Should inhaled corticosteroids be used in the long term treatment of chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is a progressive disease with alveolar destruction (emphysema) and bronchiolar fibrosis (obstructive bron chitis) in variable proportions. Reducing disease progression, as assessed by forced expiratory volume in 1 second (FEV1) decline, health-related qual ity of life, exacerbation rate and mortality, is a more realistic outcome t han physiological improvement. This paper reviews all the published studies of at least 100 patients follo wed for at least 2 years. Studies have included patients with mild COPD (Co penhagen City Lung Study) to advanced symptomatic disease [Inhaled Steroids in Obstructive Lung Disease (ISOLDE)], with 2 studies of those with relati vely early symptoms [European Respiratory Society Study on Chronic Obstruct ive Pulmonary Disease (EUROSCOP) and Lung Health-2]. Exacerbation frequency , and probably severity, are reduced by high dose inhaled cortico steroids. Exacerbations are only frequent in more advanced disease, limiting the use of this outcome in EUROSCOP and Lung Health-2. Exacerbations are associated with reduced health-related quality of life. ISOLDE clearly showed a reduc ed rate in decline of the disease-specific St George's Respiratory Question naire with fluticasone propionate, partly related to the reduced exacerbati ons. The syptom component of the score showed the greatest difference betwe en placebo and fluticasone propionate. None of the larger studies were able to reproduce the statistically significant reduction in the rate of declin e in FEV1 suggested by the smaller, earlier studies. This might at least in part be as a result of the statistical modelling used which cannot adequat ely compensate for those with more rapidly progressive disease dropping out earlier. The equivalent doses of inhaled corticosteroids differed approxim ately fivefold between the major studies. The more positive results were ob tained with higher doses. Oropharyngeal adverse effects were similar to those seen in patients with a sthma; bruising was increased in one study with budesonide, otherwise adver se effects were similar to placebo. Bone loss was specifically studied in s ubgroups of patients in EUROSCOP and Lung Health-2. Budesonide 800 mug/day was associated with less bone loss than placebo, whereas triamcinolone 1200 mug/day was associated with excess bone loss. High dose inhaled corticoste roids have a favourable risk/benefit ratio in patients with advanced diseas e, particularly those with frequent exacerbations, and no benefit for those with very mild disease. It is not possible from the data to make firm reco mmendations for the important intermediate group where delaying progression is likely to lead to greatest benefit. I believe high dose inhaled steroid s are warranted for those with intermediate severity COPD, who have frequen t exacerbations or significant COPD-related symptoms.