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Forbearance With Bronchoscopy
A Review of Gratuitous Indications
Himanshu Deshwal, MD; Sameer K. Avasarala, MD; Subha Ghosh, MD; and Atul C. Mehta, MD, FCCP
Advanced technologies such as endobronchial ultrasound and electromagnetic navigation have
revolutionized the field of bronchoscopy. Its indications as a diagnostic as well as a therapeutic
tool continue to expand at a rapid pace. This growth also has led to the emergence of a new
subspecialty of interventional pulmonology and more than 40 fellowship training programs.
However, with increasing popularity and accessibility, there is a high impetus for performing the
procedure when it may be of limited value. On the basis of a literature review and our own
experience, we produced a list of conditions for which bronchoscopy is of limited value yet is
being performed frequently. Conditions such as idiopathic pulmonary fibrosis, massive he-
moptysis, cystic fibrosis, smear-negative pulmonary TB, and stage I sarcoidosis may be
approached best in a more prudent fashion, with the bronchoscopic approach reserved for
exceptional cases. We present an overview of conditions for which the expectations for bron-
choscopy exceed the evidence in the literature, and we coined the term “forbearance with
bronchoscopy”for situations in which this popular tool may not be the most appropriate initial
approach. CHEST 2018; -(-):---
KEY WORDS: bronchoscopy; forbearing bronchoscopy; guided bronchoscopy; indications for
bronchoscopy; low-yield bronchoscopy
The bronchoscope initially was introduced as
a foreign body retrieval tool; its indications
have since expanded.
1
In current practice,
both the rigid and the flexible variants are
used.
2
Transbronchial biopsy (TBBx) of the
lung parenchyma is a procedure commonly
performed for a variety of pulmonary
diseases. It can be useful in the diagnosis of
malignancy (lung or metastatic), infections
(TB, nontubercular Mycobacterium, fungal,
Cytomegalovirus,Pneumocystis jirovecii
pneumonia), rejection in recipients of lung
transplants, infiltrates in patients who are
immunocompromised, and certain diffuse
lung diseases (sarcoidosis, pulmonary
alveolar proteinosis, eosinophilic
pneumonia, berylliosis, amyloidosis,
pulmonary Langerhans cell histiocytosis,
hypersensitivity pneumonitis, lymphocytic
interstitial pneumonia, and cryptogenic
organizing pneumonia).
3
The field of bronchoscopy has been
revolutionized further by the introduction of
ABBREVIATIONS: CD = cluster of differentiation; CF = cystic fibrosis;
EBUS = endobronchial ultrasound; FB = flexible bronchoscopy; FM =
fibrosing mediastinitis; HRCT = high-resolution CT; IPF = idiopathic
pulmonary fibrosis; MDCT = multidetector CT; PN = pulmonary
nodule; SN-PTB = smear-negative pulmonary TB; TBBx = trans-
bronchial biopsy; TBNA = transbronchial needle aspiration; TTNA =
transthoracic needle aspiration
AFFILIATIONS: From the Medicine Institute (Dr Deshwal), the Res-
piratory Institute (Drs Avasarala and Mehta), and Diagnostic Radi-
ology (Dr Ghosh), Cleveland Clinic, Cleveland, OH.
CORRESPONDENCE TO: Atul C. Mehta, MD, FCCP, Department of
Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Desk
A90, 9500 Euclid Ave, Cleveland, OH 44195; e-mail: mehtaa1@ccf.org
Copyright Ó2018 American College of Chest Physicians. Published by
Elsevier Inc. All rights reserved.
DOI: https://doi.org/10.1016/j.chest.2018.08.1035
[Special Features ]
chestjournal.org 1
endobronchial ultrasound (EBUS) and newer techniques
collectively termed “guided bronchoscopy.”
4
An
ultrathin bronchoscope has been introduced to sample
subcentimeter peripheral nodules, and the therapeutic
indications for this tool also continue to expand.
5
With
the increasing popularity of bronchoscopy, a whole new
subspecialty of interventional pulmonology has
emerged, and today there are more than 40 programs in
North America providing fellowship training, with a list
that is ever growing.
6
Increasing popularity and accessibility occasionally can
become an impetus for performing bronchoscopy when
it may have a low diagnostic value or therapeutic impact.
On the basis of a literature review and our own
experience, we produced a list of conditions for which
the procedure is of limited value yet is being performed
frequently (Table 1). We coined the term “forbearance
with bronchoscopy”for such procedures when
performed with high expectations but with poor
outcomes. We believe that the indication for the
procedure should be based strictly on the risk to benefit
ratio to improve the patient’s welfare and the cost-
effectiveness of the procedure.
Cystic Fibrosis
Cystic fibrosis (CF) is an autosomal recessive disease
with an average age expectancy <40 years. Mucous
plugging, bronchiectasis, mediastinal lymphadenopathy,
and recurrent lower respiratory tract infections are its
common manifestations (Fig 1). Studies have
recommended a bronchoscopic evaluation to guide
antimicrobial therapy during CF exacerbations, and
there is some evidence to support this practice.
7
However, less invasive means such as sputum or throat
swab cultures also can predict lung colonization with
Pseudomonas aeroginosa with reasonable accuracy.
Aaron et al
8
found that induced sputum was as good as
BAL and reserved brushing to characterize genotype and
antibiotic susceptibility in chronic P aeruginosa
infection in patients with CF.
Mediastinal lymphadenopathy occurs in at least 52% of
patients with CF because of chronic inflammation and is
usually progressive, correlating with the severity of the
pulmonary disease.
9
CT scanning of the chest is a
reasonable tool to follow up interval development with
no role for bronchoscopy unless suspicion for
malignancy or lymphoma is high.
Bronchoscopy also is performed frequently for the
management of hemoptysis in patients with CF.
Guidelines on massive hemoptysis state that
bronchoscopy is of little value in source localization and
time management in this group of patients.
10
However,
bronchoscopy can be useful in patients with CF with
lobar collapse because dornase alfa can be instilled
precisely into the involved bronchopulmonary segment
to improve outcomes.
11,12
TB
Smear-negative pulmonary TB (SN-PTB) is a diagnostic
challenge. As many as 50% of patients with active
infection may have sputum-detectable SN-PTB.
13
In
such cases, using an appropriate diagnostic algorithm
becomes essential, especially in resource-limited
environments.
Induced sputum was the preferred diagnostic test for
SN-PTB until replaced by bronchoscopy. SN-PTB can
be diagnosed by using brushing, washings, or
postbronchoscopic sputum studies.
14,15
Shin et al
16
found that flexible bronchoscopy (FB) alone had
sensitivity, specificity, positive predictive value, and
negative predictive value of 75.9%, 97.2%, 95.3%, and
84.3%, respectively.
16
However, these studies compared
bronchoscopy with two or fewer induced sputum
specimens. Directly resorting to bronchoscopy possibly
could have resulted in demonstrating its higher yield.
17
Several studies have shown the yield of three induced
sputum specimens to diagnose SN-PTB to be 91% to
99% (Table 2).
