Transcript Slide 1

Bronchial Thermoplasty and Guided
Bronchoscopy Part Two
Wes Shepherd, MD
Director of Interventional Pulmonology
Associate Professor of Pulmonary and Critical Care
VCU Medical Center
Bronchial thermoplasty:
• “Reduction in airway hyperresponsiveness to methacholine by the
application of RF energy in dogs”
– 3 treated lung regions (55, 65, and 75 C) in 11 dogs (> 300 sites)
– 65-75° C significantly reduced airway response (AR) to local methacholine
challenge
– AR inversely correlated to extent of smooth muscle alteration
– Benefit persisted out to 3 years (no stenosis or anatomic deformity)
J Appl Physiol 2004;97:1946-1953
Bronchial thermoplasty:
• “A prospective feasibility study of bronchial thermoplasty in the
human airway” (1st human study)
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9 patients undergoing lung resection for cancer (nonasthmatics)
BT to segmental bronchi to be removed 1-3 weeks pre-op
Activations at 55-65°C
No adverse symptoms
Post BT bronchoscopies showed no stenosis or scarring
ASM replaced by loose connective tissue
Surgical specimens examined showed reduced ASM (> in 65°C)
• Epithelium – normal, sloughing, regenerative
• Mucous ducts /glands – metaplasia
• Cartilage – mild necrosis or new growth
CHEST 2005;127:1999-2006
Bronchial thermoplasty:
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“Asthma control during the year after
bronchial thermoplasty” (AIR trial)
– RCT in 4 countries
– 112 moderate to severe persistent
asthma age 18-65
• Worsening asthma control with
LABA withdrawal X 2 weeks
– On ICS and LABA with FEV1 6085% predicted
– PC20 < 8 mg/ml on methacholine
challenge
– BT by moderate sedation or general
anesthesia
NEJM 2007;356:1327-37
Bronchial thermoplasty:
• “Asthma control during the year after bronchial
thermoplasty” (AIR trial)
– Designed to show that BT patients had improved control when LABA
withdrawn
– Benefits also present at 3 months on ICS/LABA
– Extrapolate to 10 fewer mild exacerbations/year and 86 additional symptom
free days/year
– Nonblinded – results probably beyond placebo effect
– Adverse effects more common in treatment group immediately after procedure
but similar from 6 weeks to 12 months
• 6 hospitalizations (4 subjects – asthma exacerbation)
NEJM 2007;356:1327-37
Bronchial thermoplasty:
• “Asthma control during the
year after bronchial
thermoplasty” (AIR trial)
– Primary outcome
• Frequency of mild
exacerbations (during
LABA withdrawal for 2
weeks at 3,6,12
months)
NEJM 2007;356:1327-37
Bronchial thermoplasty:
• “Asthma control during the year after bronchial
thermoplasty” (AIR trial)
– Secondary outcomes
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Airflow
Asthma symptoms
Airway responsiveness
Symptom-free days
Rescue medication use
Asthma Quality of Life Questionnaire (AQLQ)
Asthma Control Questionnaire (ACQ)
NEJM 2007;356:1327-37
Bronchial thermoplasty:
NEJM 2007;356:1327-37
Bronchial thermoplasty:
NEJM 2007;356:1327-37
Bronchial thermoplasty:
• “Safety and efficacy of bronchial thermoplasty in
symptomatic severe asthma”
– 32 patients with severe persistent asthma
– Short term worsening of asthma symptoms
– 4 of 15 in treatment group hospitalized during treatment period (2
had segmental collapse)
– At 22 weeks BT group had significant improvements vs control
group in:
• Rescue medication use
• Pre-bronchodilator FEV1 % predicted
• Asthma control questionnaire
Am J Respir Crit Care Med 2007;176:1185-91
AIR2 – Pivotal IDE Clinical Trial
• Purpose: Pivotal US Investigational Device Exemption (IDE) Study to
support indication for use in severe asthma
• Sham controlled, double blinded
• Study Population:
• Severe persistent asthma (297 patients)
• Symptomatic despite high dose ICS + LABA
• Primary Endpoint: Asthma Quality of Life Questionnaire (AQLQ) score
• Follow-up: One year
• 5-year safety follow-up for BT subjects
Bronchial Thermoplasty Clinical Outcomes at 1-Year
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Improved asthma-related quality of life compared to control (AQLQ
score)
• 79% of BT treated patients achieved ≥ 0.5 increase
• Effect persistent across 6, 9, and 12 months
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Improved clinical outcomes compared to control:
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32% decrease in severe exacerbations
84% reduction in ER visits for respiratory symptoms
73% reduction in hospitalization for respiratory symptoms
66% less days lost from work, school and other daily activities due
to asthma
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No unanticipated device-related adverse events or deaths
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Acceptable safety profile
Castro, Am J Respir Crit Care Med. 2010;181(2):116-24
Persistence of Effect at Two Years
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Effectiveness of BT persists out to at least two years – proportion of patients
experiencing severe exacerbations comparable between years 1 and 2
Castro M, et al. Ann Allergy Asthma Immunol. 2011 Jul;107(1):65-70.
