COPD: Strategies for Diagnosis COPD: Strategies for Diagnosis and Effective Managementand Effective Management

Learning ObjectivesLearning Objectives

•• Increase your ability to recognize the early Increase your ability to recognize the early symptoms of COPDsymptoms of COPD

•• List the critical goals of COPD management List the critical goals of COPD management

•• Outline the recommended COPD therapiesOutline the recommended COPD therapies

•• Develop successful strategies to assist your Develop successful strategies to assist your patients with smoking cessation patients with smoking cessation

Accreditation StatementAccreditation Statement

Boston University School of Medicine is accredited by theBoston University School of Medicine is accredited by theAccreditation Council for Continuing Medical Education (ACCME)Accreditation Council for Continuing Medical Education (ACCME)to provide continuing medical education for physicians.to provide continuing medical education for physicians.

Boston University School of Medicine designates this educationalBoston University School of Medicine designates this educationalactivity for a maximum of activity for a maximum of 1 AMA PRA Category 1 Credit1 AMA PRA Category 1 Credit™™..Physicians should only claim credit commensurate with the extentPhysicians should only claim credit commensurate with the extentof their participation in the activity.of their participation in the activity.

In order to receive CME/CE credit for this teleconference, complIn order to receive CME/CE credit for this teleconference, complete theete theProgram Evaluation and Claim for Credit forms that is on our WebProgram Evaluation and Claim for Credit forms that is on our Websitesiteat at www.bu.eduwww.bu.edu/CME. /CME.

Target AudienceTarget AudiencePrimary care physicians, nurse practitioners, and physician assiPrimary care physicians, nurse practitioners, and physician assistantsstants

Grant SupportGrant Support

This program is supported by an educational grant from BoehringeThis program is supported by an educational grant from Boehringer r Ingelheim and Pfizer Inc.Ingelheim and Pfizer Inc.

Planning Committee Disclosures Planning Committee Disclosures

Julie WhiteJulie WhiteAdministrative DirectorAdministrative DirectorContinuing Medical EducationContinuing Medical EducationBoston University School of MedicineBoston University School of MedicineBoston, MassachusettsBoston, Massachusetts

Julie White has nothing to disclose.Julie White has nothing to disclose.

Lara ZisblattLara ZisblattContinuing Medical EducationContinuing Medical EducationBoston University School of MedicineBoston University School of MedicineBoston, MassachusettsBoston, Massachusetts

Lara Zisblatt has nothing to disclose. Lara Zisblatt has nothing to disclose.

Faculty DisclosureFaculty Disclosure

Dennis E. Niewoehner, MD Dennis E. Niewoehner, MD

Professor of MedicineProfessor of MedicineUniversity of MinnesotaUniversity of MinnesotaMinneapolis, MinnesotaMinneapolis, Minnesota

Dennis E. Niewoehner, MD, serves as a consultant, receives grantDennis E. Niewoehner, MD, serves as a consultant, receives grantsupport, and is on the speakerssupport, and is on the speakers’’ bureau for Boehringer Ingelheim and bureau for Boehringer Ingelheim and for Pfizer Inc.; and serves as a consultant for Adams Respiratorfor Pfizer Inc.; and serves as a consultant for Adams Respiratory y Therapeutics, Forest Laboratories, and GlaxoSmithKline. Therapeutics, Forest Laboratories, and GlaxoSmithKline.

Dr. Niewoehner plans to discuss offDr. Niewoehner plans to discuss off--label/investigational uses of label/investigational uses of formoterol, salmeterol, or tiotropium for managing exacerbationsformoterol, salmeterol, or tiotropium for managing exacerbationsof COPD. of COPD.

