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Background: Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR). Triamcinolone acetonide is a nasal corticosteroid preparation indicated for the treatment of seasonal and perennial AR (PAR) in different countries worldwide. Objectives: In order to determine the efficacy of triamcinolone acetonide in the treatment of PAR, the non-inferiority of triamcinolone acetonide to fluticasone propionate was assessed in Russian adults. Methods: In this randomized, double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial, a total of 260 patients with persistent PAR were randomized to receive either triamcinolone acetonide or fluticasone propionate nasal sprays for 4 weeks. The efficacy in symptom control was evaluated using the reflective total nasal symptom score (rTNSS) from baseline (day 0) to day 28. Safety was assessed through the reporting of adverse events. Results: The rTNSS mean values decreased from baseline to the end of study treatment (day 28) in both groups: –8.2 ± 3.0 in the triamcinolone acetonide arm versus –8.0 ± 2.8 in the fluticasone propionate arm. The mean difference between the groups (triamcinolone acetonide – fluticasone propionate) for rTNSS change from baseline was –0.2 (95% confidence interval –0.89 to 0.54), with an upper confidence limit of 0.54, which is lower than the non-inferiority margin of 0.8. Triamcinolone acetonide was well tolerated, with no difference in adverse event occurrence compared with fluticasone propionate. Conclusions: Triamcinolone acetonide proved to be non-inferior to fluticasone propionate in adult patients with PAR; both treatments decreased rTNSS values and showed a good safety profile. [ABSTRACT FROM AUTHOR]

The exhalation delivery system with fluticasone propionate (Xhance®) has been shown to deliver drug substantially more broadly in the nasal cavity (particularly into superior/posterior regions), with less off-target loss of drug to drip-out and swallowing, than conventional nasal sprays. This open-label study evaluated the systemic bioavailability of Xhance® by comparing the pharmacokinetic (PK) properties of a single dose of fluticasone from 3 products administering the drug using 3 different devices: Xhance®, Flonase® (fluticasone propionate inhalational nasal spray), and Flovent® HFA (fluticasone propionate inhalational aerosol). This open-label study was conducted in 2 parts. Study part 1 compared systemic exposure with a single dose of Xhance® 186 or 372 μg versus Flonase® 400 μg (3-way, 3-treatment, 3-sequence, randomized crossover in healthy subjects; n = 90). A separate study, part 2, under the same umbrella protocol, compared systemic exposure with Xhance® 372 μg versus Flovent® HFA 440 μg (2-way, 2-treatment, 2-sequence, randomized crossover in patients with mild to moderate asthma; n = 30). With Xhance® 186 μg, the geometric least squares mean (LSM) C max was higher than with Flonase® 400 μg (16.02 vs 11.66 pg/mL, respectively; geometric mean ratio [GMR], 137.42%) and the geometric LSM AUC 0–∞ values were similar (97.30 vs 99.61 pg · h/mL; GMR, 97.78%). With Xhance® 372 μg, the geometric LSM C max and AUC 0–∞ were higher than with Flonase® 400 μg (C max , 23.50 vs 11.66 pg/mL [GMR, 201.53%]; AUC 0–∞ , 146.61 vs 99.61 pg · h/mL [GMR, 147.19%]). In part 2, the geometric LSM C max and AUC 0–∞ values were lower with Xhance® 372 μg than with Flovent® HFA 440 μg (C max , 25.28 vs 40.02 pg/mL [GMR, 63.18%]; AUC 0–∞ , 205.78 vs 415.16 pg · h/mL [GMR, 49.57%]). Similar intranasal doses of Xhance® (372 μg) and Flonase® (400 μg) are clearly not bioequivalent. Systemic exposure is very low with all products. Systemic exposure is higher with Xhance® than with Flonase® and substantially lower than with Flovent® HFA 440 μg and, based on dose normalization, Flovent® HFA 220 μg. ClincalTrials.gov identifier: NCT02266927. [ABSTRACT FROM AUTHOR]

