an update in copd

An Update in COPD

John Hurst PhD FRCP

Reader in Respiratory Medicine / Honorary Consultant

University College London / Royal Free London NHS Foundation Trust

j.hurst@ucl.ac.uk

What’s new in COPD – papers affecting clinical practice

• 1. Trajectories of disease progression

• 2. Phenotyping COPD

• 3. The Airway Microbiome

• 4. Co-Morbidity in COPD

• 5. Models of Care

What’s new in COPD – affecting clinical practice

• 1. Trajectories of disease progression

• 2. Phenotyping COPD

• 3. The Airway Microbiome

• 4. Co-Morbidity in COPD

• 5. Models of Care

COPD

Chronic Bronchitis Emphysema

COPD

Chronic Bronchitis Emphysema

PATHOLOGICAL diagnosis

COPD

Chronic Bronchitis Emphysema

PATHOLOGICAL diagnosis CLINICAL diagnosis

COPD

Chronic Bronchitis Emphysema

PHYSIOLOGICAL

DIAGNOSIS:

Post-BD FEV1/FVC <0.7

COPD

Chronic Bronchitis Emphysema

PHYSIOLOGICAL

DIAGNOSIS:

Post-BD FEV1/FVC <0.7

COPD Definition

COPD, a common preventable and treatable disease, is

characterised by persistent airflow limitation that is

usually progressive and associated with an enhanced

chronic inflammatory response in the airways and the

lung to noxious particles or gases. Exacerbations and

comorbidities contribute to the overall severity in

individual patients.

WHO/GOLD 2013 (www.goldcopd.org)

COPD Definition

COPD, a common preventable and treatable disease, is

characterised by persistent airflow limitation that is

usually progressive and associated with an enhanced

chronic inflammatory response in the airways and the

lung to noxious particles or gases. Exacerbations and

comorbidities contribute to the overall severity in

individual patients.

COPD: natural history

Fletcher C and Peto R. BMJ 1977;6077:1645-1648

www.hebs.sco.nhs.uk

COPD: natural history

Fletcher C and Peto R. BMJ 1977;6077:1645-1648

www.hebs.sco.nhs.uk

[with written patient permission]

STABLE EXACERBATION

The mean decline in FEV1 was 24 ml per year in trajectory 1

(Panel A), 2 ml per year in trajectory 2 (Panel B), 53 ml per year

in trajectory 3 (Panel C), and 27 ml per year in trajectory 4 (Panel

D). The decline in FEV1 in trajectory 3 was considered to be rapid.

Accelerated decline in FEV1 is not an obligate feature of COPD.

Disease Activity and Severity

EARLY vs. LATE

MILD vs. SEVERE

SEVERITY

“Distance Travelled”

ACTIVITY

“Speed”

A B

Disease Activity and Severity

SEVERITY

“Distance Travelled”

•Cross-Sectional

– FEV1

– CT

ACTIVITY

“Speed”

•Longitudinal

– FEV1 decline rate

– CT changes

•Inflammation?

Clinical Message

• COPD is diverse. Current assessments of

disease severity do not address the more

important question of disease activity

– Rate of lung function decline

– Exacerbations

What’s new in COPD – affecting clinical practice

• 1. Trajectories of disease progression

• 2. Phenotyping COPD

• 3. The Airway Microbiome

• 4. Co-Morbidity in COPD

• 5. Models of Care

COPD

Chronic Bronchitis Emphysema

PHYSIOLOGICAL

DIAGNOSIS:

Post-BD FEV1/FVC <0.7

Complexity in COPD

Phenotypes in COPD

[with written patient permission]

FEV1 (Physiological)

Exacerbations (Clinical)

Co-Morbidities

Chronic Bronchitis (Symptom based)

Emphysema (Radiological, incl. ILD)

Inflammation

(Biomarker)

Alpha-1 (Genetic)

Needs to be STABLE and MEASURABLE. Phenotypes may overlap.

Frequent

Exacerbation

Soler-Cataluna JJ et al. Thorax 2005

Seemungal TAR et al. AJRCCM 1998

Donaldson GC et al. Thorax 2002

32 vs. 40ml/yr, p<0.05

↑Costs

∆15 units, p<0.001

32 vs. 40 ml/year, p<0.05

High Risk Patients

ECLIPSE Methodology

Recruitment

Baseline

Assessment

Number of courses of

antibiotics/steroids /

hospitalisations for

exacerbation in prior

year asked and

recorded

YEAR PRIOR

Number of courses

of

antibiotics/steroids

/ hospitalisations

for exacerbation in

year one

COUNTED

Number of courses

of

antibiotics/steroids

/ hospitalisations

for exacerbation in

year two

COUNTED

Number of courses

of

antibiotics/steroids

/ hospitalisations

for exacerbation in

year three

COUNTED

YEAR 1 YEAR 2 YEAR 3

ANALYSIS 1

How do baseline variables relate to

observed exacerbations in year 1?

