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Identifying New Strategies to Optimize the Management & Treatment of COPD

April 21, 20162016 Spring Managed Care Forum

David M. Mannino, M.D.

Professor

Department of Preventive Medicine and Environmental Health

University of Kentucky, College of Public Health

Disclosures Research Grants

– GlaxoSmithKline– Pfizer– Novartis– Astra-Zeneca

Advisory Boards– GlaxoSmithKline– Pfizer– Astra-Zeneca– Novartis– Merck– Nycomed– Forest– Amgen

Expert Witness– In Environmental Tobacco Smoke exposure cases (Plaintiffs)– Diacetyl exposure cases (Defense)– Tobacco and Lung Disease cases (Plaintiffs)

Chief Scientific Officer - COPD Foundation

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Objectives Identify approaches for COPD screening,

diagnosis, and ongoing patient monitoring

Assess the diagnosis and progression of COPD including clinical data on pulmonary function

Discuss management strategies for patients with COPD

Discuss pharmacologic and non-pharmacologic treatment options for COPD to reduce exacerbations

Educate patients and caregivers to provide clear medical instructions, assess patient preferences, and improve treatment adherence

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Recommendation Summary- Screening and Spirometry

Spirometry should not be used to screen for airflow obstruction in individuals without respiratory symptoms(Grade: strong recommendation, moderate-quality evidence).

Spirometry should be obtained to diagnose airflow obstruction in patients with respiratory symptoms (Grade: strong recommendation, moderate-quality evidence)

An Emerging Tool (CAPTURE™)

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Diagnosis/Classification

Global Initiative on Chronic Obstructive Lung Disease (GOLD) guidance

COPD Foundation Guidance

COPD Definition – GOLD 2011

Characterized by chronic airflow limitation and a range of pathologic changes in the lung, significant extrapulmonary effects, and important comorbidities

Features may include

– Chronic bronchitis (cough and sputum production)

– Emphysema (destruction of gas exchanging surfaces of the lung)

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Patient Characteristic SpirometricClassification

Exacerbationsper year

mMRC CAT

ALow Risk

Less SymptomsGOLD 1-2 ≤ 1 0-1 < 10

BLow Risk

More SymptomsGOLD 1-2 ≤ 1 > 2 ≥ 10

CHigh Risk

Less SymptomsGOLD 3-4 > 2 0-1 < 10

DHigh Risk

More SymptomsGOLD 3-4 > 2 > 2

≥ 10

Global Strategy for Diagnosis, Management and Prevention of COPD

Combined Assessmentof COPDWhen assessing risk, choose the highest risk according to GOLD grade or exacerbation history

The Future Classification of COPD?

Lung Function

Less Severe More Severe

Symptoms

Exacerbations

Targ

et T

hera

py

Polymorbidity

SGRQ/CAT

Exercise Capacity

Gau

ge S

ever

ity

Body Mass Index/Other Factors

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COPD THERAPY BASED ON SEVERITY DOMAINS

Spirometry Grades

Regular Symptoms

Exacerbations

Oxygenation

Emphysema

Chronic bronchitis

Comorbidities

Objectives Identify approaches for COPD screening, diagnosis,

and ongoing patient monitoring

Assess the diagnosis and progression of COPD including clinical data on pulmonary function

Discuss management strategies for patients with COPD

Discuss pharmacologic and non-pharmacologic treatment options for COPD to reduce exacerbations

Educate patients and caregivers to provide clear medical instructions, assess patient preferences, and improve treatment adherence

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Concepts of disease progression

Time (age)

DiseaseOnset

Sev

erit

y

AdvancedDisease

Radiographic Abnormalities

Pathological (Structural) Evidence

Biochemical and Cellular Events

Clinical Manifestations(Patient-Centered Outcomes)

Physiological (Functional) Abnormalities

Induction Latency

ExposureGeneticPredisposition

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What is Progression of COPD?

*GOLD Guidelines. Am J Respir Crit Care Med. 2004;163:1256-1276.

