Education event: COPD & its comorbidities

28 April 2018, RACV City Club, Melbourne

Education event: COPD & its comorbidities

Activity no: 125314

Before we begin

Emergency exists Rest rooms Mobile phones

OPC Support and Collaborations

Gold Sponsors Partner

Agenda – part 1

Time Presentation / Activity Presenter

9.45 – 10.00 am Introduction - Prof David Price

10.00 – 10.30 amGOLD and Australian COPDX guidelines, Australian Best Practice Guidelines for

Diabetes, Guidelines for the prevention, detection and management of chronic heart

failure in Australia: considering recent evidence

- Prof Peter Frith - Dr Anita Sharma -Prof Merlin Thomas

10.30 – 10.45 am Common co-morbidities of COPD, Heart Failure and Diabetes - Prof Peter Frith

10.45 – 11:00 amExacerbations of COPD: current state of the art in terms of differential diagnosis (vs HF),

treatment and prevention- Prof David Price

11.00 – 11.30 am Review of delegate pre-disposing activity (COPD with a co-morbidity) – Morning tea

- Prof David Price - Prof Peter Frith - Dr

Anita Sharma - Dr Kerry Hancock - Prof

Merlin Thomas

11.30 – 11.45 am Psychological factors in COPD - Dr Kerry Hancock

11.45 – 12.15 pmPanel Discussion – Inadequate and over treatment of COPD, Heart Failure and Diabetes

and implications for clinical practice.

Prof David Price - Prof Peter Frith - Dr

Anita Sharma - Dr Kerry Hancock -

Prof Merlin Thomas

12.15 – 12.45 pmGroup Discussion -Continue review of delegate pre-disposing activity (COPD, Heart

Failure, Diabetes case studies) in light of panel discussion

Prof David Price - Prof Peter Frith

- Dr Anita Sharma - Dr Kerry Hancock

- Prof Merlin Thomas

12:45 – 1.15 pm Lunch

Agenda – part 2

Time Presentation / Activity Presenter

1.15 – 1.45 pmPanel Discussion

Referrals and Investigations for COPD, Heart Failure and Diabetes. When to refer,

appropriate use of tests and biomarkers for guiding treatment (stepping up and down)

- Prof David Price - Prof Peter Frith -

Dr Anita Sharma - Dr Kerry Hancock -

Prof Merlin Thomas

1.45 – 2.45 pm

Workshop 1: Inhaler technique in COPD

………………………………………………………...………………………………………………...

Workshop 2: Interpreting spirometry

- W1: Prof David Price + nurses (LFA)

- W2: Prof Peter Frith + Dr Kerry Hancock

2.45 – 3.30 pm

Case studies

Case study 1: COPD and heart failure (role of rehab)

Case study 2: COPD and Diabetes

- Dr Anita Sharma + Prof David Price

- Dr Merlin Thomas + Prof David Price

3.30 – 3.45 pm Afternoon Tea

3.45 – 4.30 pm Discussions of learnings from meeting and post meeting follow-ups- Prof David Price

4.30 pm Event close – Exit Venue

Introduction

Our panel

Kerry Hancock

Anita Sharma Merlin ThomasPeter Frith

David Price

Dr Kerry Hancock - Principal, Chandlers Hill Surgery, Happy Valley SA;

Executive member COPD National Program, Lung Foundation Australia;

Chair, RACGP Respiratory Medicine Specific Interest Network

Prof Merlin Thomas - physician scientist in the Department of Diabetes,

Monash University, Melbourne, Australia

Prof David Price - Professor David Price is the founder and director of

OPC (Australia and UK)

Dr Peter Frith - Professor in Respiratory Medicine at Flinders University

in Adelaide, Adjunct Professor in Health Sciences at University of South

Australia, and he serves on the Boards of Directors of GOLD and of Lung

Foundation Australia (LFA)

Dr Anita Sharma - principal at Platinum Medical Centre

What COPD Looks Like Today

OPC Collaborations

Guidelines: COPD, Diabetes and Heart Failure

Chair of session: Peter Frith

Heart Failure Guidelines For Primary Care in 2018

Dr Anita Shama MBBS FRACGP

Heart Failure

HF: heart failure https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Acute-and-Chronic-Heart-Failure

• HF is complex syndrome, often underdiagnosed and undertreated due in part to

the non specific nature of presentation and presence of other co-morbidities that

compete for attention.

• HF is however ‘A SILENT KILLER’ associated with high mortality, reduced quality-

of-life, and high cost to the community.

• Mortality from HF parallels or even exceeds some cancer associated mortality:

50% of HF patients are dead at 5 years!

Heart Failure

https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Acute-

and-Chronic-Heart-Failure

• Optimum HF management involves both non-pharmacological and pharmacological

therapies and a patient centred mulit-disciplinary plan, coordinated by the GP, and

ideally involving other HCPs such as HF specialists (cardiologists/HF nurses),

dietitians, exercise therapists, social workers, psychologists and pharmacists.

