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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


COPD Management: Clinical Insights into the Future


GOAL
To provide physicians with the most current information available for the treatment and management of chronic obstructive pulmonary disease.

PROGRAM SERIES RATIONALE
This program is designed to provide pulmonologists and primary care physicians with current and practical information regarding the diagnosis and treatment of chronic obstructive pulmonary disease (COPD). There are currently many treatments that can be effective in helping to control symptoms and improve both lung function and quality of life in patients suffering from COPD. Yet, in spite of their relative efficacy, these current treatments do not target all of the manifestations of the disease state, and some may even have serious adverse effects. It is in response to these limitations and flaws that the development and application of new drug therapies, aimed to reduce the effects of inflammatory and abnormal airway-secretory responses in patients, has become a great need and a focus of significant efforts. This program will explore the existent "space for improvement" in the current management and treatment of COPD. Implementation of proper and timely diagnostic strategies, coupled with a thorough knowledge of current treatment and upcoming treatment options should help to reduce the burden of COPD in the lives of those suffering from the disease.

TARGET AUDIENCE
This activity is designed for pulmonologists and primary care physicians. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Implement the use of spirometry as a routine test for early diagnosis of COPD
  • Identify COPD in its heterogeneous manifestations
  • Recognize the potential presence of COPD in patients at risk
  • Demonstrate knowledge of the physiologic components of COPD progression

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 1 category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity: 1 hour.

Release date: February 28, 2003. Expiration date: February 28, 2005.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an unrestricted educational grant from GlaxoSmithKline.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, LLC, an HMG Company. P.O. Box 340, Somerville, NJ 08876. (908) 253-9001. Web site: www.galenpublishing.com. Copyright ©2001 by Galen Publishing, LLC. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. Bulk postage paid at Somerville, NJ Post Office and at additional mailing offices. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC. Printed on acid-free paper. BPA Membership applied for December 2000.

Full Disclosure Policy Affecting CME Activities:
As a sponsor accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. Faculty Advisors and Participating Faculty reported the following:

PROGRAM DIRECTOR

    Robert A. Wise, MD
    Professor
    Pulmonary and Critical Care Medicine
    Johns Hopkins University
    Baltimore, Maryland
    • Dr Wise reports receiving grant/research support from Boehringer Ingelheim and Otsuka Pharmaceuticals Co.

PARTICIPATING FACULTY

    Gerard J. Criner, MD
    Director, Division of Pulmonary and Critical Care Medicine
    Medical Intensive Care Unit and Ventilator Rehabilitation
    Temple University
    Philadelphia, Pennsylvania
    • Dr Criner reports receiving grant/research support from Actelion, Boehringer Ingelheim, Novartis Corporation, and Pfizer Inc.

    Gary T. Ferguson, MD
    Director
    Pulmonary Research Institute of Southwest Michigan
    Livonia, Michigan
    • Dr Ferguson reports receiving grant/research support and receiving honoraria from Boehringer Ingelheim and GlaxoSmithKline; and serving as a consultant to GlaxoSmithKline.

    Fernando Martinez, MD
    Associate Professor
    Department of Internal Medicine
    University of Michigan at Ann Arbor
    Ann Arbor, Michigan
    • Dr Martinez reports receiving grant/research support from Intermune; and serving as a consultant to Boehringer Ingelheim and GlaxoSmithKline.

    Stephen Rennard, MD
    Larson Professor of Medicine
    Pulmonary and Critical Care Medicine
    University of Nebraska Medical Center
    Omaha, Nebraska
    • Dr Rennard reports receiving grant/ research support from AstraZeneca Pharmaceuticals LP, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Novartis Corporation, Pfizer Inc, Pharmacia and Upjohn, RJ Reynolds, and Roche Pharmaceuticals; serving as a consultant to AstraZeneca Pharmaceuticals LP, Amersham Health, Aventis Behring, Bayer, Boehringer Ingelheim, Fibrogen, GlaxoSmithKline, Mitsubishi, Novartis Corporation, RJ Reynolds, Roche Pharmaceuticals, and Sankyo Pharma Inc; and serving on the speakers bureau for AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim, Fibrogen, GlaxoSmithKline, and Novartis Corporation.

