04.05.

2016

Endoscopic Lung Volume Reduction

- an overview -

R Eberhardt

Thoraxklinik am Universittsklinikum Heidelberg

Pneumologie und Beatmungsmedizin

Translational Lung Research Center Heidelberg

Deutsches Zentrum fr Lungenforschung

Chronic Obstructive Pulmonary Disease (COPD)

Global Initiative for Chronic Lung Disease 2014

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Different Types of Emphysema

panlobular

centroazinar

paraseptal bullous

Dynamic Hyperinflation

ODonnell DE et al. Chest 2000

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Mechanism of Lung Volume Reduction

DG&RE

Target Lobe Improved Improved

Volume Respiratory Exercise
Reduction Mechanics & QoL

National Emphysema Treatment Trial (LVRS)

advantage for patients with both predominantly

upper-lobe emphysema !

Patients [] with non-upper-lobe emphysema [] are

poor candidates for lung-volume reduction surgery, !

Fishman A et al. NETT Research Group, N Eng J Med 2003

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Survival NETT

all patients UL-predominance

high risk group
FEV1 < 20% plus
& low exercise capacity
homogeneous Emphysema or TLCO < 20%

Fishman A et al. NETT Research Group, N Eng J Med 2003

Endoscopic Valve Placement

EBV TS4.0 Pulmonx

IBV V7 Olympus

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Who is the ideal candidate for ELVR ?

122 meter

Who is the ideal candidate for ELVR ?

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VENT

Sciurba FC et al. New Engl J Med 2010

Sciurba FC et al. New Engl J Med 2010

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IBV European Multicenter Trial

Ninane V et al. Eur Respir J 2012

IBV European Multicenter Trial

Ninane V et al. Eur Respir J 2012

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IBV Pilot Trial

ATX = Atelektase

Springmeyer SC et al. Thorac Surg Cin 2009

Valve Placement RUL

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Complete unilateral vs. partial bilateral IBV

Eberhardt R et al. Chest 2012

Complete unilateral vs. partial bilateral IBV

Eberhardt R et al. Chest 2012

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Lobar Volume Reduction (LoVR)

Valipour A et al. Eur Respir J 2014

courtesy of VIDA Diagnotics Inc.

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ELVR & Survival

N=5

N=14

Hopkinson NS et al. Eur Respir J 2011 Venuta F et al. Chest 2012

Pneumothorax

1568602/11

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TLVR after post-interventional Pneumothorax

Gompelmann D et al. Respiration 2014

Pneumothorax

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Treatment Algorithm postinterventional Pneumothorax

Valipour A et al. Respiration 2014

Assessment of Collateral Ventilation

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Chartis Assessment

Chartis System (Pulmonx Inc./USA)

Chartis Trial

Herth F et al. Eur Respir Journal 2012

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Chartis Trial

Herth F et al. Eur Respir Journal 2012

European VENT

Herth FJF et al. Eur Respir J 2012

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Interobserver Variabilitt

Koenigkam-Santos et al. Eur J Radiol 2012

Chartis-Assessment vs. Visual Fissure Analysis

Gompelmann D et al. Respirology 2014

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Lung Quantitative Imaging (VIDA)

courtesy of VIDA Diagnostics Inc.

Software Analysis (VIDA)

courtesy of VIDA Diagnostics Inc.

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Main QCT Baseline Measurements

FI

Automated assessment of Fissure Integrity (FI)

LAC
Healthy

Emphysema
Slope of Low Attenuation Clusters (LAC)
CT-Surrogat fr intralobre Kollateralventilation

PPVV

Peripheral Pulmonary Vessel Volume (PPVV)

korreliert mit der Emphysemausprgung

Chartis-Assessment vs. QCT-Modell

Schuhmann M et al. Am J Respir Crit Care Med 2014

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Davey C et al. The Lancet 2015 Group, Eur Respir J 2013

BeLieVeR-HIFi (EBV)

50 Patienten
14 LUL, 10 RUL, 1 LLL
3 Patienten lost for FU

90 days FU EBV SoC

mean
Patients 23 24
FEV1 +24.8% +3.87%
[8.0-41.5%] [0.66 7.08%]

RV - 0.50 l - 0.13 l
[- 0.82 - 0.18 l] [- 0.28 0.02 l]

6-MWT +29 m -4m

[0 58 m] [-27 19 m]

SGRQ - 8.72 pt - 3.66 pt

[-17.22 - -0.21 pt] [-8.12 - -0.80 pt]

Atelektasen:
EBV: 8 von 23 Patienten (34.8%)
SoC: keine (0.0%)

Davey C et al. The Lancet 2015

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BeLieVeR-HIFi (EBV)

EBV CV neg.
CV pos.

SoC alle

Davey C et al. The Lancet 2015 Group, Eur Respir J 2013

BeLieVeR-HIFi (EBV)

Davey C et al. The Lancet 2015 Group, Eur Respir J 2013

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Klooster K al. New Engl J Med 2015

STELVIO (EBV)

Klooster K al. New Engl J Med 2015

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STELVIO (EBV)

Klooster K al. New Engl J Med 2015

STELVIO (EBV)

Klooster K al. New Engl J Med 2015

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STELVIO (EBV)

Klooster K al. New Engl J Med 2015

STELVIO (EBV)

Klooster K al. New Engl J Med 2015

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STELVIO (EBV)

Improvements after EBV:

in comparison to control group

FEV1 mean +22.7 % [12.2 33.3 %]

RV mean - 0.81 l [- 1.10 0.56 l]
6MWD mean +106 m [+80 133 m]
SGRQ mean - 14.7 pt [-21.8 -7.6 pt]

