Pediatric Pulmonology 31:150±164 (2001)
State of the Art
Pediatric Bronchoscopy
T. Nicolai, MD*
Summary. Diagnostic ¯exible endoscopy for pediatric respiratory diseases is performed in many
centers. Technical advances have resulted in performance of interventional bronchoscopies, and
new diagnostic indications are being explored. Indications with documented clinical bene®t
include congenital or acquired progressive or unexplained airway obstruction. Pulmonary
infections in immunode®cient children who do not respond to empirical antibiotic treatment may
be diagnosed by bronchoscopy and bronchoalveolar lavage (BAL). The potential usefulness of
bronchoscopy and BAL for managing chronic cough, wheeze, or selected cases with asthma or
cystic ®brosis requires further study. The use of transbronchial biopsies (TBB) is established in
pediatric lung transplantation. The role of TBB in the diagnosis of chronic interstitial lung disease
in children remains to be determined. For a number of interventional applications, rigid endoscopy
is required, and pediatric bronchoscopists should be trained in its use. Complications in pediatric
bronchoscopy are rare, but severe nosocomial infection or overdosing with local anesthetics has
occurred. The issues of quality control, video documentation, interobserver variability of ®ndings,
and educational standards will have to be addressed in the future as bronchoscopy use becomes
less restricted to only large pediatric pulmonary units. Pediatr Pulmonol. 2001; 31:150±164.
ß 2001 Wiley-Liss, Inc.
Key words: bronchoscopy; children; biopsy; lavage.
INTRODUCTION
The use of the ¯exible endoscope in investigating
pediatric respiratory problems like stridor in infants or
pulmonary infections in immunosuppressed children has
become routine in many centers. A number of recent
books,1±3 review articles, and position statements have
been published on this subject.4±7 The investigational use
of bronchoscopy and bronchoalveolar lavage (BAL) has
led to signi®cant insights into various pulmonary disease
processes. Retrospective studies indicate a high diagnostic yield,8±11 but the bene®t for the patient will depend on
careful evidence-based patient selection. The decision to
bronchoscope a child is best guided by anticipating the
parent's view regarding possible therapeutic consequences of the procedure. For a surprising number of
clinical situations there is either a lack of prospective data
or a lack of consensus on the utility of airway endoscopy.
New information is now available regarding possible
complications of ®beroptic bronchoscopy such as nosocomial infection or consequences of the overuse of local
anaesthetics. The issues of quality control, video documentation, interobserver variability of ®ndings, and
educational standards will have to be addressed in the
future as bronchoscopy use becomes less restricted to
large pediatric pulmonary units.
ß 2001 Wiley-Liss, Inc.
While the use of ¯exible bronchoscopy is regarded as a
standard diagnostic tool in reviews from North America,7
a recent monograph from Europe12 still regards the rigid
scope as the everyday workhorse; this difference may
have to do with local practices. However, the availability
and cost of a ¯exible bronchoscope compared with and
added to that of rigid equipment (which will allow foreign
body extraction as well as many diagnostic interventions)
play a role in many parts of the world. On the other hand,
lack of ready access to an operating theater or anesthetist,
or a tradition of limiting rigid endoscopy to surgeons,
will favor the use of a ¯exible instrument by pediatric
pulmonologists. The use of the ¯exible endoscope is
indispensable if functional assessment of the airway is
required (stridor, suspected tracheobronchomalacia). The
ease of its use under sedation and local anesthesia has
made it the ®rst choice for most diagnostic endoscopies.
The main weaknesses of ¯exible endoscopy are the subUniversitaÈt Kinderklinik MuÈnchen, Dr. von Haunerschen Kinderspital,
Munich, Germany.
*Correspondence to: Dr. T. Nicolai, UniversitaÈt Kinderklinik MuÈnchen,
Lindwurmstr. 4, 80337 MuÈnchen, Germany.
E-mail: [email protected]
Received 12 June 2000; Accepted 25 August 2000.
Pediatric Bronchoscopy
optimal delineation of the immediate subglottic area and
insuf®cient visibility if sedation is not adequate.
Rigid endoscopy is ideal for the documentation of
glottic and subglottic pathology (cleft, high ®stula) and
for interventions (e.g., foreign body extraction, stents,
laser surgery). If surgical intervention becomes necessary,
high-resolution delineation of the airway structures will
often be required by the surgeon.13 It may be necessary to
decide whether a stenosis is rigid or ¯accid by directly
probing the lesion. The use of the laryngoscope, with a
short-acting anesthetic, and inspection through an ultrathin rigid telescope, can rule out a subglottic foreign body
in severe or atypical group without touching mucosal
surfaces. This may sometimes be the safest option.14
Rigid bronchoscopy may also be necessary in some cases
for transbronchial biopsy, ®stula detection, and airway
recanalisation in tuberculosis (TB) or tumors. While the
number of children requiring rigid endoscopy is not large,
a place for both techniques will remain in the future;15 the
relative strengths of both methods are summarized in
Table 1. While it is easy to predict that many more
pediatricians will be trained in ¯exible rather than rigid
endoscopy, pro®ciency at both would be ideal.
