Reversal of chronic obstructive pulmonary disease-associated weight loss : are there pharmacological treatment options?

Poor nutritional status is associated with an increased incidence of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). While a number of factors have been shown to produce tissue catabolism, no single mechanism has been clearly identified as a primary cause for weight loss in patients with severe COPD. Without a clear understanding of the aetiology of weight loss, therapeutic strategies to reverse this process have historically been unsuccessful. A review of recent studies allows consideration of a model of mechanisms of weight loss. This model includes multiple pathways that may be activated singly or simultaneously to cause loss of weight, specifically lean body mass. These include energy imbalances, elevated levels of cytokines, tissue hypoxia and the effects of cocorticosteroid therapy. To date, interventional studies that have looked at newer pharmacotherapies such as growth hormone and anabolic steroids in patients with COPD who are losing weight have not demonstrated reversal of weight loss or improvement in nutritional status. Currently, early identification of patients at risk for weight loss and aggressive nutritional supplementation coupled with an exercise programme has demonstrated the greatest benefit. However, with increasing understanding of the mechanisms that may be implicated, new targets for therapies are being identified. Of particular research interest are molecules such as leukotrienes, hormones, tumour necrosis factor-alpha and acute-phase proteins, which are noted to be elevated in some patients with COPD-associated weight loss. Currently, inhibitors to some of these inflammatory substances are used therapeutically in other chronic illnesses such as rheumatoid arthritis and cancer cachexia. Future research may investigate their usefulness in COPD and direct new therapies that target the processes contributing to weight loss in these patients.