Combination Of Fluticasone Propionate Research Articles

Pharmacokinetic Models for Inhaled Fluticasone Propionate and Salmeterol Xinafoate to Quantify Batch-to-Batch Variability.

Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate (FP) and salmeterol xinafoate (SX). However, the pharmacokinetics (PK) batch-to-batch variability of the reference-listed drug (RLD) hindered its generic product development. This work developed the PK models for inhaled FP and SX that could represent potential batch variability. Two batches each of the reference and the test product (R1, R2, T1, T2) of Advair Diskus (100μg FP/50μg SX inhalation) were administered to 60 healthy subjects in a 4-period, 4-sequence crossover study. The failure of the bioequivalence (BE) between R1 and R2 confirmed the high between-batch variability of the RLD. Non-linear mixed effect modeling was used to estimate the population mean PK parameters for each batch. For FP, a 2-compartment model with a sequential dual zero-order absorption best described the PK profile. For SX, a 2-compartment model with a first-order absorption model best fit the data. Both models were able to capture the plasma concentration, the maximum concentration, and the total exposure (AUCinf) adequately for each batch, which could be used to simulate the BE study in the future. In vitro properties were also measured for each batch, and the batch with a higher fraction of the fine particle (diameter < 1µm, < 2µm) had a higher AUCinf. This positive correlation for both FP and SX could potentially assist the batch selection for the PK BE study.

Nasal immune gene expression in response to azelastine and fluticasone propionate combination or monotherapy.

BackgroundThe combination of the antihistamine azelastine (AZE) with the corticosteroid fluticasone propionate (FP) in a single spray, has been reported to be significantly more effective at reducing allergic rhinitis (AR) symptoms than treatment with either corticosteroid or antihistamine monotherapy. However, the biological basis for enhanced symptom relief is not known. This study aimed to compare gene expression profiles (760 immune genes, performed with the NanoString nCounter) from peripheral blood and nasal brushing/lavage lysate samples in response to nasal spray treatment.MethodsModerate/severe persistent dust mite AR sufferers received either AZE (125 μg/spray) nasal spray (n = 16), FP (50 μg/spray) nasal spray (n = 14) or combination spray AZE/FP (125 μg AZE and 50 μg FP/spray) (n = 14) for 7 days, twice daily. Self‐reported symptom questionnaires were completed daily for the study duration. Gene expression analysis (760 immune genes) was performed with the NanoString nCounter on purified RNA from peripheral blood and nasal brushing/lavage lysate samples.ResultsIn nasal samples, 206 genes were significantly differentially expressed following FP treatment; 182 genes downregulated (−2.57 to −0.45 Log2 fold change [FC]), 24 genes upregulated (0.49–1.40 Log2 FC). In response to AZE/FP, only 16 genes were significantly differentially expressed; 10 genes downregulated (−1.53 to −0.58 Log2 FC), six genes upregulated (1.07–1.62 Log2 FC). Following AZE treatment only five genes were significantly differentially expressed; one gene downregulated (−1.68 Log2 FC), four genes upregulated (0.59–1.19 Log2 FC). Immune gene changes in peripheral blood samples following treatment were minimal. AR symptoms improved under all treatments, but improvements were less pronounced following AZE treatment.ConclusionAZE/FP, FP, and AZE had diverse effects on immune gene expression profiles in nasal mucosa samples. The moderate number of genes modulated by AZE/FP indicates alternative pathways in reducing AR symptoms whilst avoiding extensive local immune suppression.

In Vitro Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles.

