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JMCPJOURNAL OF MANAGED CARE PHARMACY®

Overview of Chronic Obstructive Pulmonary Disease:New Approaches to Patient Management

in Managed Care Systems

Dick D. Briggs, Jr., MD

Diana I. Brixner, PhD, RPh

H. Eric Cannon, PharmD

Dorothy L. George, PharmD

SupplementJuly 2004

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Dick D. Briggs, Jr., MD, is emeritus professor and Eminent Scholar chair in pulmonary dis-eases at the University of Alabama at Birmingham, where he continues to be active full-time.He also serves as chief medical officer for Best Doctors Worldwide Healthcare Services,Boston, Massachusetts. Briggs has been past-president of both the American College of ChestPhysicians and the Association of Pulmonary and Critical Care Medicine Program Directors.In 2001, he was selected as a master fellow by the American College of Chest Physicians. Hewas director of the Division of Pulmonary Allergy and Critical Care and was vice chairmanof the Department of Medicine at UAB. Briggs received his medical degree from WashingtonUniversity School of Medicine and completed his internship and residency at UAB.

Diana I. Brixner, PhD, RPh, is associate professor and chair of the Department of PharmacyPractice at the University of Utah College of Pharmacy, Salt Lake City. She is also executivedirector of the Pharmacotherapy Outcomes Research Center, where she works with healthcare providers at the College of Pharmacy and the university hospital and clinics to impactpatient care through the appropriate use of pharmaceuticals. Previously, Brixner was execu-tive director of the National Managed Care Accounts Department at NovartisPharmaceuticals, and she has held various positions at SmithKline Beecham. She received herBS in pharmacy from the University of Rhode Island and her PhD in medicinal chemistryfrom the University of Utah.

H. Eric Cannon, PharmD, is director of pharmacy services at IHC Health Plans, a divisionof Intermountain Health Care, Salt Lake City, Utah. In this role, he works to develop, imple-ment, and administer programs to control cost and utilization of pharmaceuticals within theIHC system. Through IHC Health Plans, he is working to incorporate outcomes-based phar-macoeconomics research in the formulary process. Cannon is also chairman of Utah AWARE,an alliance of health care providers and the pharmaceutical industry working to educate thepublic about appropriate antibiotic use. He received his PharmD from Idaho State University.

Dorothy L. George, PharmD, is senior associate director of Cerner Health Insights, BeverlyHills, California, where she is responsible for oversight and coordination of all client engage-ments of the consulting group. She also serves as a project manager and developer for healthmanagement programs and practice guidelines, evaluates health services utilization patternsfrom research databases, and performs assessments of products and services. PreviouslyGeorge was assistant director of pharmaceutical services at UCLA Medical Center. Shereceived her PharmD and completed her clinical residency at UCSF, San Francisco,California.

F A C U L T Y

Table of Contents

Overview of Chronic Obstructive Pulmonary Disease:New Approaches to Patient Management

in Managed Care Systems

S2 Introduction Diana I. Brixner, PhD, RPh

S3 Chronic Obstructive Pulmonary Disease Overview: Prevalence, Pathogenesis, and TreatmentDick D. Briggs, Jr., MD

S11 Chronic Obstructive Pulmonary Disease Treatment Options Dorothy L. George, PharmD

S17 Assessing the Need for a Clinical COPD Care Program in a Managed Care Organization H. Eric Cannon, PharmD

S22 Continuing Education*:Record of Completion, Posttest, and Program Evaluation

This supplement was funded by an unrestricted grant from Boehringer Ingelheim and Pfizer Inc. Articles in this supplement are based on the proceedings of a symposium held October 16, 2003, at the Academy ofManaged Care Pharmacy’s 2003 Educational Conference in Montreal, Quebec, Canada, and supported by an unrestricted educational grant from Boehringer Ingelheim and Pfizer Inc.

*A total of .15 CEUs (1.5 contact hours) will be awarded for successful completion of this continuing education program (ACPE Program No. 068-999-04-022-L04).

Copyright© 2004, Academy of Managed Care Pharmacy, Inc. All rights reserved. No part of this publicationmay be reproduced or transmitted in any form or by any means, electronic or mechanical, without writtenpermission from the Academy of Managed Care Pharmacy.

All articles published represent the opinions of the authors and do not reflect the official policy or views of the Academy of Managed Care Pharmacy, the authors’ institutions, Boehringer Ingelheim, or Pfizer Inc. unless so specified.

DIANA I. BRIXNER, PhD, RPh

I N T R O D U C T I O N

Chronic obstructive pulmonary disease (COPD) is a partially reversible inflammatory airway disease that isassociated in later stages with pulmonary symptomology

—predominantly chronic dyspnea, cough, sputum pro-duction, and sometimes wheezing—and in all stages with progressive airflow obstruction that not only erodes patients’quality of life but also notably elevates their risks for morbidityand mortality.1 Currently, COPD is the fourth leading cause ofdeath in the United States. The total direct and indirect healthcare costs associated with COPD exceed $30 billion annually,and this economic burden is expected to increase in response tothe persistent increase in COPD prevalence.2,3

COPD is preventable in its earliest phase and treatable in allstages. Yet, asymptomatic patients at risk for COPD—chiefly cigarette, cigar, and pipe smokers—are not always tested for pulmonary function impairment by their primary care physicians, and patients with symptoms of COPD may be misdiagnosed as having asthma.

To enhance the understanding of the pathophysiology andtreatment of COPD in patients, as well as the impact of thiscostly disorder on managed care providers, payers, and members, a symposium was held in Montreal, Quebec, Canada,on October 16, 2003. During this symposium, experts on thepathophysiology and treatment of COPD and in the field ofmanaged care delivery provided their unique perspectives onapproaches for COPD diagnosis, treatment, and management inthe managed care system. This supplement to the Journal ofManaged Care Pharmacy comprises 3 articles based on the evidence-based data presented during this symposium. Thesearticles are intended to advance the understanding of COPD inclinical and managed care settings.

DISCLOSURES

The author received an honorarium from Boehringer Ingelheim and Pfizer Inc.for participation in the symposium upon which this article is based. She discloses no conflict of interest or any potential bias regarding this article.

REFERENCES

1. Lundback B, Lindberg A, Lindstrom M, et al. Not 15 but 50% of smokersdevelop COPD? Report from the Obstructive Lung Disease in NorthernSweden studies. Respir Med. 2003;97:115-22.

2. Chojnowski D. “GOLD” standards for acute exacerbation in COPD. NursePract. 2003;28:26-35.

3. Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med. 2000;343:269-80.

DIANA I. BRIXNER, PhD, RPh, is associate professor and chair, Department ofPharmacy Practice, and executive director, Pharmacotherapy Outcomes ResearchCenter, University of Utah College of Pharmacy, Salt Lake City.

AUTHOR CORRESPONDENCE: Diana I. Brixner, PhD, RPh, Associate Professorand Chair, Department of Pharmacy Practice [or] Executive Director,Pharmacotherapy Outcomes Research Center, University of Utah College ofPharmacy, 30 South 2000 East, Room 258, Salt Lake City, Utah 84112. Tel: (801)581-3182; Fax: (801) 585-6160; E-mail: [email protected]

Copyright© 2004, Academy of Managed Care Pharmacy. All rights reserved.

Author

Target AudiencePharmacists and other health care practitioners in a managedcare environment

Learning ObjectivesUpon completion of this session, the participant will be able to

1. describe COPD and its prevalence and burden of illness on patients, society, and managed care systems;

2. discuss current treatment options via an evidence-based management approach;

3. illustrate the impact of new treatment options on current patterns of care; and

4. review COPD patient management within managed care systems.

J Manag Care Pharm. 2004;10(4)(suppl S-a):S2

S2 Supplement to Journal of Managed Care Pharmacy JMCP July 2004 Vol. 10, No. 4, S-a www.amcp.org

Chronic Obstructive Pulmonary Disease Overview:Prevalence, Pathogenesis, and Treatment

DICK D. BRIGGS, JR., MD

DICK D. BRIGGS, JR. MD, is an emeritus professor and Eminent Scholar chair,Division of Pulmonary, Allergy, and Critical Care, Department of Medicine,University of Alabama at Birmingham.

AUTHOR CORRESPONDENCE: Dick D. Briggs, Jr., MD, Eminent Scholar Chair,Division of Pulmonary, Allergy, and Critical Care, Department of Medicine,University of Alabama at Birmingham, 459 Boshell Building—UAB MedicalCenter, Birmingham, Alabama 35294-0012. Tel: (205) 934-6015; Fax: (205) 934-6009; E-mail: [email protected]


Author

ABSTRACT

OBJECTIVE: To discuss the current clinical data on the prevalence, pathogenesis,staging, and treatment of chronic obstructive pulmonary disease (COPD).

DATA SOURCES: This article reviews the results of published studies and presentsdata from current guidelines and expert opinion.

CONCLUSIONS: An insidious disorder that is asymptomatic early, COPD (the preferred term for patients with chronic bronchitis and emphysema) prevalencehas increased in recent decades, adding a significant burden to patients and thehealth care system. COPD, an inflammatory disorder secondary to the chronicinhalation of principally tobacco smoke, induces a progressive deterioration inpulmonary function with a marked increase in morbidity and mortality over time.The signs and symptoms of COPD, which appear in many patients only afterforced expiratory volume in 1 second (FEV1) is <50% predicted, should not beconfused with asthma, because these two diseases display grossly differentinflammatory processes, etiologies, clinical courses, responses to treatment,and outcomes. The effective management of COPD relies primarily on earlyidentification, changing smoking habits, and the use of bronchodilators toimprove pulmonary function, symptoms, acute exacerbation rate, quality of life,mortality, and comorbidities. With early detection and aggressive treatment, thenatural history of this disease can be improved. Office spirometry for all smokersand ex-smokers as well as those with respiratory symptoms is mandatory as ameans of achieving early diagnosis and improving long-term outcomes.

KEYWORDS: COPD, Prevalence, Pathophysiology, Treatment, Smoking, Spirometry

J Manag Care Pharm. 2004;10(4)(suppl S-a):S3-S10

Costly and largely preventable, chronic obstructive pul-monary disease (COPD), which includes emphysema andchronic bronchitis, is now the most common form of

chronic lung disease. In the United States alone, COPD has beendiagnosed in 16 million people—14 million with chronic obstruc-tive bronchitis and only 1.8 million with significant clinicalemphysema.1 Disconcertingly, its mortality has increased dramat-ically over the last several decades: 163% since 1965.2

COPD is the only top-5 killer with increasing mortality, proba-bly because we have not sought early diagnosis and prevention aswe have with coronary artery disease, cancers, and stroke. COPDis not a disease restricted to the elderly. In fact, more than 70% ofpatients with COPD are under the age of 65 years; these working-age individuals account for half of all outpatient visits, nearly twothirds of all emergency room visits, and about one third of allhospitalizations for COPD treatment.2 Since the mean age tostart smoking in the United States is now about 10.5 years,COPD is appearing frequently in the 30- to 40-year-old agegroup.1 Indeed, in terms of both direct and indirect health careexpenses, COPD costs are estimated at more than $30 billionper year, including more than 150 million disability days(Figure 1).3 And, if present trends continue, these costs willlikely increase substantially in the future.

