update in copd - woemawoema.org/files/wohc2012/post_grad/wohc2012_woodruff.pdf · update in copd...

Update in COPDUpdate in COPD

Prescott G. Woodruff, MD, MPHPrescott G. Woodruff, MD, MPHAssociate Professor of MedicineAssociate Professor of Medicine

UCSFUCSFDivision of Pulmonary and Critical CareDivision of Pulmonary and Critical Care

Faculty DisclosuresFaculty Disclosures

Personal financial interests in commercial entities thatPersonal financial interests in commercial entities thatare relevant to my presentation(s) or other faculty roles:are relevant to my presentation(s) or other faculty roles:

Prescott Woodruff, MD, MPH

Genentech, Research Grant (completed), Co-inventor on patent applicationRegulus, Unfunded research collaboration (reagents)Pfizer, CTI Strategic AllianceMedImmune, Consultant (completed)

Burden of disease: Understand the need for early recognition, prevention, and treatment of COPD

COPD diagnosis: Importance of spirometry, symptom and exacerbation assessment

Current treatment options: Review current GOLD guidelines Recent Advances: azithromycin for the prevention ofexacerbations

The Future of COPD: Phenotyping in COPD

ObjectivesObjectives

••Chronic BronchitisChronic Bronchitis

••EmphysemaEmphysema

••Chronic Airflow limitationChronic Airflow limitation

COPD: Breadth of the DefinitionCOPD: Breadth of the Definition

GOLD Consensus Report, December 2011

“COPD, a common preventable and treatabledisease is characterized by persistent airflow limitation..”

“Airflow limitation is usually progressive and is associatedassociatedwith an enhanced chronic inflammatorywith an enhanced chronic inflammatoryresponseresponse in the airways and the lung to noxious particlesor gases.”

“Exacerbations and comorbidities Exacerbations and comorbidities contribute tothe overall severity in individual patients.”

COPD: Preventable and TreatableCOPD: Preventable and Treatable

COPD is a Major Public Health ProblemCOPD is a Major Public Health Problem

16.3 million office visits each year due to COPD16.3 million office visits each year due to COPD11

672,000 hospitalizations each year for COPD672,000 hospitalizations each year for COPD22

•• 21% mortality rate at one year after being hospitalized21% mortality rate at one year after being hospitalizedfor a COPD exacerbation in a large VA cohortfor a COPD exacerbation in a large VA cohort33

COPD is currently the 3rd-leading cause of death in theCOPD is currently the 3rd-leading cause of death in theUnited StatesUnited States44

Total costs for COPD estimated at $49.9 billion in 2007Total costs for COPD estimated at $49.9 billion in 2007

1. National Institutes of Health, National Heart, Lung & Blood Institute. Morbidity and Mortality: 2009 chart book on cardiovascular, lung andblood diseases. www.nhlbi.nih.gov/resources/docs/cht-book.htm. Accessed September 13, 2010.

2. American Lung Association. Trends in chronic bronchitis and emphysema: morbidity and mortality. February 2010. www.lungusa.org.Accessed September 13, 2010.

3. McGhan R, et al. Chest. 2007;132:1748-1755.4. WHO. Chronic respiratory diseases. 2011. http://ww.who.int/respiratory/copd/burden/gn. Accessed July 2, 2011.5. American Lung Association. Trends in chronic bronchitis and emphysema: morbidity and mortality. February 2010. www.lungusa.org

Percent Change in Age-AdjustedPercent Change in Age-AdjustedUS Death RatesUS Death Rates

3.0

2.5

2.0

1.5

1.0

0.5

01965-1998 1965-1998 1965-1998 1965-1998 1965-1998

CoronaryCoronaryHeartHeart

DiseaseDisease

StrokeStroke OtherOtherCVDCVD

All OtherAll OtherCausesCauses

-64%-64%-59%-59% -35%-35% -7%-7%

COPDCOPD

+163%+163%

Global Initiative for Chronic Obstructive Lung Disease. NHLBI/WHO workshop report. 2001. http://www.goldcopd.com/workshop/toc.html. Accessed: 14 November 2003.

Occupational or Work-related COPD isOccupational or Work-related COPD isalso a Major Public Health Problemalso a Major Public Health Problem

Population Attributable Risk is 15-20%Population Attributable Risk is 15-20%

Total costs for Occupational COPD estimated at $5Total costs for Occupational COPD estimated at $5billion annually in the US alonebillion annually in the US alone

Balmes in Environmental and Occ Med, Rom 4Balmes in Environmental and Occ Med, Rom 4thth Ed, 2007. Ed, 2007.