Background: Wixela Inhub (trademarks of Viatris, Inc.) is a dry powder inhaler (DPI) that delivers a fixed-dose combination of fluticasone propionate and salmeterol and is approved as a generic equivalent to Advair Diskus (trademarks of GlaxoSmithKline plc) for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The dosing performance of DPIs is dependent on the patient's inspiratory capability, which may be impacted in disease populations such as those with severe COPD. The objective of this study was to evaluate the in vitro dose delivery of fluticasone propionate and salmeterol from the Inhub inhaler with in vivo inhalation profiles of severe COPD patients, using two types of breathing simulator with different modes of operation. Materials and Methods: Two breathing simulators (Si-Plan and Copley BRS3100) were used with United States Pharmacopoeia (USP) <601> apparatus 5 (Next Generation Impactor and accessories) to measure the total emitted dose and fine particle mass of fluticasone propionate and salmeterol for Wixela Inhub (250/50 mcg) using 13 severe COPD patient inhalation profiles. Results: Wixela Inhub demonstrated low flow dependency across the range of COPD patient profiles tested (peak inspiratory flow rate 60.8-84.9 L minute-1), when assessed by total emitted dose and fine particle mass. The results were similar to literature results reported for fluticasone propionate from the Diskus inhaler, tested using a proprietary breathing simulator and Andersen Cascade Impactor. Comparison between the breathing simulators showed no significant difference in fluticasone propionate results, but a small difference was observed between the breathing simulators for salmeterol total emitted dose and fine particle mass. Conclusions: This study demonstrates that severe COPD patients are likely to achieve a consistent inhaled dose from Wixela Inhub, with low flow dependency observed within this patient population. In addition, both breathing simulators, which differ significantly in design, produced similar results for fluticasone propionate, but yielded slightly (but statistically significant) different results for salmeterol.

A Single Inhaler Combining a Corticosteroid and Long-Acting Beta-2 Agonist for Maintenance with Additional Doses for Reliever Therapy (SMART): Obstacles for Asthma Patients in the USA.

A Single Inhaler Combining a Corticosteroid and Long-Acting Beta-2 Agonist for Maintenance with Additional Doses for Reliever Therapy (SMART): Obstacles for Asthma Patients in the USA.

A generic fluticasone propionate and salmeterol dry powder inhaler: Evidence of usability, function, and robustness.

Background: A generic combination of fluticasone propionate and salmeterol xinafoate inhalation powder in a premetered, multidose, nonreusable inhaler was recently approved. Objective: To assess the performance of the generic device. Methods: Findings from three studies with regard to device usability, function, and robustness were reviewed. Results: In a study to assess device function in patients and healthy volunteers, the generic device was successfully used by patients with asthma and chronic obstructive pulmonary disease who were either dry powder inhaler users or dry powder inhaler-naive, even though they were not trained beyond being provided the instructions for use. In a study to measure inhaled flow rates generated by patients and healthy volunteers, the generic device consistently simulated the delivery of a full dose of drug, even to patients with severe respiratory disease and reduced inspiratory flow rates. Although the generic device had a slightly higher airflow resistance, this study demonstrated that this difference did not result in any clinically meaningful differences in terms of drug delivery. Pressure drop, a key parameter that drives the fluidization and aerosolization of the powder dose, was found to be comparable between the devices. In an open-label study, the generic device met all U.S. Food and Drug Administration specifications for device robustness after 21.5 days of twice-daily dosing via oral inhalation among 111 participants with asthma or chronic obstructive pulmonary disease. All inhalers tested demonstrated conformity with a pharmacopeia with respect to key quality parameters (assay, delivered dose uniformity, aerodynamic size distribution). There was no evidence of chemical degradation of the active ingredients, nor of microbial or water ingress into the powder, as a result of inhaler use.

Effect of nebulized formoterol, ipratropium bromide, and furosemide in combination with fluticasone propionate on arterial blood gases of premature calves with respiratory distress syndrome

The purpose of this study was to determine the clinical effect of nebulized formoterol (FM), ipratropium bromide (IB) and furosemide (FS) with a combination of fluticasone propionate (FP) on the lung function in premature calves with Respiratory Distress Syndrome (RDS). Thirty-six premature calves with RDS were divided into six groups. All groups received the standard treatment, including oxygen and support treatment. The first group (D1) took the standard treatment. The following combinations of nebulized drugs were used: FP for D2, FP+FM for D3, FP+IB for D4, FP+FS for D5, and FP+IB+ FM+FS for D6. The treatment period (72 h) involved the application of FM (15 µg totally/12 h), IB (2 µg/kg/12 h), FS (1 mg/kg/12 h) and FP (15 µg/kg/12 h) for five minutes. A significant increase in blood pH, PaO 2 , SatO 2 and a decrease in PaCO 2 and lactate were seen in all groups that received nebulized treatment. However, in the D1, a statistical difference was observed only in PaCO 2 . D6 showed the highest PaO 2 andlowest PaCO 2 values amongst all the groups at the 72 nd h. No statistical difference was observed between the NG. Nebulized FM, IB and FS with FP combination in premature calves with RDS, in addition to the standard treatment showed a significant curative effect on lung function.

