acos working group meeting
TRANSCRIPT
ASTHMA–COPD OVERLAP SYNDROME WORKING GROUP MEETING
CHAIR: Nicolas Roche
DATE: Saturday September 3rd
TIME: 10.30–11.45AM
VENUE: Royal College of General Practitioners; 30 Euston Square, London, UK
Agenda
• “Proof of Concept Study” – review o Agreed methodology – UK Pilot results – Approach 1 (claims-
based approach) – Approach 2 (similarities/differences vs
Approach 1) o Phase I extension to other databases
o Phase II – clinical implications • Other study ideas
PROOF OF CONCEPT STUDY
– AGREED METHODOLOGY – UK PILOT RESULTS
– APPROACH 2 – ROLL OUT TO OTHER DATABASES – PHASE II: CLINICAL IMPLICATIONS
Background / rationale
• 2014, GINA and GOLD published their first joint statement on Asthma-COPD Overlap Syndrome (ACOS)1
o Current thinking now recommends reference to ACO rather than ACOS based on the clinical implications of the term “syndrome”2
• Various criteria for diagnosis of ACO have been proposed2-4
• The lack of a gold standard definition is a barrier to ACO research and to understanding the biology of the condition and optimum management approaches5
1. GINA-GOLD Diagnosis of disease of chronic airflow limitation: Asthma, COPD and asthma-COPD overlap syndrome (ACOS), 2014; 2. Barnes PJ. Asthma-COPD Overlap. Chest. 2016;149:7-8; 3. Miravitlles M, et al. Arch Bronconeumol 2014; 4.Koblizek V, et al. Pap Med Fac Univ Palacky Olomouc Czech Repub 2013; 5. Kankaanranta H, et al. Basic Clin Pharmacol Toxicol. 2015;6. Postma DS, Rabe KF. NEJM 2015
Definition of ACO using electronic medical records (all 5)
1. Clinical diagnosis of COPD, asthma, or both 2. Age at least 40 years 3. Ever smoker
4. Post-BD FEV1/FVC<0.7 5. Increase in post-BD FEV1 by 12% and 200mL
Aim of the Proof of Concept Study
To inform standardised methods and tools for future ACO observational research:
• Phase I: test various smoking-related ACO population definitions evaluating their respective prevalence and
agreement within and between a number of (initially Western) population-level databases.
• Phase II: characterise the demographic and clinical characteristics of different ACO definitions to guide future ACO database study design
Population Definition Summary
Definition Criterion A: COPD only
B: COPD & ASTHMA
C: ASTHMA Only
D: Reference population
A A1 A2 A3 B B1 B2 B3 C C1 C2 C3 D D1 D2 D3
Diagnosis
Clinical diagnosis, billing “diagnosis”
Dx of COPD only at 2 different encounters over 2-yr
observation period; no dx of
asthma at any encounter over the 2-yr observation period
Dx of asthma and COPD in same encounter at 2 different
encounters over 2-yr
observation period; or asthma at 1 and COPD at a
2nd encounter over the same 2-yr observation period
Dx of asthma only at 2 different encounters over 2-year observation period; no
dx of COPD at any encounter over the 2-yr observation
period
No dx of asthma or COPD over 2-yr observation period;
patient has ≥2 healthcare
encounters during this 2-yr observation period
Age >40 years Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Smoking* Smoking history ever Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes
Obstruction Post BD FEV1/FVC <70%
Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes
Reversibility
post-BD increase in FEV1 by ≥12% and ≥200mL
Ignore
Ignore
Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore Ignore Yes
*Hx of past or current smoking, or smoking cessation advice
Yes = patient fulfils this criteria; Ignore = criterion not applied
Strengths of approach • Inclusive (sensitive) approach that enables:
o Identification of ACO in patients carrying other diagnostic labels (e.g. asthma
or COPD, both or neither)
o Can be repeated across a wide range of databases
• Use of electronic medical records data increases representativeness (i.e.