18-22
Thus, obtaining at least three
induced sputum specimens in patients suspected of
TABLE 1 ]Diseases for Which Bronchoscopy Is Not the
Optimal Diagnostic or Therapeutic Tool
Disease state
Infections
1. Cystic fibrosis
2. Smear-negative pulmonary TB
Hemoptysis
Radiographic findings
1. Atelectasis in patients receiving mechanical
ventilation
2. Fibrosing mediastinitis
3. Pulmonary nodules
4. Pleural effusion
Mediastinal lymphadenopathy
1. Idiopathic pulmonary fibrosis
2. Sarcoidosis: stage I
3. Congestive lymphadenopathy
4. Calcified lymphadenopathy
5. Lymphoma
6. COPD exacerbation and lymphadenopathy
2Special Features [-#-CHEST -2018 ]
having SN-PTB is recommended prior to performing
bronchoscopy.
The Mycobacterium tuberculosis nucleic acid
amplification test has a 95% sensitivity and a
98% positive predictive value in diagnosing TB in
patients suspected of having TB.
23
It can reduce the time
from specimen collection to treatment (3 vs 14 days, P<
.0001).
24
The Centers for Disease Control and
Prevention recommends carrying out nucleic acid
amplification testing in at least one respiratory sample
along with an acid-fast bacilli smear to improve
diagnostic capabilities.
25
The Xpert MTB/RIF (MtuberculosisDNA and
resistance to rifampicin) assay is another highly
sensitive and specific test that can detect Mtuberculosis
within 2 hours, making it a good point-of-care testing
method. In addition, it has the capability of detecting
rifampin (the first-line drug for TB treatment)
resistance in respiratory samples.
26
Chakravorty et al
27
developed an Xpert MTB/RIF Ultra assay that has an
increased sensitivity and specificity to detect M
tuberculosis in smear-negative pulmonary samples as
well,makingitevenmoreaccurate.Withthe
increasing utility of these rapid tests, quick and cost-
effective decisions to initiate treatment can be made,
further bypassing the need for diagnostic
bronchoscopy, given that these tests can be performed
on respiratory samples from both sputum and BAL
with accurate results.
TABLE 2 ]Studies Comparing Induced Sputum With Bronchoscopy in Smear-Negative Pulmonary TB
Study Characteristics Results
Al Zahrani
et al
18
The combined yield of smear and culture
induced sputum was higher with a
greater number of samples.
No. of samples Smear, % Culture, %
4 98 100
39199
28191
16174
McWilliams
et al
19
Acid-fast bacilli smears in induced sputum
vs BAL
96% (sputum) vs 52% (bronchoscopy)
Ganguly et al
20
Acid-fast bacilli smears in induced sputum
vs BAL
74% (sputum) vs 58% (BAL)
Conde et al
21
Single induced sputum vs bronchoscopy No significant difference in yield
Brown et al
22
Comparison of induced sputum with
gastric washing and bronchoscopy in
patients who could not induce sputum
spontaneously
Induced sputum was more sensitive than was
gastric washing.
3 induced sputum vs 3 gastric washing
(39% vs 30%; P¼.03)
Use of bronchoscopy and BAL did not increase
sensitivity.
Figure 1 –A, B, Axial high-resolution CT scans of the chest in a patient with cystic fibrosis revealing mediastinal lymphadenopathy (circled in A).
chestjournal.org 3
Local anesthesia such as lidocaine can inhibit the
growth of Mtuberculosisorganisms.
17,28
A
concentration as low as 1 mL of 2% lidocaine is enough
to inhibit the growth of Mycobacterium.
28
Because
administration is operator dependent, an excess of
lidocaine may be used during bronchoscopy that could
inhibit the organism and lead to a lower yield for
bronchoscopy and TBBx. In addition, studies have
demonstrated purified protein derivative conversion of
up to 11% in pulmonary medicine trainees working in
the bronchoscopy unit, suggesting a potential risk of
TB transmission to health-care providers in
bronchoscopy suites.
29
In the endemic parts of the world, if the induced sputum
specimen remains negative but clinical and imaging
suspicion of TB remains high, a trial of anti-TB therapy
may be appropriate. The role of bronchoscopy should be
limited to patients with consistently negative sputum
smears, those not responding to therapy, or those in
whom there is a higher suspicion for an alternate
diagnosis.
30
Hemoptysis
The role of rigid bronchoscopy in the management of
massive hemoptysis is well established; however, that of
either rigid bronchoscopy or FB in diagnosing the source
or the cause of mild to moderate hemoptysis is still
debatable. The yield of FB in identifying the cause of
hemoptysis of any severity with a negative radiograph or
CT scan of the chest is only 16% to 21%.
31,32
In the experience of Hsiao et al
33
with 28 patients with
massive hemoptysis localized by means of radiography,
bronchoscopy was able to identify the source in 23
patients (82.1%). However, when the radiograph was
nonlocalizing, bronchoscopy was able to identify the site
in only three patients (10.7%), all of whom had
bronchiectasis and none of whom had undergone CT
scanning to identify the site.
33
Multidetector CT (MDCT) scanning has an overall
higher sensitivity in localizing the site of hemoptysis
than does FB.
34
It can identify the source of hemoptysis
in 63% to 100% of patients and is notably superior to
bronchoscopy in cases of bronchiectasis, pulmonary
infections, and lung cancer.
34
It also has the advantage of
visualizing distal airways that may be obscured by
bleeding and a sensitivity of 90% in detecting
endobronchial lesions (Fig 2).
34
Poe et al
35
identified that the presence of two of three
risk factors for malignancy (Table 3)orhemoptysisof
more than 30 mL identified 100% of cases with
bronchogenic carcinoma identified with
bronchoscopy. This finding suggests that using risk
stratification can prevent unnecessary procedures by
28%.
35
Hirshberg et al
36
also found that bronchoscopy
was more effective in locating the bleeding site in
moderate (64%) and severe (67%) hemoptysis than in
mild (49%) hemoptysis. Consequently, the combined
use of MDCT scanning and bronchoscopy may
increase accuracy in detecting the source of bleeding
(93%) compared with CT scanning alone (67%).
36
Nielsen et al
37
found that sensitivity in localizing the
source of hemoptysis in patients with lung cancer with
Figure 2 –Axial (A) and coronal (B) CT scans of the chest revealing left
endobronchial lesion (arrows) in a patient with mild, intermittent he-
moptysis. Note left lower lobe atelectasis. A carcinoid tumor was diag-
nosed at the time of curative therapeutic bronchoscopy.
TABLE 3 ]Risk Factors Associated With Malignancy and
Massive Hemoptysis
High yield of bronchoscopy in hemoptysis if any 2 of the 3
risk factors are present
35
1. Age >50 y
2. Male sex
3. Smoking history >40 pack-years
4Special Features [-#-CHEST -2018 ]
bronchoscopy was 61%, with CT scanning was
92% (P<.05), and with both modalities combined
was 97% (P¼.58); in most cases of hemoptysis from a
nonmalignant cause, the diagnosis was established
with CT scanning alone.
Thus, the need for bronchoscopy in patients with
hemoptysis is based on the severity, preexisting
diagnosis, and therapeutic potentials. It should be
performed only if MDCT scanning results are
unrevealing. Once the source is confirmed, then
therapeutic procedures such as the application of cold
saline or local vasoconstrictors, balloon tamponade,
electrocautery, laser ablation, or stent placement can be
considered.
Atelectasis in Patients Receiving Mechanical
Ventilation
Atelectasis can be classified based on its
pathophysiologic characteristics. It commonly is
diagnosed with chest imaging. Its management includes
addressing the cause and noninvasive methods such as
chest physiotherapy, mechanical percussion therapy,
positive end-expiratory pressure support, dornase alfa
instillation, and bronchodilators.
