Adrenal suppression in asthmatic children receiving low-dose inhaled budesonide: comparison between dry powder inhaler and pressurized metered-dose inhaler attached to a spacer.
BACKGROUND
Dry powder inhalers (DPI) have in recent years become a common mode for administration of inhaled corticosteroids for preventive therapy of asthma. Inhaled steroids delivered by DPI achieve increased lung deposition compared with pressurized metered-dose inhalers (pMDI), which is associated with increased therapeutic effect. This may be associated with increased systemic absorption.


OBJECTIVE
The purpose of this study was to evaluate the prevalence of adrenal suppression in children using low-dose budesonide given by DPI, as compared with pMDI attached to a large-volume spacer device (pMDI + spacer).


METHODS
In an open-labeled crossover study, 15 asthmatic children aged 5 to 15 years received 200 microg of inhaled budesonide twice daily by DPI (Turbuhaler, Astra, Draco AB, Lund, Sweden) and by pMDI + spacer, 1 month each, in a randomized order. Twenty-four-hour urine collections were performed at baseline and at the end of each of the 2 months of the study period, and urinary cortisol and creatinine were measured.


RESULTS
Baseline urinary cortisol:creatinine was 0.038 +/- 0.012 microg/mg, similar in both groups. After 1 month of DPI therapy, urinary cortisol:creatinine was reduced by 27 +/- 16% to 0.028 +/- 0.012 microg/mg (P = 0.018). Urinary cortisol:creatinine after 1 month of pMDI + spacer therapy was similar to baseline 0.037 +/- 0.019 microg/mg (P = 0.78).


CONCLUSIONS
Treatment of asthmatic children with budesonide 400 microg daily given via a DPI for 1 month was associated with hypothalamic-pituitary-adrenal axis suppression. This effect was not observed with the same dose of budesonide administered via pMDI + spacer. This indicates that systemic absorption might be reduced with pMDI + spacer therapy.
Goldberg
Shmuel
S
Department of Pediatric Respiratory Medicine, Shaare Zedek Medical Center, Hebrew University Medical School, Jerusalem, Israel.
Einot
Tsurit
T
Algur
Nurit
N
Schwartz
Shimshon
S
Greenberg
Alan C
AC
Picard
Elie
E
Virgilis
Dov
D
Kerem
Eitan
E
D000042:Absorption; D000280:Administration, Inhalation; D000293:Adolescent; D000302:Adrenal Cortex / Q000378:metabolism*; D000336:Aerosols; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001682:Biological Availability; D019819:Budesonide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003864:Depression, Chemical; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D036503:Inhalation Spacers; D008168:Lung / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011208:Powders
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D011208:Powders; D019819:Budesonide; D006854:Hydrocortisone