ANALYSIS 2

How stable is exacerbation frequency

over 3 observed years, and in relation

to patient self report?

Exacerbations and COPD Severity

Multivariate Analysis

Hurst JR et al. NEJM 2010;363:1128-1138

Multivariate Analysis

Hurst JR et al. NEJM 2010;363:1128-1138

Suggests groups of patients or ‘phenotypes’ who are

inherently susceptible versus resistant to

exacerbations (or at least reporting exacerbations)

IS THIS STABLE OVER TIME?

Exacerbation Phenotypes in COPD

Hurst JR et al. NEJM 2010;363:1128-1138

Identifying the Frequent Exacerbator

“How many courses of antibiotics and/or steroids did

you need for you chest over the last year?”

Better targeting (personalised / stratified medicine).

[with written patient permission]

GOLD 2011 Staging Revision: Exacerbations

A: Low Risk, Fewer Symptoms

B: Low Risk, More Symptoms

C: High Risk, Fewer Symptoms

D: High Risk, More Symptoms C D

A B

4

3

2

1

RISK

GOLD

Stage

≥2

1

0

RISK

Exacerbations

mMRC ≥2

CAT≥10

mMRC 0-1

CAT<10 SYMPTOMS

Clinical Message

• COPD is diverse. Therapy should be directed

against the phenotype(s) present, at baseline and

exacerbation

– Targeting the frequent exacerbator

What’s new in COPD – papers affecting clinical practice

• 1. Trajectories of disease progression

• 2. Phenotyping COPD

• 3. The Airway Microbiome

• 4. Co-Morbidity in COPD

• 5. Models of Care

This talk, circa 2006

“The healthy human airway is sterile, with several

innate immune mechanisms acting in coordination to

maintain this sterility. Smoking appears to disrupt

these innate immune mechanisms, and as a

consequence, microbial pathogens are able to

persist in the lower airway in COPD”

AJRCCM 2006

“free from bacteria or other living microorganisms; totally clean”

www.gettyimages.com

We identified 5,054 16S rRNA bacterial

sequences from 43 subjects.

The bronchial tree was not sterile, and

contained a mean of 2,000 bacterial

genomes per cm2 surface sampled.

Pathogenic Proteobacteria, particularly

Haemophilus spp., were much more frequent in

bronchi of adult asthmatics or patients with

COPD than controls.

Conversely, Bacteroidetes, particularly

Prevotella spp., were more frequent in controls

than adult or child asthmatics or COPD

patients.

“Bacterial Colonisation”

‘PPM’ Prevalence

Monso E et al. AJRCCM 1995;152:1316-1320

25% 52%

Exacerbation Ecology

Sethi S et al. J Clin Micro 2014: in press

“Volcano plots indicating taxa that are significantly increased (upper right quadrant) or decreased

(upper left quadrant) in pair-wise comparisons. Dashed lines indicate significant FDR-adjusted p-

values and changes in relative abundance of at least 2-fold. Taxa exhibiting significant changes

are coloured by phylum-level classification. Note that in addition to highlighted taxa, many other

microbiota members exhibit smaller scale changes in abundance, which cumulatively may

contribute importantly to microbiome community function.”

Viral infection predisposes to secondary

bacterial infection

AJRCCM 2013;188:1224-1231

MACROLIDES

HR for exacerbation per patient-year in the azithromycin group =0.73 (95% CI,

0.63 to 0.84; p<0.001).

Increased macrolide resistance, and hearing impairment

Clinical Message

• The presence of an organism in sputum doesn’t

necessarily mean that the organism is causing a

problem

– The field is moving quickly; we just don’t know what to

do with the data yet…

What’s new in COPD – papers affecting clinical practice

• 1. Trajectories of disease progression

• 2. Phenotyping COPD

• 3. The Airway Microbiome

• 4. Co-Morbidity in COPD

• 5. Models of Care

Case Study

A 75 year old female is

hospitalised following a

deterioration of her COPD

symptoms, consistent with an

exacerbation.

She had previously been

prescribed combination ICS-

LABA and LAMA.

She was known to have

cardiovascular disease

(previous MI) and diabetes

mellitus.

[with written patient permission]

Questions

• 1. Does the presence of IHD and diabetes affect

the outcome of the exacerbation?

• 2. What are the implications of COPD for the

therapy of IHD and diabetes?

• 3. Are these co-morbidities more likely because

of the underlying COPD, or her COPD therapy?