The utility of FB as a diagnostic or therapeutic tool
for atelectasis in patients receiving mechanical
ventilation long has been debated. Radiographic
resolution and improvements in oxygenation and
static lung compliance can be seen following
bronchoscopy.
Bronchoscopy commonly is used to treat atelectasis,
most often in the critical care setting. Bronchoscopy is
not the cornerstone of therapy for atelectasis; aggressive
noninvasive chest physiotherapy can be equally
efficacious.
38,39
Prognostically, an air bronchogram
portends a delayed response to any therapy for
atelectasis.
38,39
Marini et al
38
conducted a randomized
study comparing bronchoscopy and noninvasive
respiratory therapy among patients with atelectasis
receiving mechanical ventilation. Thirty-one subjects
were placed into one of two groups, with one group
receiving bronchoscopy followed by respiratory therapy
and the other group receiving respiratory therapy alone.
No difference was observed in the restoration of volume
loss between the two groups within first 24 and 48 hours
(P>.20).
38
Raoof et al
39
also showed that combined
kinetic and percussion therapy was a superior modality
to conventional treatments and that it obviated the need
Figure 3 –Coronal CT scans (A, B) of the chest in a patient in the ICU with bilateral lower lobe and left upper lobe atelectasis with interval resolution
of right lower lobe and left upper lobe atelectasis and improvement without resolution of left lower lobe atelectasis shown in a follow-up chest
radiograph (C). The patient was treated without bronchoscopy.
chestjournal.org 5
for bronchoscopy in 68% of patients (Fig 3). The current
recommendation is to use noninvasive methods to treat
atelectasis in patients who are critically ill.
40
FB should
be reserved for patients who cannot undergo these
treatments because of either chest wall trauma or spinal
injury.
Fibrosing Mediastinitis
Fibrosing mediastinitis (FM) is sclerosis of the
mediastinum that may occur as an inflammatory sequela
of infection such as histoplasmosis or of neoplasms such
as lymphoma, sarcoidosis, or an idiopathic process.
41
Exposure to an extrinsic antigen such as fungi may cause
a severe inflammatory response and fibrosis.
In severe cases, the fibrotic process may compress
mediastinal structures, including the airways, large
vessels, and esophagus. Diagnosis is confirmed mainly
via CT scanning of the chest. Findings of mediastinal
soft-tissue mass, calcification and evidence of collateral
vessels from chronic obstruction, peribronchial cuffing,
and interlobular septal thickening obviate the need for
biopsy (Fig 4).
EBUS transbronchial needle aspiration (TBNA) often is
attempted for diagnostic purposes; however, these
specimens mostly reveal nonconfirmatory findings of
inflammation and fibrosis without organisms.
42
Bronchoscopy also often is used for therapeutic
purposes in FM. Airway stent placement and mesh
repair have been conducted using a flexible
bronchoscope, and it may result temporarily in clinical
improvement. However, FM is a metabolically active
disease, and self-expanding metallic stents frequently
reocclude due to granuloma formation.
43
Destruction of
anatomic planes further makes such interventions
ineffective, with higher rates of complications such as
bleeding due to concomitant collateral vessels and
engorgement.
44
The utility of silicone stents in FM also
is limited due to a higher incidence of stent migration.
45
Bronchoscopy can be considered cautiously in cases of
severe symptomatic disease. However, the operator must
be aware of the substantial risk of hemorrhage and
should be prepared for it. Spray cryotherapy is a form of
noncontact cryotherapy being used for hemoptysis in
FM, with a lower rate of recurrent hemoptysis.
46
Pulmonary Nodules
A large variety of benign and malignant diseases can
manifest as pulmonary nodules (PNs) on chest
radiographs. A variety of prediction models commonly
are used to estimate the risk of a PN’s malignancy:
Mayo, Brock, Herder, and Veterans Affairs. They all
have been validated externally and have some
commonalities regarding risk factors for malignancy:
older age, current smoking or history of smoking, larger
nodule, and history of lung or extrathoracic
malignancy.
47
Biopsy commonly is performed in PNs to establish a
diagnosis; however, not all nodules need to be sampled.
Besides, there are many sampling modalities to choose
from, and the selection depends on the interaction of
multiple factors: patient, operator, and institutional
specifics. There a variety of bronchoscopic approaches.
It is essential to remember that the decision to use a
specific diagnostic modality is made on a case-by-case
basis. A limited summary of the bronchoscopic
modalities, their overall diagnostic accuracy, and factors
that may increase diagnostic yield is presented in
Table 4.
48-51
FB often is used to obtain tissue samples from a PN.
However, Zhang et al
52
found that the accuracy of
Figure 4 –A-C, Axial CT scans showing fibrosing mediastinitis with confluent soft tissues in multiple mediastinal and left hilar compartments. Marked
narrowing of the left pulmonary artery and complete occlusion of the left inferior pulmonary vein are visible. Flexible bronchoscopy is of little
diagnostic value.
6Special Features [-#-CHEST -2018 ]
conventional bronchoscopy in the preoperative workup
for PNs was only 24.3%, with a negative predictive value
of only 20.5%. This finding suggests that conventional
bronchoscopy should be used carefully in the evaluation
of peripheral nodules in the age of high-value and cost-
effective care.
The advent of newer technologies, including radial
probe EBUS, virtual bronchoscopy, and electromagnetic
navigation bronchoscopy, has resulted in increased use
of bronchoscopy in the evaluation of PN. Some studies
have shown that the procedure guided by these tools has
a higher diagnostic yield for PNs.
53-55
A meta-analysis
found the pooled diagnostic yield to be 70%.
48
However,
most studies looking at electromagnetic navigation
bronchoscopy were uncontrolled, and further
randomized trials are needed.
Despite the advancement in bronchoscopy, its
diagnostic yield remains inferior to that of
transthoracic needle aspiration (TTNA). A meta-
analysis of 48 studies showed a pooled diagnostic
accuracy of 92.1% for CT scanning-guided TTNA and
88.7% for ultrasound-guided TTNA.
56
TTNA remains
the diagnostic modality of choice for small peripheral
lesions if the patient can sustain the risk of
pneumothorax. If the tools for guided bronchoscopy
are unavailable, FB should be reserved for large
(>2 cm in diameter), centrally located lesions that
have a positive bronchus sign and for which the
certainty of the yield would justify the procedure.
Isolated Pleural Effusion
More than 1.5 million people in the United States
develop a pleural effusion each year.
57
The list of benign
and malignant causes of a pleural effusion is exhaustive.
Up to 27% of pleural effusions are due to malignancy.
58
Breast cancer and lung cancer account for more than
one-half of all malignant pleural effusions.
59
At times,
the initial radiographic manifestation of pleural effusion
might be accompanied by lung nodules or masses. In
such scenarios, the risk of malignancy is always in
question, and the most pragmatic approach would be to
analyze the pleural fluid for malignant cells. Pleural
cytology test results are positive for malignant cells in
60% of cases.
60
Complete or near complete opacification
of a hemithorax could be due to a large degree of
atelectasis caused by an endobronchial obstruction or a
large pleural effusion. Plain chest radiography
(mediastinal shift), point-of-care lung ultrasound, or
airway examination via bronchoscopy is useful in
determining the cause. In such a scenario, FB may be of
great utility for both diagnostic and therapeutic
purposes.