ANESTHESIA/SEDATION
While rigid bronchoscopy always requires the use
of general anesthesia, ¯exible endoscopy can be done
ABBREVIATIONS
ATS
BACTEC
American Thoracic Society
Radiometric detection of tuberculosis organisms in ¯uid
culture media
BAL
Bronchoalveolar lavage
BPD
Bronchopulmonary dysplasia
CCD
Charge coupled device
CF
Cystic ®brosis
CMV
Cytomegalovirus
CPAP
Continuous positive airway pressure
CT
Computed tomography
DNAse
Desoxyribonuclease
ECP
Eosinophil cationic protein
EM
Electron microscopy
EPX
Eosinophil protein X
ERS
European Respiratory Society
HIV
Human immunode®ciency virus
ICU
Intensive care unit
ILD
Interstitial lung disease
LLMI
Lipid-laden macrophage index
LTC4
Leukotriene C4
LTB4
Leukotriene B4
MRI
Magnetic resonance imaging
NICU
Neonatal intensive care unit
OLB
Open lung biopsy
PCP
Pneumocystis carinii pneumonia
PCR
Polymerase chain reaction
PEEP
Positive end expiratory pressure
TBB
Transbronchial biopsy
TB
Tuberculosis
TNF-alpha Tumor necrosis factor alpha
TXA2
Thromboxane A2
151
TABLE 1ÐRelative Strengths of Flexible and Rigid
Bronchoscopy1
Low invasiveness
Evaluating laryngeal function
Bronchoalveolar Lavage
Transbronchial biopsy
Subglottic pathology
Fistula; cleft
Preoperative assessment
Interventions
(foreign body, laser)
1
Flexible
Rigid
‡‡
‡‡
‡‡
‡‡
‡/ÿ
‡/ÿ
‡
ÿ
ÿ
‡
‡
‡‡
‡‡
‡‡
ÿ
‡‡
‡ ‡ , excellent; ‡ , good to fair; ÿ , less suitable to not possible.
under sedation. Guidelines have been laid down by the
American Academy of Pediatrics regarding the monitoring and management of children during sedation.16 Very
young children will often need deep sedation or
anesthesia for the examination to be done with a similar
degree of comfort and painlessness, as is the current
standard for other therapeutic and diagnostic procedures
in children. It is unacceptable to bronchoscope a toddler
under light sedation and restraints, thus obtaining only
suboptimal endoscopic information due to movement,
coughing, and obstructed views. Some groups, therefore,
prefer to perform ¯exible bronchoscopies in children
under general anesthesia.8,17,18
The progression from consciousness to deep sedation
and anesthesia is gradual when repeated doses of commonly used drugs like midazolam are given. The endoscopist must anticipate that protective airway re¯exes may
no longer be present and that normal respiratory control
may have ceased. A second physician should be present
to monitor the patient, because it is very dif®cult for the
bronchoscopist to observe the child while he/she performs the procedure. A published statement only requires
that someone skilled in i.v. line placement be present
during pediatric bronchoscopy.6 However, dangerous
situations may arise, which may be dif®cult to manage
without already established venous access. Commonly
used sedative procedures are shown in Table 2, but their
application requires experience.
With ¯exible bronchoscopy, the use of a local
anesthetic is routine (Table 2). It is usually applied to
the region of the vocal cords, then to the trachea above the
carina and the bronchi. It is important to adhere to safe
doses for these agents,19,20 because lethal complications
of overdoses have been reported.21 Inhalation of topical
anesthetics via a facemask is used in adults before
bronchoscopy and has been reported in children,22 but we
have found this dif®cult in children due to the bad taste
of lidocaine. When a ¯exible endoscope with a suction
channel is used, the local anesthetic can be sprayed
directly onto the larynx. However, lidocaine has been
shown to exaggerate laryngomalacia23 and should there-
152
Nicolai
TABLE 2ÐSedation/Analgesia for Fiberoptic Bronchoscopy
Nothing per os
Premedication: Age > 1 year:
Atropin
Midazolam
Sedation
i.v. line
Midazolam
And/or Propofol1
6 h food, 4 h clear liquids
0.02 mg/kg (p.o., p.r.)
0.5 mg/kg (p.r., p.o.)
Establish before start of procedure
0.1 mg/kg /dose i.v., total maximum dose 0.2±0.3 mg/kg i.v., ¯ush well; second
dose: only if insuf®cient after 1±5 min
0.5 mg/kg/dose, repeat until adequate sedation (maximum 3.5 mg/kg), followed
by (or replaced by)
0.1 mg/kg/min (apneas, hypoventilation possible)
Additionally (if required to suppress cough)1
Pethidin
0.5±2 mg/kg i.v. or
Alfentanil
0.5 mcg/kg/min or
Remifentanyl
0.05±0.1 mcg/kg/min
No codeine except possibly for CF patients >6 years, 7.5±15 mg
Topical anesthesia
Lidocaine 2%
0.5±1 mL/dose (each with 9 mL air in 10 mL syringe); maximal total dose
4 mg/kg, i.e., 0.2 mL/kg of 2% solution
First dose intranasally, second dose to vocal cords, then carina, bronchi
as required
1
Caveat: propofol and opiates (and rarely midazolam) may cause apnea. Propofol not allowed < 3 years in some countries. Postprocedure
surveillance for 2±4 h, discharge only if accompanied by adult.
fore be applied only after assessment of the larynx in
infantile stridor.
Oxygen delivery or the application of continuous
positive airway pressure (CPAP) during ¯exible endoscopy will make the procedure safer and prevent
desaturations particularly in small children. For this
purpose, oxygen administration through nasal prongs or
through the suction channel has been used.7 If the latter
method is used, the endoscopist should be aware that
local increased intra-airway pressure and possibly pneumothorax can develop if the endoscope is passed into
smaller airways. Other groups have developed ventilation
masks with appropriate ports for the endoscope;24 commercially available swivel adapters with a port may also
be used with a conventional anesthesia mask. The application of a mask will sometimes require more sedation than
the passage of the endoscope through the nose after local
anesthetic alone. A laryngeal mask airway has been used
by others,17,25±27 but deep sedation or anesthesia is
needed to tolerate this device. While all information on
upper airway dynamics is lost, contamination of the
bronchoscope is decreased; this technique is suitable for
BAL or interventional bronchoscopies.