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study

ABSTRACTBackground: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta2-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years. Objective: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age. Methods: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records. Results: The children had previously received short-acting β2-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group. Conclusions: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.

Comparison of fluticasone/formoterol with budesonide/formoterol pMDI in adults with moderate to severe persistent asthma: Results from a 12-week randomized controlled trial

BackgroundCombination therapy of inhaled corticosteroid/long acting β2-agonist (ICS/LABA) is the cornerstone of managing asthmatics who are uncontrolled with low-medium dose of ICS. The novel ICS/LABA combination of fluticasone propionate and formoterol (flu/form) provides potent anti-inflammatory and rapid bronchodilatory effect.This randomized, multi-centre, double-blind study compared the efficacy and safety of flu/form (125/6 mcg BD; Maxiflo®) with the well-established budesonide/formoterol combination (bud/form 200/6 mcg BD), both delivered through a pressurized metered dose inhaler (pMDI) in patients with moderate to severe persistent asthma over 12 weeks. MethodsThis study enrolled patients between 18 and 65 years. The primary end-point was to demonstrate non-inferiority for the mean change in the pre-dose morning peak expiratory flow values (PEF). The secondary end-points included lung function assessments, number of symptom-free days and nights, rescue medication use, day-and night-time symptom scores and safety evaluation. ResultsTwo hundred and thirty-two patients were randomized to either flu/form (n = 117) or bud/form (n = 115). At the end of 12 weeks, flu/form was non-inferior to bud/form with regards to the primary end-point of morning PEF (48.07 L/min vs. 49.03 L/min, p > 0.05). These improvements were statistically significant (p < 0.0001) vs baseline. Similar improvements were observed between the two groups for secondary efficacy end-points including FEV1, symptom-free nights, rescue medication use, day-and night-time symptom scores (p > 0.05). Flu/form exhibited a safety profile comparable to that of bud/form. ConclusionFluticasone/formoterol combination administered through a pMDI is as efficacious and well-tolerated as budesonide/formoterol and offers a new therapeutic option for patients with moderate to severe persistent asthma.

Formoterol and fluticasone propionate combination improves histone deacetylation and anti-inflammatory activities in bronchial epithelial cells exposed to cigarette smoke

BackgroundThe addition of long-acting beta2-agonists (LABAs) to corticosteroids improves asthma control. Cigarette smoke exposure, increasing oxidative stress, may negatively affect corticosteroid responses. The anti-inflammatory effects of formoterol (FO) and fluticasone propionate (FP) in human bronchial epithelial cells exposed to cigarette smoke extracts (CSE) are unknown. AimsThis study explored whether FP, alone and in combination with FO, in human bronchial epithelial cellline (16-HBE) and primary bronchial epithelial cells (NHBE), counteracted some CSE-mediated effects and in particular some of the molecular mechanisms of corticosteroid resistance. Methods16-HBE and NHBE were stimulated with CSE, FP and FO alone or combined. HDAC3 and HDAC2 activity, nuclear translocation of GR and NF-κB, pERK1/2/tERK1/2 ratio, IL-8, TNF-α, IL-1β mRNA expression, and mitochondrial ROS were evaluated. Actin reorganization in neutrophils was assessed by fluorescence microscopy using the phalloidin method. ResultsIn 16-HBE, CSE decreased expression/activity of HDAC3, activity of HDAC2, nuclear translocation of GR and increased nuclear NF-κB expression, pERK 1/2/tERK1/2 ratio, and mRNA expression of inflammatory cytokines. In NHBE, CSE increased mRNA expression of inflammatory cytokines and supernatants from CSE exposed NHBE increased actin reorganization in neutrophils. FP combined with FO reverted all these phenomena in CSE stimulated 16-HBE cells as well as in NHBE cells. ConclusionsThe present study provides compelling evidences that FP combined with FO may contribute to revert some processes related to steroid resistance induced by oxidative stress due to cigarette smoke exposure increasing the anti-inflammatory effects of FP.

