Asthma/COPD Overlap Syndrome (ACOS) REG Working Group Meeting. Presented on 17th May 2015 in Denver, Colorado, USA

1. Sunday May 17th, 7.30-9.00am (MST)
Altitude Room; Crowne Plaza, Denver, Colorado
REG Asthma/COPD Overlap Syndrome
(ACOS) Working Group Meeting

2. Agenda
TIME AGENDA ITEM
7.30–7.40 Introductions & Interests in ACOS
7.40–7.50 Summary of work to date
7.50-8.45 Proof of Concept Study Planning
7.50–8.10
8.10–8.25
8.25–8.45
• Finalize Case Definitions of ACOS
• Select Outcome Measures
• Define next steps for the ACOS project
o Databases
o Queries
o Leads
o Timelines
8.45–9.00 Potential future ACOS projects

3. Introductions & ACOS “interests”
Lead: Jerry Krishnan
• Keith Allan*
• Mona Bafadhel
• James Bailey*
• Neil Barnes*
• Marc Berger*
• Matthias Binek*
• Gary Bird*
• Guy Brusselle
• Emmanuelle Clerisme-
Beaty*
• Walter Cleymans*
• Glenn Crater*
• Paul Dorinsky*
• Jordi Estruch*
• David Evan*
• Robert Fogel*
• Armin Furtwaengler*
• Maria Gerhardsson*
• Gokul Gopalan*
• Lynn Hagger*
• Brooke Harrow*
• Susan Johnson*
• Dorothy Keininger*
• Megumi Kizawa*
• JWH Kocks
• Marek Kokot*
• Jeannine Leuenberger*
• Mark Milton-Edwards*
• Marc Miravitlles
• Karen Mezzi*
• Gabriele Nicolini*
• Akio Niimi
• Fredrik Nyberg*
• Dirkje Postma
• David Price
• Elizabeth Regan
• Luca Richeldi
• Nicolas Roche
• Guilherme Safioti*
• Peter Schweikert*
• Ulla Seppala*
• Mark Small*
• Joan Soriano
• Robert Suruki*
• Claus Vogelmeier
• Setareh Williams*

4. Progress to date: initial discussions
Rotterdam Meeting – Working Group Objectives Identified:
• General:
o Explore the nature and various forms of ACOS
o Explore treatment response in the various forms of ACOS
o Compare the characteristics and treatment response of ACOS
and its subgroups with “pure”/”standard” asthma or COPD
• eNO-specific:
o Investigate the role of eNO as a diagnostic marker of ACOS in
pts primarily diagnosed as having COPD, taking smoking into
account
o Investigate the role of eNO as a predictor for response to
treatment with ICS in COPD, taking smoking into account
• BUT FIRST… we have to “COUNT”

5. Proof of concept study
• To evaluate agreement between case definitions of
ACOS to assess the comparability of study
populations identified as having ACOS, both:
o Within a single database, and
o Across different databases
• Success will:
o Answer an important scientific question
o Build relationships for future projects

6. Prieto-Centurion, Rolle, Au, et al. AJRCCM. 2014;190:989–995
Reference study

7. Variation considering ICD9 codes only
Prieto-Centurion, Rolle, Au, et al. AJRCCM. 2014;190:989–995

8. Prieto-Centurion, Rolle, Au, et al. AJRCCM. 2014;190:989–995
Variation by case definition

9. Differences Characteristics of Patients Who Met/
Did Not Meet the Clinical Trial Reference Standard
Characteristic
Total Sample
(n = 998)
Clinical Trial Reference Standard
Yes* (n = 560) No† (n = 438) P-value
Spirometry, post-bronchodilator, %
FEV1/FVC, 70% 61 100 11 <0.0001
FEV1, 80%
predicted
72 86 55 <0.0001
6-minute-walk distance, %**
Distance walked,
350 m
53 52 54 0.67
Comorbid conditions, %
Heart failure 18 16 22 0.01
Depression 42 36 50 <0.0001
*(A + D + E + G) and †(B + C + F) in Figure 2.
**Data for 6-minute-walk distance missing in 9%
patients (9% and 10%)
Function similar despite
lung function variability
Clinical differences
“beyond the count”
Prieto-Centurion, Rolle, Au, et al. AJRCCM. 2014;190:989–995