The use of inhalation anesthesia for rigid bronchoscopy can result in occupational exposure of the personnel
above accepted safety limits.28 Appropriate technical
measures can avoid this (e.g., scavenging systems blowing fresh air from above the patient's head) and exposure
may be less during ¯exible endoscopy. Intravenous
medication is preferable in many cases. Low-dose propofol has been used for sedation and higher doses for
anesthesia. Propofol is not approved for children below
age 3 years in some countries. Higher doses can cause
apnea, and an anesthetist should be present when this
drug is used. Usually, some analgesia is also required, and
short-acting opioids appear appropriate, as no postprocedure pain is expected (Table 2).29
Monitoring during bronchoscopy has been improved
greatly by the use of pulse oximetry. If pulse oxymetry
fails due to technical or other reasons, one should not go
ahead with bronchoscopy. Endexpiratory CO2 monitoring
will allow the early detection of signi®cant airway
obstruction or apnea (no PECO2 detected) or hypoventilation (increasing PECO2) during ®beroptic endoscopy,
although absolute values will usually differ from blood
gas analyses.30,31
DOCUMENTATION
Video cameras and displays have become widely available, and ®ndings should be documented in all cases by
description, still photographs, and video. Video documentation will allow reexamination of the ®lms after the
procedure, demonstrate the results to other physicians
(e.g., if surgery is planned), and aid in discussing the
results with parents. Also, changes over time will make
comparisons possible, and this is much preferable to still
shots with a conventional camera. It is useful to have a
microphone for simultaneous recording of breath sounds
indicating phases of respiration, and voice recordings
regarding sedation status or the patient's responses to
procedures. This will allow precise documentation of
diagnoses like vocal cord paralysis or dysfunction.
Pediatric Bronchoscopy
COMPLICATIONS
Many centers perform pediatric bronchoscopies frequently (up to 600/year/center), and data from larger
surveys regarding the safety of the procedure have
become available.8 Complications of ¯exible bronchoscopy are rare, but two pediatric fatalities have been
reported.32,33 Local anesthetic overdose has been implicated in the death of a young healthy volunteer,21 and an
adult died from sepsis after BAL.34 In hospitals with
smaller numbers of endoscopies or for procedures done in
outpatient of®ces, the complication rate has only rarely
been documented.10 Some children are at greater risk
than others, e.g., transient hypoxia was reported in 23%,
and one of 30 patients experienced a bradycardic event,
when children with wheeze underwent bronchoscopy
and BAL.35 While modern sedatives may tempt one to
bronchoscope in any setting, the risks involved should not
be underestimated.
Recently, it has become clear that infection control is
an important consideration in ¯exible endoscopy, as
transmission of bacteria has been reported.36 The greatest
problem is usually proper disinfection of the thin suction
channel and valves. If endoscope surfaces become brittle
from use, bacteria may penetrate into the cracks around
the optic ®bers and cables. Therefore, leak detection with
appropriate devices must be performed regularly, and
manual cleaning with the use of brushes for the suction
canal is important immediately after each endoscopy.
Washing/disinfection machines for endoscopes will not
obviate the need for the manual removal of secretions
from the critical surfaces. Regular surveillance programs
to detect bacterial contamination are necessary at every
institution performing pediatric bronchoscopies.
While rigid bronchoscopies may cause bacteremia,37
¯exible bronchoscopy with BAL in immunocompetent
children may induce high fever but not usually bacteremia.38,39 One case of rapidly fatal septic shock in a child
with primary immunode®ciency and pneumonia33 followed BAL, this indicates that antibiotics should be considered at least immediately after the procedure in
children who are not immunocompetent and who have
acute pulmonary infections. However, most of these
children will be on empirical antibiotics even before BAL
and the rapid development of sepsis is unlikely.
DIAGNOSTIC BRONCHOSCOPIES
Clinical Indications
Inspiratory Stridor
The diagnostic utility of bronchoscopy is wellestablished for airway obstruction of unknown origin,
and the most frequent indication is congenital stridor.40
For example, in a retrospective analysis of 53 bronchoscopies for noisy breathing, it was documented that a
153
clinically meaningful result was found in 96% of cases.9
While this is a very high yield, it does not indicate that
every child with infantile stridor will bene®t from
bronchoscopy,23 similar restrictions hold for many other
applications of bronchoscopy or BAL. Most authors
agree that noisy breathing should be investigated
endoscopically when it is progressive or causes apneas,
dif®culty in feeding, or growth retardation, or when
symptoms point to a diagnosis other than infantile
laryngomalacia. During the initial clinical evaluation,
the posterior part of the tongue should be palpated at least
if apneic episodes are reported by the parents, because a
thyroglossal cyst can cause sudden asphyxiation.41 It is
now known that the endoscope must be advanced beyond
the vocal cords, even if inspiratory collapse of the
supraglottic structures is seen and felt to be responsible
for stridor. Laryngomalacia can be associated with
subglottic or tracheal obstructions such as hemangioma
or tracheomalacia in up to 15% of children.42 Vocal cord
paralysis has been implicated as the second most frequent
cause of neonatal stridor.40 Children with Chiari
malformation and respiratory dif®culties may have vocal
cord paralysis, which improves after decompression
surgery.43
Vocal cord dysfunction was recently recognized in
atypical asthma in children and adolescents (e.g., refractory to standard therapy despite good compliance, or with
severe unexplained episodes of stridor or dyspnea).44 In
adults, deep inspiration sometimes allows for direct
observation of inspiratory glottic closure, but this is more
dif®cult in children. A paradoxical inspiratory narrowing
of the anterior portion of the vocal cords has been
demonstrated in pediatric patients as well.45 However, it
is currently unknown whether this is a pathognomonic
phenomenon. A normal laryngoscopy during a symptomfree interval does not exclude the diagnosis.
Expiratory Wheezing or Rhonchi
Expiratory wheezing or rhonchi will also be an
indication for endoscopy, if other causes such as asthma
or cystic ®brosis (CF) have been ruled out, or if the
obstruction is unilateral. Foreign bodies, tracheobronchial or vascular malformations,46 and intrathoracic
airway malacia or stenosis47 are occasionally found.