In its early stages, COPD is a silent, but insidiously progressivedisease. Thus, the actual prevalence of COPD may be much higherthan the estimates gleaned from confirmed diagnoses, with thisdisease perhaps affecting up to 50 million individuals in theUnited States. (More than 70% of patients with spirometricallyproven COPD in the National Health and Nutrition ExaminationSurvey [NHANES] III study did not carry a diagnosis of COPD!).2

Not surprisingly, virtually all smokers will eventually develop

16,000

14,000

12,000

10,000

8,000

6,000

4,000

2,000

0

Tota

l C

osts

Respiratory Nonrespiratory

COPD Case Control COPD Case Control

Total Cost$7,888

P = <0.0001

Total Cost$315

16,000

14,000

12,000

10,000

8,000

6,000

4,000

2,000

0

P = <0.0001Total Cost$12,881

Total Cost$8,085

� Medical � Rx

Yu-Isenberg K, Vanderplas A, Chang E, et al. Poster presented at: ISPOR 8th AnnualInternational Meeting; May 2003; Arlington, VA.

Respiratory- Versus Nonrespiratory-RelatedTotal Health Care Costs for the Year 2000

FIGURE 1

www.amcp.org Vol. 10, No. 4, S-a July 2004 JMCP Supplement to Journal of Managed Care Pharmacy S3

Chronic Obstructive Pulmonary Disease Overview: Prevalence, Pathogenesis, and Treatment

COPD, although about 1 in 5 will develop it more rapidly thanothers.4 COPD affects whites more often than African Americansand women more often than men, although the reasons for thesedisparities have not yet been clarified. Currently, COPD is thefourth leading cause of death in the United States, and this mor-tality rate is increasing dramatically (Figure 2).5 Mortality inwomen exceeded mortality in men in 2000 for the first time.2

Alarmingly, COPD is now the leading cause of mortality and morbidity, combined, in the United States.6

COPD is characterized by chronic inflammation that inducesnarrowing of the bronchi, resulting in a progressive reduction ofairflow and dynamic hyperinflation. Primary symptoms of COPDmay include dyspnea, chronic cough, sputum production, andsometimes wheezing. However, symptoms may be absent in ordenied by patients with early disease. Although once believed tobe irreversible and inexorably progressive, COPD symptomatologycan be arrested, or even reversed, with early diagnosis, properbronchodilator treatment, and smoking cessation or decrease. Yet,to effectively manage the sequelae of this disorder, it is importantto recognize the true nature of COPD: an inflammatory diseasethat affects not only all the airways but also the entire body. In fact,the systemic manifestations of COPD inflammation, particularlyatherosclerosis,7 are responsible for much of its associated morbidity and mortality. This manuscript will provide an overviewthe pathophysiology, diagnosis, staging, and treatment of COPD.

�� Pathogenesis

COPD results principally from inhalation of toxic substances—chiefly the chemicals in cigarette, cigar, and pipe smoke—thatactivate epithelial cells to produce inflammatory mediators thattrigger chronic inflammation in all the airways and the lungparenchyma. In COPD, damaging lung inflammation arises pre-dominantly from the action of polymorphonuclear leukocytes(PMNs) and pulmonary alveolar macrophages (PAMs). These cellsof inflammation release proteases that irritate the airways, increase

mucus secretions, destroy alveolar walls, and perpetuate and exacerbate ongoing inflammation activity.8,9 In addition, elevatedlevels of certain cytokines, chiefly, interleukin (IL) -8, leukotrieneB4 (LTB4), and tumor necrosis factor (TNF) -α, amplify and per-petuate the inflammatory process in COPD, even after smokingcessation.8,9

�� COPD Pathology

In COPD, pathologic changes are detected very early in the bron-chioles, where peribronchiolar fibrosis results in airflow obstruc-tion. Early changes can also be detected in all bronchi wheremucus hypersecretion, inflammatory cells, and bronchial smoothmuscle contraction obstruct airflow. Mucus hypersecretion is asalient feature, from hypertrophy of the submucosal glands andhyperplasia of goblet cells. Neutrophil chemotactic factors alsoemanate from activated macrophages and from epithelial cells andCD8+ lymphocytes. Indeed, macrophages, by releasing neutrophilchemotactic factors and proteolytic enzymes, play a prominentrole in perpetuating the PMN inflammatory response in COPD.8-11

In COPD, chronic inflammation in all of the airways and thelung parenchyma yields accumulating pathologic changes overtime, culminating in progressively deteriorating pulmonary function.Unremitting inflammation triggers the mucus gland hypertrophy,goblet cell hyperplasia, peribronchiolar fibrosis, and thickening ofthe pulmonary vasculature that conspire to undermine pulmonaryfunctioning.8 These pathologic features of COPD, along withincreased vagal tone, trigger increases in smooth muscle tone, ciliadysfunction, edema, and diminished elastic recoil in pulmonarytissue, together obstructing airflow. Patients can no longer exhaleefficiently and, in response, lung volume increases, especially dur-ing exercise, trapping air, decreasing inspiratory capacity, andinducing dyspnea. Indeed, many people who die from COPD succumb to gas exchange defects that produce reduced oxygenand increased carbon dioxide levels in the body, i.e., respiratoryfailure. Pulmonary hypertension from hypoxemia and loss of vascular bed, and cor pulmonale, are inexorable outcomes forpatients with advanced COPD. Importantly, COPD can also causea loss of lean body mass, a manifestation of the systemic inflam-mation and catabolic status of patients with advanced disease.12

Patients with the low body mass index (BMI) of this pulmonarycachexia have higher mortality.13 Some have noted that, in patientswith COPD, the cross-sectional diameter of the quadriceps muscle predicts mortality better than diminution in FEV1.12,14

�� Diagnostic Issues

Simple, inexpensive, and reliable, spirometry is the essential diag-nostic tool for COPD confirmation. The FEV1 and forced vitalcapacity (FVC), the maximum volume of air in liters that can beforcibly and rapidly exhaled in one second or full exhalation,respectively, are mandatory measurements for identifying andstaging the severity of COPD. An early diagnosis is key to avertingmany of the deleterious consequences of COPD, and this requires

COPD Mortality Rate Increasing: PercentChange in Age-Adjusted Death Rates;United States, 1965-1998

FIGURE 2

3.0

2.5

2.0

1.5

1.0

0.5

0

Coronary Heart

Disease

Stroke Other CVD COPD All OtherCauses

-59% -64% -35% +163% -7%

1965-1998

From reference 2.



the physician to identify at-risk patients—chiefly smokers. Yet, clinicians can often overlook at-risk patients during routinepatient contacts or even during a physical examination sinceCOPD may be asymptomatic in its early phase or patients maydeny symptoms or altered lifestyle. When this occurs, diagnosismay only be confirmed late, when the patient has been smokinga pack of cigarettes a day for many years and when COPD andcomorbidities may have advanced considerably.

One simple method for assuring diagnosis of COPD early is toassess FEV1 and FVC regularly in all smokers and ex-smokers.Indeed, for smokers, spirometry should be considered a vital sign ona par with blood pressure measurements. When FEV1/FVC is <70%predicted, and FEV1 is <80% predicted, smokers have COPD.

Some physicians are reluctant to discuss smoking habits withtheir patients and incorrectly feel that there is little they can do forpatients who smoke. Some patients—especially younger, at-riskpatients—are reluctant to discuss the symptoms of their tobaccoaddiction with their physicians.1 Nonetheless, finding COPD earlynot only identifies patients with COPD but finding an abnormalFEV1 in smokers also identifies patients at higher risk for myocar-dial infarction, cerebrovascular accident, and lung cancer thansmokers without airflow obstruction.

In addition to reducing mortality risks, early treatment forCOPD can enhance the patient’s overall quality of life, improveoverall function, and decrease the rate of acute exacerbations.Despite these clear benefits, spirometry is not readily available inall primary care physicians’ offices, reducing the chances for earlydiagnosis. Physicians have perceived that spirometry is complexand costly when, in fact, new hand-held spirometers are simple,reliable, and relatively inexpensive.1

In the clinical setting, COPD is sometimes misdiagnosed andtreated as asthma, especially in women. Yet, it is important to notethat although COPD and asthma do share some clinical features,such as airflow obstruction, they are, in fact, 2 distinct disorders,with different origins, natural history, and outcomes, and certainlyrequire different treatment approaches. Importantly, in asthma,airway inflammation is characterized by increased CD4 lympho-cytes and activated eosinophiles and mast cells that affect the airways and is very responsive to corticosteroids.

Asthma usually occurs early in life and patients generally have ahistory—personal or family—of asthma or atopy. In COPD, by con-trast, the airway inflammation is characterized by predominantlyneutrophil and macrophage presence and high protease concentra-tions. These COPD cells and associated cytokines, IL-8, LTB4, andTNF-α, are not responsive to corticosteroid therapy. COPD typically presents in a smoker and usually cannot be totally reversedwith treatment.10 Clinically distinguishing COPD from asthma isbased on the evaluation of several factors (Table 1). Again, COPD isdefined as inflammation of the airways that results in an airflowobstruction measured as an FEV1/FVC of <70% and an FEV1 of<80% of predicted values, with partially reversible airflow obstruc-tion with bronchodilator therapy.15,16

�� COPD Severity—Staging

Currently several staging systems are used to classify the severityof COPD. Two of these are the Global Initiative for ChronicObstructive Lung Disease (GOLD) Criteria, updated in 2003, andthe American Thoracic Society (ATS) Criteria (Figure 3).15,17

Unlike asthma, therapy of COPD patients does not rigidly followseverity staging.1

GOLD Criteria In the new initiative, postbronchodilatory spirometry measure-ments are required to stage severity. Stage I represents mild COPDand is defined as a postbronchodilatory FEV1 of ≤80% and anFEV1/FCV of <70%. Symptoms, dyspnea, cough and sputum pro-duction, may or may not be present. Stage II, moderate COPD, is characterized by worsening airflow limitation and a post-bronchodilatory FEV1 of between 50% and 80% of predicted


COPD Asthma

Age Older Any age; many younger

Smoking Significant (20 daily/20 years) Usually insignificant

Family history Uncommon Common

Symptoms Chronic (if present) Exacerbations/remissions

Signs, x-rays, PFTs Variable Variable

Reversibility Partial More complete

NS BHR Usually present Usually present

Inflammation PAMs, PMNs, proteases EOSs, lymphs, mast cells

PFTs = pulmonary function tests; BHR = bronchial hyperreactivity; PAMs = pulmonary alveolar macrophages; PMNs = polymorphonucleocytes; EOSs= eosinophils. Adapted from reference 1.

A Differential DiagnosisTABLE 1

ATS CriteriaBased On

Simple FEV11

“New Gold” Criteria Basedon Post-BD FEV1 With

FEV1/FVC<70%2

% Predicted FEV1

100%

80%

50%

30%

0%

35%

I Mild

II Moderate

III Severe

IVVery Severe

I Mild

II Moderate

III Severe

1. AJRCCM. 1995;152:s78-s1212. NIH, NHLBI Revised Executive Summary of GOLD; updated 2003.FEV1 = forced expiratory volume in 1 second; BD = bronchodilator.FVC = forced vital capacity.

