Ten Year Follow-up of Subjects From 3 Landmark Randomized Controlled Bronchial Thermoplasty (BT) Studies
Conditions: Asthma
Sponsor: Boston Scientific Corporation

 
 
 
(cover page) 
 
Official Title of the Study: 
Ten year follow-up of subjects from 3 landmark 
randomized controlled Bronchial Thermoplasty (BT) 
Studies 
BT 10+ Study 
 
NCT#: 
NCT# 03243292 
 
Date of Document: 
30 MAY 2018 
 
 

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Ten year follow-up of subjects from 3 landmark randomized controlled 
Bronchial Thermoplasty (BT) Studies 
BT 10+ Study 
 
CLINICAL INVESTIGATION PLAN 
 
BSC Project Number: E7137 
 
National Clinical Trial (NCT) Identification Number 03243292 
Sponsored By 
Boston Scientific Corporation 
100 Boston Scientific Way 
Marlborough, MA 01752 
United States of America 
 
Boston Scientific International SA – EU Authorized Representative 
Boston Scientific Limited 
Ballybrit Business Park 
Galway 
Ireland 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
 

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Contact Information 
Role 
Contact  
Clinical Contact 
Frances Nolan, RN 
Clinical Project Manager 
Boston Scientific Corporation  
Endoscopy Clinical Affairs 
100 Boston Scientific Way 
Marlborough, MA 01752 
 
Frances.Nolan@bsci.com 
Coordinating Principal 
Investigators/Chief 
Investigator 
Dr. Rekha Chaudhuri 
Associate Specialist and Hon Clinical Associate Professor 
Respiratory Medicine 
Gartnavel General Hospital Level 7; 7C 
1053 Great Western Road 
Glasgow G12 0YN 
 
Dr. Charlene McEvoy 
Health Partners Specialty Center – Lung and Sleep Health 
401 Phalen Boulevard 
Saint Paul, MN 55130 
 
 
Original Release: May 11, 2017 
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Protocol Synopsis 
Ten year follow-up of subjects from 3 randomized controlled Bronchial 
Thermoplasty (BT) studies 
BT 10+ Study 
Study 
Objective(s) 
To confirm the long-term efficacy and safety of Bronchial Thermoplasty 
(BT) at 10 years follow-up or beyond in subjects previously enrolled in 
any of the following Boston Scientific-sponsored, controlled pre-
approval studies: AIR, RISA and AIR2. 
Test Device 
Alair System (Bronchial Thermoplasty): 
• Alair Controller 
• Alair Catheter 
Study Design 
BT 10+ is an international multi-center, prospective follow-up study on 
subjects who were previously enrolled in any of the following studies: 
AIR, RISA and AIR2 trials. 
Subjects who received active BT treatment in any of the 3 trials will be 
eligible to participate upon achieving a minimum of at least 10 years’ 
time from their last BT treatment’s 6-week follow-up.  
For each of the studies, respective control and sham subjects will also be 
eligible to participate upon achieving a minimum of at least 10 years’ 
time from 6 weeks after the fifth post-randomization visit (15 weeks 
following enrollment) for AIR and RISA subjects and 6 weeks 
following the final sham BT treatment for AIR2 sham subjects. 
Planned 
Number of 
Subjects 
In total, 429 subjects were enrolled in AIR, RISA and AIR2 at 35 
investigational sites: 260 BT subjects, 71 control (RISA and AIR) and 
98 (AIR2).   
Only the 22 sites with ≥3 BT subjects who were followed to the 5-year 
follow-up will be evaluated for participation in the study.   
These 22 sites enrolled 202 BT, 64 control, and 87 sham subjects.  
Based on historical loss to follow-up at 5 years for these trials, an 
attrition of at least 40% is assumed at or beyond 10 year follow-up. This 
long-term follow-up study is therefore expected to enroll up to 196 
subjects: up to 121 BT subjects are expected, up to 32 control (AIR & 
RISA studies) and up to 43 sham (AIR2 study) subjects. 
Note: If attrition rates are lower than expected, more than 196 subjects 
may be enrolled. 
 

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Ten year follow-up of subjects from 3 randomized controlled Bronchial 
Thermoplasty (BT) studies 
BT 10+ Study 
Planned 
Number of 
Investigational 
Sites / Countries 
Twenty-two sites in 6 countries that participated in at least one of the 
AIR, RISA and/or AIR2 clinical trials will be evaluated for participation 
in this study. 
Primary Safety 
Endpoint(s) 
Absence of clinically significant post-treatment respiratory changes, 
following BT, defined as bronchiectasis or bronchial stenosis, as 
confirmed by Pulmonary Volumetric HRCT scan at the BT 10+ study 
visit in those subjects who had a baseline Volumetric HRCT scan in the 
AIR2 Study. 
Primary 
Effectiveness 
Endpoint(s) 
Durability of the treatment effect by comparing the proportion of 
subjects who experience severe asthma exacerbations during the first 
and fifth years after BT treatment with the proportion of subjects who 
experience severe asthma exacerbations during the 12 month period 
prior to the BT 10+ study visit. 
 
Severe asthma exacerbation is defined as worsening of asthma 
symptoms requiring use of systemic corticosteroids (tablets, suspension, 
or injection) (NAEPP Guidelines, 2007). [20] 
Additional 
Endpoints 
The following additional endpoints will be evaluated for the 12 month 
period prior to the BT 10+ study visit and will be compared to the first 
and fifth years after BT treatment:  
• Severe asthma exacerbation rates (exacerbations / subject / year) 
• Emergency room visits for respiratory adverse events (rates of 
emergency room visits and proportion of subjects with 
emergency room visits for respiratory adverse events)  
• Hospitalizations for respiratory adverse events (rates of 
hospitalizations and proportion of subjects with hospitalizations 
for respiratory adverse events) 
• Respiratory Serious Adverse Events (SAEs) (rates of respiratory 
SAEs, and proportion of subjects with respiratory SAEs) 
 

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Ten year follow-up of subjects from 3 randomized controlled Bronchial 
Thermoplasty (BT) studies 
BT 10+ Study 
Follow-up 
Schedule 
For all participating subjects in the BT 10+ study, subject assessments 
can occur in one visit or they can be staged to be completed in multiple 
visits over a 30-day window. The follow-up assessment for this study 
can take place no earlier than the following:   
• 10 years after the end of the treatment period (last BT or sham 
treatment plus 6-weeks) for BT or sham subjects. 
• 10 years after the end of what was defined as their treatment 
period for control subjects. 
The study visit assessments should be completed within 30 days of the 
subject being consented to the study and will consist of the following: 
• Chart review and/or subject interview to collect clinical data on 
chronic sinusitis, GERD, obstructive sleep apnea, respiratory 
infections, and pulmonary medication usage at and up to the BT 
10+ study visit date 
• Pulmonary Volumetric HRCT scan for subjects from the AIR2 
Study 
• Pulmonary function testing including pre- and post-
bronchodilator FEV1 
• Lung volumes and diffusion capacity 
• Subject questionnaires including AQLQ, ACQ, ACT and Subject 
Satisfaction Survey, EQ5D Questionnaire  
• Physical assessment 
• Height and weight 
• Women of child-bearing potential that were enrolled in the AIR2 
study will require a pregnancy test prior to completing the 
Volumetric HRCT scan.  Pregnancy is not an exclusion from the 
study but any pregnant women will not have the Volumetric 
HRCT scan. 
 
Where available, and in line with local standard of care, the following 
additional data will be recorded in the database for exploratory analysis: 
• Allergic skin test or RAST (perennial, seasonal, mold) 

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Ten year follow-up of subjects from 3 randomized controlled Bronchial 
Thermoplasty (BT) studies 
BT 10+ Study 
• Exhaled nitric oxide (eNO) 
Completion of the BT 10+ study visit will mark the end of subject study 
participation. 
Study Duration 12-Month enrollment period.  
Key Inclusion 
Criteria 
• Subjects previously enrolled in AIR, RISA or AIR2 
• Subjects who received active BT treatment and had last BT 
treatment at least 10 years and 6 weeks prior to enrollment 
(applies to previously treated subjects only; does not apply to 
control/sham subjects) 
• Control/Sham subjects with at least 10 years of long-term 
follow-up from 6 weeks after the fifth post-randomization visit 
(15 weeks following enrollment) for AIR and RISA subjects and 
6 weeks following the final sham BT treatment for AIR2 sham 
subjects. 
• Subject is able to read, understand and sign a written Informed 
Consent to participate in the Study and able to comply with the 
study requirements 
Key Exclusion 
Criteria 
• Severe asthma exacerbation or chest infection in the past 4 
weeks. Subject entry into this study should be delayed until free 
from severe asthma exacerbation or chest infection for a 
minimum of 4 weeks.  
Statistical Methods  
Primary 
Statistical 
Hypothesis 
No formal hypothesis will be tested. Data will be summarized 
descriptively with confidence intervals, as appropriate. 
Statistical Test 
Method 
Since no formal hypothesis is tested, only descriptive statistics will be 
used to summarize the primary endpoint. 
 
