Corticosteroid sparing agents in asthma.

Chest physicians are all too aware ofthe serious side effects associated with the long term use of systemic corticosteroids, particularly weight gain, indigestion, impairment of glucose tolerance, and osteoporosis. The introduction of potent and topical inhaled corticosteroids allowed most patients on regular oral corticosteroids to reduce or stop these, but there are still patients with chronic severe asthma whose symptoms are inadequately controlled by high doses of inhaled corticosteroids and maximal bronchodilator therapy. Such patients receive increasingly frequent courses of oral corticosteroids, often culminating in their long term use. Side effects may not be a problem with a regular low dose of oral corticosteroid, but they become increasingly troublesome as higher doses are required. The management of these patients is extremely difficult and the treatment of their asthma and the side effects of corticosteroid therapy consumes much time and money. Before discussing corticosteroid sparing agents three points need to be made. Firstly, in our experience it is relatively unusual for patients with asthma who are taking inhaled treatment correctly to require more than 5-7-5 mg prednisolone per day for asthma; patients taking more than this should be investigated very carefully. Preventable factors that need to be considered include non-compliance, occupational factors, gastro-oesophageal reflux, specific antigens, and dietary factors. Anxiety about asthma deaths has led to the overuse of corticosteroids by some patients and psychosocial factors and concomitant hyperventilation syndrome can be particularly difficult to disentangle. The second point is that some patients are truly corticosteroid resistant, showing a response to bronchodilators but none to corticosteroids. '2 These patients should not be prescribed corticosteroids. More commonly, patients on oral corticosteroids with severe asthma have some response to corticosteroids although this is relatively small. These are better described as having severe asthma rather than corticosteroid resistance. Lastly, any drug that is effective in asthma whatever its mechanism of action will, by definition, have a corticosteroid sparing effect in that less oral corticosteroid will be required to achieve a given improvement in asthma control. This review will not discuss recognised asthma therapies in this category. Corticosteroid sparing agents Several agents that have been shown to have corticosteroid sparing properties in other conditions have been studied in chronic severe asthma. For this reason we have described them as corticosteroid sparing agents, although some of the studies have looked at the effect of adding, rather than substituting, these agents to existing therapy which has usually, though not always, included corticosteroids (table). Many of the trials have involved small numbers of patients and patients have not necessarily been receiving optimal doses ofinhaled corticosteroids and bronchodilators. In this review we describe the agents, their presumed mode of action, and the evidence for their efficacy in corticosteroid dependent asthma.