Recognition of work-relatedness isRecognition of work-relatedness isdifficultdifficult

Lack of a standard definitionLack of a standard definition

No typical pathology (unlikeNo typical pathology (unlikepneumoconioses)pneumoconioses)

COPD is multifactorial (concurrentCOPD is multifactorial (concurrentcigarette smoke exposure)cigarette smoke exposure)


COPD: GeneralCOPD: GeneralRisk FactorsRisk Factors

Tager et al. Tager et al. Am Rev Respir DisAm Rev Respir Dis. 1988;138:837-849; Holt. . 1988;138:837-849; Holt. ThoraxThorax. 1987;42:241-249.. 1987;42:241-249.

EstablishedEstablished ProbableProbable PossiblePossible Cigarette smokingCigarette smoking

OccupationalOccupationalexposureexposure

αα11-Antitrypsin-Antitrypsindeficiency (geneticdeficiency (geneticabnormality)abnormality)

Air pollutionAir pollution

Exposure to primaryExposure to primaryand secondaryand secondarysmokesmoke

Hyperactive airwaysHyperactive airways

AlcoholAlcohol

PovertyPoverty

Low birth weightLow birth weight

ChildhoodChildhoodrespiratory infectionsrespiratory infections

Family historyFamily history

AtopyAtopy

IgA deficiencyIgA deficiency

Blood type ABlood type A

COPD: Occupational Risk FactorsCOPD: Occupational Risk Factorsfor Chronic Bronchitisfor Chronic Bronchitis


MineralsMinerals MetalsMetals GasesGases CoalCoal

Vitreous fibersVitreous fibers

Oil mistOil mist

Portland cementPortland cement

Silica/silicatesSilica/silicates

OsmiumOsmium

VanadiumVanadium

Welding fumesWelding fumes

Organic DustOrganic Dust•• CottonCotton

•• GrainGrain

•• WoodWood

DiisocyanateDiisocyanate

Sulfur dioxideSulfur dioxide

SmokeSmoke•• Engine exhaustEngine exhaust

•• FiresFires

COPD: Occupational Risk FactorsCOPD: Occupational Risk Factorsfor Emphysemafor Emphysema


Much harder to measure, data from autopsy studiesMuch harder to measure, data from autopsy studies Gold minersGold miners

Silica exposureSilica exposure

Coal dustCoal dust

COPD: Occupational Risk FactorsCOPD: Occupational Risk Factorsfor Decline in FEV1for Decline in FEV1


Much harder to specify the cause, Population basedMuch harder to specify the cause, Population basedstudiesstudies MiscellaneousMiscellaneous

exposures to dustexposures to dustand gasesand gases






Spirometry Steps For Suspected COPDSpirometry Steps For Suspected COPD

FEVFEV11/FVC/FVCOAD (COPD orAsthma)

<70% >70%Normal

FVCFVC

STEP 1

STEP 2

>80%

ConcomitantConcomitantrestrictiverestrictive

componentcomponent

<80%

ObstructiveObstructivedisease onlydisease only

FVCFVC

RestrictiveRestrictiveAirwaysAirwaysDiseaseDisease

<80%

>80%WNL

Adapted from Fletcher et al. BMJ. 1977;1:1645-1648.

Disease must be detectable in an early stage:Disease must be detectable in an early stage:Lung Function Over TimeLung Function Over Time

FEV

FEV 11

(%) R

elat

ive

to A

ge 2

5 (%

) Rel

ativ

e to

Age

25

Never smoked or notsusceptible to smoke

StoppedSmoking at 45(Mild COPD)

Stoppedsmoking at 65(Severe COPD)Death

Disability

Smoked regularlyand susceptibleto its effects

Age (Years)5050 7575252500

Symptoms

00

2020

5050

6060

100100

8080

4040

Mannino et al. MMWR Morb Mortal Wkly Rep. 2002;51:1-16.

0

50

100

150

200

250

300

350

400

450Diagnosed with chronic bronchitis or emphysema

Airflow limitation (GOLD 1 or higher)

Rat

e pe

r 100

0 of

Pop

ulat

ion

25-44 45-54 55-64 65-74 >/=75Age (years)

Underdiagnosis of COPD in the United States Underdiagnosis of COPD in the United States

7.2%

14%

20.7%

22.9%

The Argument for Selective ScreeningThe Argument for Selective Screening

Martinez, et al., COPD, 2008;5:85. “COPD Screener”

Symptoms in COPDSymptoms in COPD

Exacerbation Frequency Increases WithExacerbation Frequency Increases WithDisease SeverityDisease Severity

1.6

1.9

2.3

0

0.5

1

1.5

2

2.5

>60% 40%-59% <40%

% Predicted FEV 1

Exa

cerb

atio

ns P

er Y

ear

Miravitlles M, et al. Respir Med. 1999;93:173-179.

