Bronchial Thermoplasty and Guided Bronchoscopy Part One Wes Shepherd, MD Director of Interventional...

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