Sa1 2017 COPD March Internal Medicine...

Strange - COPD 3/11/17

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What is new in COPD?Charlie Strange, MD

Professor of Pulmonary and Critical Care Medicine

Medical University of South Carolina

Dr. Strange is a grant recipient from the NIH, Alpha-1 Foundation, Baxalta, CSL Behring, Grifols, BTG, and Pulmonx in COPD. He is a consultant for Astra Zeneca,

CSL Behring, and Grifols for COPD.

Previous Definition of COPD

Chronic Bronchitis Emphysema

Airflow Obstruction

Asthma

Am J Respir Crit Care Med. 1995;152:S77.

COPD


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Current Definition of COPD


Airflow Obstruction

Asthma

Vestbo, J et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary. Am J Respir Crit Care Med 2013, 187(4):347-365.

.

COPD

Since 2009 COPD is now the #3 Cause of Death in the US

US Bureau of Health Statistics, 2011


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Current Definition of the Asthma-COPD Overlap Syndrome (ACOS)


Airflow Obstruction

Asthma

Vestbo, J et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary. Am J Respir Crit Care Med 2013, 187(4):347-365.

.

ACOS

Model-based COPD Prevalence by County, 2011


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Underdiagnosis of COPD in the United States

Age in Years

25-44 45-54 55-64 65-74 >75

Per

cen

tage

22.9%20.7%

14.0%

7.2%

5.2%

Diagnosed with COPD

GOLD stage II or higher

Mannino DM, MMWR 2002; 51:1-16

Diagnosis of COPD

SYMPTOMS

coughcoughsputumsputumdyspneadyspnea

EXPOSURE TO RISKFACTORS

tobaccotobaccooccupationoccupation

indoor/outdoor pollutionindoor/outdoor pollution

SPIROMETRYSPIROMETRY


5

Spirometry

0 1 2 3 4 5 6Seconds

VolumeLiters

4

3

2

1

0

FEV1FVCRestriction

Normal

Obstruction

Spirometry Interpretation

FEV1/FVC <0.70 FEV1/FVC > 0.70FVC < 80% Predicted

ObstructionFEV1

RestrictionFVC

Severe<50%

Moderate<70%

Mild<80%

VerySevere<30%

Moderate50-80%

Mild>80%

Severe30-50%

IV III II IGOLD Stage


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Age

FEV 1(L)

NormalSusceptible Smoker

SymptomsQuit

Average Smoker

5

4

3

1

2

7525 50

FEV1 in the Framingham, Copenhagen City, and Lovelace Cohorts

Lange P, et al. NEJM 2015; 373:111


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Emphysema


8

Risk Factors for COPD

Smoking Tobacco in any formMarijuanaPassive smoking

Ambient air pollution (eg. uranium)Hyperresponsive airwaysAlpha‐1 antitrypsin deficiencyHIVMarfan Syndrome, Ehler’s DanlosCutis laxaHypocomplementemic urticarial vasculitisCrack cocaine, IV RitalinPrematurity

What is Alpha-1?

• Alpha-1 Antitrypsin (AAT) Deficiency is a genetic disease in which a deficiency of AAT produces COPD and liver disease from retained misfolded AAT.

ZZZ


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You’re Not Just Identifying a Patient—You’re Discovering an Entire Family at Risk for Lung

Disease•The model

shown is based on an actual family that has been tested for Alpha-1

Alpha-1 family tree of disease

Pi MZ Pi ZZ

Pi ZZ Pi ZZ Pi ZZ Pi ZZPi MZ Pi MZuntested untestedPi MS Pi MM

untested Pi MSPi MZPi MZ Pi MZ Pi MZ Pi MZPi ZZ Pi ZZ Pi ZZ

Pi MMPi MSPi MZPi ZZuntested

Pi MZ

Pi MZPi MZ

Alpha-1 Foundation CRC Research Registry:

www.alphaoneregistry.org


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lobal Initiative for Chronic

bstructive

ung

isease

lobal Initiative for Chronic

bstructive

ung

isease

GOLD

GOLD

www.goldCOPD.com

Step Care Model of COPD Therapy

(1) Smoking Cessation

(2) Bronchodilator TherapyIpratropium and/or Beta2-Agonist

(3) Exacerbation PreventionRegular Inhaled LAMA/LABA/Corticosteroid

(4) Targeted Therapy of ExacerbationsA. Infectious Antibiotic for 7-10 daysB. Excess mucus Mucolytic/ expectorant for 2-8 wksC. Neither Corticosteroid boost for 3-14 days

(5) Expectant TherapyA. Pulmonary Rehabilitation ProgramB. NutritionC. Influenza and Pneumococcal VaccinationD. Oxygen

(6) Treat HyperinflationLung Transplant or Volume Reduction Surgery


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American Lung Association Report Card

South Carolina 2016

Grades:

