COMPARISON OF THE ANTIASTHMATIC, OROPHARYNGEAL, AND SYSTEMIC GLUCOCORTICOID EFFECTS OF BUDESONIDE ADMINISTERED THROUGH A PRESSURIZED AEROSOL PLUS SPACER OR THE TURBUHALER DRY POWDER INHALER

To determine therapeutically and systemically equivalent dosages of bu desonide inhaled through the Turbuhaler dry powder inhalation device ( Astra Pharma Production AB, Sodertalje, Sweden) or pressurized metered -dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB ), we compared these devices in a randomized, open, parallel-group tri al. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8 , 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Tu rbuhaler (n = 30) or pMDI + Nebuhaler (n = 28). Dose-dependent effects were demonstrated on asthma symptoms (p = 0.0001), daily peak expirat ory flow (p = 0.02), blood eosinophils (p = 0.0001), urinary cortisol output per day (p = 0.0001), serum cortisol (p = 0.006), serum osteoca lcin (p = 0.0001), and the oropharyngeal Candida colony count (p = 0.0 007, analysis of covariance). The ratio of the responses to the two in halation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found (p greater than or eq ual to 0.29). However, the 95% confidence limits for the ratio of thei r respective systemic effects on osteocalcin production were 0.83 to 1 .48. Thus in adults who use inhalation devices efficiently and have op timally controlled asthma, conversions from the pMDI + Nebuhaler to th e Turbuhaler may reasonably be made at milligram equivalent doses of b udesonide, then down-titrated to minimize possible systemic effects. B ecause earlier studies have shown that the Turbuhaler can double intra pulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler.