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Invasive Bronchoscopy in Pediatrics Bronchoscopy beyond Inspection and BAL

Procedures and Ethical Considerations

Israel 2012

Andrew Colin, MD

Batchelor Famil Professor of C stic Fibrosis and Pediatric Pulmonol

Director, Division of Pediatric Pulmonology



• Bronchoalveolar lavage (BAL) – ,

• Unprotected specimen brush –

• Protected specimen brush – Culture and atholo ic anal sis

• Endobronchial Biopsy

– Pathologic analysis (including EM)• Transbronchial biopsy

– Pathologic analysis



-

• acquisition of histologic samples by use of

• typically under direct visualization

• most commonly the sample is obtained

frequently from masses invading the wallor ones occupy ng e ronc a umen



“Rat-tooth” forceps

Cupped forceps“Rubber-tipped”

forceps



Size matters!

y ex e e e ze

– Ultrathin bronchoscope

• 2.2 mm, no working channel

– Thin pediatricbronchoscope

. , .channel

– Standard pediatricbronchoscope

• 3.6 mm, 1.2 mm working

– Small adult bronchoscope• 4.9 mm, 2.0 mm working

c anne



• A com limentar rocedure to bronchial

forceps that uses a brush in lieu of forceps

studies of bronchial epithelial cells and is

op m ze w en e rus s pro ec e y asheath

• such “protected” brushes are limited to

bronchosco es with lar er workin channels• some of the studies on EBB cited in the



•

– extruded to obtain sample



Safety and Quality of Endobronchial Biopsy

Children <5 years old

opsy orceps - - ympus ey e

3 years old

Saglani, Thorax, 2003



Endobronchial biopsy for research

• There are numerous publications on the

ediatric use of EBB to evaluate tissuealterations in response to disease conditions,

some of these studies also used controls

• these studies encompass predominantly

cystic fibrosis and other conditions

• e o ow ng s u one examp e o e ype

of information obtained via EBB



Airway Inflammation in Childhood Asthma

Asthma Control

Barbato, AJRCCM, 2003



Basement Membrane Thickening

in Children=

10

9

.

s*

Basement

8

7

6

P=0.052

Membrane(µm)

54

3

*s

2

1

Horizontal lines represent median values.

* Sub ects with asthma who were not ato ic.

Asthmatic Atopic Control


S Subjects with asthma who were treated with inhaled steroids.



Airway Inflammation in Childhood Asthma

Asthma Control




Procedures:

n o ronc a opsy

Clinical and ethical considerations:

Do we need to do rocedures because we can?



Endobronchial biopsy for clinical

indications

• We reviewed the existing literature in an attempt

which EBB is indicated, in the sense of having

• Specifically, we evaluated the indication(s) for a

opsy o t e ronc a mucosa, norma or

inflamed, that does not reveal an obvious lesionor a mass on the surface of the mucosa

• We failed to find convincin evidence that such

EBB is indicated for any clinical condition



Needle biopsy



EBB for specific clinical indications

• EBB for specific diagnoses, in contrast to exploratory

biopsies from the mucosal surface, appears to be

limited as well• The ERS Task Force on Flexible endoscopy of

paediatric airways [Midulla, ERJ, 2003] cites the procedure

as a we -es a s e c n ca ec n que or o a n ngciliated cells for the dx PCD

• urrent pract ce o centers or c ary sor ers s to

use predominantly nasal brush biopsy

[Noone AJRCCM 2004; Bush Arch Dis Child 2007]

and therefore tissue samples obtained by EBB are

unnecessary and consequently EBB is not indicated



Ethical perspectives of EBB

Opinions vary

• eorge a ory - t a s n on- erapeut c esearc n

Children Pediatr Pulmonol. 2006; 41:1014–1016

• us av es e u a : ou are rong, r. a ory . . .

Pediatr Pulmonol. 2006; 41:1017–1020

-

Pediatr Pulmonol. 2007; 42:656–657

• Colin & Ali Dinar - Endobronchial Biopsy in Childhood

es ; ; -

• Nicolas Regamey et al - Rebuttal

est ; ; -



Endobronchial biopsy for clinical

indications

• e arges s u y o a e s a ng c n ca

indications for the procedure included

170 pediatric patients•

persistent respiratory problems

Salva, Thorax, 2003



safety of the procedure



EBB for clinical indications

•

impact of the procedure to state that

“…

not possible owing to the variability in the patients’

” …

• Thus this large study failed to ever report the

management or consequent health of the patients,

patients is safety

Salva, Thorax, 2003



EBB for clinical indications

• The authors, however, in their conclusions

state:

“We ho e this re ort will encoura e otherpractitioners to consider endobronchial biopsy

in evaluatin children with res irator

conditions that are hard to diagnose”

• Otherwise stated the study is viewed as a

license and encoura ement to erform EBB,without ever defining what information the

bio sies rovided Colin & Ali-Dinar Chest 2007



Procedures:

Transbronchial biopsy

Usually obtained under fluoroscopic guidance



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AG – 21 o with HIV

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Procedures

Therapeutic – erapeu c avage

• Mucus plug or cast bronchitis

•

– Direct instillation of therapeutic agents• DNase, antibioitc, antifungal therapy

– Suspected foreign body (Rigid bronchoscopy backup)

– ss s ance w cu n u a on e ec ve n u a on

– Airway dilation

–

– Airway stent placement

–

– Treatment of Diffuse alveolar hemorrhage

Bronchoscopy for airway and




pu monary ee ngBronchoscopic interventions aimed at controlling

bleeding from the lung include:

• Pulmonary lavage with cold epinephrine-saline

solution• CO laser thera

• Nd-YAG laser therapy

• Insertion of Endoscopic Watanabe Spigot

• Instillation of thrombin or fibrinogen-thrombin glue





pu monary ee ng

• Intrapulmonary instillation of activated

recom nan ac or r a an

tranexamic acid, a synthetic anti-fibrinolytic

agent to control diffuse alveolarhemorrhage have been recently reported in

a series of adult patients

•with their systemic administration

Heslet, Crit Care, 2006





pulmonary bleeding• We have recently used rFVIIa as an intervention of

last resort in a 16 ear old atient with acutemyelogenous leukemia

•

dose of 50 mcg/Kg diluted in normal saline to 50.

• The hemorrhage was visualized during the

treatment was immediate, unequivocal, and

Colin, Pediatr Pulmonol, 2010



Intrauterine bronchoscopy

ER I t t i MR 1 14 11



ER - Intrauterine MR 1-14-11

ER I t t i MR 1 14 11




ER Intrauterine MR 1 14 11




I t t i RMSB



Intrauterine RMSB

U er Lobe Bronchus

Middle Lobe

Bronchus

Lower Lobe

Bronchus



Intrauterine RLL



Intrauterine LMSB



Intrauterine LUL



Intrauterine LLL



Debris / plugs





ER - Intrauterine MR



ER Intrauterine MR

1-14-11 1-28-11

A unifying model for congenital



y g g

lung pathologies

Pediatr Dev Pathol, 2006

Other papers supporting bronchial obstruction as the unifying

pathogenetic pathway for different pulmonary abnormalities

Langston, Semin Pediatr Surg, 2003

Kunisaki, J Pediatr Surg, 2006





lung pathologies

• Many of these anomalies share similar CT

findings and histopathology

• Sin le individuals ma exhibit more than

one type of malformation

proposed to be obstruction of the fetal

. .,

angs on, em n e a r urg,

Riedlinger, Pediatr Dev Pathol, 2006

Kunisaki, J Pediatr Surg, 2006

Experimental pathophysiology



p p p y gy

of airway obstruction

• Experiments of fetal lamb tracheal ligation in

u ero emons ra e e mpor ance o ung qu

dynamics on the development of normal lungs

• They concluded that the liquid in the lungs actedas an internal template or splint for the

developing lung

•impairment of lung development (e.g., CDH),

Experimental pathophysiology



p p p y gy

of airway obstruction

• This was shown, in both animal and humans

• No experimental data are available on airway

occlusion in the bronchial embryogenesis period

• It is not clear wh more distal occlusion the

proposed cause of the array of congenital

lesions discussed above results in mass-likestructures with different degrees of

lungs

Why did this bronchoscopy make




a difference?

• We submit that the underlying and unifying

detected in this child was diffuse bronchial or

ronc o ar o s ruc on

• While the scope was advancing small particles

were noted to be floating in the fluid milieu

• We think that the thera eutic effect of theprocedure lies in establishment of





a difference?

• The successful results of this intervention

airway and the peripheral lung

• e n a e oa ng par c es v ewe

through the procedure may have been

e r s o t e g ue t at e t e umen

closed, and was removed by the

combination of mechanical dilatation and

flow of the injected fluid

ER – DOL 1 3-30-11



o ume r c recons ruc on o e c es s ow ng

the defect in the left lung

ER - DOL 2 3-31-11



ER - DOL 2 3-31-11



ER – Age 4 months 7-26-11



ER – 5 month - 9-9-11



ER – 9 month - 1/13/12



Post contrast coronal MR

Interventional Bronchoscopy



Summary

tool for the pediatric practitioner

•technologies involved in the procedures haveimproved dramatically over the last two decades

• It offers an array of diagnostic options that areunique, and can be obtained with little invasiveness

• ew or zons may e open ng w n rau er neprocedures

, ,bronchoscopy as well as EBB are safe proceduresbut the risk of com lications increases withprogressive severity of the respiratory conditions

Interventional Bronchoscopy



ummary , .

Weigh the benefits vs. the risks

•procedures beyond BAL, such as EBBcontribute to clinical mana ement

• Invasive procedure such as EBB have

pathologic processes, therefore use forresearch is ethical

• Adequate presentation in the context of ale itimate research rotocol and a ro riateinformed consent are key

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