Exacerbation was defined as an increase in dyspnea, sputum volume, and/or sputum purulence.

Results based on a cross-sectional observational study of ambulatory COPD patients in Spain.General practitioners (N=201) between October 1994 and May 1995 completed a questionnaire onCOPD characteristics of 1001 patients.

-50

-40

-30

-20

-10

0

FEV 1

, mL/

year

<1.5 >1.5Exacerbations Per Year

Frequency of Exacerbations Is AssociatedFrequency of Exacerbations Is AssociatedWith a Decline in Lung FunctionWith a Decline in Lung Function

Results based on a secondary analysis of 32 patients who recorded daily FEV1. The median rate of exacerbationsseen at clinic was 1.5 per patient per year.Donaldson GC, et al. Thorax. 2002;57:847-852.

*P<0.001 -46.1

-25.3*

Patients With Frequent Exacerbations HadPatients With Frequent Exacerbations HadSignificantly Worse Quality of LifeSignificantly Worse Quality of Life

48.953.2

67.7

36.3

64.1

77.080.9

50.4

0

10

20

30

40

50

60

70

80

90

100

Total Symptoms Activities Impacts

SGR

Q S

core

Seemungal T, et al. Am J Respir Crit Care Med. 1998;157:1418-1422. Used with permission from OFFICIAL JOURNALOF THE AMERICAN THORACIC SOCIETY. © AMERICAN THORACIC SOCIETY.

Mean Difference:-15.1*




0-2 Exacerbations

3-8 Exacerbations

*P≤0.002






Treatment of Occupational COPDTreatment of Occupational COPD

PreventionPrevention

•Primary (reduce exposure to irritants)•Elimination•Engineering controls•Administrative controls•Personal protective equipment

•Secondary (screening with questionnaires andspirometry)

•“Tertiary” (the therapeutic options that will beindicated on the subsequent slides)

Treatment of COPD in GeneralTreatment of COPD in GeneralGOLD 2011 Consensus StatementGOLD 2011 Consensus Statement

Goal of the Combined COPD Assessment is toGoal of the Combined COPD Assessment is tostratify subjects based onstratify subjects based on–– Risk for exacerbations, hospitalizations and deathRisk for exacerbations, hospitalizations and death–– SymptomsSymptoms

Metrics used to stratifyMetrics used to stratify–– FEV1% predictedFEV1% predicted–– Exacerbation historyExacerbation history–– Symptoms using either the modified MedicalSymptoms using either the modified Medical

Research Council (mMRC) dyspnea score or theResearch Council (mMRC) dyspnea score or theCOPD Assessment Test (CAT) scoreCOPD Assessment Test (CAT) score

2011 GOLD Consensus Report www.goldcopd.com

Classification of Airflow LimitationClassification of Airflow Limitation

In patients with FEV1/FVC <0.70

GOLD I Mild FEV1 ≥ 80% predicted

GOLD II Moderate 50% ≤ FEV1 < 80% predicted

GOLD III Severe 30% ≤ FEV1 < 50% predicted

GOLD IV Very Severe FEV1 < 30% predicted

Modified Medical Research CouncilModified Medical Research CouncilQuestionnaire for AssessingQuestionnaire for Assessing

BreathlessnessBreathlessnessGrade 0 I only get breathless with strenuous exercise

Grade 1 I get short of breath when hurrying on the level or walkingup a slight hill

Grade 2 I walk slower than people of the same age on the levelbecause of breathlessness, or I have to stop for breathwhen walking on my own pace on the level

Grade 3 I stop for breath after walking about 100 m or after a fewminutes on the level

Grade 4 I am too breathless to leave the house or I am breathlesswhen dressing or undressing

CAT: COPD Assessment TestCAT: COPD Assessment Test

http://www.catestonline.org/images/pdfs/CATest.pdf

GOLD 2011 Consensus StatementGOLD 2011 Consensus Statement !!!!