 

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Table of Contents 
2.1. Table of Figures .....................................................................................................15 
2.2. Table of Tables ......................................................................................................15 
1. 
INTRODUCTION ................................................................................................................16 
1.1. Background ............................................................................................................16 
1.2. Prior Clinical Trials ..............................................................................................16 
1.3. Conclusion ..............................................................................................................17 
2. 
DEVICE DESCRIPTION ......................................................................................................17 
2.1. The Alair Catheter ................................................................................................18 
2.2. Alair RF Controller...............................................................................................19 
2.3. Alair Accessory Kit ...............................................................................................19 
3. 
STUDY OBJECTIVES .........................................................................................................19 
4. 
STUDY ENDPOINTS ...........................................................................................................19 
4.1. Primary Safety Endpoint ......................................................................................19 
4.1.1. 
Definition ..................................................................................................19 
4.1.2. 
Additional Considerations ........................................................................19 
4.2. Primary Efficacy Endpoint ..................................................................................20 
4.3. Additional Endpoints ............................................................................................20 
5. 
STUDY DESIGN .................................................................................................................20 
5.1. Scale and Duration ................................................................................................21 
5.2. Treatment and Control .........................................................................................21 
5.3. Justification for the Study Design ........................................................................21 
6. 
SUBJECT SELECTION ........................................................................................................21 
6.1. Study Population and Eligibility ..........................................................................21 
6.2. Inclusion Criteria ..................................................................................................22 
6.3. Exclusion Criteria .................................................................................................22 
7. 
SUBJECT ACCOUNTABILITY .............................................................................................22 
7.1. Point of Enrollment ...............................................................................................22 
7.2. Withdrawal ............................................................................................................22 

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7.3. Enrollment Controls .............................................................................................22 
8. 
STUDY METHODS .............................................................................................................23 
8.1. Data Collection ......................................................................................................23 
8.2. Study Candidate Screening ..................................................................................25 
8.3. Informed Consent .................................................................................................25 
8.4. Study Visits ............................................................................................................25 
8.4.1. 
Study Visit Timing ...................................................................................25 
8.4.2. 
Study Visit Assessments ...........................................................................25 
8.5. Study Completion ..................................................................................................26 
8.6. Source Documents .................................................................................................26 
8.7. Local Laboratory ..................................................................................................27 
9. 
STATISTICAL CONSIDERATIONS ......................................................................................27 
9.1. Endpoints ...............................................................................................................27 
9.1.1. 
Primary Effectiveness Endpoint ...............................................................27 
9.1.2. 
Primary Safety Endpoint ...........................................................................27 
9.2. Hypothesis ..............................................................................................................28 
9.3. Sample Size ............................................................................................................28 
9.4. Statistical Methods ................................................................................................28 
9.4.1. 
Analysis Sets .............................................................................................28 
9.4.2. 
Control of Systematic Error/Bias ..............................................................28 
9.4.3. 
Number of Subjects per Investigative Site ...............................................28 
9.4.4. 
Data Analyses ...........................................................................................28 
9.4.5. 
Interim Analyses .......................................................................................29 
9.4.6. 
Subgroup Analyses ...................................................................................29 
9.4.7. 
Justification of Pooling .............................................................................29 
9.4.8. 
Changes to Planned Analyses ...................................................................29 
10. DATA MANAGEMENT .......................................................................................................29 
10.1. Data Collection, Processing, and Review ............................................................29 
10.2. Data Retention .......................................................................................................30 
10.3. Core Laboratories .................................................................................................30 
11. AMENDMENTS ..................................................................................................................30 
12. DEVIATIONS .....................................................................................................................30 

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13. DEVICE/EQUIPMENT ACCOUNTABILITY .........................................................................31 
14. COMPLIANCE ....................................................................................................................31 
14.1. Statement of Compliance ......................................................................................31 
14.2. Investigator Responsibilities ................................................................................31 
14.2.1. Delegation of Responsibility ....................................................................32 
14.3. Institutional Review Board/ Ethics Committee ..................................................33 
14.4. Sponsor Responsibilities .......................................................................................33 
14.5. Insurance ................................................................................................................33 
15. MONITORING ....................................................................................................................34 
16. POTENTIAL RISKS AND BENEFITS ...................................................................................34 
16.1. Anticipated Adverse Events .................................................................................34 
16.2. Risks associated with Participation in the Clinical Study .................................34 
16.3. Risk Minimization Actions ...................................................................................34 
16.4. Anticipated Benefits ..............................................................................................35 
16.5. Risk to Benefit Rationale ......................................................................................35 
17. SAFETY REPORTING .........................................................................................................35 
17.1. Reportable Events by investigational site to Boston Scientific .........................35 
17.2. Definitions and Classifications .............................................................................36 
17.3. Relationship to Study Device(s) ...........................................................................37 
17.4. Investigator Reporting Requirements .................................................................39 
17.5. Boston Scientific Device Deficiencies ...................................................................40 
17.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators ...................40 
18. INFORMED CONSENT........................................................................................................41 
19. SUSPENSION OR TERMINATION .......................................................................................42 
19.1 Premature Termination of the Study ..................................................................42 
19.2 Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC Approval .................................................................................................42 
19.3 Requirements for Documentation and Subject Follow-up ................................42 
19.4 Criteria for Suspending/Terminating a Study Site ............................................43 
20. PUBLICATION POLICY ......................................................................................................43 

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21. REIMBURSEMENT AND COMPENSATION FOR SUBJECTS .................................................44 
21.1. Subject Reimbursement........................................................................................44 
21.2. Compensation for Subject’s Health Injury ........................................................44 
22. BIBLIOGRAPHY .................................................................................................................45 
23. ABBREVIATIONS AND DEFINITIONS .................................................................................47 
23.1. Abbreviations ........................................................................................................47 
23.2. Definitions ..............................................................................................................47 
24. APPENDICES .....................................................................................................................49 
Appendix A ......................................................................................................................50 
 
55 
Appendix B ......................................................................................................................56 
Appendix C ......................................................................................................................59 
Appendix D ......................................................................................................................60 
Appendix E ......................................................................................................................61 
          
 
2.1. Table of Figures 
Figure 1: The Alair System ..................................................................................................... 18 
 
2.2. Table of Tables 
Table 6.2-1: Inclusion Criteria ................................................................................................ 22 
Table 6.3-1: Exclusion Criteria ............................................................................................... 22 
Table 8.1-1: Data Collection ................................................................................................... 24 
Table 8.6-1: Source Documentation Requirements ................................................................ 26 
Table 17.2-1: Safety Definitions ............................................................................................. 36 
Table 17.3-1: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 38 
Table 17.4-1:  Investigator Reporting Requirements for SAEs, AEs and ADEs ................... 39 
Table 23.1-1: Abbreviations ................................................................................................... 47 
Table 23.2-1: Definitions ........................................................................................................ 47 

