Effects Of Fluticasone Furoate Research Articles

The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro

BackgroundAirway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.MethodsWe investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses.ResultsIL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction.ConclusionThis study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.

A randomized, double-blind, placebo-controlled, parallel-group study of once-daily inhaled fluticasone furoate on the hypothalamic\u2013pituitary\u2013adrenocortical axis of children with asthma

BackgroundTo evaluate the effects of fluticasone furoate on the hypothalamic–pituitary–adrenocortical axis, and the safety and tolerability of fluticasone furoate treatment in children with asthma.MethodsThis was a randomized, double-blind, placebo-controlled, multicenter, stratified, parallel-group, non-inferiority study of fluticasone furoate 50 µg inhalation powder administered once daily. The study enrolled children (aged 5–11 years inclusive) with a documented diagnosis of asthma for ≥ 6 months and a Childhood Asthma Control Test score of > 19. After a 7–14-day run-in period, eligible subjects were stratified by age and randomized to fluticasone furoate 50 µg once daily or placebo once daily via ELLIPTA for 6 weeks. The primary endpoint was the change from baseline (expressed as a ratio) in 0–24-h weighted mean serum cortisol at the end of the treatment period.ResultsFifty-six randomized subjects received fluticasone furoate 50 µg once daily and 55 received placebo. The primary analysis was performed in the serum cortisol population (n = 104) and demonstrated that fluticasone furoate 50 µg once daily was non-inferior to placebo (ratio = 0.93; 95% confidence interval 0.8096, 1.0620), as the lower limit of the 95% confidence interval for the geometric mean treatment ratio of fluticasone furoate 50 µg once daily versus placebo was greater than 0.80. Findings from the intent-to-treat population (n = 111) were similar.ConclusionsSix weeks of treatment with inhaled fluticasone furoate 50 µg once daily had no clinically relevant effect on the hypothalamic–pituitary–adrenocortical axis function of children, as measured by 24-h serum cortisol profiles. The primary analysis showed that fluticasone furoate 50 µg once daily was non-inferior to placebo. Fluticasone furoate 50 µg once daily was well tolerated and no new safety concerns emerged during the study.Trial registrationThis study is registered in ClinicalTrials.gov (NCT02483975). Date of submission: 25 June 2015.

Effect of Fluticasone Furoate on Methacholine Challenge

Effect of Fluticasone Furoate on Methacholine Challenge

Effect of Fluticasone Furoate and Vilanterol on Exacerbations of Chronic Obstructive Pulmonary Disease in Patients with Moderate Airflow Obstruction

Inhaled corticosteroids have been shown to decrease exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Their effects in patients with milder airflow obstruction remain unclear. This was an analysis of exacerbations in the SUMMIT (Study to Understand Mortality and Morbidity) study. In a double-blind, randomized controlled trial, once-daily inhaled placebo, fluticasone furoate (FF; 100 μg), vilanterol (VI; 25 μg), or the combination of FF/VI was administered. The primary outcome was all-cause mortality. Exacerbations of COPD were an additional predefined endpoint. A total of 1,368 centers in 43 countries and 16,485 patients with moderate COPD and heightened cardiovascular risk were included in the study. Compared with placebo, FF/VI reduced the rate of moderate and/or severe exacerbations by 29% (95% confidence interval [CI], 22-35; P < 0.001) and the rate of hospitalized exacerbations by 27% (95% CI, 13-39; P < 0.001). These relative effects were similar regardless of whether subjects had a history of exacerbation in the year before the study or an FEV1 <60% or ≥60% of predicted. The number needed to treat was not influenced by baseline FEV1 but was influenced by the history of exacerbations. FF/VI also reduced the rate of exacerbations treated with corticosteroids alone or with corticosteroids and antibiotics but not the rates of those treated with antibiotics alone. Patients with moderate chronic airflow obstruction experienced a reduction in exacerbations with FF/VI compared with placebo, irrespective of a history of exacerbations or baseline FEV1. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676; GSK Study number 113782).

Effects of Fluticasone Furoate on Clinical and Immunological Outcomes (IL-17) for Patients With Nasal Polyposis Naive to Steroid Treatment.

We investigated the effect of topical steroids on clinical outcomes and related immune response of chronic rhinosinusitis with nasal polyp (CRSwNP) patients and in eradicating some polyps. We want to explore a new potential mechanism linked to Th-17 cells. Prospective, double-blind, placebo-controlled studies with 24 allergic and nonallergic patients were randomized to either placebo or fluticasone furoate for 12 weeks. Assessment of clinical response, endoscopic score with biopsies of the inferior turbinate, and polyps before and after treatment were performed. Biopsies were stained for T-cells, eosinophils, neutrophils, and IL-17A/F. Steroid treatment improved the mean symptoms scores from 7.12 to 4.02 (P < .01) and the polyp score from 5.13 to 3.31 (P < .05), but the comparison with placebo was not statistically significant in nonallergics due to insufficient study power. Steroid treatment decreased eosinophil counts on allergics but not neutrophils or T-cells. The IL-17A/F expression was higher in nonallergics with high neutrophil counts and was inclined by steroids. Compared to baselines, IL-17 cells were significantly less in allergic individuals and were not observed in allergics and with high neutrophil counts. Topical steroids were more effective on certain nasal polyp phenotypes. Identification of polyp phenotype might be essential to ensure a better therapeutic response to intranasal corticosteroids.

Effect of Fluticasone Furoate in Patients with Japanese Cedar Pollinosis

Effect of Fluticasone Furoate in Patients with Japanese Cedar Pollinosis

Effect of Fluticasone Furoate in Patients with Japanese Cedar Pollinosis

Effect of Fluticasone Furoate in Patients with Japanese Cedar Pollinosis

Effect of Fluticasone Furoate on Interleukin 6 Secretion From Adenoid Tissues in Children With Obstructive Sleep Apnea

To determine the effect of intranasal corticosteroid therapy on T-regulatory cells and other inflammatory cytokines in adenoid tissues in children with obstructive sleep apnea syndrome. Randomized, prospective, exploratory study. Academic pediatric otolaryngology practice in a tertiary care children's hospital. Participants included 24 children between the ages of 2 and 12 years who were undergoing adenotonsillectomy for polysomnogram-documented obstructive sleep apnea syndrome. Children were randomized to either no treatment (n = 13) or treatment with fluticasone furoate nasal spray, 55 μg/nostril daily (n = 11), for 2 weeks before adenotonsillectomy. Adenoid tissue was obtained at the time of the procedure. The number of tissue T-regulatory cells, as determined by staining with FOXP3, CD4, and CD25, was the primary outcome measure. Staining for interleukin (IL)-10 and transforming growth factor-β protein by immunohistochemistry, and adenoid mononuclear cell spontaneous and induced release of cytokines (IL-10, IL-6, IL-12, IL-13, tumor necrosis factor, and transforming growth factor β) were secondary outcomes. Cells isolated from fluticasone furoate nasal spray-treated adenoid tissue released significantly less IL-6 spontaneously as well as upon stimulation with anti-CD3 monoclonal antibody (P = .05) compared with nontreated adenoid tissue. There were no significant differences in the number of CD4/FOXP3-, CD25/FOXP3-, or transforming growth factor β-positive cells. Intensity of staining for IL-10 was also comparable between the groups. In this study, we show reduction of IL-6, a proinflammatory cytokine, in adenoid tissue obtained from children with obstructive sleep apnea syndrome treated with fluticasone furoate nasal spray. This reduction could contribute to the clinical efficacy of this class of medications in the treatment of childhood obstructive sleep apnea syndrome.