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FEVFEV11 and Risk for Exacerbations, and Risk for Exacerbations,Hospitalization and DeathHospitalization and Death

Combined placebo data from TORCH, Uplift andCombined placebo data from TORCH, Uplift andECLIPSEECLIPSE

GOLDspirometric

level

Exacerbations /year

Hospitalizations/ year

3-year mortality

GOLD I - - -

GOLD II 0.7 – 0.9 0.11 – 0.2 11%

GOLD III 1.1 – 1.3 0.25 – 0.3 15%

GOLD IV 1.2 – 2.0 0.4 – 0.54 24%


Relationship between FEV1 andRelationship between FEV1 andQuality of LifeQuality of Life


GOLD 2011 consensus statementGOLD 2011 consensus statementShort of breath walking onthe level? NO

2 or more Exacerbationsin Prior Year? YES

OR

FEV1<50%

Short of breath walking onthe level? YES

2 or more Exacerbationsin Prior Year? YES or

OR

FEV1<50%

Short of breath walkingon the level? NO

2 or more Exacerbationsin Prior Year? NO AND

FEV1>50%

Short of breath walkingon the level? YES

2 or moreExacerbations in PriorYear? NO AND

FEV1>50%A B

C D

Achievable Outcomes of TherapyAchievable Outcomes of Therapyin COPDin COPD

Bronchodilators are effective in improvingBronchodilators are effective in improvingairflow and lung volumeairflow and lung volume

Symptomatic patients with appropriateSymptomatic patients with appropriatetreatment can expecttreatment can expect–– Relief of dyspneaRelief of dyspnea–– Improvement of exercise toleranceImprovement of exercise tolerance–– Improvement of quality of lifeImprovement of quality of life–– Decrease in exacerbationsDecrease in exacerbations

Celli et al. Eur Respir J. 2004;23:932-946; Global Initiative for Chronic Obstructive LungDisease. Executive Summary Updated 2004. Available at:http://www.goldcopd.com/workshop/toc.html. Accessed November 14, 2004.

GOLD 2007 Treatment OverviewGOLD 2007 Treatment Overview

GOLD Stage IMild

IIModerate

IIISevere

IVVery Severe

Active reduction of risk factors: influenza vaccineAdd short-acting bronchodilators when needed

Add regular Rx with ≥1 long-actingbronchodilator when needed. Add rehabilitation

Add inhaled corticosteroids(ICS) if repeated exacerbations

Add O2*Consider surgery

GOLD Executive Committee. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2006:1-88.

* If chronic respiratory failure.

GOLD 2011 Treatment OverviewGOLD 2011 Treatment Overview

PatientGroup

First Choice Second Choice Alternative Choice

A SAMA PRN orSABA PRN

LAMA orLABA orSABA and SAMA

Theophylline

B LAMA or LABA LAMA & LABA SABA and/or SAMATheophylline

C ICS + LABA orLAMA

LAMA & LABA PDE4 inhibitorSABA and/or SAMATheophylline

D ICS + LABA orLAMA

ICS & LAMA orICS & LABA & LAMA orICS & LABA & PDE4 inhibitor orLAMA & LABA orLAMA & PDE4 inhibitor

CarbocysteineSABA and/or SAMATheophylline

GOLD 2011 Treatment OverviewGOLD 2011 Treatment OverviewPatientGroup

First Choice Second Choice For Whom is thisAppropriate?

A SAMA PRN orSABA PRN

LAMA orLABA orSABA and SAMA

Not short of breath on the level< 2 exacerbations in prior yearFEV1>50%

B LAMA orLABA

LAMA & LABA Short of breath on the level< 2 exacerbations in prior yearFEV1>50%

C ICS + LABA orLAMA

LAMA & LABA Not short of breath on the level≥ 2 or more Exacerbations inFEV1<50%

D ICS + LABA orLAMA

ICS & LAMA orICS & LABA & LAMA orICS & LABA & PDE4inhibitor orLAMA & LABA orLAMA & PDE4 inhibitor

Short of breath on the level≥ 2 or more Exacerbations inFEV1<50%

New therapeutic optionsNew therapeutic optionsthe MACRO Studythe MACRO Study

Time to First exacerbationEffect of azithromycin

Median = 174 days

Median = 266 days

HR = 0.73 (0.63, 0.84), P < 0.001






Future DirectionsFuture Directions


“Emphysema Predominant” “Airway Disease Predominant”


Han, et al. Radiology 2011;261(1):274

SummarySummary

Occupational COPD represents a significantOccupational COPD represents a significantsocietal burden but is difficult to diagnose insocietal burden but is difficult to diagnose inany given patientany given patient

Treatment includes prevention strategies andTreatment includes prevention strategies andthe usual COPD therapiesthe usual COPD therapies

GOLD guidelines for COPD assessment andGOLD guidelines for COPD assessment andtherapy have been significantly revised intherapy have been significantly revised in20112011

Better distinction of the type of COPD anyBetter distinction of the type of COPD anyspecific patient has is comingspecific patient has is coming…… ““phenotypingphenotyping””

update in copd - woemawoema.org/files/wohc2012/post_grad/wohc2012_woodruff.pdf · update in copd...

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