    Steven Shapiro, MD
    Parker B. Francis Professor of Medicine
    Harvard Medical School
    Chief, Division of Pulmonary and Critical Care Medicine
    Brigham and Women's Hospital
    Boston, Massachusetts
    • Dr Shapiro reports receiving grant/research support from GlaxoSmithKline, Pfizer Inc, and Wyeth; and serving as a consultant for Dyax Corporation, GlaxoSmithKline, Pfizer Inc, and Millennium Pharmaceuticals Inc.

    Donald Tashkin, MD
    Professor, Division of Pulmonary and Critical Care Medicine
    UCLA School of Medicine
    Los Angeles, California
    • Dr Tashkin reports receiving grant/research support from Boehringer Ingelheim, GlaxoSmithKline, and Merck & Co Inc; and serving as a consultant to GlaxoSmithKline.

Notice:
In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

COPD: State of Affairs
Robert A. Wise, MD*

The umbrella term "chronic obstructive pulmonary disease (COPD)" is used often to refer to patients with chronic bronchitis and emphysema, the 2 most common smoking-related disorders. Other chronic obstructive diseases such as asthma, bronchiectasis, cystic fibrosis, and bronchiolitis obliterans are generally considered separate disorders with distinct pathologies. Physiologically, COPD is defined by nonreversible pulmonary function impairment, with breathing-related symptoms that include chronic cough, exertional dyspnea, expectoration, and wheezing. Because COPD in its early stages is often clinically silent, recent efforts aimed at reducing the high COPD morbidity and mortality have emphasized basic lung-function testing and careful history taking to diagnose early disease, categorize severity, and initiate appropriate therapy.

Opportunities for Improved COPD Management
COPD experts met in Baltimore, Maryland, on November 15 and 16, 2002, to explore the opportunities for improvement in the current management of COPD and to, hopefully, provide a clear direction for the busy primary care clinician. The following questions were discussed in a series of presentations and roundtable discussions: Will early detection improve outcomes? If so, who should be screened? Will any current treatments, other than smoking cessation, actually slow the relentless increase in COPD mortality rates? Can these treatments at least relieve symptoms and provide a better quality of life for patients? What does the evidence show? What do the guidelines say? How often are available therapies actually employed? What about the new therapies in development? How do they work and how might they improve the situation?

A major opportunity highlighted by the discussants involved prevention and early diagnosis and intervention. In many cases of COPD today, the disease is recognized only after the patient is hospitalized with advanced manifestations. And even if a patient is diagnosed earlier with COPD, many clinicians mistakenly believe that only basic symptomatic therapy is available. While smoking cessation, of course, must remain the central element of all long-term prevention efforts, an all-consuming focus on this key behavioral strategy must not distract clinicians from the currently available treatments that can improve symptoms, increase lung function, prevent complications, and possibly delay progression. COPD is a disease that is actually quite easy to diagnose in its early mild stages, and yet COPD remains underdiagnosed and undertreated. Clearly, there is room for improvement in identifying and treating more patients with COPD while limiting exacerbations and improving quality of life.1

Another major opportunity identified in the discussion involved the development of new therapies for COPD. Current treatments do not target all manifestations of the disease, have variable effects on morbidity and mortality, and also are limited by adverse effects. Thus, many research efforts are now targeting the distinctive inflammatory and abnormal airway secretory responses found in patients with COPD. Such research efforts should interest primary care clinicians for the possible information provided about future respiratory therapies and the mechanisms, adverse effects, and relative efficacies of the current array of drugs used to treat lung disorders.

COPD Pathophysiology is Focus of This Issue
The first presentation at the roundtable—and the focus of this issue of Advanced Studies in Medicine (the first in a series of 3 issues devoted to COPD)—was given by Steven Shapiro, MD, professor of medicine at Harvard Medical School and chief of pulmonary and critical care medicine at Brigham and Women's Hospital in Boston, Massachusetts. By exploring the underlying pathophysiology of COPD, Dr Shapiro provided a solid framework for understanding why chronic bronchitis and emphysema are difficult to treat with current therapies. His review of the genetic risk factors, inflammatory responses, and the roles of proteases and cytokines in COPD also initiated a discussion of the most promising potential new treatment targets.