• HF is commonly classified according to assessment of LVEF. Patients are generally

described as having HF with normal or preserved LVEF (HFpEF) [LVEF ≥50%] or HF

reduced LVEF (HFrEF) [LVEF of <40%]. There is now also an entity HFmEF that

refers to patients with EF in the grey zone (40-49%)

EF: ejection fraction; GP: general practitioner; HCP: health care practitioner; HF:

heart failure; HFmEF: heart failure and midrange ejection fraction; HFpEF: heart

failure with preserved ejection fraction; LVEF: left ventricular ejection fraction

Heart Failure Patients Suffer From

Recurrent Hospitalisation

1. Gheorghiade M, et al. Am J Cardiol 2005;96:11-17LV: left ventricular

PATIENT’S

JOURNEY

With each hospitalisation, there is likely myocardial and renal damage which contributes to progressive LV or renal dysfunction, leading to an inevitable downward spiral.1

Diagnostic

Algorithm for CHF

BNP: B-type natriuretic peptide; CHF: congestive heart failure;

JVP: jugular venous pressure; LVEF: left ventricular ejection

fraction; MI: myocardial infarction; PND: paroxysmal nocturnal

dyspnoea

HF Current Guidelines in Australia (LVEF<40%)

Heart foundation guidelines for

the prevention, detection and

management of CHF in

Australia from October 2011

NYHA IVNYHA II to III

Mortality in HFrEF Remains High Despite the

Introduction of New Therapies that Improve Survival

1. McMurray et al. Eur Heart J 2012;33:1787–847; 2. SOLVD Investigators. N Engl J Med 1991;325:293–302;

3. CIBIS-II Investigators. Lancet 1999;353:9–13; 4. Pitt et al. N Engl J Med 1999;341:709-17;–50;

5. Granger et al. Lancet 2003;362:772–6; 6. Go et al. Circulation 2014;129:e28-e292;

7. Yancy et al. Circulation 2013;128:e240–327; 8. Levy et al. N Engl J Med 2002;347:1397–402HF: heart failure; HFrEF: heart failure with reduced ejection fraction

• Survival rates in chronic HF have improved with the introduction of new therapies1

16%(4.5% ARR; mean follow up of

41.4 months)

SOLVD-T1,2

34%(5.5% ARR; mean follow up

of 1.3 years)

CIBIS-II3

Reducti

on in r

ela

tive

risk o

f

mort

ality

vs p

lacebo

30%(11.0% ARR; mean follow

up of 24 months)

RALES4

17%(3.0% ARR; median follow-

up of 33.7 months)

CHARM-

Alternative5

ACEI* β-blocker* MRA* ARB*

• However, significant mortality remains: ~50% of patients die within 5 years of diagnosis6–8

*On top of standard therapy at the time of study (except in CHARM-Alternative where background ACEI therapy was excluded). Patient populations varied between trials and as such relative risk

reductions cannot be directly compared. SOLVD (Studies of Left Ventricular Dysfunction), CIBIS-II (Cardiac Insufficiency Bisoprolol Study II) and RALES (Randomized Aldactone Evaluation Study)

enrolled chronic HF patients with LVEF≤35%. CHARM-Alternative (Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity) enrolled chronic HF patients with LVEF≤40%

Take Home Message

HF: heart failure; NYHA: New York Heart Association https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Acute-and-Chronic-Heart-Failure

• Diagnose HF early (targeted approach) and start treatment in early stage of

disease (NYHA II and early NYHA III)

• Optimise background therapies Ace-I, b-blockers, diuretics, MRAs

• Consider option of ARNI if symptoms persist- ‘STABLE’ is not good enough

• Do not forget lifestyle measures (fluid/salt balance, nutrition, exercise,

psychological support, etc.)

• HF patients are ‘fragile’, and at risk of sudden decompensation hospitalisation,

and sudden death

Diabetes Guidelines

Professor Merlin Thomas

Type 2 diabetes is the most likely diagnosis if:

FBG ≥7.0 mmol/L*

OR

HbA1c ≥6.5% (48 mmol/mol)*

OR

2 hour postprandial glucose ≥11 mmol/L on OGTT

*First result must be confirmed with FBG or second test

DIAGNOSTIC CRITERIA FOR TYPE 2 DIABETES

RACGP. General practice management of type 2 diabetes. 2014–15. p14.

Diabetes* increases the risk of CV events

Emerging Risk Factors Collaboration, Lancet 2010;375:2215–2222.

Coronary heart disease

Coronary death

Non-fatal MI

Cerebrovascular disease

Ischaemic stroke

Haemorrhagic stroke

Unclassified stroke

Other vascular deaths

2.00 (1.83–2.19)

2.31 (2.05–2.60)

1.82 (1.64–2.03)

2.27 (1.95–2.65)

1.56 (1.19–2.05)

1.84 (1.59–2.13)

1.73 (1.51–1.98)

HR (95% CI)

26,505

11,556

14,741

3799

1183

4973

3826

Cases (n)

1 2 4Hazard ratio (diabetes vs no diabetes)

Outcome

2

* independent to age, smoking status, body mass index and systolic blood pressure

DM

Does the patient have macrovascular disease?

− Cardiac ischemia (silent or overt)

− Peripheral arterial disease

− Cerebrovascular/carotid disease

AND if the patient is NOT at glycemic target

Does the patient have

microvascular disease?

− Retinopathy

− Kidney disease (ACR≥2.0)

− Neuropathy

Is the patient...

− age ≥55 with additional CV risk factors?

− age ≥40?− age ≥30, and diabetes >15 years?

− warranted for statin therapy based on the Canadian

Statin1

+

ACEi/ARB2

+

ASA3

Liraglutide, Empagliflozin or Canagliflozin4

Statin1

+

ACEi/ARB2

Statin1

YES

YES

YES

NO

N

O

Circulation (2016)

Modern diabetes control has really changed the risk of complications

STENO-2

7.8 years

∆Median

survival

7.9 years

Gæde, et al Diabetologia (2016)

Intensive

Standard

Years since randomisation

Cu

mu

lati

ve

Mo

rta

lity

In some countries, older adults are clearly in the majority

0

50

100

150

200

250

300

350

20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+Tho

usa

nd

s

>50% of adults

with diabetes are 65+

Australia

In the aged, the choice of agent should focus on drug safety, especially

protecting against hypoglycaemia, heart failure, renal dysfunction, bone

fractures and drug interactions. Strategies specifically minimising the

risk of low blood glucose may be preferred.

Common comorbidities of COPD – Heart

Failure & Diabetes

Chair of session: Peter Frith

COPD & its Comorbiditiesfor OPC Australia

Peter Frith

Lung Foundation Australia

Global Initiative for chronic Obstructive Lung Disease

Flinders University College of Medicine & Public Health

University of South Australia Health Sciences Faculty

EmphysemaDominant

Chronic Bacteria

Bronchiectasis

COPDWith frequentExacerbations

COPD. A complex spectrum of phenotypes

COPD withoutfrequent

exacerbations

NeutrophilicAsthma

Chronic BronchitisPhenotype

Asthma-COPD

Overlap

COPD with Eosinophilia

LAMA + LABA

ICS + LABA or LAMA

Antibiotics

Relevant vaccinationsPulmonary rehabilitation / maintain activity

Avoid smoking, pollution and infections

COPD & Comorbid diseases

• COPD is very common (1 in 7 of Australians over age 45)

• Other chronic conditions are also common• Cardiovascular and cerebrovascular diseases

• Diabetes mellitus and endocrine disorders

• Osteoporosis and degenerative joint diseases

• Asthma

• Sleep breathing disorders

• Lifestyle factors are shared across some of these

• COPD has not only shared prevalence but also has systemic effects

COPD is not all smoking-relatedPrimary and secondary prevention are not uniform Comorbidities are not uniform

Agusti A & Faner R. Lancet Respir Med 2018 Feb 26

P Frith. Med Today 2013; 14:36-44

Comorbidities measured in COPD patients

MC Smith, JP Wrobel. Internat J COPD 2014; 9:871-888

Comorbidities can occur with any COPD severityA Agusti, et al. Respir Res 2010; 11:122

Co-occurrence worsens outcomes in most conditionsD Mascarenhas, et al. Am Heart J 2008; 155:521-525

Exacerbation risk and severity increase with comorbidityJA Westerik, et al. Respir Res 2017; 18:31

Principles of managing COPD

• Primary prevention• Target all smoking• Reduce home and atmospheric air pollution

• Detect COPD in all who really have it• Targeted screening• Confirm and quantify airways obstruction with spirometry• Clarify comorbid symptom confusion

• Control symptoms• Optimise bronchodilators (drugs and devices) for the individual• Enhance exercise capacity and willingness to be active

• Reduce risks of deterioration• Prevent and reduce impact of exacerbations• Detect and treat exacerbations early and well• Prolong life• Avoid harm (respiratory and comorbidities)

Severe COPD exacerbations are deadly

S Suissa et al. Thorax 2012; 67: 957-63

Kaplan-Meier survival function for the cohort of 73,106 patients from the time of their firstever hospitalisation for a COPD exacerbation over the 17-year follow-up period.

Risk of AMI and Stroke increase post COPD exacerbation

0.0

0.5

1.0

1.5

2.0

2.5

1-5 days 6-10 days 11-15 days 16-49 days

IHDStoke

Rel

ativ

e R

isk

Adapted from G Donaldson et al. Chest 2010; 137(5): 1091-97

COPD and Chronic Heart Failure have similar symptoms

DJA Janssen et al. J Pall Med 2011;14:735-743

(n=105) (n=80)

Mean age=66.3[SD 9.2], 61.9% male Mean age=76.2[SD 8.3], 67.5% male

Indexes developed to prognosticate in COPD

• Considering COPD alone• BODE (BMI, FEV1, mMRC dyspnea, exercise capacity)

• BR Celli et al. NEJM 2004; 350:1005-1012

• ADO (Age, mMRC dyspnea, FEV1)• MA Puhan et al. Lancet 2009; 374:704-711

• DOSE (mMRC dyspnea, FEV1, smoking status, exacerbation frequency)• RC Jones et al. Am J Respir Crit Care Med 2009; 180:1189-1195

• Including Comorbidites• COTE

• M Divo et al. Am J Respir Crit Care Med 2012; 186:155-161

Anxiety (6 points) Lung, oeasophageal, pancreas cancer (6)

Other cancers (2) Hepatic cirrhosis (2)

Atrial Fibrillation/flutter (2) Diabetes with neuropathy (2)

Pulmonary fibrosis (2) Chronic heart failure (1)

Gastric/Duodenal ulcers (1) Coronary artery disease (1)

Complexity of care vs complexity of lung disease & comorbidites

LEGW Vanfleteren et al. Eur Respir J 2017; 49:1601696

Management of COPD beyond the lungs

LEGW Vanfleteren et al. Lancet Respir Med 2016; 4:911-924

Management of COPD beyond the lungs

LEGW Vanfleteren et al. Lancet Respir Med 2016; 4:911-924

Self management interventions for COPD DO NOT reduce exacerbations of COPD

Odds Ratio = 0.01 (-0.28, 0.29) A Lenferink et al. Cochrane Database Syst Rev 2015; 10.1002/12651858.CD011682

Self management interventions for COPD DO reduce respiratory hospitalisations

Odds Ratio = 0.69 (0.51, 0.94)

