This program consists of an MP3 audio file and this PDF monograph. The audio portion will require approximately 60 minutes to complete. Reading the monograph and completingthe post-test will require an additional 60 minutes.

1. Print a copy of this PDF monograph file which includes the post-test and program evaluation.

2. Read the monograph in its entirety.

3. Play the audio file by clicking on the play button.

4. After reading the monograph and listening to the audio, complete the post-test andevaluation found on the last two pages of this monograph. Mail the pages according to the printed instructions. A certificate of credit for satisfactory completion (70% or better)will be mailed within 4 to 6 weeks.

I N S T R U C T I O N S

1

Release Date: May 28, 2006 • Credit Expiration Date: May 28, 2008

James F. Donohue, MDProfessor of MedicineChief, Division of Pulmonary and

Critical Care MedicineUniversity of North Carolina School of MedicineChapel Hill, North Carolina

Target AudienceThis educational activity is designed to meet the needs of primarycare physicians, nurses, nurse practitioners, and physician assis-tants with an interest in the epidemiology, diagnosis, and manage-ment of chronic obstructive pulmonary disease or asthma.

Learning ObjectivesUpon completion of this activity, the participant should be able to:

• Describe the pathophysiology of COPD and asthma, and theunique pathogenic characteristics of each condition

• Discuss the early diagnosis of COPD, the staging of diseaseseverity, and the use of FEV1 reduction as a prognostic indicator

• Describe the latest pharmacological therapy for mild, moder-ate, and severe COPD and asthma

• Discuss the optimal smoking cessation approaches that pri-mary care providers can adopt for the prevention of COPD intheir patients

ABBREVIATIONS USEDAP-1, activated protein 1ATS, American Thoracic SocietyCOPD, chronic obstructive pulmonary diseaseDPI, dry-powder inhalerERS, European Respiratory SocietyFEV1, forced expiratory volume in 1 second

FDA, Food and Drug AdministrationFVC, forced vital capacityGOLD, Global Initiative for Chronic Obstructive Lung DiseaseICS, inhaled corticosteroidIL, interleukinLABD, long-acting bronchodilatorLBA, long-acting beta agonistLHS, Lung Health StudyMDI, multi-dose inhalerNHLBI, National Heart, Lung, and Blood InstitutePFT, pulmonary function test(ing)ROSU, reliever/oral steroid useSABD, short-acting bronchodilatorTNF, Tumor necrosis factorTORCH, Towards A Revolution in COPD Health study

Ketan Sheth, MD, MBA Medical DirectorLafayette Allergy & Asthma ClinicLafayette, Indiana

Family Medicine Consultant: William A. Schwer, MD Chairman Department of Family MedicineRush University Medical Center • Chicago, IL

Interviewer: Seymour I. Schlager, MD, PhDCONFLICT OF INTEREST STATEMENT James F. Donohue, MD discloses that he has received compensation as a member of speakers’bureaus and advisory boards for GlaxoSmithKline.

Ketan K. Sheth, MD, MBA, FAAAAI discloses that he has received compensation as a member ofspeakers’ bureaus for AstraZeneca, GlaxoSmithKline, Pfizer Inc, sanofi-aventis, and Schering-Plough; for product consultation for Altana Inc., and GlaxoSmithKline, and as a member of adviso-ry committees for Altana Inc., and GlaxoSmithKline. He also is a shareholder in Merck & Co., Inc.

William A. Schwer, MD reports that he has no significant financial interest or other relationshipswith the manufacturer(s) of any commercial product(s) or service(s) discussed in this educationalpresentation or with the commercial supporter of this activity.

Seymour I. Schlager, MD, PhD discloses that he has received compensation as a product consultantfor Abbott Laboratories and is a share holder of Abbott Laboratories and Pfizer Inc.

This educational activity may contain discussion of published and/or investigational uses of pharma-ceutical agents. Some uses of these agents may not have been approved by the FDA. Please refer tothe official prescribing information for each product for discussion of approved indications, con-traindications, and warnings.

CREDIT STATEMENTSPhysician CME: This activity has been planned and implemented in accor-dance with the Essential Areas and polices of the Accreditation Council for

Continuing Medical Education (ACCME) through the joint sponsorship of AKH Inc. and MedicalCommunications Media, Inc. AKH Inc. is accredited by the ACCME to provide continuing medicaleducation for physicians.

AKH Inc. designates this educational activity for a maximum of 2 AMA PRA Category 1Credit(s)™. Physicians should only claim credit commensurate with the extent of their participationin the activity.

Release Date: May 28, 2006 • Credit Expiration Date: May 28, 2008

AAFP CME: This activity has been reviewed and is acceptable for up to 2 Prescribed credits by theAmerican Academy of Family Physicians. AAFP accreditation begins 8/1/06. Term of approval isfor one year from this date with option for yearly renewal.

Physician Assistant CME: This program has been reviewed and is approved for a maxi-mum of 2 hours of AAPA Category I (Preapproved) CME credit by the PhysicianAssistant Review Panel of the American Academy of Physician Assistants. Approval is

valid for one year from the issue date of May 28, 2006. Participants may submit the self-assess-ment at any time during that period.

This program was planned in accordance with AAPA’s CME Standards for Enduring MaterialPrograms and for Commercial Support of Enduring Material Programs.

Nursing CE: AKH Inc. is accredited as a provider of continuing nursing education bythe American Nurses Credentialing Center's Commission on Accreditation. AKH Inc.designates this educational activity for 2.4 contact hours.

Release Date: May 28, 2006 • Credit Expiration Date: May 28, 2008

Nurse Practitioner CE: AKH Inc. is approved as a provider of nurse practitionercontinuing education by the American Academy of Nurse Practitioners. Provider#030803. AKH Inc. designates this educational activity for 2.4 contact hour(s).

Release Date: May 28, 2006 • Credit Expiration Date: May 28, 2008

It should take approximately 120 minutes to listen to the CD discussion, read the monograph andcomplete the self-assessment. Successful completion of the self-assessment, defined as a cumulativescore of at least 70% correct, is required to earn credit. Participation is free.

©2006, Medical Communications Media, Inc. All Rights Reserved.

This publication is designed for use with an audio CD. None of the con-tents may be reproduced in any form without prior written permission

of the publisher. The opinions expressed in this publication and audio CD are those of thespeakers and do not necessarily reflect the opinions or recommendations of their affiliatedinstitutions, the publisher, AKH Inc., or GlaxoSmithKline. Any medications, or other diag-nostic or treatment procedures discussed by the program speakers should not be utilized byclinicians without evaluation of their patients' conditions and of possible contraindicationsor risks, and without a review of any applicable manufacturer's product information andcomparison with the recommendations of other authorities.

Supported through an educational grant from

Published by...

