Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice

Division of Allergy and Immunology, Joy McCann Culverhouse Airway Disease Research Center, University of South Florida College of Medicine and James A, Haley VA Hospital, Tampa, FL, USA.
Virology Journal (Impact Factor: 2.18). 02/2006; 3(1):32. DOI: 10.1186/1743-422X-3-32
Source: PubMed


Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation.
Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined.
The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal.
Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.

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    • "The combination of long acting í µí»½-agonists (LABA) and inhaled corticosteroid is more effective in treatment of asthma than increasing the dose of inhaled corticosteroid (ICS) [5] [6] [7] [8]. Suppression of the inflammatory process by LABA is also indicated in in vitro and in vivo animal studies [9] [10] [11]. Treatment with fluticasone propionate (FP) and salmeterol (SM) improved allergen-induced airway remodeling [12] and was able to control peripheral blood Tcell activation in asthmatic patients more efficiently [12]. "
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    ABSTRACT: The effect of duration of administration of fluticasone propionate and salmeterol on tracheal responsiveness to ovalbumin and total and differential white blood cell in sensitized guinea pig was examined. Six groups of guinea pigs (n = 7) were sensitized to ovalbumin. Three groups of them were subjected to inhaled fluticasone propionate and salmeterol, one group during sensitization (A), one group after that (for 18 days, B), and the other one during sensitization but with 18 days delay before measurements (C). Three other groups were treated with placebo in the same manner. The tracheal responsiveness to ovalbumin and total and differential white blood cells of three placebo groups were significantly higher than those of control group (P < 0.001 for all cases). Tracheal responsiveness to ovalbumin and total and differential white blood cell in treated groups with fluticasone propionate and salmeterol were significantly decreased compared to those of placebo groups (nonsignificant to P < 0.001). The improvement in all variables in treatment groups A and C were more pronounced than group B. The results showed that fluticasone propionate and salmeterol had a prevention effect on tracheal hyperresponsiveness to ovalbumin and lung inflammation which was more pronounced when administered during than after sensitization.
    Full-text · Article · Jan 2014 · The Scientific World Journal
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    • "Additional benefit can be obtained with the regular use of combinations of ICS and LABA. Besides LTRA, LABAs also have antiviral as well as bronchodilator effects.26 In the present study, approximately one-half of the patients in both LTRA+ and LTRA− groups had used LABAs, and the incidences of URIs, acute asthma exacerbations without URI, and URI-induced acute asthma exacerbations were comparable between those taking and not taking LABAs (data not shown). "
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    ABSTRACT: Upper respiratory tract infections (URIs) represent the most frequent cause of acute asthma exacerbations. It has yet to be determined whether leukotriene receptor antagonist (LTRA) treatment prevents URI-induced acute asthma exacerbations in adults. The objective of the present study was to evaluate the preventive effects of LTRA treatment on URI-induced acute asthma exacerbations. The incidences of URI alone, acute asthma exacerbation without URI, and URI-induced acute asthma exacerbation were determined retrospectively by analyzing diary and medical records of 321 adult asthmatic patients (mean age, 56.3 ± 17.2 years; male/female ratio, 117:204) over 1 year. Results were compared between patients who had been taking an LTRA (n = 137) and those who had never taken any LTRA (n = 184) during the study periods. Significantly fewer URIs alone and acute asthma exacerbations without URI occurred in patients with than in those without prophylactic daily use of LTRA. LTRA treatment significantly reduced the durations of URIs alone and of total acute asthma exacerbations, as well as the incidence of mild exacerbations of asthma. In contrast, in patients with URI-induced acute asthma exacerbations, LTRA treatment failed to significantly reduce the interval between URI onset and acute asthma exacerbation, as well as the duration and severity of both URIs and acute asthma exacerbations. Use of an LTRA for adult asthmatic patients appears to reduce the incidences of URIs alone and acute asthma exacerbations without URI, but it failed to prevent URI-induced acute asthma exacerbations once a URI occurred.
    Full-text · Article · Mar 2013
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    • "Significantly, these two drugs acted synergistically when used in combination (Volonaki et al., 2006). Fluticasone and salmeterol have also been shown to inhibit, in an additive or even synergistic manner, rhinovirus-induced chemokine (RANTES, IL-8, IP-10 (interferon-g-inducible protein of 10 kDa; aka CXCL10), ENA-78 (epithelial cell-derived neutrophil-activating peptide of 78 amino acids, aka CXCL5)) release from BEAS-2B cells (Edwards et al., 2006), and this enhanced efficacy seemingly can be extrapolated to in vivo systems (Singam et al., 2006). Indeed, the AHR and inflammation in sensitized mice exposed to respiratory syncytial virus is more effectively suppressed by the combination of salmeterol and fluticasone than either drug alone. "
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    ABSTRACT: There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS) -- i.e. glucocorticoid -- and an inhaled long-acting beta(2)-adrenoceptor agonist (LABA) is superior to each component administered as a monotherapy alone in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet 2003, 361: 449-456; N Engl J Med 2007, 356: 775-789) reporting for the 'TRial of Inhaled STeroids ANd long-acting beta(2)-agonists (TRISTAN)' and 'TOwards a Revolution in COPD Health (TORCH)' international study groups also demonstrated the superior efficacy of LABA/ICS combination therapies over ICS alone in the clinical management of chronic obstructive pulmonary disease. This finding has been independently confirmed indicating that the therapeutic benefit of LABA/ICS combination therapies is not restricted to asthma and may be extended to other chronic inflammatory diseases of the airways. Despite the unquestionable benefit of LABA/ICS combination therapies, there is a vast gap in our understanding of how these two drugs given together deliver superior clinical efficacy. In this article, we review the history of LABA/ICS combination therapies and critically evaluate how these two classes of drugs might interact at the biochemical level to suppress pro-inflammatory responses. Understanding the molecular basis of this fundamental clinical observation is a Holy Grail of current respiratory diseases research as it could permit the rational exploitation of this effect with the development of new 'optimized' LABA/ICS combination therapies.
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