0 At Risk

I Mild

II Moderate

III Severe

IV Very Severe

Health

Prevalent DiseaseProgressive Disease

Death

???“Restriction”

Incident Disease

Chronic Bronchitis Emphysema

Asthma

IrreversibleAirflow Obstruction

ReversibleAirflow Obstruction

AJRCCM 1995 ; 152: S77-121

COPD Phenotypes ??

Restriction?

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Pre-natal factorsPoverty Indoor air pollution

Effect of early childhood events on the natural history of COPD

Smoking, indoor & outdoor exposures

Courtesy of Prof. Sonia Buist

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Adapted from Fletcher and Peto, Burrows

Natural History of Lung Function Changes

Overall Organ Decline

Courtesy of Prof. Bart Celli

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Horseracing Effect

Fletcher et al, The Natural History of Chronic Bronchitis and Emphysema, 1976Burrows et al, ARRD, 1987

50

30

40

60

20FE

V1

(% o

f ag

e-ad

just

ed r

efer

ence

val

ue)

Age (years)

Adapted from Decramer M, Cooper CB. Thorax 2010; 65: 837-841.

Hockey Match??

GOLD II

GOLD III

GOLD IV

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Lung Function in 1000 “COPD” Patients

Kohler, D et al. Thorax 2003;58:825

14% 30%

Hoffman et at, PATS 2006

Perfusion Heterogeneity

GOLD 0 COPD

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Hoffman et at, PATS 2006

Imaging Airways

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Quantifying Emphysema

Coxson et al, Acad Rad 2005

DLCO and Progression of Obstruction

Harvey at al, ERJ, in Press

Normal DLCO (> 80%) at Baseline

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DLCO and Progression of Obstruction

Harvey at al, ERJ, in Press

Low DLCO (<= 80%) at Baseline

Summary

Spirometry remains the best means of routinely classifying abnormality I patients with COPD

Emerging subgroups/phenotypes of patients with normal airflow but

– Emphysema on CT Scan OR

– Impaired diffusion OR

– Severe Symptoms OR

– Exacerbation-like events

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Objectives Identify approaches for COPD screening, diagnosis, and

ongoing patient monitoring

Assess the diagnosis and progression of COPD including clinical data on pulmonary function

Discuss management strategies for patients with COPD

Discuss pharmacologic and non-pharmacologic treatment options for COPD to reduce exacerbations

Educate patients and caregivers to provide clear medical instructions, assess patient preferences, and improve treatment adherence

Nonpharmacologic Therapy to Manage COPD

Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease. Updated 2008.

PATIENT EDUCATION

OXYGEN THERAPYSURGICAL AND NON-SURGICAL ALTERNATIVES

PULMONARY REHABILITATION

SMOKING CESSATION VACCINATION

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Existing Pharmacologic Treatment OptionsAnti-inflammatory

Corticosteroids

Bronchodilators

β-agonistsAlbuterol

Levalbuterol

AnticholinergicIpratropium

CombinationSal + FluticasoneFor + BudesonideFor + Fluticasone

β-agonists (LABA)SalmeterolFormoterol

ArformoterolAnticholinergic (LAMA)

TiotropiumAclidinum

LABA/LAMA CombinationTheophylline

Short-acting Long-acting

PDE4 Inhibitors –Roflumilast

Antibiotics ????? Statins ?????

GOLD Therapy at Each Stage of COPD

• FEV1/FVC <0.70

• FEV1 ≥80% predicted

I: Mild II: Moderate III: Severe IV: Very Severe

• FEV1/FVC <0.70

• 50% ≤FEV1 <80% predicted

• FEV1/FVC <0.70

• 30% ≤FEV1 <50% predicted

• FEV1/FVC <0.70

• FEV1 <30% predicted or FEV1 <50% predicted plus chronic respiratory failure

Add regular treatment with one or more long-acting bronchodilators (when needed):Add pulmonary rehabilitation