good external validity)
• Diagnoses at health encounters over the most recent 2-year period: o Allows us to start with a clinician diagnosis o Controls for secular trends in coding o Use of shorter observation period will pre-select for individuals with more
active disease
• Subsequent study phases will explore the clinical impact of these
definitions (e.g. on treatment response, health outcomes)
Limitations of approach • Some databases do not have diagnosis at each healthcare encounter, e.g. Majorica
and the Dutch Asthma & COPD database:
o Ignores diagnosis established at a visit before the 2-year observation period
o Subsequent study envisioned using clinical diagnosis established at any time
over a 5 or 10 year period
• Thresholds for some criteria (e.g., age at least 40 yrs; ever smoker; 200 mL and 12%
reversibility) are arbitrary, but based on consensus and feasibility using electronic
health records
o Alternate definitions can be explored in subsequent analyses, using clinical
sensible outcomes (e.g., treatment response) to establish appropriate criteria
o Pack-years smoked rarely coded as discrete data in electronic medical records;
reliability also unclear
• Does not capture second hand smoking exposure, biomass or occupational
exposures
UK Pilot Work
Database & Study Design Database • The UK’s Optimum Patient Care Research Database
• Fully anonymised UK primary care data
• Historical medical records for >2.9 million patients from >576 primary care practices across the UK
• Ethical approval for medical research & used for multiple peer-review publications
Study Design • Historical cohort study
• Patients with 2 years of continuous records within the observation period 1 January 2014-31 December 2015
Population Definition Summary
*Hx of past or current smoking, or smoking cessation advice
Yes = patient fulfils this criteria; Ignore = criterion not applied
Population Definition Summary
Definition Criterion A: COPD only
B: COPD & ASTHMA
C: ASTHMA Only
D: Reference population
A A1 A2 A3 B B1 B2 B3 C C1 C2 C3 D D1 D2 D3
Diagnosis
Clinical diagnosis, billing “diagnosis”
Dx of COPD only at 2 different encounters over 2-yr
observation period; no dx of
asthma at any encounter over the 2-yr observation period
Dx of asthma and COPD in same encounter at 2 different
encounters over 2-yr
observation period; or asthma at 1 and COPD at a
2nd encounter over the same 2-yr observation period
Dx of asthma only at 2 different encounters over 2-year observation period; no
dx of COPD at any encounter over the 2-yr observation
period
No dx of asthma or COPD over 2-yr observation period;
patient has ≥2 healthcare
encounters during this 2-yr observation period
Age >40 years Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Smoking* Smoking history ever Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes
Obstruction Post BD FEV1/FVC <70%
Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes
Reversibility
post-BD increase in FEV1 by ≥12% and ≥200mL
Ignore
Ignore
Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore Ignore Yes
*Hx of past or current smoking, or smoking cessation advice
Yes = patient fulfils this criteria; Ignore = criterion not applied
A: Clinical diagnosis of COPD only
B: Clinical diagnosis of asthma and COPD
C: Clinical diagnosis of Asthma only
D: Reference population
A3/A (A2/A defines
COPD)
B3/B B2/B
C3/C C2/C
D3/D D2/D
Proposed ACO Prevalence within the Populations A–D
Definition Criterion A: COPD only
B: COPD & ASTHMA
C: ASTHMA Only
D: Reference population
A A1 A2 A3 B B1 B2 B3 C C1 C2 C3 D D1 D2 D3
Diagnosis
Clinical diagnosis, billing “diagnosis
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Age >40 years Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Smoking* Smoking history ever Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes
Obstruction Post BD FEV1/FVC <70%
Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes
Reversibility
post-BD increase in FEV1 by ≥12% and ≥200mL
Ignore
Ignore
Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore
Ignore Yes Ignore Ignore Ignore Yes
All patients in the Optimum Patient Care Research Database (OPCRD)
N=2,790,704
Continuous records from 1 Jan 2014-31 Dec 2015
N= 290,024
≥2 coded healthcare encounters*
N = 233,054
n= 2,500,680 ≤2 years of continuous records in the obs’n period 1 Jan 2014-31 Dec 2015
Population A: Clinical diagnosis of
COPD only N=1,017
Population B: Clinical diagnosis of Asthma and COPD
N=398
Population C: Clinical diagnosis of
Asthma only N=857
Population D: Reference
N=1,497
*A – Clinical diagnosis of COPD only: Diagnosis of COPD only at 2 different encounters over 2-year observation period; no diagnosis of asthma at any encounter over the 2-year period; B – Clinical diagnosis of Asthma and COPD: Diagnosis of asthma and COPD in same encounter at 2 different encounters over 2-year observation period; or asthma at 1 encounter and COPD at a 2nd encounter over the same 2-year obs period; C – Clinical diagnosis of Asthma only: Diagnosis of asthma only at 2 different encounters over 2-year observation period; no diagnosis of COPD at any encounter over the 2-year period; D – Reference population: No diagnosis of asthma or COPD over 2-year observation period; patient has 2 or more healthcare encounters during this 2-year period
Non-missing data to assess age, smoking history,
obstruction and reversibility N= 3,769
n= 56,970 ≤2 coded healthcare encounters for asthma and/or COPD or neither in
the period 1 Jan 2014-31 Dec 2015
n= 229,285 No data present for ≥1 of the
following: age; smoking history; airflow obstruction; airway reversibility
A: Clinical diagnosis of COPD only
B: Clinical diagnosis of asthma and COPD
C: Clinical diagnosis of Asthma only
D: Reference population
A3/A = 20.5% B2/B = 61.8% B3/B = 32.1%
C2/C = 20.8% C3/C = 14.4%
D2/D = 19.7% D3/D = 8.0%
Proposed ACO Prevalence within the Populations A–D
Definition Criterion A: COPD only
B: COPD & ASTHMA
C: ASTHMA Only
D: Reference population
A A1 A2 A3 B B1 B2 B3 C C1 C2 C3 D D1 D2 D3
Diagnosis
Clinical diagnosis, billing “diagnosis
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Age >40 years Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Smoking* Smoking history ever Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes
Obstruction Post BD FEV1/FVC <70%
Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes
Reversibility
post-BD increase in FEV1 by ≥12% and ≥200mL
Ignore
Ignore
Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore
Ignore Yes Ignore Ignore Ignore Yes
Summary: ACO prevalence using EMR
o Approach has strengths and weaknesses
o ACO prevalence varies depending on source population – 20%* if clinical dx COPD only – 32%* or 62% if clinical dx asthma + COPD – 14%* or 21% if clinical dx asthma only – 8%* or 20% if neither dx
*ACO definition requires airflow reversibility
o Future studies
– Add cross-sectional analyses to examine how patterns of comorbid conditions vary depending on the source clinical population
– Compare results with similar cross-sectional analyses in different population-based databases
– Cohort studies to evaluate outcomes using different ACO definitions
Phase I – Approach 2 (working with clinician diagnoses)
Population Defns Approach 1 vs 2
Claims-based Approach Clinical Database Approach
Different
No Change
Approach 2 Population Defn Summary
*Hx of past or current smoking, or smoking cessation advice
Yes = patient fulfils this criteria; Ignore = criterion not applied
