ERS International Congress Amsterdam

26–30 September 2015

Live pulmonary endoscopy

Emphysema and severe asthma

Thank you for viewing this document.

We would like to remind you that this material is the

property of the author. It is provided to you by the ERS

for your personal use only, as submitted by the author.

©2015 by the author

Tuesday, 29 September 2015

13:00 – 14:30

Room Auditorium RAI

You can access an electronic copy of these educational materials here:

http://www.ers-education.org/2015LEemphysema

To access the educational materials on your tablet or smartphone please find below a list of apps to

access, annotate, store and share pdf documents.

Apple iOS

Adobe Reader - FREE - http://bit.ly/1sTSxn3

With the Adobe Reader app you can highlight, strikethrough, underline, draw (freehand), comment

(sticky notes) and add text to pdf documents using the typewriter tool. It can also be used to fill out

forms and electronically sign documents.

Mendeley - FREE - http://apple.co/1D8sVZo

Mendeley is a free reference manager and PDF reader with which you can make your own searchable

library, read and annotate your PDFs, collaborate with others in private groups, and sync your library

across all your devices.

Notability - €3.99 - http://apple.co/1D8tnqE

Notability uses CloudServices to import and automatically backup your PDF files and allows you to

annotate and organise them (incl. special features such as adding a video file). On iPad, you can

bookmark pages of a note, filter a PDF by annotated pages, or search your note for a keyword.

Android

Adobe Reader - FREE - http://bit.ly/1deKmcL

The Android version of Adobe Reader lets you view, annotate, comment, fill out, electronically sign

and share documents. It has all of the same features as the iOS app like freehand drawing,

highlighting, underlining, etc.

iAnnotate PDF - FREE - http://bit.ly/1OMQR63

You can open multiple PDFs using tabs, highlight the text and make comments via handwriting or

typewriter tools. iAnnotate PDF also supports Box OneCloud, which allows you to import and export

files directly from/to Box.

ezPDF Reader - €3.60 - http://bit.ly/1kdxZfT

With the ezPDF Reader you can add text in text boxes and sticky notes; highlight, underline, or

strikethrough texts or add freehand drawings. Add memo and append images, change colour /

thickness, resize and move them around as you like.

Live pulmonary endoscopy

Emphysema and severe asthma

AIMS: Endoscopic lung volume reduction (ELVR) for severe emphysema and bronchial thermoplasty

for severe asthma are new treatment possibilities for patients with obstructive lung diseases. The

techniques that will be demonstrated are endobronchial valve Chartis measurements, endobronchial

coils, and bronchial thermoplasty.

TARGET AUDIENCE: General pulmonologists and residents.

CHAIRS: P. L. Shah (London, United Kingdom), A. Valipour (Vienna, Austria)

SESSION PROGRAMME

13:00 Opening lecture: endoscopic therapies for emphysema and asthma

A. Valipour (Vienna, Austria)

Patient advocate (AMC)

T. Lapperre (Singapore, Singapore)

Patient advocate (UMCG)

N. ten Hacken (Groningen, Netherlands)

Endobronchial coils

D. Slebos (Groningen, Netherlands) F. Sciurba (Pittsburgh, United States of America)

Bronchial thermoplasty

G. Cox (Hamilton, Canada) P. Bonta (Amsterdam, Netherlands)

Endobronchial valves and Chartis measurement

D. Slebos (Groningen, Netherlands) F. Sciurba (Pittsburgh, United States of America)

14:00 Emphysema and severe asthma: question and answer session

A. Valipour (Vienna, Austria) P. Shah (London, United Kingdom)

14:15 Concluding lecture: Which patient should I refer for ELVR/BT?

P. Shah (London, United Kingdom)

BOOKLET CONTENTS PAGE

Endoscopic therapies for asthma and emphysema 4

Which patient should i refer for ELVR/BT 16

Additional resources 42

Faculty disclosures 43

Faculty contact information 44

Endoscopic therapies for emphysema and asthma

Prof. Dr. Arschang Valipour

Department of Respiratory and Critical Care Medicine

Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology

Otto Wagner Hospital

Sanatoriumstr. 2

1140 Vienna

AUSTRIA

arschang.valipour@wienkav.at

4

Endoscopic therapies for asthma and emphysema

Arschang Valipour

Arschang Valipour, MD, FCCP, Assoc. Professor

Ludwig-Boltzmann-Institute for COPD and

Respiratory Epidemiology

Otto-Wagner-Spital

Vienna, Austria

5

Conflict of interest disclosureI have the following, real or perceived direct or indirect conflicts of interest that

relate to this presentation:

Affiliation / financial interest Nature of conflict / commercial company name

Tobacco-industry and tobacco corporate affiliate relatedconflict of interest

N.A.

