe pneumothorax on chest radiograph
word derived from “pneuma – air” and “thorax – (defined as lung collapse >10% of hemithorax).
chest”) was first coined in 1803 by Jean Marc Gas-
pard Itard,2 a French physician and student of Recurrence
Rene Laennec (1781–1826). Laennec3 would later Recurrence of pneumothorax following an initial
describe the clinical and anatomic details of pneu- episode is common; this necessitates pneumo-
mothorax in 1819. Most cases of pneumothorax thorax management plans to consider the likeli-
were initially believed to be secondary to pulmo- hood of recurrence and need for recurrence
nary tuberculosis.4 Kjaergaad5 in 1932 provided prevention interventions. The reported rates of
the first modern description of primary sponta- recurrence following spontaneous pneumothorax
neous pneumothorax (PSP) wherein he made a is highly variable because of heterogeneities in
clear distinction of “pneumothorax simple” (ie, protocols, population, treatment algorithms, and
pneumothorax in young patients with no apparent follow-up periods in different studies.11 Long-
lung disease) versus pneumothorax secondary to term follow-up studies show PSP recurrence rate
pulmonary tuberculosis. This distinction was ranging between 16% and 52%.11–14 One age-
important because patients with pulmonary tuber- stratified longitudinal epidemiologic study from
culosis in those days would be confined long-term Taiwan reported a PSP recurrence rate of
in sanitoriums. 23.7%15 and a similar study from France had a
PSP recurrence rate of 28%; most pneumothorax
EPIDEMIOLOGY recurrence was seen in the first year following the
Incidence index episode.16 A recent systematic review (29
studies involving 13,548 patients) reported similar
The reported incidence of pneumothorax varies findings of overall PSP recurrence rate of 32%
depending on study regions and may be lower (29% 1-year recurrence)14; recurrence was three
than the real incidence because of underreporting times more among females (odds ratio, 3.03) and
and underdiagnosis in asymptomatic patients. smoking cessation reduced recurrence risk by
Epidemiologic studies have shown an overall inci- four-fold (odds ratio, 0.26).
dence of spontaneous pneumothorax of 16.8 per Recurrence is higher in SSP (40%–56% in
100,000 population per year (24/100,000/year for different studies)17,18 and occurs earlier, usually
males; 9.8/100,000/year for females) in England.6 within 6 months of the initial episode.19 The risk
The incidence of spontaneous pneumothorax of multiple subsequent pneumothorax episodes,
from Sweden (Stockholm, 1975–1984) was lower without prevention intervention, also remains.12
at 18/100,000/year in males and 6/100,000/year In one retrospective study by Voge and Anthracite,
in females.7 The age-adjusted incidence of PSP 28% patients had a second episode, 23% had a
and secondary spontaneous pneumothorax third episode, and 14% developed a fourth
(SSP) in the United States was 4.2 and 3.8 per episode of spontaneous pneumothorax.20
100,000 population per year, respectively.8
The peak incidence of spontaneous pneumo-
CLASSIFICATION OF PNEUMOTHORAX
thorax shows a clear bimodal distribution: PSP is
Classification by Size
most commonly seen in patients between 15 and
34 years and the incidence of SSP is highest in pa- Several methods have been described to measure
tients older than 55 years.6 The incidence of pa- and classify pneumothorax size. Light index calcu-
tients with pneumothorax who need lates pneumothorax size from the ratio of cubed
hospitalization is reported to be 11.1 per 100,000 diameters of collapsed lung and hemithorax on a
population per year (16.6/100,000/year for males chest radiograph (pneumothorax size [%] 5 100
and 5.8/100,000/year for females).6 The annual [1 average lung diameter3/average hemi-
cost of spontaneous pneumothorax management thorax diameter3]) and shows good correlation
in the United States is estimated to be $130 with the volume of air removed (Fig. 2).21 Collin for-
million.9 mula to estimate pneumothorax volume from a
The incidence of asymptomatic pneumothorax chest radiograph was derived based on helical
is harder to assess. One retrospective study that computed tomography (CT) volumetrics22 and
reviewed 101,709 chest radiographs performed uses three interpleural distances measured at
during routine medical check-ups of university stu- specified points (a, b, and c); the estimated pneu-
dents in Tokyo, Japan reported a pneumothorax mothorax volume is calculated by formula
Pneumothorax: Classification and Aetiology 713
Fig. 1. Chest radiograph of a patient who developed bilateral pneumothorax (A) following computed tomogra-
phy (CT)-guided lung biopsy of a right lower lobe nodule (B). Sternotomy wires from a previous coronary artery
bypass graft are noted. The coronary artery bypass graft surgery resulted in communication between right and
left pleural cavities across the mediastinum leading to bilateral pneumothorax following right lung biopsy. Chest
radiograph performed 2 hours after placement of an intercostal catheter in the right pleural cavity shows
improvement of pneumothorax on both sides (C).
Y 5 4.2 1 (4.7 [a 1 b 1 c]) (Fig. 3). CT scans us- without causing complete lung collapse; and (3)
ing three-dimensional measurements are more ac- complete pneumothorax, for total lung collapse
curate than chest radiographs in calculating (Fig. 4). The American College of Chest Physicians
pneumothorax size. (ACCP) pneumothorax guidelines classify pneu-
Several international guidelines recommend mothorax size depending on the distance from
assessing pneumothorax size using chest radio- the apex of the collapsed lung to the ipsilateral
graph measurements to guide treatment interven- thoracic cupola.9 This distance is greater
tions. The Spanish Society of Pulmonology and than 3 cm with a large pneumothorax and less
Thoracic Surgery23 classifies pneumothorax, than 3 cm with a small pneumothorax (Fig. 5).
based on morphologic and anatomic criteria, into This method can lead to overestimation of pneu-
(1) partial pneumothorax, when the visceral pleura mothorax size with a predominantly apical pneu-
is only partially detached from the chest wall, such mothorax. The British Thoracic Society (BTS)
as in isolated apical pneumothorax; (2) incomplete pneumothorax guidelines classify pneumothorax
pneumothorax, when both visceral and parietal size based on the interpleural distance measured
pleurae are fully separated from apex to base but at the level of the hilum.24 The interpleural distance
is less than 2 cm in a small pneumothorax and cor-
relates with a pneumothorax occupying less than
50% of the hemithorax volume (Fig. 6).24,25 Inter-
pleural distance of greater than 2 cm helps to iden-
tify a pneumothorax that could be drained safely
by needle or chest drain decompression without
causing lung injury.26
There is poor agreement between international
guidelines and studies of pneumothorax size and
management strategies. A study comparing the
BTS, ACCP, and Belgian Society of Pulmonology
guidelines showed agreement in only 47% of
cases.27 A different study showed that adherence
in a UK hospital to the BTS guidelines was seen in
70% of PSP cases and to ACCP guidelines in
32%, and resulted in conflicting management rec-
ommendations depending on the guidelines
used.28 A pneumothorax typically resolves by
2% per day without intervention29 and therefore,
it was believed that a large pneumothorax is best
Fig. 2. Light method to measure pneumothorax vol- treated by pleural drainage and rapid lung
ume: Pneumothorax % 5 100 [1-b3/a3].
714 Huan et al
results from direct injury to the chest wall or lung.

