Inhaled corticosteroids and mortality in COPD: are we there yet?

A broader indication for inhaled corticosteroids (ICS) in COPD has been sought for some time. The recent meta‐analysis by Sin et al¹ suggesting protection against all‐cause mortality is therefore of some interest. Although not universally confirmed,²,³ this tantalising concept is being prospectively evaluated in a 3 year study of high dose ICS (fluticasone propionate 500 μg twice daily, alone or in combination with a long acting β agonist) in COPD patients with forced expiratory volume in 1 second (FEV₁) <60%.⁴

But how might this protection be afforded? Local effects may teleologically provide organ specific protection, potentially reflected by reduced frequency or severity of pulmonary exacerbations. However, COPD is recognised as a systemic inflammatory condition associated with raised systemic inflammatory markers such as C‐reactive protein, and this marker is increasingly recognised as an independent risk factor for cardiac mortality.⁵

Important questions revolving around the determinants of all‐cause mortality, both generally and in COPD, remain unresolved. How, for instance, should we interpret a positive trial outcome without comparative data regarding the relative impacts of the modification of such risk factors as smoking cessation, diet, exercise, and weight reduction? Secondly, if the benefits provided by corticosteroids could be largely attributed to systemic anti‐inflammatory activity, then systemic corticosteroid dosing may be more efficient and potentially cheaper. Finally, these questions will be further complicated by uncertainties regarding dosing, the need for concomitant long acting β agonists, and adverse effect thresholds.

Currently recommended indications for ICS in COPD include the prevention of exacerbations in those with FEV₁ <50% and “the prevention of decline in health status”.⁶,⁷ Clarification and the beneficial extension of these indications would be welcomed.