Tracheomalacia is common after esophageal atresia and
tracheo-esophageal atresia, and is easily identi®ed by the
often almost total collapse of the tracheal lumen at the
site of the crossing brachiocephalic artery.48 Other diagnostic options such as a lateral chest X-ray, computed
tomography (CT) scan, and magnetic resonance imaging
(MRI), will often not give suf®cient information to
obviate endoscopy. Compression of the left main stem
bronchus was the focus of a recent article,49 and the most
frequent cause seems to be an abnormal prespinal position
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Nicolai
of the descending aorta, which compresses the bronchus
against the left pulmonary artery. Left atrial enlargement
can also compromise the lumen of the left main-stem
bronchus.
A particularly dif®cult diagnosis is bronchomalacia,50,51
and no generally accepted diagnostic criteria are available. While central airway closure during quiet spontaneous breathing must be considered abnormal, the same
would be normal when the patient coughs or uses
expiratory muscles during bronchoscopy. It has been
suggested that in normal airways the cross-sectional area
will not decrease by more than 25% during spontaneous
breathing.52 However, this study used an unspeci®ed
clinical diagnosis of tracheobronchomalacia as the gold
standard and analyzed only seven cases and eight controls, which makes it dif®cult to generalize the ®ndings.
The endoscope itself may cause increased resistance with
forced inspiration and active expiration, leading to a false
diagnosis of tracheobronchomalacia, or to inadvertent
positive end-expiratory pressure (PEEP) and stenting of
the airway (masking real tracheobronchomalacia). No
data are available on the normal in vivo stability of
children's airways during bronchoscopy (e.g., transmural
pressures vs. changes of airway size and collapse), but
animal experiments show a greatly increased collapsibility of immature airways.53 It is dif®cult to make a ®rm
diagnosis of tracheobronchomalacia from a bronchoscopic examination alone at the present time.
Chronic Cough, Wheezy Bronchitis
Bronchoscopy is often included in the diagnostic
workup of unexplained chronic cough and wheeze, but
the diagnostic yield will depend largely on patient
selection. Other diseases, such as CF, asthma, immunode®ciency, gastroesophageal re¯ux, and chronic aspiration, should be ruled out before endoscopy, and cough
variant asthma will be a frequent diagnosis.54 A recent
study found that a diagnosis can be made with simple
clinical approaches including a therapeutic trial (e.g.,
with bronchodilators or antacids) in most children with
chronic cough.55 However, a few important diagnoses
such as a nonobstructing unsuspected foreign body or
tracheomalacia/stenosis will be made only by endoscopy.
In our experience, this justi®es bronchoscoping children
with chronic cough or wheeze after careful clinical
investigations have failed to achieve a diagnosis. A
retrospective case series used bronchoscopy and BAL to
investigate 30 young children with recurrent wheeze
poorly responsive to bronchodilators, who mostly had
been tentatively labeled asthmatic.35 Tracheomalacia was
found in 12 and treated with aortopexy in one; the
®ndings from BAL culture and cytology were more
dif®cult to interpret. Bacteria (11%) and viruses (33%)
were isolated, and abnormal cell differential was reported
in 41% of cases. However, it was not reported how the
treatment was adjusted based on the BAL results, and
what change in clinical outcome was achieved on the
basis of BAL and bronchoscopy. Therefore, the clinical
utility and possible bene®t from BAL in this situation
remains to be determined.
The diagnostic value of bronchoscopy in suspected
chronic aspiration or gastroesophageal re¯ux associated
respiratory symptoms has been reviewed.56 In infants,
endoscopy (sometimes combined with esophagoscopy)
may be necessary if aspiration is strongly suspected and a
lateral chest X-ray in the prone position with contrast
®lling of the esophagus has ruled out a ®stula (e.g., to
identify a laryngeal cleft).57 While BAL and the lipid
laden macrophage index (LLMI) have been advocated as
a useful indicator for chronic aspiration,58 others have
found considerable overlap with various bronchopulmonary disorders and normal children, making the LLM
of questionable value.59,60 It appears that the lipids in the
lipid-laden macrophages may represent endogenous
digested lipids from in¯ammatory processes rather than
exogenous aspirated material. One study investigated
children <18 months old with recurrent wheeze which
was poorly responsive to bronchodilators,35 and while
four patients with proven re¯ux had an elevated LLMI,
two of these also had adenovirus cultured from the
airways, making the LLMI ®ndings dif®cult to interpret.
Increases in LLMI have also been found after lipid
infusions61 and in a child with veno-occlusive disease of
the lung. Interestingly, aggressive surgical management
of suspected re¯ux-associated respiratory disease de®ned
by LLMI and other tests has been advocated by one group
in a study of highly preselected patients, while no
controls or conservative treatment trials were included.62
There is no consensus whether bronchoscopy or BAL has
a diagnostic role in the absence of anatomical abnormalities such as ®stulas or clefts in these children. The
LLMI can only provide some additional information in
the wider clinical assessment leading to a diagnosis of
chronic aspiration. Other tools such as nuclear (milk)
scans, two-point pH-metry of the esophagus, or a
therapeutic trial with proton pump inhibitors63 may be
more important than bronchoscopy. The use of methylene
blue-colored feeds and subsequent bronchoscopy has
been proposed for the diagnosis of salivary aspiration in
children with neurological abnormalities.64 However, it is
unclear whether salivary aspiration alone causes pulmonary damage. Therefore, the clinical value of this
technique remains unproven.