One-third of the children who suffer from first-time wheezing are estimated to experience recurrences; however, no standard therapeutic strategy with which to prevent these recurrences currently exists. A few studies have compared the three drugs commonly used for the treatment of persistent asthma in children to identify the most effective one for preventing recurrent wheezing. In this study, in an aim to determine the most effective of these drugs, we recruited patients <5 years of age with recurrent wheezing at our hospital, and assigned them randomly to either the oral montelukast [leukotriene receptor antagonist (LTRA)], the inhaled fluticasone propionate (FP), or the inhaled budesonide suspension (BUD) groups for 12-week treatments. We then determined the treatment efficacy (symptomatic improvement) by recording the number of wheezing episodes and emergency visits, the daily treatment cost, the mean accumulated down time and the patient compliance; we then compared the results among the groups. All treatments were found to be equally effective. The daily cost of inhaled FP was lower than that of oral LTRA and inhaled BUD (P<0.00001). The difference in the mean accumulated down time between these groups was not significant (P=0.132). The adherence (patient compliance) to LTRA was significantly higher than the adherence to inhaled corticosteroids (ICS) (P<0.017). On the whole, the findings of this study indicated that all three treatments prevented recurrent wheezing in our pediatric population. FP was found to be more convenient, to require fewer doses, and that it could be easily adjusted. Patient adherence/compliance to treatment was significantly better with LTRA than with ICS. [ABSTRACT FROM AUTHOR]

Background and purpose of the study:Pseudomonas aeruginosa commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. P. aeruginosa carries flagellin that stimulates toll-like receptor (TLR)-5; however, the role of flagellin in the pathogenesis of COPD remains unclear. The aim of the study was to evaluate the mechanisms of the flagellin-induced innate immune response in bronchial epithelial cells, and to assess the effects of anti-inflammatory agents for treatment. Materials and methods: We stimulated BEAS-2B cells with P. aeruginosa-derived flagellin, and assessed mRNA expression and protein secretion of interleukin (IL)-6 and IL-8. We also used mitogen-activated protein kinases (MAPK) inhibitors to assess the signaling pathways involved in flagellin stimulation, and investigated the effect of clinically available anti-inflammatory agents against flagellin-induced inflammation. Results: Flagellin promoted protein and mRNA expression of IL-6 and IL-8 in BEAS-2B cells and induced phosphorylation of p38, ERK, and JNK; p38 phosphorylation-induced IL-6 production, while IL-8 production resulted from p38 and ERK phosphorylation. Fluticasone propionate (FP) and dexamethasone (DEX) suppressed IL-6 and IL-8 production in BEAS-2B cells, but clarithromycin (CAM) failed to do so. Conclusions:P. aeruginosa-derived flagellin-induced IL-6 and IL-8 production in bronchial epithelial cells, which partially explains the mechanisms of progression and exacerbation of COPD. Corticosteroids are the most effective treatment for the suppression of flagellin-induced IL-6 and IL-8 production in the bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

Background: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.Methods: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.Results: When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.Conclusions: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.). [ABSTRACT FROM AUTHOR]

• Fluticasone propionate and triamcinolone acetonide led to physiological effects. • Glucocorticoids altered expression of target genes encoding important pathways. • Glucocorticoid mixtures were additive. • Mixture activity supports the concentration addition concept. • Additive action of glucocorticoids may have adverse consequences. Many synthetic glucocorticoids from medical applications occur in the aquatic environment. Whether they pose a risk for fish health is poorly known. Here we investigate effects of glucocorticoids fluticasone propionate (FLU) and triamcinolone acetonide (TRI) as single steroids and as ternary mixtures with clobetasol propionate (CLO) in zebrafish embryos. Exposure to FLU and TRI in a range of concentrations between 0.099 and 120.08 μg/L led to concentration-related decrease in muscle contractions and increase in heart rate at 0.98 and 1.05 μg/L, respectively, and higher. Genes encoding for proteins related to glucose metabolism (g6pca , pepck1), immune system regulation (fkb p5 , irg1l, socs3 , gilz) and matrix metalloproteinases mmp-9 and mmp-13 showed expressional alterations, as well as genes encoding for the progestin receptor (pgr) and corticosteroid dehydrogenase (hsd11b2). FLU accelerated hatching and led to embryotoxicity (immobilization and edema). Ternary mixtures (FLU + TRI + CLO) induced the same physiological and toxicological effects at concentrations of individual glucocorticoids of 11.1–16.37 μg/L and higher. Heart rate was increased in the mixture at concentrations as low as 0.0885−0.11 μg/L of each steroid. Glucocorticoids in mixtures showed additive activity; the fold-changes of transcripts of 19 target genes were additive. Together, our data show that glucocorticoids act additively and their joint activity may be of concern for developing fish in contaminated environments. [ABSTRACT FROM AUTHOR]