An update regarding the treatment of nonallergic rhinitis.

The review presents some information on known options for treatment of nonallergic rhinitis (NAR) with introduction to new therapies. The merits and limitations of recent advancements in pharmacotherapy of this common problem are briefly discussed as well. Intranasal corticosteroids are first-line therapy for NAR. Fluticasone propionate and beclomethasone remain the only topical corticosteroids approved for NAR. The use of azelastine - another first-line option - has also been found to be effective even though NAR is a nonallergic entity by definition. Combination of fluticasone propionate and azelastine is a promising option in achieving better symptom reduction. Coadministration of intranasal corticosteroid and topical decongestants is an attractive topic that requires additional safety studies before recommending treatment. Although promising, no scientifically valid recommendation can be made for treatment of NAR with capsaicin. Surgical options in patients with refractory NAR are limited. New studies demonstrate a lack of correlation between objective outcome of radiofrequency ablation of the inferior turbinate and subjective patient symptoms. The heterogeneity in clinical presentation makes NAR treatment a daily challenge for otolaryngologists. The diversity of clinical studies with use of unique outcome measures limit systematic reviews which may be instrumental in providing strong recommendations.

Population pharmacokinetics of fluticasone propionate/salmeterol using two different dry powder inhalers

The combination of fluticasone propionate (FLP) and salmeterol (SAL) is often used in clinical practice for the treatment of pulmonary disorders. The purpose of this study was to explore the pharmacokinetics (PK) of inhaled FLP and SAL, after concomitant administration, in healthy male and female subjects using two dry powder inhalers. Plasma concentration (C)–time (t) data were obtained from a single dose, two-sequence, two-period, crossover (2×2) bioequivalence (BE) study. Activated charcoal was co-administered in order to prohibit absorption from the gastrointestinal tract. A number of 60 subjects were recruited, while 57 of them completed the study and were included in the PK analysis. Initially, PK parameters of FLP and SAL were estimated using the classic non-compartmental methods. Subsequently, BE assessment was applied to the estimated PK parameters of the two dry powder inhalers. Special focus was placed on the population PK analysis of the C–t data, which were pooled together. ‘Treatment’ (i.e., test or reference) and ‘period’ of the BE study were considered as covariates. A variety of structural and residual error models were tested to find the one which best described the plasma C–t data of FLP and SAL. Demographic data were also evaluated for their impact on the PK parameters. Several goodness-of-fit criteria were utilized. The non-compartmental PK estimates of this study were in agreement with previously reported values. The population PK analysis showed that FLP data were described by a two-compartment model with first-order absorption and elimination kinetics. Body weight was found to affect significantly absorption rate constant, inter-compartmental clearance, and volume of distribution of the peripheral compartment. As body weight increases, the values of these PK parameters also rise. For SAL, the best results were obtained when a two-compartment disposition model was used assuming very rapid absorption kinetics (like intravenous bolus) and first-order elimination kinetics. Gender was found to be a significant covariate on clearance, with men exhibiting higher clearance than women.