COPD: Optimal Approaches COPD: Optimal Approaches for Effective Primary Care for Effective Primary Care

Dennis E. Niewoehner, MDDennis E. Niewoehner, MDProfessor of MedicineProfessor of Medicine

University of MinnesotaUniversity of MinnesotaMinneapolis, MinnesotaMinneapolis, Minnesota

COPD Definition and PathophysiologyCOPD Definition and Pathophysiology

•• COPD is defined as a preventable and COPD is defined as a preventable and treatable lung disease characterized by treatable lung disease characterized by airflow limitation that is not fully reversibleairflow limitation that is not fully reversible11

•• PathophysiologyPathophysiology–– Chronic bronchitis, particularly small airwaysChronic bronchitis, particularly small airways

–– Emphysema Emphysema

COPD = chronic obstructive pulmonary disease.

1. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2006. http://www.goldcopd.org.

COPD PrevalenceCOPD Prevalence

•• ~12.1 million Americans have COPD~12.1 million Americans have COPD11

•• As many as 24 million Americans may have COPD, As many as 24 million Americans may have COPD, based on data from lung function studies and National based on data from lung function studies and National Health and Nutrition Examination SurveysHealth and Nutrition Examination Surveys1,21,2

•• COPD occurs later in adulthood, as soon COPD occurs later in adulthood, as soon as the early 40s, in both males and femalesas the early 40s, in both males and females

•• COPD prevalence increases with ageCOPD prevalence increases with age–– Historically, COPD has been seen as a male disease Historically, COPD has been seen as a male disease

–– The gender balance is shifting and COPD has The gender balance is shifting and COPD has been increasing among women over the past been increasing among women over the past 20 years20 years22

1. NHLBI. Data Fact Sheet: Chronic Obstructive Pulmonary Disease. NIH Publication 03-5229.Bethesda, Md: US DHHS; 2003.

2. CDC. Surveillance Summaries, August 2, 2002. MMWR. 2002;51(No. SS-6).

COPD: The RealityCOPD: The RealityMany patients are <65 yrs of ageMany patients are <65 yrs of age

•• ~50% of COPD patients are younger than age 65~50% of COPD patients are younger than age 6511

•• Patients <65 yrs accounted for 67% of COPD office Patients <65 yrs accounted for 67% of COPD office visits and 43% of hospitalizationsvisits and 43% of hospitalizations22

1. Tinkelman D, Corsello P. Am J Manag Care. 2003;9:767-771.2. Sin DD, et al. Am J Respir Crit Care Med. 2002;165:704-707.

COPD: The RealityCOPD: The RealityMany patients are womenMany patients are women

•• In 2000, women accounted for 63% of COPD casesIn 2000, women accounted for 63% of COPD cases•• COPD mortality rates for women (1980COPD mortality rates for women (1980--2000) have 2000) have

increased by 182% increased by 182% •• In 2000, COPD hospitalizations for women In 2000, COPD hospitalizations for women

outnumbered those for men (404,000 vs. 322,000)outnumbered those for men (404,000 vs. 322,000)Mannino DM, et al. MMWR. 2002;51(6 suppl):1-16.

COPD MortalityCOPD Mortality

•• Of the top 5 causes of death, COPD is the Of the top 5 causes of death, COPD is the 44thth leading cause of death in the USleading cause of death in the US11

•• About 120,000 people die from COPD each About 120,000 people die from COPD each yearyear22

•• Of the leading causes of death, COPD is the Of the leading causes of death, COPD is the only one on the increaseonly one on the increase22

•• By 2020, COPD will become the 3By 2020, COPD will become the 3rdrd leading leading cause of death worldwidecause of death worldwide11

1. National Center for Health Statistics. US DHHS, CDC, 2001. 2. CDC. Surveillance Summaries, August 2, 2002. MMWR. 2002;51(No. SS-6).

COPD Morbidity COPD Morbidity (cont(cont’’d)d)

•• COPD accounts for ~1.5 million visits to COPD accounts for ~1.5 million visits to Emergency Departments each year due to Emergency Departments each year due to disease exacerbationdisease exacerbation11

•• ~2% of all hospitalizations are due to COPD~2% of all hospitalizations are due to COPD22

•• COPD accounts for approximately 14 million COPD accounts for approximately 14 million office visits per yearoffice visits per year33

1. Parshall MB. Nurs Res. 1999;48:62-70. 2. Mannino DM, et al. Respir Care. 2002;47:1184-1199. 3. Minkoff NB. J Manag Care Pharm. 2005;11(6 suppl A):S3-S7.