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Procedure Safety:
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850 bronchoscopies performed in patients with severe asthma (558 BT and
292 Sham procedures)
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No device-related deaths or major adverse events
• e.g., Pneumothorax, airway stenosis or focal narrowing
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More respiratory adverse events were reported in the BT group in the shortterm after the procedure
• Typically occurring within one day and resolving within one
week with standard care
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Fewer respiratory adverse events, hospitalizations and ER visits in the BT
group during post-treatment perioda
Castro, Am J Respir Crit Care Med. 2010;181(2):116-24
Respiratory Symptoms Resulting in Hospitalization
Following Procedure
BT (N=190)
Sham (N=98)
19 Hospitalizations in 16 Subjects
No. of Events (Incident Rate %)
2 Hospitalizations in 2 Subjects
No. of Events (Incident Rate %)
Asthma Aggravated
12 (6.3%)
Atelectasis
3 (1.6%)
Lower Resp.
Tract Infection
1 (0.5%)
Hemoptysis
1 (0.5%)
Low FEV1
1 (0.5%)
Aspirated Prosthetic
Tooth in Airway
1 (0.5%)
Asthma Aggravated
Castro, Am J Respir Crit Care Med. 2010;181(2):116-24
2 (2.0%)
Contraindications
• Active respiratory infection
• Asthma attack or changing dose of systemic corticosteroids (up
or down) in the past 14 days
• Recent severe asthma exacerbation
• Known bleeding disorder
• Patient is unable to stop taking anticoagulants, antiplatelet
agents, aspirin or non-steroidal anti-inflammatory medications
(NSAIDS) before the procedure with physician guidance
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Post-Procedure/Patient Follow Up
• Patient contacted via phone at 1, 2 and 7 days to assess post
procedure status
• Office visit at 2 to 3 weeks to assess clinical stability and
schedule subsequent BT procedures as appropriate
• Patient returns to care of primary asthma physician for long term
asthma management following BT
• Patient may be evaluated for step-down therapy to determine
lowest level of medication necessary to maintain asthma control
Long-Term Safety
• 5 year follow-up in Feasibility, AIR Trials & 4 year follow-up
in RISA trial:
– Stable pulmonary function
– No clinical complications based on AE reporting
• Annual CT scans for 5 years (Feasibility Study):
– All patients doing well
– No clinically significant findings
• BT treatment has excellent safety profile long-term
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Long Term Data: AIR 2
• 162 of 190 (85%) of treated patients in AIR 2 followed 5 years
• Safety:
– No pneumothorax, intubation, arrhythmia, or death
– No decrease in FEV1
– No structural changes in airway (HRCT)
• Efficacy:
– Reduction in severe exacerbations persisted
– ED visits reduced 78% (vs 12 months prior to treatement)
– No change in respiratory adverse events or respiratory
hospitalizations in years 2-5 vs year 1 post BT
J Allergy Clin Immunol 2013;132:1295-302
Long Term Data: AIR 2
J Allergy Clin Immunol 2013;132:1295-302
Procedure Reimbursement
• CPT codes now category 1 effective January 1, 2013
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>230 sites nationwide
• 10 sites in Virginia
• Coverage policies and payment vary by payer – small number of
insurance companies covering currently
• Commercial payers starting to post positive coverage policies