In most cases of isolated pleural effusion, there is no
role for bronchoscopy. The diagnostic workup
TABLE 4 ]Bronchoscopic Modalities Used in Assessment of Pulmonary Nodules
Method
Overall Diagnostic
Accuracy
Factors That Improve Diagnostic Accuracy (Corresponding Diagnostic
Accuracy)
Transbronchial biopsy 28%-80%
49
- Size >2cm
49
- Lesions not located in the periphery
- Presence of bronchus sign
Radial probe EBUS (with use of
extended working channel or
guide sheath)
69%
50
- Size >5.1 cm (88%)
50
- Concentric view (84%)
50
Convex probe EBUS 87%
51
- Size >2cm
51
- Use of rapid on-site cytology
51
- Distal lesions in which the bronchoscope can be wedged
into place for stabilization
51
- Neoplastic lesions (95.3%)
51
Virtual bronchoscopic navigation 72%-74%
49
- Lesions >2cm
- Newer technology such as bronchoscopic trans-
parenchymal nodule access system (Archimedes Sys-
tem, Broncus Medical) (100%)
49
Electromagnetic navigation
bronchoscopy
67%
48
- Bronchus sign
- Upper lobe location
- Size <3cm
Ultrathin bronchoscopy 57%-70%
49
- Use in combination with radial probe EBUS (69%)
EBUS ¼endobronchial ultrasound.
chestjournal.org 7
largely is centered on the results of the pleural fluid
analysis.
Idiopathic Pulmonary Fibrosis
The condition of idiopathic pulmonary fibrosis (IPF)
can be diagnosed by means of either high-resolution
CT (HRCT) scanning or open lung biopsy. At HRCT
scanning, IPF is diagnosed by exclusion of other
diseases and typical findings of usual interstitial
pneumonia. According to revised American Thoracic
Society, European Respiratory Society, Japanese
Respiratory Society, and Latin American Thoracic
Association guidelines, lung biopsy is not required in
patients with no environmental exposure, connective
tissue disease, or drug toxicities and definite usual
interstitial pneumonia diagnosed on the basis of
HRCT scanning findings.
61-63
In this regard, the value
of TBBx performed via FB is limited. To our
knowledge, the role of cryobiopsy in establishing the
diagnosis of IPF still remains to be studied. BAL also
may be performed to help differentiate IPF from other
fibrotic lung diseases (sarcoidosis, hypersensitivity
pneumonitis, nonspecific interstitial pneumonitis, and
interstitial lung disease related to connective tissue
disease). BAL demonstrating lymphocytosis (>30%)
is postulated to suggest a non-IPF diagnosis in a
patient with radiographically visible fibrotic lung
disease.
64
The clinical utility of this finding is still
under debate.
64,65
In patients with IPF, bronchoscopy often is performed
to assess mediastinal lymphadenopathy, which is a
common finding seen in approximately 60% of
cases.
66
Thesizeandthenumberofenlargedlymph
nodes directly correlate with the severity of the IPF.
67
This lymphadenopathy is usually a sequela of chronic
inflammation and not a concurrent infection or
neoplasm. Bronchoscopy should be avoided under
such circumstances unless there is a high suspicion of
malignancy (Fig 5).
Bronchoscopy also is performed in patients with IPF
presenting with acute respiratory failure. Diffuse
alveolar hemorrhage, infections, and acute
exacerbation of interstitial lung disease are the
common causes of such a presentation. Bronchoscopy
is of low diagnostic yield in assessing the cause of
respiratory failure under such circumstances.
Bronchoscopy is of any therapeutic impact in <25%
of patients, and there is no mortality difference
between those with and those without positive
findings at bronchoscopy.
68
Besides, the procedure is
associated with high rate of complications (25%).
68
BAL also leads to increased risk in patients with acute
exacerbation of interstitial lung disease.
69
FB might be
Figure 5 –A-D, Axial high-resolution CT scans showing typical usual interstitial pneumonia with honeycombing or multilayered cysts with peripheral,
subpleural, and basilar predominance (C, D) along with mediastinal lymphadenopathy (circled in B).
8Special Features [-#-CHEST -2018 ]
of diagnostic value in patients who are receiving
immunosuppressive regimens or who have clinical
concerns about diffuse alveolar hemorrhage; however,
meticulous patient selection is essential.
70
Stage I Sarcoidosis
Sarcoidosis is a granulomatous disorder that commonly
manifests as bilateral hilar adenopathy and pulmonary
reticular opacities. More than one-half of all patients
with active disease receive the diagnosis at stage I when
spontaneous resolution is common.
A tissue diagnosis is not necessary for most patients with
stage I sarcoidosis.
71
The risk of missing a more sinister
diagnosis such as lymphoma is a common
counterargument in favor of tissue sampling. Several
studies have proven that the lack of symptoms and
clinical findings have a strong negative predictive value
against a malignant process in patients with
radiographic evidence of bilateral hilar adenopathy.
72
Statistical models that account for the incidence of
sarcoidosis estimate that the likelihood of finding an
alternative diagnosis via invasive biopsy in a patient with
stage I sarcoidosis is 5 in 10,000 (Fig 6).
73
BAL often is performed to differentiate between
sarcoidosis and hypersensitivity pneumonitis, favoring
performance of FB. The most frequently assessed
parameters in this scenario are the cell counts and
proportions of lymphocyte subpopulations; a high ratio
of cluster of differentiation (CD)4 to CD8 point toward
sarcoidosis. In a study of 562 patients who underwent
BAL for the evaluation of interstitial lung disease, both
IPF and sarcoidosis had ratios of CD4 to CD8 >1.0.
74
In another study, the lymphocyte subset ratio was
assessed in patients with clinical and histologic evidence
of sarcoidosis. The ratio of CD4 to CD8 of <1was
found in less than 12% of patients.
75
However, the
diagnostic value of the BAL lymphocyte subset ratio also
is modified by the radiographic stage of sarcoidosis and
the patient’s smoking status. In summary, BAL with an
elevated ratio of CD4 to CD8 should be used in context
with the clinicoradiologic picture and should not form
the sole basis for diagnosing sarcoidosis.
Although many centers rely on TBNA for diagnosing
sarcoidosis, the data behind its use must be analyzed
carefully. Early EBUS-TBNA studies used a patient
population that was rich with sarcoidosis. More than
90% of patients in these studies received a final diagnosis
of sarcoidosis.
76
A majority of sarcoidosis studies also
originated from tertiary medical centers flush with
highly skilled operators and experienced pathologists.
EBUS-TBNA performed in a less experienced center
yielded a nondiagnostic rate of 73%.
77
Also, most EBUS-
TBNA studies have never defined the entry criteria for
patient selection, thereby limiting the generalizability of
the results.
The presence of a noncaseating granuloma is an
essential piece of information used to diagnose
sarcoidosis. However, it is not an all-or-nothing finding.
Although conventional and advanced bronchoscopic
methods are available for sampling purposes, the
priority should be pursuing the least invasive approach.
In patients who may have stage I sarcoidosis, this may be
as simple as taking a careful history and performing a
thorough physical examination. In summary, the clinical
acumen of the operator is paramount in estimating any
potential benefit of bronchoscopy in this patient
population.
Congestive Lymphadenopathy
More than five million people in the United States and
an estimated 23 million people worldwide have
congestive heart failure.
78,79
Mediastinal
lymphadenopathy is not an uncommon finding in
patients with congestive heart failure and often is
referred to as “congestive adenopathy.”To our
Figure 6 –Chest radiograph showing bilateral symmetric hilar lymph-
adenopathy in a patient with stage I sarcoidosis. In most instances,
tissue diagnosis is not mandatory.
chestjournal.org 9
knowledge, it was first reported in the literature in 1998
and can be found in 54% to 68% of patients with
congestive heart failure.