Direct and Indirect Costs of COPDDirect and Indirect Costs of COPD

•• Estimated direct medical costs for COPD are Estimated direct medical costs for COPD are approximately $18 billion per yearapproximately $18 billion per year11

•• Indirect costs due to missing work or Indirect costs due to missing work or premature death have been estimated as high premature death have been estimated as high as $14 billion per yearas $14 billion per year11

–– COPD is associated with numerous coCOPD is associated with numerous co--morbidities, morbidities, such as anxiety/depression and osteoporosis such as anxiety/depression and osteoporosis

•• Approximately 70% of all healthcare expenditures for Approximately 70% of all healthcare expenditures for COPD are related to acute exacerbations of COPDCOPD are related to acute exacerbations of COPD22

1. NHLBI. Data Fact Sheet: Chronic Obstructive Pulmonary Disease. NIH Publication 03-5229. Bethesda, Md: US DHHS; 2003. 2. Hilleman DE, et al. Chest. 2000;118:1278-1285.

COPD: Etiologic FactorsCOPD: Etiologic Factors1,21,2

EstablishedEstablished ProbableProbable PossiblePossible•• Cigarette smokingCigarette smoking

•• Exposure to Exposure to 2nd2nd--hand smokehand smoke

•• Occupational Occupational exposure exposure

•• αα11--Antitrypsin Antitrypsin deficiencydeficiency

•• Air pollutionAir pollution

•• HyperHyper--reactive reactive airwaysairways

•• Alcohol Alcohol

•• Poverty Poverty

•• Low birth weightLow birth weight

•• Childhood Childhood respiratory respiratory infectionsinfections

•• Family historyFamily history

•• AtopyAtopy

•• IgA deficiencyIgA deficiency

•• Blood type ABlood type A

1. Tager IB, et al. Am Rev Respir Dis. 1988;138:837-849. 2. Holt PG. Thorax. 1987;42:241-249.

Suspected COPD Patients:Suspected COPD Patients:Insights From the Basic H&PInsights From the Basic H&P

•• A current/former smoker?A current/former smoker?•• Breathing difficulties during mild exercise or at night?Breathing difficulties during mild exercise or at night?•• Restricting physical activity?Restricting physical activity?•• Complaining about exercise intolerance?Complaining about exercise intolerance?•• Having a productive morning cough? A cough lasting Having a productive morning cough? A cough lasting

more than 2 weeks?more than 2 weeks?•• Having a decline in activities of daily living (ADLs)?Having a decline in activities of daily living (ADLs)?

–– Groceries now being delivered?Groceries now being delivered?–– No longer walking to work? Using a golf cart instead of walking?No longer walking to work? Using a golf cart instead of walking?–– How is job performance?How is job performance?

COPD = chronic obstructive pulmonary disease; H&P = history and physical.Ferguson GT, et al. Chest. 2000;117:1146-1161.

Who Should Have Office Who Should Have Office Spirometry?Spirometry?

•• Anyone with one or more of the Anyone with one or more of the ““cardinalcardinal””symptoms of COPDsymptoms of COPD–– Unexplained dyspnea Unexplained dyspnea -- most importantmost important–– Productive coughProductive cough–– Wheezing or chronic chest congestionWheezing or chronic chest congestion

•• Repeat spirometry needed only if major Repeat spirometry needed only if major worsening of symptoms. It is not a useful worsening of symptoms. It is not a useful guide to therapyguide to therapy

Ferguson GT, et al. Chest. 2000;117:1146-1161.