2

IntroductionChronic obstructive pulmonarydisease (COPD) is a syndromecharacterized and defined by asingle physiological parameter:limitation of expiratory airflow.1

COPD has gained interest as amajor public health concern andis currently the focus of intenseresearch because of its persistent-ly increasing prevalence, mortali-ty, and disease burden. COPDcurrently ranks as the fourth lead-ing cause of death in the UnitedStates, surpassed only by heartdisease, cancer, and cerebrovascu-lar disease.2,3 Indeed, COPD isone of the leading causes of dis-ability worldwide and the onlydisease for which prevalence andmortality rates continue to rise.One of the more troubling aspectsof COPD is that it is under-recog-nized by patients, underdiagnosedby physicians, and arguablyundertreated. Clearly, it is imper-ative that primary care providersunderstand the pathophysiologicbasis of COPD, how to accuratelydiagnose and stage the disease,and treat it appropriately bymatching therapy to diseaseseverity. In addition, COPD is alargely preventable disease, and itis incumbent on the primary careprovider to appreciate optimalstrategies to help their patientsstop smoking and take other stepsto prevent disease progression.

Similarly, asthma is a complexsyndrome, the incidence ofwhich has increased over the pastseveral decades.4 UnlikeCOPD, for many patients, asth-ma has its roots in infancy,resulting in a complex constella-

tion of symptoms that may befound in both adults and chil-dren.5 To properly managepatients with this disease, theprimary care provider must com-prehend the pathogenic mecha-nisms underlying the many vari-ants of asthma, identify factorsthat initiate, intensify, and modu-late the inflammatory responseof the airway, and determine howthese immunologic and biologicprocesses produce the character-istic airway abnormalities.5

This monograph is intended toprovide an overview of these twoimportant obstructive respiratorydiseases with the goal of provid-ing practical information for themanagement of patients withCOPD and asthma in the primarycare setting. The following topicswill be covered; in all cases, simi-larities and distinctions betweenthe two conditions will be high-lighted:

• Prevalence and epidemiology

• Pathogenesis and pathophysi-ology

• Diagnosis and staging of the disease

• Prevention and treatmentstrategies

Prevalence andEpidemiologyObstructive lung diseases such asasthma and COPD constitute aserious public health issue withsignificant financial and resourceburdens on the health care sys-tem. In 2002, almost 15 millionadults and more than 6 millionchildren were diagnosed withasthma. The disease accounted fornearly 2 million emergencydepartment visits, 500,000 hospi-talizations, and 5,000 deaths eachyear, with estimated direct andindirect annual costs to the healthcare system of $14.5 billion(Figure 1).6-10

Similarly, over 20 millionAmericans suffer from some formof COPD.1,2 COPD is responsiblefor more than 1.5 million emer-

Prevalence of asthma and COPD in the United States6-10

FIGURE 1

3

gency department visits, 726,000hospitalizations, 120,000 deaths,and more than $32 billion in directand indirect costs each year(Figure 1).6-10 The prevalence ofCOPD is likely to be underesti-mated for several reasons, includ-ing the delay in establishing thediagnosis, the variability in defin-ing the disease, and the lack ofage-adjusted estimates. Ageadjustment is important becausethe prevalence of COPD in indi-viduals under the age of 45 yearsis low, while the prevalence ishighest in patients over 65 years ofage. Approximately 65% of thepatients treated for COPD in theUnites States are more than 65years old and the prevalence of thedisease in those over 65 is fourtimes higher than in the 45- to 64-year-old group.11,12 In contrast,the onset of asthma generallyoccurs early in life, although somepatients may present with asthmafor the first time in late adulthood.In total, data from NHANES IIIsuggest that approximately 44 mil-lion Americans (adults and chil-dren) have evidence of impairedlung function, involving eitherCOPD or asthma. 7

Pathogenesis andPathophysiologyBoth asthma and COPD are char-acterized by airflow obstructionand chronic persistent airwayinflammation, and many patientswith asthma have characteristicsof COPD, an overlap that oftenmakes it difficult to establish anaccurate diagnosis (Figure 2). 13

Indeed, the similarities between

COPD and asthma were noted inthe 1960s with the introduction ofthe Dutch hypothesis, suggestingthat various types of airwayobstruction are merely differentexpressions of a single diseasespectrum that requires predispos-ing host-derived and environmen-tal factors for their onset (e.g.,genetic factors, airway hyper-responsiveness, atopy, gender,age, exposure to allergens, andsmoking).14-16

In 2004, the American ThoracicSociety (ATS) and the EuropeanRespiratory Society (ERS)described COPD as “…a prevent-able and treatable disease statecharacterized by airflow limita-tion that is not fully reversible.The airflow limitation is usuallyprogressive and is associated withan abnormal inflammatoryresponse of the lungs to noxiousparticles or gases, primarilycaused by cigarette smoking.Although COPD affects the lungs,it also produces significant sys-temic consequences.”17 The ATS

/ERS statement also supports theposition that COPD and asthmaoften coexist.

COPD typically presents inmidlife and is characterized byprogressive airflow limitation andairway inflammation leading to agradual and irreversible loss oflung function; the primary condi-tions that fall under the termCOPD are chronic bronchitis andemphysema (Figure 2).17 On theother hand, asthma is character-ized by chronic airway inflamma-tion associated with widespreadbut variable airflow obstruction.Most asthmatics suffer fromepisodic airway obstruction,unlike patients with COPD whohave progressive airway obstruc-tion. Further, unlike COPD, air-flow obstruction in asthma oftenreverses completely either sponta-neously or with treatment.18,19

Airflow obstruction in COPD isassociated with an abnormalinflammatory response of thelungs to toxic particles or gases,

The overlap of asthma and COPD13

FIGURE 2

4

including tobacco smoke (eitherdue to directly smoking or fromsecond-hand smoke), or throughoccupational exposure to coaldust, asbestos, and chemicals.8,15

Because the majority of diagnosedCOPD is related to tobacco expo-sure, there has been considerablework to define the link betweentobacco smoke and ongoing air-way and parenchymal remodeling.Multiple pathogenic mechanismslikely contribute to the develop-ment of COPD (see below).

In addition, since only 20% ofsmokers acquire COPD, geneticpredisposition seems to play animportant role in the pathogenesisof this disease.15 For example,patients with a genetic deficiencyin alpha 1-antitrypsin are prone todevelop early-onset emphysema. 15

Another important factor linkingsmoking to inflammation may beoxidative stress induced by oxi-dants found in cigarette smoke;reactive oxygen species such assuperoxide anions and hydrogenperoxide generated as a conse-quence of oxidative stress canpropagate the inflammatoryresponse by activating severalredox-sensitive transcription fac-tors (e.g., NF-kappa B and acti-vated protein 1 [AP-1]) that canupregulate expression of a num-ber of proinflammatorycytokines.20,21 These cytokinescan trigger and propagate aninflammatory cascade as shownin Figure 3.22 Cigarette smokeinduces epithelial cells and alve-olar macrophages to releasetumor necrosis factor-α (TNFα),which in turn, increases produc-tion of interleukin 8 (IL-8); both

of these cytokines are potentchemoattractants that cause aninflux of monocytes, neutrophilsand CD8 lymphocytes. Thesecells, when acted upon by proin-flammatory cytokines, are stimu-lated to release proteinases thatcontribute to alveolar septal dis-ruption, fibrosis, and mucushypersecretion.13, 22-25 Thisadaptive immune response con-tinues in the peripheral airwaysof patients with COPD even aftersmoking cessation.26