Objective: The Asthma Salford Lung Study demonstrated the effectiveness of initiating once-daily fluticasone furoate/vilanterol (FF/VI) versus continuing usual care in asthma patients in UK primary care [1]. Here, we report a secondary analysis in a subset of patients with fluticasone propionate/salmeterol (FP/Salm) as their baseline intended maintenance therapy, to evaluate the relative effectiveness of initiating FF/VI versus continuing FP/Salm. Methods: Adults with symptomatic asthma were randomised to initiate FF/VI 100[200]/25 µg or continue FP/Salm. The Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), Work Productivity and Activity Impairment Asthma questionnaire, severe exacerbations, salbutamol inhaler prescriptions and serious adverse events (SAEs) were recorded throughout the 12-month treatment period. Results: One thousand two hundred and sixty-four patients (FF/VI 646; FP/Salm 618) were included in this subset analysis; 978 had baseline ACT score <20 and were included in the primary effectiveness analysis (PEA) population. At week 24, odds of patients being ACT responders (total score ≥20 and/or improvement from baseline ≥3) were significantly higher with FF/VI versus FP/Salm (71% vs. 56%; odds ratio 2.03 [95% CI: 1.53, 2.68]; p < 0.001 [PEA]). Significant benefit with FF/VI versus FP/Salm was also observed for AQLQ responders, activity impairment due to asthma, exacerbation rates, and salbutamol inhalers prescribed. No significant between-group differences were observed for impairment while working or work absenteeism due to asthma. Conclusions: For patients in primary care, initiating FF/VI was significantly better than continuing with FP/Salm for improving asthma control and quality of life, and reducing asthma exacerbations, with no notable difference in SAEs. ClinicalTrials.gov: NCT01706198. [ABSTRACT FROM AUTHOR]

Glucocorticoids, such as fluticasone propionate (FP), are used for the treatment of inflammation and alleviation of nasal symptoms and allergies, and as an antipruritic. However, both short- and long-term therapeutic use of glucocorticoids can lead to muscle weakness and atrophy. In the present study, we evaluated the feasibility of the nanodelivery of FP with poly(dl-lactide-co-glycolide) (PLGA) and tested in vitro function. FP-loaded PLGA nanoparticles were prepared via nanoprecipitation and morphological characteristics were studied via scanning electron microscopy. FP-loaded nanoparticles demonstrated an encapsulation efficiency of 68.6% ± 0.5% with a drug loading capacity of 4.6% ± 0.04%, were 128.8 ± 0.6 nm in diameter with a polydispersity index of 0.07 ± 0.008, and displayed a zeta potential of –19.4 ± 0.7. A sustained in vitro drug release pattern was observed for up to 7 days. The use of fluticasone nanoparticle decreased lipopolysaccharide (LPS)-induced lactate dehydrogenase release compared with LPS alone in C2C12 treated cells. FP also decreased expression of LPS-induced inflammatory genes in C2C12 treated cells as compared with LPS alone. Taken together, the present study demonstrates in vitro feasibility of PLGA-FP nanoparticle delivery to the skeletal muscle cells, which may be beneficial for treating inflammation. [ABSTRACT FROM AUTHOR]

Purpose: To establish an in vivo-relevant Transwell dish-based dissolution test system for the "respirable" aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products. Methods: "Respirable" ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell's supporting membrane. Results: While three ICSs with high-to-intermediate solubility enabled the first-order "sink" and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order "non-sink", slow and limited dissolution. The aerosol dissolution rate constants (kdiss) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection. Conclusions: The in vivo-relevant Transwell dish-based "respirable" aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products. [ABSTRACT FROM AUTHOR]

