Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma.
OBJECTIVE
Inhalers combining long acting beta2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma.


METHODS
Twenty-nine patients with mean FEV1 (+/- SEM) of 78 +/- 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 microg + formoterol 12 microg (BUD + FM) combination twice daily followed by 1 week of BUD 400 microg alone twice daily, or 4 weeks of fluticasone propionate 250 microg + salmeterol 50 microg (FP + SM) combination twice daily followed by 1 week of FP 250 microg alone twice daily. Measurements were made at baseline and following each randomized treatment.


RESULTS
FEV1 increase from pretreatment baseline as mean (+/- SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 +/- 1%) vs BUD (2 +/- 1%), and for FP + SM (8 +/- 1%) vs FP (2 +/- 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 +/- 1%), BUD (24 +/- 1%), FP + SM (23 +/- 1%) and FP (23 +/- 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 +/- 35.5) vs BUD (281.1 +/- 52.8), and with FP + SM (553.1 +/- 34.1) vs FP (368.3 +/- 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments.


CONCLUSIONS
Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.
Lee
Daniel K C
DK
Asthma & Allergy Research Group, Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY.
Jackson
Catherine M
CM
Currie
Graeme P
GP
Cockburn
Wendy J
WJ
Lipworth
Brian J
BJ
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001980:Bronchi / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D000068299:Salmeterol Xinafoate
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000068759:Formoterol Fumarate