The diagnosis of primary ciliary abnormalities usually
requires a stepwise approach excluding other diseases
before airway epithelium is directly investigated. Early
chronic upper (rhinitis, sinusitis, and otitis) and lower
respiratory tract involvement is almost universally
seen, and situs inversus is expected in 50% of cases of
Pediatric Bronchoscopy
Kartagner's syndrome. After a nasal brush biopsy and
direct observation of the movement of cilia during an
infection-free period has repeatedly shown the absence of
normal beating, an airway biopsy (4±8 specimens) for
electron microscopy (EM) is required. No data are
available to suggest increased ef®ciency of bronchial
over nasal biopsies for this purpose. In children, the
carinal edges are the easiest bronchial regions to biopsy;
however, they contain few ciliated cells. Due to the cost
and time required to make the diagnosis by EM,
bronchial biopsies for EM cannot be the standard of care
in the evaluation of children with chronic respiratory
problems. A recent report has shown that a careful clinical
assessment before biopsy and EM can avoid unnecessary
and expensive investigations. With this approach, primary
ciliary abnormalities were found in about one third of
samples taken.65 Also, screening the biopsy samples
under light microscopy for ciliated epithelium before EM
can prevent the expensive misadventure of processing
specimens containing no ciliated epithelium.
Bronchoscopy in the Intensive Care Unit (ICU)
Considerable progress has been made in the use of
bronchoscopy in intubated children in intensive care.66,67
With small ¯exible endoscopes (e.g., 2.2 mm OD), even
premature infants can be endoscoped through the endotracheal tube. While these endoscopes often have no
suction channel, conventional suctioning through the tube
immediately before endoscopy will usually allow suf®cient visualization. Proposed uses have been to check for
tube obstruction, obviating the change of the endotracheal tube,68 demonstrating the exact position of the tip
of the tube,69 and the diagnosis of airway obstruction in
lobar overin¯ation.70 However, signi®cant oxygen desaturation and even transient bradycardia were observed in
14% of such procedures despite the use of an adapter
allowing uninterrupted ventilation.71 While these problems may decrease with even smaller endoscopes, bronchoscopy has yet to become a universally accepted
diagnostic proceedure and is not routine in many neonatal
ICUs (NICUs). The frequently detected granulation
tissue after deep suctioning has led to restricting the use
of suction catheters to the lumen of the endotracheal
tube.7 In our experience, bronchoscopy is a very useful
technique in selected cases. However, its routine use to
locate the tip of the endotracheal tube in newly intubated
neonates is unnecessary, because these children will
usually require a chest X-ray for other reasons.
Airway endoscopy (particularly laryngoscopy) is
useful in failure to extubate due to stridor.72,73 Granulations may be removed or respond to local application of
corticosteroids,74 while cicatricical lesions or subglottic
cysts may be incised surgically or with a laser.75,76 Vocal
cord paralysis may resolve or have an intracranial
155
77
etiology, and arytenoid dislocation can be identi®ed.78
In selected cases with severe acute stridor, ¯exible
pharyngoscopy may be done in an ICU setting without
sedation to identify a retropharyngeal abscess, purulent
tracheitis,79 and the now rare epiglottitis.80
Bronchoscopy can be useful in children with airway
obstruction after cardiac surgery.81 Typical ®ndings
include the obstruction of the left main-stem bronchus
due to shunts or an enlarged pulmonary artery or left
atrium. After a Fontan procedure, plastic bronchitis, consisting of chylous condensates forming bronchial casts,
may require extraction by suction. This condition may
respond to heparin, but not to locally applied lytic
substances.82
A recent report described the successful use of DNAse
after bronchoscopic diagnosis of unilateral endoluminal
obstruction in a carefully documented case of a ventilated
child, with lobar atelectasis in status asthmaticus, which
was refractory to conventional maximal therapy.83
Tracheostomy
Surprisingly little objective information exists regarding the management and monitoring of pediatric
tracheostomies, but a consensus paper has recently been
published by the American Thoracic Society (ATS) and
the European Respiratory Society (ERS).84 Surveillance
bronchoscopies (rigid or ¯exible) are usually done every
6±12 months, and more often in infants. However, few
data are available to support any recommendation. If
decannulation is not planned, only the trachea around and
below the tracheostomy tube needs to be inspected. No
anaesthetic or sedation is needed for this purpose if the
¯exible endoscope is passed through the cannula and then
slowly pulled out together with the tracheotomy tube. A
recent paper describes the use of bronchoscopy in
children with burns, to determine when early tracheotomy is indicated to avoid tube placement in a severely
in¯amed subglottic area.85
Techniques
Bronchoalveolar Lavage
The use of BAL for diagnostic purposes appears
attractive, as it is a relatively simple procedure with few
side effects. A recent report by an ERS task force
regarding technical aspects and normal values has been
published.20 Some details of BAL (aliquot volume and
number as well as exact processing techniques of the
samples) have not been universally accepted, although it
is unlikely that using less than 3 1 mL/kg will return
suf®cient material for examination in small children. The
®rst aliquot may be analyzed separately.20,86 Normal
values should in principle be established for each laboratory and endoscopy unit, but this could be dif®cult due to
ethical and practical reasons. Normal values for cell
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Nicolai
content, surfactant components, and proteins have been
established for children.20,87±89 However, prospective
studies analyzing the complication rate and bene®t in
various situations (e.g., unexplained chronic or recurrent
cough/bronchitis in young children) are lacking. The
diagnostic ef®ciency will be greatly in¯uenced by patient
selection and will therefore vary between studies, unless
stringent entry criteria are applied.
Reported indications include pulmonary infections
of the immunode®cient or immunosuppressed child,
e.g., with HIV,90 or after bone marrow transplant (52%
positive)91,92 refractory to standard empirical treatment.