SpirometrySpirometry

NormalNormalFEVFEV11

55

FVCFVC

22 33 44 55 776600 11

FVCFVC

FEVFEV11

COPDCOPD

SecondsSeconds

FEV1

FVC

FEV1/FVC

44

3LitersLitersExpired

3

Expired 22

11

00

Features of COPD

Goals of COPD ManagementGoals of COPD Management

•• Prevent disease progressionPrevent disease progression•• Relieve symptomsRelieve symptoms•• Improve lung functionImprove lung function•• Improve exercise toleranceImprove exercise tolerance•• Improve health statusImprove health status•• Prevent and treat complicationsPrevent and treat complications•• Prevent and treat exacerbationsPrevent and treat exacerbations•• Reduce mortalityReduce mortalityGlobal strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2006. http://www.goldcopd.org

Treatment of COPD According Treatment of COPD According to Spirometric Stage of Diseaseto Spirometric Stage of Disease

Add long-term oxygen if chronic respiratory failure.Consider surgical treatments

Add inhaled glucocorticosteroids if repeated exacerbations

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

Active reduction of risk factor(s); influenza vaccinationActive reduction of risk factor(s); influenza vaccinationAddAdd shortshort--acting bronchodilator (when needed)acting bronchodilator (when needed)

• FEV1/FVC <0.70• FEV1 ≥80% predicted

• FEV1/FVC <0.70• 50% ≤FEV1

<80% predicted

• FEV1/FVC <0.70• 30% ≤FEV1 <50%

predicted

• FEV1/FVC <0.70• FEV1 <30%

predicted plus chronic respiratory failure

I: MildI: Mild II: ModerateII: Moderate III: SevereIII: Severe IV: Very SevereIV: Very Severe

NHLBI/WHO Global Initiative for Chronic Obstructive Lung DiseaseNHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease.. November 2006.November 2006.NHLBI/WHO Global Initiative for Chronic Obstructive Lung DiseaseNHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease.. November 2006.November 2006.

COPD TherapiesCOPD Therapies

•• Smoking cessationSmoking cessation

•• BronchodilatorsBronchodilators

•• Antibiotics*Antibiotics*

•• Corticosteroids*Corticosteroids*

•• OxygenOxygen

•• ImmunizationsImmunizations

•• Rehabilitation/selfRehabilitation/self--managementmanagement

•• SurgerySurgery*Off*Off--label indication.label indication.

Prevention of COPDPrevention of COPDSmoking CessationSmoking Cessation

2.82.8

2.02.0

2.62.6

2.22.2

2.42.4

00 66 101044 8822

Sustained quittersSustained quitters

Continuing smokersContinuing smokers

Mea

n FE

VM

ean

FEV 11

(L)

(L)

Years of followYears of follow--upup

Anthonisen NR, et al.Anthonisen NR, et al. Am J Respir Crit Care Med.Am J Respir Crit Care Med. 2002;166:6752002;166:675--679.679.

Smoking Cessation InterventionsSmoking Cessation Interventions

InterventionIntervention StudiesStudies EvaluatedEvaluatedAbsolute Increase Absolute Increase in Cessation Ratein Cessation Rate

Brief clinician contactBrief clinician contact 16 (Cochrane)16 (Cochrane)7 (US DHHS)7 (US DHHS)

2%2%2.3%2.3%

Group counselingGroup counseling 6 (Cochrane)6 (Cochrane)58 (US DHHS)58 (US DHHS)

10%10%3.1%3.1%

Nicotine gumNicotine gum 51 (Cochrane)51 (Cochrane)13 (US DHHS)13 (US DHHS)

8%8%6.6%6.6%

Nicotine nasal sprayNicotine nasal spray 4 (Cochrane)4 (Cochrane)3 (US DHHS)3 (US DHHS)

12%12%16.6%16.6%

BupropionBupropion(300 mg/d SR)(300 mg/d SR)

7 (Cochrane)7 (Cochrane)2 (US DHHS)2 (US DHHS)

10%10%13.2%13.2%

DHHS = Department of Health and Human Services; SR = sustained rDHHS = Department of Health and Human Services; SR = sustained release.elease.Marlow SP, Stoller JK.Marlow SP, Stoller JK. Respir Care.Respir Care. 2003;48:12382003;48:1238--1254.1254.

