Step-down therapy with low-dose fluticasone-salmeterol combination or medium-dose hydrofluoroalkane 134a-beclomethasone alone.
BACKGROUND
Options for step-down therapy include use of inhaled corticosteroids alone or in combination with a long-acting beta2-agonist.


OBJECTIVE
We sought to evaluate step-down therapy with a fluticasone propionate-salmeterol (FP-SM) combination administered through a dry powder inhaler (DPI; Advair Diskus) versus a medium dose of hydrofluoroalkane 143a-beclomethasone dipropionate (HFA-BDP) administered through a breath-actuated pressurized metered-dose inhaler (QVAR Autohaler).


METHODS
Thirty-nine patients with uncontrolled moderate-to-severe asthma were treated with 1000 microg of DPI-administered BDP twice daily (DPI-BDP) for 4 weeks and then randomized to 200 microg of HFA-BDP twice daily (n = 20) or 100 microg of FP and 50 microg of SM twice daily (FM-SM; n = 19) for 8 weeks in a double-blind, double-dummy, parallel-group design. We measured the provocative dose of methacholine producing a 20% fall in FEV1 (methacholine PD20) as the primary outcome, with secondary outcomes being lung function, surrogate inflammatory markers, diary card responses, quality of life, and safety.


RESULTS
There was a 0.9 (95% confidence interval, 0.5-1.2) doubling dose improvement in methacholine PD20 comparing asthma before versus after DPI-BDP. HFA-BDP maintained this improvement, whereas FP-SM produced a further significant improvement, amounting to a 1.1 (95% confidence interval, 0.2-2.1) doubling dose difference at 8 weeks for FP-SM versus HFA-BDP. Effects on FEV1, peak expiratory flow, and quality of life (symptoms and emotions) were similar to those on methacholine PD20, with a significant difference between FP-SM and HFA-BDP. Suppression of plasma and urinary cortisol and serum osteocalcin levels occurred with DPI-BDP, but values returned to baseline levels within 1 month of HFA-BDP or FP-SM administration.


CONCLUSIONS
After high-dose inhaled corticosteroid, stepping down with the combination inhaler conferred further improvements in bronchoprotection, bronchodilatation, and clinical control, but not inflammatory markers, compared with that seen with a medium dose of inhaled corticosteroid.
Fowler
Stephen J
SJ
Asthma and Allergy Research Group, Department of Clinical Pharmacology and Therapeutic, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
Currie
Graeme P
GP
Lipworth
Brian J
BJ
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068298:Fluticasone; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011788:Quality of Life; D012129:Respiratory Function Tests; D000068299:Salmeterol Xinafoate; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000420:Albuterol; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001507:Beclomethasone; D001993:Bronchodilator Agents; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; D000068299:Salmeterol Xinafoate; C094049:apaflurane; D005466:Fluorocarbons