80,81
Congestive
lymphadenopathy is common in patients with acute
uncompensated congestive heart failure without
diastolic dysfunction and in patients with coronary
artery disease without heart failure.
82
It is a maker of
volume overload, not of systolic dysfunction.
Occasionally, mediastinal lymphadenopathy is found
among patients with uncorrected congenital heart
disease. Similarly, up to 18% of patients with PAH can
have mediastinal lymphadenopathy.
83
This adenopathy
often resolves with appropriate treatment. Keeping in
mind the clinical context and nonmalignant nature of
mediastinal lymphadenopathy, an attempt to obtain
tissue in such cases would be of low diagnostic value. If
there is a doubt, repeat chest CT scanning should be
performed to assess for regression in the size of the
lymph nodes once the patient has been deemed
euvolemic (Fig 7).
Calcified Lymph Nodes
Calcified mediastinal lymph nodes have a broad
differential diagnosis.
84
Often, they are noted as
incidental findings at chest imaging. There are limited
data regarding the effects of calcification on the yield
of EBUS-TBNA. In a study of 236 patients who
underwent EBUS-TBNA, lymph node calcification was
a factor that contributed to inadequate sampling or a
false-negative result.
85
However, Shweihat et al
80
demonstrated that in patients living in a
histoplasmosis endemic area, the presence of
calcification does not affect the yield of EBUS-TBNA.
At present, sampling a calcified mediastinal lymph
node via EBUS-TBNA should be caveat emptor for
any bronchoscopist (Fig 8,Table 5).
Lymphoma
Mediastinal lymphadenopathy is a common
manifestation of all types of lymphoma. EBUS-TBNA is
a valuable tool to identify several causes of mediastinal
lymphadenopathy. However, its role in diagnosing
lymphoma, particularly Hodgkin lymphoma, remains
controversial.
86
Small sample size limits confirmation of
lymph node architecture, Reed-Sternberg cells, extent of
sclerosis, and extent of any granulomatous component,
all of which are essential to confirm and plan the therapy
for the condition. This difficulty may lead to a high
discordance between the cytologic findings at EBUS-
TBNA and histopathologic data obtained by more
Figure 7 –A, Chest radiograph of a patient with acute exacerbation of heart failure. Coronal (B) and axial (C, D) CT scans showing congestive
lymphadenopathy in a case of acute exacerbation of heart failure (circles in B and C), with resolution after treatment with diuretics (circle in D). Note
pacemaker (A).
10 Special Features [-#-CHEST -2018 ]
invasive means. In other words, among patients with a
high likelihood of having Hodgkin disease, EBUS-TBNA
may not be the ideal diagnostic test.
Several studies have shown high sensitivity and
specificity of EBUS-TBNA for lymphomas.
87
However, most of the results have been for recurrent
disease or in cases of non-Hodgkin lymphomas and
ultimately required confirmation with
mediastinoscopy or surgical biopsy.
88
EBUS-TBNA
has a sensitivity of only 61% to 78% for newly
diagnosed non-Hodgkin lymphoma.
89,90
Immunohistochemical and flow cytometric
assessment of TBBx specimens is important because
these assessments determine the type of treatment
required for patients with lymphoma. Patients
suspected of having lymphoma for the first time
ultimately require surgical biopsy to characterize the
type of lymphoma further. In addition, the yield of
TBBx in diagnosing lymphoma may differ
significantly in different studies because of the
availability of rapid on-site microscopic examination,
which may not be available at all institutions.
91
The
utility of 19-guage needle significantly increases the
yieldinlungmalignancybutstillfallsshortfor
diagnosing Hodgkin lymphoma because subsequent
mediastinoscopy is required for further subtyping.
92
Studies also have demonstrated increased blood
contamination of the sample with larger needles.
93
EBUS-TBNA could be reserved for recurrent
lymphomas or in selected cases of high suspicion for
non-Hodgkin lymphomas.
94
Lymphadenopathy and Acute Exacerbation of
COPD
Approximately one-half of the patients with COPD
demonstrate mediastinal lymphadenopathy on a CT
scan of the chest.
95
It is more frequent with heavy
smoking, chronic bronchitis, and bronchial wall
thickening. Performing an invasive procedure without
suspicion for an alternate diagnosis can be detrimental.
There is increased risk of hypoxemia with bronchoscopy
in patients with COPD and pulmonary hypertension.
Towe et al
96
found that BAL in patients with severe
COPD is associated with increased risk of
pneumothorax, bleeding, respiratory failure, and
pneumonia (OR, 6.49; 95% CI, 1.68-24.3; P<.006). BAL
may cause airway obstruction and disequilibration of the
pressure of intraalveolar gases and, as a result, leakage
into the pleural cavity, leading to pneumothorax.
97
Studies have shown that clinical presentation with self-
reported sputum purulence and multiple exacerbations
(>4 in a year) and severe airway obstruction correlates
well with distal airway bacterial infection.
98
There is no
indication for bronchoscopy to document lower
respiratory tract infection among patients presenting
with acute exacerbation of COPD.
Contraindications for Bronchoscopy
As with any procedure, there are absolute and relative
contraindications to FB. Overall, bronchoscopy is a safe
TABLE 5 ]Causes of Calcified Mediastinal Lymphadenopathy
Cause Common Uncommon
Infectious TB
Histoplasmosis
Pneumocystis jirovecii pneumonia
Noninfectious Sarcoidosis
Silicosis
Amyloidosis
Scleroderma
Neoplastic Treated lymphoma Thyroid carcinoma
Osteogenic sarcoma
Bronchial carcinoid tumors
Mucinous ovarian cystadenoma
Mucinous colonic adenocarcinoma
Figure 8 –Axial CT scan showing dense lymph node calcifications in
bilateral, symmetric hilar and multiple mediastinal compartments in a
patient with sarcoidosis.
chestjournal.org 11
procedure, and most contraindications are relative. The
most crucial physiologic contraindication is the inability
to provide adequate oxygenation to the patient during
the procedure. The combination of sedation and partial
blockage of the airway with the bronchoscope itself can
impede oxygenation. Another major contraindication is
either endogenous or iatrogenic coagulopathy.
99
Increased intracranial pressure also is considered a
contraindication to the procedure.
A discussion of risk vs benefit always should be
considered prior to performing the procedure. It is
mandatory that the procedure be performed by an
experienced bronchoscopist or under his or her
supervision.
Summary
FB is a relatively safe procedure, yet like other invasive
procedures, the ability to perform should not translate
into the necessity to perform. It can be considered in
clinical scenarios in which a high diagnostic yield is
anticipated. Alternative modalities of investigation
should be sought when the pretest probability of
diagnostic yield from bronchoscopy is low. The operator
should be well versed with indications,
contraindications, diagnostic yield alternatives, and the
relative cost of the procedure. Vascular endothelial
growth factor D is a biomarker that is emerging as a
promising diagnostic tool for
lymphangioleiomyomatosis, a destructive lung
disease.
100,101
Several biomarkers are currently under
study to detect various types of rejection in patients with
lung transplants. Cylex Immune Cell Function Assay
(ImmuKnow; Cylex, Inc) was approved by the Food and
Drug Administration and is being studied for use in lung
transplant rejections.