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Clinical Summary of
Bronchial Thermoplasty
• Despite a transient worsening of asthma
– Typically occurring within one day and resolving
within one week with standard care
• Patients experience long term benefits out to at least
one year:
– Improvement in quality of life
– Decrease in severe exacerbations
– Decrease in ER visits
– Decrease in days lost from work or school
Castro, et. al. AJRCCM, 2010
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Guided Bronchoscopy:
• Virtual bronchoscopy (CT image only)
• Virtual bronchoscopy navigation (Olympus, Broncus)
• Electromagnetic navigational bronchoscopy (ENB)
(Superdimension, Veran)
• Radial EBUS (peripheral endobronchial ultrasound)
• Ultrathin bronchoscopy
• CT fluoroscopy bronchoscopy
Guided Bronchoscopy:
• Diagnostic:
– Biopsy of peripheral pulmonary nodules
– Biopsy of lymph nodes
• Therapeutic:
– Placement of fiducial markers for radiation
– Marking (“tattooing”) nodules prior to surgical resection
– Delivery of a therapeutic agent or device (chemo, cryo, etc)
Guided Bronchoscopy:
• Standard flexible bronchoscopy limited ability to reach peripheral
lung nodules
– Peripheral nodules < 20 mm
• Outer third of lung yield = 14%
• Central two-thirds yield = 31%
• Yield higher if “bronchus sign” present on CT
(uncommon in small lesions)
CHEST 2000;117:1049-54
Electromagnetic Navigational Bronchoscopy:
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“GPS” for the bronchial tree
Uses CT 3-D data
Radiologic and endobronchial mapping
Electromagnetic guidance catheter in real time
Extended working sheath to peripheral lesion for biopsy instruments
Electromagnetic Navigational Bronchoscopy:
• Planning (pre-procedure):
– CT chest with or without contrast
– DICOM on CD into system
– Target selection – lesion center and at end of airway if
possible
– System creates 3D bronchial tree and “road map”
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Electromagnetic Navigational Bronchoscopy:
• Procedure:
– Deep sedation/general anesthesia
– Room set up – electromagnetic board
– Load planning data into computer
– Patient position and lead placement
– Rapid on-site cytology
– Fluoroscopy via C-arm on designated gurney
– Bronchoscopy (therapeutic scope)
• Routine airway exam
• Registration done by driving bronchoscope into all lobes
Electromagnetic Navigational Bronchoscopy:
SuperDimension
Electromagnetic Navigational Bronchoscopy:
• “Electromagnetic navigation diagnostic bronchoscopy in peripheral
lung lesions”
CHEST 2007;131:1800-1805
Electromagnetic Navigational Bronchoscopy:
• “Meta-analysis of guided bronchoscopy for the
evaluation of the pulmonary nodule”
– 39 studies met criteria (> 3000 patients)
– Pooled diagnostic yield 70%
– Pneumothorax 1.5% (chest tube 0.6%)
Technology
# Studies
Weighted yield %
Virtual Bronch
10
72.0
ENB
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67.0
Guide Sheath
10
73.2
Ultrathin
11
70.0
R-EBUS
20
71.1
CHEST 2012;142(2):385-393
Electromagnetic Navigational Bronchoscopy:
• “Multimodality Bronchoscopic Diagnosis of
Peripheral Lung Lesions”
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RCT of radial EBUS vs ENB vs both (120 patients)
Combined – EBUS probe through EWC to confirm within lesion
Forceps without fluoro
Pneumothorax rates 5-8%
Diagnostic yield:
• Combined 88%
• EBUS
69%
• ENB
59%
AJRCCM 2007;176:36-41