The use of large volume low pressure nasal saline with fluticasone propionate for the treatment of pediatric acute rhinosinusitis

ObjectivesFluticasone propionate and nasal saline irrigation have been used in the treatment of sinonasal diseases for a long time. Our study investigates the effect of the combination of large volume low pressure nasal saline irrigation and fluticasone propionate for the treatment of pediatric acute rhinosinusitis. MethodsNinety-one pediatric patients with acute rhinosinusitis were included in our study. The patients were randomized into two groups. The first group (n=45) was treated with standard therapy (antibiotherapy+nasal decongestant) for 2 weeks, the second group was treated with the large volume low pressure nasal saline+fluticasone propionate combination for 3 weeks. The clinical scores, radiologic evaluations (X-ray Waters view), peak nasal inspiratory flow (PNIF) measurements, total symptom scores and hematologic parameters (WBC, CRP, ESR) of the patients were evaluated and compared. ResultsThere were no significant differences in between the two groups regarding age, gender, height and weight. Even though the clinical scores of Group 2 improved more rapidly, there were no significant differences in between groups regarding clinical scores by the 21st day. There were no significant differences in post treatment radiologic evaluations (Waters graphy). Both groups had significant improvement of their post treatment PNIF values, yet the improvement was more marked in Group 2 than in Group 1. The rhinorrhea, nasal congestion, throat itching and cough symptoms improved more rapidly in Group 2 than in Group 1. Post-treatment nose itching and sneezing symptoms were significantly less in Group 2. The values of hematologic parameters were significantly reduced at the end of the 3rd week in both groups. ConclusionsOur study is a first in investigating the combined use of large volume low pressure nasal saline and fluticasone propionate in acute pediatric rhinosinusitis, and the results reveal that the combination therapy was effective. Low pressure large volume nasal saline+fluticasone propionate combination can be employed as a new line of therapy for the treatment of pediatric acute rhinosinusitis, either by itself or combined with standard therapy.

The clinical effect of salmeterol and fluticasone propionate combined with tiotropium in the treatment of chronic obstructive pulmonary disease

Objective To investigate the clinical effects of salmeterol and fluticasone propionate combined with tiotropium in treatment of chronic obstructive pulmonary disease （COPD）.Methods 78 patients with COPD were randomly divided into two groups according to hospitalized order ,the control group（n=39）was given salmeterol and fluticasone propionate on the basis of the conventional treatment while the observation group （ n=39 ） was given tiotropium on the basis of the control group .The clinical efficacy and adverse events were compared between the two groups.Results After treatment,FVC,FEV1 and FEV1/FVC of the observation group were （1.90 ±0.19） L, （2.26 ±0.25）L and（68.41 ±5.65）%,which were significantly higher than those before treatment （t2 =9.92, 11.62,9.72;t1=9.70,8.76,9.41,all P〈0.05）and of the control group（t=8.37,7.72,7.52,all P〈0.05）;the incidenceof adverse reactions had no statistically significant between the two groups （χ2 =2.207, P 〉0.05 ）. Conclusion Salmeterol and fluticasone propionate combination of tiotropium in the treatment of COPD has significant effect,and it can effectively alleviate clinical symptoms and improve lung function ,so it is safe and reliable,which should be widely applied in clinical . Key words: salmeterol and fluticasone propionate; tiotropium; Pulmonary Disease,Chronic Obstructive

A Prescription event monitoring (PEM) study to assess safety and health outcomes of Airtec SF (Salmeterol Fluticasone propionate combination) in Indian population

Background: Asthma management has been fraught with several challenges especially for partly or uncontrolled cases. Incremental dosage strategy with salmeterol, fluticasone propionate combination offers stable yet effective control of symptoms preventing further exacerbations. However, there is limited evidence available on the need and safety profile of this incremental dosage strategy with the combination especially in Indian settings. To examine the safety and adverse clinical outcomes of Airtec SF when prescribed in patients with well- or poorly controlled persistent asthma. Methods: Based on the principle of prescription event monitoring (PEM) for safety reporting, this study was conducted at 20 centers across India. PEM study booklets with study questionnaire were provided to capture information related to adverse “events” during the observation period of 30 days. Results: Data of 384 patients were analyzed, with a mean age 44.5 years. 39% (n=150) were newly diagnosed and 61% (n=234) being in poorly controlled asthma status (i.e., partly or uncontrolled asthma). Of them, 42% (161), 44% (n=169) and 14% (54) patients were diagnosed with mild, moderate or severe persistent asthma, respectively. These were prescribed with metered-dose inhaler (n=187) or dry powder inhaler (n=197) formulations. 56% (n=216) patients suffered from concomitant allergic rhinitis. Among newly diagnosed patients with moderate to severe asthma dosage were tapered in 5.5% (n=3) cases. Dosage consistency was well-maintained in 98.2% (n=155) among partial or uncontrolled asthmatics with moderate to severe asthma with exacerbation rate of 1.9% (n=3). Adverse events including infective pneumonitis and upper respiratory tract infection were transient with none requiring treatment withdrawal. Conclusion: Use of Airtec SF was safe and well-tolerated with a negligible rate of exacerbations in Indian population especially amongst poorly controlled asthma patients.

