Rapid effect of inhaled ciclesonide in asthma: a randomized, placebo-controlled study.
BACKGROUND
Ciclesonide is a novel inhaled corticosteroid for the treatment of asthma, and it is important to measure the onset of effect of this therapy on airway hyperresponsiveness (AHR), exhaled nitric oxide (NO), and levels of eosinophils in induced sputum.


METHODS
In a randomized, double-blind, crossover study, 21 patients with mild asthma inhaled ciclesonide 320 microg (ex-actuator) qd, ciclesonide 640 microg (ex-actuator) bid, and placebo for 7 days. Exhaled NO and AHR to adenosine monophosphate (AMP), measured as the provocative concentration of AMP producing a 20% reduction in FEV1 (PC20FEV1), were assessed after inhalation on days 1, 3 and 7. Eosinophil levels in induced sputum were also measured.


RESULTS
Ciclesonide 320 microg qd and 640 microg bid produced significantly greater improvements in PC20FEV1 compared with placebo on day 1 (within 2.5 h), and on days 3 and 7 (all p < 0.0001). On day 3, both ciclesonide doses significantly reduced exhaled NO levels by - 17.7 parts per billion (p < 0.0001) and - 15.4 parts per billion (p < 0.003) vs placebo, respectively. Significant reductions were maintained during the study with both ciclesonide doses (p < 0.01). A nonsignificant trend towards a decrease in eosinophil cell numbers was observed after 7 days of ciclesonide treatment, especially in patients receiving the higher dose.


CONCLUSIONS
A single dose of ciclesonide decreased AHR to AMP and exhaled NO within 3 h, while FEV, improved at 3 days and 7 days.
Erin
Edward M
EM
National Heart and Lung Institute Clinical Studies Unit, Imperial College, London, UK.
Zacharasiewicz
Angela S
AS
Department of Pediatric and Adolescent Medicine, Pulmonary and Infectious Diseases, Wilhelminenspital, Vienna, Austria.
Nicholson
Grant C
GC
National Heart and Lung Institute Clinical Studies Unit, Imperial College, London, UK.
Tan
Andrew J
AJ
National Heart and Lung Institute Clinical Studies Unit, Imperial College, London, UK.
Neighbour
Helen
H
National Heart and Lung Institute Clinical Studies Unit, Imperial College, London, UK.
Engelstätter
Renate
R
Nycomed GmbH, Konstanz, Germany.
Hellwig
Michael
M
Nycomed GmbH, Konstanz, Germany.
Kon
Onn Min
OM
St. Mary's Hospital, Paddington, London, UK.
Barnes
Peter J
PJ
Department of Thoracic Medicine, Imperial College, London, UK.
Hansel
Trevor T
TT
National Heart and Lung Institute Clinical Studies Unit, Imperial College, London, UK. Electronic address: t.hansel@ic.ac.uk.
D000280:Administration, Inhalation; D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004804:Eosinophils; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D011282:Pregnenediones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013183:Sputum / Q000166:cytology
D018926:Anti-Allergic Agents; D011282:Pregnenediones; D009569:Nitric Oxide; C120481:ciclesonide