Arbitrary COPD Severity StagingFIGURE 3


values. In Stage III, severe COPD, further worsening occurs andpostbronchodilatory FEV1 deteriorates to between 30% and 50%of predicted values. Finally, Stage IV, severe COPD, is defined as postbronchodilatory FEV1 ≤30% of predicted values, with orwithout symptoms, or postbronchodilatory FEV1 of ≤30% of predicted values and/or chronic respiratory failure. The GOLD criteria are more complex because they require post-bronchodilatory measurements and, thus, are more time consuming in the office routine.17

ATS Criteria The ATS criteria categorize the severity of COPD into 3 stages: I (Mild), II (Moderate), and III (Severe), based simply on FEV1

measurements (Figure 3). With a per-patient COPD health carecost of $1,681 per year, patients with Stage I COPD, (an FEV1

>50% of predicted values) utilize fewer health care resources thanthose with Stage II or III, mainly because they have a reduced riskof acute exacerbations.18 Yet, even patients with Stage I COPD doexperience acute exacerbations, may have dyspnea, cough or spu-tum, and have reduced quality of life and an increased risk forcomorbidities, such as lung cancer, stroke and cardiac disease. Thevast majority of patients with COPD have Mild Stage I disease.19,20

Many patients with Moderate ATS Stage II COPD (an FEV1 of

between 35% and 49% of predicted values) are often sympto-matic, and their rate of exacerbations is increased relative to Stage I.Thus, these patients experience even a greater diminution in qual-ity of life, along with an expected increase in per-patient healthcare costs to $5,037 yearly.19,20 Severe Stage III COPD, defined asan FEV1 of <35% of predicted values, has an enormous impact onsymptoms and patient quality of life and a high rate of acute exac-erbations. Not surprisingly, these patients with severe COPD havelarge COPD health care expenditures, with an annualized perpatient health care cost of $10,812.19,20

An assessment of disease severity in all patients with COPD inSweden recently showed that the more severe the disease, thegreater the cost of treatment (Table 2). Relative expenditures aresimilar to those in the United States.19 But the surprising aspect ofthis study was that only 4% of all COPD patients have severe disease, while 83% are mild and 17% moderate, using a severitystaging similar to the ATS. Thus, in COPD, prevention, early diagnosis, and averting disease progression can result in substantiallong-term cost benefits for managed care providers as well as therapeutic benefits for members.

Clearly, health care resource utilization is directly related toCOPD severity, with hospitalization accounting for most of thedirect medical expenditures (68.5%).18 The steady rise in hospital-ization costs and drug expenditures for the treatment of COPDhighlights the importance of effective and early management(Table 3).

�� COPD Treatment

Two key objectives of COPD management—including attenuatingpulmonary and systemic inflammation and, thus, preventing disease progression—are currently unachievable. Alleviatingsymptoms, improving function and quality of life, reducing acuteexacerbations, and reducing mortality risk are very importantgoals that are currently achievable.9

Patient education and lifestyle changes remain the initial stepsin any comprehensive therapy program intended to achieve thesegoals. Despite a host of pharmacologic therapies available for themanagement of COPD (Table 4), a lifestyle change—smoking cessation or significant decreases—remains a very effective firststep for altering the natural history and outcome of this insidious disorder in all stages of COPD. Even ex-smokers alsorequire bronchodilators, however.

FEV1 deteriorates approximately 30 mL per year for normalsstarting at age 25. For smokers, the average decline doubles to atleast 60 mL/year but, for some, declines of 150+ mL are seen. If apatient stops smoking, the accelerated rate of decline of FEV1

slows.21 In fact, even a reduction in smoking can decrease the rateof deterioration and produce an improvement in FEV1 over thosewho continue smoking at their previous levels. A change in smokinghabits not only helps improve symptoms, acute exacerbations,and quality of life for COPD patients but it also decreases all-causemortality. The use of bupropion, nicotine replacement, and formal

Severity % of COPD Population % of Total Costs

Mild 83 29(FEV1 >50% predicted)

Moderate 13 41(FEV1 35% to 49% predicted)

Severe 4 30(FEV1 <35% predicted)

FEV1 = forced expiratory volume in 1 second.Adapted from reference 19.

Disease Severity of COPD in Sweden: A Total Population Study

TABLE 2

% of Total Costs % COPD-Related

Hospital admissions 68.5 27.8

Outpatient clinic visits 12.1 14.2

Office visits 9.7 17.8

Prescribed drugs 9.7 34.8

Emergency department 7.9 28.8

Note: 20% of patients account for 74% of costs; comorbidity costs are very high forCOPD patients. Adapted from reference 18.

Direct Medical Expenditures in COPD Patients

TABLE 3



behavioral counseling may be the most effective and patient-acceptable means to assist the habit change.22 All of theseapproaches are cost effective.

Other beneficial nonpharmacologic approaches to the management of COPD include reducing the risks for infections,oxygen supplementation, improved BMI, formal pulmonary rehabilitation, and even the surgical procedures of lung volumereduction surgery or lung transplant for a few carefully selectedpatients. Respiratory infections, primary causes of acute exacerbations in COPD, can be reduced by the use of influenzaand pneumococcus vaccines. A recent study from England indicated that a general population of elderly people who receivedboth influenza and pneumococcal vaccines reduced their mortality risk by 57%.23 One might expect greater impact in aCOPD population. Moreover, long-term oxygen therapy mayextend life and improve cognitive function and exercise tolerancein patients with COPD whose resting pulmonary arterial oxygentension (PaO2) is below 55 mm Hg. However, this approachrequires continuous long-term oxygen use for 15 to 18 hours perday. Pulmonary rehabilitation with 2 months of concentrated,monitored exercise at least 3 times a week and long-term mainte-nance exercise can also help to improve patients with COPD.12,24

In fact, even a good personal exercise plan is crucial for all COPDpatients, regardless of the disease stage. Proper nutrition andincreased BMI can reduce mortality risks in patients who have lowBMI. For selected patients with emphysema and severe COPD,but no severe comorbidities, lung volume reduction surgery or lungtransplantation may be life-saving, though costly, alternatives.17,25,26

Cornerstone Therapy: Bronchodilators Inhaled bronchodilators, alone or in combination, are the primarypharmacologic treatments for COPD (Table 4). Because of their

efficacy, they may be the best alternatives for reducing long-termhealth care costs. Safety, efficacy, and convenience make long-acting agents, especially once-a-day tiotropium, the drugs ofchoice. Not only do these agents improve symptoms, includingdyspnea, patient function, and quality of life, but they also reducethe rate of acute exacerbations and, consequently, hospitalizationsand mortality. However, patients must be educated on the properuse of these medications and delivery systems because failure touse inhalation devices as directed easily compromises their safetyand efficacy.

Pharmacologic therapy with bronchodilators is the cornerstonetreatment for COPD patients who have been educated about theirdisease, vaccinated for influenza and pneumococcal disease, andwho are working to achieve and sustain smoking abstinence. Manyshort- and long-acting bronchodilators are available in 3 generalclasses: anticholinergics, β2-agonists, and methylxanthines.1,8,9,17,27

In most guidelines, anticholinergic drugs are first-tier bron-chodilators because of their safety and efficacy.1,28 Ipratropium, a6-hour duration inhaled anticholinergic, has been available forsome time.27,29 Tiotropium, an anticholinergic with 24-hour plusduration of action after daily dosing, was approved recently by theU.S. Food and Drug Administration (FDA).20 Anticholinergicsblock muscarinic receptors for acetyl choline in the tracheo-bronchial tree, preventing vagally released acetyl choline fromcausing bronchoconstriction and increased mucus secretion inCOPD.20 Anticholinergics accomplish many of the managementobjectives of the GOLD initiative in all stages of COPD, with mini-mal side effects (dry mouth). They increase FEV1, FVC, and qualityof life, while decreasing symptoms, including dyspnea, and acuteexacerbations.27,30-32

Most guidelines suggest the addition of a second broncho-dilator of a different class if COPD patients persist with symptoms


Agent, Recommended Dosing Schedule AE ↓ Active Versus . . . Reference

Tiotropium, qd 28% versus placebo (P)* Brusasco et al. 2003.54

(approved by FDA, January 30, 2004) 13% versus salmeterol Vincken et al. 2002.32

24% versus ipratropium Bates et al. 2003;167(7)948-52.55

22% to 26% versus P, men and women aged >60 years*

Ipratropium, qid 33% versus albuterol* Friedman et al. 1999.56

Salmeterol, bid 20% ↓ versus 30.4% ↓ P* Mahler et al. 1999.51

28.8% ↓ versus 32.9% ↓ P Rennard et al. 2001.52

(6 of 7 studies, not significant ↓) Tashkin and Cooper 2004.50

Formoterol, bid “↓Bad Days” versus P or ipratropium bromide Dahl et al. 2001.48

Ipratropium + albuterol, qid 38% ↓ versus albuterol alone* Friedman et al. 1999.56

Ipratropium, qid + salmeterol, bid 67% versus P; 39% versus salmeterol van Noord et al. 2000.57

Salmeterol + fluticasone† (50/500, bid) 25% versus P* Calverley et al. 2003.53

Salmeterol, bid + theophylline oral 50% versus theophylline alone ZuWallack et al. 2001.58

Formoterol, bid + budesonide† 24% versus P* Bates et al. 2003;167(7)948-52.55

* P<0.05. † Off-label dosing: not FDA approved. qd = once a day; bid = twice a day; qid = 4 times a day.

Bronchodilators That Decrease Acute Exacerbations (AE) of COPDTABLE 4


or acute exacerbations on one drug.1,9,15 A longer acting β2-agonist,usually 12- to 14-hour duration formoterol or salmeterol twice aday, is chosen. Those drugs are effective inhaled bronchodilatorsin COPD.33 In the COPD patient with underlying cardiovasculardisease, selective β1-blockers (e.g., atenolol) can be added to prevent the increased risk of unstable angina or myocardialinfarction from long- or short-acting β2-agonists.34,35 Short-actingβ2-agonists, such as albuterol, are not used as monotherapy in theregular, long-term management of COPD but may be used as rescue medication, usually combined with ipratropium bromide.36

Today, methylxanthines are used infrequently for their bron-chodilatory effect but, rather, are added to therapy of advancedCOPD patients with pulmonary hypertension and cor pulmonale(especially with right ventricular failure). These drugs decreasepulmonary artery pressure and pulmonary vascular resistance,while improving cardiac output, renal blood flow, and glomerularfiltration rate. Blood level measurements are required if methyl-xanthines are used, with levels below 12 mcg/mL being ideal.37,38

At present, there are no inhaled corticosteroid (ICS) medica-tions approved by the FDA for use in COPD. Multiple large,lengthy, international trials have failed to show improved out-comes with these drugs.39-42 The combination of 50 mcg salme-terol/250 mcg fluticasone twice a day has recently been approvedfor COPD by the FDA, with warnings not to go to higher dosesbecause of steroid side effects.43 Recent studies of ICS use in COPDpatients have revealed not only dose-related decreases in bonedensity but also dose-related increases in hip and other fractures(26% to 35% higher than non-ICS patients).44

Based on currently available evidence, once-a-day tiotropiumappears to be a safe and efficacious drug for all COPD patients inall stages of disease, mild through very severe.45,46 If a patient con-tinues to have symptoms and/or frequent exacerbations, additionof a long acting β2-agonist twice a day seems best. Formoterol,because of rapid onset of bronchodilatation, consistent effect ondyspnea improvement, and decrease in exacerbation rate33,47-49

appears to be a prudent choice over salmeterol, which has sloweronset of action, has not decreased exacerbation rate in 6 of 7 studies, and has inconsistent effects on dyspnea.50-52

For a small number of special patients, some “add-on” agentsmay be useful. Methylxanthines have utility in cor pulmonale.37,38

For patients with severe disease on daily tiotropium plus twice-daily formoterol but who are still having symptoms and/or frequent exacerbations (≥3/year), an off-label trial of ICS for 6 weeks to 6 months is justified.53 If objective evidence (e.g., decreased acute exacerbations rate, increased FEV1,increased 6-minute walk distance) of ICS efficacy is not found, theICS should be stopped because of side effects.