Budget Impact Analysis of a Fixed-Dose Combination of Fluticasone Propionate and Formoterol Fumarate (FP/FORM) in a Pressurized Metered-Dose Inhaler (pMDI) for Asthma

The economic burden of asthma on the UK National Health Service (NHS) is the largest among allergic diseases. Current asthma guidelines recommend adding a long acting β2-agonist (LABA) to a low-dose inhaled corticosteroid (ICS) in patients who are on ICS monotherapy and have uncontrolled asthma. The fixed-dose combination of fluticasone propionate and salmeterol xinafoate (FP/SAL), available in a pressurized metered-dose inhaler (pMDI) device, is the most commonly prescribed ICS/LABA combination. An additional fixed-dose combination of fluticasone propionate and formoterol fumarate (FP/FORM) in pMDI is now available. In a 12-week non-inferiority study, FP/FORM demonstrated comparable efficacy to FP/SAL. The present analysis estimates the annual budget impact for the UK NHS using FP/FORM as an alternative to FP/SAL. Current pMDI prescribing data were from a real-world UK patient database (Cegedim Strategic Data). Annual costs to the NHS for drug acquisition, administration, and monitoring were estimated for FP/FORM and FP/SAL and used to assess the potential budget impact for the NHS for the use of FP/FORM instead of FP/SAL. Varying rates of uptake, adherence, adverse event-related costs, and resource use associated with switching treatment were assessed in scenario analyses. Assuming similar levels of ICS use with both regimens, annual drug acquisition costs per person were lower with FP/FORM (£412) than with FP/SAL (£509). The difference in acquisition costs and otherwise comparable input costs between the treatments, results in potential annual savings of £15,110,279 to the NHS, assuming uptake of FP/FORM over FP/SAL in 50% of existing patients. The introduction of FP/FORM results in cost savings for the NHS in all of the assessed scenario analyses. The comparable efficacy and lower acquisition costs of FP/FORM compared with FP/SAL make it a cost-saving option for the UK NHS for the treatment of asthma patients requiring combination maintenance therapy using a pMDI.

Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma

This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 μg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 μg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. ( ISRCTN60408425).

A Review of Salmeterol&amp;ndash;Fluticasone Propionate in Combination: Its Use in the Treatment of Chronic Obstructive Pulmonary Disease

Tiotropium bromide (TIO), a long-acting anticholinergic bronchodilator, is now used world-wide for the treatment of Chronic Obstructive Pulmonary Disease (COPD). However, the GOLD guidelines recommend another, or additional medication for symptomatic patients with GOLD stage III or IV disease, forced expiratory volume in 1 second (FEV1) less than 50% of the predicted value, and repeated exacerbations. Several lines of evidence such as the TRISTAN study have shown the synergistic effects of a salmeterol–fluticasone propionate combination (SFC), with significant improvements of pulmonary function, health status, exacerbation rates, and quality of life in patients with COPD, compared with using individual components of SFC. But they didn’t obtain any improvement in the data for mortality, which is our major clinical concern. The TORCH study is a major study which investigated all-cause mortality rates, but it showed no significant difference of mortality among SFC, individual drugs and placebo groups. The INSPIRE study showed significant improvement of mortality in the SFC treatment group, compared with the TIO. However, the higher incidence of pneumonia in the SFC group remains a subject of debate. Some studies showed that SFC therapy has lower medical costs with good patient compliance, which may become a reason for choosing the therapy. The new 2010 NICE GOLD Guideline recommends the “triple” therapy with SFC and TIO, when the FEV1% predicted is less than 50% in the presence of persistent exacerbations or breathlessness. The advantages of “triple” therapy may outweigh the disadvantages of each medication. This review focuses upon the therapeutic potential of SFC for the treatment of COPD.