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Introduction 
2.3. 
Background 
Asthma is a common chronic non-communicable disease that affects as many as 334 million 
people of all ages in all parts of the world. It is a cause of substantial burden to people, often 
causing a reduced quality of life, not only due to its physical effects, but also its 
psychological and social effects. The various estimates of its economic burden, mostly due to 
productivity loss, are all significant. (The Global Asthma Report 2014). [1] 
Asthma is a common chronic disorder of the airways that is complex and characterized by 
variable and recurring symptoms, airflow obstruction, bronchial hyper-responsiveness, and 
an underlying inflammation.  Excessive and inappropriate constriction of airway smooth 
muscle (ASM) is recognized as a predominant feature of asthma. Presently, there is no 
known cure for asthma. Despite the availability of a number of medications, there remains an 
unmet medical need for patients with asthma who continue to have symptoms despite 
optimal medical therapy. 
People with asthma can have other concurrent respiratory diseases. Bronchiectasis is 
common in patients with severe asthma. [15] Patients with both bronchiectasis and asthma 
have a higher rate of hospitalization due to a severe asthma attack. [17] 
Bronchiectasis (BXSIS) is defined by dilation, or ectasia of the airways of the bronchus.  The 
primary clinical manifestation of bronchiectasis is chronic or refractory infection. [18] 
Bronchostenosis is seen in asthma patients that have an infection such as a cold.  Symptoms 
include fever, and severe coughing due to attempts to clear secretions. Inability to clear 
secretions can result in atelectasis. Bronchostenosis is a definite, localized, stricture-like 
narrowing of a bronchus. [19} 
The AlairTM Bronchial Thermoplasty System was developed as a novel system designed to 
deliver radiofrequency energy to the airways of asthmatic patients.  Bronchial thermoplasty 
(BT) is a non-pharmacologic, bronchoscopic treatment for subjects 18 years and older with 
severe persistent asthma that is not well controlled with inhaled corticosteroids (ICS) and 
long-acting beta-agonists (LABA).  During the BT procedure, radiofrequency energy is used 
to heat the airway walls in a controlled manner.  The mechanism of action is, in part, a 
lasting reduction in ASM mass due to the heat produced during the procedure [1-5]  The 
reduction in ASM was associated with the clinical improvement seen in patients undergoing 
BT. [3, 4] 
2.4. 
Prior Clinical Trials 
Several randomized controlled clinical trials of BT have been performed in subjects with 
moderate to severe asthma, such as the AIR2 trial and others. [8-11]  In these trials, subjects 
who underwent BT experienced significantly improved clinical outcomes, including 
decreased numbers of asthma exacerbations, ER visits and hospitalizations as well as 
improved quality of life after the procedure.  In addition to these randomized controlled 
trials, open-label studies are needed to confirm the safety and efficacy of BT when performed 

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in clinical practice compared to clinical outcomes of subjects who participated in previously 
reported randomized trials of BT. [12, 13] 
The pivotal AIR2 (“Asthma Intervention Research 2”) trial was a randomized, sham-
controlled trial of the BT system in subjects with severe persistent asthma.  This trial 
demonstrated that over a 12-month follow-up period after BT treatment, BT-treated subjects 
(n=190) experienced clinically relevant improvements in many outcome measures. These 
improvements persisted through 5 years of follow-up.  The detailed methods and results from 
the AIR2 study are described by Castro et al [14]and Wechsler et al [11].  
The Alair system received premarket approval (PMA) from the FDA in April 2010.  
Subsequently, the “Post-FDA Approval Clinical Trial Evaluating BT in Severe Persistent 
Asthma (PAS2)” study was initiated in fulfillment of FDA requirements for PMA approval.  
PAS2 is an ongoing prospective, open-label, observational, multi-center study. The 
objectives of the PAS2 study are to evaluate durability of treatment effectiveness in real-
world clinical practice and to continue to evaluate the short-term and longer-term safety 
profile of the Alair System for BT in the United States and Canada in subjects 18 years and 
older with severe persistent asthma. 
2.5. 
Conclusion 
The BT 10+ study will be the first look at BT subjects beyond 5 years. The evaluation of 
baseline Volumetric HRCT scans from the BT subjects from the AIR2 study and comparison 
to the 10 year follow-up Volumetric HRCT scan will provide objective safety data to 
determine if significant post-treatment changes of Bronchiectasis or Bronchostenosis exist  
3. Device Description 
Bronchial thermoplasty with the Alair System is a non-pharmacologic, device-based 
treatment option for subjects with asthma. The bronchial thermoplasty procedure with the 
Alair System involves the delivery of controlled radio frequency (RF) energy to the airway 
walls as a method for reducing the amount of ASM. The Alair System is designed for 
treatment of the airways distal to the mainstem bronchi from 10 mm in diameter down to 
airways of ≥ 3 mm in diameter.  These airways normally represent about 80% of the total 
airways resistance in humans2.  Bronchial thermoplasty is currently staged in 3 treatment 
sessions with a different region of the lung being treated during each session (one lower lobe 
in session 1; the second lower lobe in session 2; and both upper lobes in session 3).  
Treatment sessions are routinely scheduled at least 3 weeks apart. 
The Alair System, shown in Figure 1, is comprised of an Alair Catheter, an Alair RF 
Controller, and accessories. 

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Error! Reference source not found.: The Alair System 
 
3.1. 
The Alair Catheter 
The Alair Catheter is a sterile, single-use, disposable device. The purpose of the Catheter is 
to deliver therapeutic RF energy to the treatment sites in the airway. The Catheter consists of 
the following key sub-components: 
• 
An electrode array, located at the distal end of the catheter, that contains the 
electrodes and the temperature sensor (the electrodes make tissue contact and 
deliver therapeutic RF energy) 
• 
A long flexible catheter shaft that is inserted into the working channel of a flexible 
bronchoscope  
• 
A handle that is used to expand (open) and relax (closed) the electrode array 
• 
An electrical cable that connects to the RF Controller 
• 
The Catheter is connected to the RF Controller using the catheter receptacle on the 
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3.2. 
Alair RF Controller 
The Alair RF Controller provides temperature-controlled delivery of RF energy to the Alair 
Catheter. The Controller is reusable and provided non-sterile. It does not come into direct 
contact with the patient. 
3.3. 
Alair Accessory Kit 
The Alair System has two accessories, a footswitch and a patient return electrode. The 
footswitch assembly comprises a commercially available switch, cable, and connector. It 
connects to the RF Controller front panel and is used to initiate the RF energy delivery. The 
patient return electrode is used to complete the current path to the RF Controller. The 
footswitch is provided in the Alair RF Controller Accessory Kit, along with a region-specific 
power cord and the Operator’s Manual. The patient return electrode is a standard, 
commercially available return electrode, and is not provided by Boston Scientific (BSC). 
4. Study Objectives 
The objective of this study is to confirm the long-term efficacy and safety of BT at 10 years 
follow-up or beyond in subjects previously enrolled in any of the following Boston 
Scientific-sponsored, controlled pre-approval studies; AIR, RISA or AIR2. 
5. Study Endpoints 
5.1. 
Primary Safety Endpoint 
5.1.1. Definition 
The safety endpoint is defined as the absence of clinically significant post-treatment changes 
following BT, defined as bronchiectasis or bronchial stenosis, as confirmed by Pulmonary 
Volumetric HRCT scan at the BT 10+ study visit in those subjects who also had a baseline 
Volumetric HRCT scan in the AIR2 Study. 
5.1.2. Additional Considerations 
Baseline Volumetric HRCT scans were not collected in the AIR and RISA studies. Only the 
AIR2 study mandated Volumetric HRCT scan at the baseline study visit. Therefore, only 
AIR2 subjects with available baseline Volumetric HRCT scans will be evaluated for the 
primary safety endpoint. Volumetric HRCT scans will be collected in both BT and sham 
subjects at the BT-10+ study visit.  
The Volumetric HRCT scans will be reviewed by an independent radiologist qualified to 
read chest images and a pulmonologist qualified to interpret the radiologist’s findings.  
Baseline and follow-up HRCT images at 10 years or beyond will be read by an independent 
pulmonary radiologist. Upon completing this assessment, the radiologist will assess whether 

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findings in follow-up images were new observations, improvements from baseline or 
deteriorations from baseline. The radiologist’s findings will then be reviewed by an 
independent pulmonologist who will attribute a clinical significance to each finding based on 
the subject’s information, including lung function and AE profiles, Volumetric HRCT scans 
at 5 years follow-up (where available) as well as occurrence and timing of respiratory events 
and severe exacerbations. 
A Volumetric HRCT scan protocol will be developed to include guidelines to be followed by 
the independent reviewers to ascertain whether there are significant post treatment changes, 
following BT, defined as bronchiectasis or bronchial stenosis.   
5.2. 
Primary Efficacy Endpoint 
The primary effectiveness endpoint is defined as durability of the treatment effect by 
comparing the proportion of subjects who experience severe asthma exacerbations during the 
first and fifth years after BT treatment with the proportion of subjects who experience severe 
asthma exacerbations during the 12 month period prior to the BT 10+ study visit. 
Severe asthma exacerbation is defined as worsening of asthma symptoms requiring use of 
systemic corticosteroids (tablets, suspension, or injection) (NAEPP Guidelines, 2007). [20] 
5.3. 
Additional Endpoints 
The following additional endpoints will be evaluated for the 12 month period prior to the BT 
10+ study visit and compared to the first and fifth years following BT treatment:  
• Severe asthma exacerbation rates (exacerbations / subject / year) 
• Emergency room visits for respiratory adverse events (rates of emergency room visits 
and proportion of subjects with emergency room visits for respiratory adverse events)  
• Hospitalizations for respiratory adverse events (rates of hospitalizations and 
proportion of subjects with hospitalizations for respiratory adverse events) 
• Respiratory Serious Adverse Events (SAEs) (rates of respiratory SAEs, and 
proportion of subjects with respiratory SAEs)  
 