Grants/research support (to myself, my institution or department):

Boehringer Ingelheim

Honoraria or consultation fees: Pulmonx, PneumRx, Olympus, Boehringer Ingelheim, GSK, Novartis, Astra Zeneca, Chiesi

Participation in a company sponsored bureau: N.A.

Stock shareholder: N.A.

Spouse/partner: N.A.

Other support or other potential conflict of interest: N.A.

This event is accredited for CME credits by EBAP and speakers are required to disclose their potential conflict of interest going back 3 years prior to this presentation. The intent of this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgment. It remains for audience members to determine whether the speaker’s interests or relationships may influence the presentation.Drug or device advertisement is strictly forbidden.

6

RATIONALE FOR ENDOSCOPIC

TREATMENT OF EMPHYSEMA

• Lung volume reduction surgery in selected

patients is associated with improvements in

lung function, exercise capacity, QoL, and

survival, but….

7

Naunheim KS et al., J Thorac Cardiovasc Surg 2006

• Tracheostomy

• Weaning Failure

• Reintubation

• Pneumonia

• Myocardial Infarct

• Pulmonary Embolism

• Arrythmias

• Ventilation > 3 days

MORBIDITY AND MORTALITY

ASSOCIATED WITH LVRS

8

Naunheim KS et al., J Thorac Cardiovasc Surg 2006

There is a need for

minimal invasive alternatives

to surgical LVR!

MORBIDITY AND MORTALITY

ASSOCIATED WITH LVRS

9

RATIONALE FOR ENDOSCOPIC

TREATMENT OF SEVERE ASTHMA

1FitzGerald JM, et al. Can Respir J. 2006;13:253-259.

CACG, Canadian Asthma Consensus Guidelines; GP, General Practitioner 10

RATIONALE FOR ENDOSCOPIC

TREATMENT OF SEVERE ASTHMA

Dockrell M, et al. Allergy. 2007;62(2):134-141.

• In a phone survey of 1300 patients from the UK, France, Germany, Spain and Sweden, many patients with severe asthma reported that their normal daily activities were restricted as a result of their condition

11

ENDOSCOPIC TREATMENTOF OBSTRUCTIVE AIRWAYS DISEASE

• Endoscopic Valve Therapy

• RECOIL Procedure

• Bronchial Thermoplasty

• Polymeric Lung Volume Reduction

• Bronchoscopic Thermal Vapor Ablation

• Airway Bypass

• Targeted Lung Denervation Therapy

• Pneumostoma

• BioLVR, Endobronchial Cryotherapy,...12

13

PATIENT SELECTION IS CRUCIAL FOROPTIMAL RISK-BENEFIT

14

AIMS OF THE SESSION

• To understand patient selection, the procedure related set-up,

and the technique of interventional procedures to treat severe

asthma and emphysema.

• To see how procedures are being performed in real-life.

• To have the opportunity to interact with top international

experts in the field of interventional pulmonology.

15

Endoscopic therapies for emphysema and asthma

Dr Pallav L Shah

Royal Brompton Hospital

Sydney Str.

SW3 6NP London

United Kingdom

pallav.shah@imperial.ac.uk

16

WHICH PATIENT SHOULD I REFER

FOR ELVR/BT

Pallav Shah

Royal Brompton Hospital

Chelsea & Westminster Hospital

Imperial College

17

Conflict of Interest Disclosure

❑I have the following, real or perceived direct or indirect conflicts of interest that

relate to this presentation:

Affiliation / financial interest Nature of conflict / commercial company name

Tobacco-industry and tobacco corporate affiliate

related conflict of interestNONE

Grants/research support (to myself, my institution

or department):

PneumRx, Holariio, Uptake and Pulmonx reimbursed the Royal

Brompton Hospital and Chelsea & Westminster Hospital for clinical

trial expenses (RENEW trial, RESET coil randomised trial)

Honoraria or consultation fees: Olympus, Medtronic, BTG, PneumRx, Pulmonx, CSA Medical

Participation in a company sponsored bureau: PneumRx, Boston Scientific, Pulmonx

Stock shareholder: NONE

Spouse/partner: NONE

Other support or other potential conflict of

interest:

Boston Scientific, Erbe, Olympus/Keymed, Cook Medical, PneumRx,

Medtronic, Immotech, Pulmonx sponsorship to Imperial College for an

annual interventional bronchoscopy course

This event is accredited for CME credits by EBAP and speakers are required to disclose their potential conflict of interest going back 3 years prior to this presentation. The intent of this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgment. It remains for audience members to determine whether the speaker’s interests or relationships may influence the presentation.Drug or device advertisement is strictly forbidden.