More commonly, pneumothorax occurs spontane-
ously without preceding injury or trauma. Sponta-
neous pneumothorax is broadly classified into
PSP and SSP; PSP occurs in patients with
“normal” lungs and no apparent abnormalities on
chest radiographs, whereas SSP develops in pa-
tients who have underlying lung disease.24
Tension pneumothorax
It should be emphasized that tension pneumo-
thorax is a pathophysiologic, and not a radiologic,
diagnosis because patients with a large pneumo-
thorax but without cardiopulmonary collapse often
get misdiagnosed to have tension pneumothorax.
Tension pneumothorax is rarely seen among
spontaneously breathing patients with PSP33 and
SSP. It is more likely to occur among patients
Fig. 3. Collin formula: Pneumothorax volume 5 with traumatic pneumothorax and those receiving
4.2 1 [4.7 (a 1 b 1 c)]. positive pressure mechanical ventilation32; the
pneumothorax progresses rapidly because of
ongoing positive pressure ventilation to cause
re-expansion. However, precise measurements of
cardiorespiratory collapse.32,34 It is important to
pneumothorax size may not have as much clinical
recognize tension pneumothorax because, unlike
value as previously thought with increasing evi-
large PSP and SSP that usually do not require im-
dence suggesting that a symptom-driven man-
mediate drainage, tension pneumothorax requires
agement algorithm, rather than based on
emergency decompression.34
pneumothorax size alone, might be more
beneficial.30,31 Traumatic pneumothorax
Pneumothorax caused by injuries to the chest or
lung is classified as traumatic.35 Traumatic pneu-
Classification by Pathophysiology and
mothorax may be iatrogenic, as a complication
Etiology
following medical procedures or interventions;
Pneumothorax is classified by underlying etiology and noniatrogenic, when caused by blunt or pene-
and pathophysiology; the clinical presentation, trating chest injuries, such as following motor
pneumothorax progress or resolution, likelihood vehicle accident trauma and falls (Fig. 7).35,36
of pneumothorax recurrence, and management Greater than 10% of trauma patients may develop
strategies can vary significantly (Box 1).24 Tension blunt chest injury-related pneumothorax that is
pneumothorax is a rare, life-threatening condition associated with mortality rates of 5% to 20%37
that develops when air trapped within the pleural from life-threatening hemothorax, tension pneumo-
cavity under positive pressure leads to cardiopul- thorax, and damage to surrounding major organs,
monary compromise.32 Traumatic pneumothorax such as the thoracic aorta.35 Chest wall defects
Fig. 4. Left partial left pneumothorax (A). Left incomplete pneumothorax (B). Left complete pneumothorax (C).
requires management by thoracic and/or trauma

surgeons.
Iatrogenic pneumothorax develops following
complications from medical interventions, such
as transbronchial lung biopsy, transthoracic nee-
dle aspiration,38,39 lung cryobiopsy,40,41 central
vascular catheter insertion,42 pacemaker inser-
tion,43 thoracentesis,44 and barotrauma in me-
chanically ventilated patients (Fig. 8).36 Iatrogenic
pneumothorax may be difficult to identify in intu-
bated patients who develop barotrauma; the sub-
tle deep sulcus sign on supine chest radiographs
in these patients should be carefully looked for,
otherwise delayed diagnosis of pneumothorax
can result in significant morbidity and even death.
Rare cases of iatrogenic pneumothorax associ-
ated with chest acupuncture,45,46 colonoscopy,47
breast augmentation,48 and radiofrequency abla-
tion (Fig. 9) have also been reported.
The overall prevalence of iatrogenic pneumo-
Fig. 5. The ACCP pneumothorax guidelines classify thorax varies depending on the nature, frequency,
pneumothorax size based on lung apex-cupola dis- and setting of medical interventions being per-
tance of <3 cm (small pneumothorax) or >3 cm (large formed. One study reported a 1.36% prevalence
pneumothorax). of iatrogenic pneumothorax related to invasive
medical interventions, 57% of which were emer-
from penetrating chest injuries allows external air to gency procedures.36 The most common causes
be entrained into the pleural space during inspira- of iatrogenic pneumothorax are central venous
tion leading to open traumatic pneumothorax.35 catheter insertions, thoracentesis, and mechanical
Noniatrogenic traumatic pneumothorax often ventilation.49 Iatrogenic pneumothorax is more
prevalent in teaching hospitals compared with
nonteaching hospitals in the United States,50 ac-
counting for 56% of all pneumothorax cases
among inpatients.49
Procedure-, patient-, and operator-related fac-
tors mainly determine the likelihood of iatrogenic
pneumothorax (Box 2).
Primary spontaneous pneumothorax

Patients with PSP may have underlying risk factors
and lung abnormalities that are not initially
apparent on chest radiographs. Tobacco smoking
is the single most important risk factor for
PSP.26,30 Up to 88% of patients with PSP are
smokers in large-scale observational studies.7 A
smoker, compared with nonsmokers, has a 9-
fold risk in females and a 22-fold risk in males of
developing PSP with a strong dose-response link
between the number of cigarettes smoked and
pneumothorax risk.7 Cannabis smoking also in-
creases risk of developing spontaneous pneumo-
thorax30,51,52 and is associated with development
Fig. 6. The BTS pneumothorax guidelines classify
of emphysematous changes and bullous lung dis-
pneumothorax size based on interpleural distance of
<2 cm (small pneumothorax) or >2 cm (large pneumo- ease.30,51 Height and male sex are both important
thorax). Interpleural distance of >2 cm helps to iden- risk factors for PSP.8 PSP is three- to six-fold more
tify a pneumothorax that could be drained safely by common in men than in women.8,33 It is hypothe-
needle or chest drain decompression without causing sized that in tall men, pleural blebs may develop
lung injury. because of greater mechanical stretching of lung
716 Huan et al
Box 1 hypoxemia, hypercapnia, and respiratory failure