6. Study Design 
BT 10+ is an international multi-center, prospective follow-up study on subjects who were 
enrolled in the AIR, RISA and AIR2 trials. 
All subjects who received active BT treatment in the 3 trials will be eligible to participate 
upon achieving a minimum of at least 10 years’ time from their last BT treatment’s 6-week 
follow-up.  
For each of the studies, respective control and sham subjects will also be eligible to 
participate upon achieving a minimum of at least 10 years’ time from 6 weeks after the fifth 

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post-randomization visit (15 weeks following enrollment), for AIR and RISA subjects and 6 
weeks following the final sham BT treatment for AIR2 sham subjects. 
 
6.1. 
Scale and Duration 
In total, 429 subjects were enrolled in AIR, RISA and AIR2 at 35 investigational sites: 260 
BT, 71 control (RISA and AIR) and 98 sham (AIR2) subjects.   
Only the 22 sites with ≥3 BT subjects who were followed to the 5-year follow-up will be 
evaluated for participation in the study. 
These 22 sites enrolled 202 BT, 64 control, and 87 sham subjects.  Based on historical loss to 
follow-up at 5 years for these trials, an attrition of at least 40% is assumed at or beyond 10 
year follow-up. This long-term follow-up study is therefore expected to enroll up to 196 
subjects: up to 121 BT subjects, up to 32 control (AIR & RISA studies) and up to 43 sham 
(AIR2 study) subjects. 
Note: If attrition rates are lower than expected, more than 196 subjects may be enrolled. 
6.2. 
Treatment and Control 
This is a 10+ years or beyond follow-up study for subjects previously enrolled in the AIR, 
RISA or AIR2 trials. Subjects that were treated with BT, as well as control and sham subjects 
will be evaluated for participation in the study. 
Sham and control subjects that have undergone BT treatment outside of the respective studies 
prior to reaching the 10+ year visit will not be analyzed as part of the control/sham group. 
These subjects will be analyzed as a separate group. 
6.3. 
Justification for the Study Design 
To date subjects enrolled in clinical studies investigating the safety and efficacy of BT have 
not been followed beyond 5 years. This study will provide long-term follow-up (10+ years) 
data of subjects treated with BT as well as sham and control subjects from 3 key randomized 
controlled studies: AIR, RISA and AIR2 data on the safety of BT and durability of treatment 
effect at or beyond 10 years post treatment will be collected prospectively from enrolled 
subjects during a single study visit.  
7. Subject Selection  
7.1. 
Study Population and Eligibility  
The inclusion and exclusion criteria are included in Sections 6.2 and 6.3 below.  
 

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7.2. 
 Inclusion Criteria 
Table 7.2-1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria 
• Subjects previously enrolled in AIR, RISA or AIR2 
• Subjects who received active BT treatment and had last BT treatment 
at least 10 years prior to enrollment (applies to previously treated 
subjects only; does not apply to control/sham subjects).  
• Control/Sham subjects with at least 10 years of long-term follow-up 
from 6 weeks after the fifth post-randomization visit (15 weeks 
following enrollment) for AIR and RISA subjects and 6 weeks 
following the final sham BT treatment for AIR2 sham subjects. 
• Subject is able to read, understand and sign a written Informed 
Consent to participate in the Study and able to comply with the study 
requirements 
 
7.3. 
Exclusion Criteria 
Subjects who meet any one of the following criteria will be excluded from this clinical study 
Table 7.3-1: Exclusion Criteria 
Clinical 
Exclusion 
Criteria 
• Severe asthma exacerbation or chest infection in the past 4 weeks. 
Subject entry into this study should be delayed until free from severe 
asthma exacerbation or chest infection for a minimum of 4 weeks.  
8. Subject Accountability 
8.1. 
Point of Enrollment 
The point of enrollment in the study is the date the informed consent form is signed by the 
subject.  
8.2. 
Withdrawal 
All subjects enrolled in the study (including those that are withdrawn, voluntarily withdraw, 
or are lost to follow-up) shall be accounted for and documented.  If a subject withdraws from 
the study, the reason(s) for the withdrawal shall be documented. 
8.3. 
Enrollment Controls 
As all subjects enrolled in this study will have been subjects from the AIR, RISA or AIR2 
trials, all who meet the Inclusion Criteria may be consented and enrolled within the 12-month 
enrollment period.   

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9. Study Methods 
9.1. 
Data Collection 
Data will be collected in line with the endpoints above and according to the schedule 
contained in Table 8.1-1.  All data will be collected using a web-based set of electronic case 
report forms (eCRFs). 

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Table 9.1-1: Data Collection 
 
Procedure/Assessment 
Enrollment 
Study 
Evaluations 
Informed consent process, including informed consent signature date (can be signed and testing 
completed afterwards on another date or on the same date) 
X 
 
Demographics prior to enrollment 
 
X 
Physical assessment, weight, and height 
 
X 
Pre-BD FEV1 
 
X 
Post-BD FEV1 
 
X 
Lung volumes 
 
X 
Diffusion capacity 
 
X 
Lung Volumetric HRCT scan (AIR2 subjects who also had a Volumetric HRCT scan at baseline 
only ) 
 
X 
Pulmonary medication use 
 
X 
Asthma Quality of Life Questionnaire (AQLQ) 
 
X 
Asthma Control Test (ACT) 
 
X 
Asthma Control Questionnaire (ACQ) 
 
X 
Subject Satisfaction Survey (BT treated subjects only) 
 
X 
Subject Productivity Questionnaire 
 
X 
Severe asthma exacerbations, respiratory SAEs, hospitalizations for respiratory adverse events, 
Emergency room visits for respiratory adverse events for 12 month prior to enrollment through 
study exit 
 
X 
Pregnancy test for women of child-bearing potential that were enrolled in AIR2 study prior to 
completing Volumetric HRCT scan 
 
X 
Allergic Skin Test or RAST (perennial, seasonal, mold) (if per local standard of care) 
 
X 
Exhaled Nitric Oxide (eNO) (if per local standard of care) 
 
X 
Assessment of BT treatment outside of AIR, RISA, or AIR2 studies (control/sham subjects only) 
 
X 

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9.2. Study Candidate Screening 
Only subjects who participated in the prior BSC-sponsored BT studies (AIR, RISA, or AIR2) 
will be screened for enrollment in the BT 10+ study.  
Permission will be requested from the respective site Ethics Committee (EC) or Internal 
Review Board (IRB) to collect cause of death information for AIR, RISA and AIR2 subjects 
who died after exiting the study. 
9.3. Informed Consent 
Subjects interested in participating in the study will sign an Informed Consent Form prior to 
study specific tests being performed during the Evaluation Visit. 
9.4. Study Visits 
9.4.1. Study Visit Timing 
For all participating subjects in the BT 10+ study, subject assessments can occur in one visit 
or they can be staged to be completed in multiple visits over a 30-day window. The follow-
up assessment for this study can take place no earlier than the following: 
• Ten (10) years after the end of the treatment period (last BT or sham treatment plus 6-
weeks) for BT or sham subjects. 
• Ten (10) years from 6 weeks after the fifth post-randomization visit (15 weeks 
following enrollment) for the control subjects from the AIR and RISA Studies. 
9.4.2. Study Visit Assessments 
The following assessments are to be completed: 
• Demography 
• Medical History for 12 months prior to enrollment 
• Collection of clinical data on chronic sinusitis, GERD and Obstructive Sleep Apnea 
• Physical Assessment including weight and height  
• Assessment of BT treatment outside of AIR, RISA and AIR2 studies (control/sham 
subjects only) 
• Spirometry test to include both Pre and Post BD Forced Expiratory Volume in 1 
second: Pre-BD FEV1 
• Lung volumes 
• Diffusion capacity 
• Pulmonary Volumetric HRCT scan (BT treated subjects only) 
• Pulmonary medication use 

