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INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of respiratory-related morbidity and mortality. Inhaled steroids are frequently used in patients with moderate to severe disease and may lead to adrenal suppression. OBJECTIVES: The aim of this study was to compare the effect of inhaled budesonide/formoterol with inhaled fluticasone/salmeterol in severe COPD. METHODS: It was a prospective open-label crossover study of 22 patients. Adrenal suppression was measured by overnight urinary cortisol/creatinine ratio. The measurements were taken while patients were on either combination for at least 4 weeks. RESULTS: A total of 12 patients completed the study. The mean age was 64 years (8 males, 4 females). The mean FEV1 was 1 L (range, 0.5-1.8). There was no significant difference in adrenal suppression measured by overnight urinary cortisol/creatinine ratio (budesonide 5.2 ± 4.3, fluticasone 4.7 ± 3.1; 95% CI -2.2 to 1.2; P = 0.52) and urinary cortisol concentration (budesonide 51 ± 53, fluticasone 43 ± 31 [nmol/l]; 95% CI -35 to 20; P = 0.56). CONCLUSION: Inhaled budesonide and fluticasone have no significantly different effect on adrenal function in moderate to severe COPD. The adverse event profile of high-dose inhaled steroids should not influence the choice of medication. [ABSTRACT FROM AUTHOR]