Genetic susceptibility to oxidativestress induced by cigarette smokemay also explain why somesmokers develop COPD and oth-ers do not. Smokers who developCOPD appear to have a higherdegree of oxidative stress thanthose with a similar smoking his-tory but no evidence of COPD.26

Although bronchial inflammationcharacterizes both COPD andasthma, the pathogenic inflamma-tory processes of these diseasesdiffer significantly (Table 1).13

The characteristic physiologicabnormality in asthma iseosinophilic inflammation;indeed, an increase in activatedand degranulating eosinophils hasbeen demonstrated in bronchialbiopsies and bronchoalveolarlavage of asthma patients.5,13

Unlike the neutrophil and CD8-lymphocyte predominance inCOPD, CD4+ lymphocytesorchestrate an eosinophilicinflammation and mast celldegranulation that characterizethe bronchoconstrictor responsesin acute asthma. In addition, IgEantibodies have been linked to theinitiation and persistence of air-way responses to allergens.5

COPD Is a Disease of Inflammation22

FIGURE 3

5

In asthma, inhaled allergensencounter dendritic cells that linethe airway, and these cellsmigrate to draining lymph nodeswhere they present processedallergen (antigen) to T- and B-cells. The B-cells are inducedthrough a complex series of costimulatory signals to produceIgE, which binds to high-affinityreceptors on the surface of mastcells in tissue. When the allergensubsequently interacts with thereceptor-bound IgE molecules,activation and degranulation ofthe mast cells occur, resulting inrelease of histamine andleukotrienes, and causing smoothmuscle constriction that results inthe early-phase airway obstruc-tion seen in asthma.5 Prolonged,late-stage reactions develop as aresult of the release of cytokinesand chemokines (IL-4, IL-5, IL-13) generated by the residentinflammatory cells in the lung(Table 1).5 These molecules areresponsible for the maintenanceof airway obstruction in asthma.

Moreover, there are systemicconsequences of the inflammato-ry responses associated with

COPD. For example, there isample literature demonstratingthe association of inflammatorymediators such as TNFα and IL-6 (both markedly increased inCOPD) with abnormalities inbody composition, weight loss,peripheral muscle wasting andloss of performance, and func-tional status.27-29 Findings ofincreased muscle apoptosis andshifts in muscle fiber composi-tion may be related to the sys-temic inflammatory processesassociated with COPD. Othermanifestations of systemicinflammation in COPD includean increased prevalence of osteo-porosis and central nervous sys-tem defects.30,31 Finally, there isa growing interest in the role ofinflammation in coronary arterydisease progression and its poten-tial association with COPD andpulmonary inflammation.32

Diagnosis andDisease StagingCOPDThe diagnosis of COPD is largelyhistory- and symptom-driven,which can be problematic sincethere is an imperfect relationshipbetween the severity of airflowlimitation and the presence ofsymptoms. However, a diagnosisof COPD should be suspected inany patient presenting with achronic cough, sputum production,or exertional dyspnea, especially ifthere is a history of exposure tocigarette smoke.4 Unfortunately,physical examination is a relative-ly insensitive means of diagnosingCOPD, especially in mild to mod-erate disease.33

In the primary care setting, thedocumentation of airflow obstruc-tion is a universally-recommendedrequirement for the diagnosis ofCOPD, thus making pulmonaryfunction testing (PFT) through theuse of spirometry essential to thediagnosis and staging of the sever-ity of this disease.17 Expertguidelines for the diagnosis ofCOPD are readily available andrelatively straightforward: thediagnosis of COPD can be madewhen the ratio between the forcedexpiratory volume in 1 second(FEV1) and the forced vital capac-ity (FVC) falls below 0.7.17

Despite these widely-acceptedrecommendations, the utilizationof spirometry in the primary caresetting, where early diagnosis ismost likely to be accomplished,remains inconsistent. Recentstudies have shown that spirome-try can be reproducibly performed

Inflammation - differences between asthma and COPD13

TABLE 1

Inflammatory cells

Inflammatory mediators

Inflammatory effects

Asthma

Mast cells, EOS, CD4+ (Th2) cells,macrophages +

LTB4, histamine, IL-4, IL-5, IL-13eotaxin, RANTES

All airwaysEpithelial shedding, fibrosis+,

No parenchymal involvement, mucus

COPD

Neutrophils, CD8+(Tc) cells,macrophages ++

LTB4, TNF-alpha, IL-8, GRO

Peripheral airways and alveoliEpithelial metaplasia,

fibrosis ++, parenchymaldestruction, mucus

6

in the primary care setting withmodest training and with littleadditional time per patient; eachPFT assessment can be completedin 4 minutes or less.34,35

Spirometry is necessary not onlyfor the diagnosis of COPD, butalso for the assessment of severityof disease and for following apatient’s response to therapy.Recently, the ATS/ERS TaskForce and the NHLBI/WHOGlobal Initiative for ChronicObstructive Lung Disease(GOLD) released the GOLDguidelines—a method of “stag-ing” COPD patients for severityof disease.1,17 As shown in Table2, the GOLD guidelines stratifyCOPD by disease severity,FEV1/FVC ratios, and FEV1 %predicted (based on the patient’sage, gender, height, and ethnicbackground), and relate these val-ues to clinical symptoms.1,17 Thevalue of spirometry in COPDpatients is not only for diagnosis

and staging, but also to predictthe natural history of the diseasein a given patient and to guideaggressiveness of therapy andsmoking cessation efforts. Forexample, a recent retrospectiveanalysis of more than 15,000adults with COPD assessed therelationship between GOLD sta-tus and clinical outcomes. Thestudy showed that patients withGOLD stage 3 or 4 diseasedemonstrated the most rapidlydeclining lung function over time(adjusted odds ratio 2.4; 95% CI2.1-2.7) and an increased risk ofdeath (adjusted odds ratio 1.4;95% CI 1.2-1.7) compared withpatients with less severe COPD.36

To complete the diagnostic evalua-tion of a patient suspected of hav-ing COPD, a chest X-ray shouldbe considered to rule out infection,large airway lesions, heart disease,obstruction by a foreign object, ora malignancy as the cause of thepatient’s symptoms.

AsthmaOn the other hand, the diagnosisof asthma depends more on histo-ry, physical findings, and age-related factors. Recurrentepisodes of coughing or wheezingare almost always due to asthmain children and many adults.4,37

Medical history findings thatincrease the probability of asthmainclude:

• Episodic wheeze, chest tightness, shortness of breath, cough

• Symptoms that worsen in thepresence of allergens, irri-tants, or exercise

• Symptoms that worsen atnight, awakening the patient

• History of allergic rhinitis oratopic dermatitis

• Family history of asthma,allergy, sinusitis, or rhinitis

Similarly, certain physical exami-nation findings can help in thediagnosis of asthma:

• Sounds of wheezing during normal breathing or a prolonged phase of forced exhalation

• Increased nasal secretions,mucosal swelling, sinusitis,rhinitis, or nasal polyps

• Atopic dermatitis, eczema,or other signs of allergic dermatitides

It should be noted that the absenceof physical findings (i.e. a normallung examination) does notexclude the diagnosis of asthma.