• Smokefree Air F• Tobacco Prevention and Control

Spending F• Cigarette Taxes F• Cessation Coverage F

South Carolina Spending on Tobacco Control 2016

• State Funding for Tobacco Control Programs: $5,000,000

• Federal Funding for State Tobacco Control Programs: $1,124,509

• Total Funding for State Tobacco Control Programs: $6,124,509

• CDC Best Practices State Spending Recommendation: $51,000,000

• Percentage of CDC Recommended Level: 12.0%

• State Tobacco-Related Revenue: $228,500,000

http://www.lung.org/our-initiatives/tobacco/reports-resources


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GOLD COPD

C D

A B

Spirometry(GOLD Class)

Exacerbations

Symptoms(mMRC/CAT)

0-1/<10 ≥ 2/≥10

Hospitalizations

1

2

3

4

≤10

≥2≥1

Classes of Medications

SABA= Short acting beta agonists (eg. albuterol)SAMA= Short acting muscarinic antagonists (eg. ipratropium)

LABA = Long acting beta agonistsLAMA= Long acting muscarinic antagonists

ICS= Inhaled corticosteroids

LTA= Leukotriene antagonists (eg. montelukast)

PDE4 inhibitors (roflumilast)


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Global Strategy for Diagnosis, Management and Prevention of COPDManage 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

Lung Health Study I2 puffs ipratropium TID x 5 years using

electronic dosimeter

Compliance

%

1 2 3 4 5

10

20

30

40

50

60

70 Self-reported

Cannister weight

Cannister dumping

>100actuations

in 3 hrs.Years

12%


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Currently Available Single Agent Bronchodilators

Albuterol 0.18 mg 2.5 mg 28(Ventolin, Proventil, Proair)

Levoalbuterol (Xopenex) 0.09 mg 0.63-1.25 mg 14-28Ipratroprium (Atrovent) 0.36 mg 0.5 mg 28

Salmeterol (Serevent) 0.42 mg 0.50mg BIDOladaterol (Striverdi) 2. 5mcg QDIndacaterol (Arcapta) 75 mcg QDFormoterol (Foradil, Perforomist) 12 mcg BID 20 mcg BIDAformoterol (Brovana) 15 mcg BID

Tiotroprium (Spiriva) 0.18 mg QDAclidinium (Tudorza) 0.4 mg BIDUmeclidinium (Incruze) 62.5 mcg QDGlycopyrolate (Seebri) 44 mcg QD

Drug MDI2 Puffs

DPI / Mist

NebulizerDose

MDI to Equal Neb

Management of ExacerbationsObjective Strategy

Acute

Relieve dyspneaSABA +/- short acting

anticholinergic

Reduce airway inflammation

Systemic corticosteroids

Improve lung function

Systemic corticosteroids

Eradicate infections Antibiotics

Maintenance Reduce risk of new

exacerbation

Smoking cessation

Pharmacotherapy •LAMA•LABA

•LAMA/LABA•LABA/ICS

Immunizations•Influenza

•Pneumonia

Pulmonary rehab

Self-management supportAnzueto A. Am J Med Sci. 2010]


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LAMA/LABATiotropium/Olodaterol Boeringher

IngelheimStiolto Respimat®

Vilanterol/Umeclidiniumbromide

GlaxoSmithKline Anoro Ellipta®

Glycopyronium/Indacaterol Novartis Pharmaceuticals

Ultibron Breezhaler®

Glycopyrronium/formoterol

fumarate

AstraZeneca Bevispi Aerosphere®

Fluticasone propionate/ Salmeterol

GlaxoSmithKline, Elpen

Advair Diskus®, Advair HFA®

Budesonide/Formoterol AstraZeneca Symbicort®

Mometasone/Formoterol Merck Dulera® for asthma, investigational COPD

Fluticasone furoate/ Vilanterol

GlaxoSmithKline Breo Ellipta®

ICS /LABA

Exacerbation Rates on LAMA/LABA vs ICS (N=3358)

Wedzicha JA. NEJM 2016.


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SUMMIT(Study to Understand Mortality and

Morbidity in COPD)

• 16,000 patients randomized to one of 4 arms:• Fluticasone furoate/vilanterol 100/25 ug• Fluticasone furoate 100ug• Vilanterol 25 ug• Placebo

• Time to event trial for 1000 events

• Primary endpoint all cause mortality • FF/V 12.2% decrease from placebo (P=0.14)

• Secondary endpoint time to first exacerbation• FF/V decreased by 20% • (HR 0.80, 95% confidence interval 0.73 – 0.86)

Vestbo J, et al. Eur Resp J 2013:41:1017-22www.clinicaltrials.gov (NCT01313676)

NPPV in Acute Exacerbations of COPD:Risk of “Treatment Failure”

(Mortality, Intubation)

Ram FS et al. Cochrane Database Syst Rev. 2003;1:CD004104.Reproduced with permission. Lightowler JV et al. BMJ. 2003;326:185-190.


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GoldSealMirage

IQ

SoftFitSimplicity

Spectrum

Breeze

PhantomTotal face mask

Oxygen• Improved mortality in individuals with resting pO2

<55 mmHg• 24 hours/day is better than 12 hours per day

• Improved exercise and quality of life in individuals who have O2 desaturation <88% when given oxygen with exercise. No change in other outcomes.