10. Case Definitions: Proposed
Criterion
ACOS Case Definition
1a 2a 1b 2b 1c 2c 1d 2d
Age (yrs) >40 >40 >40 >40 >40 >40 >40 >40
Post BD
FEV1/FVC
<70%
(not used as a
criterion) Any
value or no data
available
<70%
(not used as a
criterion) Any
value or no data
available
<70%
(not used as a
criterion) Any
value or no data
available
<70%
(not used as a
criterion) Any
value or no data
available
Broncho-
dilator
response
>400 ml
increase in
FEV1 post
bronchodilator
(not used as a
criterion) Any
value or no data
available
>400 ml
increase in
FEV1 post
bronchodilator
(not used as a
criterion) Any
value or no data
available
>400 ml
increase in
FEV1 post
bronchodilator
(not used as a
criterion) Any
value or no data
available
>400 ml
increase in
FEV1 post
bronchodilator
(not used as a
criterion) Any
value or no data
available
PYs smoked
(current or
past)
>10 >10 >10 >10 >10 >10 >10 >10
Physician
diagnosis
(e.g., based
on billing
diagnosis)
COPD
(including
emphysema,
COPD, or
chronic
bronchitis)
COPD
(i) “ACOS”
(ii) “Asthma
COPD
Overlap
Syndrome”
(iii) “Asthma”
and “COPD”
listed at the
same visit
(i) “ACOS”
(ii) “Asthma
COPD
Overlap
Syndrome”
(iii) “Asthma”
and “COPD”
listed at the
same visit
Asthma Asthma
No dx of
asthma,
ACOS,
COPD
No dx of
asthma,
ACOS,
COPD
Definitions with / without lung function data will enable comparison
of the differences between these patients

11. Outcome measures
• Number/proportion of patients meeting each case definition
• Level of agreement between case definitions
• Number/proportion of patients with atopy (any of the following):
o Physician diagnosis of eczema
o Physician diagnosis of allergic rhinitis
o Eosinophilia (cut off >200/μl; REG COPD blood eosinophilia study used ≥450μl)1
o Positive skin prick test
o Positive IgE to ≥1 allergen
• Number/proportion with respiratory-related exacerbations, any of the
following:
o Physician diagnosis of asthma exacerbation;
o Physician diagnosis COPD exacerbation;
o ≥1 courses of prednisolone courses in the past 12 months;
o ≥1 courses of systemic antibiotics in the past 12 months for lower respiratory
tract infection
• Treatment?
1. Kenneth D. McClatchey.Clinical Laboratory Medicine. Lippincott Williams & Wilkins, 2002

12. Next Steps…

13. Database Sources
Database Name
National / International
coverage
Source of funding Primary WG Contact
SPIROMICS U.S. NHLBI Jerry Krishnan
CONCERT U.S. NHLBI Jerry Krishnan
COSYCONET Germany BMBF Claus Vogelmeier
OPCRD UK RiRL Victoria Carter
MarketScan
(US Claims Data)
US AZ Setareh Williams
HealthCore
(US Claims Data)
US AZ Setareh Williams
Optum Humedica
(EMR)
US AZ Setareh Williams
SIDIAP-Catalonia Catalonia (Spain) Health ministery Marc Miravitlles
COBRA France
INSERM and multiple
companies
N Roche
COLIBRI France Multiple sponsors N Roche
INITIATIVES France Boehringer Ingelheim N Roche
Dutch Asthma / COPD
Service
Netherlands
routine Health care/
University Medical Center
Groningen / CERTE
diagnostic lab
Janwillem Kocks

14. Next steps & timelines
Report back on key issues:
• Suitability of dataset
• Mechanism to obtain access to data sources:
o Data query request form?
o Study outline / protocol?
o Administrative contact
• Roles & responsibilities:
o Query leads
• Working Group Call: early/mid-July

15. New Ideas and Future Projects

16. Next Meeting
Homework deadline:
Early / Mid July!