As COPD worsens, lung function progressively deterioratesand the rate of acute exacerbations increases markedly. Indeed,acute exacerbations in COPD account for most physician visitsand hospitalizations, often in the intensive care unit, and mayresult in death. Seventy percent of the total cost of COPD is spent

on acute exacerbations, and exacerbations are the most importantdeterminate of quality of life in COPD patients. Acute exacerba-tion rate can be decreased greatly by regular daily use of long-acting bronchodilators (especially anticholinergics), vaccination,pulmonary rehabilitation, and decreased smoking.

Over the long-term, clinicians should monitor patients treatedfor COPD regularly to evaluate their status and treatment plan effec-tiveness. Objective functional improvement or deterioration can beassessed through the use of a 6-minute walk distance, rest or exercise inspiratory capacity, and FEV1.1 In addition, the numberand severity of acute exacerbations should be carefully monitored.

�� Conclusions

COPD is an inflammatory disease that not only ravages the air-ways but also affects the entire body, especially the cardiovascularsystem, augmenting atherosclerosis that is responsible for signifi-cant morbidity and mortality associated with COPD. Nearly 95%of COPD in the United States is related to smoking; however,many smokers are unaware that they have COPD. In addition, notall doctors ask their patients about their smoking habits and per-form office spirometry, the mandatory diagnostic tool that mustbecome a part of a routine examination for smokers.

The prevalence of COPD and its associated health care costs aresignificant and growing. As the population ages, the morbidity andmortality associated with COPD will take an ever-increasing tollon already-strained health care resources. With early diagnosisand comprehensive treatment, coupled with smoking cessation orreduction plus long-acting bronchodilators, vaccines, and pul-monary rehabilitation, this course can be dramatically altered.Pharmacologic interventions, especially the use of broncho-dilators, can remediate symptoms and improve the patient’s quality of life. Long-term treatment and monitoring are essential ifthe management of COPD is to be successful—COPD is not anirreversibly disabling disorder.

DISCLOSURES

The author received an honorarium from Boehringer Ingelheim and Pfizer Inc.for participation in the symposium upon which this article is based. He hasreceived funding from numerous pharmaceutical companies for clinicalresearch, consulting, and speaking but discloses no conflict of interest orpotential bias regarding this article.

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Chronic obstructive pulmonary disease (COPD) is the onlydisease among the principal causes of death that is con-tinuing to increase in prevalence and mortality.1 The high

morbidity and mortality rates have been associated with a failureto identify at-risk patients and provide effective intervention andtreatment. Patients frequently postpone seeking a physician’s helpuntil extensive lung damage has occurred, thereby delaying effective treatment.2

Treatment may also be inappropriate. Patients with COPD maybe treated with drugs that are effective in treating asthma but areless effective in treating COPD since the 2 diseases have differentpathophysiologies.3 While no pharmacologic treatment yet existsthat will halt COPD’s progression, current and new therapies canplay an important role in preventing and controlling symptoms,reducing the frequency and severity of exacerbations, and improv-ing health status and exercise tolerance.4

�� Goals of Treatment

The overall approach to the management of stable COPD is a step-wise increase in treatment, depending on the disease severity.4

Effective management includes both nonpharmacologic meas-ures—education about the disease and exacerbations, smokingcessation, an exercise plan, nutrition counseling, vaccines forinfluenza and pneumococcus, and pulmonary rehabilitation—andpharmacologic treatment. According to the Global Initiative forChronic Obstructive Lung Disease (GOLD) guidelines, the goals ofCOPD management are to4

• prevent disease progression,• relieve symptoms,• improve exercise tolerance,• improve health status,• prevent and treat complications,• prevent and treat exacerbations, and• reduce mortality.

Smoking Cessation Smoking cessation is the only intervention that has been shownto slow the progression of COPD.5 COPD management mustinclude a discussion on smoking cessation, with the use of phar-macologic cessation therapy (e.g., nicotine replacement, bupro-pion) when necessary.

�� Drugs Used in the Treatment of COPD

Bronchodilators Inhaled bronchodilators are the cornerstone of symptomatic man-agement of COPD, and include β2-agonists, anticholinergics, andmethylxanthines. Individual response to therapy varies, and thechoice of a bronchodilator or bronchodilator combination is tailored to patient response. Short-acting bronchodilators have aquick onset of action and, thus, are useful on an as-needed basisfor rescue. Long-acting bronchodilators are taken on a regular

Chronic Obstructive Pulmonary Disease Treatment Options DOROTHY L. GEORGE, PharmD

DOROTHY L. GEORGE, PharmD, is senior associate director, Cerner HealthInsights, Beverly Hills, California.

AUTHOR CORRESPONDENCE: Dorothy L. George, PharmD, SeniorAssociate Director, Cerner Health Insights, 9100 Wilshire Blvd., Suite 655 East,Beverly Hills, CA 90212. Tel: (310) 598-4460; Fax: (816) 936-1860; E-mail: [email protected]


Author

ABSTRACT

OBJECTIVE: To discuss current therapies for the treatment of chronic obstructivepulmonary disease (COPD) and their efficacy and use according to current treat-ment guidelines.

SUMMARY: The overall approach to the management of stable COPD is a step-wise increase in treatment, depending on disease severity. Inhaled broncho-dilators are the cornerstone of symptomatic management of COPD and includeβ2-agonists, anticholinergics, and methylxanthines. Short-acting β2-agonist bronchodilators (e.g., albuterol) have a quick onset of action and are useful forrescue. Long-acting bronchodilators are taken on a regular basis to prevent or reduce symptoms and include β2-agonists saleterol and formoterol and anticholinergics ipratropium bromide and tiotropium bromide. Methylxanthines have decreased in usage due to potential toxicity. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines are an international initiative, updated in 2003. GOLD staging consists of 5 levels of severity; treatment guidelines recommend a step-wise approach, with short- and long-acting bronchodilators as the cornerstone of therapy.

CONCLUSION: Appropriate pharmacologic treatment of symptomatic COPD can result in reduced patient limitations and health care utilization and improved health-related quality of life.

KEYWORDS: COPD, COPD management, COPD treatment, Bronchodilators,β2-agonists, Anticholinergics, GOLD intitiative



Chronic Obstructive Pulmonary Disease Treatment Options

basis to prevent or reduce symptoms. Combining bronchodilatorsmay result in improved efficacy and decreased risk of side effectscompared with the continual increase in dose of a single broncho-dilator.4 While bronchodilators may cause only a small increase inforced expiratory volume in 1 second (FEV1) (<10%) in patientswith COPD, they may improve symptoms and exercise toleranceby reducing hyperinflation and, therefore, dyspnea.5

β2-agonists. Short-acting β2-agonists (e.g., albuterol) have arapid onset of action that provides prompt relief of symptoms.Because their duration of action is short, they typically must begiven 4 to 6 times daily to achieve sustained bronchodilation.Long-acting β2-agonists (e.g., salmeterol, formoterol) have a pro-longed duration of action and are effective in sustaining broncho-dilation with twice-daily dosing. Long-acting β2-agonists demonstrate superior efficacy compared with placebo, while datacomparing them with ipratropium (an anticholinergic with anintermediate duration of action) are mixed.6,7

In a 12-week, randomized, double-blind, double-dummy,placebo-controlled parallel group trial of 411 symptomatic COPDpatients without significant concurrent disease, salmeterolxinafoate (42 mcg, twice a day [bid]) was superior to placebo andipratropium (36 mcg, 4 times a day [qid]) in improving lung func-tion (P<0.0001). Compared with placebo at the end of 12 weeks,dyspnea, as measured by the Total Dyspnea Index (TDI), was significantly improved for ipratropium but not for salmeterol,although salmeterol demonstrated significant improvement overplacebo at most other measurement points. Salmeterol and ipra-tropium both significantly reduced the need for supplementalalbuterol compared with placebo, but there was no significant difference between salmeterol and ipratropium. Salmeteroldelayed the time to onset of exacerbations compared with placebo (P = 0.0052) and ipratropium (P = 0.0411), but there was no significant difference in the overall rate of exacerbations.

Both salmeterol and ipratropium significantly enhanced health-related quality of life (HRQoL) compared with placebo, as meas-ured by the chronic respiratory disease questionnaire (CRDQ),both in terms of increases in the CRDQ score (P = 0.007) and inthe proportion of patients achieving a clinically important increaseof at least 10 points in the total score (salmeterol, P = 0.002; ipra-tropium, P = 0.041). Of note, the baseline average FEV1 for the salmeterol group was significantly higher than for the ipratropiumand placebo groups.6

Similarly, a 12-week, double-blind, randomized, parallel-group, placebo-controlled study of 780 COPD patients found thatinhaled formoterol (12 mcg or 24 mcg bid) was superior to place-bo and ipratropium (40 mcg qid) in bronchodilation, as measuredby the area under the curve FEV1 (0 to 12 hours). Formoterol significantly decreased the use of rescue medication comparedwith both placebo (P<0.001) and ipratropium (P = 0.014).Formoterol significantly improved HRQoL (as measured by ananalysis of covariance of the increases in the St. George’sRespiratory Questionnaire [SGRQ] total score) compared withplacebo whereas ipratropium did not.7 In these clinical trials,adverse events of long-acting β2-agonists were considered compa-rable to placebo.6,7

Anticholinergics. Quarternary ammonium anticholinergicagents are more effective in the treatment of COPD than asthma.5

There are 2 inhaled anticholinergics available in the United States:ipratropium and the newly approved long-acting agent tiotropium.Because of their relatively long onset of action (up to 60 minutes)and long duration of action (6 to 8 hours, ipratropium; >24 hours, tiotropium), anticholinergics are effective at providingsustained bronchodilation but are not used for short-term rescue.The combination of albuterol and ipratropium bromide (as a sin-gle inhaler) has been effective in reducing the rate of exacerbationsand thereby improving cost-effectiveness.8 The addition of ipra-tropium to salmeterol has also been effective in improving lungfunction measurements.9 Ipratropium is delivered via a metered-dose inhaler (MDI).

The new anticholinergic agent, tiotropium bromide, differsfrom ipratropium in its pharmacokinetic properties. Cholinergicstimulation induces bronchial smooth muscle contraction. Threesubtypes of human muscarinic receptors are found on airwaysmooth muscle: the M1, M2, and M3 receptors. Broncho-constriction is mediated by M1 and M3 receptors. The M2 receptorsubtype acts as an inhibitory receptor; stimulation of the M2receptor inhibits the release of acetylcholine at cholinergic nerveendings. Thus, inhibition of the M1 and M3 receptors, but not theM2 receptor, is the desired objective to achieve optimal broncho-dilation with anticholinergic agents. Tiotropium has a significantly longer dissociation half-life from M3 receptors (34.7 hours compared with 0.26 hours for ipratropium) andmuch shorter dissociation half-life from M2 subtype receptors. In vitro and in vivo studies show that tiotropium has a long duration of action, providing bronchodilation for more than

Inhaled Corticosteroids

Study Dyspnea QoL Exacerbation Rate

Paggiaro, 1998. NS — NS*Fluticasone

Vestbo, 1999. NS — NSBudesonide

Burge, 2000; Spencer, 2001. — SlowedFluticasone

Lung Health, 2000. Improved NS† NSTriamcinolone

Calverly, 2003. Improved NSFluticasone-salmeterol

* Fewer severe exacerbations. † SF-36, not respiratory-specific. QoL = quality of life;NS = not significant.