Definition Criterion A: COPD only
B: COPD & ASTHMA
C: ASTHMA Only
D: Reference population
A A1 A2 A3 B B1 B2 B3 C C1 C2 C3 D D1 D2 D3
Diagnosis
Clinical diagnosis, billing “diagnosis”
APPROACH 2: Physician Dx of COPD within 5-years of the 2-yr observation period; no dx
of asthma over the same period
Sensitivity analysis: repeat using a 10-year Dx window
APPROACH 2: Physician Dx of COPD and Asthma (or
ACO) within 5-years of the
2-yr observation period Sensitivity analysis: repeat
using a 10-year Dx window
APPROACH 2: Physician Dx of Asthma within 5-years of the 2-yr observation period;
no dx of COPD over the same period
Sensitivity analysis: repeat using a 10-year Dx window
APPROACH 2: No physician Dx of Asthma, COPD or ACO
within 5-years of the 2-yr
observation period Sensitivity analysis: repeat
using a 10-year Dx window
Age >40 years Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Smoking* Smoking history ever Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes Ignore Yes Yes Yes
Obstruction Post BD FEV1/FVC <70%
Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes Ignore Ignore Yes Yes
Reversibility
post-BD increase in FEV1 by ≥12% and ≥200mL
Ignore
Ignore
Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore Ignore Yes Ignore Ignore Ignore Yes
Phase I – Other Eligible Databases
Database eligibility criteria Inclusion: • To be eligible for inclusion in the study, databases must be “population-based”, requiring
them to be largely representative of the broad, heterogeneous population treated within everyday routine care in their respective country of origin. The following types of population-based studies may be eligible: o Clinical databases (e.g. primary care databases)
o Administrative/billing-based (e.g. insurance claims records) • All eligible databases must also meet the following inclusion criteria:
o Have at least two continuous years of “recent” (within the last 10 years: 2006-2015) clinical data o Have produced at least one publication in a peer reviewed journal o Include variables permiting:
– Evaluation of patient age (i.e. patient age or date/year of birth) – Evidence of current or past smoking (e.g. smoking status, pack years, prescription of
smoking cessation therapy/advice).
Exclusion: • To maximise the external validity of the study findings and avoid biasing outcomes by
working within pre-selected populations unrepresentative of the diversity of patients managed in routine clinical practice, the following will not be eligible for inclusion in the initial phase of this study:
• Clinical trials databases • Case series of patients
Database information: summary (I)
DATABASE
Details Provided Country Type of Sample Source of data – Clinical Data (EMR) or
Administrative/Billing Data
To establish the "representativeness" of the population within the database
(e.g. selected for trial inclusion; unselective convenience sampling; representative of the population as a whole)
National origin of the patients within the dataset
To indicate whether the data includes direct information about a helathcare encounter (i.e. recorded in their electronic medical records) or indirect information as coded for insurance or
administrative claims purposes
Indication of the ability of each dataset to identify the 12 populations (COPD A–C; Asthma A–C; ACOS A–C and
Control A–C) proposed for revaluation
Dutch ASTHMA / COPD Service
People with respiratory symptoms treated by their GP. With or without inhalation medication. Both diagnostic
and follow up. The Netherlands
Electronic medical record, but not all visits are recorded for other encounters other than the visits to the A/C service
12 of 12
Adelphi Respiratory Disease Specific Programme
