Systemic inflammation in chronic obstructive pulmonary disease: may adipose tissue play a role? Review of the literature and future perspectives

Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease. Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation. On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. results from lung-to plasma spillover of inflammatory mediators. On the other hand, obesity-related hypoxia results in local inflammatory response within adipose tissue per se, and may contribute to elevations in circulatory mediators by spillover from the adipose tissue to the systemic compartment. The extent to which systemic hypoxia contributes to the adipose tissue inflammation remains unknown. We assume that in patients with COPD and concurrent obesity at least three factors play a role in the systemic inflammatory syndrome: the severity of pulmonary impairment, the degree of obesity-related adipose tissue hypoxia, and the severity of systemic hypoxia due to reduced pulmonary functions. The present review summarizes the epidemiological and clinical evidence linking COPD to obesity, the role of adipose tissue as an endocrine organ, and the role of hypoxia in adipose tissue inflammation.

Figure 1

Concept of differential contribution of lung-to-blood translocation of inflammatory proteins versus adipose tissue inflammation to the overall systemic inflammatory phenotype in COPD. We suggest that in patients with mild COPD and concurrent obesity, adipose tissue (AT) is the key contributor to systemic inflammation, whereas in those with severe COPD, lung-to-blood translocation of inflammatory proteins plays the major role.

Figure 2

Proposed mechanistic links between the combined effects of obesity-related local adipose tissue hypoxia, reduced lung function-related systemic hypoxia, and bronchial inflammation-related increased lung-to-plasma translocation of inflammatory mediators on systemic inflammatory profile in patients with COPD.