102
The utility of these biomarkers as a first-line
investigation will increase exponentially for better
classifying phenotypes and diagnosing several diseases,
such as lymphangioleiomyomatosis and acute rejection
in lung transplant. However, bronchoscopy and TBBx
remain standard practice because of their high yield.
Acknowledgments
Financial/nonfinancial disclosures: None declared.
References
1. Haas AR, Vachani A, Sterman DH. Advances in diagnostic
bronchoscopy. Am J Respir Crit Care Med. 2010;182(5):589-597.
2. Panchabhai TS, Mehta AC. Historical perspectives of
bronchoscopy: connecting the dots. Ann Am Thorac Soc.
2015;12(5):631-641.
3. Mehta AC, Jain P. Interventional Bronchoscopy: A Clinical Guide.
New York, NY: Humana Press; 2013:15-16.
4. Ong PG, Debiane LG, Casal RF. Recent advances in diagnostic
bronchoscopy. J Thorac Dis. 2016;8(12):3808-3817.
5. Narula T, Machuzak MS, Mehta AC. Newer modalities in the
work-up of peripheral pulmonary nodules. Clin Chest Med.
2013;34(3):395-415.
6. Akulian J. IP Fellowship Programs. 2018; http://aippd.org/
members/. Accessed January 1, 2018.
7. Hilliard TN, Sukhani S, Francis J, et al. Bronchoscopy following
diagnosis with cystic fibrosis. Arch Dis Child. 2007;92(10):898-899.
8. Aaron SD, Kottachchi D, Ferris WJ, et al. Sputum versus
bronchoscopy for diagnosis of Pseudomonas aeruginosa biofilms in
cystic fibrosis. Eur Respir J. 2004;24(4):631-637.
9. Don CJ, Dales RE, Desmarais RL, Neimatullah M. The
radiographic prevalence of hilar and mediastinal adenopathy in
adult cystic fibrosis. Can Assoc Radiol J. 1997;48(4):265-269.
10. Flume PA, Mogayzel PJ Jr, Robinson KA, Rosenblatt RL, Quittell L,
Marshall BC. Cystic fibrosis pulmonary guidelines: pulmonary
complications—hemoptysis and pneumothorax. Am J Respir Crit
Care Med. 2010;182(3):298-306.
11. Slattery DM, Waltz DA, Denham B, O’Mahony M, Greally P.
Bronchoscopically administered recombinant human DNase for
lobar atelectasis in cystic fibrosis. Pediatr Pulmonol. 2001;31(5):
383-388.
12. McLaughlin AM, McGrath E, Barry R, Egan JJ, Gallagher CG.
Treatment of lobar atelectasis with bronchoscopically administered
recombinant human deoxyribonuclease in cystic fibrosis? Clin
Respir J. 2008;2(2):123-126.
13. Kunkel A, Abel Zur Wiesch P, Nathavitharana RR, Marx FM,
Jenkins HE, Cohen T. Smear positivity in paediatric and adult
tuberculosis: systematic review and meta-analysis. BMC Infect Dis.
2016;16:282.
14. Wallace JM, Deutsch AL, Harrell JH, Moser KM. Bronchoscopy
and transbronchial biopsy in evaluation of patients with suspected
active tuberculosis. Am J Med. 1981;70(6):1189-1194.
15. Chawla R, Pant K, Jaggi OP, Chandrashekhar S, Thukral SS.
Fibreoptic bronchoscopy in smear-negative pulmonary
tuberculosis. Eur Respir J. 1988;1(9):804-806.
16. Shin JA, Chang YS, Kim TH, Kim HJ, Ahn CM, Byun MK.
Fiberoptic bronchoscopy for the rapid diagnosis of smear-negative
pulmonary tuberculosis. BMC Infect Dis. 2012;12:141.
17. Iyer VN, Joshi AY, Boyce TG, et al. Bronchoscopy in suspected
pulmonary TB with negative induced-sputum smear and
MTD((R)) Gen-probe testing. Respir Med. 2011;105(7):1084-1090.
18. Al Zahrani K, Al Jahdali H, Poirier L, René P, Menzies D. Yield of
smear, culture and amplification tests from repeated sputum
induction for the diagnosis of pulmonary tuberculosis. Int J Tuberc
Lung Dis. 2001;5(9):855-860.
19. McWilliams T, Wells AU, Harrison AC, Lindstrom S, Cameron RJ,
Foskin E. Induced sputum and bronchoscopy in the diagnosis of
pulmonary tuberculosis. Thorax. 2002;57(12):1010.
20. Ganguly KC, Hiron MM, Mridha ZU, et al. Comparison of sputum
induction with broncho-alveolar lavage in the diagnosis of smear-
negative pulmonary tuberculosis. Mymensingh Med J. 2008;17(2):
115-123.
21. Conde MB, Soares SL, Mello FC, et al. Comparison of sputum
induction with fiberoptic bronchoscopy in the diagnosis of
tuberculosis: experience at an acquired immune deficiency
syndrome reference center in Rio de Janeiro, Brazil. Am J Respir
Crit Care Med. 2000;162(6):2238-2240.
22. Brown M, Varia H, Bassett P, Davidson RN, Wall R, Pasvol G.
Prospective study of sputum induction, gastric washing, and
bronchoalveolar lavage for the diagnosis of pulmonary tuberculosis
in patients who are unable to expectorate. Clin Infect Dis.
2007;44(11):1415-1420.
23. Marks SM, Cronin W, Venkatappa T, et al. The health-system
benefits and cost-effectiveness of using Mycobacterium tuberculosis
12 Special Features [-#-CHEST -2018 ]
direct nucleic acid amplification testing to diagnose tuberculosis
disease in the United States. Clin Infect Dis. 2013;57(4):532-542.
24. Peralta G, Barry P, Pascopella L. Use of nucleic acid amplification
tests in tuberculosis patients in California, 2010-2013. Open Forum
Infect Dis. 2016;3(4):ofw230.
25. Updated guidelines for the use of nucleic acid amplification tests in
the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep.
2009;58:7-10.
26. Blakemore R, Story E, Helb D, et al. Evaluation of the analytical
performance of the Xpert MTB/RIF assay. J Clin Microbiol.
2010;48(7):2495-2501.
27. Chakravorty S, Simmons AM, Rowneki M, et al. The new Xpert
MTB/RIF Ultra: improving detection of Mycobacterium
tuberculosis and resistance to rifampin in an assay suitable for
point-of-care testing. MBio. 2017;8(4).
28. Conte BA, Laforet EG. The role of the topical anesthetic agent in
modifying bacteriologic data obtained by bronchoscopy. N Engl J
Med. 1962;267:957-960.
29. Malasky C, Jordan T, Potulski F, Reichman LB. Occupational
tuberculous infections among pulmonary physicians in training.
Am Rev Respir Dis. 1990;142(3):505-507.
30. Saadeh A, Patil N, Selig J, Bates J, Mukasa L. Is bronchoscopy being
overutilized in tuberculosis diagnosis? Arkansas experience 2009-
2015. Open Forum Infect Dis. 2016;3(suppl 1). 222-222.
31. Tsoumakidou M, Chrysofakis G, Tsiligianni I, Maltezakis G,
Siafakas NM, Tzanakis N. A prospective analysis of 184 hemoptysis
cases: diagnostic impact of chest x-ray, computed tomography,
bronchoscopy. Respiration. 2006;73(6):808-814.