Smoking Cessation: Continuous Smoking Cessation: Continuous Abstinence Rates With VareniclineAbstinence Rates With Varenicline

Gonzales D, et al.Gonzales D, et al. JAMA. JAMA. 2006;296:472006;296:47--55.55.

Note: All between-treatment-group comparisons are statistically significantly different except where noted.

Jorenby DE, et al.Jorenby DE, et al. JAMA. JAMA. 2006;296:562006;296:56--63.63.

Weeks 9-52

P = .057

0

20

5

10

15

25

30

35

40

45

50

Con

tinuo

us A

bstin

ence

, %

Weeks 9-12 Weeks 9-24

Varenicline (n=352)Bupropion SR (n=329)Placebo (n=344)

Weeks 9-12 Weeks 9-24 Weeks 9-520

20

5

10

15

25

30

35

40

45

50

P = .08

Varenicline (n=344)Bupropion SR (n=342)Placebo (n=341)

Con

tinuo

us A

bstin

ence

, %

Stable COPDStable COPDBronchodilator TherapyBronchodilator Therapy

∆∆FE

VFE

V 11(%

)(%

)

00 22 44 66 88

Ipratropium Bromide andIpratropium Bromide andAlbuterol Sulfate

4040Albuterol Sulfate

IpratropiumIpratropiumAlbuterolAlbuterol

3030

2020

1010

00

Hours After Test DoseHours After Test Dose

FEVFEV1 1 = forced expiratory volume in 1 second.= forced expiratory volume in 1 second.In chronic obstructive pulmonary disease, a combination of ipratIn chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more ropium and albuterol is more effective than either agent alone.effective than either agent alone. Chest. Chest. 1994;105:14111994;105:1411--1419.1419.

Salmeterol for Stable COPDSalmeterol for Stable COPD

SalmeterolSalmeterol0.50.5 IpratropiumIpratropium

PlaceboPlacebo0.40.4

∆∆FE

VFE

V 11(L

)(L

)

0.30.3

0.20.2

0.10.1

00

Mahler DA, et al.Mahler DA, et al. Chest. Chest. 1999;115:9571999;115:957--965.965.

22 44 66 88 1010 1212

Time (hours)Time (hours)

FEVFEV1 1 = forced expiratory volume in 1 second.= forced expiratory volume in 1 second.

Tiotropium AM Dosing: Tiotropium AM Dosing: Improvement in FEVImprovement in FEV11 Over 24 HoursOver 24 Hours

0.70.7

0.80.8

0.90.9

1.01.0

1.11.1

1.21.2

1.31.3

––33 00 33 66 99 1212 1515 1818 2121 2424

Tiotropium (Tiotropium (nn=37)=37)Placebo (Placebo (nn=33)=33)

FEV

FEV 11

(L)

(L)

9 9 AMAM 3 3 PMPM 9 9 PMPM 3 3 AMAM 9 9 AMAM

Time (hours)Time (hours)FEVFEV1 1 = forced expiratory volume in 1 second.= forced expiratory volume in 1 second.CalverleyCalverley PM, et al.PM, et al. Thorax. Thorax. 2003;58:8552003;58:855--860.860.

