Effect of Combining Salmeterol and Fluticasone on the Progression of Airway Remodeling

• Published in: American journal of respiratory and critical care medicine 2002-10, Vol.166 (8), p.1128-1134
• Main Authors: Vanacker, Nele J, Palmans, Els, Pauwels, Romain A, Kips, Johan C
• Format: Article
• Language: English
• Subjects: Administration, Topical; Adrenergic beta-Agonists - administration & dosage; Adrenergic beta-Agonists - pharmacology; Albuterol - administration & dosage; Albuterol - analogs & derivatives; Albuterol - pharmacology; Androstadienes - administration & dosage; Androstadienes - pharmacology; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Bronchi - metabolism; Bronchi - pathology; Bronchoalveolar Lavage Fluid - cytology; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - pharmacology; Cell Count; Collagen - metabolism; Drug Combinations; Eosinophils - pathology; Fibronectins - metabolism; Fluticasone; Glucocorticoids; Goblet Cells - pathology; Leukocyte Count; Lung - pathology; Male; Medical sciences; Neutrophils; Ovalbumin - immunology; Pharmacology. Drug treatments; Rats; Rats, Inbred BN; Respiratory Hypersensitivity - pathology; Respiratory system; Salmeterol Xinafoate
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200203-191OC

In subjects insufficiently controlled with low to moderate doses of inhaled corticosteroids, adding beta-agonists is clinically more beneficial than increasing the dose of inhaled corticosteroids. In the present study, we investigated the effect of adding salmeterol to fluticasone on allergen-induced airway inflammation and remodeling. Sensitized rats, in which characteristics of remodeling had been induced by ovalbumin exposure every 2 days from Days 14 to 28, were further exposed to ovalbumin or PBS from Days 29 to 42. During the last 2 weeks, before allergen exposure, rats were treated with aerosolized fluticasone propionate (10 mg), salmeterol (1 mg), salmeterol (1 mg) plus fluticasone propionate (10 mg), or placebo. After 4 weeks of ovalbumin exposure, the airways showed inflammatory changes, goblet cell hyperplasia, and enhanced fibronectin and collagen deposition. Salmeterol in monotherapy decreased bronchoalveolar lavage fluid eosinophil number but had no influence on structural changes. Combining salmeterol with fluticasone propionate counteracted goblet cell hyperplasia, but increased the amount of fibronectin and collagen in the airway wall. These effects of salmeterol did not influence airway responsiveness. We conclude that the combination of salmeterol and fluticasone propionate enhances aspects of allergen-induced airway remodeling. This is not accompanied by changes in airway responsiveness.