32. Lee YJ, Lee SM, Park JS, et al. The clinical implications of
bronchoscopy in hemoptysis patients with no explainable lesions in
computed tomography. Respir Med. 2012;106(3):413-419.
33. Hsiao EI, Kirsch CM, Kagawa FT, Wehner JH, Jensen WA,
Baxter RB. Utility of fiberoptic bronchoscopy before bronchial
artery embolization for massive hemoptysis. AJR Am J Roentgenol.
2001;177(4):861-867.
34. Larici AR, Franchi P, Occhipinti M, et al. Diagnosis and
management of hemoptysis. Diagn Interv Radiol. 2014;20(4):299-
309.
35. Poe RH, Israel RH, Marin MG, et al. Utility of fiberoptic
bronchoscopy in patients with hemoptysis and a nonlocalizing
chest roentgenogram. Chest. 1988;93(1):70-75.
36. Hirshberg B, Biran I, Glazer M, Kramer MR. Hemoptysis: etiology,
evaluation, and outcome in a tertiary referral hospital. Chest.
1997;112(2):440-444.
37. Nielsen K, Gottlieb M, Colella S, Saghir Z, Larsen KR,
Clementsen PF. Bronchoscopy as a supplement to computed
tomography in patients with haemoptysis may be unnecessary. Eur
Clin Respir J. 2016;3:31802.
38. Marini JJ, Pierson DJ, Hudson LD. Acute lobar atelectasis: a
prospective comparison of fiberoptic bronchoscopy and respiratory
therapy. Am Rev Respir Dis. 1979;119(6):971-978.
39. Raoof S, Chowdhrey N, Raoof S, et al. Effect of combined kinetic
therapy and percussion therapy on the resolution of atelectasis in
critically ill patients. Chest. 1999;115(6):1658-1666.
40. Ray K, Bodenham A, Paramasivam E. Pulmonary atelectasis in
anaesthesia and critical care. Contin Educ Anaesth Crit Care Pain.
2014;14(5):236-245.
41. Goodwin RA, Nickell JA, Des Prez RM. Mediastinal fibrosis
complicating healed primary histoplasmosis and tuberculosis.
Medicine (Baltimore). 1972;51(3):227-246.
42. Ferguson TB, Burford TH. Mediastinal granuloma: a 15-year
experience. Ann Thorac Surg. 1965;1:125-141.
43. Saad CP, Murthy S, Krizmanich G, Mehta AC. Self-expandable
metallic airway stents and flexible bronchoscopy: long-term
outcomes analysis. Chest. 2003;124(5):1993-1999.
44. Kern R, Peikert T, Edell E, et al. Bronchoscopic management of
airway compression due to fibrosing mediastinitis. Ann Am Thorac
Soc. 2017;14(8):1353-1355.
45. Folch E, Keyes C. Airway stents. Ann Cardiothorac Surg. 2018;7(2):
273-283.
46. Kamatham M, Wellikoff A, Holladay R, Downie G. Chronic
submassive hemoptysis: unusual treatment. Chest. 2014;146(4):
762A.
47. Al-Ameri A, Malhotra P, Thygesen H, et al. Risk of malignancy in
pulmonary nodules: a validation study of four prediction models.
Lung Cancer. 2015;89(1):27-30.
48. Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided
bronchoscopy for the evaluation of the pulmonary nodule. Chest.
2012;142(2):385-393.
49. Musani AI. Interventional pulmonology: an update. Clin Chest
Med. 2018;39(1):i.
50. Chen A, Chenna P, Loiselle A, Massoni J, Mayse M, Misselhorn D.
Radial probe endobronchial ultrasound for peripheral pulmonary
lesions: a 5-year institutional experience. Ann Am Thorac Soc.
2014;11(4):578-582.
51. Almeida FA, Salam S, Mehta AC, et al. Sampling utility of the
convex probe endobronchial ultrasound visible intrapulmonary
lesion. J Bronchology Interv Pulmonol. 2018;25(4):290-299.
52. Zhang Y, Zhang Y, Chen S, et al. Is bronchoscopy necessary in the
preoperative workup of a solitary pulmonary nodule? J Thorac
Cardiovasc Surg. 2015;150(1):36-40.
53. Mukherjee S, Chacey M. Diagnostic yield of electromagnetic
navigation bronchoscopy using a curved-tip catheter to aid in the
diagnosis of pulmonary lesions. J Bronchology Interv Pulmonol.
2017;24(1):35-39.
54. Bowling MR, Brown C, Anciano CJ. Feasibility and safety of the
transbronchial access tool for peripheral pulmonary nodule and
mass. Ann Thorac Surg. 2017;104(2):443-449.
55. Gildea TR, Mazzone PJ, Karnak D, Meziane M, Mehta AC.
Electromagnetic navigation diagnostic bronchoscopy: a prospective
study. Am J Respir Crit Care Med. 2006;174(9):982-989.
56. DiBardino DM, Yarmus LB, Semaan RW. Transthoracic needle
biopsy of the lung. J Thorac Dis. 2015;7(suppl 4):S304-S316.
57. Light RW. Pleural effusions. Med Clin North Am. 2011;95(6):1055-
1070.
58. Porcel JM, Esquerda A, Vives M, Bielsa S. Etiology of pleural
effusions: analysis of more than 3,000 consecutive thoracenteses.
Arch Bronconeumol. 2014;50(5):161-165.
59. Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ.
Management of a malignant pleural effusion: British Thoracic
Society Pleural Disease Guideline 2010. Thorax. 2010;65(suppl 2):
ii32-ii40.
60. Asciak R, Rahman NM. Malignant pleural effusion: from
diagnostics to therapeutics. Clin Chest Med. 2018;39(1):181-193.
61. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/
ALAT statement: idiopathic pulmonary fibrosis—evidence-based
guidelines for diagnosis and management. Am J Respir Crit Care
Med. 2011;183(6):788-824.
62. Wells AU. The revised ATS/ERS/JRS/ALAT diagnostic criteria for
idiopathic pulmonary fibrosis (IPF): practical implications. Respir
Res. 2013;14(suppl 1):S2.
63. Wells AU. Managing diagnostic procedures in idiopathic
pulmonary fibrosis. Eur Respir Rev. 2013;22(128):158-162.
64. Wells AU, Kokosi MA. Point: should BAL be routinely performed
in the diagnostic evaluation of idiopathic pulmonary fibrosis? Yes.
Chest. 2017;152(5):917-919.
65. Mooney JJ, Collard HR. Counterpoint: should BAL be routinely
performed in the diagnostic evaluation of idiopathic pulmonary
fibrosis? No. Chest. 2017;152(5):919-922.
66. Souza CA, Muller NL, Lee KS, Johkoh T, Mitsuhiro H, Chong S.
Idiopathic interstitial pneumonias: prevalence of mediastinal
lymph node enlargement in 206 patients. AJR Am J Roentgenol.
2006;186(4):995-999.
67. Jung JI, Kim HH, Jung YJ, Park SH, Lee JM, Hahn ST. Mediastinal
lymphadenopathy in pulmonary fibrosis: correlation with disease
severity. J Comput Assist Tomogr. 2000;24(5):706-710.
chestjournal.org 13
68. Arcadu A, Moua T. Bronchoscopy assessment of acute respiratory
failure in interstitial lung disease. Respirology. 2017;22(2):352-359.