A Lenferink et al. Cochrane Database Syst Rev 2015; 10.1002/12651858.CD011682

Medication regimen complexity affects outcomes in COPD combined with non-COPD diagnoses

• Dosage, device complexity and timing of respiratory medications

• Dosage, timing and routes of non-COPD medications

• Medication regimen complexity index (MRCI)• J George et al. Ann Pharmacother 2004; 38:1369-1376

• RECOMMENDATIONS

• Minimise multiple dosing frequencies

• Minimise numbers of and harmonise inhaler devices

• Time non-COPD medications with COPD medication dosing

• NA Negewo et al. Internat J COPD 2017; 12:2929-2942

Biomarkers for patients with COPD in primary care

• ‘C’ - Diagnosis & differential (acute and stable phase symptoms)• Spirometry; spirometry reversibility

• Blood eosinophils; FeNO

• BNP, procalcitonin, CRP, low interleukin-15, high interleukin-8

• ‘O’ - Management• Future risk - History of moderate and severe exacerbations; blood eosinophils

• Current impact - Level of symptom impact (mMRC; CAT; CCQ; SGRQ; CRQ)

• Comorbidities

• ‘P’ - Prognosis• Spirometry; pO2; pCO2; BODE Index; ADO; DOSE; AKPS; fibrinogen

• Comorbidities

• ‘X’ - Exacerbation • Symptom increment

What to look out for at a 14-day post-discharge check-up to predict early unplanned readmission &/or refer to specialist

• COPD severity scores

• Symptoms out of proportion to spirometry or unusual/unexpected• Heart failure / heart disease• Anaemia• Asthma• Lung cancer

• Blood eosinophil count (>350)

• Adherence to prescribed bronchodilators & correct use of device

• Exacerbations in the previous year

• Possession & use of action plans

• Pack-years and duration of smoking and ongoing smoking

• Level of airways obstruction (FEV1 % predicted)

Exacerbations of COPD and Heart Failure: current state of the art in terms of differential diagnosis, treatment

and prevention

Chair of session: David Price

Exacerbations of COPD: current state of the art in terms of differential diagnosis vs heart

failure, treatment and prevention

Chair of session: David Price

CI: confidence interval; OR: odds ratio

Jones R, et al. Lancet Respir Med 2014;2:267-276;

Wedzicha JA, Seemungal TA. Lancet 2007;370:786-96

‘Exacerbations’ Before Diagnosis to After Diagnosis

OR (95% CI)

N = 38, 859

First year after diagnosis 3.16 (3.01, 3.32)*

Second year after diagnosis 2.81 (2.67, 2.96)**

* Adjusted for age, gender, place of diagnosis & year of diagnosis

** Adjusted for age, gender & year of diagnosis

Patients with frequent exacerbations

Higher mortality

Greater airway

inflammation

Poorer quality

of life

Faster decline

in lung function

More hospital

admissions

COPD: chronic obstructive pulmonary disease Kerkhof M, Price DB et al. Int J Chron Obstruct Pulmon Dis 2015;10:2439–2450

COPD Exacerbation Risk Prediction

Risk factors associated with 2+ exacerbations in COPD

MRC: medical research council Price D, et al. Unpublished data

Patients with COPD and HF are More Breathless

than Patients with COPD Alone

Study endpoint: time to first LABA or LAMA prescription after COPD diagnosis

Patients are censored at the end of patient records (extraction or leaving practice), death, or heart failure diagnosis after COPD diagnosis in the COPD only cohort

COPD: chronic obstructive pulmonary disease; HF: heart failure Lipworth B, Price D et al. Heart 2016; 102(23): 1934

Underuse of Beta-Blockers in Patients with HF and COPD

Prescription of BB and ACEI/ARB for patients with HF and COPD according to inhaler therapy

Prescription of BB and ACEI/ARB for patients with HF alone versus patients with HF and COPD

ICS: inhaled corticosteroid; LABA: long-acting β2-agonist;

LAMA: long-acting muscarinic antagonist

1. Yang et al., The COPD-X Plan 2016, Version 2.46; Lung Foundation Australia

2. Australian Pharmaceutical Benefits Scheme, 2017 http://www.pbs.gov.au/pbs/home

3. Harrison et al. Intern Med J., 2017;47:1310–13

COPD and ICS in Australia

COPD and ICS indication in Australia

Inhaled corticosteroids should be considered in patients:• with post-bronchodilator FEV1 <50% predicted and who experience >2 exacerbations in 12 months 1,2

ICS monotherapy is not indicated in COPD 1,2

In patients with coexisting asthma and COPD, ICS monotherapy can sometimes be used together with LAMA, LABA or LAMA/LABA fixed dose combination inhalers (as the ICS would be indicated for asthma) 1,2

But in reality...Of 707 COPD patients identified from the lung function test database at a tertiary Australian hospital;

52.4% of patients with a post-bronchodilator FEV1 ≥50% were prescribed an ICS 3

...inappropriate use of ICS in Australia?

http://www.pbs.gov.au/pbs/home

Yang et al., The COPD-X Plan 2017, Version 2.52; Lung Foundation Australia

Treatment of COPD Exacerbations: COPD-X Guidelines

GOLD 2018 – Treatment of COPD Exacerbations

GOLD 2018 (http://goldcopd.org/)

Change in GOLD recommendations: LABA/LAMA as preferred

treatment for the majority of COPD patients

PDE4-inh = phosphodiesterase 4 inhibitor

Adapted from GOLD 2016;