Evaluation of controller medication efficiency in patients with moderate and severe uncontrolled asthma

Evaluation of efficiency of controller medication (combination of fluticasone propionate and Salmeterol) in 40 patients (age from 18 to 65 years) with moderate (n = 15) and severe (phenotype brittle n = 10, asthma with fixed obstruction n = 15) uncontrolled asthma was evaluated in open prospective trial. It was observed, that all patients with moderate asthma achieved control criteria (GINA, 2006) to 12th week of treatment with combination of fluticasone propionate and Salmeterol. Improvement of clinical-functional indexes was observed in patients with severe asthma to 24th week of therapy. 5 patients with brittle asthma achieved controlled and partly controlled asthma to 24th week therapy. Controlled asthma was not reach through the patients with fixed obstruction asthma, whereas increase of clinical-functional parameters was observed, usage of inhaled combined therapy allowed us to reduce oral steroids dose in 4 patients of this group.

Effects of Salmeterol and Fluticasone Propionate Combination versus Fluticasone Propionate on Airway Function and Eosinophilic Inflammation in Mild Asthma

Salmeterol and fluticasone propionate combination (SFC) provides better asthma control than fluticasone propionate (FP) alone, however, little is known on the effects of differential treatments on airway function and inflammation in patients with mild asthma. We randomized 27 mild persistent asthma patients treated with the equivalent of 400 microg beclomethasone dipropionate to receive SFC (50/100 microg , 13 patients) or FP (100 microg , 14 patients) twice daily for 8 weeks. We compared the effects of SFC and FP on pulmonary function assessed by spirometry and impulse oscillometry (IOS), eosinophil percentage of induced sputum and serum, and with asthma symptoms and control after each treatment. We observed that SFC significantly improved forced expiratory volume in one second (p < 0.05), IOS measurements of total resistance R5 (p < 0.01), central resistance R20 (p < 0.05), and distal reactance X5 (p < 0.01) compared with FP. The percentage of eosinophils in sputum, but not in serum, decreased significantly more in the SFC group than in the FP group (p < 0.05). There was also a significant improvement in symptom control in the SFC group (p < 0.05). These findings suggest that SFC is more useful than FP in mild asthma cases. The clinical benefit of SFC provides evidence that IOS and induced sputum allows for the detection of changes in airway function and inflammation.

Combination of fluticasone propionate and salmeterol potentiates the suppression of cigarette smoke-induced IL-8 production by macrophages

Cigarette smoke is the major risk factor for the development of chronic obstructive pulmonary disease (COPD). Macrophages are suggested to orchestrate the chronic inflammatory response and tissue destruction associated with COPD by secreting interleukin (IL)-8, a major neutrophil chemoattractant. The combination of inhaled corticosteroids and long-acting β 2-adrenoceptor agonists are increasingly used as maintenance therapy in patients with COPD. The aim of this study was to determine whether combined fluticasone propionate, a corticosteroid, and salmeterol, a long-acting β 2-adrenoceptor agonist, can suppress IL-8 production by human macrophages. To mimic resident macrophages in the lung, human monocytes were cultured for 5 days in medium containing Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF). In human Monocyte-Derived Macrophages, we found that cigarette smoke medium strongly enhanced IL-8 release in a time- and concentration-dependent manner. IL-8 release by cigarette smoke was significantly suppressed in a concentration-dependent manner by fluticasone and salmeterol. Coincubation of the drugs potentiated the inhibitory effect on cigarette smoke medium-induced IL-8 production and longer preincubation times resulted in more IL-8 inhibition. Interestingly, preincubation of cells with suboptimal concentration of salmeterol for 4 h before fluticasone administration for 30 min potentiates the inhibitory effect of fluticasone on IL-8 release. In conclusion, combination therapy may provide benefits over monotherapy for the treatment of COPD patients.