Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma.
BACKGROUND
The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined.


METHODS
Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed.


RESULTS
Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time.


CONCLUSIONS
These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs.


BACKGROUND
clinicaltrial.gov; Identifier: NCT00525772.
Duong
MyLinh
M
Department of Medicine, McMaster University, 1200 Main St West, Room 3U-24, Hamilton, ON, Canada L8N 3Z5. duongmy@mcmaster.ca
Subbarao
Padmaja
P
Adelroth
Ellinor
E
Obminski
George
G
Strinich
Tara
T
Inman
Mark
M
Pedersen
Soren
S
O'Byrne
Paul M
PM
D000293:Adolescent; D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D011282:Pregnenediones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013147:Spirometry; D013183:Sputum / Q000737:chemistry*
D018926:Anti-Allergic Agents; D011282:Pregnenediones; C120481:ciclesonide