Budesonide and fluticasone and adrenal suppression.

Sir,

We read with interest the article “Comparison of the effect of high-dose inhaled budesonide and fluticasone on adrenal function in patients with severe chronic obstructive pulmonary disease” by Fahim et al.[1] It was concluded in the article that inhaled budesonide (800 μg) and fluticasone (1000 μg) had the same effect on adrenal function in moderate to severe COPD. We would like to make the following comments:

We agree with the authors’ statement in the discussion section that several previous studies report significant adrenal suppression with fluticasone. Moreover, there were increased levels of markers of bone metabolism with 1000 μg of fluticasone (an effect absent with smaller doses).[2]

Only one comparative study showed equal adrenal suppression by fluticasone and budesonide (which the author quoted). However, five other studies reported greater suppression by fluticasone in a dose of 750 μg or more per day in adults (and a larger number of studies in children).[3]

Fluticasone also fares worse than newer inhaled corticosteroids like ciclesonide.[4] We agree with the authors of your paper that studies on adrenal suppression are biased by several confounding factors like the device used to deliver the drug or the patient's condition. However, a strong and nearly consistent trend favors budesonide and ciclesonide in that respect.

Given the small number of patients (12) in the study, the confidence intervals (CI) for the results are not conclusive. The urinary cortisol–creatinine ratios of budesonide and fluticasone were: 5.2 ± 4.3 and 4.7 ± 3.1, CI −2.2 to 1.2, respectively, and for urinary cortisol the ratios were 51 ± 53 and 43 ± 31, CI −35 to 20, respectively. With a larger number of patients, the tests may have favored budesonide.

The study compared the effects of budesonide and fluticasone. Without comparing these with the pre-steroid baseline levels of cortisol, it is possible that both drugs resulted in adrenal suppression.

Osteoporosis is an important and common co-morbidity of COPD. Although studies are divided on the presence of an association between osteoporosis and inhaled corticosteroids, other systemic effects like skin thinning and delayed wound healing are proven risks.[5] These effects are age related, which makes them more relevant to COPD.[5] Therefore, the risk versus benefit should be assessed individually, and the inhaled corticosteroid with the least adrenal suppression selected. Ciclesonide (not approved for COPD) seems, on available evidence, to be the safest, followed by budesonide.