Effect of fluticasone and salmeterol on tracheal responsiveness to ovalbumin and lung inflammation, administrated during and after sensitization.
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ABSTRACT:
SUBMITTER: Gholamnezhad Z
PROVIDER: S-EPMC3916101 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Asthmatic airways are inflamed and undergo remodelling. Inhaled corticosteroids and long-acting ?2-agonist combinations are more effective than inhaled corticosteroid monotherapy in controlling disease exacerbations, but their effect on airway remodelling and inflammation remains ill-defined. This study evaluates the contribution of inhaled fluticasone and salmeterol, alone or combined, to the reversal of bronchial remodelling and inflammation. Severely asthmatic horses (6 horses/group) were treated with fluticasone, salmeterol, fluticasone/salmeterol, or with antigen avoidance for 12 weeks. Lung function, central and peripheral airway remodelling, and bronchoalveolar inflammation were assessed. Fluticasone/salmeterol and fluticasone monotherapy decreased peripheral airway smooth muscle remodelling after 12 weeks (p?=?0.007 and p?=?0.02, respectively). On average, a 30% decrease was observed with both treatments. In central airways, fluticasone/salmeterol reversed extracellular matrix remodelling after 12 weeks, both within the lamina propria (decreased thickness, p?=?0.005) and within the smooth muscle layer (p?=?0.004). Only fluticasone/salmeterol decreased bronchoalveolar neutrophilia (p?=?0.03) to the same extent as antigen avoidance already after 8 weeks. In conclusion, this study shows that fluticasone/salmeterol combination decreases extracellular matrix remodelling in central airways and intraluminal neutrophilia. Fluticasone/salmeterol and fluticasone monotherapy equally reverse peripheral airway smooth muscle remodelling.
| S-EPMC5562887 | biostudies-other
Project description:Clinical trials of a combination therapy of an inhaled corticosteroid, fluticasone propionate (FP), with a long-acting beta2-agonist, salmeterol (Sal), have demonstrated a greater improvement in lung function and in quality of life measures after the combination compared with either component of alone. In a subanalysis of the data of the TRISTAN study, Sal/FP reduced exacerbation rates in COPD patients with a baseline FEV1 < 50% of predicted. A combination therapy of budesonide and formoterol improved quality of life and FEV1, and reduced exacerbations better than either component alone. In studies of FP or of Sal/FP in COPD, there was a reduction in all-cause mortality by 25% relative to placebo. Sal/FP has anti-inflammatory effects in COPD airways. FP inhibits markers of systemic inflammation, and it is not known whether Sal/FP has an advantage over FP alone. While long-acting beta2-agonists such as Sal can be recommended for treatment of moderate COPD, addition of inhaled steroid therapy such as FP should be considered in more severe disease.
| S-EPMC2707153 | biostudies-other
Project description:Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD. However, the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known. This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol (FP/SAL) or SAL alone.Patients (n?=?639) aged ?40 years were randomized to either twice-daily inhaled FP/SAL 250/50 ?g or SAL 50 ?g. Primary, and secondary, endpoints were rates of recurrent severe, and moderate/severe, exacerbations of COPD. Lung function, health outcomes and levels of biomarkers of systemic inflammation were also assessed.There was no statistically significant treatment difference in rates of recurrent severe exacerbations (treatment ratio 0.92 [95% CI: 0.58, 1.45]) and moderate/severe exacerbations (0.82 [0.64, 1.06]) between FP/SAL and SAL in the intent-to-treat population. Pre-dose morning FEV1 change from baseline was greater (0.10 L [0.04, 0.16]) with FP/SAL than SAL. No treatment difference was seen for other endpoints including patient-reported health outcomes and biomarker levels for the full cohort.No significant treatment difference between FP/SAL and SAL was seen in COPD exacerbation recurrence for the complete cohort. Treatment benefit with FP/SAL over SAL (treatment ratio 0.68 [0.47, 0.97]) was seen in patients having FEV1???30% and prior exposure to ICS. No unexpected safety issues were identified with either treatment. Patients with the most severe COPD may be more refractory to treatment.ClinicalTrials.gov (identifier NCT01110200). This study was funded by GlaxoSmithKline (study number ADC113874).
| S-EPMC4176847 | biostudies-literature
Project description:The effects of adipose derived stromal cells (ASCs) were evaluated on tracheal responsiveness and biochemical parameters in guinea pigs model of chronic obstructive pulmonary disease (COPD). Thirty six guinea pigs were divided into 6 groups including: Control, COPD, COPD+intratracheal delivery of PBS (COPD+ITPBS), COPD+intravenous delivery of PBS (COPD+IVPBS), COPD+intratracheal delivery of ASCs (COPD+ITASC) and COPD+intravenous injection of ASCs (COPD+IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was then performed and after 14 days, tracheal responsiveness, concentration of interleukin-8 (IL-8) in serum and broncho-alveolar lavage fluid (BALF), as well as total and differential white blood cells (WBC) counts were evaluated. Tracheal responsiveness, total WBC counts, neutrophil and eosinophil percentage in BALF as well as concentration of IL-8 in serum and BALF significantly increased but lymphocyte percentage decreased in COPD compared to the control group (P<0.05 to p<0.001). Cell therapy was able to restore the tracheal hyper-responsiveness and the increased IL-8 concentration in serum and BALF of COPD-ITASC but not COPD-IVASC animals (P<0.05 for all cases). Total WBC in BALF also showed a significant decrease in both treated groups and the percentages of eosinophils, neutrophils and lymphocytes in BALF were reversed in COPD-ITASC compared to COPD-ITPBS animals (P<0.05 to P<0.001). Therefore, intratracheal cell therapy with ASC can decrease tracheal hyperresponsiveness and lung inflammation in cigarette smoke induced-COPD which may be helpful in attenuation of the severity of disease in patients suffering from COPD.
