Review
Inflammation in COPD: Implications for Management

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Abstract

Chronic obstructive pulmonary disease (COPD) is recognized by the Global Initiative for Chronic Obstructive Lung Disease guidelines as an inflammatory disease state, and treatment rationales are provided accordingly. However, not all physicians follow or are even aware of these guidelines. Research has shown that COPD inflammation involves multiple inflammatory cells and mediators and the underlying pathology differs from asthma inflammation. For these reasons, therapeutic agents that are effective in asthma patients may not be optimal in COPD patients. COPD exacerbations are intensified inflammatory events compared with stable COPD. The clinical and systemic consequences believed to result from the chronic inflammation observed in COPD suggest that inflammation intensity is a key factor in COPD and exacerbation severity and frequency. Although inhaled corticosteroids are commonly used and are essential in asthma management, their efficacy in COPD is limited, with only a modest effect at reducing exacerbations. The importance of inflammation in COPD needs to be better understood by clinicians, and the differences in inflammation in COPD versus asthma should be considered carefully to optimize the use of anti-inflammatory agents.

Section snippets

Stable Disease

Chronic inflammation in the small airways and lung parenchyma of COPD patients has been demonstrated by tissue biopsies, sputum analyses, and postmortem samples.9, 10, 11 In COPD, repeated exposure to noxious particles, usually tobacco smoke, can trigger a distinct inflammatory cascade (Figure)5, 12 in the small airways and lung parenchyma involving several different cell types (eg, neutrophils, macrophages, lymphocytes) and inflammatory mediators (eg, growth factors, cytokines, chemokines,

Stable Disease

Both COPD and asthma involve bronchial inflammation and airflow limitation; however, inflammatory processes of these diseases differ (Table 1, Figure).5, 12 In the tracheobronchial lumen of COPD patients, neutrophils are increased substantially over macrophages, while in asthma patients, the characteristic inflammatory process involves eosinophils. In most COPD patients, eosinophils are not prominent, except when experiencing an exacerbation or with concomitant asthma.15 Furthermore, COPD or

Stable COPD

Clinical and systemic consequences are believed to result from chronic inflammation in the lungs of COPD patients. Although conclusive longitudinal studies have not been performed, cross-sectional studies have correlated inflammation and COPD severity. For instance, lung function decline has been linked to increased inflammatory markers such as sputum neutrophils, myeloperoxidase levels, fibrinogen, and CRP.38 Airway inflammatory cells (eg, neutrophils, macrophages, lymphocytes) and also

Currently Available Drugs for Stable COPD

Goals for successful COPD management include immediately relieving and reducing symptom burden and the risk of adverse health events (eg, exacerbations) that may affect patients in the future.4 Drugs approved by the US Food and Drug Administration (FDA) for use in COPD include theophylline; the long-acting muscarinic antagonist (LAMA) tiotropium; long-acting beta-2 agonists (LABAs) formoterol, arformoterol, salmeterol, and indacaterol; LABA/inhaled corticosteroid (ICS) combinations

Perception of Inflammation in COPD and Impact on Practice Patterns

In addition to making recommendations for COPD diagnosis and management, the GOLD guidelines define COPD as a disease that is associated with an enhanced inflammatory response.4 However, many physicians are not aware of these guidelines,91, 92 and thus may not be familiar with the COPD-specific characteristics of this inflammatory response. It is important for primary care physicians to understand that the inflammatory processes and components differ in COPD and asthma in order to optimize COPD

Conclusions

In COPD patients with severe airflow obstruction, significant symptoms, or frequent exacerbations, anti-inflammatory therapy is often indicated and recommended in current guidelines.4 Although some inflammatory characteristics in COPD overlap with those seen in asthma, their underlying inflammatory patterns differ, and each disease responds differently to anti-inflammatory therapy. A clearer understanding of these differences will allow practitioners to choose the optimal therapy for each

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    • Cited by (0)

    Funding: This review is based on an expert working group meeting held on February 26, 2010 in Philadelphia, PA and an expert roundtable held on June 28, 2010 in Chicago, Ill. The meetings and publication of these proceedings were supported by Forest Research Institute, a wholly owned subsidiary of Forest Laboratories, Inc. (Jersey City, NJ). Medical writing and editorial assistance provided by Morgan C. Hill, PhD of Prescott Medical Communications Group (Chicago, Ill) was made possible by funding from Forest Research Institute.