GOLD 2018 (© 2018 Global Strategy for Diagnosis, Management and Prevention

of COPD all rights reserved. Use is by express license from the owner)

GOLD 1

GOLD 2

GOLD 3

GOLD 4

CAT ≥10

mMRC ≥2

CAT <10

mMRC

0−1N

o. o

f exa

ce

rba

tion

s/y

ea

r

≥2

or ≥1

leading to

hospital

admission

Based on combined assessment of airflow limitation,

symptoms and exacerbations

0

1 (not

leading to

hospital

admissio

n)

ICS + LABA or LAMA ICS + LABA and/or

LAMA

LABA and LAMA or

LABA and PDE4-inh or

LAMA and PDE4-inh

ICS+LABA and LAMA or

ICS+LABA and PDE4-

inh or

LABA and LAMA or

LAMA and PDE4-inh

SABA or SAMA p.r.n. LABA or LAMA

LABA or LAMA or

SABA and SAMA LABA and LAMA

Recommended first choice

Alternative choice

(Symptoms)

(Breathlessness)

GO

LD

cla

ssific

atio

n o

f a

irflo

w lim

ita

tio

n GOLD Group C GOLD Group D

GOLD Group A GOLD Group B

Group A Group B

Group C Group D

A bronchodilator

Continue, stop or

try alternative

class

of bronchodilator

Evaluate effectA long-acting

bronchodilator

(LABA or LAMA)

LAMA + LABA

Persistent

symptoms

LAMA +

LABA

Further

exacerbation(s)

LABA +

ICS

LAMA +

LABA

Consider

roflumilast if FEV1

<50% pred. and

patient has chronic

bronchitis

Further

exacerbation(s)

Consider

macrolide (in

former smokers)

LAM

ALABA

+ ICS

LAMA +

LABA + ICS

Further

exacerbation(s)

Persistent

symptoms/further

exacerbations

LAMA

2016 2018

Preferred

treatment

Significant improvement in lung function1 and rate of

exacerbations2 with LABA/LAMA vs ICS/LABA

• SFC: salmeterol/fluticasone propionate1. Vogelmeier et al. Lancet Respir Med 2013

2. Wedzicha JA, et al. N Engl J Med 2016

73 mL,

p<0.0001

123 mL,

p<0.0001 138 mL,

p<0.0001

1.60 1.59 1.561.68 1.71 1.70

FE

V1

AU

C 0

–1

2h

( L

)

Day 1 Week 12 Week 26

Primary endpoint

1.7

1.6

1.5

1.4

1.8

1.60 1.68 1.59 1.71 1.56 1.70

SFC 50/500 μg b.i.d.

(n=264)IND/GLY 110/50 μg q.d. (n=258)

Patients with a history of a COPD exacerbation needing treatment with antibiotics, systemic

corticosteroids or hospitalization in the year leading up to and including randomization were excluded. Data are least-squares mean ± SE

1.19 0.98

RR (95% CI)

0.83 (0.75, 0.91),

P<0.001

IND/GLY 110/50 μg q.d. (n=1651)SFC 50/500 μg b.i.d. (n=1656)

17% reduction

1.5

Mo

de

rate

or

se

ve

re

exa

ce

rba

tio

ns (

an

nu

aliz

ed

ra

te)

0.75

1.0

1.25

0.5

0.25

0

Patients were required to have a documented history of at least one COPD exacerbation

during the previous year for which they received treatment with systemic glucocorticoids,

antibiotics, or both

BDP/FF/G: beclometasone dipropionate/formoterol fumarate/glycopyrronium

bromide; IND/GLY: indacaterol/glycopyrronium Papi A, et al. Lancet 2018. pii: S0140-6736(18)30206-X

TRIBUTE: Study Results

Favours Triple Therapy Favours LAMA/LABA

≥ Eosinophils 2%

0.5 1 1.5

Rate Ratio

< Eosinophils 2%

0.664 0.978

0.806

0.711 1.251

0.943

p = 0.685

p = 0.029

Adjusted rate of moderate-to-severe, moderate, and severe COPD exacerbations

Lipson DA, et al. N Engl J Med 2018

IMPACT Trial – Triple Therapy vs Dual Therapy in COPD

• Objective: To evaluate the effects of 52 weeks of a once-daily combination of FF-UMEC-VI (triple therapy) with FF-VI, or UMEC-VI, on the

rate of moderate or severe COPD exacerbations

Annual rate of moderate or severe exacerbations (Eosinophils < 150 cells/ml):

0.85 (95% CI, 0.80 to 0.91) with triple therapy,

1.06 (95% CI, 0.99 to 1.14) with FF-VI, and

0.97 (95% CI, 0.88 to 1.07) with UMEC-VI

Despite GOLD recommendations,

ICS are prescribed for all severities

Patients (%)0 10 20 30 40 50 60 70 80 90 100

Group C* (n=13) 46237.77.715.4

Group D (n=604)

2.1 0.72.11.81 0.5

58.414.93.16.96.52

Group B (n=739)

Group A (n=152)

1.6 0.5

2 0.7 2.61.3

1.9 0.42.4 1.5

6.5 7.4 26.7 7

11.8

22.221.8

233.337.57.99.9

GO

LD

Gro

up

52%

41%

77%

83% Short-acting bronchodilator only

LABA

LAMA

LAMA + LABA

ICS

ICS + LAMA

ICS/LABA

ICS + LABA (single agents)