Complicationa:
Pneumothorax rate 17.6 %
Mortality 2.9 %
1 patient died / not procedure related

Klooster K et al. Abstract ATS Congress 2015

Klooster K et al. Abstract ATS Congress 2015

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ELVR Non-Blocking Devices

BTVA Uptake medical Coils PneumRx PLVR AerisTherapeutics

PneumRx Coils

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X-ray after LVRC

RESET

Shah P et al. Lancet Respiratory 2013

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PneumRx Coils in homogeneous Emphysema

Rtot RV 6MWD SGRQ

Klooster K et al. Respiration 2014

Slebos DJ et al. Respiration 2015

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LVRC: metaanalysis

Slebos DJ et al. Respiration 2015

LVRC: metaanalysis

Slebos DJ et al. Respiration 2015

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Slebos DJ et al. Respiration 2015

LVRC: metaanalysis

Slebos DJ et al. Respiration 2015 ; erratum

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LVRC: metaanalysis

Slebos DJ et al. Respiration 2015

Hartman JE et al. Respirology 2015; 20: 319-326

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LVRC: longterm results

Hartman JE et al. Respirology 2015; 20: 319-326

LVRC: longterm results

Hartman JE et al. Respirology 2015; 20: 319-326

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LVRC: longterm results

Hartman JE et al. Respirology 2015; 20: 319-326

LVRC: longterm results

Hartman JE et al. Respirology 2015

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PneumRx Coils & incomplete Fissures

Kontogianni K et al. Respiration 2014

Complications after LVRC

Slebos DJHartmann JE et
et al. Chest al. Respirology 2014
2012

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Fatal Pneumonia after LVRC left UL

2014

Bronchial Thermal Vapor Ablation (BTVA)

InterVapor-System

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Bronchial Thermal Vapor Ablation (BTVA)

Bronchial Thermal Vapor Ablation (BTVA)

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Vapor Segmental Ablation

Lobar volume reduction too much injury

per procedure for some Right Lung Left Lung

Reduce volume treated per procedure

by breaking into 2 procedures

Facilitates reduction the more

diseased segments

Preserved segments available for treatment

over time as disease progresses
Less More
Disea Disea
sed sed

CONFIDENTIAL Uptake Medical Corp

STEP-UP RCT Primary Endpoint FEV1

20% FEV1 (ml) Improvement

14.7% 12.8%
p= p=
15% 10.1% <.0001 .0039
Treated from Control
CMI p = .0047
10% Treated Arm

5%

0%
Control Arm
-5%
3 Mo 6 Mo 12 Mo
N = 43 IV N = 41 IV N = 44 IV
N = 22 C N = 23 C N = 23 C

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STEP-UP RCT Primary Endpoint SGRQ

-14 SGRQ-C Improvement

Treated from Control
Treated Arm
-10 -6.6 -12.1
p= -9.7 p=
.0243 p= .0021
-6 .0021
CMI

-2

Control Arm

2
3 Mo 6 Mo 12 Mo
N = 44 IV N = 42 IV N = 44 IV
N = 22 C N = 23 C N = 23 C

CONFIDENTIAL Uptake Medical Corp

STEP-UP RCT Secondary Endpoints

3 months 6 months 12 months

control vs control vs control vs
Variable treated treated treated
6MWT (m) 29.4 30.51^ 3.6
FVC %
6.1* 7.4* 6.9*
Predicted
FVC (ml) 163.7 243.1* 238.5*
RV %
-2.7 -14.6* -10.2
Predicted
RV (ml) -44.1 -302.5* -237.4
CAT Total
-4.4* -2.82 -3.6*
Score 1p ^ Clinically Meaningful
* p<0.05 = 0.0614
Improvement

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STEP-UP RCT Safety

Treatment Arm (45 patients) Control Arm (24 patients)

181-360 days
0-180 days after 181-360 days 0-180 days after
after
treatment* after treatment** randomization
randomization
N (%) N (%) N (%)
N (%)
Exacerbation 11 (24%) 7 (16%) 1 (4%) 2 (8%)

Pneumonia/Pneumonitis 8 (18%) 0 (0%) 2 (8%) 2 (8%)

Pneumothorax 1 (2%) 0 (0%) 0 (0%) 0 (0%)

Complications Requiring:
Surgery 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Chest tube(s) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Re-bronchoscopy 0 (0%) 0 (0%) 0 (0%) 0 (0%)
ICU-stay 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Hemoptysis 1 (2%) 0 (0%) 0 (0%) 0 (0%)
Death 1 (2%) 0 (0%) 0 (0%) 0 (0%)
Any RSAE 16 (36%) 7 (16%) 3 (13%) 4 (17%)
*180 days after treatment session 1 or 90 days after treatment session 2 **181-360 days after treatment session 1 or 91-270 days after
treatment 2
Data presented as number of patients (% of patients) RSAE = Respiratory serious adverse event

Bronchial Thermal Vapor Ablation (BTVA)

Patients with at least one segment

that is as healthy as the lower lobe
are ideal candidates for vapor.
Patients with upper lobe predominant emphysema
with incomplete fissures and or CV
are good candidates for vapor.

Proper patient selection is how we continue

to improve patient outcomes.

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Eberhardt R et al. J COPD 2015

Summary

Endobronchial Lung Volume Reduction Techniques

feasible and effective
minimal-invasive and safe
different devices/techniques

Patient Selection is important

collateral ventilation measurement
subgroup therapy
homogeneous/heterogeneous emphysema

Treatment in Centers of Expertise

management of complications
review physiologic implications of the procedures
Why does it work and why not?

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ralf.eberhardt@med.uni--heidelberg.de
ralf.eberhardt@med.uni

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