A retrospective analysis of 21 immunocompromised
children identi®ed fungi in 47% and bacteria in 25%, and
reported a clinically meaningful result in 76%.9 However,
the achievable clinical bene®t will depend on the overall
prognosis of these severely ill patients. In children with
cancer and pulmonary in®ltrates, the yield was lower (12/
60 or 27%), and the authors noted that while positive
BAL results will be helpful, negatives have to be interpreted with caution.93 Only positive BAL results, with
pathogens that do not normally colonize the respiratory
tract (Pneumocystis carini (PCP), Legionella, and Mycobacterium tuberculosis (TB)) can be considered diagnostic,20 and negative results should not delay empirical
antimicrobial therapy if clinically indicated. While it has
been suggested that early BAL may achieve more positive
samples,20,94 no prospective study has been carried out
examining the relative bene®t of both approaches as
children are treated prophylactically against PCP and
cytomegalovirus (CMV) (i.e., BAL before vs. after
empirical treatment has been tried). Many oncologists
currently adhere to the latter practice, and BAL is only
needed in a few patients in our experience. BAL may also
aid in the diagnosis of immunocompetent children with
unexplained respiratory distress and pulmonary in®ltrates,
e.g., eosinophilic pneumonia95 or previously unsuspected
pathogens.96
The diagnostic use of BAL with modern microbiological methods (radiometric detection of TB organisms in
¯uid culture medium, BACTEC; or polymerase chain
reaction, PCR) for the detection of acid fast bacteria97
may be indicated when standard methods of isolation
(gastric lavage) fail, or a resistant strain is suspected and
cannot be isolated from other sources. The sensitivity of
detecting TB organisms in BAL specimens seems to be
lower than that in gastric aspirates.98,99 If endobronchial
disease is seen, the yield with BAL may be higher.100
It seems to be reasonable to endoscope children with
TB when endobronchial disease or airway compression
is suspected. This will aid in deciding whether to give
steroids,101,102 and BAL should be included if the
organism has not yet been identi®ed by other means.
No study has directly compared the results of BAL
with histological ®ndings in biopsy-proven chronic inter-
stitial lung disease (ILD). Some data indicate that BAL
may give useful diagnostic information in these children
in about 20% of cases,103 and BAL has been recommended in all children with this diagnosis.20 It may
be diagnostic in histiocytosis (> 5% CD1a ‡ cells104),
alveolar proteinosis (neonatal surfactant protein B de®ciency105), and hemosiderosis.106 BAL could be useful in
allergic alveolitis and for monitoring activity in sarcoidosis.107,108 However, at present BAL is not diagnostic in
most cases of ILD.109 In our experience, many parents
will more easily agree with a stepwise diagnostic plan
including BAL before biopsy than with a ®rst-line
surgical lung biospy.
Transbronchial Biopsy (TBB)
The use of transbronchial biopsies in children has been
advocated after lung transplantation if rejection is
suspected and cannot be differentiated by other means
from complications such as infection. A sensitivity for
acute vs. chronic rejection of 88% vs. 60% with a
speci®city of 91% vs. 100% has been reported.110±112
Methods have been described to easily in¯ate biopsy
samples by applying negative pressure in a syringe during
®xation in order to achieve optimal specimens.113 As
repeated open lung biopsies after lung transplantation are
impractical, TBB is the established standard procedure in
this clinical situation, although no direct comparison with
open lung biopsy (OLB) has been or probably ever will
be performed.
The use of TTB in chronic ILD has been described, but
a prospective comparison with OLB would be eventually
needed to clarify its role. While one study reported similar
proportions of diagnostic samples for TBB and OLB, the
patients were not selected randomly to undergo either
procedure; rather, TBB was performed when it appeared
likely to give useful information.103 The main problem
with TBB in ILD is the relatively small size of the tissue
sample, which is due to the small biopsy forceps ®tting
through the thin working channels of pediatric bronchoscopes. Ingenious methods have been described to
circumvent this problem in younger children. A suction
catheter can be endoscopically placed114 and the larger
biopsy forceps advanced through its lumen. However, the
reported results were mostly (probably correctly) negative, and it is unclear for what diagnostic purposes TBB
may be useful, given the fact that even open lung biopsy
in small children with ILD often remains inconclusive or
nonspeci®c (10/13 cases103).
Bronchography
The need for bronchography to detect bronchiectasis
has been greatly reduced by the use of CT. The latter is
usually suf®cient if surgical resection of a destroyed lobe
is considered.9 However, the sensitivity and speci®city of
Pediatric Bronchoscopy
CT vs. bronchography in children for the diagnosis of
bronchiectasis has not been formally studied.
The usefulness of ®berscopic tracheobronchial contrast
delivery in children has been demonstrated.115,116 In
children with cardiovascular anomalies, tracheoangiography can demonstrate the exact location and mechanism of
the airway compression. If a cardiac catheterization is
indicated for cardiologic evaluation, the combined technique may obviate the need for a CT scan or MRI.117
Other Diagnostic Uses
Severe or recurrent hemoptysis is rare in children
except in CF, and endoscopy is indicated in non-CF
children after supraglottic bleeding sources or coagulation anomalies have been ruled out.118 Sometimes foreign
bodies or vascular malformations (e.g., Osler's syndrome,
varices) are found,119 or pulmonary hemosiderosis may
be diagnosed via BAL analysis.120
Airway abnormalities (stenoses, malacia, granulation
tissue) have been described in a high proportion of
children with chronic lung disease of prematurity or
bronchopulmonary dysplasia (BPD),70,121 in whom aspiration may contribute to a prolonged course.118 The
usefulness of bronchoscopy in BPD has been described;121
this report stated that management was somehow directly
affected by the results of the procedure in 41%. However,
the exact therapeutic consequences and the clinical
bene®ts were not described. Many of the children in this
report were intubated or tracheotomized and may not be
comparable to today's typical presentation of this disease.
Also, it was not reported what proportion of children with
BPD they represented and why the decision to endoscope
was exactly made. This makes it dif®cult to recommend
bronchoscopy for children with severe BPD as a routine
tool. In our experience, endoscopy will only be useful in
rare and selected cases with BPD when localized stenosis
(usually tracheal or subglottic) is a clinically suspected
problem.