| S-EPMC4203716 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08-3.00 h, 0.03-0.10 h and 0.03-0.10 h, respectively) and were eliminated with mean half-lives of 9.29-10.44 h, 6.09-12.39 h and 0.25-47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250-750 µg and 50-150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.
| S-EPMC7042003 | biostudies-literature
Project description:The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients.The trial was a 12-week multicentre, randomised, double-blind, double dummy study; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 ?g or FP/S 500/50 ?g twice daily. The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre-dose in the first 30 minutes in forced expiratory volume in the first second (FEV1). Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St. George's Respiratory Questionnaire, six minute walking test and COPD exacerbations.BDP/FF was equivalent to FP/S in terms of TDI score and superior in terms of FEV1 change from pre-dose (p < 0.001). There were no significant differences between treatments in secondary outcome measures, confirming overall comparability in terms of efficacy and tolerability. Moreover, a clinically relevant improvement (>4 units) in SGRQ was detected in the BDP/FF group only.BDP/FF extrafine combination provides COPD patients with an equivalent improvement of dyspnoea and a faster bronchodilation in comparison to FP/S.ClinicalTrials.gov: NCT01245569.
| S-EPMC4008134 | biostudies-literature
Project description:BackgroundUmeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD). This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.MethodsPatients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg. Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.ResultsImprovements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001). UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL. Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George's Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks. The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.ConclusionsOnce-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.Trial registrationNCT01822899 Registration date: March 28, 2013.
| S-EPMC4545560 | biostudies-literature
Project description:BACKGROUND:Fluticasone propionate 50 ?g/salmeterol xinafoate 25 ?g (FP/SAL) is widely used in adults and children with asthma, but there is sparse information on its use in very young children. METHODS:This was a randomized, double-blind, multicentre, controlled trial conducted in children aged 8 months to 4 years. During a 2-week run-in period, they all received FP twice daily. At randomization, they commenced FP/SAL or FP twice daily for 8 weeks. All were then given FP/SAL only, in a 16-week open-label study continuation. Medications were inhaled through an AeroChamber Plus with attached face mask. The primary end-point was mean change in total asthma symptom scores from baseline to the last 7 days of the double-blind period. Analyses were undertaken in all children randomized to treatment and who received at least one dose of study medication. RESULTS:Three hundred children were randomized 1:1 to receive FP/SAL or FP. Mean change from baseline in total asthma symptom scores was -3.97 for FP/SAL and -3.01 with FP. The between-group difference was not statistically significant (P = 0.21; 95% confidence interval: -2.47, 0.54). No new safety signals were seen with FP/SAL. CONCLUSION:This is the first randomized, double-blind study of this size to evaluate FP/SAL in very young children with asthma. FP/SAL did not show superior efficacy to FP; no clear add-on effect of SAL was demonstrated. No clinically significant differences in safety were noted with FP/SAL usage.
| S-EPMC6850202 | biostudies-literature
Project description:BackgroundEndpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD. In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.MethodsData were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD. Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George's Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.ResultsUsing D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001). With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).ConclusionThese data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD. Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population.
| S-EPMC5422319 | biostudies-literature
Project description:BackgroundRecent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefore sought to determine whether MSCs are present in the lungs of ovalbumin (OVA)-sensitized and challenged mice, a model of allergic airways disease.MethodsBalb/c mice were sensitized and challenged with PBS or OVA over a 25 day period. Flow cytometry as well as colony forming and differentiation potential were used to analyze the emergence of MSCs along with gene expression studies using immunochemical analyses, quantitative polymerase chain reaction (qPCR), and gene expression beadchips.ResultsA CD45-negative subset of cells expressed Stro-1, Sca-1, CD73 and CD105. Selection for these markers and negative selection against CD45 yielded a population of cells capable of adipogenic, osteogenic and chondrogenic differentiation. Lungs from OVA-treated mice demonstrated a greater average colony forming unit-fibroblast (CFU-F) than control mice. Sorted cells differed from unsorted lung adherent cells, exhibiting a pattern of gene expression nearly identical to bone marrow-derived sorted cells. Finally, cells isolated from the bronchoalveolar lavage of a human asthma patient showed identical patterns of cell surface markers and differentiation potential.ConclusionsIn summary, allergen sensitization and challenge is accompanied by an increase of MSCs resident in the lungs that may regulate inflammatory and fibrotic responses.
| S-EPMC2949728 | biostudies-literature