Efficacy of Inhaled Corticosteroids in the Treatment of COPD

TABLE 1



24 hours in patients with COPD.3

In clinical trials, tiotropium (18 mcg daily) has been comparedwith placebo, ipratropium (40 mcg qid), and salmeterol (50 mcgbid). In the ipratropium-comparator trials, tiotropium significantlyimproved lung function, dyspnea, and HRQoL; reduced supple-mental (rescue) albuterol use; and delayed first exacerbation andtime to hospitalization due to exacerbation compared with ipra-tropium. Adverse events were similar between the 2 groups, withthe exception of an increase in dry mouth in the tiotropium group.10

In a comparison of health outcomes between treatment withtiotropium, salmeterol, or placebo, tiotropium but not salmeterolwas associated with a significant delay in time to onset of the firstexacerbation (P<0.02 versus placebo) and fewer exacerbations perpatient year (1.07 tiotropium versus 1.23 salmeterol and 1.49placebo; P = 0.025 for tiotropium versus placebo, not statisticallysignificant for salmeterol versus placebo and tiotropium versus salmeterol). Health resource utilization was also lower in thetiotropium group, with 0.1 hospital admissions per patient year,compared with 0.17 for salmeterol and 0.15 for placebo (the difference was not statistically significant). The number of dayspatients were unable to perform usual daily activities was 8.3 in thetiotropium group, compared with 11.1 in the salmeterol group and10.9 in the placebo group (P<0.05 for tiotropium versus placebo).

Tiotropium also improved lung function, HRQoL, and dysp-nea. Tiotropium resulted in significantly greater bronchodilationthan salmeterol as measured by the trough FEV1 at the end of the6-month study period (P<0.05). Compared with placebo, the dif-ference in the proportion of patients who achieved a clinicallymeaningful improvement in the SGRQ total score was significantlyhigher for tiotropium (P<0.05), but was not for salmeterol. Bothtiotropium and salmeterol resulted in a higher proportion ofpatients achieving clinically important improvements in the TDIscore compared with placebo. Researchers concluded that exacer-bations of COPD and health resource usage were positively affectedby daily treatment with tiotropium.11 Tiotropium is delivered viathe breath-activated HandiHaler dry powder device.

Methylxanthines. Theophylline, one of the oldest broncho-dilators, is available for long-acting bronchodilation as a sustained-release oral formulation. While it is effective in the treatment ofCOPD, its potential toxicity has led to a decline in usage. Inhaledbronchodilators are preferred.4

Corticosteroids Inhaled corticosteroids (ICSs) are a mainstay of chronic asthmaand are widely prescribed for COPD. However, COPD’s inflam-mation differs from that of asthma and is less responsive or non-responsive to inhaled or oral corticosteroids.5 Clinical trials of ICSsin COPD have only shown consistent reduction in exacerbationfrequency in patients with moderate-to-severe COPD (as definedby spirometric criteria).12-15 In these studies, ICS use has impactedCOPD symptoms and HRQoL inconsistently. The results of clinical trials that evaluated the effect of ICSs (including an ICS

fluticasone-salmeterol combination) on dyspnea, HRQoL, andexacerbation rates are summarized in Table 1.

A meta-analysis of ICS trials found that corticosteroids did notappear to affect the long-term goal of decreasing the decline in

GOLD Treatment Approach

Stage 0: Stage I: Stage II: Stage III: Stage IV:At Risk Mild Moderate Severe Very Severe

• Normal • FEV1/FVC • FEV1/FVC • FEV1/FVC • FEV1/FVCSpirometry <70% <70% <70% <70%

• Chronic • FEV1 ≥80% • 50% < FEV1 • 30% < FEV1 • FEV1 <30%Symptoms <80% <50% or Chronic

Resp. Failure

GOLD Initiative: COPD Treatment TABLE 3

Avoid risk factors; influenza vaccination

Add short-acting bronchodilator when needed

Add regular treatment with 1 or more long-acting bronchodilators

Add inhaled corticosteroids if repeated exacerbations

Add O2 if chronic resp.failure

GOLD = Global Initiative for Chronic Obstructive Lung Disease;FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity;HF = heart failure.


GOLD = Global Initiative for Chronic Obstructive Lung Disease; RCT = randomized controlled trial.

Evidence Sources of DefinitionCategory Evidence (Evidence is from…)

A RCTs • End points of well-designed RCTs withRich body consistent pattern of findingsof data • Substantial numbers of studies involving

substantial numbers of participants

B RCTs • End points of intervention studies of Limited body limited number of patients, post hoc or of data subgroup analysis of RCTs, or

meta-analysis of RCTs• Trials that are few, small, in a

population different than target, or have inconsistent results

C Nonrandomized • Outcomes of uncontrolled or or observational nonrandomized trials or from observationalstudies studies

D Panel consensus • Based on clinical experience or knowledgejudgment • Category is used only when guidance was

deemed valuable but clinical literatureinsufficient

GOLD Levels of Evidence TABLE 2

or Right HF• RiskFactors

• With or WithoutSymptoms • With or Without

Symptoms• With or Without

Symptoms


FEV1.16 Also, in clinical trials of fluticasone in combination withsalmeterol as a single inhaler, the combination did not reduceexacerbations and did not result in clinically meaningful improve-ments in quality of life (measured by a variety of instruments) thanplacebo, long-acting β-agonist, or ICS alone.15,20,21 Based upon theevidence available at this time, ICS is recommended only inpatients with severe and very severe COPD (GOLD classification)and frequent exacerbations.4

�� COPD Treatment Guidelines

The American Thoracic Society (ATS) first created guidelines forthe treatment of COPD in 1986; the guidelines were updated in1995. While they have a high degree of familiarity among physicians in the United States and a high degree of credibility,they were not developed using an explicit evidence-basedmethodology (i.e., they are largely consensus-based) and are due

for revision in 2004. The GOLD guidelines are an international initiative, cospon-

sored by the National Institutes of Health and the World HealthOrganization. The guidelines were originally created in 2001, withan update issued in 2003. The 2003 revision expanded the classi-fication of severity from 4 to 5 stages, ranging from 0 (at risk) toIV (very severe COPD). The GOLD guidelines were developed tohave global applicability and provide the evidence-based founda-tion for local development of treatment algorithms. The GOLDinitiative is both evidence- and consensus-based. Levels of evidence are assigned to treatment recommendations and rangefrom “A” to “D.” (Table 2)

Treatment Recommendations: GOLD Initiative The maintenance treatment of COPD utilizes a step-up approach,with therapies added as the disease progresses and the severity of

Drug Trade Name(s) Dosing Maximum Dose per 24 Hours

Long-Acting β2-agonists (LABA)

Formoterol fumarate Foradil Capsule: 12 mcg, bid 24 mcg Salmeterol xinafoate Serevent Aerosol: 42 mcg (2 inhalations), bid

Powder: 50 mcg (1 inhalation), bid

Short-Acting β2-agonist (SABA)

Albuterol sulfate Proventil 200 mcg (1 inhalation) every 4 to 6 hours, N/AVentolin or 2.5 mg, tid or qid, via nebulizer

Anticholinergics

Ipratropium bromide Atrovent 36 mcg (2 inhalations), qid 500 mcg (12 inhalations)

Tiotropium bromide18 Spiriva 18 mcg (1 capsule), once daily N/A

Corticosteroids*

Beclomethasone dipropionate Qvar 42 mcg per inhalation; 2 inhalations, tid 10 inhalationsVanceril or bid, or 4 inhalations, qid

Budesonide Pulmicort 200 to 400 mcg (1 to 2 inhalations), bid, N/Aor 400 to 800 mcg (2 to 4 inhalations), bid,depending on patient history with corticosteroids

Fluticasone propionate Flovent Aerosol: 88 mcg, bid, up to 220 mcg, bid, 440 mcg, bid, 880 mcg, bid,depending on patient history with inhaled for patients previously takingcorticosteroids; up to 880 mcg, bid, for oral corticosteroidspatients with a history of oral corticosteroidsPowder: 100 to 500 mcg, bid, depending on 500 mcg, bid, 1,000 mcg, bid, patient history with inhaled corticosteroids; up to for patients with a history500 mcg, bid, for patients with a history of oral corticosteroidsof oral corticosteroids

Triamcinolone acetonide Azmacort 110 mcg (2 inhalations), tid or qid 16 inhalations

Combination drugs

Fluticasone19 Advair 1 inhalation, bid, 250 mcg/50 mcgpropionate/salmeterol inhalation powder

Ipratropium bromide/albuterol Combivent 42 mcg/206 mcg (2 inhalations), qid 12 inhalations

Inhaled Therapies for the Management of COPD17TABLE 4

* Labeling indications do not specifically include COPD, chronic bronchitis, or emphysema. bid = twice a day; tid = 3 times a day; qid = 4 times a day; N/A = not available.



symptoms increases. Regular treatment must be maintained at thesame level for long periods of time, with adjustments as needed fordisease progression or side effects. Because no existing medicationcan modify the long-term decline in lung function that is charac-teristic of COPD, therapy is aimed at decreasing symptoms andcomplications. Treatment responses are individual and may varyfrom patient to patient.

In the GOLD initiative, treatment begins at Stage 0 (at risk),with the avoidance of risk factors and the administration of theinfluenza vaccination, and ends with Stage IV (very severe), withthe addition of long-term oxygen therapy and the consideration ofsurgical interventions.4 Table 3 summarizes therapy at each stageof COPD, following the GOLD guidelines.

Stage 0. At this stage, spirometry is normal, but the patientpresents with chronic symptoms, such as cough and sputum pro-duction. Education is key to treatment. All members of the healthcare team must stress smoking cessation to the patient, and anannual influenza vaccination should be administered. Influenzahas been associated with significant adverse health effects in elderly patients with COPD, and the use of an annual vaccinationhas been shown to result in substantial benefits to the patient and health care system, including fewer outpatient visits and hospitalizations and reduced mortality.22

Stage 1 (Mild COPD). The use of a short-acting inhaled bron-chodilator, such as albuterol, is recommended on an as-neededbasis.

Stage II (Moderate COPD). Regular treatment with a long-acting bronchodilator is recommended (Evidence A), with sup-plemental use of a short-acting bronchodilator for rescue. Long-acting β2-agonists, such as inhaled formoterol and salmeterol, havea duration of action ≥12 hours and require twice-daily dosing.Inhaled ipratropium bromide is a short-acting anticholinergic witha duration of action of 6 to 8 hours. The recently approvedtiotropium bromide has a duration of action ≥24 hours andrequires once-daily dosing. A combination of β2-agonist and anti-cholinergic may also be recommended at this stage, since com-bining drugs with different mechanisms may increase the degreeof bronchodilation achieved without increasing side effects. Singledrugs may be administered in combination, or a combinationproduct may be used. In the United States, albuterol and ipra-tropium are available as a combination product. Oral theophyllinemay also be used in Stage II, although it is less preferred becauseof toxicity risks.

Stage III (Severe COPD). At this stage, the addition of ICS aspart of regular maintenance therapy is recommended if the patientexperiences frequent exacerbations (e.g., 3 exacerbations in thelast 3 years) while receiving bronchodilator therapy (Evidence A).ICS agents include beclomethasone, budesonide, fluticasone, andtriamcinolone. For patients requiring both a bronchodilator andICS, a combination product of fluticasone/salmeterol is available.

Table 4 summarizes recommended dosing of inhaled therapiesfor management of COPD, according to their labeled indications.