69. Sakamoto K, Taniguchi H, Kondoh Y, et al. Acute exacerbation of
IPF following diagnostic bronchoalveolar lavage procedures. Respir
Med. 2012;106(3):436-442.
70. Jain P, Sandur S, Meli Y, Arroliga AC, Stoller JK, Mehta AC. Role
of flexible bronchoscopy in immunocompromised patients with
lung infiltrates. Chest. 2004;125(2):712-722.
71. Hirsch FR, Wynes MW, Gandara DR, Bunn PA Jr. The tissue is the
issue: personalized medicine for non-small cell lung cancer. Clin
Cancer Res. 2010;16(20):4909-4911.
72. Winterbauer RH, Belic N, Moores KD. Clinical interpretation of
bilateral hilar adenopathy. Ann Intern Med. 1973;78(1):65-71.
73. Reich JM. Tissue confirmation of presumptive stage I sarcoidosis.
J Bronchology Interv Pulmonol. 2013;20(2):103-105.
74. Jara-Palomares L, Martín-Juan J, Gómez-Izquierdo L, Cayuela-
Domínguez A, Rodríguez-Becerra E, Rodríguez-Panadero F.
Bronchoalveolar lavage findings in patients with diffuse interstitial
lung disease: prospective study of a cohort of 562 patients [in
Spanish]. Arch Bronconeumol. 2009;45(3):111-117.
75. Kantrow SP, Meyer KC, Kidd P, Raghu G. The CD4/CD8 ratio in
BAL fluid is highly variable in sarcoidosis. Eur Respir J.
1997;10(12):2716-2721.
76. Costabel U, Bonella F, Ohshimo S, Guzman J. Diagnostic
modalities in sarcoidosis: BAL, EBUS, and PET. Semin Respir Crit
Care Med. 2010;31(4):404-408.
77. Lange TJ, Kunzendorf F, Pfeifer M, Arzt M, Schulz C.
Endobronchial ultrasound-guided transbronchial needle aspiration
in routine care: plenty of benign results and follow-up tests. Int J
Clin Pract. 2012;66(5):438-445.
78. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke
statistics: 2013 update—a report from the American Heart
Association. Circulation. 2013;127(1):e6-e245.
79. McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical
epidemiology of heart failure: public and private health burden. Eur
Heart J. 1998;19(suppl P):P9-P16.
80. Shweihat YR, Perry J, Etman Y, et al. Congestive adenopathy: a
mediastinal sequela of volume overload. J Bronchology Interv
Pulmonol. 2016;23(4):298-302.
81. Slanetz PJ, Truong M, Shepard JA, Trotman-Dickenson B,
Drucker E, McLoud TC. Mediastinal lymphadenopathy and hazy
mediastinal fat: new CT findings of congestive heart failure. AJR
Am J Roentgenol. 1998;171(5):1307-1309.
82. Chabbert V, Canevet G, Baixas C, et al. Mediastinal
lymphadenopathy in congestive heart failure: a sequential CT
evaluation with clinical and echocardiographic correlations. Eur
Radiol. 2004;14:881-889.
83. Moua T, Levin DL, Carmona EM, et al. Frequency of mediastinal
lymphadenopathy in patients with idiopathic pulmonary arterial
hypertension. Chest. 2013;143(2):344-348.
84. Naidich DP, Srichai MB. Computed Tomography and Magnetic
Resonance of the Thorax. 4th ed. Philadelphia, PA: Wolters Kluwer
Lippincott Williams & Wilkins; 2007:364-368.
85. Kennedy MP, Jimenez CA, Morice RC, et al. Factors influencing the
diagnostic yield of endobronchial ultrasound-guided transbronchial
needle aspiration. J Bronchology Interv Pulmonol. 2010;17(3):202-208.
86. Du Rand IA, Barber PV, Goldring J, et al. British Thoracic Society
guideline for advanced diagnostic and therapeutic flexible
bronchoscopy in adults. Thorax. 2011;66(suppl 3):iii1.
87. Kennedy MP, Jimenez CA, Bruzzi JF, etal. Endobronchial
ultrasound-guided transbronchial needle aspiration in the
diagnosis of lymphoma. Thorax. 2008;63(4):360-365.
88. Marshall CB, Jacob B, Patel S, et al. The utility of endobronchial
ultrasound-guided transbronchial needle aspiration biopsy in the
diagnosis of mediastinal lymphoproliferative disorders. Cancer
Cytopathol. 2011;119(2):118-126.
89. Erer OF, Erol S, Anar C, Aydo
gdu Z, Özkan SA. Diagnostic yield of
EBUS-TBNA for lymphoma and review of the literature. Endosc
Ultrasound. 2017;6(5):317-322.
90. Gandotra S, Dotson T, Lamar Z, Bellinger C. Endobronchial
ultrasound transbronchial needle aspiration for the diagnosis
of lymphoma. J Bronchology Interv Pulmonol. 2018;25(2):97-
102.
91. Grosu HB. EBUS-TBNA for the diagnosis of lymphoma: time to
give in? J Bronchology Interv Pulmonol. 2018;25(3):165-166.
92. Tyan C, Patel P, Czarnecka K, et al. Flexible 19-gauge
endobronchial ultrasound-guided transbronchial needle aspiration
needle: first experience. Respiration. 2017;94(1):52-57.
93. Nakajima T, Yasufuku K, Takahashi R, et al. Comparison of 21-
gauge and 22-gauge aspiration needle during endobronchial
ultrasound-guided transbronchial needle aspiration. Respirology.
2011;16(1):90-94.
94. Bandyopadhyay D, Panchabhai TS, Mehta AC. EBUS-TBNA for
the diagnosis of lymphoma: still an Achilles heel. Ann Am Thorac
Soc. 2015;12(9):1263-1264.
95. Kirchner J, Kirchner EM, Goltz JP, Obermann A, Kickuth R.
Enlarged hilar and mediastinal lymph nodes in chronic obstructive
pulmonary disease. J Med Imaging Radiat Oncol. 2010;54(4):333-
338.
96. Towe CW, Ho VP, Kazakov J, et al. Severe chronic obstructive
pulmonary disease is not associated with complications after
navigational bronchoscopy procedures. Ann Thorac Surg.
2017;104(1):290-295.
97. Krueger JJ, Sayre VA, Karetzky MS. Bronchoalveolar lavage-
induced pneumothorax. Chest. 1988;94(2):440-441.
98. Soler N, Agustí C, Angrill J, et al. Bronchoscopic validation of the
significance of sputum purulence in severe exacerbations of chronic
obstructive pulmonary disease. Thorax. 2007;62:29-35.
99. Abuqayyas S, Raju S, Bartholomew JR, Abu Hweij R, Mehta AC.
Management of antithrombotic agents in patients undergoing
flexible bronchoscopy. Eur Respir Rev. 2017;26(145).
100. Nijmeh J, El-Chemaly S, Henske EP. Emerging biomarkers of
lymphangioleiomyomatosis. Expert Rev Respir Med. 2018;12(2):95-
102.
101. Young LR, Lee HS, Inoue Y, et al. Serum VEGF-D concentration as
a biomarker of lymphangioleiomyomatosis severity and treatment
response: a prospective analysis of the Multicenter International
Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial.
Lancet Respir Med. 2013;1(6):445-452.
102. Berastegui C, Roman J, Monforte V, et al. Biomarkers of pulmonary
rejection. Transplant Proc. 2013;45(9):3163-3169.
14 Special Features [-#-CHEST -2018 ]