Background: The novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single spray (MP-AzeFlu) was compared with a first-line intranasal antihistamine spray (AZE) in Russian seasonal allergic rhinitis (SAR) patients. Methods: Moderate-to-severe SAR/rhinoconjunctivitis patients (n = 149; aged 18–65 years) were randomized to receive MP-AzeFlu (137/50 μg AZE/FP per spray) or AZE (137 μg/spray), both as 1 spray/nostril twice daily, in a multicenter, open-label, 14-day, parallel-group trial. The primary outcome was change from baseline in morning and evening reflective total nasal symptom score (rTNSS). Secondary end points included: change from baseline in reflective total ocular symptom score (rTOSS), reflective total of 7 symptom scores (rT7SS), 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score, and EuroQol-5D (EQ-5D) questionnaire score. Results: When compared with AZE-treated patients, those treated with MP-AzeFlu experienced significantly greater reductions in rTNSS (difference: –2.47; 95% confidence interval [CI] –3.65 to –1.30; p < 0.001), rTOSS (difference: –1.62; 95% CI –2.32 to –0.92; p < 0.001), and rT7SS (difference: –4.34; 95% CI –5.98 to –2.70; p < 0.001). Superior relief observed on day 2 with MP-AzeFlu versus AZE was sustained throughout the study. MP-AzeFlu-treated patients experienced a greater improvement in QoL than AZE-treated patients as measured by overall RQLQ score (mean ± SD 2.91 ± 1.08 vs. 2.05 ± 1.15) and EQ-5D score (mean ± SD 87.4 ± 10.3 vs. 83.0 ± 12.8). MP-AzeFlu was well tolerated. Conclusions: MP-AzeFlu was superior to AZE in reducing moderate-to-severe SAR symptoms, providing earlier and more complete symptom relief. [ABSTRACT FROM AUTHOR]

Relation between the aerosol dose deposited on the cover slip test surface and the fractional clearance with the perfusate from the Dissolv It at one hr. The three test substances salmeterol (SAL), budesonide (BUD) and fluticasone propionate (FP) were deposited on the cover slips at doses ranging from 0.23 to 29 µg/cm2. The normalized clearance rate of all three substances were sensitive to dose, but the low soluble FP was more so than BUD and SAL. The surface area of the air/liquid interface in the lungs is substantial, so deposited doses of aerosol medicines per interface surface area when administered via the inhalation route is always quite low. However, in most in vitro systems used for dissolution testing of dry powder inhalables, the dose per surface area is generally much higher. The aim of this study was to investigate in one in vitro lung dissolution system, the Dissolv It , the manner in which the deposited dose per test surface area of drug particles influences the simulated dissolution- and absorption rate. Here we used the dissolution test method Dissolv It to investigate the influence on dissolution behavior by varying the deposited surface density of tested drugs. Dry powders of three different active pharmaceutical ingredients with different solubilities were used; salmeterol, budesonide and fluticasone propionate. It was found that by varying the dose density from 0.23 to 29 µg/cm2 the dissolution- and absorption rate of test particles was affected for all three substances, with decreasing relative dissolution rates above certain dose limits. The effect was much more prominent with the least soluble fluticasone propionate. In contrast, in a real lung it has been shown that a tenfold increase of the even less soluble fluticasone furoate did not affect the pulmonary dissolution- and absorption as measured in the ex vivo isolated perfused rat lung. This indicates that the deposited particle dose on the test surface used must be carefully considered in all in vitro dissolution testing apparatuses used for inhalation drugs, especially when aiming for in vitro - in vivo correlations. Conclusive data show that in the Dissolv It system consistent normalized dissolution- and absorption data can be obtained if the deposition density of test substance are kept below 1 µg/cm2 and the variability between the initial drug doses is smaller than 10–15% expressed as standard deviation. [ABSTRACT FROM AUTHOR]