Stage IV (Very severe COPD). The administration of long-term oxygen is recommended if the patient experiences chronicrespiratory failure. Long-term administration of oxygen (>15 hours per day) has been shown to increase survival inpatients with COPD.23

Other guidelines, such as the Veteran’s Administration/Department of Defense guidelines, are developed for a specifichealth system and utilize an evidence-based methodology withconsensus used where inadequate evidence existed.24 All of theselocally developed guidelines are similar, with bronchodilators asthe foundation of therapy and corticosteroids held in reserve forspecified situations.

�� Conclusion

The medical management of COPD begins with the identificationof the Stage 0, at-risk patient. Interventions, including smokingcessation, should be initiated immediately. The appropriate phar-macologic treatment of symptomatic COPD can result in reducedpatient limitations and health care utilization and improvedHRQoL.

DISCLOSURES

The author received an honorarium from Boehringer Ingelheim and Pfizer Inc.for participation in the symposium upon which this article is based. She dis-closes that she is employed by a health care consulting firm that has beenengaged by pharmaceutical and biotech manufacturers, including those withan interest in COPD.

REFERENCES

1. Petty TL. Scope of the COPD problem in North America. Chest. 2000;117(5 suppl 2): 326S-331S.

2. Ferguson GT. Management of COPD. Postgrad Med. 1998;103:1-13.

3. Barnes PJ. Novel approaches and targets for treatment of chronic obstruc-tive pulmonary disease. Am J Respir Care Med. 1999;160(5 pt 2):S72-S79.

4. Global Initiative for Chronic Obstructive Lung Disease. Global strategy fordiagnosis, management and prevention of chronic obstructive pulmonary dis-ease. NHLBI/WHO Workshop report, updated 2003. Available at: www.gold-copd.com. Accessed May 20, 2004.

5. Barnes PJ. Chronic obstructive pulmonary disease. New Engl J Med. 2000;343:269-80.

6. Mahler DA, Barbee RA, Gross NJ, Yancey SW, Anderson WH. Efficacy ofsalmeterol xinafoate in the treatment of COPD. Chest. 1999;115:957-65.

7. Dahl R, Greefhorst LAPM, Nowak D, et al. Inhaled formoterol dry powderversus ipratropium bromide in chronic obstructive pulmonary disease. Am JRespir Crit Care Med. 2001;164:778-84.

8. Friedman M, Serby CW, Menjoge SS, Wilson JD, Hilleman DE, Witek TJ.Pharmacoeconomic evaluation of a combination of ipratropium plus albuterolcompared with ipratropium alone and albuterol alone in COPD. Chest. 1999;115:635-41.

9. van Noord JA, de Munck DR, Bantje TA, Hop WC, Akveld ML, Bommer AM.Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium. Eur Respir J. 2000;15:876-85.

10. Vincken W, van Noord JA, Greefhorst APM, et al. Improved health outcomes in patients with COPD during 1 year’s treatment with tiotropium.Eur Respir J. 2002;19:208-16.



11. Brusasco V, Hodder R, Miravitlles M, et al. Health outcomes followingtreatment for six months with once-daily tiotropium compared with twice-daily salmeterol in patients with COPD. Thorax. 2003;58:399-404.

12. Vestbo J, Sorensen T, Lange P, Brix A, Torre P, Viskum K. Long-term effectof inhaled budesonide in mild and moderate chronic obstructive pulmonarydisease: a randomized controlled trial. Lancet. 1999;353:1819-23.

13. Lung Health Study Research Group. Effect of inhaled triamcinolone onthe decline in pulmonary function in chronic obstructive pulmonary disease.New Engl J Med. 2000;343:1902-09.

14. Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK.Randomised, double-blind, placebo-controlled study of fluticasone propionatein patients with moderate to severe chronic obstructive pulmonary disease:the ISOLDE trial. BMJ. 2000;520:1297-303.

15. Calverley P, Pauwels R, Vesbo J, et al. Combined salmeterol and fluticas-one in the treatment of chronic obstructive pulmonary disease: a randomizedcontrolled trial. Lancet. 2003;361:1660.

16. Highland KB, Strange C, Heffner JE. Long-term effects of inhaled cortico-steroids on FEV1 in patients with chronic obstructive pulmonary disease. A meta-analysis. Ann Intern Med. 2003;138:969-73.

17. Kelly WJ, ed. Physician’s Drug Handbook, 10th ed. Philadelphia, PA:Lippincott Williams & Wilkins; 2003.

18. Spiriva (prescribing information). Ridgefield, CT: Boehringer IngelheimPharmaceuticals, Inc.; 2003.

19. Advair (prescribing information). Research Triangle Park, NC:GlaxoSmithKline; 2004.

20. Mahler DA, Wire P, Horstman D, et al. Effectiveness of fluticasone propi-onate and salmeterol combination delivered via the Diskus device in the treat-ment of chronic obstructive pulmonary disease. Am J Respir Crit Care Med.2002;166:1084-91.

21. Hanania NA, Darken P, Horstman D, et al. The efficacy and safety of fluti-casone propionate (250 microg)/salmeterol (50 microg) combined in theDiskus Inhaler for the treatment of COPD. Chest. 2003;124:834-43.

22. Nichol KL, Baken L, Nelson A. Relation between influenza vaccinationand outpatient visits, hospitalization, and mortality in elderly persons withchronic lung disease. Ann Intern Med. 1999;130:397-403.

23. Nocturnal Oxygen Therapy Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. AnnIntern Med. 1980;93:391-98.

24. Medical Advisory Panel for the Pharmacy Benefits Management StrategicHealthcare Group. The pharmacologic management of chronic obstructivepulmonary disease. Updated 2002. Department of Veterans Affairs, VeteransHealth Administraiton, Publication No. 02-0012. Available at: www.vapbm.org.Accessed May 20, 2004.


Assessing the Need for a Clinical COPD Care Program in a Managed Care Organization

H. ERIC CANNON, PharmD

H. ERIC CANNON, PharmD, is director, pharmacy services, IHC HealthPlans, Intermountain Health Care, Salt Lake City, Utah.

AUTHOR CORRESPONDENCE: H. Eric Cannon, PharmD, Director,Pharmacy Services, IHC Health Plans, Intermountain Health Care, 36 SouthState St., Suite 1900, Salt Lake City, UT 84111. Tel: (801) 442-3352; Fax: (801) 442-3006; E-mail: [email protected]


Author

To manage care effectively, managed care organizations(MCOs) necessarily must determine where best to placeresources and funds. Due to their unique ability to iden-

tify and treat patients with serious chronic conditions such aschronic obstructive pulmonary disease (COPD), MCOs ideallycan improve patient outcomes and reduce the costs of care.

Specifically, because COPD is often underdiagnosed andimproperly treated in family practice settings,1 MCOs canencourage primary care physicians to adhere to diagnosis andtreatment guidelines that have been shown to result in lowerCOPD utilization levels and costs.2 In addition, through the use ofsophisticated information systems, MCOs can create systemwideclinical care programs for COPD patients, including the develop-ment and implementation of treatment guidelines and measure-ment of clinical outcomes resulting from the program.

Before undertaking such efforts, however, MCOs shoulddetermine whether the prevalence and costs of COPD warrantthe resources that would be required and whether useful evidence-based treatment guidelines for COPD are available tohelp develop an effective program. In addition, MCOs shouldanalyze existing patterns of COPD management within the system in order to identify potential areas that could beimproved with a systemwide clinical program.

Intermountain Health Care (IHC), an integrated not-for-profit health care system based in Salt Lake City, Utah, hasrecently taken these steps. IHC—which ranked number one inModern Healthcare’s top 100 integrated health care networks in2000, 2002, and 20033—consists of 21 hospitals, 150 medicalfacilities and physician offices, 450 physician employees(including 350 primary care physicians), 2,500 affiliatedphysicians, and 300 employee pharmacists. The health plancovers 480,000 lives and 500,000 affiliate lives.

The IHC integrated information system enables it to capture and evaluate COPD clinical data from medical claims,pharmacy claims, laboratory, pathology, radiology, hospitals,clinics, home care, and mental health components. Figure 1shows how data are captured and how clinical programs aredeveloped at IHC.

�� Determining the Prevalence of COPD

An analysis of IHC data suggests that COPD may be under-diagnosed among its plan members. Only 553 of the 292,800adult plan members (approximately 2 adults per 1,000) havebeen diagnosed with COPD.4 In comparison, 60 adults per1,000 report that they had physician-diagnosed COPD in theUnited States.5 Because the vast majority of individuals withCOPD are smokers,1,6 lower smoking rates in IHC’s geographicregion may account for the lower prevalence at IHC. While

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a systemic inflam-matory condition, is costly and often devastating to patient quality of life. COPD isalso greatly underdiagnosed and often inappropriately treated. A managed careorganization therefore evaluated whether a systemwide COPD clinical programwithin its organization may be appropriate. The organization examined the currentprevalence, costs, and adherence to clinical treatment guidelines.

OBJECTIVE: To identify the prevalence and costs of COPD within the managed careorganization and to ascertain whether the condition could be better managedusing a systemwide clinical program.

CONCLUSION: Both diagnosis and treatment of COPD would likely be improvedwith a comprehensive clinical COPD care program that would include measuringoutcomes, stratifying COPD patients by risk, and initiating disease state manage-ment efforts.

KEYWORDS: COPD management, COPD outcomes, Clinical COPD program



23% of all American adults report that they smoke, only 12.8%of adults in Utah smoke.7

An underdiagnosis for COPD within IHC would not beunexpected, however, based on national statistics. While anestimated 10 million U.S. adults reported that they had physi-cian-diagnosed COPD in 2000,5 National Health and NutritionExamination Survey (NHANES) III data suggest that more thandouble that number (approximately 24 million adults) actuallyhave evidence of impaired lung function.5 Additionally, morethan 71.7% of the population with a low level of lung functiondid not have a current diagnosis of obstructive lung disease in2000; 46.2% of those with moderate-to-severe impairment didnot have a current diagnosis.8 Most underdiagnosis occurs inpatients with mild-to-moderate COPD.8

Additionally, the incidence of COPD and mortality fromCOPD are both increasing nationwide.5 From 1980 to 2000, therate of persons with self-reported COPD increased from 55.8 to60 per 1,000 adults. In the same period, COPD mortality ratesincreased from 40.7 to 66.9 per 100,000 adults.5 Based onthese data, it seems likely that COPD is underdiagnosed at IHCand that the prevalence is higher among IHC members than theclinical data indicate.

�� Determining the Costs of COPD Care

Improving the quality of service delivered to the patient is theforemost concern for IHC and its physicians. IHC recognizesthat when high-quality care is delivered, cost benefits will follow. Costs are easily measured, however, and can indicatehow well COPD and COPD exacerbations are managed.

Based on claims data gathered by IHC, the average totalannual cost of treatment for a COPD patient is $13,654.4 Thisamount represents all costs of medical care, including directcare for COPD. The average number of prescriptions filled eachyear, for any condition, is 49 per COPD patient.

The total annual cost of care of $13,654 per patient at IHCmay be higher than expected, based on available evidence. Onestudy of 413 patients found that the median annual cost ofCOPD care per patient was $1,681 for stage I COPD patients,$5,037 for stage II COPD patients, and $10,812 for stage IIICOPD patients.2 Patients in this study were staged based onpredicted versus actual forced expiratory volume in 1 second(FEV1) values. Forty percent of these total costs were due tohospitalizations.

Similarly, the main costs for COPD care at IHC are not due tothe medications used to control the disease, but to the exacerba-tions of COPD. While medications account for only $2,647,medical costs—including emergency room visits and hospitalstays—account for $11,007.4 Reducing the number of exacerba-tions would therefore reduce overall costs considerably.