As in COPD, spirometry may beuseful, since asthma is strongly

GOLD Disease Stratification Guidelines for Severity of COPD1,17

TABLE 2

GOLD Severity Postbronchodilator FEV1, Clinical symptomsStage FEV1/FVC % predicted

0 At risk > 0.7 ≥ 80 Asymptomatic smoker, ex-smoker, or chronic cough/sputum

1 Mild COPD ≤ 0.7 ≥80 Breathlessness when hurrying or walking up slight hill

2 Moderate ≤ 0.7 50-80 Breathlessness causing patient to COPD stop after walking about 100 m or

after a few minutes on level ground

3 Severe COPD ≤ 0.7 30-50 Breathlessness resulting in patient too breathless to leave the house,

4 Very Severe ≤ 0.7 < 30 breathlessness after undressing,COPD presence of chronic COPD respiratory

failure, or clinical signs of rightheart failure

7

suggested by findings of partiallyreversible airflow obstruction.Here, spirometry should be per-formed as a 2-stage process:

• First, airflow obstructionshould be established by find-ing FEV1 < 80% predictedand FEV1/FVC < 0.65

• Second, reversibility shouldbe established by demonstrat-ing that FEV1 increases > 12%and at least 200 mL aftertreatment with a short-actinginhaled beta2-agonist (e.g.,albuterol or terbutaline)

In addition, it may be advisable toperform a broad investigation ofclinical factors that are known tocontribute to asthma in an effortto reduce or eliminate thesecomorbid conditions:

• Allergy testing (skin testing orin vitro tests)

• Nasal examination and/orcomputed tomography of the sinuses

• Assessment for gastro-esophageal reflux

In children under 5 years of age,spirometry is difficult to perform,so a trial of asthma medicationsmay aid in the diagnosis when thehistory and physical examinationfindings listed above are present.

There are several different meth-ods for determining asthmaseverity levels—the patient-reported severity measures andthe Reliever/Oral Steroid Use(ROSU) method are the mostuseful in that they correlate mostclosely with the Asthma Qualityof Life Questionnaire scores, the

Work Performance Scale score,and the Physical and MentalComponent scales of the SF-36disability instrument.37 Fromthis, asthma severity may bestaged as mild intermittent, mildpersistent, moderate persistent,or severe persistent based prima-rily on the inhaled beta2-agonistuse per year, modified secondari-ly by the use of oral steroids (seeTable 3).37 The most often usedmethod of determining asthmastaging is based on the NationalHeart Lung and Blood Institute’s(NHLBI) classification of asthmaseverity, which can be found athttp://www.nhlbi.nih.gov/health/prof/lung/asthma/pract-gde/practgde.pdf (See Table 3).Using these parameters, asthmacan be classified as mild inter-mittent, mild persistent, moder-ate persistent or severe persist-ent. As in COPD, classificationof asthma severity can be usedto guide therapy and helppatients understand the nature of their disease.

Prevention andTreatmentSmoking CessationThe most compelling treatment ofCOPD consists of aggressiveapproaches to smoking cessation.The sentinel study in this field isthe Lung Health Study (LHS),which studied nearly 6,000 smok-ers between the ages of 35 and 80years of age with mild airflowobstruction, and randomized thesepatients to aggressive smokingcessation therapy versus usualcare.38 As shown in Figure 4,patients who were able to achievean 85% reduction or completecessation in smoking over thelong term (sustained quitters) pre-served a significantly higher per-centage of their lung functioncompared with those who quitsmoking intermittently or not atall, as measured by FEV1 % ofpredicted values.38 Men andwomen who quit at the beginningof the LHS had an FEV1 rate ofdecline of 30.2mL/year and 21.5mL/year, respectively, compared

Reliever/Oral Steroid Use (ROSU) Method forStaging Asthma Severity37

TABLE 3

Severity Level Inhaled beta-2 agonist use/yr Oral steroids/yr

Severe persistent > 6 canisters <2 Ô mild persistent

Moderate persistent 4-6 canisters 0 Ô mild persistent(≤ 24 inhalations/week) ≥ 3 Ô severe

Mild persistent 2-3 canisters 2 Ô moderate(≤ 12 inhalations/week) ≥ 3 Ô severe

Mild intermittent ≤ 1 canister 1 Ô mild persistent2 Ô mod persistent≥3 Ô severe

These guidelines can also be found at: http://www.nhlbi.nih.gov/health/prof/lung/asthma/practgde/practgde.pdf

8

with a decline of 66.1 mL/year inmen and 54.2 mL/year in womenwho continued to smoke. After11 years of follow-up, 38% ofcontinuing smokers had an FEV1

< 60% of the predicted normalvalue compared with 10% of thesustained quitters (Figure 4)38 Inthis study, smoking cessation wasalso associated with improvedsymptoms and improved long-term mortality (hazard ratio, 1.18;95% CI 1.02-1.37) compared withusual care.39

Physicians and other health careprofessionals working in the pri-mary care setting are in a uniqueposition to identify tobacco usersand provide effective intervention.In 2000, the efficacy of a varietyof smoking cessation methodswas systematically reviewed by aUnited States Public HealthServices (USPHS) committeeduring the development of an evi-dence-based clinical practiceguideline for physicians. The

USPHS panel concluded thatthere was sufficient clinical evi-dence supporting the use of 2 dis-tinct smoking cessation methods:

• Behavioral counseling

• Pharmacotherapy with nico-tine replacement products uti-lizing a variety of drug deliv-ery forms (see below)

A combination of counseling andpharmacotherapy produced thebest results.40 There was no evi-dence to support the efficacy ofother methods, such as hypnosisor acupuncture. The resultingUSPHS clinical guidelines recom-mend that clinicians routinely andconsistently deliver a brief 5-stepintervention in their office prac-tice called the “5 A’s”:

• Ask about tobacco use atevery visit

• Advise all tobacco users to stop

• Assess their willingness tomake a quit attempt

• Assist the patient in quitting

• Arrange follow-up contact tosupport their efforts

In addition, the USPHS guidelinessuggest that it is important to pro-vide patients with pharmacologicaids for smoking cessation; theseare reviewed in Table 4.40 Sevenpharmacologic aids have beenapproved by the US Food & DrugAdministration (FDA) for use inthe treatment of nicotine depend-ence: nicotine replacement thera-pies delivered by patch, gum,vapor inhaler, nasal spray, orlozenge, and a non-nicotine pill(bupropion). On May 11, 2006,FDA granted approval to a newclass of agent, varenicline, as apharmacologic aid to smokingcessation therapy (see Table 4).Full prescribing information forthis new agent can be found athttp://www.chantix.com.

