Differential anti-inflammatory effects of large and small particle size inhaled corticosteroids in asthma.
BACKGROUND
Extra-fine particle formulations of hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) exhibit clinical effects comparable with conventional particle formulations of chlorofluorocarbon beclometasone dipropionate (CFC-BDP) at half the dose. There is little data comparing their effects on inflammation. We have evaluated the effects of HFA-BDP and CFC-BDP on pulmonary and systemic markers of asthmatic inflammation.


METHODS
A double-blind randomized crossover trial was undertaken comparing the anti-inflammatory effects of HFA-BDP (100 and 400 microg/day) and CFC-BDP (200 and 800 microg/day). Treatment with montelukast was evaluated as add-on to the higher dose of BDP.


RESULTS
Compared with baseline after withdrawal of usual asthma therapy, 100 microg of HFA-BDP significantly attenuated serum eosinophilic cationic protein levels (0.61-fold change, 95% CI 0.49-0.77; a 39% reduction, P < 0.001), but 200 microg of CFC-BDP did not (0.87-fold change, 95% CI 0.63-1.23; P = 1). A dose of 800 microg of CFC-BDP and 400 microg of HFA-BDP led to reductions in exhaled nitric oxide (0.57-fold change, 95% CI 0.44-0.73; a 43% reduction, P < 0.001 and 0.65-fold change, 95% CI 0.47-0.91; a 35% reduction, P = 0.008, respectively); and peripheral eosinophils (-74 cells/microl, 95% CI -146 to -2; P = 0.020 and -77 cells/microl, 95% CI -140 to -14; P = 0.012, respectively). Montelukast further reduced exhaled nitric oxide (0.81-fold change, 95% CI 0.66-0.98; P = 0.028) with 400 microg HFA-BDP and eosinophils (-44 cells/microl, 95% CI -80 to -8; P = 0.012) with 800 microg CFC-BDP, but not vice versa.


CONCLUSIONS
Chlorofluorocarbon beclometasone dipropionate and HFA-BDP have differential effects on pulmonary and systemic inflammation, which dictate the additive effects of montelukast.
Menzies
D
D
Asthma and Allergy Research Group, University of Dundee, Dundee, UK.
Nair
A
A
Hopkinson
P
P
McFarlane
L
L
Lipworth
B J
BJ
D000085:Acetates / Q000627:therapeutic use; D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000737:chemistry*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D017402:Chlorofluorocarbons / Q000008:administration & dosage; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy; D009569:Nitric Oxide / Q000032:analysis; D010316:Particle Size; D011804:Quinolines / Q000627:therapeutic use; D013440:Sulfides; D005466:Fluorocarbons
D000085:Acetates; D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D001507:Beclomethasone; D017402:Chlorofluorocarbons; D003521:Cyclopropanes; D006845:Hydrocarbons, Fluorinated; D009569:Nitric Oxide; D011804:Quinolines; D013440:Sulfides; C093875:montelukast; C094049:apaflurane; D005466:Fluorocarbons