Taking pharmacologic management of COPD into the future: combination therapies strike a critical balance in symptom relief

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Date: Jan. 2003
From: The Journal of Critical Illness(Vol. 18, Issue 1)
Publisher: CMP Medica, LLC
Document Type: Article
Length: 3,968 words

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Chronic obstructive pulmonary disease (COPD) is disabling and often fatal, and acute exacerbations are a primary reason for ICU admission and use of emergency department services. Prompt restoration of airflow is imperative. A primary challenge is coming up with an individualized management strategy that reduces risk factors, is useful when a patient's symptoms are stable, and also helps reduce episodes of exacerbations. Current pharmacologic therapies, which have been based on objective improvements in expiratory airflow, include inhaled bronchodilators such as the anticholinergic ipratropium, short- and long-acting [B.sub.2]-agonists, and theophylline. Tiotropium, which is not yet available in the United States, may become a useful addition to the therapeutic choices. Novel phosphodiesterase 4 inhibitors, including roflumilast, piclamilast, and cilomilast, are being investigated. As pathophysiologic mechanisms become clearer, combining drugs that have different mechanisms and durations of action m ay prove key in leveraging the greatest symptom control with the fewest side effects. Giving a first-generation [B.sub.2]-adrenergic agonist, such as albuterol, for example, together with an antimuscarinic agent is pharmacologically reasonable from the standpoints of both efficacy and safety. (J Crit Illness. 2003; 18(1):33-42)


Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of chronic morbidity and mortality in the United States. (1) Its prevalence and impact are increasing, and the World Bank/World Health Organization has projected that it will rank fifth in 2020 as a global burden of disease. (2,3) The economic and public health impact of COPD is staggering, because it is a chronic condition that requires long-term care, frequent primary care physician visits, and use of emergency department and hospital services. Thus, there is a pressing need to discover new therapies that control symptoms and prevent disease progression.

An increased understanding of the pathophysiologic mechanisms of COPD has helped researchers identify potential targets for new treatments. These include many chemoattractants and cytokines that drive the inflammatory responses in COPD; the signal transduction pathways activated during these processes; the mediators released, including proteases and oxidants; and the cellular responses that lead to abnormalities in tissue functions, such as mucociliary clearance and repair.

Increased interest in COPD is reflected in research of new pharmacologic therapies and in the number of important pulmonary guidelines that have been published since 1974 at both local and international levels. (4) Pharmacologic and nonpharmacologic measures are aimed at improving the quality of care for patients who have COPD, with smoking cessation mandatory for all patients, to slow the progression of lung function loss.

In this article, we concentrate on the pharmacologic options in COPD treatment. We start by reviewing the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition and staging of COPD. (5) We then identify the available agents in treatment and outline appropriate strategies for management. Finally, we highlight new areas of research that may help guide management in the future.


In the GOLD guidelines, COPD is defined as a "disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an...

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Gale Document Number: GALE|A97113790