Other ICS/LABA-containing combinations

ICS/LABA + LAMA

LAMA + ICS + LABA (single agents)

Other treatment

Vestbo J, et al. Respir Med 2014;

Price D et al. Int J Chron Obstruct Pulmon Dis 2014;9:889–905

COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung

Disease;

ICS: inhaled corticosteroid; LABA: long-acting beta-agonist; LAMA: long-acting muscarinic antagonist;

LTRA: leukotriene receptor antagonist; SABA: short-acting beta-agonist; SAMA: short acting muscarinic

Other potential risks of ICS use in patients with COPD

include bone fractures and cataracts

Price D, et al. Prim Care Respir J 2013

Randomized

controlled trial

Observational study

onlySystematic review

Pneumonia ✔ ✔ ✔

Tuberculosis ✔ ✔

Bone fractureNo effect on fracture

risk✔ ✔

Skin thinning/

easy bruising✔

Cataract ✔

Diabetes ✔

Oropharyngeal

candidiasis✔ ✔ ✔

ICS* Dose in COPD and Onset of Diabetes/Osteoporosis

HR for ICS* vs. non-ICS, diabetes onset, stratified by GOLD

groups

Effect sizes of the different dosing strata

Study design: Historical matched cohort study utilising primary care medical record data from CPRD and OPCRD.

Inclusion criteria: Clinician-diagnosed COPD; Age ≥ 40 years;

ICS* cohort: ≥ 2 ICS* prescriptions per year; Non-ICS cohort: ≥ 2 LABA, LAMA and/or LAMA/LABA prescriptions per year

CPRD: ICS*, n=10395; LAMA/LABA, n=3543

OPCRD: ICS*, n=14,983; LAMA/LABA, n=5,013

CPRD: ICS*, n=11098; LAMA/LABA, n=3928

OPCRD: ICS*, n=15722; LAMA/LABA, n=5406

* *

Voorham J, Price D et al. Unpublished Data

• 1 year, multinational, randomised, double-blind, parallel-group and active-controlled study

• 6-week run-in period on triple therapy (tiotropium 18mcg OD, salmeterol 50mcg BID, fluticasone 500mcg BID)

• 1:1 allocation into double blind phase that contains active control and stepwise step-down from 500 mcg fluticasone to

250mcg, 100mcg and placebo - Stepwise reduction was done at every 6 weeks

Magnussen H, et al. Respir Med 2014;108(4):593-9

WISDOM: Study Design

Sc

ree

nin

g Triple

TherapyTio - 18µg QD

Sal - 50µg BD

Flu - 500µg BD

Week

Visit

-7

1

-6

2

Ra

nd

om

iza

tio

n (

1:1

)

0

3

6

4

12

5

18

6

52

13

Run-in

ICS (remained in triple therapy from run-in)

Stepwise ICS withdrawal (remained on standard dose of

tiotropium and Salmeterol )

250µg BD 100µg BD 0µg BD (placebo) Stable Treatment500µg BD

Primary endpoint: time to the first moderate or severe COPD exacerbation during the 12-month study period

Magnussen H, et al. N Engl J Med 2014;371:1285–94

WISDOM: Unanswered Question – Who Needs Triple?

Calverley PMA, et al. Am J Respir Crit Care Med 2017;196(9):1219-1221

WISDOM: ICS Withdrawal Only Increased Exacerbation Risk in Patients

With ≥2 Prior Exacerbations and Elevated Blood Eosinophils

Total study population = 2,485

ICS monotherapy is not indicated for COPD without asthma

IPCRG Algorithm: How to Identify if a Patient

Would Benefit from ICS (Step 2)

Kaplan A, et al. IPCRG Desktop Helper No. 6, 2017

ICS + LABA + LAMA

Triple Therapy

Does the patient have a high

exacerbation risk?• ≥2 exacerbations or ≥1 exacerbation leading

to hospitalization in the previous 12 months?

- AND -

Does the patient have elevated blood

eosinophils?• ≥400 cells/mm3?

Continue ICS in

combination with

optimal long-acting

bronchodilation

Yes

No

From step 1

(patient does not have asthma)

History/

examination

Continue to: How to withdraw ICS in

COPD patients who don’t need it

Biomarker

Monitor for

potential ICS-

related adverse

events; continued

exacerbation

despite biomarker

may indicate lack

of efficacy of ICS

or need for

additional therapy

COPD: chronic obstructive pulmonary disease; ICS: inhaled corticosteroid; IPCRG: International Primary Care

Respiratory Group; LABA: long-acting beta-agonist; LAMA: long-acting muscarinic antagonist

IPCRG Algorithm: How to Identify if a Patient

Would Benefit from ICS (Step 1)

ICS + LABAICS + LABA +

LAMA

(Triple Therapy)

Does the patient have asthma?• Documented history of asthma, with or without

atopy, diagnosed before the age of 40 years,

or family history of asthma?

• A large degree of reversibility of airflow

limitation (>15% and 400 mL in post-

bronchodilator FEV1)?

Continue ICS in

combination with

optimal long-acting

bronchodilation

Monitor for

potential ICS-

related adverse

events; continued

exacerbation

despite biomarker

may indicate lack

of efficacy of ICS

or need for

additional therapy

Yes

No No

Continue to:

Step 2

Treatment at

assessment

consultation

History/

examination

Continue to:

How to withdraw

ICS in COPD

patients who

don’t need it

Kaplan A, et al. IPCRG Desktop Helper No. 6, 2017

COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in one second; ICS: inhaled

corticosteroid;

IPCRG: International Primary Care Respiratory Group; LABA: long-acting beta-agonist; LAMA: long-acting muscarinic

antagonist

Review of delegate pre-disposing activity

Psychological factors in COPD

Presenter: Dr Kerry Hancock

Rationale

• The 2017 GOLD report proposed a revised assessment scheme for patients with COPD.