• No data that oxygen improves mortality with O2 sats >88% despite intermittent desaturations <88%.


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Manage Stable COPD Rehabilitation

All COPD-patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).

Progressive Hyperinflation Reduces Inspiratory Capacity

Cooper CB. Am J Med. 2006;119:S21.

Normal Mild Moderate Severe

COPD

VT

FRC/EELV

ICHypotheticalDyspneaThreshold

IC

IRV

ERV

RV

TLC


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Zephyr-Endobronchial Valves (EBV)

Intrabronchial Valves (IBV)

PneumRx®

Elevair™ Endobronchial

Coil

InterVapor -Bronchoscopic Thermal Vapor

Ablation (BTVA)

PulmonX

Spiration

PneumRx

Uptake

Tis

sue

com

pre

ssio

n

Mechanism of Action

Flo

w r

egu

lati

on

Product

BTVA uses heated water vapor to produce a thermal reaction leading to an initial localized inflammatory response followed by permanent fibrosis and atelectasis with subsequent reduction in lung volume.

Image

Coils are delivered to the lung in a straight configuration through a bronchoscope. Once deployed, LVRC reduces the diseased lung volume by coiling up thereby compressing the diseased tissue and allowing expansion of the healthier areas

One-way valves prevent air from entering the blocked emphysematous segment, while allowing the venting of expired gas and bronchial secretions, leading to atelectasis of the isolated segments with subsequent reduction in lung volume.


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The RePneuⓇ Lung Volume Reduction Coil (LVRCⓇ)

Self actuating Nitinol implant

LV

RC

Pro

ced

ure

Courtesy of Dr. Gaetan Deslee


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Disease Management Programs for COPD

761 COPD patients entered into program with 1.5 hour orientation + spirometry

Randomized to program vs controlMonthly nurse telephone calls for 1 year.

Prednisone use, tiotroprium use, antibiotic courses all P<0.05 different between groups

COPD Hospitalization (p<0.0001)

COPD Hosp or ER Visits (p<0001)

Rice KL, et al. Am J Respir Crit Care Med. 2010


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Patient Centered Care and Self-Efficacy

Hospice

Pulmonary Rehabilitation

RT

Specialist

PCP

Patient(Home &

Community)

SNF

Acute Rehab

LTACHospital

EDUC

Patient/caregiver Education

Problem solving skill mastery

Social participation

Pulmonary Pulmonary

MUSC Medical Center

Number of Discharges

168

Number of Readmissions

34

Readmissions Rate

20.2%

Excess Readmissions

Ratio

0.9929

Chronic Obstructive Pulmonary Disease (COPD)

Figures are calculated from publicly available data in CMS's FY 2016 IPPS Final Rule Impact File notice, Estimated amounts may differ from actual final figures.


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Symptom Status Update

Patients With Moderate and Severe COPD Record Daily Respiratory Symptoms

• Breathlessness (Modified Borg Scale)

• Sputum Quantity, Color, and Consistency

• Peak Flow Measurements

• Presence of Temperature Over 100°F

• Presence of Any Cough, Wheeze, Sore Throat or Nasal Congestion

Current Guidelines Based on ATS/ERS Guidelines

HGE Exacerba on Treatment Severity Score

None Mild (any FEV1)

Mild‐Moderate

(FEV1 > 50%)

Moderate‐Severe

(FEV1 < 50%)

Severe (any FEV1)

Score

0‐1 1‐1.9 2‐2.9 2‐2.9 >3

Ac on 1 Con nue present care

Increase albuterol

Increase albuterol

Increase albuterol

Increase albuterol

Ac on 2 No changes needed

Increase ipratropium




Ac on 3 Add albuterol or ipratropium if on solo BDA therapy

Increase albuterol +/‐ ipratropium

Increase both albuterol and ipratropium

Increase both albuterol and ipratropium

Ac on 4 +/‐ Prednisone +/‐ Prednisone Prednisone

Ac on 5: If purulent mucous add an bio c

Symptom Deviation ScoreSymptom Deviation Score Suggested Treatment Based on Score

Suggested Treatment Based on Score

Time to TreatTime to Treat


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COPD CO-PILOT: First Prospective Randomized TrialPA-SCOPE: Impact of Early Telemedicine AECOPD Intervention on Daily Dyspnea Score

PA-SCOPE: Impact of Early Telemedicine AECOPD Intervention on Daily Peak Flow

05

1015202530

Mild Moderate SevereFre

q.

of

Exa

cerb

atio

n

Exacerbation Severity

Frequency of Exacerbation v. Exacerbation Severity

Call Center

Standard of Care

*

* P<0.001

Criner G, 2016

Conclusions

• The COPD world has many new options for therapy, some of them pharmacologic

• New inhalers improve convenience

• Large unmet need in compliance with medications

• Much more focus on integrated care will drive COPD therapy

Sa1 2017 COPD March Internal Medicine...

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