Prevention of Exacerbations:Prevention of Exacerbations:Inhaled LongInhaled Long--acting Beta Agonists*acting Beta Agonists*

*Off*Off--label indication.label indication.Relative Risk (95% CI) of ExacerbationRelative Risk (95% CI) of Exacerbation

Favors LABAFavors LABA Favors PlaceboFavors Placebo

0.20.2 110.50.5 22 55

Mahler 2002BrusascoCalverley 1CelliChapmanRennardVan NoordMahler 1999Boyd

SubtotalCalverley 2AalbersRossiWadboDahlSzafranski

SubtotalTotal 0.82 (0.76 0.82 (0.76 –– 0.90)0.90)

0.84 (0.74 0.84 (0.74 –– 0.97)0.97)

0.81 (0.73 0.81 (0.73 –– 0.90)0.90)

SalmeterolSalmeterol

FormoterolFormoterol

LABA = longLABA = long--acting beta agonists.acting beta agonists.Wilt T, et al. AHRQ Report 05Wilt T, et al. AHRQ Report 05--E017E017--2, 2005.2, 2005.

VA Tiotropium Trial:VA Tiotropium Trial:Primary Outcomes*Primary Outcomes*

>>1 Exacerbation (%)1 Exacerbation (%) >>1 COPD Hospitalization (%)1 COPD Hospitalization (%)

4040 1212P = P = .037.037 P = P = .056.056

3030 9932.232.227.927.9

9.59.5

7.07.02020 66

1010 33

00 00PlaceboPlacebo TiotropiumTiotropium PlaceboPlacebo TiotropiumTiotropium

*Off*Off--label indication.label indication.Niewoehner DE.Niewoehner DE. Ann Intern Med. Ann Intern Med. 2005;143:3172005;143:317--326.326.

Antibiotics for COPD Exacerbations:Antibiotics for COPD Exacerbations:Do They Work?Do They Work?

Alonso 1992Alonso 1992

Anthonisen 1987Anthonisen 1987

Elmes 1965Elmes 1965

Jorgensen 1992Jorgensen 1992

Pines 1968Pines 1968

Pines 1972Pines 1972

TotalTotal

Favors placeboFavors placeboFavors antibioticFavors antibiotic

Relative Risk (95% CI)Relative Risk (95% CI)StudyStudy

0.67 (0.56 0.67 (0.56 -- 0.80)0.80)

0.10.1 11 22 55 10100.50.50.20.2

Ram FSF, et al. Cochrane Database of Systematic Reviews 2006, IsRam FSF, et al. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD004403.sue 2. Art. No.: CD004403.

Antibiotics for COPD Exacerbations: Antibiotics for COPD Exacerbations: Is One Better Than Another? Is One Better Than Another?

00

2020

4040

6060

8080

100100

MoxifloxacinMoxifloxacin AmoxicillinAmoxicillin ClarithromycinClarithromycin CefuroximeCefuroxime--axetilaxetil

n = 354 n = 88 n = 114 n = 174

% C

linic

al S

ucce

ss%

Clin

ical

Suc

cess

Wilson R, et al; MOSAIC Study Group.Wilson R, et al; MOSAIC Study Group. Chest. Chest. 2004;125:9532004;125:953--964.964.

SCCOPE:SCCOPE:Time to First Treatment FailureTime to First Treatment Failure

00 6060 120120 18018000

2020

4040

6060

Days on StudyDays on Study

PlaceboPlacebo22--week steroidweek steroid88--week steroidweek steroid

% F

ailu

re%

Fai

lure

SCCOPE = The Systemic Corticosteroids in Chronic Obstructive PulSCCOPE = The Systemic Corticosteroids in Chronic Obstructive Pulmonary monary Disease Exacerbations.Disease Exacerbations.Niewoehner DE, et al.Niewoehner DE, et al. N Engl J Med. N Engl J Med. 1999;340:19411999;340:1941--1947.1947.

Primary Outcome Primary Outcome -- EUROSCOPEUROSCOP

5050

00

--5050

--100100

--150150

--200200

00 66 1212 1818 2424 3030 3636--66

Budesonide Budesonide ((n n = 634)= 634)

Placebo Placebo ((n n = 643)= 643)

Study drugstarted∆∆

FEV

FEV 11

(mL)

(mL)

Study MonthStudy Month

Pauwels RA, et al.Pauwels RA, et al. N Engl J Med. N Engl J Med. 1999;340:19481999;340:1948--1953.1953.