Classification of pneumothorax by because of poor lung reserve.33
pathophysiology Air enters the pleural cavity via various routes
including (1) alveolar and visceral pleural rupture
1. Tension pneumothorax causing an alveolopleural fistula, such as with
2. Traumatic pneumothorax emphysema and necrotizing pneumonia; (2) via
the lung interstitium; and (3) via the mediastinal
a. Iatrogenic pneumothorax
pleura causing a pneumomediastinum.33
b. Noniatrogenic pneumothorax
Chronic obstructive pulmonary disease Chronic
3. Spontaneous pneumothorax
obstructive pulmonary disease (COPD) is the
a. Primary spontaneous pneumothorax most frequent lung disease associated with
b. Secondary spontaneous pneumothorax SSP.33,54 Data from a large English hospital data-
base that recorded all admissions for spontaneous
pneumothorax showed that 61% of cases were
caused by COPD and predominantly affected
tissue in the apex during growth or because the
males (73% vs 27% females)6; the proportion of
lung tissue in the apex grows faster than accom-
COPD as a cause for pneumothorax also
panying vasculature and outstrips its blood
increased by 9% between 1968 and 2016. Another
supply.53
study reported that 80% of all spontaneous pneu-
mothoraces requiring inpatient treatment were
caused by COPD, interstitial lung disease, and
Secondary spontaneous pneumothorax malignancy.55
SSP can occur in association with many primary The most common mechanism for development
lung diseases33 and systemic conditions with of spontaneous pneumothorax in patients with
lung involvement. Compared with PSP, patients COPD is by rupture of emphysematous blebs
with SSP are typically older.6 The BTS pneumo- and bullae.53 Patients with COPD, especially in
thorax guidelines recommended including pa- the presence of significant air-trapping and lung
tients older than 50 years and/or those with hyperinflation, are also at increased risk of iatro-
significant smoking history as having SSP, even genic pneumothorax from procedures, such as
when the chest radiograph appears normal, in central vascular catheter insertion, trans-thoracic
view of their high likelihood of having underlying lung biopsy, and transbronchial lung biopsy.53
lung pathology.24 Dyspnea is the most common
presenting feature in SSP unlike with PSP, where Tuberculosis Pulmonary tuberculosis is the most
patients commonly present with chest pain.33 Pa- common cause for SSP in endemic areas.56 Spon-
tients with SSP can rapidly develop cyanosis, taneous pneumothorax occurs when a tubercu-
lous cavity ruptures into the pleural space or
from direct tuberculous invasion and necrosis of
lung parenchyma and visceral pleura.53 A long-
term follow-up study of 872 patients treated for
spontaneous pneumothorax in Gran Canaria,
Spain found the pneumothorax was tuberculosis-
related in 5.4%57; this may be higher in
tuberculosis-endemic areas. It is estimated that
0.6% to 1.4% of patients with pulmonary tubercu-
losis will develop SSP during the course of their
treatment.58,59 Tuberculosis-related pneumo-
thorax can lead to empyema, acute respiratory
failure, cachexia, and persistent bronchopleural
fistula.60 The overall burden of tuberculosis-
related pneumothorax is likely to be significant
because of the high incidence of tuberculosis
worldwide.
Other pulmonary infections SSP can develop

Fig. 7. Traumatic right-sided pneumothorax in an with typical and atypical pulmonary infections.
elderly woman with displaced rib fractures (arrow) Common bacterial pneumoniae secondary to
following a fall. Klebsiella, Staphylococcus, Pseudomonas, and
mechanisms and characteristic lung cyst pat-

terns on high-resolution CT (HRCT) imaging. The
diseases are individually rare but collectively
form a significant minority. They are broadly clas-
sified based on their underlying etiology into (1)
neoplastic, such as lymphangioleiomyomatosis
(LAM) and pulmonary Langerhans cell histiocyto-
sis (PLCH); (2) developmental, such as Birt-Hogg-
Dube (BHD) syndrome and neurofibromatosis; (3)
lymphoproliferative, such as lymphocytic intersti-
tial pneumonia; (4) infectious, such as P jirovecii
and staphylococcal pneumonia; and (5)
smoking-related, such as smoking-related
PLCH.68 DCLDs with overlapping features may
be included in multiple categories.
The characteristic cystic patterns of different
DCLDs are often diagnostic. The cysts develop
Fig. 8. Chest radiograph showing left-sided iatrogenic following inflammatory or infiltrative destruction
pneumothorax that developed 2 hours following per- and/or replacement of alveolar septa, small air-
manent pacemaker insertion. ways and blood vessels in the secondary lung lob-
ules. Spontaneous pneumothorax, often recurrent,
is the presenting manifestation in greater than
anaerobic organisms may result in unilateral 50% of cases in many DCLDs; early diagnosis of
SSP,54 caused by direct invasion and necrosis of DCLDs at this stage has therapeutic implications
lung and visceral pleura (Fig. 10). Pneumothorax in cases where the natural disease course is modi-
associated with Pneumocystis jirovecii pneumonia fiable with pharmacologic and nonpharmacologic
(PCP) is commonly bilateral.61–63 Patients with interventions, such as sirolimus in LAM and smok-
HIV64 infection and PCP are particularly at risk of ing cessation in PLCH.
developing a pneumothorax (9% vs 2%–4% of
non-HIV patients with PCP).62,63 An aspergilloma Lymphangioleiomyomatosis LAM is caused by
can rupture into the pleural cavity to cause pneu- infiltration of the lung by smooth muscle cells
mothorax.65,66 The novel corona virus 2019 that are growth-activated by mutations in the tu-
(COVID-19) infection is also associated with pneu- berous sclerosis genes and spread through blood
mothorax (incidence of 1%); the 28-day survival in and lymphatics.69,70 Infiltration and destruction of
this cohort was not significantly different to airways, lymphatics, and blood vessels by the
COVID-19 patients without.67 smooth muscle cells lead to the formation of
thin-walled, uniformly distributed lung cysts
Diffuse cystic lung disease Diffuse cystic lung dis- (Fig. 11A, B).71 Cyst rupture results in recurrent
ease (DCLD) is group of heterogenous lung dis- pneumothorax. LAM is often not recognized to
eases with diverse pathophysiologic be the cause for pneumothorax in young patients
Fig. 9. Chest radiograph showing iatrogenic right-sided pneumothorax following radiofrequency ablation (RFA)
of right upper lobe tumor (A). CT scan of chest (axial and coronal views) shows a bronchopleural fistula and
breach of visceral pleura (arrows) caused by RFA leading to iatrogenic pneumothorax (B, C).
718 Huan et al
Box 2 and without an HRCT scan, pneumothorax in pa-