Cisplatin is a chemotherapeutic drug known to induce hearing loss. Although corticosteroids may help to mitigate the ototoxic side effects of cisplatin, there are complications associated with their systemic and prolonged use. The goal of this study is to test the efficacy of extended-release fluticasone propionate intracochlear implant particles to protect against cisplatin-induced hearing loss. We used guinea pigs (n = 9) injected with cisplatin (IP, 12 mg/kg weight). Fluticasone particles were delivered to the cochlear scala tympani through the round window membrane into the right ears of the guinea pigs (left ears being used as a control) two weeks prior to cisplatin administration, and hearing function was evaluated by ABR and DPOAE before implantation, immediately before cisplatin administration, and 2 weeks after the challenge with cisplatin. Data was statistically evaluated using paired t -test analysis. No significant differences were observed in ABR threshold between control and implanted ears on day 14 (23.9 ± 2.3 dB vs. 25.6 ± 1.3 dB, P = 0.524), whereas the significant cisplatin-induced hearing loss in control animals (23.9 ± 2.3 dB at day 14 vs. 40.7 ± 2.5 dB at day 28, P ≤ 0.0001) was prevented in implanted animals (25.6 ± 1.3 dB at day 14 vs. 25.0 ± 3.1 at day 28, P ≥ 0.85). A similar, though not statistically significant, trend was observed in DPOAE responses in untreated ears (7.9 ± 5.8 dB at day14 vs. −0.5 ± 5.3 dB at day 28, P = 0.654) as compared to treatment (11.1 ± 3.4 dB at day 14 vs. 13.6 ± 4.8 dB at day 28, P = 0.733). These results suggest that fluticasone intracochlear implants are safe and able to provide effective otoprotection against cisplatin-induced hearing loss in the guinea pig model. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), subfoveal choroidal thickness (SFCT), and central retinal thickness (CRT) in asthmatic children who were under inhaled corticosteroid treatment by using Swept-Source Optical Coherence Tomography (SS-OCT). Material and methods: Fifty-three children were prospectively analyzed in the study. Group 1 included 31 asthmatic children and group 2 included 22 healthy children. Asthmatic children received a dose 250 μg daily of inhaled fluticasone propionate (Flexotide, GlaxoSmithKline, Middlesex, UK). Allergy parameters including, exposure to smoke, eosinophil count, percentage of eosinophils, immunoglobuline (Ig) E levels, number of asthma attacks, number of sensitivity to allergens and follow-up time were recorded. The RNFLT, GCLT, SFCT, and CRT were analyzed with SS-OCT and the data were compared between the groups. Results: There were 13 girls (41.9%) and 18 boys (58.1%) in group 1 and 13 girls (59.1%) and 9 boys (40.9%) in group 2 (p = 0.22). The mean age was 9.3 ± 2.2 years in group 1 and 9.9 ± 1.5 years in group 2 (p = 0.08). The mean CRT (239.26 ± 34.56 µm versus 226.82 ± 26.23 µm, p = 0.22) and mean SFCT (273.97 ± 40.95 µm versus 280.41 ± 32.78 µm, p = 0.54) did not significantly differ between the groups. The superior, inferior, and average RNFLT were significantly lower in group 1 than group 2 (p < 0.05). There were significant correlations between total corticosteroid dose and RNFLT (p < 0.05) and between IgE levels and GCLT (p < 0.05). Conclusions: The SS-OCT revealed that asthmatic children under inhaled corticosteroid treatment have lower RNFLT than healthy subjects. [ABSTRACT FROM AUTHOR]

Background: The design of inhaler devices may potentially influence adherence/persistence and outcomes in asthma. Objective: The primary objective was to assess asthma control and any change in the quality of life in patients using an intuitive dry powder inhaler containing fluticasone propionate/salmeterol (AirFluSal®, Forspiro®,) for the treatment of asthma in everyday practice. Methods: ASSURE was a multicenter, noninterventional, open-label, prospective study in patients with asthma, aged ≥12 years and treated with the Forspiro device in Denmark, Sweden and Norway. Patients' opinions of their asthma control were assessed by the Asthma Control Test (ACT) questionnaire and asthma-related quality of life by the Mini Asthma Quality of Life Questionnaire (miniAQLQ) at baseline and at two follow-up visits (approximately 4–8-week intervals). Results: Of 321 patients enrolled in the study, 299 received at least one dose of fluticasone propionate/salmeterol via the Forspiro device and 204 had evaluable data at the baseline visit and at least one later visit. Patients showed improvements in asthma control and quality of life during the study. The mean sum score of ACT increased from 18.0 (SD 4.5) at visit 1 to 19.9 (4.2) at visit 2 and 20.5 (4.3) at visit 3. Overall, 38.2% of patients improved by the minimal clinically important difference (MCID) of ≥3 points (45.6% among those with a baseline score below 23 [ie, not already well controlled]). The mean score on the miniAQLQ increased from 5.16 (SD 1.24) at visit 1 to 5.58 (SD 1.20) at visit 2 and 5.82 (SD 1.04) at visit 3. Overall, 42.6% of patients improved by the MCID of ≥0.5. Conclusion: This real-life study suggests that treatment with fluticasone propionate/salmeterol via the Forspiro device can improve asthma symptom control and quality of life. [ABSTRACT FROM AUTHOR]