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• Asthma Quality of Life Questionnaire (AQLQ) 
• Asthma Control Test (ACT) 
• Asthma Control Questionnaire (ACQ) 
• Subject Satisfaction Survey (BT treated subjects) 
• EQ5D Questionnaire 
• Respiratory SAEs in the prior 12 months 
• Severe asthma exacerbations in the prior 12 months 
• Hospitalizations for respiratory adverse events in the prior 12 months 
• Emergency room visits for respiratory adverse events in the prior 12 months 
• Women of child-bearing potential that were enrolled in the AIR2 study will require a 
pregnancy test prior to completing the Volumetric HRCT scan.  Pregnancy is not an 
exclusion from the study but any pregnant women will not have the Volumetric 
HRCT scan. 
• Where available: 
o Allergic skin test or RAST (perennial, seasonal, mold) 
o Exhaled nitric oxide (eNO) 
 
9.5. 
Study Completion 
Completion of the Evaluations in section 8.4 will mark the end of the subject study 
participation. 
9.6. 
Source Documents 
It is preferable that original source documents are maintained, when available. In lieu of 
original source documents, certified copies are required to be maintained.  A certified copy is 
a copy (irrespective of the type of media used) of the original record that has been verified 
(i.e., by a dated signature or by generation through a validated process) to have the same 
information, including data that describe the context, content, and structure, as the original. 
Source documentation includes but is not limited to those items noted in Error! Reference 
source not found.. 
Table 9.6-1: Source Documentation Requirements 
Requirement 
Disposition 
Demographic and Physical Exam 
Retain at center 
Assessment of BT treatment outside of AIR, RISA, 
and AIR2 studies (control/sham subjects only)  
Retain at center 
Spirometry test report 
Retain at center 

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Table 9.6-1: Source Documentation Requirements 
Requirement 
Disposition 
Volumetric HRCT scan report (AIR2 subjects who 
also had a Volumetric HRCT scan at baseline only) 
Retain at center 
Volumetric HRCT scan (AIR2 subjects who also had 
a Volumetric HRCT scan at baseline only only) 
Send to HRCT Core Lab 
Lung volume test report 
Retain at center 
Diffusion capacity test report 
Retain at center 
Asthma Quality of Life Questionnaire (AQLQ) 
Retain at center 
Asthma Control Test (ACT) 
Retain at center 
Asthma Control Questionnaire (ACQ) 
Retain at center 
Subject Satisfaction Survey (BT subjects only) 
Retain at center 
EQ5D Questionnaire 
Retain at center 
Hospitalization and/or death records as applicable 
Retain at center 
 
9.7. 
Local Laboratory  
A Core Lab will be utilized for Volumetric HRCT scan imaging repository and archiving for 
this study.  
10. Statistical Considerations 
10.1. Endpoints 
10.1.1. Primary Effectiveness Endpoint 
The primary effectiveness endpoint is defined as durability of the treatment effect by 
comparing the proportion of subjects who experience severe asthma exacerbations during the 
first and fifth year after BT treatment with the proportion of subjects who experience severe 
asthma exacerbations during the 12 month period prior to the BT 10+ study visit. 
 
Severe asthma exacerbation is defined as worsening of asthma symptoms requiring use of 
systemic corticosteroids (tablets, suspension, or injection) (NAEPP Guidelines, 2007). [20] 
10.1.2. Primary Safety Endpoint 
The primary safety endpoint is defined as the absence of clinically significant post-treatment 
changes following BT, defined as bronchiectasis or bronchial stenosis, as confirmed by 
Pulmonary Volumetric HRCT scan at the BT 10+ study visit. 

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10.2. Hypothesis 
No formal hypothesis will be tested for both the primary effectiveness and safety endpoints 
since this is an observational study. 
10.3. Sample Size  
Only the 22 sites with ≥3 BT subjects who were followed out to the 5 year follow-up visit 
will be evaluated for participation in the study.  Based on historical loss to follow-up at 5 
years for these trials, an attrition rate of at least 40% is expected at or beyond 10 years of 
follow-up. This long-term follow-up study is therefore expected to enroll up to 121 BT 
subjects, up to 32 control (AIR & RISA studies) and up to 43 sham (AIR2 study) subjects. 
Note that if attrition rates are lower than expected, more than 196 subjects may be enrolled. 
10.4. Statistical Methods 
Since no formal hypothesis is tested, only descriptive statistics will be used to summarize the 
primary effectiveness and safety endpoints. 
10.4.1. Analysis Sets 
All subjects who signed an informed consent and are enrolled in this study will be included 
in the Intent to Treat (ITT) analysis set.  Since this is a long-term follow-up study using 
subjects form past studies and involves no treatment, the intention is to analyze data for all 
subjects enrolled.  Thus, no further analysis sets will be required. 
10.4.2. Control of Systematic Error/Bias 
All subjects who have been evaluated for the inclusion/exclusion criteria and have signed the 
ICF will be eligible for enrollment in the study. Visual and/or electronic data review will be 
performed to identify possible data discrepancies. Manual and/or automatic queries will be 
created in the EDC system and will be issued to the site for appropriate response. Site staff 
will be responsible for resolving queries in the database.  
10.4.3. Number of Subjects per Investigative Site 
The intention is to enroll as many subjects as possible from the 3 preceding studies. The 
number of subjects enrolled for each site in the 3 previous studies is the upper limit for the 
number of subjects that will be enrolled in this study. 
10.4.4. Data Analyses 
Descriptive statistics will be presented for all ITT subjects. The mean (± standard deviation) 
will be used to describe continuous variables with a normal distribution and the median (and 
interquartile range) will be used to describe continuous variables with a skewed distribution. 
Frequency tables will be used to summarize discrete variables.  Proportions of subjects with 
adverse events and SAEs will be reported. 

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Subjects will be analyzed in the following treatment groups: 
• BT – subjects who were treated with BT during the AIR, RISA, or AIR2 studies, 
• Control/sham – subjects who were treated as control or sham subjects during the AIR, 
RISA, or AIR2 studies and did not have BT treatment before the BT 10+ study visit, 
and 
• Post-study BT – subjects who were treated as control or sham subjects during the 
AIR, RISA, or AIR2 studies and had BT treatment before the BT 10+ study visit. 
10.4.5. Interim Analyses  
No formal interim analyses are planned for the purpose of stopping this study early. Informal 
interim analysis may be conducted for the purpose of submissions of abstracts to major 
professional meetings. 
10.4.6. Subgroup Analyses 
There are no planned subgroup analyses. 
10.4.7. Justification of Pooling 
The analyses will be presented using data pooled across centers. If deemed appropriate, 
stratified and multivariate analysis techniques, including Chi-square test or logistic 
regression will be used to assess differences between study centers to justify pooling data 
across centers. 
10.4.8. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analysis will be 
documented in an amended Statistical Analysis Plan. Changes from the planned statistical 
methods after performing the analysis will be documented in the clinical study report along 
with a reason for the deviation. 
11. Data Management 
11.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 

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The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC System 
and will be issued to the site for appropriate response. Site staff will be responsible for 
resolving queries in the database. 
11.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain, at the 
investigative site, all essential study documents and source documentation that support the 
data collected on the study subjects in compliance with applicable regulatory requirements.  
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Sites are required to inform Boston Scientific in 
writing where paper or electronic files are maintained in case files are stored off site and are 
not readily available. 
11.3. Core Laboratories 
This study requires of a core laboratory for repository and archiving of Volumetric HRCT 
scan.  Appropriate certifications and documentation records are required to be maintained at 
the site for laboratory and/or vendors.   
12. Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/FDA/CA) of the revised protocol must be obtained prior to implementation. 
13. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC of any deviation from the investigational plan to protect 
the life or physical well-being of a subject in an emergency, and those deviations which 
affect the scientific integrity of the clinical investigation. Such notice shall be given as soon 
as possible, but no later than 5 working days after the emergency occurred, or per prevailing 
local requirements, if sooner than 5 working days.  