Factors associated with iatrogenic tients with early LAM may be misdiagnosed as
pneumothorax PSP.
LAM can occur either as part of the tuberous
1. Procedure-related sclerosis complex LAM or sporadically in patients
a. Elective versus emergency procedure without tuberous sclerosis; the latter almost al-
ways develops in females of childbearing age.72
b. Intervention type
In addition to spontaneous pneumothorax, LAM
i. Involving lung: transbronchial lung bi- is associated with angiomyolipoma (Fig. 11C),73
opsy and trans-thoracic needle biopsy lymphangiomyoma, chylous ascites, and chylous
have higher risks pleural effusions. LAM is diagnosed based on the
ii. Not involving lung: pacemaker and characteristic cystic pattern on CT, without
central vascular catheter insertion needing a lung biopsy, when it is associated with
have a lower risk tuberous sclerosis, angiomyolipoma, or chylo-
iii. Number of biopsies thorax,74 or when the serum vascular endothelial
iv. Biopsy needle size growth factor (VEGF)-D level is greater than 800
pg/mL.75
c. Imaging guidance (versus not)
Pulmonary Langerhans cell histiocytosis PLCH is
i. CT for trans-thoracic approaches
most commonly seen in young smokers; 10% to
ii. Ultrasound for central vascular cath- 20% of patients with PLCH develop a spontaneous
eter insertion and thoracentesis
pneumothorax.76,77 PLCH is characterized by peri-
2. Patient-related bronchiolar accumulation of Langerhans cells that
a. Patient anatomy: body mass index, previ- are specialized dendritic cells regulating mucosal
ous interventions at same site, scarring airway immunity and activated by cigarette
smoke–induced cytokine mediation.78,79 The char-
b. Uncooperative or restless patient
acteristic HRCT pattern is of nodular and cystic ab-
c. Underlying lung disease: severe emphy- normalities, predominantly in the upper and middle
sema, bullous lung disease lung zones (Fig. 12). The bizarrely shaped cysts are
3. Operator-related different to the uniform, thin-walled cysts seen with
most other DCLDs. Smoking cessation and avoid-
a. Experience
ance of second-hand smoke may result in stabiliza-
b. Skill tion and resolution of PLCH.
Birt-Hogg-Dube Syndrome BHD is an autosomal-
dominant disorder characterized by the triad of
hair follicle and renal tumors, and pulmonary cysts
that typically manifest in the fourth to fifth
decade.80 Patients with BHD have a 50-fold risk
of developing pneumothorax compared with the
general population81 and a 75% pneumothorax
recurrence rate.82 BHD may be more common
than initially believed with studies reporting 5%
to 10% prevalence in young adults presenting
with pneumothorax.83,84 Cyst rupture results in
pneumothorax formation; however, pneumothorax
in the absence of cysts is also reported.85 BHD is
caused by mutations in the FLCN gene, which en-
codes folliculin, a tumor suppressor protein. Cyst
formation in BHD occurs following activation of
the mTOR pathway causing adhesion protein de-
fects that damage the alveolar-septal junction.86
The characteristic pattern in BHD is of variably
sized, round-lentiform-shaped, thin-walled cysts
Fig. 10. CT chest (axial view) shows necrotizing lung with a predominantly basal and subpleural distri-
abscess with bronchopleural fistula (arrow) in the bution (Fig. 13A–C).87 Renal tumors are seen in
left upper lobe causing spontaneous pneumothorax. greater than 25% of patients with BHD and require
Fig. 11. CT chest axial (A) and coronal (B) views showing characteristic thin-walled uniformly shaped and distrib-
uted cysts of LAM in a young female presenting with recurrent left-sided pneumothorax. CT abdomen (C) shows a
left-sided angiomyolipoma (arrow) in the same patient.
active screening and surveillance. BHD should be of childbearing age.88,89 Based on clinical and
suspected in young patients with spontaneous pathologic findings, pneumothorax in women of
pneumothorax, skin lesions resembling folliculo- childbearing age is classified into three groups:
mas (Fig. 13D, E), and renal tumors and in those (1) catamenial pneumothorax (with or without
with a similar family history. endometriosis), (2) endometriosis-related nonca-
Other rare inherited and genetic disorders, such tamenial pneumothorax (pneumothorax occurring
as neurofibromatosis and Ehlers-Danlos syn- outside the menstrual period but with pathologic
drome, with characteristic DCLD patterns on findings of endometriosis), and (3) idiopathic pneu-
HRCT are also associated with high risk of sponta- mothorax (noncatamenial and nonendometriosis
neous pneumothorax and recurrence (Fig. 14). with no underlying cause identified).90
Catamenial pneumothorax is associated with
Pneumothorax in women of childbearing age The the menstrual cycle and typically occurs within
overall incidence of pneumothorax is lower among 72 hours before and after the onset of menstrual
females; however, there are unique conditions that period. Catamenial pneumothorax is likely under-
present with recurrent spontaneous pneumo- diagnosed; a study of menstruating women under-
thorax and occur only, or predominantly, in women going surgery for spontaneous pneumothorax
found a catamenial cause in 30%.91 It is usually
unilateral, predominantly on the right side, and
associated with thoracic and/or extrathoracic
endometriosis.92,93 Pneumothorax develops
when endometrial tissue in the lung and visceral
pleura ruptures. The endometrial tissue is thought
to reach the lung and pleura by intra-abdominal
migration, micrometastatic seeding, or lympho-
vascular spread. Endometriosis-related pneumo-
thorax can also develop following rupture of
pelvic endometriosis and transgenital or trans-
diaphragmatic tracking up of air through diaphrag-
matic defects into the pleural space.94 Single or
multiple fenestrations are present in the tendinous
part of the diaphragm and nodules are seen on the
diaphragmatic/visceral pleura (Fig. 15A–E). The
diaphragmatic defects may be missed at the
time of surgery unless carefully searched for;
without plication of the diaphragmatic defects,
pneumothorax can recur in patients with extra-
Fig. 12. CT chest (axial view) showing characteristic
thoracic endometriosis.
nodules and bizarrely shaped cysts, predominantly in
The correlation between development of pneu-
the upper and middle lung zones, in a young smoker
with PLCH. mothorax to menstrual periods is not always
720 Huan et al
Fig. 13. CT chest axial (A, B) and coronal (C) views show round, lentiform-shaped, thin-walled cysts with a pre-
dominantly basal and subpleural distribution in a patient with BHD. BHD is associated with skin lesions formed
by folliculomas (D, E).
apparent and the diagnosis of thoracic endometri- pneumothorax development.100,101 A higher blood
osis may only be made when endometrial nodules level of aluminum has been noted among patients
are seen at the time of surgery. The nodules have with spontaneous pneumothorax102 leading to the
glandular cells, endometrial stroma, and postulation that aluminum might play a role in forma-
hemosiderin-laden macrophages and test positive tion of subpleural blebs and bullous lesions and
for estrogen and progesterone receptors. CD10 pneumothorax development.102
staining on the resected specimen is useful to
identify endometriosis tissue following resection.
Another important diagnosis to consider in PATHOGENESIS
young females presenting with recurrent pneumo- The exact pathogenesis and mechanisms of spon-
thorax is LAM (described previously). 95 taneous pneumothorax remain unclear. Although it
was believed earlier that PSP occurs in patients
Miscellaneous causes Pressure swings secondary with no underlying lung abnormalities, several
to changes in atmospheric pressure during thunder- factors have been identified that predispose to
storms and with high altitude,96 air pollution,97 expo- pneumothorax development. An interplay of
sure to loud music,98 playing musical instruments, lung-related abnormalities, such as subpleural
and blowing of balloons99 have been reported to blebs (Fig. 16A–C) and bullae (Fig. 16D),26,103
cause spontaneous pneumothorax. Anorexia nerv- visceral pleural porosity,104 emphysema-like
osa has been found to be associated with pneumo- changes (ELCs),105 chronic small airway inflam-
thorax. The risk of developing subsequent mation,104,106 and abnormal levels of matrix metal-
contralateral spontaneous pneumothorax is higher loproteinases (MMP),107,108 and environmental
among underweight patients; malnutrition of pneu- factors, such as smoking, is now thought to lead
mocytes may be a possible mechanism leading to to pneumothorax development and recurrence.
Fig. 14. CT chest axial (A, B) and sagittal (C) views showing skin neurofibroma nodules (arrows) in a patient with
neurofibromatosis and presenting with spontaneous right-sided pneumothorax.
Blebs, Bullae, and Pleural Porosity multiple factors are likely involved. Air leak from
ruptured blebs and bullae is not always present
Pleural blebs and bullae are demonstrated in pa-
(3.6%–73%) during surgery for spontaneous
tients with PSP using advanced imaging tech-
pneumothorax.111 Pneumothorax recurrence is
niques, such as CT and fluorescein-enhanced
high (up to 20%) when only bullectomy, and no
autofluorescence during thoracic surgery.
surgical pleurodesis, is performed.112,113 Addi-
Resected lung specimens show features of inflam-
tional to visible blebs or bullae, the pleura may
mation, disruption or absence of mesothelial cells,
also be abnormal with diffuse “pleural porosity.”
and presence of micropores measuring 10 to
Fluorescein-enhanced autofluorescence assess-
20 mm in diameter.104 How these then lead to
ment during thoracoscopy in patients with PSP
pleural bleb and bullae formation is unknown.30
can reveal abnormal areas of fluorescein leakage
It is also unclear whether these lesions are solely
on the visceral pleura even in areas that appeared
responsible for air leak development109,110;
normal on white-light inspection.112
Fig. 15. CT chest axial (A) and sagittal (B) views showing subpleural nodules (arrows) representing thoracic endo-
metriosis in a patient with catamenial pneumothorax. Ultrasound confirmed the presence of pelvic endometriosis
(C). Multiple reddish-brown endometrial nodules were seen on the diaphragmatic pleura during video-assisted
thoracoscopic surgery (D, E).
722 Huan et al
Fig. 16. CT chest axial (A) and coronal (B) views showing bilateral apical blebs (arrows). An apical bleb is seen on
direct visualization during video-assisted thoracoscopic surgery (C). CT chest (axial view) shows multiple large left
upper lobe bullae (arrows) and spontaneous secondary pneumothorax (D).
Emphysema-like changes MMP-2, MMP-7, and MMP-9 has been noted in