The USPHS panel also identifiedthe tricyclic antidepressant nor-triptyline and the antihypertensiveclonidine for which there is evi-dence of efficacy for smokingcessation; these agents have notyet been approved by the FDA forthis indication.40

Pharmacologic Intervention in COPDThe goals of treatment in COPDpatients include reduction ofsymptoms, improvement in physi-ologic function, limitation ofcomplications, and arresting exac-erbations of disease.41 Severaltreatment algorithms have beendeveloped for patients withCOPD. Sutherland and Cherniakhave devised a comprehensivealgorithm that encompasses

Loss of Lung Function over 11 Years in the Lung Health Study38

FIGURE 4

9

Pharmacologic Aids for Smoking Cessation40

TABLE 4

Product

Transdermal patch*†24 hr (eg, Nicoderm CQ)16 hr (eg, Nicotrol)

Nicotine polacrilex gum(Nicorette)*†2 mg (< 25cigarettes/day)4 mg (>/= 25 ciga-rettes/day)

Vapor inhaler (NicotrolInhaler)*

Nasal spray (Nicotrol NS)*

Lozenge (CommitLozenge)*†2 mg (first cigarette > 30min waking)4 mg (first cigarette </=30 min waking)

Sustained-release bupro-pion (Zyban or WellbutrinSR)*

Nortriptyline**

Clonidine**

Varenicline* (Chantix)

Dose

7-, 14-, or 21-mg patch wornfor 24 hrs5-, 10-, or 15-mg patch wornfor 16 hrs

1 piece/1-2 hrs (wks 1-6); 2-4hrs (wks 7-9); 4-8 hrs (wks10-12); up to 24 pieces/day

6-16 cartridges/day (deliv-ered dose, 4 mg/cartridge);taper use in last 6-12 wks oftherapy

1-2 doses/hr (1 mg total; 0.5 mg in each nostril);minimum treatment: 8

doses/day; maximum treatment: 40 mg/day

1 lozenge/1-2 hrs (weeks 1-6); 2-4 hrs (weeks 7-9); 4-8hrs (weeks 10-12)

150 mg/day for 3 days, then150 mg twice a day; treatmentstarted 1 week before quit date.

75-100 mg/day‡

0.1-0.3 mg twice a day; treat-ment started on quit date orup to 3 days before quit date

0.5 mg daily for 3 days, then0.5 mg twice daily for 4 days,then 1 mg twice daily untilthe end of treatment

TreatmentDuration

8 wk

8-12 wk

3-6 mo

3-6 mo

12 wk

7-12 wk (up to6 mo to main-tain abstinence)

12 wk

3-10 wk

7-10 weeks

CommonSide Effects

Skin irritation, insomnia

Mouth irritation, sorejaw, dyspepsia, hiccups

Mouth and throat irritation, cough, dyspepsia

Nasal irritation, sneez-ing, cough, teary eyes,runny nose

Insomnia (less than5% of users), nausea,hiccups, coughing,heartburn, andheadache

Insomnia, dry mouth,agitation

Dry mouth, sedation,dizziness, blurredvision, shaky hands

Dry mouth, sedation,dizziness, drowsiness,constipation

Nausea, changes indreams, constipation,gas, vomiting

Instructions

Every morning, place a fresh patch on a rela-tively hairless area of skin between the waistand neck. If sleep disruption occurs, removethe patch at bedtime. Use a hydrocortisonecream for minor skin reactions.

Chew the gum slowly until mint or pepper istasted. Then park the gum between the cheekand gum to permit absorption through the oralmucosa. Repeat when taste subsides and con-tinue for approximately 30 minutes. Avoid eat-ing or drinking for 15 minutes before and dur-ing use.

Avoid eating or drinking for 15 minutes beforeand during use.

Do not sniff, inhale, or swallow during admin-istration because this increases irritatingeffects. Tilt the head back slightly duringadministration.

Suck on the lozenge until it dissolves. Do notbite or chew it like a hard candy, and do notswallow it. Avoid eating or drinking for 15 minutes before use.

Limit alcohol intake.

Use may cause sedation, a driving hazard. Riskof overdose should be considered carefully;produces cardiotoxic effects.

Clonidine lowers blood pressure in most patientsand so should be monitored when using. Use ofeither oral or transdermal form may cause seda-tion, a driving hazard. Do not stop using abrupt-ly as rebound hypertension may result.

Varenicline binds to nicotine receptors in thebrain, reducing the need for nicotine duringsmoking withdrawal; this binding also dampens the effects of nictotine derived fromcigarettes in patients who have a relapse during smoking cessation efforts

Nicotine-Replacement Therapies

Non-nicotine Therapies

* Approved by the FDA as a smoking cessation aid. † Over-the-counter medication. ** Not approved by the FDA as a smoking cessation aid. The USPHS clinical guideline recommends as a second-line drug for smoking cessation.‡ Treatment should be started 10-28 days before the quit date at a dose of 25 mg per day, and the dose should be increased as tolerated.

10

health care maintenance, drugtherapy, and supplemental thera-py for these patients (Figure 5).41

Because patients with reducedlung function may be asympto-matic, these authors have con-cluded that spirometry is indicat-ed to guide therapy and treat-ment, and should be initiatedwhenever reduced lung functionis demonstrated, with or withoutthe presence of symptoms. Thisalgorithm suggests that patientsmay initially require only as-needed therapy with a singleshort-acting anticholinergic agentor beta-agonist (Figure 5). Aspatients progress to moderate orsevere disease, or for those withincreasing or persistent symp-toms, an inhaled long-actingbronchodilator (LABD) or acombination of a short- or long-acting anticholinergic agent and abeta-agonist may be used.41

Table 5 summarizes the mostcommonly-used short- and long-acting inhaled bronchodilatorsand their appropriate use.41

In response to advances from epi-demiologic studies and pivotal,well-controlled clinical trials, theATS/ERS updated their standardsfor treating COPD patients in2004.17 While some guidelines(like the Sutherland and Cherniakalgorithm reviewed above) relyheavily on spirometric results forguiding pharmacologic and non-pharmacologic therapies, theATS/ERS guidelines shown inFigure 6 suggest a predominantlysymptom-based approach to treat-ment.17 Bronchodilator therapy ispivotal in the management ofpatients with COPD. Inhaled

LABDs are preferred agents overshort-acting agents. Both long-acting beta-agonists (salmeteroland formoterol) and a long-actinganticholinergic (tiotropium) havebeen shown to result in sustainedimprovement in lung function,health status, and exercise toler-ance, and to reduce COPD exacer-

bations.39,42 Although the FDAhas not approved the use ofinhaled corticosteroids alone forthe treatment of COPD, 2 recentmeta-analyses demonstrated thatuse of these agents for at least 2years can reduce the rate in deteri-oration of pulmonary function andresult in a 30% decrease in the

Duration and Administration of Inhaled Bronchodilators41

TABLE 5

Drug

Short-actingAlbuterol sulfate

Ipratropium bromide

Long-actingFormoterol fumarateSalmeterol xinafoateTiotropium bromide

Duration

4-6 hr4-6 hr

8-12 hr8-12 hr

More than 24 hr

Usual Dose*

Two puffs every 4 hr (MDI, 90 µg/puff)Two puffs every 4 hr (MDI, 18 µg/puff)