Convenience sample of consecutive outpatients visiting their physician (both primary and specialist
care settings)
France, Germany, Italy, Spain, UK, USA,
Japan, China, Canada Electronic Medical Records
9 of 12 • Unable to identify the 3x Control Populations as
survey only includes patients with a asthma or COPD diagnosis
Optimum Patient Care Research Database (OPCRD)
Patients registered at UK primary care practices that receive the Optimum Patient Care Clinical Service. Enriched sample of patients with ≥1 prescription or
diagnosis of obstructive lung disease (as initially only OLD pts received the OPC review)
UK Electronic Medical Records 12 of 12
• Only a subgroup of patients will have reversibility data (required to evaluate the 4 x C Populations)
SIDIAP
Records for patients treated by the Catalan Health Institute (CHI) – the chief provider of medical services in Catalonia. 5,8 million patients (>80% population); 274 Primary Care Centres in Catalonia; 3,400 GPs
Spain (Catalonia Region) Electronic Medical Records 12 of 12
MAJOrca Real-world Investigation in COPD and Asthma database (MAJORICA)
Combined data from the primary care system (e-SIAP), the hospital claims system (FIC), and the
pharmacy database (RELE) in the Balearics, Spain. Covers all health-care utilisation of the permanent inhabitants of the Balearics (≥1.1 million people)
Majorca Electronic medical records 12 of 12 (TBC)
PCORnet Common Data Model
Population-based (anyone with ≥1 healthcare encounter for any reason at contributing healthcare
facilities) USA Electronic Health Records 12 of 12
HealthCore
Automated computerized claims data and enrollment for approximately 51 million lives with at least medical
enrollment, and nearly 33 million lives with medical and pharmacy enrollment information from 14 Blue Cross and/or Blue Shield (BCBS) licensed plans
USA
Administrative / Billing Data +
linked medical records (from EMR review study)
12 of 12 • All A populations will be identifiable
• All B and C populations (requiring reversibility and obstruction data) will only be identifiable in those
with linked claims + chart review data
MarketScan Commercial, Medicare Supplemental, and Medicaid
contain >200 million patients since 1995. USA Administrative/Billing Data
4 of 12 • Only group A can be evaluated and only based on codes for smoking cessation (i.e. no smoking code, but inference of smoking history based on code for
smoking cessation advice)
Optum Humedica
Proprietary database containing health plan administrative and claims records. The data derive
from commercial health plans and Medicare Advantage programs.
USA Adminsitrative/Billing Data
4 of 12 • Only group A can be evaluated and only based on codes for smoking cessation (i.e. no smoking code, but inference of smoking history based on code for
smoking cessation advice)
Information has not been provided for: COBRA (France); COLIBRI (France); INITIATIVES (France); SPIROMICS (USA); CONCERT(USA); COSYCONET (Germany). These databases do not meet the eligibility criteria of “random or representative samples” so will not be eligible for inclusion in the first phase of this population characterization and agreement study
Database information: summary (II)
DATABASE
Evaluation year
Number of unique patients with ≥1 HCP contact
(for asthma, COPD, both of ACOS) in the evaluation year
Number of unique patients with ≥2 HCP contacts
(for asthma, COPD, both of ACOS) in the evaluation year
Number of unique patients with ≥1 HCP contact
not coded for asthma, ACOS or COPD in the evaluation year
Number of unique patients with ≥2 HCP contact
(for any reason) in evaluation year
Latest 12-month period for which data are available
This criterion is designed to capture the total number of asthma, COPD and ACOS