patients presenting with pneumothorax107,108,118
ELCs are low density areas that are seen separate
and may be independent risk factors.108 It is not
to pleural blebs and bullae on CT lung imaging in
clear if cigarette smoking–related oxidative
patients with PSP and believed to be caused by
changes and inflammation influence MMP
early gas trapping and inflammation.114 The
levels.108
mean lung density on lung parenchymal density
assessment with CT is lower among patients Chronic Small Airway Inflammation
with PSP and worse in smokers compared with
control subjects.105 Changes of emphysema Chronic small airway inflammatory changes are
have also been observed in resected lung tissue present in the lungs of patients with spontaneous
in PSP.105 pneumothorax; it is unclear whether these inflam-
matory changes are simply smoking-related ab-
normalities or if they actually contribute to
Matrix Metalloproteinase
pneumothorax development. Histologic findings
MMPs are a family of zinc-dependent enzymes of postinflammatory fibrosis, chronic bronchiolitis
involved in wound healing, tissue remodeling, with pigmented macrophages and focal emphy-
and angiogenesis.115,116 Various types of MMPs sema, and respiratory bronchiolitis have been
(eg, MMP-2 and MMP-9) are produced by bron- noted in wedge resection specimens of patients
chial epithelial cells, alveolar macrophages, and with recurrent or persistent spontaneous
type-II pneumocytes117; overexpressions of pneumothorax.104,106,119
FUTURE DIRECTIONS poitrine. Paris: De l’imprimerie des Sourds-Muets;

1803.
Significant gaps in knowledge remain regarding 3. Laennec RTH. De l’auscultation médiate: ou traité
classification, pathogenesis, management, and du diagnostic des maladies des poumons et du
outcomes of pneumothorax. The current pneumo- coeur. Paris: Brosson et Chaudé; 1819.
thorax classification of spontaneous pneumo- 4. Hyde B, Hyde L. Spontaneous pneumothorax:
thorax into PSP and SSP, based on clinical and contrast of the benign idiopathic and the tuber-
radiologic findings, is simplistic. With improved culous types. Ann Intern Med 1950;33(6):
understanding of the underlying pathogenetic 1373–7.
mechanisms, the distinction between PSP and 5. Kjaergaad H. Spontaneous pneumothorax in the
SSP as separate entities rather than the ends of apparently healthy. Acta Med Scand 1932;43:
a continual disease spectrum has blurred. An 1–159.
“ideal” future classification system should take 6. Gupta D, Hansell A, Nichols T, et al. Epidemiology
into consideration (1) patient risk factors and path- of pneumothorax in England. Thorax 2000;55(8):
ogenetic mechanisms, (2) underlying lung disease 666–71.
and abnormalities on high-resolution imaging of 7. Bense L, Eklund G, Wiman L-G. Smoking and the
the lung, (3) patient symptoms and severity, and increased risk of contracting spontaneous pneu-
(4) improved risk stratifications to guide interven- mothorax. Chest 1987;92(6):1009–12.
tions and recurrence prevention. The role of 8. Melton LJ, Hepper NGG, Offord KP. Incidence of
ELCs, hormonal markers and biomarkers, such spontaneous pneumothorax in Olmsted County,
as CD10 levels in women of childbearing age, Minnesota—1950 to 1974. Am Rev Respir Dis
and MMP-9 in pneumothorax development and 1979;120(6):1379–82.
recurrence are important areas of research. Ad- 9. Baumann MH, Strange C, Heffner JE, et al. Man-
vancements in imaging technology and artificial in- agement of spontaneous pneumothorax: an Amer-
telligence algorithms may offer novel applications ican College of Chest Physicians Delphi consensus
to improve diagnosis and risk stratification in the statement. Chest 2001;119(2):590–602.
future. 10. Mitani A, Hakamata Y, Hosoi M, et al. The incidence
and risk factors of asymptomatic primary sponta-
CLINICS CARE POINTS neous pneumothorax detected during health
check-ups. BMC Pulm Med 2017;17(1):1–6.
11. Schramel FM, Postmus PE, Vanderschueren RG.
Current aspects of spontaneous pneumothorax.
Patients with primary spontaneous pneumo- Eur Respir J 1997;10(6):1372–9.
thorax may have underlying risk factors and
12. Sadikot R, Greene T, Meadows K, et al. Recurrence
lung abnormalities that are not easily
of primary spontaneous pneumothorax. Thorax
apparent on initial chest imaging.
1997;52(9):805–9.
Tension pneumothorax is a pathophysiologic, 13. Olesen WH, Lindahl-Jacobsen R, Katballe N, et al.
NOT a radiologic, diagnosis.
Recurrent primary spontaneous pneumothorax is
Tobacco smoking is the an important risk fac- common following chest tube and conservative
tor for both primary and secondary sponta- treatment. World J Surg 2016;40(9):2163–70.
neous pneumothorax. 14. Walker SP, Bibby AC, Halford P, et al. Recurrence
Recurrent spontaneous pneumothorax is a rates in primary spontaneous pneumothorax: a
common presenting manifestation in diffuse systematic review and meta-analysis. Eur Respir
cystic lung diseases. J 2018;52(3).
An interplay between lung-related abnor- 15. Huang YH, Chang PY, Wong KS, et al. An age-
malities and environmental factors is the stratified longitudinal study of primary spontaneous
likely pathogenetic mechanisms of sponta- pneumothorax. J Adolesc Health 2017;61(4):
neous pneumothorax in most cases. 527–32.
16. Bobbio A, Dechartres A, Bouam S, et al. Epidemi-
ology of spontaneous pneumothorax: gender-
related differences. Thorax 2015;70(7):653–8.
17. Lippert H, Lund O, Blegvad S, et al. Independent
REFERENCES
risk factors for cumulative recurrence rate after first
1. Light RW. Pleural diseases. 3rd edition. Baltimore: spontaneous pneumothorax. Eur Respir J 1991;
Williams & Wilkins; 1995. 4(3):324–31.
2. Itard JMG. Dissertation sur le pneumothorax, ou les 18. Videm V, Pillgram-Larsen J, Ellingsen O, et al.
congestions gazeuses qui se forment dans la Spontaneous pneumothorax in chronic
724 Huan et al
obstructive pulmonary disease: complications, pneumothorax: a systematic review. Ann Surg

