Systemic Effects of COPD: Just the Tip of the Iceberg

The Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease defines COPD as “a preventable and treatable disease with some significant extra-pulmonary effects that may contribute to the severity in individual patients” ([1]). It is interesting to note that this definition highlights the systemic effects of COPD even before mentioning that COPD is “also” characterized by poorly reversible airflow limitation ([1]). This is not to diminish the central role of chronic airflow obstruction in patients with COPD, but to underlie the clinical relevance that many of the extra-pulmonary manifestations of the disease can have in some patients ([2]).

Yet, this paradigm has permeated clinical practice very slowly. The ATS/ERS guidelines were the first to include it in their recommendations, and this was just four years ago ([3])! In contrast, as early as in 1966, Burrows et al. had already described two distinct COPD phenotypes, the “blue bloater” and the “pink puffer,” the latter being characterized by marked weight loss and skeletal muscle atrophy (cachexia) ([4]). It was not, however, until 1993 when Schols et al. identified weight loss in COPD as a prognostic factor that, importantly, was independent of the degree of airflow limitation ([5]). Since this seminal observation, many different investigators have contributed to identify the presence of chronic low-level systemic inflammation (in combination with other factors such as a sedentary life style, tissue hypoxia and malnutrition, among others) as a key mechanism in the pathogenesis of many (if not all) the systemic effects of COPD ([6], [7]). In this issue of the Journal of COPD, Decramer and colleagues ([8]) summarizes the presentations and discussions of a round-table meeting of experts held in Miami (Florida, USA) in December 2006. In this review, they addressed the issue of systemic inflammation and comorbidities in COPD, including deconditioning, exercise intolerance and skeletal muscle dysfunction, osteoporosis, metabolic abnormalities, anxiety and depression and cardiovascular morbidity and mortality, as well as the potential for therapeutic intervention. The reader will find in the paper by Decramer et al. a valuable resource of updated information, which is clearly ordered, presented and discussed.

Unfortunately, however, it just represents the tip of the iceberg in this field because many questions remain still open. For instance, the origin, prevalence and relationship to different COPD phenotypes of systemic inflammation is unclear ([9]). Likewise, its response to anti-inflammatory therapy is controversial ([10], [11]) and, more importantly, the potential effects on clinically relevant outcomes derived from its therapeutic manipulation is unknown. Also, whether or not the use of systemic inflammatory biomarkers (alone or in combination) ([12], [13]) can help clinicians to manage COPD patients is an area of great current interest ([14]) but clearly in need of much more research and validation. Of note, three major multi-center studies currently being conducted (ECLIPSE ([15]), COPDGene, (http://www.copdgene.org) and Spiromics (http://researchfunding.duke.edu/detail.asp?OppID = 3890) will try to answer many of these questions.

Last but not least, the realization that patients with COPD often suffer from other concurrent diseases, either caused directly by COPD (systemic effects) and/or by common risk factors such as smoking or aging (comorbidities) ([16]), have direct implications on patient care. Yet, current clinical guidelines focus almost exclusively in single diseases. This situation applies to all major chronic diseases, including COPD, type II diabetes, osteoporosis or chronic heart failure, and is clearly suboptimal ([17]). Furthermore, it may be even detrimental for patients, as illustrated by the recent observations that β -blocker drugs that are commonly used in the treatment of heart failure and thought to be prohibited in COPD can be safely used in these latter patients ([18]). It is imperative, therefore, that future clinical guidelines take into account the prevalence, complexity and heterogeneity of all these age-related chronic diseases (including COPD) in order to provide the best possible care.

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