Bronchoscopy has been used to gain new information
regarding the composition and cellularity of BAL ¯uid in
CF, particularly in asymptomatic infants and to detect
early infection. While this is a promising tool for future
directions in cystic ®brosis research and treatment, its
routine application for therapeutic decisions is not
established. Recent papers have described a discrepancy
in microbiological ®ndings between oropharyngeal and
lower airway cultures which may be of clinical signi®cance.17,18 However, cultures were not taken during
clinical exacerbations, and a con®rmation of the results
and their practical consequences for the management of
cystic ®brosis will be necessary.123 It has been suggested
that children may be treated according to their oropharyngeal culture, and bronchoscopic lower airway culture is
performed if no rapid response to appropriate therapy is
157
124
observed. A recent small study reported BAL in 9/16
children with CF clinically useful (e.g., to exclude
Pseudomonas infection). However, therapeutic interventions for mucus clearance have rarely resulted in
objective sustained improvements.121 Currently, the use
of bronchoscopy for therapeutic interventions in CF is not
supported by the evidence, but it may have a role in
diagnosis of infections.17,124
BAL has been used in pediatric asthma to validate
markers of airway in¯ammation (e.g., circulating in¯ammatory mediators or breath condensate composition), and
for guidance of therapy, at least in severe or steroidresistant cases.126 However, bronchoscopy in asthma
remains investigational at present, because it is unknown
how to interpret cell and mediator content of alveolar
¯uid in clinical practice.127
INTERVENTIONAL AIRWAY ENDOSCOPY
Foreign Bodies
At present there appears to be little reason to change
from rigid to ¯exible bronchoscopy for foreign body
extraction. Many foreign bodies are friable (e.g., nuts),
and a method that pulls them into the distal opening of the
rigid bronchoscope and en-bloc extraction of bronchoscope and foreign body128 allows a quick removal without
the use of forceps, which tend to break soft foreign bodies
into pieces. It seems reasonable to use a ¯exible bronchoscope to explore those children who have a rather low
likelihood of foreign body aspiration, and switch to rigid
bronchoscopy when one has actually been found.129 It is
important that pediatric intensive care is available to deal
with possible complications of foreign body aspiration
and the extraction procedure.
Laser Therapy of Airway Stenoses
Interventional airway endoscopy is used to treat
obstructions of the laryngeal region or trachea. No consensus exists as to the optimal treatment of subglottic
hemangioma, and tracheostomy is still the treatment
favored by some groups.130 Others have reported the
application of intralesional steroids in children with subglottic hemangiomas, which is done during laryngoscopy
and followed by intubation for some days.131,132 Careful
CO2 laser resection of a part of the hemangioma is usually
suf®cient to avoid tracheostomy or intubation in most
children, even with large subglottic hemangiomas.133,134
The use of lasers for the deroo®ng of thyroglossal or
laryngeal cysts, and cicatricical subglottic narrowing,
have been described. Large subglottic cysts can develop
after endotracheal tube injury, may complicate BPD and
can be resected easily with a laser.75 Lasers with mostly
super®cial and minimal deep tissue energy coupling
should be used. This will avoid damage to the delicate
158
Nicolai
structures of the larynx as well as the perichondrium of
the airway, and the development of secondary stenoses.135
The construction of small rigid ventilating endoscopes
with a mirror system to direct a CO2 laser beam, which
has minimal deep tissue penetration but must be applied
through a mirror system, has made it possible to treat
such lesions even in the larynx of neonates, and in the
trachea of older children.136 Also, the use of KTP lasers
through a rigid endoscope has been described.137 Comparisons of different types of lasers for subglottic hemangiomas suggest less scarring with CO2 than with Neodym
YAG lasers.134
Lasers have been employed to remove granulation
tissue (e.g., at the site of a tracheostomy before decannulation), or infectious tumors (e.g., nontuberculous mycobacterial granulomas138), and cicatricical obstructing
lesions in the trachea.139 Bronchogenic cysts have been
incised endoscopically with lasers,140 and transthoracic
surgical removal may be aided by intraoperative ¯exible
endoscopy.141
Endoscopic Drug Application
The use of laser or forceps for the removal of laryngeal
(or tracheobronchial) obstructing papillomas is a routine
application of pediatric airway endoscopy. No data are
available to suggest which method of removal is superior.
As the surgical removal cannot cure papillomatosis, intralesional application of interferon or cidofovir is currently
being investigated,142,143 as well as photodynamic
therapy.144 This requires the use of rigid endoscopy,
special needles, and the availability of pediatric intensive
care in case of secondary swelling or other complications.
Stents
The use of airway stents has become routine in adults
with malignant airway stenosis, and was recently described in a series of children after tracheoplasty.145,146
Also, children with severe tracheobronchomalacia or
obstructing malignancies have been successfully treated
with temporary stents,147 but serious questions remain
as to their long-term safety, particularly when extrinsic
compression of the airway by a vessel is to be relieved by
the stent.148 Technical improvements and better materials149 may make them an attractive alternative to other
interventions, such as aortopexy in children with intractable airway symptoms after repair of esophageal atresia,
or in selected cases after cardiac surgery.150 However,
their use remains experimental at present and should only
be used as a last resort.
Other Endoscopic Interventional Procedures
Fiberoptic intubation of the dif®cult airway can be of
great help, particularly in neonates with mandibular
hypoplasia and other facial abnormalities.151 The endoscopic closure of esophagotracheal ®stulas with glue and
laser has been tried with success, but a high initial recurrence rate is reported.152 However, many isolated ®stulas
can be effectively and safely closed without thoracotomy
in a relatively short operation from a cervical approach.
In these cases, the advantages of the endoscopic technique appear small compared to the considerable morbidity due to delayed endoscopic closure and prolonged
gavage feeding. Endoscopic balloon dilatation of airway
stenoses,153 particularly in BPD patients, has been described.154±156 However, no systematic prospective study
has delineated the clinical importance of stenotic lesions
and the utility of interventional bronchoscopy in children
with BPD. In our experience, such interventions are only
rarely necessary.
