Effects of high-dose inhaled fluticasone propionate on the hypothalamic-pituitary-adrenal axis in asthmatic patients with severely impaired lung function.
BACKGROUND
The effects of high-dose fluticasone propionate therapy on dynamic cortisol stimulation in severe asthma are unknown.


OBJECTIVE
To evaluate the human corticotropin-releasing factor (hCRF)-stimulated plasma cortisol response to fluticasone propionate therapy in severe asthmatic patients with impaired airway caliber (forced expiratory volume in 1 second [FEV1] < 60% of predicted) and in control subjects.


METHODS
Ten severe asthmatic patients (mean FEV1, 47% of predicted) and 10 controls (mean FEV1, 104% of predicted) received fluticasone propionate, 2,000 microg/d, via a 750-mL primed spacer for 2 weeks. Plasma cortisol levels before and after hCRF stimulation and overnight 10-hour urinary cortisol excretion corrected for creatinine concentration (OUCC) were measured at baseline after washout and 12 hours after the last dose of fluticasone propionate.


RESULTS
Baseline values before fluticasone propionate use were not significantly different in asthmatic patients vs controls for plasma cortisol before and after hCRF stimulation and OUCC. Comparing values at baseline vs after fluticasone propionate use, there was no significant suppression of plasma cortisol levels before (378.2 vs 357.4 nmol/L) or after (510.5 vs 507.9 nmol/L) hCRF stimulation or OUCC (8.2 vs 7.5 nmoL/mmoL) in asthmatic patients. In controls, all outcomes were significantly suppressed comparing values before vs after fluticasone propionate therapy: plasma cortisol levels before (423.5 vs 200.2 nmol/L; P = .002) and after (503.5 vs 291.1 nmol/L; P = .001) hCRF stimulation and OUCC (6.5 vs 2.4 nmol/mmol; P = .002).


CONCLUSIONS
Patients with severe persistent asthma and impaired airway caliber seem to be protected from developing systemic adverse effects with high-dose fluticasone propionate therapy, as evaluated by basal and dynamic measures of hypothalamic-pituitary-adrenal axis activity.
Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
Daniel K C
DK
Lee
Caroline E
CE
Bates
Graeme P
GP
Currie
Louise M
LM
Cowan
Lesley C
LC
McFarlane
Brian J
BJ
Lipworth
D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use; D001798:Blood Proteins; D001944:Breath Tests; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D047091:Eosinophil Granule Proteins; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D036501:Metered Dose Inhalers; D009569:Nitric Oxide / Q000032:analysis; D010366:Peak Expiratory Flow Rate; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012260:Ribonucleases / Q000097:blood; D000068299:Salmeterol Xinafoate; D013806:Theophylline / Q000008:administration & dosage / Q000627:therapeutic use
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D004983:Ethanolamines; D009569:Nitric Oxide; D000068299:Salmeterol Xinafoate; D003404:Creatinine; D013806:Theophylline; D000068298:Fluticasone; D012260:Ribonucleases; D001507:Beclomethasone; D000420:Albuterol; D000068759:Formoterol Fumarate; D006854:Hydrocortisone