patients in the database within the proposed 12-month evaluation period
Patients with ACOS based co-coding of asthma and COPD within a 12-month window & presumptive diagnosis of
asthma or COPD in patients 2 consistent asthma or COPD codes in the 12-month
period
Total number of potential control patients in the database within the
proposed 12-month evaluation period
Number of potential control patients within the database – those with ≥2 encounters, neither of which have a
diagnosis of Asthma, COPD or ACOS in the 12-month period
Dutch ASTHMA / COPD Service Jan 2013–31 Dec 2014
Asthma: 1694 COPD: 946 ACOS: 324
Unnecessary as code for ACOS exists within the Netherlands Control: 3918 TBC
Adelphi Respiratory Disease Specific Programme
Dec 2014–Nov 2015 Asthma: 5,501 COPD: 5,071
ACOS: 449 (physician-confirmed)
0; database contains pt data from 1 encounter only Control: not available (n=0) Control: not available (n=0)
Optimum Patient Care Research Database (OPCRD)
March 31 2011 – April 1 2012
Asthma, COPD or Both: 119,540 Asthma: subset of above COPD: subset of above ACOS: subset of above
Asthma, COPD or Both: 40726 Asthma: subset of above COPD: subset of above ACOS: subset of above
Control: 40726 TBC
SIDIAP Jan 07 2013–Dec 31 2013
Asthma, COPD or Both: 275,615 Asthma: subset of above COPD: subset of above ACOS: subset of above
Asthma, COPD or Both: 174,180 Asthma: subset of above COPD: subset of above ACOS: subset of above
TBC TBC
MAJORICA
1 January 2014–31 December 2014
(data collection period
2011-2014)
based on ICD ever Asthma: 45,800 COPD: 27,871 ACOS: 5,093
Asthma: <45,800 COPD: <27,871 ACOS: <5100
Subset of 68,578 Subset of 68,578
PCORnet Common Data Model
1 January 2014 – 31 December 2014
All patients: 100,000,000 million records (total)
Asthma: ~6 million asthma patients (based on prevalence estimate);
COPD: ~6 million asthma patients (based on prevalence estimate);
ACOS: TBC
Asthma: TBC COPD: TBC ACOS: TBC
TBC TBC
HealthCore May 1 2014 – April 30 2015
Asthma, COPD or Both: 603,001 (ICD-9 codes 491.xx–496.xx)
Asthma: subset of above COPD: subset of above ACOS: subset of above
Asthma, COPD or Both: 312,075 (ICD-9 codes 491.xx–496.xx)
Asthma: subset of above COPD: subset of above ACOS: subset of above
Control: not available (n=0) Control: not available (n=0)
MarketScan Jan 01 2013–Dec 31 2013
Asthma, COPD or Both: 1,998,509 Asthma: subset of above COPD: subset of above ACOS: subset of above
Asthma, COPD or Both: 1,436,631
Asthma: subset of above COPD: subset of above ACOS: subset of above
Control: not available (n=0) Control: not available (n=0)
Optum Humedica Jan 01 2013–Dec 31 2013
Asthma, COPD or Both: 1,248,091 Asthma: subset of above COPD: subset of above ACOS: subset of above
Asthma, COPD or Both: 883,404 Asthma: subset of above COPD: subset of above ACOS: subset of above
Control: not available (n=0) Control: not available (n=0)
Available datasets: summary DATABASE Time for completion of Stage 1 Cost for completion of Stage 1
1. Dutch ASTHMA / COPD Service 8 weeks EUR 10,000
(~2 months post-doc salary)
2. Adelphi Respiratory Disease Specific Programme ≤ 4 weeks £0
3. Optimum Patient Care Research Database (OPCRD) 4-6 weeks £10,000
4. SIDIAP 6 weeks EUR 1,500
5. MAJORICA TBC TBC
6. PCORnet Common Data Model Data available Sept 2016;
analysis estimate ? TBC
7. HealthCore 3 weeks $4,167
(if manual programming required)
8. MarketScan "1 day" ?
9. Optum Humedica "1 day" ?
Which databases should be included in the Protocol?
?
✓
X Valuable for repeat analysis and validation when available
Phase II – Clinical Implications
Demographics A: Clinical diagnosis of
COPD only
B: Clinical diagnosis of
asthma and COPD
C: Clinical diagnosis of Asthma only
D: Reference population