    Conflicts of Interest: The authors of this article have disclosed the following industry relationships. Sanjay Sethi, MD has consulted or participated in advisory boards for: AstraZeneca, Boehringer Ingelheim, Forest, GlaxoSmithKline, Medimmune, Merck, and Novartis; is a member of the Speakers' Bureau for AstraZeneca, Boehringer Ingelheim, Forest, and Pfizer (>$10,000 each); and has received research/grant support from AstraZeneca, GlaxoSmithKline, Pulmatrix, and Medical Acoustics.

    Donald A. Mahler, MD works as a consultant to AstraZeneca, Boehringer Ingelheim, DeepBreeze, Forest, GlaxoSmithKline, Merck, Novartis, and Sunovion (<$10,000 each); has received research/grant support from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Sunovion; serves on the advisory boards of DeepBreeze, Forest, GlaxoSmithKline, Merck, Novartis, and Sunovion.

    Philip Marcus, MD, MPH was a member of the Speakers' Bureau for GlaxoSmithKline, Boehringer Ingelheim, Teva, Sunovion, Merck (<$10,000 each) and Novartis, Genentech (>$10,000 each); worked as a consultant to Genentech, Sunovion, Teva, Forest, and Nycomed (<$10,000 each); received research/grant support from AstraZenecq, GlaxoSmithKline, Forest; served on the advisory boards of Genentech, Sunovion, and Nycomed.

    Caroline Owen, MD, PhD serves as a consultant to Wyeth Pharmaceuticals (<$10,000) and has received research/grant support for a chronic obstructive pulmonary disease (COPD) project from Pulmatrix Inc.

    Barbara Yawn, MD, MSc works as a consultant for COPD to Novartis (<$10,000); has received research/grant support related to COPD from Novartis, Boehringer Ingelheim-Pfizer, and AstraZeneca; serves on the COPD advisory boards of Boehringer Ingelheim, Teva, Forest, Genentech, GlaxoSmithKline, and Novartis.

    Stephen Rennard, MD has consulted for: ABIM, Able Associates, Adelphi Research, Align2 Acton, APT Pharma/Britnall, American Thoracic Society, Beilenson, Boehringer Ingelheim, BoomCom, Britnall and Nicolini, Capital Research, Chiesi, Clarus Acuity, CommonHealth, Complete Medical Group, Consult Complete, COPDForum, DataMonitor, Decision Resources, Dunn Group, Easton Associates, Equinox, Frankel Group, Fulcrum, Gerson Lehman, Globe Life Sciences, Guidepoint, Health Advanced, Hoffmann LaRoche, Informed, Insyght, KOL Connection, Leerink Swan, M. Pankove, McKinsey, MDRxFinancial, Medimmune, Merck, Novartis, Oriel, Osterman, Pearl, Penn Technology, Pennside, PharmaVentures, Pharmaxis, Prescott, Price Waterhouse, Propagate, Pulmonary Reviews, Pulmatrix, Reckner Associates, Recruiting Resource, Roche, Sankyo, Schering, Schlesinger Medical, Scimed, Smith Research, Sudler and Hennessey, Summer Street Research, Talecris, Think Equity, UBC, Uptake Medical, Vantage Point Management (<$10,000 each) and Almirall/Prescott, AstraZeneca, Boehringer Ingelheim (ACCP), Nycomed, Pfizer, Forest, GlaxoSmithKline (>$10,000 each); has given lectures for: American Association for Respiratory Care, Almirall, American College of Osteopathic Physicians, Asan Medical Center, American Thoracic Society, California Society of Allergy, CME Incite, COPD Foundation, Creative Education Concepts, Dey, Duke University, Forest, France Foundation, HSC Medical Education, Information TV, Lung Association, Novartis (Horsham), Nycomed, Otsuka, PeerVoice, Pfizer, Shaw Science, University of Washington, University of Alabama-Birmingham, and VA Sioux Falls.

    Authorship: This manuscript is an original work, and all authors participated in the drafting, reviewing, and final approval of this manuscript. Dr. Marcus passed away after manuscript preparation and approval.

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