• We examined the prevalence of common comorbidities in patients with an established diagnosis and those started on maintenance therapy for the first time by GOLD group.

83Halpin DMG, Price D, et al. Unpublished data

Methods

• Study population:− 6940 patients with a recorded diagnosis of COPD on 1/1/2014 in the Optimum

Patient Care Research Database (ALL), and− 876 patients newly initiated on maintenance therapy (NMT) in 2014 with a two

year follow-up were studied.

• Both cohorts had data on comorbidities, the number of exacerbations in the previous 12 months, and mMRC & FEV1 in the year 2014.


Prevalence of Comorbidities in All Patients with Diagnosis of COPD

85

Cn=881 (12.7%)

Diabetes mellitus 14.8%Osteoporosis 7.3%

Cardiovascular disease 9.1%Heart failure 1.0%Pneumonia 2.0%

Anxiety/Depression 23.2%

Dn=1004 (14.5%)




An=3116 (44.9%)




Bn=1939 (27.9%)




Halpin DMG, Price D, et al. Unpublished data

In ALL patients (n=6940) there were no clear differences in prevalence of comorbidities between the groups except for anxiety/depression which was nearly twice as prevalent in patients in Group D compared with group A.

Prevalence of Comorbidities in Patients with Diagnosis of COPD Initiating Maintenance Therapy


In NMT patients (n=876) there were also no clear differences in prevalence of comorbidities between the groups except for osteoporosis which was more common in patients in groups B & D.

Cn=120 (13.7%)




Dn=79 (9.0%)




An=424 (48.4%)




Bn=253 (28.9%)




Conclusion

• Comorbidities are common in people with COPD and many are already present at the time maintenance therapy is initiated.


Contact Our Team

88

www.optimumpatientcare.org/australia

@optimumpatientcareaustralia

@OPCare

https://www.linkedin.com/company/

optimum-patient-care

• One that provides information not already available from the clinical assessment

• Aids in clinical decision making

• Has a short turnaround time

• Is inexpensive

What is a good bio-marker?

What is BNP and NT-proBNP

Causes for Elevated Natriuretic Peptide Levels

Reccommendations for Biomarkers in HF

BNP Consensus Algorithm

Medicare Reimbursement of BNP testing in Australia

Latest recommendations from Cardiac Society of Australia and New Zealand ( CSANZ ) state that GPs should consider BNP testing in the following scenarios:

• to diagnose, rule out or to differentiate heart failure from other potential clinical conditions in a patient presenting with dyspnoea , and access to an echo is unavailable or delayed.

BNP testing is however not reimbursed in primary care settings and out of pocket cost should be discussed with the patient.

Dr Garry Jennings, Chief Medical Advisor, National Heart Foundation

Workshops

Who really has COPD? Spirometry Interpretation for GPs (in 25 minutes!)

Dr Kerry Hancock

Professor Peter Frith April 28th 2018, Melbourne

Declarations - Dr Kerry Hancock

• Pharmaceutical companies who undertake research , develop and / or market medicines prescribed to patients with COPD

• Advisory Board fees, Leadership Forum attendances, presentation fees

• Spirometry Learning Module

• LFA Executive National COPD Program Coordinating Committee

COPD is confirmed by the presence of persistent airflow limitation

(post-bd FEV1/FVC <0.7)

• pre and post-bronchodilator spirometry

• use proper technique

• post-bd FEV1/FVC ratio <0.7 and FEV1 <80% predicted

• airflow limitation that isn’t fully reversible

• interpret borderline spirometry results with caution

• particularly in older (>65yr) and younger patients (<45yr)

• those without a history of smoking or exposure to occupational/environmental pollutants or dust

• if borderline spirometry, consider alternative diagnoses and investigate appropriately

COPD: Under - diagnosis and Mis - diagnosis

• Under-diagnosis is high (50%)

• Misclassification COPD

• Tas 31% in 31 practices (Walters 2011)

• 18% normal

• NSW 42% in 44 practices (Zwar 2011)

• 20% normal

• Vic 37% in 41 practices (Laing 2018 )

• 31% normal

Are we good at interpreting spirometry?

• Sydney 36 practices (Zwar 2016) • case finding

• 10,234 patients invited, 1641 spiro tests

• PNs trained in spirometry + mentoring/feedback

→ 75% traces met quality standards

• decision support via interpretive tool kit

• GPs on-line training COPD guidelines

• 287 “new cases COPD” / 1641 spiro tests (18%)

• 78 (27%) did NOT have FEV1/FVC < 0.7

Early intervention for chronic obstructive pulmonary disease by practice nurse and GP teams: a cluster randomized trial (PELICAN study)Nicholas A Zwar,et al. Family Practice, Volume 33, Issue 6, 1 December 2016, pp 663–670

Steps of Spirometry Interpretation Strategy✓ Patient demographics

✓ Predicted Values

✓ Patient history & clinical presentation

Test quality – acceptability + repeatability

Flow Volume Curve(s)

FEV1/FVC ratio (FER)

FEV1 percent predicted

FVC

Bronchodilator response Spirometry Interpretation Module – Spirometry Interpretation Strategy ©

✓ Check the test qualityAcceptability criteria:

1. They are free from artefacts

2. Have good starts

3. Have a satisfactory exhalation

Repeatability criteria:After 3 acceptable spirograms have been obtained, apply the following tests:

1. Are the two largest FVC within 150mls?

2. Are the two largest FEV1 within 150mls?

ADVOCACY | AWARENESS | EDUCATION | SUPPORT | RESEARCH

Patient related problems

≥ 3 acceptable curves

repeatability:FVC ≤ 150ml FEV1 ≤ 150ml

Possibly not valid

YES!