The focus of the second COPD-related issue of Advanced Studies in Medicine will be practical management strategies. What works and what doesn't? Stephen Rennard, MD, professor of pulmonary and critical care medicine at the University of Nebraska Medical Center in Omaha, Nebraska, will provide his perspective on the value and absolute necessity of smoking cessation as a societal goal. Gary T. Ferguson, MD, associate professor at Wayne State University and director of the Pulmonary Research Institute of Southwest Michigan in Livonia, Michigan, will address the best evidence-based approaches for COPD management. Dr Ferguson will summarize and comment on the recent treatment guidelines issued by GOLD (The National Heart Lung and Blood Institute/World Health Organization Global Strategy for the Diagnosis, Management, and Prevention of COPD) and will also provide clinicians with practical insights for overcoming the most common COPD treatment hurdles.

Specific treatments will be explored in the third and final COPD issue. Gerard J. Criner, MD, professor and director of pulmonary and critical care medicine at Temple University in Philadelphia, Pennsylvania, will review the current options for symptomatic relief of COPD. He will discuss existing interventions such as bronchodilators and corticosteroids and whether or not these agents might improve lung function, reduce exacerbation frequency, improve quality of life, and reduce the economic burden of hospitalization. Dr Rennard will preview potential new strategies for COPD treatment, evaluating potential targets such as proteases, adhesion molecules, c-AMP, oxidative products, cytokines, and mucoregulatory agents. As the role of lung inflammation in the pathogenesis of COPD has increased in recent years, researchers have become more interested in new anti-inflammatory agents such as the specific inhibitors of phosphodiesterase (PDE) type 4—the main enzyme involved in immune, inflammatory, and airway smooth muscle cells. Several PDE4 inhibitors and other novel anti-inflammatory agents are now in the later stages of clinical development.

Need for Increased COPD Awareness
A recurring theme in the roundtable panel's discussions was the need for increased awareness of COPD among the general public, the primary care physicians who manage most patients with COPD, and the decision makers who distribute funding for medical care and research. COPD is the fourth leading cause of mortality in the United States, yet it ranks 27th in research funding2,3 (Table). This funding gap has grown larger as the mortality rates for other major diseases in the United States have decreased in the past 3 decades (eg, coronary heart disease by 59%; stroke, 64%; other cardiovascular disease, 35%). Meanwhile, COPD deaths have increased by an extraordinary 163% over the 1965 to 1998 time period.4

Clinicians and their medical groups are concerned about the lack of COPD awareness by healthcare systems. For example, while the number of physician visits for COPD increased from 9.3 million in 1985 to 16 million in 1995,4 most large health organizations still focus their disease management resources on other chronic diseases. This relative invisibility of COPD may be attributable to the lingering confusion about COPD definitions and coding or, perhaps, to the disease's strong link with smoking, which in turn feeds nihilistic assumptions about the lack of treatment efficacy beyond smoking cessation.

Whatever its origin, low COPD awareness in the medical community is contributing to less-than-optimal medical care for millions of Americans. The contributors to this educational program hope their reviews, discussions, and case studies in this and the next 2 issues of Advanced Studies in Medicine will increase the willingness of physicians to recognize and aggressively treat more cases of COPD in their everyday practice.

COPD Prevalence and Mortality are Increasing
As an introduction to the roundtable discussions, recent COPD statistics as reported by various US government health agencies are included. These summarized data are sobering. In 2000, an estimated 10 million adults reported physician-diagnosed COPD. According to data from the third National Health and Nutrition Examination Survey, more than twice this self-reported number of patients have spirometric evidence of impaired lung function,1 yet another indicator of the size of underdiagnosed population with this disease.

The increase in smoking by women after World War II is now reflected in both the prevalence and mortality statistics. During the 1980s and 1990s, for example, the prevalence of COPD increased gradually for men while rising markedly for women. Physicians tend to diagnose COPD or emphysema more easily in men than in women with similar clinical features.5 However, rates of COPD hospitalization—a much firmer endpoint—also confirm that the number of hospital admissions for women with COPD surpassed the number of men admitted in the mid-1990s.6

In a most disturbing turnaround in COPD trends, mortality in women (59 936 deaths in 2000) is now higher than in men (59 118 in 2000) (Figure). The COPD death rate increased from 20.1 per 100 000 women in 1980 to 56.7 per 100 000 women in 2000; for men, the rate over this period increased marginally, from 73.0 per 100 000 to 82.6 per 100 000.1 In addition, results from the American Cancer Society's classic surveys of smokers (the Cancer Prevention Studies) show that COPD increased in smokers in recent decades, while coronary heart disease and stroke mortality decreased. The rate of increase from the early 1960s to the early 1980s was approximately 41% for men and 250% for women.7,8 While these data may simply reflect better treatments for competing mortalities (eg, heart disease) and shifting diagnoses (eg, from pneumonia to COPD), it may also reflect changes in cigarette content or in smoking styles (eg, women may have evolved from light smokers to heavy smokers). Whatever the cause, it is clear that more women are dying from COPD today than ever before.