The high cost of treating exacerbations and treatment fail-ures is demonstrated in clinical studies as well. Investigation of2,414 patients with chronic bronchitis and COPD found that


Systemwide Disease Management Implementation

FIGURE 1

Unique Feature — Systemwide Disease Management Implementation

Health Plans

• QI - Initiates NCQA/HEDISinitiatives with ClinicalPrograms and tracks compliance

• Provider Relations - assistsin distibution of CPMs tophysicians

• Claims/Member Services -collects claims and servicequality data such as member complaints

• Advocates - schedule appointments for preventive care

• Advocates - channel members to appropriateproviders

• HCS - provide care management and diseasemanagement service (medicine, surgery, Rx)

• HCS - meets with deliverysystem to monitor andimprove CPMs

Hospitals/Health Services

• Leads Clinical ProgramLeadership Team to manage/monitor performance

• Provide inpatient and outpatient care management support

• Provide disease-specificeducation - refer to HPI for long-term care management

• Produce patient and physician education materials

• eBusiness group Webenables education andreporting materials

Physician Division• Oversees development

of CPMs• Implements standard

physician orders• Provides physician

communication, education, and monitoring

Claims, Rx,Labs, Pathology,Radiology, Hospital, Clinic,Home care,Medicine/surgery, MentalHealth

Clinical and claims data are captured from claims, pharmacy, laboratory, pathology,

radiology, hospitals, clinics, home care, medical/surgical, and mental health

components. Based on these data, NCQA/HEDIS initiatives are used to develop

clinical programs and for tracking program compliance. The programs are distributed

to physicians, and claims services collect claims data and other quality data, such

as member complaints. Advocates are used to schedule appointments for preventive

care and channel members to appropriate providers. Care management services

provides care managers, physicians, and pharmacists. Clinical programs data are

integrated and monitored for adherence.

Physicians in the system oversee development of clinical programs, implement

standard physician orders, and provide physician communication and education on

practice guidelines. Hospitals and clinics manage and monitor performance, provide

management support and education, produce patient and physician education materials,

and disseminate education and reporting materials on the organization’s Web site.

QI = quality improvement; NCQA/HEDIS = National Committee for QualityAssurance/Health Plan Employer Data and Information Set; CPM = clinical program model; HCS = Health Care Services department; Rx = prescription; HPI = Health Plans Inc. (a division of IHC).



the average cost of treating an acute exacerbation of chronicbronchitis is $159. If a treatment failure occurs, the averagesubsequent cost for the failure is $477.50.9 (A treatment failurewas defined as an unscheduled visit to the general practitionerwithin a month of the initial exacerbation leading to a change inprescription, an emergency department visit, or a hospitaladmission.)

In view of the costs for COPD care, particularly frompatients with severe COPD who are at high risk of exacerba-tions, it is apparent that IHC is suffering large losses due toCOPD. Additionally, because 17% of the patients with COPDaccount for 71% of the cost of care for COPD patients at IHC, 4

risk stratification and other disease management efforts forhigh-risk patients may be effective. Studies also indicate astrong correlation between the severity of COPD and the totalcost of treatment.2

�� Assessing “Treatability”

Studies show that, while COPD is a prevalent and costly condi-tion that can lead to severe exacerbations and contributes toother common causes of morbidity and mortality,1,2,8 smokingcessation and therapies to reduce inflammation can be expectedto alter the course and prognosis of the disease.1,6,8

In addition, evidence-based treatment guidelines for COPDhave been developed by the National Heart, Lung, and BloodInstitute and World Health Organization and endorsed by theAmerican Thoracic Society.10 The Global Initiative for ChronicObstructive Lung Disease (GOLD) guidelines assessed interven-tions that can improve symptomatology and slow or stop theprogress of COPD. These include: • smoking cessation• reduction of exposure to environmental pollutants• the use of appropriate pharmacotherapy, including

oxygen if indicated• administration of yearly influenza vaccination • exercise training programs• bullectomy (excision of a bullae to improve lung

function) and lung transplant (conclusive results are notyet available on lung volume reduction surgery) These treatments and interventions have been shown to

reduce exacerbations and improve the health status of COPDpatients.10 Furthermore, adherence with these guidelines canresult in lower health care costs due to COPD.2

�� Comparing COPD Care With Treatment Guideline Recommendations

Based on the GOLD guidelines, IHC developed a pharmacologyalgorithm for the office-based treatment of COPD in the organ-ization. The algorithm was compared with current drug utiliza-tion at IHC. (All products in the GOLD guidelines are includedin the IHC formulary.)

The pharmacology algorithm adapted by IHC from the

GOLD guidelines is as follows:• first-line therapy—ipratropium (4 to 8 puffs, 4 times a day

[qid]) • second-line therapy—if the outcome is suboptimal, either

change to ipratropium bromide/albuterol sulfate combination(Combivent; 3 to 4 puffs, qid) or add albuterol (2 puffs, qid)to the ipratropium.

• third-line therapy—if the outcome is still suboptimal,increase the ipratropium bromide/albuterol sulfate comna-tion or ipratropium plus albuterol dosage to 4 to 8puffs. Other options are change to long-acting oral theophylline (8 mcg/ml to 12 mcg/ml) or change to ipratropium (4 to 8 puffs, qid) plus a long-acting beta agonist and possibly an inhaled corticosteriod.

• fourth-line therapy—if the outcome is still suboptimal, add an inhaled corticosteroid and oxygen. (Oxygen mayalso be added in previous lines of therapy, if necessary.)4

Because there was evidence of extreme variation in thenumber of doses of ipratropium required to treat IHC patientseffectively, a dose higher than the maximum U.S. Food andDrug Administration (FDA) label dosage was used in the algorithm in order to achieve optimal control. Small studies indi-cate that doses of ipratropium 4 times that of the recommendedFDA label may be necessary to improve exercise performance.11,12

When reviewing IHC drug utilization data, IHC ascertainedthat anticholinergics are the first-line choice for treating COPD,in line with the recommended algorithm. Nearly one quarter(21%) of patients are prescribed leukotriene modifiers, which,while they may provide limited benefits in mild-to-moderateasthma, have not been proven effective in the treatment ofCOPD. Currently, there is a lack of good clinical data demon-strating the effectiveness of antileukotrienes in COPD. Most of the trials are in small populations and of short duration.13,14

The high use of leukotrienes in the IHC population could indi-cate a lack of physician understanding about currently availabletreatment recommendations and published literature in the COPDfield. In addition, 65% of members with COPD are prescribedinhaled corticosteroids, generally along with bronchodilators andother medications. Although no specific target number has beenestablished for the use of inhaled corticosteroids, 65% is a higherutilization of inhaled corticosteroids than expected, based on thepublished literature.15-17 Fluticasone/salmeterol inhalation powder(Advair) is also used commonly, alone or in combination withinhaled corticosteriods. The use of corticosteroid products in thetreatment of COPD can provide benefit in some patients withCOPD. This is supported by the recent FDA approval of fluticasone/salmeterol inhalation powder for the treatment of COPD.15-17

�� Reviewing Current COPD Care

Although IHC does not utilize a formal, systemwide clinicalCOPD program for managing patients, various elements of sucha program have been implemented. The Pharmacy and


Therapeutics Committee, which consists of the 5 clinical pharmacists and approximately 20 physicians, routinelyreviews new product studies, including those for COPD, anddisseminates the information to physicians, if applicable. Thecommittee is currently reviewing the new COPD treatmentproduct tiotropium (Spiriva). Also being reviewed are new dataon the use of fluticasone/salmeterol inhalation powder for COPD,a recent new indication for the combination asthma drug.

In addition, IHC employs approximately 20 nurses who are caremanagers and 5 clinical pharmacists who work in the health plan,all of whom are dedicated solely to clinical functions such as review-ing new drugs, physician interventions, disease management, andpatient education and interventions. COPD is one of a number ofconditions that care managers and pharmacists address proactively.Care managers contact all COPD patients who have an emergencyroom visit or hospitalization to offer care management. The estab-lished goals of COPD care management include • disease progression prevention, • symptoms relief, • exercise tolerance improvement, • patient health status improvement, • complication/exacerbation prevention and treatment, • mortality reduction, and• treatment side-effect minimization.

Specific care management objectives are • facilitating smoking cessation, • encouraging exercise, • counseling the patient on obesity treatment and nutrition, • promoting influenza and pneumococcus vaccination, • providing oxygen therapy when needed, • encouraging compliance with prescribed medications, • providing patient education, referring to specialists when

needed, and • monitoring for concomitant diseases.

Unfortunately, 29% of IHC patients refuse the care managementservices offered to them. Although formal surveys have not beenused to identify the reason for the refusals, many patients state thatthey do not need the intervention because they are receiving carefrom their physician. Even patients who refuse care managementare sent educational materials through the mail on the importanceof smoking cessation and other treatment issues.

The COPD pharmacology algorithm outlined above is pro-vided to care managers and pharmacists for internal educationand to evaluate treatments in uncontrolled COPD patients. Basedon the reviews, care managers may make suggestions to patientsand physicians for treatment changes. Clinical pharmacists alsoprovide cost detailing to educate physicians on cost-effectivetreatments for COPD.

�� Elements of an Evidence-Based, Systemwide Clinical COPD Program

IHC compared these elements used at IHC with recommenda-tions for managing high-cost conditions from the Institute of

Medicine (IOM). These recommendations were developed byIOM to reduce the burden of illness and improve health caredelivery. In its recommendations, IOM lists 15 chronic condi-tions, including COPD, for which a systemwide approach tocare should be implemented. Specifically, IOM recommendsthat MCOs develop information systems that can identifypatients with COPD, allow program developers to select thebest treatments for COPD patients, and measure the outcomesof these treatments.

IHC is currently able to identify members with a diagnosisof COPD through a member identification process. Selectingthe best treatments and measuring outcomes would be the nextstep for IHC if a systemwide clinical program were developed.Such programs are already in place for diabetes, congestiveheart failure, and asthma. At IHC, clinical program develop-ment and implementation are physician-driven processes. Caremodels and educational material would therefore be developedin collaboration with physicians. In addition, physicians wouldbe able to choose those pieces of the clinical program that bestfit their practices.

IHC further recognizes that COPD management should be asystemwide program administered through physician officesand done in conjunction with clinical programs that involvephysicians, the health plan, and hospitals. IHC uses its Web siteand other physician forums to distribute the program, educa-tional information, and reports to physicians, hospitals, clinics,advocates, and care managers and would do so with a COPDcare program as well.

In IHC clinical care programs, 3 classes of outcomes aretracked by the IHC integrated clinical data system:• total costs of care.• physical outcomes (the measurement of complications and

therapeutic goals). • service outcomes (perception of quality, including satisfac-

tion levels for patients, families, purchasers, employees,and professionals). Service outcomes also include accessissues, such as waiting times for service. In general, if thecosts and physical outcomes goals are met, service out-comes are also positive.Results of these measurements are used to identify areas

for improvement, and IHC provides patient-specific COPDinformation to physicians, such as patients’ current status andproblems with patient adherence to medication regimens.Physicians can, in turn, step up treatment or encourage thepatient to adhere to the treatment plan.

Tracked over time, these measurements would indicatewhether COPD outcomes are improving and suggest possiblestrategies such as increasing patient education and participationin smoking cessation programs. The measurements would alsoallow IHC to assess both physician and patient adherence withthe care program guidelines.

Stratifying patients by risk would also be essential and is recommended in the GOLD guidelines.10 Because 17% of




COPD patients account for 71% of the cost of COPD care atIHC, a clinical program that includes risk stratification andcloser management of high-risk patients could prove effectivefor reducing medical utilization levels due to COPD.

