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

Abstract

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.

Therapeutic effects of co-inhaled roflumilast or formoterol and fluticasone on asthma-induced ultrastructural changes in murine airways

“…Failure of long acting β2 agonists (formoterol) to improve remodeling in the current study agrees with a previous study which showed that in OVA -sensitized and -challenged BALB/c mice, LABA treatment (salmeterol) exaggerated airway inflammation, remodeling, and hyperresponsiveness due to mucus metaplasia, while fluticasone separately or combined with salmeterol reduced airway inflammation and remodeling [10].Moreover, aerosolized combined salmeterol and fluticasone in rats reversed goblet cell hyperplasia, but increased fibronectin and collagen in the airway wall [23]. In addition, in asthmatic patients adding salmeterol to ICS reduced airway muscular tone and improved expiratory flows, but exerted a little effect on remodeling shown by decreasing number of vessels in the airway lamina propria [24].…”

Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone

“…Treatment with fluticasone during this last 2 weeks of allergen challenge inhibits the additional increase in collagen deposition [43]. It is of interest that combining salmeterol with fluticasone during the last 2 weeks of this rat asthma model results in increased airway wall thickness and deposition of collagen and fibronection in the lungs [44].…”

Comparison of Leukotriene Receptor Antagonist and Theophylline in Addition to Inhaled Corticosteroid in Adult Asthma: A Meta-Analysis

“…However, LABA is not primarily an antiinfl ammatory drug, and does not appear to have any clinically important anti-infl ammatory or proinfl ammatory effect (Sindi et al, 2009). Furthermore, the effect of LABA on airway remodeling remains controversial (Orsida et al, 2001;Vanacker et al, 2002). Thus, LTRA or theophylline as the add-on medication to ICS should be reconstructed.…”