A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma

• Published in: Respiratory medicine Vol. 101; no. 6; pp. 1218 - 1228
• Main Authors: Fardon, Tom, Haggart, Kay, Lee, Daniel K.C, Lipworth, Brian J
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.06.2007; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Airway management; Albuterol - analogs & derivatives; Albuterol - therapeutic use; Androstadienes - administration & dosage; Anti-cholinergic; Asthma; Asthma - drug therapy; Asthma - physiopathology; Biological and medical sciences; Body plethysmography; Breath Tests - methods; Bronchodilation; Bronchodilator Agents - therapeutic use; Chronic obstructive pulmonary disease, asthma; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug dosages; Drug therapy; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume - drug effects; Glucocorticoids - administration & dosage; Humans; Male; Medical sciences; Middle Aged; Nitric Oxide - metabolism; Plethysmography, Whole Body; Pneumology; Pulmonary/Respiratory; Quality of Life; Salmeterol Xinafoate; Scopolamine Derivatives - therapeutic use; Tiotropium Bromide; Treatment Outcome; Vital Capacity - drug effects; United Kingdom > UK; Anti-cholinergic; Bronchodilation; Body plethysmography; Concept; Lung disease; Respiratory disease; Tiotropium bromide; Salmeterol; Exploration; Fluticasone; Posology; Asthma; Bronchus disease; Obstructive pulmonary disease; Severe; Body; Dose; Plethysmography; Pneumology
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2006.11.001

Summary We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV1 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 μg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 μg BD/salmeterol 100 μg BD/HFA-tiotropium bromide18 μg od; or (b) fluticasone propionate 500 μg BD/salmeterol 100 μg BD matched placebo. Measurements of spirometry and body plethysmography were made. Adding salmeterol to half the dose of fluticasone led to a mean improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0–69.0) l/min [ p <0.05]; and RAW of 0.98 (0.14–1.8) cm H2 O/l/s [ p <0.05]. Adding salmeterol/tiotropium produced similar improvements in PEF and RAW, but also improved FEV1 by 0.17 (0.01–0.32) l [ p <0.05]; FVC 0.24 (0.05–0.43) l [ p <0.05] and reduced exhaled NO by 2.86 (0.12–5.6) ppb [ p <0.05]. RV and TLC were not altered by either treatment; there were no significant changes in symptoms or quality of life compared with baseline. Addition of salmeterol/tiotropium to half the dose of fluticasone afforded small, but significant improvements in pulmonary function. These effects were not associated with commensurate changes in subjective symptoms or quality of life.