Chest

Chest

Volume 139, Issue 1, January 2011, Pages 165-173
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Translating Basic Research into Clinical Practice
Systemic Manifestations of COPD

https://doi.org/10.1378/chest.10-1252Get rights and content

COPD is characterized by a poorly reversible airflow limitation resulting from chronic inflammation, mainly due to tobacco exposure. Over the past few years, the understanding of COPD has evolved from it being a disease affecting the lungs to it being a complex, heterogeneous, and generalized disorder in an aging population. Extrapulmonary comorbidities significantly complicate the management and influence the prognosis of patients with COPD. Although certain comorbidities like cardiovascular diseases share some risk factors with COPD, such as cigarette smoking, other frequently observed comorbidities, including musculoskeletal wasting, metabolic syndrome, and depression, cannot be easily attributed to smoking. There is increasing evidence that chronic inflammation is a key factor in COPD and that inflammation might be the common pathway linking these comorbidities and explaining why they typically develop together. Physicians treating patients with COPD need to become aware of these extrapulmonary aspects. Any patient with COPD should be carefully evaluated for comorbidities and the systemic consequences of COPD since they not only influence the prognosis but also have an impact on disease management. The treatment of COPD is no longer focused exclusively on inhaled therapy but is taking on a multidimensional approach, especially because the treatment of the comorbidities might positively affect the course of COPD itself.

Section snippets

Local and Systemic Inflammation in COPD

The airflow limitation in COPD results from airway inflammation due to an abnormal response of the lungs to noxious particles or gases.3 In Western countries, smoking is the main risk factor for the development of COPD, and 90% of patients are current or past smokers. Smoking is the most important risk factor not only for COPD but also for many other chronic diseases and certain cancers. Smoking triggers a local inflammatory response throughout the whole tracheobronchial tree, and pathologic

COPD: Part of a Systemic Disease?

The growing evidence that systemic inflammation is a key driver in COPD and is present in many other chronic diseases associated with COPD probably no longer justifies the concept that COPD is a disease restricted to the lungs. The majority of patients with COPD die from cardiovascular disorders or cancer, not respiratory disease.31, 32, 33, 34 One can distance COPD from the traditional view, which was basically centered on the presence of chronic airflow obstruction, in that it has been

Implementation in Clinical Daily Routine

Comorbidities and systemic features present in patients with COPD not only have prognostic value but also result in implications for medical treatment. Until now, the pharmacologic treatment of patients with COPD has been centered mainly on the lungs, specifically the bronchi, and is primarily symptomatic. Considering the different aspects in the pathogenesis of COPD and the evidence that treatment of certain comorbidities positively affects the course of the disease itself, treatment

Pulmonary Rehabilitation

Physical activity is significantly reduced in patients with COPD and gradually declines with higher GOLD and BODE stages of the disease.50 Reduced physical activity is also an independent predictor of increased levels of high-sensitivity CRP, IL-6, and fibrinogen in COPD patients,51 and there is increasing evidence that persons who are physically inactive have higher levels of systemic inflammatory markers compared with persons who are physically active.52 Assuming that systemic inflammation is

Pharmacologic Interventions

Until recently, there have been no specific pharmacologic treatments of COPD; the available therapies are “borrowed” from asthma and adapted to COPD, even though the underlying inflammatory pattern in asthma is very different.54 Most of the large clinical trials have shown that the available drugs for COPD do not significantly modify the long-term decline in FEV1, the hallmark of the disease.55, 56 Pharmacologic treatment of COPD is therefore still mainly used to decrease symptoms, reduce the

Future Directions

There is consistent evidence that the understanding of COPD has evolved from a disease limited to the airways to a complex and multicomponent syndrome characterized by pulmonary and systemic inflammation. Chronic diseases, including COPD, share common aspects, and chronic systemic inflammation seems to be one of the linking elements. The origin of this systemic inflammation is still unclear. Because smoking itself induces an inflammatory response and therefore interferes with the postulated

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Rabe has consulted for, participated in advisory board meetings with, and received lecture fees from AstraZeneca, Boehringer, Chiesi Pharmaceuticals, Pfizer, Novartis, Nycomed, MSD, and GaxoSmithKline (GSK). The Department of Pulmonology, and, therefore, Dr Rabe, as head of the department, received grants from Novartis, AstraZeneca, Boehringer Ingelheim, Nycomed, Roche, and GSK from

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