Finally, based on GOLD guidelines, IHC would also encour-age primary care physicians to take an active role in detectingand treating COPD. Diagnosis can be readily achieved in theprimary care setting by reviewing the patient’s smoking historyand using office-based spirometry initially for diagnosis and,later, for disease staging and follow-up monitoring.

�� Summary

IHC is currently prioritizing resources, and the need for devel-oping and implementing a COPD clinical care program is stillbeing examined. Both national and IHC data indicate that manypeople with COPD are not diagnosed, however, and once diag-nosed, are not always prescribed optimal treatments. Because ofthese findings, and the relatively high costs for treating COPDpatients in IHC, a system-wide, evidence-based, physician-driven clinical COPD care program may be effective in slowingdisease progress, improving patient outcomes, and reducingcostly exacerbations.

DISCLOSURES

The author received an honorarium from Boehringer Ingelheim and Pfizer Inc.for participation in the symposium upon which this article is based. He discloses no conflict of interest or potential bias regarding this article.

REFERENCES


2. Hilleman DE, Dewan N, Malesker M, Friedman M. Pharmacoeconomicevaluation of COPD. Chest. 2000;118:1278-85.

3. Reilly P. Still leader of the pack. Mod Healthc. March 3, 2002.

4. Data on file. Intermountain Health Care, Salt Lake City, Utah.

5. Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronicobstructive pulmonary disease surveillance—United States, 1971-2000.MMWR CDC Surveill Summ. 2002;51:1-16.

6. Kanner RE, Anthonisen NR, Connett JE. Lower respiratory illnesses pro-mote FEV1 decline in current smokers but not ex-smokers with mild chronicobstructive pulmonary disease. Results from the Lung Health Study. Am JRespir Crit Care Med. 2001;164:358-64.

7. Centers for Disease Control and Prevention. Behavioral Risk FactorSurveillance System; Tobacco Use—2002. Available at: http://www.apps.nccd.cdc.gov/brfss/list.asp?cat=TU&yr=2002&qkey=621&state=All. Accessed April,29, 2004.

8. Petty TL. Scope of the COPD problem in North America—early studies ofthe prevalence and NHANES III Data: Basis of early identification and inter-vention. Chest. 2000;117(5 suppl 2):326S-31S.

9. Miravitlles M, Murio C, Guerrero T, Gisbert R. Pharmacoeconomic evalua-tion of acute exacerbations of chronic bronchitis and COPD. Chest. 2002;121:1449-55.

10. Pauwels RA, Buist AS, Calverley PMA, Jenkins CR, Hurd SS. Global strategyfor the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic ObstructiveLung Disease (GOLD) workshop summary. Am J Respir Crit Care Med.2001;163:1256-76.

11. Ikeda A, Nishimura K, Koyama H, Tsukino M, Mishima M, Izumi T. Doseresponse study of ipratropium bromide aerosol on maximum exercise perform-ance in stable patients with chronic obstructive pulmonary disease. Thorax.1996;51:48-53.

12. Tsukino M, Nishimura K, Ikeda A, Hajiro T, Koyama H, Izumi T. Effects of theophylline and ipratropium bromide on exercise performance in patientswith stable chronic obstructive pulmonary disease. Thorax. 1998;53:269-73.

13. Rubinstein I, Kumar B, Schriever C. Long-term montelukast therapy inmoderate to severe COPD—a preliminary observation. Respir Med. 2004;98:134-38.

14. Zuhlke IE, Kanniess F, Richter K, et al. Montelukast attenuates the airwayresponse to hypertonic saline in moderate to severe COPD. Eur Respir J.2003;22:926-30.

15. Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticas-one in the treatment of chronic obstructive pulmonary disease: a randomizedcontrolled trial. Lancet. 2003;361:449-56.

16. Hanania NA, Darken P, Horstman D, et al. The efficacy and safety of fluti-casone propionate (250 µg)/salmeterol (50 µg) combined in the diskus inhalerfor the treatment of COPD. Chest. 2003;124:834-43.

17. Mahler DA, Wire P, Horstman D, et al. Effectiveness of fluticasone propi-onate and salmeterol combination delivered via the diskus device in the treat-ment of chronic obstructive pulmonary disease. Am J Respir Crit Care Med.2002;166:1084-91.



Continuing EducationOverview of Chronic Obstructive Pulmonary Disease:

New Approaches to Patient Management in Managed Care Systems

Date: __________________________

In order to receive CE credit for this program, you must complete this form and the Program Evaluation form in addition to

completing the posttest with a score of at least 70% (forms may be photocopied). Please mail all materials to Continuing

Pharmacy Education, University of Utah College of Pharmacy, 421 Wakara Way, #208, Salt Lake City, UT 84108, or fax them

to (801) 585-7547. To receive credit, these forms must be received by July 1, 2005.

This continuing education program is made available through an unrestricted grant from Boehringer Ingelheim and Pfizer Inc.

All information will be kept confidential; it is used only for the processing and mailing of your CE statement. You must complete and sign this form in order to receive CE credit for completing this program.

❑ I verify that I have completed the program and posttest for “Overview of Chronic Obstructive Pulmonary Disease: New Approaches to Patient Management in Managed Care Systems.”

Signature:

Please print your name as you would like it to appear on the CE certificate:

Last name: First name:

Company: State & License no:

Address:

City: State: ZIP:

Daytime phone: Social Security no:

Fax number: E-mail:

Member Type: ❑ Active ❑ Supporting Associate ❑ Student ❑ Nonmember

The University of Utah College of Pharmacy is approved by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. A total of 0.15 CEUs (1.5 contact hours) will be awarded to pharmacists for successful completion of this continuing education program. Successful completion is defined as receiving a minimum score of 70% on the

posttest and completion of the Program Evaluation form. Continuing education statements will be mailed to pharmacists within 60 days of receipt of the Record of Completion, Posttest, and Program Evaluation forms. Universal Program No. 068-999-04-022-L04(expiration date: 7/1/05).

RECORD OF COMPLETION

State License no.

A B C D

1. ❒ ❒ ❒ ❒2. ❒ ❒ ❒ ❒3. ❒ ❒ ❒ ❒4. ❒ ❒ ❒ ❒5. ❒ ❒ ❒ ❒

A B C D

6. ❒ ❒ ❒ ❒7. ❒ ❒ ❒ ❒8. ❒ ❒ ❒ ❒9. ❒ ❒ ❒ ❒

10. ❒ ❒ ❒ ❒

A B C D

11. ❒ ❒ ❒ ❒12. ❒ ❒ ❒ ❒13. ❒ ❒ ❒ ❒14. ❒ ❒ ❒ ❒15. ❒ ❒ ❒ ❒

Posttest Answers:

1. COPD is currently thea. leading cause of death in the United States.b. third leading cause of death in the United States.c. fourth leading cause of death in the United States.d. tenth leading cause of death in the United States.

2. The majority of COPD patients area. under 65 years of age.b. over 70 years of age.c. over 75 years of age.d. over 80 years of age.

3. What percentage of COPD is considered smoking-related?a. 100%b. 95%c. 75%d. 50%

4. Which description best characterizes COPD?a. An inflammatory disease restricted to the lungsb. An inflammatory disease restricted to the bronchiolesc. A pulmonary disease similar to pneumoniad. An inflammatory disorder that affects not only the

airway but the entire body

5. Patients with COPD can be identified in a physician’s office bya. CBC and an x-ray.b. x-ray and spirometry.c. spirometry and a smoking history.d. x-ray and a smoking history.

6. Based on the spirometry, the threshold for a diagnosis of COPD is a. FEV1/FVC <70% and FEV1 <80% of predicted values.b. FEV1/FVC <50% and FEV1 <60% of predicted values.c. FEV1 <90% of predicted values.d. FVC <70% of predicted values.

7. What percentage of patients with diagnosed COPD presentwith the mild form of the disease?a. 33%b. 50%c. 72%d. 83%

8. The first step in the management of COPD is a. corticosteroid therapy.b. bronchodilatory therapy.c. leukotriene-antagonist therapy.d. smoking cessation or reduction.

9. Which of the following is currently the cornerstone pharmacotherapy for COPD?a. Inhaled corticosteroids.b. Oral corticosteroids.c. Bronchodilators.d. Beta-blockers.

10. Which once-daily anticholinergic agent has reduced exacerbation rates and dyspnea in patients with COPD?a. Ipratropiumb. Albuterolc. Tiotropiumd. Salmeterol

POSTTEST

Continuing EducationOverview of Chronic Obstructive Pulmonary Disease:

New Approaches to Patient Management in Managed Care Systems

Please indicate the correct answers on the Record of Completion.



11. The inflammatory cells linked to COPD are usually notresponsive toa. β-agonists.b. corticosteroids.c. anticholinergics.d. methylxanthines.

12. A small percentage reduction in FEV1 over time is a. always indicative of COPD.b. normal with aging.c. associated with asthma.d. usually caused by smoking.

13. In the managed care setting, COPD is oftena. underdiagnosed.b. overdiagnosed.c. effectively managed.d. almost always misdiagnosed as asthma.

14. With COPD, the main cost driver for health care organizations isa. chronic treatment.b. treatment of exacerbations in the hospital setting.c. medication costs.d. nursing home costs.

15. Which of the following is a GOLD guideline for the prevention and management of COPD?a. Smoking cessationb. Yearly influenza vaccinationc. Exercise trainingd. All of the above

Using the scale above for questions 1-4, please rate how well you willbe able to accomplish the following objectives based upon successfulcompletion of the program.

Objectives:1. describe COPD and its prevalence and burden of illness on

patients, society, and managed care systems;

2. discuss current treatment options via an evidence-based management approach;

3. illustrate the impact of new treatment options on current patternsof care; and

4. review COPD patient management within managed care systems.

Using the scale above for questions 5 and 6, please indicate the num-ber that best expresses your opinion.

5. What is your overall rating of this program?

6. How would you rate the pertinence of this program material toyour practice?

7. To what degree was there promotional bias? (check one)a. Not at allb. Somewhatc. A great deal

8. To what degree do you anticipate changes in patient care as aresult of the material presented? (circle one)

1 2 3 4 5No change Significant change

9. Please indicate the length of time it took to complete this program.(circle selection(s))Hours: 1 2 3Minutes: 0 15 30 45

10. Please rate the difficulty factor for completing this CE program.(circle selection) Easy Moderate Difficult

11. Please rate your willingness to recommend this program to col-leagues. (circle selection)Very willing Willing Not willing

12. Please indicate which venue you prefer for obtaining continuingeducation. (circle selection)

PROGRAM EVALUATION

Live sessions Other:___________________________

Overview of Chronic Obstructive Pulmonary Disease:New Approaches to Patient Management in Managed Care Systems

Scale For Questions 1–4

1 = Not at all2 = Not very well3 = Somewhat well4 = Well5 = Very well

Scale For Questions 5 and 6

1= Poor2= Fair3= Good4= Very good5= Excellent

Participant’s name: Date: ________________

Your assistance in the evaluation process is greatly appreciated. Please return this form with the posttest answers.

Written monograph Slides Videos Internet-based


JMCPJMCPSupplementJOURNAL OF MANAGED CARE PHARMACY ®

Documents

JOURNAL OF MANAGED CARE PHARMACYamcp.org/data/jmcp/July04Supplement1.pdf · Journal of Managed Care Pharmacy Supplements to the Journal of Managed Care Pharmacyare intended to support