Prevention of Exacerbations:Prevention of Exacerbations:Inhaled CorticosteroidsInhaled Corticosteroids

ICS = inhaled corticosteroids.ICS = inhaled corticosteroids.Wilt TJ, et al. AHRQ Report 05Wilt TJ, et al. AHRQ Report 05--E017E017--2, 2005.2, 2005.

Relative Risk (95% CI) of ExacerbationRelative Risk (95% CI) of Exacerbation0.20.2 110.50.5 22 55

Burge Burge Calverley 03 Calverley 03

Mahler 02 Mahler 02 van der Valk van der Valk

Paggiaro Paggiaro SubtotalSubtotal

Bourbeau Bourbeau Calverley 04 Calverley 04

Szafranski Szafranski Vestbo Vestbo

SubtotalSubtotal

FluticasoneFluticasone

BudesonideBudesonide

Weir Weir SubtotalSubtotal

TotalTotal

BeclomethasoneBeclomethasone0.64 (0.41 0.64 (0.41 -- 1.00)1.00)

0.78 (0.66 0.78 (0.66 -- 0.91)0.91)

0.81 (0.68 0.81 (0.68 -- 0.95)0.95)

0.78 (0.70 0.78 (0.70 -- 0.88)0.88)

Favors ICSFavors ICS Favors PlaceboFavors Placebo

LongLong--term Oxygen for COPD:term Oxygen for COPD:NOTT TrialNOTT Trial

1.01.0

Surv

ival

Pro

port

ion

Surv

ival

Pro

port

ion

NOTT = Nocturnal Oxygen Therapy Trial Group; HTC = hematocrit. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med. 1980;93:391-398.

Months on StudyMonths on Study

00

0.80.8

0.60.6

0.40.4

0.20.2

66 1212 1818 363630302424 424200

OO22 18 hours/day18 hours/day

OO2 2 12 hours/day12 hours/day P P = .01= .01

LongLong--term Oxygen for COPD:term Oxygen for COPD:Moderate HypoxemiaModerate Hypoxemia

Months on StudyMonths on Study

Surv

ival

Pro

port

ion

Surv

ival

Pro

port

ion

Gorecka D, et al.Gorecka D, et al. Thorax. Thorax. 1997;52:6741997;52:674--679.679.

1.001.00

0.750.75

0.500.50

0.250.25

00

ControlsControls

Chronic oxygenChronic oxygen

242400 72724848 9696

Prevention of COPD Prevention of COPD HospitalizationHospitalization: : Influenza VaccinationInfluenza Vaccination

160160

120120

8080

4040

00Influenza 1Influenza 1 Influenza 3Influenza 3Influenza 2Influenza 2Interim 1Interim 1 Interim 2Interim 2

VaccinatedVaccinated

UnvaccinatedUnvaccinated

Res

pira

tory

Hos

pita

lizat

ions

/R

espi

rato

ry H

ospi

taliz

atio

ns/

1000

Pat

ient

1000

Pat

ient

-- Yea

rsYe

ars

PeriodPeriod

Nichol KL, et al.Nichol KL, et al. Ann Intern Med. Ann Intern Med. 1999;130:3971999;130:397--403.403.

Efficacy of Pulmonary RehabilitationEfficacy of Pulmonary Rehabilitation

Walking distance (m)Walking distance (m)Quality of life (CRQ score)Quality of life (CRQ score)

00

5050

100100

150150

200200

250250

ControlControl RehabilitationRehabilitation

2020

1616

1212

88

44

00PlaceboPlacebo RehabilitationRehabilitation

BaselineBaseline 6 weeks6 weeks 1 year1 year

CRQ = Chronic Respiratory Disease Questionnaire.CRQ = Chronic Respiratory Disease Questionnaire.Griffiths TL, et al.Griffiths TL, et al. Lancet.Lancet. 2000;355:3622000;355:362--368.368.

QUESTIONSQUESTIONS