18

•PneumRx reimbursed the Royal Brompton Hospital and Chelsea &

Westminster Hospital for clinical trial expenses (RENEW trial,

RESET coil randomised trial)

•Holario reimbursed the Royal Brompton Hospital and Chelsea &

Westminster Hospital for clinical trial expenses (Airflow trial)

•Uptake medical reimbursed the Royal Brompton Hospital for clinical

trial expenses (Step Up trial)

•Pulmonx reimbursed the Royal Brompton Hospital for clinical trial

expenses (Liberate trial)

•Boston Scientific, Erbe, Olympus/Keymed, Cook Medical, PneumRx,

Medtronic, Immotech, Pulmonx sponsorship to Imperial College for

an annual interventional bronchoscopy course

•Consultancy Activity for Olympus/Keymed, PneumRx, Medtronic,

Broncus, CSA Medical & Pulmonx sponsorship

Conflict of Interest Disclosure

19

Introduction

AIMS

• Understand which patients should be considered for endoscopic

lung volume reduction

• Key investigations that assist in selection of optimal patients for

endoscopic lung volume reduction

• Understand which patients should be considered for bronchial

thermoplasty

• Understand key contra-indications for bronchial thermoplasty

20

Established diagnosis of emphysema and on Optimal Medical

Treatment

• Stopped smoking

• Long acting anticholinergics (LAMA)

• Combination inhaled steroids and long acting beta agonists

(LABA)

• Completed pulmonary rehabilitation & on maintenance regime

(PR)

Patient Selection for Lung Volume

Reduction Therapies

Clinical Characteristics

21

• Evidence of moderate to severe airflow obstruction FEV1< 50%

predicted ie GOLD stage 3/4 (D)

• FEV1:FVC ratio < 0.6

• Hyperinflation: residual volume >175% predicted or RV/TLC ratio

of >0.58

• Transfer factor >20% predicted (>15% for selected therapies)

• Exercise limitation (6MWT 150 to 400m)

Patient Selection for Lung Volume

Reduction Therapies

Physiological Characteristics

22

• Hypoxia PaO2 < 6.0 kPA (45mmHg)

• Hypoxia PaCO2 > 8.0 kPA (60mmHg)

• Transfer factor <20% predicted (<15% for selected therapies)

• FEV1< <20% predicted (<15% for selected therapies)

• No Exercise limitation (6MWT >400m)

Patient Selection for Lung Volume

Reduction Therapies

Physiological Characteristics which exclude LVR Therapies

23

Exclude significant co-morbidity

• bronchiectasis

• new pulmonary nodules/suspected lung cancer

• irreversible unstable conditions eg cerebro-vascular disease

• pulmonary hypertension (echocardiography measurements of

PAP >50mmHg

Patient Selection for Lung Volume

Reduction Therapies

Co-morbidity

24

• Fissure Integrity

• Heterogenity

• Severity

• presence of significant

co-morbidity ie

bronchiectasis

Patient Selection for Lung Volume

Reduction Therapies

Radiological Characteristics

25

Patient Selection for Lung Volume

Reduction Therapies

Radio-nuclide scintigraphy

26

Lobe Right§Lung

LeftLung

Upper 3 2

Middle 2 n/a

Lower 2 2

Defining Homogenous /Heterogenous

Disease

Protocol grades: % emphysema

(low attenuation % voxels ≤-910)

0:no destruction;

1: 1-25%

2: 26-50%;