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 Deviations from the investigational plan, with the reason for the deviation, must be 
documented and reported to the sponsor using the EDC. Sites may also be required to report 
deviations to the IRB/EC, per local guidelines and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions will be put into place by the sponsor. 
14. Device/Equipment Accountability 
No device accountability is required for this study. 
15. Compliance 
15.1. Statement of Compliance 
This Study will be conducted in accordance with ISO 14155: Clinical Investigation of 
Medical Devices for Human Subjects – Good Clinical Practice, ethical principles that have 
their origins in the Declaration of Helsinki, and pertinent individual country laws and 
regulations. Collection of data in the Study shall not begin until the required 
approval/favorable opinion from the IRB/EC and/or regulatory authority has been obtained, 
if appropriate. Any additional requirements imposed by the IRB/EC or regulatory authority 
shall be followed, if appropriate. 
15.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation 
plan/, ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB/EC, and prevailing local and/or 
country laws and/or regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Prior to beginning the study, sign the Protocol Signature page documenting his/her 
agreement to conduct the study in accordance with the protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 

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• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the investigational device when it is used/operated by the subject. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
• Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
15.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, are competent to perform the tasks they have been delegated, and 
adequate supervision of those to whom tasks are delegated. Where there is a sub-investigator 
at a site, the sub-investigator should not be delegated the primary supervisory responsibility 
for the site. The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  

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15.3. Institutional Review Board/ Ethics Committee 
Prior to gaining Approval-to-Enroll status, the investigational site will provide to the sponsor 
documentation verifying that their IRB/EC is registered or that registration has been 
submitted to the appropriate agency, as applicable according to national/regulatory 
requirements.   
A copy of the written IRB/EC and/or competent authority approval of the protocol (or 
permission to conduct the study) and Informed Consent Form, must be received by the 
sponsor before recruitment of subjects into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
 
Any amendment to the protocol will require review and approval by the IRB before the 
changes are implemented to the study.  All changes to the ICF will be IRB approved; a 
determination will be made regarding whether a new ICF needs to be obtained from 
participants who provided consent, using a previously approved ICF. 
 
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by local/country or IRB/EC requirements. Copies of the Investigator’s reports 
and the IRB/EC continuance of approval must be provided to the sponsor.  
15.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO) will have access to these 
confidential records. Authorized regulatory personnel have the right to inspect and copy all 
records pertinent to this study. Study data collected during this study may be used by BSC 
for the purposes of this study, publication, and to support future research and/or other 
business purposes, such as overseeing and improving the performance of its device, new 
medical research and proposals for developing new medical products and procedures. All 
data used in the analysis and reporting of this study or shared with a third-party researcher 
will be without identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
15.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 

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16. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, verification will be conducted to ensure that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
17. Potential Risks and Benefits 
17.1. Anticipated Adverse Events  
The following anticipated adverse events (AE) have been identified for this study as risks of 
the subject’s asthma diagnosis. They are not expected to occur at an increased rate or severity 
due to the subject’s participation in this clinical study. 
• Severe asthma exacerbations 
• Respiratory adverse events 
• Potential device related AEs are described in the Alair DFU 
17.2. Risks associated with Participation in the Clinical Study 
The following tests are routinely performed as standard of care for people with asthma: 
• Pulmonary Function Tests are low risk procedures. They may occasionally cause 
dizziness and/or slight chest discomfort due to muscle soreness, but these are self-
limited. 
• Volumetric HRCT scan: Study Subjects will have radiation exposure as a result of the 
Volumetric HRCT scans required. The doses of radiation used typically are so small 
that the risk of these procedures is difficult to measure. 
17.3. Risk Minimization Actions 
Additional currently unknown long-term risks of bronchial thermoplasty may exist.  As this 
study does not include a bronchial thermoplasty procedure, additional risk from participation 
in the study is limited to those associated with the study’s standard of care assessments (such 
as HRCT). Risks of standard of care follow-up assessments can be minimized through 
compliance with this protocol, performing procedures in the appropriate hospital 
environment, adherence to subject selection criteria, close monitoring of the subject's 

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physiologic status during research procedures and/or follow-ups and by promptly supplying 
BSC with all pertinent information required by this protocol. 
Subjects will only be selected if they have participated on one of the previous BT studies. 
17.4. Anticipated Benefits 
There may not be any potential benefit from participating in this study.  However, medical 
science and future subjects may benefit from your participation. 
17.5. Risk to Benefit Rationale 
As a ten-plus year follow-up evaluation of subject previously treated with BT under a 
separate protocol and separate consent.  The only new risks with the trial are those associated 
with Volumetric HRCT scans and pulmonary function testing.  The benefit of, for the first 
time, evaluating BT and SHAM or control subjects from prior BT studies is anticipated to 
provide beneficial information to the medical community that outweighs these risks. 
18. Safety Reporting 
18.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All respiratory Serious Adverse Events 
• All fatal Serious Adverse Events 
• All respiratory Adverse Events 
• New findings/updates in relation to already reported events 
When possible, the medical diagnosis should be reported as the adverse event term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, it should be submitted 
as an adverse event. 
Any AE event required by the protocol, experienced by the study subject after informed 
consent and once considered enrolled in the study (as defined in study subject classification 
section), whether during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity of 
frequency during the course of the investigation. Death should not be recorded as an AE, but 
should only be reflected as an outcome of ONE (1) specific SAE (see Table 17.2-1 for AE 
definitions). 

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18.2. Definitions and Classifications 
Adverse event definitions are provided in Table 17.2-1. Administrative edits were made on 
the definition of serious adverse event from ISO 14155and MEDDEV 2.7/3 for clarification 
purposes. 
Table 18.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the investigational 
medical device.  
NOTE 1: This includes events related to the investigational medical device 
or comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Note: This definition meets the reporting objectives and requirements of ISO 
14155 and MEDDEV 2.7/3. 
Adverse event that: 
a) Led to death, 
b) Led to serious deterioration in the health of the subject as defined by 
either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of the study   medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies 
or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
study medical device. 
NOTE 2: This definition includes any event resulting from use 
error or intentional abnormal use of the study medical device. 

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Table 18.2-1: Safety Definitions 
Term 
Definition 
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
18.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study procedure. 

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Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
- the event has no temporal relationship with the use of the investigational device 
or the procedures; 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the 
device or procedure; the serious event can be attributed to another cause (e.g. an 
underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the investigational device 
used for diagnosis, when applicable; harms to the subject are not clearly due to use 
error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Unlikely Related 
The relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly Related 
The relationship with the use of the investigational device is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/ clinical condition or/and an effect of another device, drug or 
treatment). Cases were relatedness cannot be assessed or no information has been 
obtained should also be classified as possible. 
Probably Related 
The relationship with the use of the investigational device seems relevant and/or 
the event cannot be reasonably explained by another cause, but additional 
information may be obtained. 

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Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Causal Relationship 
The serious event is associated with the investigational device or with procedures 
beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with investigational device use/application 
or procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the investigational device used for 
diagnosis, when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious event. 
 
18.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 17.4-1. 
 
Table 18.4-1:  Investigator Reporting Requirements for SAEs, AEs and ADEs 
Event 
Classification 
Communication 
Method  
Communication Timeline post-market studies**  
(MEDDEV 2.12/2 :  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Serious Adverse 
Event (respiratory 
and/or fatal) 
Complete AE eCRF 
page with all available 
new and updated 
information. 
• 
Within 10 business days after becoming aware 
of the event or as per local/regional 
regulations. 
 
• 
Reporting required through the end of the 
study. 
Provide all relevant 
source documentation 
(de-identified) for 
reported event. 
• 
When documentation is available (recommend 
within 60 calendar days). 

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Table 18.4-1:  Investigator Reporting Requirements for SAEs, AEs and ADEs 
Event 
Classification 
Communication 
Method  
Communication Timeline post-market studies**  
(MEDDEV 2.12/2 :  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Adverse Event 
(respiratory) 
Complete AE eCRF 
page, which contains 
such information as date 
of AE, treatment of AE 
resolution, assessment 
of seriousness and 
relationship to the 
procedure. 
• 
In a timely manner (e.g., recommend within 30 
business days) after becoming aware of the 
information. 
 
• 
Reporting required through the end of the 
study. 
Adverse Device 
Effects 
Complete AE eCRF 
page, which contains 
such information as date 
of AE, treatment of AE 
resolution, assessment 
of seriousness and 
relationship to the 
procedure. 
• 
In a timely manner (e.g., recommend within 30 
business days) after becoming aware of the 
information. 
 