As dire as these COPD mortality statistics appear, clinicians must understand that the real number of COPD-implicated deaths in the United States may be even greater. As with COPD prevalence, COPD mortality is greatly underreported. In the Tecumseh study, only 21% of men and 6% of women with an official clinical COPD diagnosis had COPD listed on their death certificates.9 Similarly, in a 20-year prospective study in Finland of patients with COPD, only 29% of men and 33% of women had COPD listed on their death certificates.10 In a British prospective study of patients with hypoxia and advanced COPD, only 38% were reported as dying from respiratory failure.11 As revealed by these double checks of death certificates, clinicians have for years overlooked (or at least underreported) COPD as a prime contributor to patient mortality. The links between COPD and the complications of COPD—such as the chest infections, pulmonary emboli, arrhythmias, and lung cancer reported in the British study—have been lost. Thus, COPD mortality is underestimated because the disease is usually cited, if it is cited at all, as a contributory rather than an underlying cause of death. All of which explains why COPD statistics reflect only the tip of the COPD mortality iceberg.

The failure to report COPD on death certificates should be of concern to all medical personnel, not just epidemiologists because the failure also betrays the tendency of clinicians to overlook COPD in the clinic as a serious and treatable disease. Because of the lack of awareness of treatments for COPD in its early and moderate stages, clinicians have focused instead on managing the disease's late-stage complications. A disconnection exists between the underlying disease and the complications; just as diabetes contributes directly to excess cardiovascular and neurologic morbidity and mortality, COPD contributes directly to a full array of heart and lung ailments. Just as early comprehensive diabetes management has become the goal for reducing the heavy burden of diabetes complications, early COPD management must become the new paradigm for management of this pervasive disease.

REFERENCES
1. Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance-United States, 1971-2000. Centers for Disease Control and Prevention. MMWR Surveill Summ. 2002;5(6):1-16.
2. Minino AM, Arias E, Kochanek KD, Murphy SL, Smith BL. Deaths: final data for 2000. Natl Vital Stat Rep. 2002;50(16):1-119.
3. Gross CP, Anderson GF, Powe NR. The relation between funding by the National Institutes of Health and the burden of disease. N Engl J Med. 1999;340:1881-1887.
4. NHLBI. Morbidity & Mortality: 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases. Available at: http://www.nhlbi.nih.gov/resources/docs/02_chtbk.pdf. Accessed December 11, 2002.
5. Chapman KR, Tashkin DP, Pye DJ. Gender bias in the diagnosis of COPD. Chest. 2001;119:1691-1695
6. National Center for Health Statistics. Figure 14: Trend in COPD Hospitalization by Sex, 1979-1998. National Hospital Discharge Survey. 1988-1998.
7. Thun MJ, Day-Lally CA, Calle EE, Flanders WD, Heath CW Jr. Excess mortality among cigarette smokers: changes in a 20-year interval. Am J Public Health. 1995;85:1223-1230.
8. Wise RA, Szklo M, Matanoski G, Neugut AI. Workshop discussion panel III: Implications of the changing tobacco-related mortality from COPD in the CPS-1 and CPS-2 surveys. Prev Med. 1997;26(4):457-459.
9. Higgins MW, Keller JB. Trends in COPD morbidity and mortality in Tecumseh, Michigan. Am Rev Respir Dis. 1989;140(3, Pt 2):S42-S48.
10. Vilkman S, Keistinen T, Tuuponen T, Kivela SL. Survival and cause of death among elderly chronic obstructive pulmonary disease patients after first admission to hospital. Respiration. 1997;64(4):281-284.
11. Zielinski J, MacNee W, Wedzicha J, et al. Causes of death in patients with COPD and chronic respiratory failure. Monaldi Arch Chest Dis. 1997;52(1):43-47.

*Professor, Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.