Bronchial Thermoplasty and Guided Bronchoscopy Part One

Wes Shepherd, MD

Director of Interventional Pulmonology

Associate Professor of Pulmonary and Critical Care

VCU Medical Center

Objectives:

• Describe the physiologic background of asthma and tissue effects of bronchial thermoplasty

• Summarize the current treatment evidence for bronchial thermoplasty and indications/contraindications

• Identify the various modalities of guided bronchoscopy and their utility

Disclosure:

Financial relationships to disclose:•Consulting– Boston Scientific, CSA Medical•Grants - Allegro Diagnostics, Veracyte, Spiration•Royalties – UpToDate

•No off label use of any product will be discussed

Asthma:Prevalence, Morbidity and Mortality

Approximately 11 People Die From Asthma Each Day in the US

13.6 Million Unscheduled Office Visits Annually

0.5 Million HospitalizationsAnnually

Approximately 4000 Asthma-Related Deaths

22.2 Million People Are CurrentlyDiagnosed With Asthma

National Center for Health Statistics, CDC, 2005; http://www.cdc.gov/nchs/products/pubs/pubd/hestats/asthma/asthma.html

1.8 Million Emergency Room Visits Annually

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Stepwise Approach for Managing Asthma

Short-acting Beta2-agonists

Low-dose Inhaled Corticosteroids (ICS)

Low-dose ICS + Long-acting Beta2-agonists (LABA)

or Medium-dose ICS

Medium-dose ICS + LABA

High-dose ICS + LABAand Consider Omalizumab

High-dose ICS + LABA + Oral Corticosteroids

and Consider Omalizumab

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Adapted from National Asthma Education and Prevention Program (NAEPP) Guidelines. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute, NIH Publication No. 07-4051, Revised August 2007.

Challenges in Managing Severe Asthma

• Prevalence of severe asthma (NAEPP) = 5-10%

• Many patients remain symptomatic despite standard of care medications

• High economic costs and resource utilization associated with medications, hospitalizations, physician visits and lost days of work/school ~ $20.7B

• Additional therapeutic treatment options are needed

Bronchial thermoplasty:

• Asthma:– Acute and chronic airway inflammation– Thickened airway walls– Increased mucous glands and goblet cells– Increased blood vessels– Thickening of airway smooth muscle (ASM)

Bronchial thermoplasty:

• Acute asthma attack – Allergic stimuli– Nonallergic – infection, cold, exercise, irritant

• Cascade always leads to ASM contraction• Which airways cause the problem in asthma ?

– Most baseline airway resistance lies in the conducting airways > 2 mm

– Primary site of resistance uncertain in acute asthma• Diffuse narrowing of small airways ?• Narrowing of large airways ?• Generalized narrowing of all airways ?

Bronchial thermoplasty:

NEJM 2007;356:1367-69

Bronchial thermoplasty:

• Functional role of smooth muscle ?– Extends down to respiratory bronchioles– No strong experimental evidence for its purpose– Proposed functions:

• Peristalsis for mucous clearance• Promote lymphatic and venous flow• Improving cough• Airway stabilization• Others

– ASM seems to be uniquely heat sensitive

Reduce Airway Smooth Muscle (ASM)

Reduce Bronchoconstriction

Reduce Asthma Exacerbations

Improve Asthma Quality of Life

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Bronchial Thermoplasty – Reduces ASM

Indications for Bronchial Thermoplasty:

• Severe asthma• Adult asthmatics (≥ 18 years old)• Inadequate control despite combination of inhaled

corticosteroids (ICS) and a long-acting β2-agonist (LABA)• Able to undergo bronchoscopy

Alair Bronchial Thermoplasty System Instructions for Use 12

Bronchial thermoplasty:

J Bronchol 2007;14:115-123

How does BT work?

• The device consists of a small flexible tube with four expandable wires at the tip

• It is placed through a standard flexible bronchoscope through the mouth or nose

How does BT work?

• The wires are expanded against the walls of the airway and thermal energy is delivered

• This sequence of energy delivery is continued until all targeted airways have been treated.

Treatment Method

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Bronchial Thermoplasty with the Alair® System

Application of RF Energy

• Temperature controlled energy (650 C) is delivered to airway wall for 10 seconds per activation – no permanent damage to epithelium

Procedure Overview

• Patient evaluated pre-procedure to verify stability and ability to undergo bronchoscopy

• Prophylactic OCS initiated 3 days prior, day of and day after procedure

• Local anesthesia administered – lidocaine and albuterol nebulizer

• Patient placed under moderate or deep sedation

• RF energy delivered to airways ~30-60 activations per procedure and completed within 40-60 minutes

• Patient monitored 2-4 hours post-op and discharged home same day• Lung function stable within 80% of pre-procedure post BD FEV1

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Bronchial thermoplasty:

• Technique:– Flexible bronchoscopy with moderate or deep sedation– Tightly controlled RF energy via a catheter to airways 3 mm -10 mm

(no burn)– Right middle lobe excluded (RML syndrome)– Target temperature controlled to avoid perforation or airway stenosis– 3 bronchoscopies each about 3 weeks apart

Bronchial thermoplasty:

• Technique:– Gel-type electrode on patient to complete circuit– RF or high frequency compatible scopes– Minimum 2.0 mm working channel– Therapeutic scope not recommended– 3 procedures helps reduce procedure length, edema, and

bronchospasm– Inspect previous treatment sites for healing– Meticulous treatment tracking to avoid duplicate or missed

treatments (use a “map”)

Bronchial thermoplasty:

J Bronchol 2007;14:115-123

Canine Model: Airway on left treated with bronchial thermoplasty. Airway on right was not treated.Cox et al. Eur Respir Journal. 2004;24: 659-663

Airway Responsiveness to Local Methacholine Challenge

UNTREATED

Ciliated EpitheliumASM

Parenchyma Parenchyma

Ciliated Epithelium ASM Reduced

TREATEDMasson’s Trichrome stain

Reduced Airway Smooth Muscle

• 3 years post-treatment (canine model)

Bronchial Thermoplasty Clinical Studies

AIR = Asthma Intervention Research StudyAIR2 = Asthma Intervention Research 2 StudyRISA = Research in Severe Asthma Study