• 
Reporting required through the end of the 
study. 
Provide all relevant 
source documentation 
(de-identified) for 
reported event. 
Serious Adverse 
Device Effects 
Complete AE eCRF 
page with all available 
new and updated 
information. 
• 
Within 2 business days after becoming aware 
of the event or as per local/regional 
regulations. 
 
• 
Reporting required through the end of the 
study. 
Provide all relevant 
source documentation 
(de-identified) for 
reported event. 
• 
In a timely manner (e.g., recommend within 30 
business days) after becoming aware of the 
information. 
 
• 
Reporting required through the end of the study 
18.5. Boston Scientific Device Deficiencies 
Since this a 10+ year follow-up study, and there is no device used for this study, device 
deficiencies will not be collected.  
18.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators and regulatory authorities, as applicable.  

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The Principal Investigator is responsible for informing the IRB/EC, and regulatory 
authorities of SAEs as required by local/regional regulations. 
19. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC, or central IRB, if 
applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB/EC.  Any modification requires acceptance from BSC prior to use of 
the form.  The ICF must be in a language understandable to the subject and if needed, BSC 
will assist the site in obtaining a written consent translation. Translated consent forms must 
also have IRB/EC approval prior to their use.  Privacy language shall be included in the body 
of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• Ensure important new information is provided to new and existing subjects throughout 
the clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  

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Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., FDA requirement is within 5 working days of 
learning of such an event). Any violations of the informed consent process must be reported 
as deviations to the sponsor and local regulatory authorities (e.g. IRB/EC), as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC. The new version of the ICF must be approved by 
the IRB/EC. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the site’s IRB/EC. The IRB/EC will determine the subject population to be re-
consented. 
20. Suspension or Termination 
19.1 Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or business reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, will 
be notified in writing in the event of study termination. 
19.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval 
Any investigator, or associated IRB/ EC or regulatory authority may discontinue 
participation in the study or withdrawal approval of the study, respectively, with suitable 
written notice to Boston Scientific. Investigators, associated IRBs/ECs, and regulatory 
authorities, as applicable, will be notified in writing in the event of these occurrences. 
19.3 Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB/EC and regulatory authorities, as applicable, will be notified. Detailed information on 
how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 

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to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
19.4 Criteria for Suspending/Terminating a Study Site 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB/EC and regulatory authorities, as applicable, will be notified. Detailed information on 
how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
21. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC will submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study. Boston Scientific Corporation adheres to the Contributorship Criteria set forth in 
the Uniform Requirements of the International Committee of Medical Journal Editors 
(ICMJE; http://www.icmje.org). In order to ensure the public disclosure of study results in a 
timely manner, while maintaining an unbiased presentation of study outcomes, BSC 
personnel may assist authors and investigators in publication preparation provided the 
following guidelines are followed. 
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The Co-lead investigators are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  

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22. Reimbursement and Compensation for Subjects 
22.1. Subject Reimbursement 
There will be no subject compensation for participating in the post-approval study. Subjects 
can be reimbursed for moderate travel expenses. 
22.2. Compensation for Subject’s Health Injury 
Boston Scientific Corporation will purchase an insurance policy to cover the cost of potential 
health injury for study subjects, and if required by applicable law.  
 
 

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23. Bibliography 
1. Marks G, Pearce N, Strachan D, and Asher I. “The Global Burden of Disease Due to 
Asthma.” In: The Global Asthma Report 2014. Auckland, New Zealand: Global 
Asthma Network, 2014. Pp. 16-21. 
2. Chakir J, Haj-Salem I, Gras D, Joubert P, Beaudoin EL, Biardel S, Lampron N, 
Martel S, Chanez P, Boulet LP, Laviolette M. Effects of Bronchial Thermoplasty on 
Airway Smooth Muscle and Collagen Deposition in Asthma. Ann Am Thorac Soc 
2015; 12: 1612-1618. 
3. Pretolani M, Dombret MC, Thabut G, Knap D, Hamidi F, Debray MP, Taille C, 
Chanez P, Aubier M. Reduction of airway smooth muscle mass by bronchial 
thermoplasty in patients with severe asthma. Am J Respir Crit Care Med 2014; 190: 
1452-1454. 
4. Pretolani M, Dombret MC, Thabut G, Knap D, Hamidi F, Debray MP, Taille C, 
Chanez P, Aubier M. Reduction of airway smooth muscle mass by bronchial 
thermoplasty in patients with severe asthma. Am J Respir Crit Care Med 2014; 190: 
1452-1454. 
5. Pretolani M, Bergqvist A, Thabut G, Dombret MC, Knapp D, Hamidi F, Alavoine L, 
Taille C, Chanez P, Erjefalt JS, Aubier M. Effectiveness of bronchial thermoplasty in 
patients with severe refractory asthma: clinical and histopathological correlations. J 
Allergy Clin Immunol 2016. 
6. Salem IH, Boulet LP, Biardel S, Lampron N, Martel S, Laviolette M, Chakir J. Long-
Term Effects of Bronchial Thermoplasty on Airway Smooth Muscle and Reticular 
Basement Membrane Thickness in Severe Asthma. Ann Am Thorac Soc 2016; 13: 
1426-1428. 
7. Denner DR, Doeing DC, Hogarth DK, Dugan K, Naureckas ET, White SR. Airway 
Inflammation after Bronchial Thermoplasty for Severe Asthma. Ann Am Thorac Soc 
2015; 12: 1302-1309. 
8. Dombret MC, Alagha K, Boulet LP, Brillet PY, Joos G, Laviolette M, Louis R, 
Rochat T, Soccal P, Aubier M, Chanez P. Bronchial thermoplasty: a new therapeutic 
option for the treatment of severe, uncontrolled asthma in adults. Eur Respir Rev 
2014; 23: 510-518. 
9. Castro M, Cox G. Asthma outcomes from bronchial thermoplasty in the AIR2 trial. 
Am J Respir Crit Care Med 2011; 184: 743-744. 
10. Castro M, Rubin A, Laviolette M, Hanania NA, Armstrong B, Cox G. Persistence of 
effectiveness of bronchial thermoplasty in patients with severe asthma. Ann Allergy 
Asthma Immunol 2011; 107: 65-70. 
11. 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. Effectiveness and safety of bronchial thermoplasty in the treatment of severe 

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asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J 
Respir Crit Care Med 2010; 181: 116-124. 
 
12. 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. Bronchial 
thermoplasty: Long-term safety and effectiveness in patients with severe persistent 
asthma. J Allergy Clin Immunol 2013; 132: 1295-1302. 
13. Bicknell S, Chaudhuri R, Lee N, Shepherd M, Spears M, Pitman N, Cameron E, 
Cowan D, Nixon J, Thompson J, McSharry C, Thomson NC. Effectiveness of 
bronchial thermoplasty in severe asthma in 'real life' patients compared with those 
recruited to clinical trials in the same centre. Ther Adv Respir Dis 2015; 9: 267-271. 
14. Doeing DC, Mahajan AK, White SR, Naureckas ET, Krishnan JA, Hogarth DK. 
Safety and feasibility of bronchial thermoplasty in asthma patients with very severe 
fixed airflow obstruction: a case series. J Asthma 2013; 50: 215-218.13. 
Castro M, 
Musani AI, Mayse ML, Shargill NS. Bronchial thermoplasty: a novel technique in the 
treatment of severe asthma. Ther Adv Respir Dis 2010; 4: 101-116. 
15. Dimakou K, Gousiou A, Toumbis M, Kaponi M, Chrysikos S, Thanos L, 
Triantafillidou C. Investigation of bronchiectasis in severe uncontrolled 
asthma.  Clinical Respiratory Journal 2017; May 24. doi: 10.1111/crj.12653. [Epub 
ahead of print]. PMID:  28544140 
 
16. Luján M, Gallardo X, Amengual MJ, Bosque M, Mirapeix RM, Domingo 
C.  Prevalence of bronchiectasis in asthma according to oral steroid 
requirement:  influence of immunoglobulin levels.  Biomedical Research 
International 2013; 2013:109219. doi: 10.1155/2013/109219. Epub 2013 Nov 13. 
 
17. Ozis T, Turktas H.  The Impact of Bronchiectasis in Clinical Presentation of Asthma. 
Southern Medical Journal 2007; 100:  468-471. 
 