treatment and recurrences. Eur J Respir Dis 2015;261(6):1068–78.
1987;71(5):365–71. 35. Galvagno SM, Nahmias JT, Young DA.
19. Baumann MH. Management of spontaneous pneu- Advanced trauma life supportÒ Update 2019:
mothorax. Clin Chest Med 2006;27(2):369–81. management and applications for adults and
20. Voge V, Anthracite R. Spontaneous pneumothorax special populations. Anesthesiology 2019;37(1):
in the USAF aircrew population: a retrospective 13–32.
study. Aviat Space Environ Med 1986;57(1): 36. Celik B, Sahin E, Nadir A, et al. Iatrogenic pneumo-
939–49. thorax: etiology, incidence and risk factors. Thorac
21. Light RW. Pleural diseases. Baltimore, MD: Lippin- Cardiovasc Surg 2009;57(05):286–90.
cott Williams & Wilkins; 2007. 37. Battle CE, Hutchings H, Evans PA. Risk factors that
22. Collins CD, Lopez A, Mathie A, et al. Quantification predict mortality in patients with blunt chest wall
of pneumothorax size on chest radiographs using trauma: a systematic review and meta-analysis.
interpleural distances: regression analysis based Injury 2012;43(1):8–17.
on volume measurements from helical CT. AJR 38. Huang Y, Huang H, Li Q, et al. Transbronchial lung
Am J Roentgenol 1995;165(5):1127–30. biopsy and pneumothorax. J Thorac Dis 2014;
23. Rivas de Andrés JJ, Jiménez López MF, Molins Ló- 6(Suppl 4):S443.
pez-Rodó L, et al. [Guidelines for the diagnosis 39. Galli JA, Panetta NL, Gaeckle N, et al. Pneumo-
and treatment of spontaneous pneumothorax]. thorax after transbronchial biopsy in pulmonary
Arch Bronconeumol 2008;44(8):437–48. fibrosis: lessons from the multicenter COMET trial.
24. MacDuff A, Arnold A, Harvey J. Management of Lung 2017;195(5):537–43.
spontaneous pneumothorax: British Thoracic Soci- 40. Dhooria S, Sehgal IS, Aggarwal AN, et al. Diag-
ety Pleural Disease Guideline 2010. Thorax 2010; nostic yield and safety of cryoprobe transbronchial
65(Suppl 2):ii18–31. lung biopsy in diffuse parenchymal lung diseases:
25. Henry M, Arnold T, Harvey J. BTS guidelines for the systematic review and meta-analysis. Respir Care
management of spontaneous pneumothorax. Tho- 2016;61(5):700–12.
rax 2003;58(Suppl 2):ii39. 41. Gershman E, Fruchter O, Benjamin F, et al. Safety
26. Bintcliffe OJ, Hallifax RJ, Edey A, et al. Sponta- of cryo-transbronchial biopsy in diffuse lung dis-
neous pneumothorax: time to rethink manage- eases: analysis of three hundred cases. Respira-
ment? Lancet Respir Med 2015;3(7):578–88. tion 2015;90(1):40–6.
27. Kelly A-M, Druda D. Comparison of size classifica- 42. Tsotsolis N, Tsirgogianni K, Kioumis I, et al. Pneu-
tion of primary spontaneous pneumothorax by mothorax as a complication of central venous cath-
three international guidelines: a case for interna- eter insertion. Ann Transl Med 2015;3(3).
tional consensus? Respir Med 2008;102(12): 43. Kirkfeldt RE, Johansen JB, Nohr EA, et al. Pneumo-
1830–2. thorax in cardiac pacing: a population-based
28. Yoon J, Sivakumar P, O’Kane K, et al. A need to cohort study of 28 860 Danish patients. Europace
reconsider guidelines on management of primary 2012;14(8):1132–8.
spontaneous pneumothorax? Int J Emerg Med 44. Gordon CE, Feller-Kopman D, Balk EM, et al. Pneu-
2017;10(1):1–3. mothorax following thoracentesis: a systematic re-
29. Kelly A-M, Weldon D, Tsang AY, et al. Comparison view and meta-analysis. Arch Intern Med 2010;
between two methods for estimating pneumothorax 170(4):332–9.
size from chest X-rays. Respir Med 2006;100(8): 45. Corado SC, Santos MG, Quaresma L, et al. Pneu-
1356–9. mothorax after acupuncture. BMJ Case Rep
30. Tschopp J-M, Bintcliffe O, Astoul P, et al. ERS task 2019;12(6):e228770.
force statement: diagnosis and treatment of pri- 46. Ying X, Wang P, Xu P, et al. Pneumothorax associated
mary spontaneous pneumothorax. Eur Respir J with acupuncture: a systematic review and analysis.
2015;46(2):321–35. J Altern Complement Med 2016;4(4):17–25.
31. Brown SGA, Ball EL, Perrin K, et al. Conservative 47. Gupta A, Hammad Zaidi KH. Pneumothorax after
versus interventional treatment for spontaneous colonoscopy–a review of literature. Clin Endosc
pneumothorax. N Engl J Med 2020;382(5):405–15. 2017;50(5):446.
32. Noppen M, de Keukeleire T. Pneumothorax. Respi- 48. Senthilkumaran S, Balamurugan N, Menezes RG,
ration 2008;76(2):121–7. et al. Bilateral pneumothorax following breast
33. Noppen M. Spontaneous pneumothorax: epidemi- augmentation: beware and be aware. Indian J Plast
ology, pathophysiology and cause. Eur Respir Surg 2012;45(3):579.
Rev 2010;19(117):217–9. 49. Kogos A, Alakhras M, Hossain Z, et al. Iatrogenic
34. Roberts DJ, Leigh-Smith S, Faris PD, et al. Clinical pneumothorax: etiology, morbidity, and mortality.
presentation of patients with tension Chest 2004;126(4):893S.
50. John J, Seifi A. Incidence of iatrogenic pneumo- immunocompetent patient in Cameroon. Case
thorax in the United States in teaching vs. non- Rep Surg 2018;2018.
teaching hospitals from 2000 to 2012. J Crit Care 66. Zhang W, Hu Y, Gao J, et al. Pleural aspergillosis
2016;34:66–8. complicated by recurrent pneumothorax: a case
51. Johnson MK, Smith RP, Morrison D, et al. Large report. J Med Case Rep 2010;4(1):1–4.
lung bullae in marijuana smokers. Thorax 2000; 67. Martinelli AW, Ingle T, Newman J, et al. COVID-19
55(4):340–2. and pneumothorax: a multicentre retrospective
52. Wu T-c, Tashkin DP, Djahed B, et al. Pulmonary case series. Eur Respir J 2020;56(5).
hazards of smoking marijuana as compared with 68. Gupta N, Vassallo R, Wikenheiser-Brokamp KA,
tobacco. N Engl J Med 1988;318(6):347–51. et al. Diffuse cystic lung disease. Part I. Am J Re-
53. Light RW, Lee YCG. Pneumothorax in adults: spir Crit Care Med 2015;191(12):1354–66.
epidemiology and etiology. In: UpToDate (proceed- 69. Henske EP, McCormack FX. Lymphangioleiomyo-