• 4. Is this really an exacerbation, or an undetected

co-morbidity?

The COPD “Co-Morbidome”

Divo M et al. AJRCCM 2012;186:pp 155–161

Mortality in COPD

COPD and Cardiovascular Disease

Cumulative incidence of first MI Cumulative incidence of first CVA

The Absence of Evidence

Study A • able to use medication correctly

• Serious, uncontrolled disease (including

serious psychological disorders) likely to

interfere with the study and/or likely to

cause death within the 3-year study

duration

Study B • Able to inhale study drug

• Significant diseases other than COPD

which, in the opinion of the investigator,

may either put the patient at risk

because of participation in the study or

a disease which may influence the

results of the study or the patient’s

ability to participate in the study.

• A recent history (i.e., six months or less)

of myocardial infarction.

• Any unstable or life threatening cardiac

arrhythmia or cardiac arrhythmia...

• Hospitalization for heart failure (NYHA

Class III or IV) within the past year.

• Patients with known moderate to severe

renal impairment.

Clinical Message

• Many patients with COPD have many other

diagnoses (‘co / multi-morbidities’) – Some of these are more prevalent in COPD through shared risk factors,

therapy, or ‘systemic consequences’

– These may impact the course of COPD, or complicate COPD therapy, and

COPD can impact the natural history of the co-morbidity

• However co-morbidity arises, outcomes will be

better with a take a personalised, holistic

approach to COPD management

What’s new in COPD – papers affecting clinical practice

• 1. Trajectories of disease progression

• 2. Phenotyping COPD

• 3. The Airway Microbiome

• 4. Co-Morbidity in COPD

• 5. Models of Care

Sources

Methodology

• Regular national COPD Audits: 2003, 2008, 2014

• Organisational

• Secondary Care

• Primary Care

• PR

• “All first-episode admitted exacerbations February

– April 2015”

• COPD Admissions risen 13% since 2008

Dataset

• 13414 patient exacerbations

• 100% of Trusts in E+W took part

• 183 English units in 142 Trusts

• Median (IQR) 61 (38-86) per unit

• Median (IQR) percentage of audit cases to total

eligible (coded!) cases 67% (48%-91%)

Socio-Demographics

• First COPD audit in which females make up the majority (51%) of cases.

• Admitted patients were notably deprived in respect of income, employment, health

deprivation/disability and education/skills/training.

• There is a clear association between age and area of residence with deprivation;

younger COPD patients in England and more likely to live in the more deprived

areas.

National RFH

Female 51% 50%

Mean Age (y) 72 71.4

Living in Most Deprived Quintile 34% 22%

Outcomes

• Mortality has fallen from 7.5-8% in 2003 and 2008

• Mortality doesn’t vary by day of admission, except

highest deaths on a Tuesday for patients admitted

on a Monday (and case-mix the same)

• Mortality 6.8% vs. 3.6% with consolidation

• LOS has fallen from 6→5 →4 days

7/7 working?

Specialist Advice

• Takes longer to see a specialist (if at all) for those

in at the weekend, and on a Monday

• Recording of key information better if see a

specialist

• Recommendation:

– All patients whose primary diagnosis is COPD

exacerbation should receive a specialist respiratory

opinion within 24 hours of admission. Patients with

COPD exacerbation who need to remain in hospital

should be managed on a respiratory ward.

Camden Model

Integrated COPD Care Community Respiratory Service

Close working links with both Acute Trusts

Regular MDT and joint clinics

Shared governance

Primary Care education and support

Case finding

Close links with others teams

London Respiratory Value Pyramid

Clinical Message

• How can you achieve cost-effective care of

patients with COPD in your services?

Questions

• Fixed airflow obstruction (‘COPD’) may arise as

an adult consequence of premature lung disease

– 1 YES

– 2 NO

– 3 Unsure

Questions

• It is possible to identify specific groups of COPD

patients who respond better to specific therapies

(stratified medicine)

– 1 YES

– 2 NO

– 3 Unsure

Questions

• I would prescribe antibiotics to a patient with

COPD who has Haemophilus influenzae identified

on a routine sputum culture

– 1 YES

– 2 NO

– 3 Unsure

Questions

• Most patients with COPD will die with, not from

their COPD

– 1 YES

– 2 NO

– 3 Unsure

Questions

• 7 days access to specialist care is likely to

improve outcomes in COPD

– 1 YES

– 2 NO

– 3 Unsure

Summary

• Diversity of COPD

– Trajectories of decline, disease severity and activity

– Phenotype based care

• The Airway Microbiome

• The Importance of Co-Morbidity in COPD

• The challenges of unplanned care in COPD

Thank You

Comments and Questions

j.hurst@ucl.ac.uk