18. Robert J. Mason, V. Courtney Broaddus, Thomas R Martin, Talmadge E King, Dean 
Schraufnagel, John F. Murray, and Jay A. Nadel.  Murray and Nadel’s Textbook of 
Respiratory Medicine, 5th Edition.  Published by Elsevier Health Sciences 
(Amsterdam, The Netherlands).  2010. 
19. Prickman LE, Moersch HJ.  Bronchostenosis complicating allergic and infectious 
asthma.  Annals of Internal Medicine 1940; 14(3): 387-392. 
 
20. NHLBI.NIH.gov Expert Panel Report 3 (EPR-3):  Guidelines for the Diagnosis 
and Management of Asthma – Summary Report 2007.  
https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-
guidelines/summary-report-2007.  Accessed March 22, 2017 

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24. Abbreviations and Definitions  
24.1. Abbreviations 
Abbreviations are shown in Table 23.1-1           
Table 23.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ACQ 
Asthma Control Questionnaire 
ACT 
Asthma Control Test 
ADE 
Adverse Device Effects 
AIR 
Randomized Clinical Trial of the Alair® System for  the Bronchial 
Thermoplasty Treatment of Asthma 
AIR2 
Safety and Effectiveness of the Alair® System for the Treatment of Asthma: 
A Multicenter Randomized Clinical Trial 
(Asthma Intervention Research (AIR2) Trial) 
AQLQ 
Asthma Quality of Life Questionnaire 
AE 
Adverse Event 
ASM 
Airway Smooth Muscle 
BSC 
Boston Scientific Corp. 
BT 
Bronchial Thermoplasty 
CRF (eCRF) 
Case Report Form (electronic Case Report Form) 
DFU 
Directions for Use 
ER 
Emergency Room 
FEV1 
Forced Expiratory Volume in 1 second:  FEV1 (pre- and post-bronchodilator) 
GCP 
Good Clinical Practice 
HRCT 
High Resolution Computed Tomography Scan 
ICH 
International Council for Harmonization 
ICS 
Inhaled Corticosteroids 
LABA 
Long Acting Beta Agonist 
PEF 
Peak Expiratory Flow 
RF 
Radio Frequency 
RISA 
Multicenter Randomized Clinical Trial of Bronchial Thermoplasty with the 
AlairTM System for the Treatment of Severe Asthma 
SADE 
Serious Adverse Device Effects 
SAE 
Serious Adverse Events 
24.2. Definitions 
Terms are defined in Table 23.2-1.  
Table 23.2-1: Definitions 
Term 
Definition 
Bronchiectasis 
Bronchiectasis is defined by dilation, or ectasia of the airways of the bronchus. 
Bronchostenosis 
Bronchostenosis is a definite, localized, stricture-like narrowing of a bronchus 

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Table 23.2-1: Definitions 
Term 
Definition 
Pneumonia   
 
Pneumonia will be diagnosed only if a subject has: 
1. Compatible clinical presentation (e.g., fever, cough, purulent sputum, etc.), 
AND 
2. Chest x-ray showing the presence of a new infiltrate consistent with 
clinical pneumonia. 
Severe Asthma 
Exacerbation 
Severe asthma exacerbation is defined as worsening of asthma symptoms 
requiring use of systemic corticosteroids (tablets, suspension, or injection) 
(NAEPP Guidelines, 2007). 
 
For subjects already routinely taking systemic corticosteroids, a severe asthma 
exacerbation is defined as a worsening of asthma symptoms requiring any 
increase in daily dose of systemic corticosteroids. 
 
Note: Short term prophylactic increases in dose around the time of the treatment 
procedures will not be considered severe asthma exacerbations in the absence of 
worsening symptoms. 
 
For consistency, courses of systemic corticosteroids in excess of baseline 
separated by 1 week or more will be treated as separate severe asthma 
exacerbations. 
 
All asthma exacerbations (worsening of asthma symptoms) should be recorded 
as respiratory adverse events termed “asthma aggravated.”  Asthma 
exacerbations associated with increases in steroid use as described above will be 
counted as severe asthma exacerbations. 
 
Severity of Adverse 
Events 
1. Mild: Awareness of signs or symptoms, but easily tolerated and transient; 
causing no loss of time from normal activities; symptoms would not require 
medication (other than short-acting bronchodilators) or a medical treatment; 
signs and symptoms are transient. 
2. Moderate: Marked symptoms and discomfort severe enough to cause 
moderate interference with subject’s usual activities. Symptomatic treatment 
is possible. 
3. Severe: Incapacitating with inability to do work or usual activities; signs and 
symptoms may be of systemic nature or require medical intervention and/or 
treatment.  Hospitalization may be required or prolonged. 
 
The Physician will determine both the intensity of the adverse event and the 
event’s relationship to BT treatment. 
Source Data  
(ISO 14155:2011) 
All information in original records of clinical findings, observations, or other 
activities in a clinical investigation, necessary for the reconstruction and 
evaluation of the clinical investigation. 
Source Document 
(ISO 14155:2011) 
Printed, optical or electronic document containing source data. Examples: 
Hospital records, laboratory notes, device accountability records, 
photographic negatives, radiographs, records kept at the investigation site, at 
the laboratories and at the medico-technical departments involved in the 
clinical investigation. 
 
 

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. 
 
25. Appendices 
A. 24.1 Asthma Quality of Life Questionnaire (AQLQ) score 
B. 24.2 Asthma Control Questionnaire  
C. 24.3 Asthma Control Test (ACT) score 
D. 24.4 Subject Satisfaction Survey  
E. 24.5 Subject EQ5D Questionnaire 
 
 
 

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Appendix A 
Asthma Quality of Life Questionnaire (AQLQ) score 

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Appendix B  
Asthma Control Questionnaire 

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Appendix C 
Asthma Control Test (ACT) score 
 

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Appendix D 
Subject Satisfaction Survey 
 
Would subject undergo the Bronchial Thermoplasty procedure if he/she had to do it all over 
again? 
 
Yes 
No 
 
 
Would subject recommend this treatment to a friend or family member? 
 
Yes 
No 
 
 
 
 
 
 

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Appendix E 
Subject EQ5D Questionnaire 
Under each heading, please tick the ONE box that best describes your health TODAY 
Mobility 
  I have no problems in walking about 
 
 
  I have slight problems in walking about 
 
 
  I have moderate problems in walking about 
 
 
  I have severe problems in walking about 
 
 
  I am unable to walk about 
 
 
 
Self-Care 
  I have no problems washing or dressing myself 
 
 
  I have slight problems washing or dressing myself 
 
 
  I have moderate problems washing or dressing myself 
 
 
  I have severe problems washing or dressing myself 
 
 
  I am unable to wash or dress myself 
 
 
 
Usual Activities (e.g. work, study, housework, family or leisure activities) 
  I have no problems doing my usual activities 
 
 
  I have slight problems doing my usual activities 
 
 
  I have moderate problems doing my usual activities 
 
 
  I have severe problems doing my usual activities 
 
 
  I am unable to do my usual activities 
 
 
 
Pain/Discomfort 
  I have no pain or discomfort 
 
 
  I have slight pain or discomfort 
 
 
  I have moderate pain or discomfort 
 
 
  I have severe pain or discomfort 
 
 
  I have extreme pain or discomfort 
 
 
 
Anxiety/Depression 
  I am not anxious or depressed 
 
 
  I am slightly anxious or depressed 
 
 
  I am moderately anxious or depressed 
 
 
  I am severely anxious or depressed 
 
 
  I am extremely anxious or depressed 
 
 
 
 
 
 
 
UK (English) © 2009 EuroQol Group EQ-50"' is a trade mark of the EuroQol Group 
 
 

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We would like to know how good or bad your health is TODAY. 
 
 
• 
This scale is numbered from 0 to 100. 
 
 
• 
100 means the best health you can imagine. 
0 means the worst health you can imagine. 
 
 
• 
Mark an X on the scale to indicate how your health is TODAY. 
 
• 
Now, please write the number you marked on the scale in the box 
below. 
 
 
 
 
 
 
YOUR HEALTH TODAY=  
 
The best health 
you can imagine 
100 
 
95 
 
  90 
 
85 
 
80 
 
75 
 
70 
 
65 
 
60 
 
55 
 
50 
 
45 
 
40 
 
35 
 
30 
 
25 
 
20 
 
15 
 
10 
 
5 
 
0 
The worst 
health you 
can imagine 
 UK (English) © 2009 EuroQol Group EQ-50"' is a trade mark of the EuroQol Group