3:51-75%

4:76-100%

CT scores

27

CT Post Processing

Case

PH

Distance

Transformation

Features

28

CT Post Processing

29

Centrilobular Pattern

Phenotypes of Emphysema

30

Panacinar Pattern

Phenotypes of Emphysema

31

Paraseptal Pattern

Phenotypes of Emphysema

32

Poor Patient Selection:expensive mistake & poor

outcomes

33

Strategy

• Unilateral occlusion

Selection

• intact fissure or absent collateral ventilation

• heterogenity (greater than 15% difference in degree

of destruction between upper & lower lobes

Survival

• atelectasis of target lobe indicative of response &

long term survival

Summary: Endobronchial Valves

34

• Strategy

• insertion of 8-12 coils per lung

• staged procedure unilateral then treat contra-lateral

side when required

• Selection

• broad patient selection

• homogenous to heterogenous disease

• avoid very bullous disease

• Survival

• long term effect on coil tension is unclear (longest

follow up about 72 months

Summary: RePneu Coils

35

LVR Algorithm

Clinical TrialsCoils

Sealants

Steam

Emphysema optimal medical RX

FEV1<50% and RV>175% , RV/TLC>0.58, 6MWT 150-400m

Severe Co-morbidity

- bronchiectasis

-suspected cancer

-PHT

-PaO2<7.0kPa

-PaCO2>7.0 kPa

Homogenous

LVRS

Severe hyperinflation

TLCO>20%

FEV1>20%

Clinical TrialsLVRS

Coils

Valves

Sealants

Emphysema

optimal pharmacological & non pharmacological treatments

-smoking cessation

-optimal diet

-pulmonary rehabilitation

-consider oxygen therapy

-vaccination

-consider all patients for lung transplant

consider

Lung Transplant

CT Features

Heterogenous

No Collateral Ventilation Collateral Ventilation

Valves LVRS

ANY

MDT & PATIENT CONSENSUS

36

Mild Moderate Severe

BT Studies in Asthma

Feasibilityn = 16

AIRn = 109

AIR2n = 297

RISAn = 32

37

Feasibility(n = 16)

AIR(RCT; n = 108)

RISA(RCT; n = 32)

AJRCCM, v176, Sep 2007 AJRCCM, v173, May 2006 NEJM, v356, Mar 2007

All of the above were shown to be significant (p < 0.05), except where noted.

AIR 2(RCT; n = 297)

AJRCCM v181 Jan 2010

■ Well Tolerated

■ Lung Function

■ Symptom Free Days

■ Persistent Effect

■ AQLQ

■ Exacerbations

■ Rescue Medications

■ Symptom Free Days

■ AQLQ

■ ACQ

■ Rescue Medications

■ Oral Steroids

(p=0.12)

■ AQLQ

■ Severe Exacerbations

■ ER visits

■ Days lost work/school

BT Studies in Asthma

38

Indications for Bronchial Thermoplasty

• FDA license: Alair Bronchial thermoplasty device is approved for the

treatment of adult patients (18 years of age) with severe persistent asthma that

is not controlled on combination of high dose inhaled corticosteroids (ICS)

and long acting bronchodilators (LABA)

• The European Respiratory Society/American Thoracic Society (ERS/ATS) task

force in 2014 strongly recommended consideration of bronchial thermoplasty

in adults with severe asthma in a context of institutional review board (IRB)-

approved systematic registry or as part of a clinical study

• The American College of Chest Physicians (ACCP/CHEST 2014) that “all public

and private insurers provide coverage and payment for bronchial

thermoplasty ..... for those adult patients with severe persistent,

poorly‐controlled asthma who continue to experience asthma exacerbations,

emergency department visits and hospitalizations despite maximal medical

treatment”

39

Patient Selection

• Adults with severe persistent asthma

• Symptomatic despite treatment with combination of high dose

inhaled corticosteroids (ICS) and long acting bronchodilators

(LABA)

• Patients requiring maintenance oral steroids

• Patients on STEP 4/5 of GINA guidelines

40

Main Contraindications

• Significant Respiratory co-morbidity: Bronchiectasis, ABPA, Vocal

cord dysfunction, Churg-Strauss syndrome, drug reactions,

congestive heart failure, bronchiolitis obliterans, chronic sinus

problems, severe GERD, excessive dynamic airway collapse, and

tracheobronchomalacia

• Pacemaker, Implanted Defibrillator, other implanted electronic device

• sensitivity to drugs required to perform the bronchoscopy e.g.

midazolam, lidocaine,

• Known problems with coagulopathy

• Active respiratory infection within 14 days of the procedure

• Unstable asthma within 14 days of the procedure

• contra-indications to bronchoscopy

41

Additional course resources

Readings, guidelines and E-learning resources

1. Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, Chung KF, Laviolette

M; RISA Trial Study Group., Safety and efficacy of bronchial thermoplasty in symptomatic,

severe asthma, Am J Respir Crit Care Med. 2007 Dec 15;176(12):1185-91. Epub 2007 Sep 27

2. Kaukel P, Herth FJ, Schuhmann M., Bronchial thermoplasty: interventional therapy in asthma,

Ther Adv Respir Dis. 2014 Feb; 8(1):22-9. doi: 10.1177/1753465813509302. Epub 2013 Dec 10

3. Pavord ID1, Thomson NC, Niven RM, Corris PA, Chung KF, Cox G, Armstrong B, Shargill

NS, Laviolette M; Research in Severe Asthma Trial Study Group. et al., Safety of bronchial

thermoplasty in patients with severe refractory asthma, Ann Allergy Asthma Immunol. 2013 Nov;

