Effects of hydrofluoroalkane and dry powder-formulated corticosteroids on sputum inflammatory markers in asthmatic patients.
BACKGROUND
Inhaled corticosteroids are powerful drugs that can suppress airway inflammation in asthmatic patients. Deposition of most of the inhaled corticosteroid occurs mainly in the central airways. However, a new hydrofluoroalkane formulation of beclomethasone dipropionate (HFA-BDP) is preferentially deposited in the distal airways. Inflammatory characteristics of induced sputum have been shown to differ in samples collected early after sputum induction compared with later.


OBJECTIVE
To compare the effects of HFA-BDP and budesonide in a dry powder inhaler (DPI-BUD) on inflammatory cells and inflammatory cytokine expression in early and late induced sputa compared with placebo.


METHODS
Seventeen patients with mild, intermittent bronchial asthma were randomly assigned to two treatment groups: eight patients received HFA-BDP and nine patients received DPI-BUD. Each patient was treated with one of the active treatments and placebo (for four weeks), with a two-week washout interval in between. Inflammatory cells and expression of interleukin (IL)-4 and IL-5 were measured in early and late induced sputa before and after active treatment, as well as before and after placebo treatment using immunocytochemistry and in situ hybridization.


RESULTS
Compared with placebo, eosinophils were significantly reduced in both early and late induced sputa after HFA-BDP treatment (P<0.05), whereas DPI-BUD had a significant effect only on early induced sputum. Both HFA-BDP and DPI-BUD decreased IL-4 expression in early and late induced sputa, but the effect was more prominent with HFA-BDP. IL-5 expression was reduced in both early and late induced sputa after HFA-BDP treatment. DPI-BUD significantly decreased IL-5 expression in early but not in late induced sputum. The number of lymphocytes was not altered by either treatment.


CONCLUSIONS
HFA-BDP reduced eosinophilic inflammation and T helper 2-type cytokine expression in both early and late induced sputa, whereas the effect of DPI-BUD on inflammation was predominantly demonstrated in early induced sputum.
Hauber
H
H
Meakins-Christie Laboratories, McGill University, Montreal, Canada.
Taha
Rame
R
Bergeron
Celine
C
Migounov
Vladimir
V
Hamid
Qutayba
Q
Olivenstein
Ron
R
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000335:Aerosol Propellants / Q000627:therapeutic use*; D000465:Algorithms; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000627:therapeutic use*; D015415:Biomarkers; D019819:Budesonide / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D004311:Double-Blind Method; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000627:therapeutic use*; D008214:Lymphocytes; D008297:Male; D011208:Powders / Q000627:therapeutic use; D013183:Sputum / Q000166:cytology; D005466:Fluorocarbons
D000305:Adrenal Cortex Hormones; D000335:Aerosol Propellants; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone; D015415:Biomarkers; D019819:Budesonide; D016207:Cytokines; D006845:Hydrocarbons, Fluorinated; D011208:Powders; C094049:apaflurane; D005466:Fluorocarbons