One inhalation twice daily (DPI, 12 µg/inhalation)One inhalation twice daily (DPI, 50 µg/inhalation)One inhalation twice daily (DPI, 18 µg/inhalation)

* MDI denotes metered-dose inhaler, and DPI dry-powder inhaler

A Comprehensive Algorithm for the Treatment of COPD41

FIGURE 5

11

relative risk of exacerbations.43,44

More recently, treatment guide-lines support the use of combina-tions of drugs of different classesto achieve improved clinical out-comes. For example, the combi-nation of a long-acting beta-ago-nist and an inhaled corticosteroidhas been recommended.41 Whenadministered in combination in asingle inhaler, fluticasone and sal-meterol resulted in an improve-ment in FEV1 that was main-tained for 12 to 24 weeks, com-pared to either agent alone.45,46

A 3-year prospective study(TORCH) was initiated to furtherevaluate the usefulness of thiscombination.47 The initial resultsof the TORCH study were pre-sented at the American ThoracicSociety Meeting in May 2006;the results showed that there wasa 17% relative reduction in mor-tality over 3 years for patientsreceiving the combination of sal-meterol + fluticasone propionatecompared with those treated withplacebo (P=0.052). This was thefirst study to investigate theeffects of pharmacotherapy onall-cause mortality in patientswith COPD.

Pharmacologic Intervention in AsthmaThe guidelines established in 2005by the Global Initiative for Asthma(GINA), in conjunction withNHLBI, are shown in Figure 7.19

A rapid-acting inhaled beta-2agonist should be used as neededfor most patients with mild inter-mittent asthma.19 For mild per-sistent asthma, the guidelines rec-ommend low-dose inhaled gluco-

GINA/NHLBI Guidelines for the Preferred Treatment of Asthma19

FIGURE 7

FIGURE 6

ATS/ERS Algorithm for Pharmacologic Management of COPD Patients17

12

corticoids daily. In a recentstudy, the use of once-dailybudesonide by these patients wasshown to decrease the risk ofsevere exacerbations.48 Moderatepersistent disease should be treat-ed with low- to medium-doseinhaled corticosteroids and long-acting beta-agonists (Figure 7).Severe persistent asthma necessi-tates the use of high-dose inhaledsteroids, an LABD, and an oralsteroid. For all levels of diseaseseverity, a short-acting inhaledbeta-2 agonist should be used asneeded and be available as a res-cue medication.19 Two recentstudies (one in the US and one inEurope) investigated whetherinhaled corticosteroids (ICS)used in children with a positiveasthma predictive index (e.g., fre-quent bouts of wheezing and apositive response to treatmentwith fluticasone propionate) andwho were under 3 years of agewould have disease-modifyingactivity in these patients.49,50

Both studies concluded that inpreschool children at high riskfor asthma, ICS therapy does notalter the natural history of thedisease and that the risk ofwheezing will persist beyond thefirst years of life in childrentreated with ICS therapy.49,50

Nonpharmacologic Interventionsin COPD and AsthmaAside from smoking cessationefforts which were discussedabove, other nonpharmacologicinterventions should be institutedin patients with COPD or asthma.Pulmonary rehabilitation isdesigned to address secondaryconditions associated with COPD,

such as cardiac deconditioning,peripheral muscle dysfunction,reduction in total and lean bodymass, anxiety, and poor copingskills. Pulmonary rehabilitationis most effective when deliveredas a multifaceted program incor-porating individually tailored aer-obic physical training, compre-hensive education about the dis-ease, psychosocial counseling,and nutritional support.41 Ahealthy lifestyle, physical activity,and adherence to therapy shouldbe encouraged. Pulmonary reha-bilitation efforts have been shownto improve dyspnea, exercise abil-ity, and health status, and reducehealth care utilization.17,41

In addition, long-term oxygentherapy is recommended inpatients in whom the resting par-tial pressure of arterial oxygen is55 mm Hg or less or if the oxy-gen saturation falls below 88%; inthese patients, supplemental oxy-gen has been shown to improvesurvival, exercise, sleep, and cog-nition.17,41 The guidelines alsosupport the use of influenza vac-cination for all patients withCOPD. Patients with COPD orespecially, asthma should becounseled to avoid exposure toenvironmental triggers that mightaffect symptom control.

Lung-volume reduction surgerycan reduce hyperinflation andshould be considered in patientswith severe upper-lobe emphyse-ma, poor exercise tolerance, anda poor response to pharmacothera-py alone.41 A small, randomized,controlled trial that comparedlung-volume-reduction surgery

with medical therapy in patientswith severe emphysema demon-strated improved lung function,exercise capacity, and quality oflife 6 to 12 months after surgery.51

Single-lung transplantation is analternative surgical option forpatients with end-stage emphyse-ma who have FEV1 < 25% of pre-dicted normal value and who havecomplications such as pulmonaryhypertension, marked hypoxemia,and hypercapnia.52

ConclusionsAlthough COPD and asthma are 2different forms of chronic pul-monary disease, there is consider-able overlap in presentation andmanagement. Both conditions arecaused by an interaction betweenintrinsic, genetic factors and envi-ronmental exposures. The patho-physiology of COPD and asthmainvolve multiple immunologically-mediated components, resulting inairway inflammation, obstruction,and hyperresponsiveness.Treatment of these diseases issimilar in that they can both bemanaged with pharmacologic andnonpharmacologic strategiesfocused on treating bronchocon-striction and airway inflammation.

13

1. Pauwels RA, Buist AS, CalverleyPM, et al. Global strategy for thediagnosis, management, and preven-tion of chronic obstructive pul-monary disease. NHLBI/WHOGlobal Initiative for ChronicObstructive Lung Disease (GOLD)workshop summary. Am J RespirCrit Care Med. 2001;163:1256-1276.

2. NHLBI morbidity and mortalitychartbook, 2000. Available at:http://www.nhlbi.nih.gov/resources/docs/cht-book.htm. Accessed April25, 2006.

3. Statistics. World Health Report 2000.World Health Organization, Geneva.Available at: http://www.who.int/whr/2000/en/statistics.htm. AccessedApril 25, 2006.

4. Mannino DM, Homa DM, AkinbamiLJ, et al. Surveillance for asthma—United States, 1980-1999. MMWRMorb Mortal Wkly Rep. 2002;51(SS-1):1-14.

5. Busse WW, Lemanske RF Jr.Asthma. N Engl J Med.2001;344:350-362.

6. American Lung Association.LungUSA. Available at:http://www.kintera.org/site/apps/s/search.asp?c=dvLUK90oE&b=34706.Accessed May 1, 2006.

7. National Center for Health Statistics.Centers for Disease Control andPrevention. Fastats. 2005. Availableat: http://www.cdc.gov/nchs/fastats/Default.htm. Accessed May 1, 2006.

8. NHLBI. US Department of Healthand Human Services. Chronicobstructive pulmonary disease. Datafact sheet. March 2003. Available athttp://www.nhlbi.nih.gov/health/pub-lic/lung/other/copd_fact.pdf.Accessed May 1, 2006.