Interpret with caution

✓ Interpret

Flo

w

RestrictionObstruction Mixed

Abnormal Ventilatory Function

Normal (age dependent)

Volume

Flo

w

Flo

w

normalairflow limitation (rev / irrev) restrictive or patient performance related?

✓ Assess the Flow Volume Curves: spirometric patterns

FEV1 : to assess severity of obstruction

• Mild • Moderate • Severe

RESTRICTION

OBSTRUCTION

Airflow limitation • Reversible• Non-reversible (fixed)

COPD: FEV1 / FVC < 0.7

COPD: FEV1< 80% predicted

✓ Looking at the numbers!

✓ Is FVC reduced ?Is there a restrictive pattern?

• consider suboptimal patient performance

• early test termination

• failure to inspire completely

• if ‘true’ restrictive pattern (i.e. 3 acceptable and repeatable trials) refer to accredited laboratory for confirmation by measurement of total lung capacity

• is there a mixed obstructive/restrictive pattern ?

• ratio and FVC < LLN

• early airway closure may mirror a restrictive pattern

✓ Is there significant reversibility?

If FEV1:

• > 400mL following bronchodilator, strongly consider asthma

(or co-existing asthma and COPD)

• < 400mL (but ≥ 200mL and ≥ 12%) consider co-existing asthma and COPD or an asthma component depending on history and pattern of symptoms

N

Plethismography and lung volumes studies are

needed

NN

Spirometric Patterns – summary

Spirometry Training Courses

• National Asthma Council

• Asthma Australia

• The Lung Health Promotion Centre (Alfred) https://www.lunghealth.org/

• Queensland Health

• Indigenous Respiratory Outreach Care (IROC) Program

• Spirometry Training Professionals

• A list of registered training organisations offering spirometry can be found on the Australian Government Department of Education and Training website.

https://www.lunghealth.org/

https://training.gov.au/Search/SearchOrganisation?nrtCodeTitle=HLTHPS004&scopeItem=Unit&tabIndex=1&ImplicitNrtScope=True&orgSearchByScopeSubmit=Search&IncludeUnregisteredRtosForScopeSearch=False

Resources for Performance and Interpretation of Spirometry

ATS / ERS Guidelines:

Pellegrino R, Viegi G, Brusasco V, et al Interpretive strategies for lung function tests. Eur Respir J. 2005;26(5):948-968..

Miller MR, et al. Standardisation of spirometry. Eur Respir J 2005: 26(2): 319-338

Australian Resources:

Johns DP , Burton D, and Swanney MP. Spirometer Users’ and Buyers Guide; Melbourne: National Asthma Council Australia, 2013. Revised 2015

https://www.nationalasthma.org.au/living-with-asthma/how-to-videos/performing-spirometry-in-primary-care

https://www.nationalasthma.org.au/living-with-asthma/resources/health-professionals/information-paper/spirometry-quick-reference-guide

Johns DP and Pierce R. Pocket Guide to Spirometry, 3rd edition. Sydney: McGraw-Hill Australia, 2011 ISBN 9780071716193

Abramson M, et. al. COPD-X Concise Guide for Primary Care. Brisbane. Lung Foundation Australia. 2014

https://www.nationalasthma.org.au/living-with-asthma/how-to-videos/performing-spirometry-in-primary-care

https://www.nationalasthma.org.au/living-with-asthma/resources/health-professionals/information-paper/spirometry-quick-reference-guide

In pairs …..

- consider the following case study - assess and interpret the two spirometry tests using the spirometry assessment tool

Mr DD

• 62 yo male truck driver

• T2DM

• IHD/ CABVG

• Childhood pneumonia & “bronchitis”

• Current smoker – approx 50PY

• Recent increase in cough

• CXR – “mild hyperinflation”, no sinister abnormalities

• Spirometry 2010 and 2015

Group activity: Case Studies

Case Study 2

QUESTION 3

If he was found to have diabetes.

How would you manage his diabetes?

QUESTION 1

Case Study 2: COPD and Diabetes

QUESTION 1

Should he be on a long acting

bronchodilator? What would sway you?

QUESTION 3

If he was found to have diabetes, how

would you treat his diabetes?

QUESTION 2

Should you screen him for diabetes?

If so, when and how?

QUESTION 4

If he was found to have diabetes.

How would you manage his COPD

differently?

QUESTION 5.

What is his risk of a CV event in the next five years? How would this change if he had diabetes? What would you

change to his CV risk management if he had diabetes?

Case Study 1: COPD HF

QUESTION 2

What would you do?

• Short term

• Long term

QUESTION 1

What are your considerations?

What do you do in terms of investigations?

QUESTION 3

What would you amend in terms of treatment?

QUESTION 4

What are your review plans and what would trigger

you to refer the patient?

Anne presents for scripts and says ‘feeling fine but have shortened my daily walk with the dog’

Thank you

Education event: COPD & its comorbidities

Documents