Extensive BAL in alveolar proteinosis has been
described in small children,157,158 and the use of balloon
catheters with a distal opening (e.g., pulmonary wedge
pressure catheters) will allow massive unilateral lavage
through an endotracheal tube. In our experience, endoscopic control of the exact position and tight ®t of the
balloon with a very thin endoscope enhance the safety of
this intervention.
Investigational Use
Bronchoscopy has been used to advance our understanding of pediatric lung diseases mainly by gaining
lavage ¯uid and cells. Insulin-like growth factor II and its
binding protein were increased in BAL ¯uid in children
with ILD.159 Bronchiolitis obliterans,160 chronic organ
rejection after lung transplantation,161 and the development of BPD after neonatal respiratory distress162 have
all been investigated with the use of BAL. Eosinophils
were present in a small study in asymptomatic atopic
asthma but not in recurrent wheeze with infections,163
while the eosinophil activation markers eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in BAL
correlated with lung function and airway reactivity.164,165
Tumor necrosis factor (TNF)-alpha was released spontaneously by macrophages in the BAL of wheezy infants.166
During acute asthma attacks in children, leukotriene C4
(LTC4) and B4 (but not thromboxane A2 (TXA2)) were
found to be increased.167 Abnormal levels of surfactant
proteins and decreased glutathione have been found in CF
with infection,168,169 and may contribute to lung disease.
Recently, persistent airway obstruction after an acute
viral illness was linked to chronic adenoviral infection.170
Adenovirus was isolated from some young children with
chronic wheeze,31 although its pathogenetic relevance
remains unclear. In a recent paper, bronchoscopy was
used to assess the delivery of inhaled DNAse into the
airways of children with CF;171 this elegant method
may be applicable to other inhaled substances. All these
Pediatric Bronchoscopy
observations may well have clinical applications in the
future, and more discoveries can be expected.
EDUCATIONAL ISSUES
Technical training for diagnostic endoscopy is currently provided using self-made phantoms, animal
models, and supervised clinical endoscopies. Further improvement would be possible with the use of recently
developed virtual simulation trainers for adult bronchoscopy, which could be adapted to the pediatric age group.
A real endoscope is used to intubate a simulated respiratory system which can be observed on a video screen;
these systems include breathing movements, bleeding,
secretions, etc., and it responds to the manipulations of
the scope by the endoscopist.
A major issue remains quality assessment at each level
(indication, diagnostic yield, complications, quality of
documentation, and overall cost-effectiveness). Surprisingly few data are available to answer these questions.
Achievable quality of care in different clinical settings
(e.g., smaller outpatient clinics compared to larger teaching hospitals) has not been determined. One of the
training and quality control issues which has only rarely
been assessed is intra- and interobserver variability. A
recent study analyzed intraobserver variability and found
that only a >30% change in airway obstruction was
detectable with suf®cient accuracy.172
FUTURE DIRECTIONS
Prospective multicenter studies on the ef®cacy and
safety of bronchoscopy for some of the more frequently
encountered clinical situations will allow improved
clinical decision-making, based on a higher level of
evidence. While many of the published studies report the
diagnostic yield on all patients endoscoped, lavaged, or
biopsied, the eligible patient population and the selection
criteria are not uniformly reported. This makes it impossible to generalize the ®ndings and a high diagnostic yield
will not automatically translate into a reasonable bene®t
for patients. The most suitable outcome variables will
therefore have to be carefully selected in future studies.
Also, studies should be extended to settings other than
large pediatric respiratory centers in order to re¯ect
clinical reality. This will allow us to better adhere to
the advice given by Schellhase and Fan in 1995173:
``Bronchoscopy should only be performed if the information to be gained or the expected therapeutic bene®t
outweigh the potential risk to the child, however small.''
Better techniques for transbronchial biopsies and their
interpretation in small children may justify the use of
TBB instead of open lung biopsies for an extended range
of situations other than the patient after lung transplantation (e.g., chronic ILD). Pediatric airway endoscopy
allows for local delivery of drugs. The segmental
159
instillation of surfactant has been used in adult ARDS
and may be tried in children with BPD and long-standing
segmental atelectasis. In children with severe airway
papillomatosis, the in®ltration of antiviral drugs could
become a useful method. New indications for interventional techniques like stent placement or removal may
ensue with the development of better stent materials.
However, further study is required to establish their use in
situations other than after surgical airway reconstruction.
Technological advances in the future may change
pediatric bronchoscopy. Ever smaller endoscopes with
working channels are being developed.174 The use of
charged couple device (CCD) cameras at the tip of the
endoscope rather than ®beroptic transmission of the picture has been used in gastroenterological endoscopies; a
prototype is currently being tested. Intrabronchial ultrasound to delineate peribronchial tissue has become available for adults, and with further miniaturization may be
applicable to extrinsic airway compression in children as
well.
Video libraries with speci®c diagnoses or training
sequences would be of great help. Such databases could
be made available through Internet sites of recognized
pediatric respiratory societies and could contribute to
improve the overall quality of pediatric bronchoscopy.
The use of electronic media for obtaining second opinions
or expert advice on video-documented endoscopies will
save time, and avoid repeat examinations or travel to a
distant center. Also, information for parents and patients
may be made available in this way.
CONCLUSIONS
Pediatric bronchoscopy has come of age and is being
used for diagnostic and therapeutic purposes in an
increasing number of clinical situations. In the future,
it will be necessary to analyze its effectiveness and
patient bene®t in prospective studies, while concurrently
improving its technical possibilities. It has become an
increasingly important research instrument probing
pathophysiologic concepts, monitoring, and possibly
applying therapies locally. The use of electronic media
as a training facility, and to present scienti®cally sound
information regarding diseases diagnosed or treated by
bronchoscopy, will require additional effort, as well as
scienti®cally and clinically sound guidance. However, it
promises better treatment and information for patients
and parents, and may provide additional services for the
appropriately trained pediatric pulmonologist.
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