111(5):402-7. doi: 10.1016/j.anai.2013.05.002. Epub 2013 Jun 13

4. Wechsler ME, Laviolette M, Rubin AS, Fiterman J, Lapa e Silva JR, Shah PL, Fiss E, Olivenstein

R, Thomson NC, Niven RM, Pavord ID, Simoff M, Hales JB,McEvoy C, Slebos DJ, Holmes

M, Phillips MJ, Erzurum SC, Hanania NA, Sumino K, Kraft M, Cox G, Sterman DH, Hogarth

K, Kline JN, Mansur AH, Louie BE,Leeds WM, Barbers RG, Austin JH, Shargill NS, Quiring

J, Armstrong B, Castro M; Asthma Intervention Research 2 Trial Study Group. et al., Bronchial

thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma, J

Allergy Clin Immunol. 2013 Dec; 132(6):1295-302. doi: 10.1016/j.jaci.2013.08.009. Epub 2013

Aug 30

5. Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, Fiss

E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, Duhamel DR, McEvoy

C, Barbers R, Ten Hacken NH, Wechsler ME, Holmes M, Phillips MJ, Erzurum S, Lunn

W, Israel E, Jarjour N, Kraft M, Shargill NS, Quiring J, Berry SM, Cox G; AIR2 Trial Study

Group., Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a

multicenter, randomized, double-blind, sham-controlled clinical trial, Am J Respir Crit Care

Med. 2010 Jan 15;181(2):116-24. doi: 10.1164/rccm.200903-0354OC. Epub 2009 Oct 8

42

Faculty disclosures

Dr Peter I. Bonta work benefited from the research grants provided by Boston Scientific and St Jude.

Dr Gerard P. Cox is an investigator in clinical trials of Bronchial Thermoplasty with funding from

Asthmatx Inc. (now part of Boston Scientific). He has also received speaker's fees from Boston

Scientific for talks on management of severe asthma including the role of Bronchial Thermoplasty.

Dr Frank Sciurba has received research support from PneumRx and Pulmonx.

Dr Pallav L. Shah has received personal fees from Broncus, Olympus, PneumRX and Pulmonx as

consultant on scientific advisory board. His work benefited from sponsorship for a bronchoscopy

course from ERBE, Cook medical, Superdimension, Boston Scientific, Aquilant, Broncus, Pulmonx,

Olympus and PneumRX. His institutions has received also a research funding from PneumRX

Dr Dirk-Jan Slebos performed several clinical trials using the coil technology, is advisor to PneumRx

Inc, as well as received travel grants and speakers fees for scientific presentations and educational

activities for PneumRx Inc.

Prof. Dr Arschang Valipour has received grants or research support from Boehringer Ingelheim, as

well as Honoraria or consultation fees from Pulmonx, PneumRx, Olympus, Boehringer Ingelheim,

GSK, Novartis, Astra Zeneca, Chiesi

43

Faculty contact information

Dr Peter I. Bonta

Academic Medical Center Amsterdam

Meibergdreef 9

1105 AZ Amsterdam Zuid-Oost,

NETHERLANDS

p.i.bonta@amc.uva.nl

Dr Gerard P. Cox

FIRH T2123

St.Josephs' Healthcare

McMaster University

50 Charlton Ave East

L8N 4A6 ON Hamilton

CANADA

coxp@mcmaster.ca

Dr Therese Lapperre

Department of Respiratory and Critical care

Medicine

Singapore General Hospital

Outram Rd

Singapore 169608

SINGAPORE

lapperre@me.com

Dr Frank Sciurba

UPMC Montefiore Hospital - NW628

3459 Fifth Avenue

Pittsburgh, PA 15213

UNITED STATES OF AMERICA

sciurbafc@upmc.edu

Dr Pallav L Shah

Royal Brompton Hospital

Sydney Str.

SW3 6NP London

United Kingdom

pallav.shah@imperial.ac.uk

Dr Dirk-Jan Slebos

Dept of Pulmonary Diseases

University Medical Center of Groningen

P.O. Box 30001

9700 RB Groningen

NETHERLANDS

d.j.slebos@int.umcg.nl

Prof. Dr Arschang Valipour

Department of Respiratory and Critical Care

Medicine

Ludwig-Boltzmann-Institute for COPD and

Respiratory Epidemiology

Otto Wagner Hospital

Sanatoriumstr. 2

1140 Vienna

AUSTRIA

arschang.valipour@wienkav.at

Dr Nicolaas H.T. ten Hacken

Pulmonary Department

University Medical Center Groningen

P.O. Box 30001

9700 RB Groningen

NETHERLAND

n.h.t.ten.hacken@umcg.nl

44