9. Mannino DM, Homa DM, AkinbamiLJ, et al. Chronic obstructive pul-monary disease surveillance—UnitedStates, 1971-2000. Respir Care.2002;47:1184-1199.

10. NHLBI/NIH. National Heart, Lung,and Blood Institute/National

ReferencesInstitutes of Health. Morbidity &Mortality: 2002 Chart Book onCardiovascular, Lung, and BloodDiseases, May 2002.

11. Hurd S. The impact of COPD onlung health worldwide: epidemiolo-gy and incidence. Chest. 2000;117(suppl 2):1S-4S.

12. Sullivan SD, Ramsey SD, Lee TA.The economic burden of COPD.Chest. 2000;117(suppl 2):5S-9S.

13. Barnes PJ. Mechanisms in COPD:differences from asthma. Chest.2000;117(suppl 2):10S-14S.

14. Postma DS, Boezen HM. Rationalefor the Dutch hypothesis. Allergyand airway hyperresponsiveness asgenetic factors and their interactionwith environment in the developmentof asthma and COPD. Chest.2004;126:96S-104S.

15. Donohue JF, Ohar JA. Inflammationand treatment in asthma and COPD.Pulmonary and Critical Care Update.2003. Available at:http://www.chestnet.org/education/online/pccu/vol16/les-sons19_20/lesson19/print.php.Accessed May 3, 2006.

16. Orie NGM, Sluiter HJ, Vries KD, etal. The host factor in bronchitis. In:Orie NGM, Sluiter HJ, eds.Bronchitis: An International Sym-posium. April 1960. Springfield, IL:Charles C. Thomas. 1961, pp. 44-59.

17. Celli BR, MacNee W, ATS/ERS TaskForce. Standards for the diagnosisand treatment of patients withCOPD: a summary of the ATS/ERSposition paper. Eur Respir J.2004;23:932-946.

18. Global Initiative for ChronicObstructive Lung Disease (GOLD).Global strategy for the diagnosis,management, and prevention ofchronic obstructive pulmonary dis-ease. NHLBI/WHO Workshop. April1998. Available at: http://www.gold-copd.com/revised.pdf#search=’Global%20Initiative%for%20Chronic%20Obstructive%20Lung%20

Disease. Accessed May 1, 2006.

19. Global Initiative for Asthma (GINA).Global strategy for asthma manage-ment and prevention. NIH publica-tion No. 02-3659. Management seg-ment: Chapter 7. January 2005.Available at: http://www.ginasthma.com/download.asp?intId=96.Accessed May 1, 2006.

20. MacNee W. Pulmonary and systemicoxidant/antioxidant imbalance inchronic obstructive pulmonary dis-ease. Proc Am Thorac Soc.2005;2:50-60.

21. Ito K, Ito M, Elliott WM, et al.Decreased histone deacetylase activi-ty in chronic obstructive pulmonarydisease. N Engl J Med.2005;352:1967-1976.

22. Barnes PJ, Hansel TT. Prospects fornew drugs for chronic obstructivepulmonary disease. Lancet.2004;364:985-996.

23. Saetta M, DiStefano, Maestrelli P, etal. Activated T-lymphocytes andmacrophages in bronchial mucosa ofsubjects wiuth chronic bronchitis. AmRev Respir Dis. 1993;147:301-306.

24. Saetta M, DiStefano, Turato G, et al.CD8+ T-lymphocytes in peripheralairways of smokers with chronicobstructive pulmonary disease. Am JRespir Crit Care Med.1998;157:822-826.

25. Hogg JC. Pathophysiology of airflowlimitation in chronic obstructive pul-monary disease. Lancet.2004;364:709-721.

26. Hogg JC, Chu F, Utokaparch S, et al.The nature of small-airway obstruc-tion in chronic obstructive pul-monary disease. N Engl J Med.2004;350:2645-2653.

27. Eid AA, Ionescu AA, Nixon LS, etal. Inflammatory response and bodycomposition in chronic obstructivepulmonary disease. Am J Respir CritCare Med. 2000;164:1414-1418.

14

28. deGodoy I, Donahoe M, CalhounWJ, et al. Elevated TNF-alpha pro-duction by peripheral blood mono-cytes of weight-losing COPDpatients. Am J Respir Crit Care Med.1996;153:633-637.

29. Debigare R, Marquis K, Cote CH, etal. Catabolic/anabolic balance andmuscle wasting in patients withCOPD. Chest. 2003;124:83-89.

30. Incalzi RA, Caradonna P, Ranieri P, etal. Correlates of ostreoporosis inchronic obstructive pulmonary dis-ease. Respir Med. 2000;94:1079-1084.

31. Wagena EJ, Huibers MJ, vanSchayck CP. Antidepressants in thetreatment of patients with COPD:possible associations between smok-ing cigarettes, COPD, and depres-sion. Thorax. 2001;56:587-588.

32. Hunninghake DB. Cardiovasculardisease in chronic obstructive pul-monary disease. Proc Am ThoracSoc. 2005;2:44-49.

33. Badgett RG, Tanaka DJ, Hunt DK, etal. Can moderate chronic obstructivepulmonary disease be diagnosed byhistorical and physical findingsalone? Am J Med. 1993;94:188-196.

34. Schermer TR, Jacobs JE, ChavannesNH, et al. Validity of spirometrictesting in a general practice popula-tion of patients with chronic obstruc-tive pulmonary disease (COPD).Thorax. 2003;58:861-866.

35. van Schayck CP, Loozen JM,Wagena E, et al. Detecting patientsat high risk of developing chronicobstructive pulmonary disease ingeneral practice. Cross-sectional casefinding study. BMJ. 2002;324:1370-1375.

36. Mannino DM, Reichert MW, DavisKJ. Lund function decline and out-comes in an adult population. Am JRespir Crit Care Med.2006;173:985-990.

37. Erickson SR, Kirking DM. Variationin the distribution of patient-reportedoutcomes based on different defini-tions of defining asthma severity. CurrMed Res Opin. 2004;20:1863-1872.

38. Anthonisen N, Connett JE, MurrayRP. Smoking and lung function ofLung Health Study participants after11 years. Am J Respir Crit Care Med.2002;166:675-679.

39. Anthonisen NR, Skeans MA, WiseRA, et al. Lung Health StudyResearch Group. The effects of asmoking cessation intervention on14.5-year mortality. A randomizedclinical trial. Ann Intern Med. 2005;142:233-239.

40. Fiore MC, Bailey WC, Cohen SJ, etal. Treating tobacco use and depend-ence. Clinical Practice Guidelines.Rockville, MD: US Department ofHealth and Human Services. PublicHealth Service; 2000.

41. Sutherland ER, Cherniak RM.Management of chronic obstructivepulmonary disease. N Engl J Med.2004;350:2689-2697.

42. Anzueto A, Tashkin D, Menjoge S,et al. One-year analysis of longitudi-nal changes in spirometry in patientswith COPD receiving tiotropium.Pulm Pharmacol Therapeut.2005;18:75-81.

43. Sutherland ER, Allmers H, Ayas NT,et al. Inhaled corticosteroids reducethe progression of airflow limitationin chronic obstructive pulmonarydisease: a meta analysis. Thorax.2003;58:937-941.