ings), Light RW (Ed), UpToDate, Waltham, MA. matosis: a wolf in sheep’s clothing. J Clin Invest
2020. 2012;122(11):3807–16.
54. Chen C-H, Liao W-C, Liu Y-H, et al. Secondary 70. McCormack FX, Travis WD, Colby TV, et al. Lym-
spontaneous pneumothorax: which associated phangioleiomyomatosis: calling it what it is: a low-
conditions benefit from pigtail catheter treatment? grade, destructive, metastasizing neoplasm. Am
Am J Emerg Med 2012;30(1):45–50. J Respir Crit Care Med 2012;186(12):1210–2.
55. Hallifax RJ, Goldacre R, Landray MJ, et al. Trends 71. Ferrans V, Yu Z-X, Nelson W, et al. Lymphangioleio-
in the incidence and recurrence of inpatient-treated myomatosis (LAM) a review of clinical and morpho-
spontaneous pneumothorax, 1968-2016. JAMA logical features. J Nippon Med Sch 2000;67(5):
2018;320(14):1471–80. 311–29.
56. Shamaei M, Tabarsi P, Pojhan S, et al. Tuberculosis- 72. Crino PB, Nathanson KL, Henske EP. The tuberous
associated secondary pneumothorax: a retrospec- sclerosis complex. N Engl J Med 2006;355(13):
tive study of 53 patients. Respir Care 2011;56(3): 1345–56.
298–302. 73. Ryu JH, Hartman TE, Torres VE, et al. Frequency of
57. Freixinet JL, Caminero JA, Marchena J, et al. Spon- undiagnosed cystic lung disease in patients with
taneous pneumothorax and tuberculosis: long-term sporadic renal angiomyolipomas. Chest 2012;
follow-up. Eur Respir J 2011;38(1):126–31. 141(1):163–8.
58. Ihm HJ, Hankins JR, Miller JE, et al. Pneumothorax 74. Johnson SR, Cordier J-F, Lazor R, et al. European
associated with pulmonary tuberculosis. J Thorac Respiratory Society guidelines for the diagnosis
Cardiovasc Surg 1972;64(2):211–9. and management of lymphangioleiomyomatosis.
59. Blanco-Perez J, Bordón J, Pi L, et al. Pneumo- Eur Respir J 2010;35(1):14–26.
thorax in active pulmonary tuberculosis: resur- 75. Young LR, VanDyke R, Gulleman PM, et al. Serum
gence of an old complication? Respir Med 1998; vascular endothelial growth factor-D prospectively
92(11):1269–73. distinguishes lymphangioleiomyomatosis from
60. Saad SB, Melki B, El Gharbi LD, et al. Pneumo- other diseases. Chest 2010;138(3):674–81.
thorax tuberculeux: prise en charge diagnostique 76. Vassallo R, Ryu JH, Schroeder DR, et al. Clinical
et thérapeutique. Revue de Pneumologie Clinique outcomes of pulmonary Langerhans’-cell histiocy-
2018;74(2):81–8. tosis in adults. N Engl J Med 2002;346(7):484–90.
61. Radhi S, Alexander T, Ukwu M, et al. Outcome of 77. Mendez JL, Nadrous HF, Vassallo R, et al. Pneumo-
HIV-associated Pneumocystis pneumonia in hospi- thorax in pulmonary Langerhans cell histiocytosis.
talized patients from 2000 through 2003. BMC Chest 2004;125(3):1028–32.
Infect Dis 2008;8(1):1–10. 78. Tazi A, Bonay M, Bergeron A, et al. Role of
62. Afessa B. Pleural effusions and pneumothoraces in granulocyte-macrophage colony stimulating factor
AIDS. Curr Opin Pulm Med 2001;7(4):202–9. (GM-CSF) in the pathogenesis of adult pulmonary
63. Rivero A, Perez-Camacho I, Lozano F, et al. Etiol- histiocytosis X. Thorax 1996;51(6):611–4.
ogy of spontaneous pneumothorax in 105 HIV- 79. Tazi A, Moreau J, Bergeron A, et al. Evidence that
infected patients without highly active antiretroviral Langerhans cells in adult pulmonary Langerhans
therapy. Eur J Radiol 2009;71(2):264–8. cell histiocytosis are mature dendritic cells: impor-
64. Grams ST, von Saltiel R, Mayer AF, et al. Assess- tance of the cytokine microenvironment. The J Im-
ment of the reproducibility of the indirect ultra- munol 1999;163(6):3511–5.
sound method of measuring diaphragm mobility. 80. Kunogi M, Kurihara M, Ikegami TS, et al. Clinical
Clin Physiol Funct Imaging 2014;34(1):18–25. and genetic spectrum of Birt–Hogg–Dube syn-
65. Nonga BN, Jemea B, Pondy AO, et al. Unusual drome patients in whom pneumothorax and/or mul-
life-threatening pneumothorax complicating a tiple lung cysts are the presenting feature. J Med
ruptured complex aspergilloma in an Genet 2010;47(4):281–7.
726 Huan et al
81. Zbar B, Alvord WG, Glenn G, et al. Risk of renal 95. McCormack FX, Gupta N, Finlay GR, et al. Offi-
and colonic neoplasms and spontaneous pneumo- cial American Thoracic Society/Japanese Respi-
thorax in the Birt-Hogg-Dube syndrome. Cancer ratory Society clinical practice guidelines:
Epidemiol Biomarkers Prev 2002;11(4):393–400. lymphangioleiomyomatosis diagnosis and man-
82. Toro JR, Pautler SE, Stewart L, et al. Lung cysts, agement. Am J Respir Crit Care Med 2016;
spontaneous pneumothorax, and genetic associ- 194(6):748–61.
ations in 89 families with Birt-Hogg-Dubé syn- 96. Alifano M, Parri SNF, Bonfanti B, et al. Atmospheric
drome. Am J Respir Crit Care Med 2007; pressure influences the risk of pneumothorax:
175(10):1044–53. beware of the storm! Chest 2007;131(6):1877–82.
83. Johannesma PC, Reinhard R, Kon Y, et al. Preva- 97. Bertolaccini L, Alemanno L, Rocco G, et al. Air
lence of Birt–Hogg–Dubé syndrome in patients pollution, weather variations and primary sponta-
with apparently primary spontaneous pneumo- neous pneumothorax. J Thorac Dis 2010;2(1):9.
thorax. Eur Respir J 2015;45(4):1191–4. 98. Noppen M, Verbanck S, Harvey J, et al. Music: a
84. Ren HZ, Zhu CC, Yang C, et al. Mutation analysis of new cause of primary spontaneous pneumothorax.
the FLCN gene in Chinese patients with sporadic Thorax 2004;59(8):722–4.
and familial isolated primary spontaneous pneumo- 99. Shiferaw Dejene FA, Jack K, Anthony A. Pneumo-
thorax. Clin Genet 2008;74(2):178–83. thorax, music and balloons: a case series. Ann
85. Onuki T, Goto Y, Kuramochi M, et al. Radiologically Thorac Med 2013;8(3):176.
indeterminate pulmonary cysts in Birt-Hogg-Dubé 100. Huang T-W, Lee S-C, Cheng Y-L, et al. Contralateral