1,017 398 857 1,497Male 561 (55.2) 172 (43.2) 338 (39.4) 695 (46.4)Female 456 (44.8) 226 (56.8) 519 (60.6) 802 (53.6)
Age Mean (SD) 71.0 (9.7) 68.7 (10.8) 59.7 (16.6) 58.6 (17.5)Non-smoker n (%) 75 (7.37) 65 (16.3) 386 (45.0) 598 (40.0)Current smoker n (%) 297 (29.2) 110 (27.6) 130 (15.2) 331 (22.0)Ex-smoker n (%) 645 (63.4) 223 (56.0) 341 (39.8) 568 (37.9)Underweight, n (%) 48 (4.7) 13 (3.3) 14 (1.6) 36 (2.4)Healthy weight, n (%) 328 (32.3) 116 (29.2) 225 (26.3) 430 (28.7)Overweight, n (%) 342 (33.6) 123 (30.9) 276 (32.2) 467 (31.2)Obese, n (%) 296 (29.1) 145 (36.4) 340 (39.7) 541 (36.1)Missing, n (%) 3 (0.3) 1 (0.25) 2 (0.2) 23 (1.5)Cardiovascular, n (%) 458 (45.0) 148 (37.2) 240 (28.0) 441 (29.5)IHD, n (%) 235 (23.1) 82 (20.6) 107 (12.5) 201 (13.4)Heart Failure, n (%) 55 (5.4) 22 (5.5) 17 (2.0) 38 (2.5)Hypertension, n (%) 303 (29.8) 98 (24.6) 214 (25.0) 263 (17.6)Diabetes, n (%) 565 (55.6) 204 (51.3) 413 (48.2) 673 (45.0)Bronchiectasis, n (%) 51 (5.0) 27 (6.8) 25 (2.9) 27 (1.8)Rhinitis, n (%) 161 (15.8) 102 (25.6) 258 (30.1) 263 (17.6)Rhinitis (active), n (%) 77 (7.6) 58 (14.6) 156 (18.2) 126 (8.4)Eczema, n (%) 246 (24.2) 102 (25.6) 228 (26.6) 301 (20.1)Osteoporosis, n (%) 124 (12.2) 66 (16.6) 92 (10.7) 120 (8.0)GERD, n (%) 203 (20.0) 82 (20.6) 151 (17.6) 221 (14.8)GERD (active), n (%) 161 (15.8) 66 (16.6) 126 (14.7) 165 (11.0)Cerebrovascular, n (%) 114 (11.2) 24 (6.0) 48 (5.6) 108 (7.2)Chronic Kidney Disease, n (%) 124 (12.2) 52 (13.1) 71 (8.3) 122 (8.2)Myocardial Infarction, n (%) 89 (8.8) 38 (9.6) 41 (4.8) 59 (3.9)Anxiety and Depression, n (%) 111 (10.9) 45 (11.3) 99 (11.6) 150 (10.0)
Comorbidities
Total Population
Gender
Smoking History
BMI
Clinical Outcomes (per protocol) • Presence of atopy, defined as ≥1 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) o Positive skin prick test o Positive to ≥1 allergen
• Smoking history: o Pack years, where available o Duration of smoking, defined as:
– For ex-smokers: years between first current smoking / active smoking code and non-smoker or smoking cessation code
– For current smokers: years between first current smoking record and year of study / cross sectional analysis
• Historical “onset” of disease: o Duration of asthma, defined as years between first recorded asthma diagnosis / encounter
and year of study / cross-sectional analysis o Duration of COPD, defined as years between first recorded COPD diagnosis / encounter
and year of study / cross-sectional analysis o Time between first recorded asthma diagnosis/encounter and first COPD diagnosis/
encounter
Clinical Outcomes (per protocol) • COPD severity: in terms of GOLD status (where evaluable)
• Comorbidities: o Cardiovascular disease o Other chronic respiratory conditions o Diabetes o Gastroesophageal reflux disease (GERD) o Charleson Comorbidity Index o Lung Cancer
• Respiratory treatment: Current management (i.e. during the phase 1 24-month cross-sectional analysis period), records (prescriptions for / claims data) for the following, and combinations of the following, will be examined: SABA, SAMA, LABA, LAMA, ICS, theophylline, LTRA, Roflumilast, chronic azithromycin.
• Exacerbations: Functional consequences of different definitions, (i) proportion of patients and (ii) annualised rate of respiratory-related exacerbations over the phase 1 24-month evaluation period, where a respiratory-related event is defined as any of the following: o Physician diagnosis of asthma exacerbation; o Physician diagnosis COPD exacerbation; o Accident & Emergency / Emergency Room attendance with a lower respiratory code o Hospital admission with a lower respiratory code o A course of prednisolone o A course of systemic antibiotics coded for a lower respiratory tract infection