44. Alsaeedi A, Sin DD, McAlister FA.The effects of inhaled corticosteroidsin chronic obstructive pulmonarydisease: a systematic review of ran-domized placebo-controlled trials.Am J Med. 2002;113:59-65.

45. Kavuru M, Melamed J, Gross G, etal. Salmeterol and fluticasone propi-onate combined in a new powderinhalation device for the treatment ofasthma: A randomized, double-blind,placebo-controlled trial. J AllergyClin Immunol. 2000;105:1108-1116.

46. Hanania NA, Darken P, Horstman D,et al. The efficacy and safety of fluti-casone propionate (250 mg)/salme-terol (50 mg) combined in the discusinhaler for the treatment of COPD.Chest. 2003;124:834-843.

47. TORCH. The TORCH (Towards a rev-olution in COPD health) survival studyprotocol. The TORCH Study Group.Eur Respir J. 2004;24:206-210.

48. Pauwels RA, Pederson S, BusseWW, et al. Early intervention withbudesonide in mild persistent asth-ma: a randomized, double-blind trial.Lancet. 2003;361:1071-1076.

49. Guilbert TW, Morgan WJ, Zeiger RS,et al. Long-term inhaled corticos-teroids in preschool children at highrisk for asthma. N Engl J Med.2006;354:1985-1997.

50. Bisgaard H, Hermansen MN, LolandL, et al. Intermittent inhaled corti-costeroids in infants with episodicwheezing. N Engl J Med.2006;354:1998-2005.

51. Geddes D, Davies M, Koyama H, etal. Effect of lung-volume-reductionsurgery in patients with severeemphysema. N Engl J Med.2000;343:239-245.

52. Arcasoy SM, Kotloff RM. Lungtransplantation. N Engl J Med.1999;340:1081-1091.

15

Name ________________________________________________________________________________________ Degree/title ________________________

Specialty __________________________________Hospital, or Practice Name __________________________________________________________________

Address __________________________________________________________________________________________________________________________

City______________________________________________________________________________________ State______ Zip ______________________

Phone ______________________________ FAX ____________________________________ E-mail ____________________________________________

(last) (first) (middle)

1. What percentage of smokers develops COPD, suggesting agenetic predisposition for the disease?a. 10% b. 20% c. 35% d. Over 50%

2. Oxidative stress is thought to play an important role in thedevelopment of COPD. Oxidative stress:a. Is induced by oxidants found in cigarette smokeb. Causes upregulation of proinflammatory cytokines,

primarily TNFα and IL-8c. Occurs to a higher degree in smokers with COPD than

in smokers without COPDd. All of the above

3. Immunologic distinctions in the pathogenesis of COPD andasthma include:a. CD4+ lymphocytes predominate in COPD, but not asthmab. IgE antibodies and eosinophils play a pivotal role in asthmac. Cytokines are not thought to play a role in late-stage

reactions in asthmad. All of the above

4. The diagnosis of COPD can be made by spirometricfindings thata. FEV1 < 0.7 c. FEV1/FVC < 0.7b. FVC < 0.7 d. FVC/FEV1 < 0.7

5. Severe COPD, GOLD Stage 3, is characterized bya. FEV1 = 30-50% predicted normal valueb. Breathlessness when walking up a slight hillc. FEV1 = 50-80% predicted normal valued. FEV1/FVC > 0.7

6. The most effective approach(es) to effecting smokingcessation is (are):a. Counselingb. Pharmacotherapyc. Counseling and pharmacotherapyd. Counseling, pharmacotherapy, and hypnotherapy

7. Which of the following is NOT approved by FDA aspharmacotherapy for smoking cessation?a. Nicotine patch c. Nicotine vapor inhalerb. Bupropion d. Nortriptyline

8. ATS/ERS guidelines for treatment of persistent symptomsof COPD recommend starting with aa. Short-acting bronchodilatorb. Long-acting bronchodilatorc. Inhaled corticosteroidd. Oral theophylline

9. The combination of which of the following in a singleinhaler has been shown to achieve improved clinicaloutcomes in COPD?a. Albuterol and ipratropiumb. Formoterol and salmeterolc. Salmeterol and tiotropiumd. Fluticasone and salmeterol

10. GINA guidelines for treatment of mild persistent asthmarecommend starting with a. Low-dose inhaled steroidb. High-dose inhaled steroidc. Daily dosing of a long-acting bronchodilatord. Oral steroid

PLEASE CIRCLE THE MOST APPROPRIATE ANSWER TO THE FOLLOWING QUESTIONS.

06 GS COPD PCS-2

CME/CE POST-TEST To receive credit, please print or type the information requested below, complete the followingpost-test and program evaluation, remove form at perforation, and mail it in an envelope to: Medical Communications Media, 2288Second Street Pike, Wrightstown, PA 18940. Successful completion of the self-assessment is required to earn credit. Successfulcompletion is defined as a cumulative score of at least 70% correct. A CME/CE statement will be mailed at no charge within 4-6 weeks.

Please check which type of credit you are applying for:

m Physician CME: I am claiming _____AMA PRA Credits™m Physician Assistant Category I (Preapproved) CME Credit (AAPA credit expires May 28, 2007)m AAFP Prescribed credit (expires August 1, 2007)m Nursing CEm Nurse Practitioner CE

Release Date: May 28, 2006 • Credit Expiration Date: May 28, 2008

16

PROGRAM EVALUATIONPlease complete this program evaluation so that we may continue to provide you with high-quality educational activities.

INDICATE YOUR ANSWER BY CIRCLINGTHE APPROPRIATE NUMBER.

Release Date: May 28, 2006 • Credit Expiration Date: May 28, 2008

STRONGLY AGREE STRONGLY DISAGREE

1. As a result of my participation in this activity, I am better able to:

Describe the pathophysiology of COPD and asthma, and the unique pathogenic characteristics of each condition. 5 4 3 2 1

Discuss the early diagnosis of COPD, the staging of disease severity,and the use of FEV1 reduction as a prognostic indicator. 5 4 3 2 1

Describe the latest pharmacological therapy for mild, moderate, and severe COPD and asthma. 5 4 3 2 1

Discuss the optimal smoking cessation approaches that primary careproviders can adopt for the prevention of COPD in their patients. 5 4 3 2 1

2. This activity increased my awareness and understanding of the subject matter. 5 4 3 2 1

3. The information provided in this activity will be useful to me professionally. 5 4 3 2 1

4. Do you anticipate any changes in your diagnosis or management of asthma and COPD as a result of this program? Please explain: q Yes q No

5. Was the content clear and well organized? If no, please explain: q Yes q No

6. The faculty are knowledgeable and up-to-date. If no, please explain: q Yes q No

7. Was the activity objective and scientifically balanced, and free of commercial bias? q Yes q NoIf no, please explain

8. The audio CD and workbook format is an effective way to present this material. q Yes q No

9. What clinical problems related to asthma and COPD are you or your colleagues facing about which you would like to learn more?

10. Additional comments:

06 GS COPD PCS-2