syndrome. Ann Thorac Surg 2014;97(2):682–5. recurrence of primary spontaneous pneumothorax.
86. Kumasaka T, Hayashi T, Mitani K, et al. Character- Chest 2007;132(4):1146–50.
ization of pulmonary cysts in Birt–Hogg–Dubé syn- 101. Biffl WL, Narayanan V, Gaudiani JL, et al. The man-
drome: histopathological and morphometric agement of pneumothorax in patients with anorexia
analysis of 229 pulmonary cysts from 50 unrelated nervosa: a case report and review of the literature.
patients. Histopathology 2014;65(1):100–10. Patient Saf Surg 2010;4(1):1–4.
87. Tobino K, Hirai T, Johkoh T, et al. Differentiation be- 102. Han S, Sakinci U, Kose SK, et al. The relationship
tween Birt–Hogg–Dubé syndrome and lymphan- between aluminum and spontaneous pneumo-
gioleiomyomatosis: quantitative analysis of thorax; treatment, prognosis, follow-up? Interactive
pulmonary cysts on computed tomography of the cardiovascular and thoracic surgery. Interact Car-
chest in 66 females. Eur J Radiol 2012;81(6): diovasc Thorac Surg 2004;3(1):79–82.
1340–6. 103. Mitlehner W, Friedrich M, Dissmann W. Value of
88. Alifano M, Legras A, Rousset-Jablonski C, et al. computer tomography in the detection of bullae
Pneumothorax recurrence after surgery in women: and blebs in patients with primary spontaneous
clinicopathologic characteristics and manage- pneumothorax. Respiration 1992;59(4):221–7.
ment. Ann Thorac Surg 2011;92(1):322–6. 104. Ohata M, Suzuki H. Pathogenesis of spontaneous
89. Alifano M, Roth T, Broe SC, et al. Catamenial pneu- pneumothorax: with special reference to the ultra-
mothorax: a prospective study. Chest 2003;124(3): structure of emphysematous bullae. Chest 1980;
1004–8. 77(6):771–6.
90. Legras A, Mansuet-Lupo A, Rousset-Jablonski C, 105. Bintcliffe OJ, Edey AJ, Armstrong L, et al. Lung
et al. Pneumothorax in women of child-bearing parenchymal assessment in primary and second-
age: an update classification based on clinical and ary pneumothorax. Ann Am Thorac Soc 2016;
pathologic findings. Chest 2014;145(2):354–60. 13(3):350–5.
91. Rousset-Jablonski C, Alifano M, Plu-Bureau G, et al. 106. Lichter I, Gwynne J. Spontaneous pneumothorax in
Catamenial pneumothorax and endometriosis- young subjects: a clinical and pathological study.
related pneumothorax: clinical features and risk fac- Thorax 1971;26(4):409–17.
tors. Humanit Rep 2011;26(9):2322–9. 107. Chen C-K, Chen P-R, Huang H-C, et al. Overex-
92. Joseph J, Sahn SA. Thoracic endometriosis syn- pression of matrix metalloproteinases in lung tissue
drome: new observations from an analysis of 110 of patients with primary spontaneous pneumo-
cases. Am J Med 1996;100(2):164–70. thorax. Respiration 2014;88(5):418–25.
93. Haga T, Kurihara M, Kataoka H, et al. Clinical-path- 108. Huang Y-F, Chiu W-C, Chou S-H, et al. Association
ological findings of catamenial pneumothorax: of MMP-2 and MMP-9 expression with recurrences
comparison between recurrent cases and non- in primary spontaneous pneumothorax. Kaohsiung
recurrent cases. Ann Thorac Cardiovasc Surg J Med Sci 2017;33(1):17–23.
2013;20(3):202–6. 109. Baumann MH. Do blebs cause primary sponta-
94. Visouli AN, Zarogoulidis K, Kougioumtzi I, et al. neous pneumothorax?: Pro: blebs do cause pri-
Catamenial pneumothorax. J Minim Invasive Gyne- mary spontaneous pneumothorax. J Bronchol
col 2014;6(Suppl 4):S448. Interv Pulmonol 2002;9(4):313–8.
110. Noppen M. Do blebs cause primary spontaneous (ERS monograph). Sheffield, UK: European Respi-
pneumothorax?: Con: blebs do not cause primary ratory Society; 2020. p. 193–210.
spontaneous pneumothorax. J Bronchol Interv Pul- 115. Ohbayashi H. Matrix metalloproteinases in lung
monol 2002;9(4):319–23. diseases. Curr Protein Pept Sci 2002;3(4):409–21.
111. Noppen M. Management of primary spontaneous 116. Cathcart J, Pulkoski-Gross A, Cao J. Targeting ma-
pneumothorax. Curr Opin Pulm Med 2003;9(4): trix metalloproteinases in cancer: bringing new life
272–5. to old ideas. Genes Dis 2015;2(1):26–34.
117. Chakrabarti S, Patel KD. Matrix metalloproteinase-
112. Noppen M, Dekeukeleire T, Hanon S, et al. Fluores-
2 (MMP-2) and MMP-9 in pulmonary pathology.
cein-enhanced autofluorescence thoracoscopy in
Exp Lung Res 2005;31(6):599–621.
patients with primary spontaneous pneumothorax
118. Chiu W-C, Lee Y-C, Su Y-H, et al. Correlation of
and normal subjects. Am J Respir Crit Care Med
matrix metalloproteinase-2 and-9 expression
2006;26–30.
with recurrences in primary spontaneous pneu-
113. Linde K, Clausius N, Ramirez G, et al. Are the clin- mothorax patients. J Thorac Dis 2016;8(12):
ical effects of homoeopathy placebo effects? A 3667.
meta-analysis of placebo-controlled trials. Lancet 119. Cottin V, Streichenberger N, Gamondes J, et al.
1997;350(9081):834–43. Respiratory bronchiolitis in smokers with sponta-
114. Hallifax R, Walker S, Marciniak S. Pneumothorax: neous pneumothorax. Eur Respir J 1998;12(3):
how to predict, prevent and cure. Pleural disease 702–4.

Pneumothorax

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Pneumothorax

Classification and Etiology

INTRODUCTION knowledge and understanding of underlying risks

Clin Chest Med 42 (2021) 711–727

results from direct injury to the chest wall or lung.

requires management by thoracic and/or trauma

Primary spontaneous pneumothorax

Box 1 hypoxemia, hypercapnia, and respiratory failure

Other pulmonary infections SSP can develop

mechanisms and characteristic lung cyst pat-

Box 2 and without an HRCT scan, pneumothorax in pa-

Emphysema-like changes MMP-2, MMP-7, and MMP-9 has been noted in

FUTURE DIRECTIONS poitrine. Paris: De l’imprimerie des Sourds-Muets;

obstructive pulmonary disease: complications, pneumothorax: a systematic review. Ann Surg

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