A method was developed and validated for analysis of Formoterol Fumarate and Fluticasone Propionate in dry powder inhaler formulations. Separation was achieved on a HiQ Sil C18HS, 250×4.6 mm, 5 µm column using a mobile phase consisting of Acetonitrile: 0.01 M Ammonium Dihydrogen Phosphate solution (80:20%v/v) at a flow rate of 1ml/min PDA detection at 215.0 nm. This method is validated according to ICH guidelines, which include linearity, precision, accuracy, specificity, robustness. The result obtained were within the acceptance criteria as per ICH guidelines. [ABSTRACT FROM AUTHOR]

Background: Amongst the common problems faced globally, Allergic Rhinitis (AR) is very distressing at times. This is an inflammatory response to either known or unknown allergen. The symptomatic relief in AR using topical steroid Fluticasone propionate and antihistaminic Azelastine Hydrochloride in a combination has been studied. Very few studies showing comparison between these two drugs in a combination and steroid alone are available in the literature. Aim and Objectives: To study the effectiveness of topical treatment using corticosteroid Fluticasone propionate and antihistaminic in a combination versus Fluticasone propionate alone in patients of AR. Material and Methods: The cases presented with symptoms of allergic rhinitis were randomized in two groups at start of treatment. All cases of Group I were treated with Fluticasone propionate whereas of Group II with Fluticasone propionate and Azelastine hydrochloride combination. In each group, the individual symptom scores were recorded pre-treatment and post-treatment at the end of four weeks with the help of symptom evaluation scale. Based on these individual symptom scores, the Total Symptom Score (TSS) was calculated. The effectiveness of group specific drugs was evaluated by comparing individual and TSS. Results: After four weeks, both TSS and individual symptom score were reduced in either group (p<0.05). Further, Group II specific drug was found more effective than Group-I in relieving symptoms of AR. Conclusion: TSS decreased by an average of 84.14% in Group-I (i.e. treated with Fluticasone propionate) and by 91.16% in Group-II (i.e. treated with Fluticasone propionate and Azelastine hydrochloride I in a combination). [ABSTRACT FROM AUTHOR]

Abstract Eosinophilic esophagitis (EoE) is a multifactorial esophageal inflammation, with a genetic predisposition, which combines a deficient esophageal mucosal barrier, an abnormal immune reaction to environmental allergens mediated by Th2 interleukins, immediate esophageal lesions and dysmotility, with secondary remodeling and fibrosis. Symptoms include reflux, abdominal pain, and food impaction, with a variation according to age. Fibroscopy shows major and minor endoscopic and histologic criteria, with a mucosal count ≥ 15 eosinophils/high power field (Eo/hpf). A new entity has been defined, where gastroesophageal reflux disease (GERD) and EoE share responsibility: the PPIs-sensitive form of EoE (PPI-REE). Children with fibroscopy showing ≥ 15 Eo/hpf need a second endoscopy following 8 weeks of PPI treatment. EoE has a strong association with other atopic disorders. Allergy testing (specific IgE blood test and skin prick tests [SPTs]) identifies patients at risk of anaphylaxis (14.8% of cases). The dietary therapy is based on a 4- to 12-week elimination test followed by endoscopy to check the disappearance of eosinophilic infiltration. The "dietary approaches are the amino acid-based formula, the allergy testing-based targeted diet, and the six-food elimination diet (empirical elimination of milk, wheat, soy, eggs, peanut/nuts, and fish/seafood). A recent first-line trial elimination of milk has been suggested, with wheat as a second elimination, if necessary. Dietary therapy allows remission and catch-up growth in 65% of cases. Swallowed topical steroids (budesonide in viscous gel or fluticasone propionate for nebulization) are an alternative, for which efficacy varies according to clinical and/or histological criteria and with relapses occurring at dosage tapering. Their use may be restricted by side effects, such as oral and/or esophageal candidiasis. The impact on long-term bone health and growth is unknown. Maintenance therapy is not standardized and is team-dependent, combining or not elimination diets and long-term steroids. The long-term risk of EoE is esophageal stenosis (25%) and endoscopic dilation may be repeated. Biotherapies have shown isolated histological improvement without significant clinical efficacy. [ABSTRACT FROM AUTHOR]