Add inhaled glucocorticosteroids if repeated exacerbations

Add long-term oxygen if chronic respiratory failureConsider surgical treatments

Global Initiative for Chronic Obstructive Lung Disease (GOLD). NHLBI/WHO Workshop report. www.goldcopd.com

Active reduction of risk factor(s): influenza vaccinationAdd short-acting bronchodilator (when needed)

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Patient Characteristic SpirometricClassification

Exacerbationsper year

mMRC CAT

ALow Risk

Less SymptomsGOLD 1-2 ≤ 1 0-1 < 10

BLow Risk

More SymptomsGOLD 1-2 ≤ 1 > 2 ≥ 10

CHigh Risk

Less SymptomsGOLD 3-4 > 2 0-1 < 10

DHigh Risk

More SymptomsGOLD 3-4 > 2 > 2

≥ 10

Global Strategy for Diagnosis, Management and Prevention of COPD

Combined Assessmentof COPD

When assessing risk, choose the highest risk according to GOLD grade or exacerbation history

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Pharmacologic Therapy(Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.)

Patient First choice Second choice Alternative Choices

ASAMA prn

orSABA prn

LAMAor

LABA or

SABA and SAMA

Theophylline

BLAMA

orLABA

LAMA and LABASABA and/or SAMA

Theophylline

C

ICS + LABAor

LAMALAMA and LABA

PDE4-inh.SABA and/or SAMA

Theophylline

D

ICS + LABAor

LAMA

ICS and LAMA orICS + LABA and LAMA or

ICS+LABA and PDE4-inh. orLAMA and LABA or

LAMA and PDE4-inh.

CarbocysteineSABA and/or SAMA

Theophylline

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COPD THERAPY BASED ON SEVERITY DOMAINS

Spirometry Grades

Regular Symptoms

Exacerbations

Oxygenation

Emphysema

Chronic bronchitis

Comorbidities

COPD ASSESSMENT TEST (CAT) WWW.CATESTONLINE.ORG/

• A CAT score over 10 suggests significant symptoms

• A change in CAT score of 2 or more suggests a possible change in health status

• A worsening of CAT score could be explained by an exacerbation, poor medication adherence, poor inhaler technique, or progression of COPD or comorbid condition. An adjustment in therapy may be needed.

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Antibiotics and COPD

Role of Chronic infection?

Inflammatory role

Resistance?

Side affects?

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Macrolides and Exacerbations

Macrolides and Exacerbations

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Cochrane Review

Steroids and COPD

Role of Inflammation

Asthma/COPD Overlap

Treatment of Exacerbations

Risk of Pneumonia

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Benefits of ICS

Benefits of ICS

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Withdrawal of Steroids in COPD

Withdrawal of Steroids in COPD

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Pneumonia Risk

Lung Volume Reduction

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Lung Volume Reduction

Endoscopic Lung Volume Reduction

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Endoscopic Lung Volume Reduction

Moving towards Personalized Therapy

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Moving towards Personalized Therapy

Moving towards Personalized Therapy

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Objectives Identify approaches for COPD screening,

diagnosis, and ongoing patient monitoring

Assess the diagnosis and progression of COPD including clinical data on pulmonary function

Discuss management strategies for patients with COPD

Discuss pharmacologic and non-pharmacologic treatment options for COPD to reduce exacerbations

Educate patients and caregivers to provide clear medical instructions, assess patient preferences, and improve treatment adherence

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Devices

Factors Involved in Nonadherence

Medication Usage Difficulties associated

with inhalers

Complicated regimens

Fears about/or actual side effects

Cost

Distance to pharmacies

Nonmedication Factors Misunderstanding/lack of

information

Fears about side effects

Inappropriate expectations

Underestimation of severity

Attitudes toward ill health

Cultural factors

Poor communication

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Conclusions

COPD treatments continue to evolve

The future may bring better phenotypic characterization and more individualized therapies

Chronic Obstructive Pulmonary Disease

COPD is a PREVENTABLE and TREATABLE disease

ATS/ERS Guidelines for the Treatment of COPD, 2004

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