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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
The goal of this issue is 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:

  • Identify the full range of COPD symptoms that decrease the patient's quality of life
  • Review the current status of existing COPD therapies
  • Recognize the potential role of combined therapy that attacks specific components of COPD
  • Assess new treatment strategies for COPD aimed specifically at lung inflammation

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: May 15, 2003. Expiration date: May 15, 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, a division of Advanced Studies in Medicine, an HMG Company. PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2003 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. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC.

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. The Program Director 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

    William C. Bailey, MD
    Professor of Medicine
    Director, Lung Health Center
    University of Alabama at Birmingham
    Birmingham, Alabama
    • Dr Bailey reports receiving honoraria from AstraZeneca LP, Boehringer Ingelheim Pharmaceuticals, and GlaxoSmithKline.

    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.

    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 Pharmaceuticals, 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 Pharmaceuticals, 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 Pharmaceuticals, Fibrogen, GlaxoSmithKline, and Novartis Corporation.

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: Exploring Treatment Options
Robert A. Wise, MD*

In the previous 2 issues of Advanced Studies in Medicine devoted to chronic obstructive pulmonary disease (COPD), our contributors reviewed fundamental issues such as the epidemiology and scope of the disease, lung pathophysiology, smoking cessation, and management with bronchodilators and inhaled corticosteroids.1,2 These articles, interviews, and case studies have been based mainly on presentations and roundtable discussions held by COPD experts in Baltimore, Maryland, on November 16, 2002. In this third and final issue in the COPD series, the focus shifts to a discussion of specific current and future therapies.

In the review by Gerard J. Criner, MD, professor of medicine and director of pulmonary and critical care medicine at Temple University School of Medicine in Philadelphia, Pennsylvania, several treatment options for COPD exacerbations and moderate-to-severe disease are described. Dr Criner goes beyond the usual interventions of bronchodilators and corticosteroids to discuss the evidence supporting use of various other strategies for COPD management. After stressing that prevention and improved management of COPD exacerbations can decrease morbidity and increase the quality of life for many patients, he provides balanced capsule summaries of the current status of antibiotics, noninvasive pulmonary ventilation, lung volume reduction surgery, renutrition and reconditioning, and nocturnal oxygen therapy.

Perhaps even more important than the data on specific treatments reviewed by Dr Criner is the attitude of aggressiveness that informs his whole review. He maintains that the full range of treatment options must be considered if the quality of life of the patient with COPD is to improve. For the most seriously ill patients, for instance, Dr Criner argues that this list of potential options must be expanded to include noninvasive positive pressure ventilation and lung volume reduction surgery. In other cases, he says a combination of therapies attacking specific components of the disease may be required. And in all instances, he reminds clinicians to be alert for the full range of COPD symptoms that decrease a patient's quality of life.

After Dr Criner's presentation, a pulmonologist stated, "COPD is more than dyspnea—many patients report that their real problem is cough, or sleep problems, or the exacerbations, or a lack of independence—specific symptoms or components of disease that may be amenable to specific interventions. We've got to start doing the small things that might help our patients." In this regard, it is reassuring to note that many recent COPD clinical trials involving new medical and surgical interventions have expanded beyond the usual physiological outcomes to include more quality-of-life parameters.

The other main review in this issue comes from Stephen Rennard, MD, professor of pulmonary and critical care medicine at the University of Nebraska Medical Center in Omaha, Nebraska. In his review of emerging pharmaceutical strategies aimed at COPD, Dr Rennard also emphasized the need for aggressive and, in some cases, combined therapy for improved management of COPD.

According to Dr Rennard, several new COPD treatment strategies will be aimed at 1 or more of the stages of lung inflammation (eg, recruitment, activation, tissue disruption) now considered integral to disease pathophysiology. By altering the pathways that mediate these inflammatory pathways, researchers are hoping to prevent the lung damage and scarring that contribute to disease symptoms or progression. A new COPD treatment strategy with an anti-inflammatory mechanism of action is inhibition of phosphodiesterase 4 (PDE4), a cyclic adenosine monophosphate-specific enzyme expressed in inflammatory cells. As described by Dr Rennard, at least 1 specific PDE4 inhibitor has already shown some encouraging results in phase II and phase III COPD clinical trials. Other anti-inflammatory strategies farther back in the research pipeline will target matrix metalloproteinases, proteases such as elastase or cathepsin, and cytokines such as tumor necrosis factor-alpha.

The possibility of halting postinflammatory tissue remodeling is yet another goal of researchers. The PDE4 inhibitors, for example, have already shown potential in altering fibroblast-mediated repair processes; agents such as inhaled corticosteroids and long-acting beta agonists are also being tested for their long-term effects on tissue remodeling. Early animal data show that retinoic acid may even stimulate growth of new alveoli.

As exciting as these new lines of research may be, Dr Rennard points out that novel uses of existing therapies should not be overlooked in the search for improved COPD outcomes. As examples, he highlights data on the potential benefits of long-acting or combination bronchodilators and drugs for muscle-gain in underweight patients.

In the years ahead, according to both Dr Rennard and Dr Criner, clinicians will be able to choose from a wider array of medical and surgical treatment options. In some cases—and this will become increasingly important as researchers learn more about COPD pathophysiology—a specific treatment will be selected to manage a specific patient. The prospect of targeted molecular therapy for patients with highly specified genotypes or phenotypes is indeed enticing. However, notwithstanding some evidence in the surgical setting of varying treatment responses based on underlying COPD pathophysiology, the likelihood of truly targeted molecular therapy for patients with COPD is still decades away. A more practical near-term strategy for improvement involves the increased use of multimodal therapy. Because COPD is a highly heterogeneous disease, such a combination of therapies makes good sense—especially if new treatments become available and if these treatments can be customized based on individual risk factors.

COPD is one of the most common and expensive chronic diseases in the United States. Current trends in smoking cessation are positive and this bodes well for American lung health. Today's clinicians, however tempted they may be, cannot skip ahead because another full generation of patients with COPD must still be managed. Indeed, the steady burden of COPD expected over the next 20 years to 30 years is "hard-wired" into the epidemiologic trend line. This coming burden of COPD cannot be avoided but, as emphasized in this 3 issue series of Advanced Studies in Medicine, it can be managed more effectively.1,2 As more clinicians and health systems learn to deal with COPD as a "no-fault" chronic disease worthy of ongoing and multifaceted intervention—and as new therapies are developed and introduced—an entire generation of patients with COPD will have a better and longer quality of life.

REFERENCES
1. COPD Management: Clinical insights into the future. Part 1 of 3. Adv Stud Med. 2003;3(2B). Available at: www.jhasim.com.
2. COPD Management: Clinical insights into the future.Part 2 of 3. Adv Stud Med. 2003;3(4B). Available at: www.jhasim.com.

*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.