Background: The Easyhaler® device-metered dry powder inhaler containing Salmeterol and Fluticasone propionate (S/F) has been developed for the treatment of patients with asthma and chronic obstructive pulmonary disease (COPD). We report two studies which evaluated the in vitro flow rate dependence of delivered dose (DD) and fine particle dose (FPD) of S/F Easyhaler versus Seretide Diskus®. Methods: A randomized controlled trial (RCT) assessed inspiratory flow parameters of S/F Easyhaler and Seretide Diskus in subgroups of patients with asthma (children, adolescents and adults, and elderly) and in COPD patients. The 10th, 50th, and 90th percentile airflow rates were determined and utilized in vitro, to evaluate flow rate dependence of DD and FPD. Flow rate dependence was evaluated relative to the result obtained at the 50th percentile and any values deviating from 100% indicated flow rate dependence. The volumetric flow rate dependence (Q) index derived from FPD at 10th and 90th percentile airflows was also evaluated. Results: Overall, 227 patients were enrolled and randomized; 216 completed the RCT. In total, 55.5% of patients were female, and the mean age was 46.3 years. Clinically relevant airflow rates (46, 68, and 85 L/min for S/F Easyhaler and 44, 71, and 96 L/min for Seretide Diskus) were carried forward into the in vitro study, which demonstrated similar flow rate dependence of DD and FPD for S/F Easyhaler compared with Seretide Diskus; all values were within ±15% limits across the 10th, 50th, and 90th percentile airflow rates. Q index results suggested that both S/F Easyhaler and Seretide Diskus are medium airflow-dependent products. Conclusions: Similar in vitro flow rate dependence of DD and FPD was demonstrated for S/F Easyhaler compared with Seretide Diskus, across a range of clinically relevant airflow rates, collected from patients with asthma and COPD. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) control is a priority in the European Union (EU), and Allergic Rhinitis and its Impact on Asthma (ARIA) has endorsed a visual analogue scale (VAS) as the new language of AR control. This study evaluated the effectiveness of MP‐AzeFlu (Dymista®, antihistamine [azelastine], and intranasal corticosteroid [fluticasone propionate]) using a VAS in real‐life clinical practice in Denmark. Methods: The multicenter, prospective, non‐interventional study included 170 patients (≥12 years) with ARIA‐defined moderate‐to‐severe AR prescribed MP‐AzeFlu. Patients assessed symptom severity using a VAS (0 to 100 mm) on days 0, 1, 3, and 7 and after ∼14 days of MP‐AzeFlu use. On day 3, patients assessed their disease as well controlled, partly controlled, or uncontrolled. Proportions of patients achieving VAS score cutoffs (well‐controlled, partly controlled) were also calculated. Results: MP‐AzeFlu reduced mean ± standard deviation VAS score from 67.1 ± 19.3 mm at baseline to 28.4 ± 23.7 mm on the last day, a reduction of 38.8 ± 27.3 mm. At day 3, 85.6% of patients considered their symptoms to be partly or well controlled. Effectiveness was consistent across disease severity, phenotype (seasonal, perennial, or combined AR), and patient age. Respectively, 28.2%, 44.2%, 61.6%, and 71.4% of patients achieved ≤38 mm well‐controlled VAS score cutoff on days 1, 3, and 7, and the last day. Conclusion: MP‐AzeFlu provided effective, rapid, and sustained symptom control in a real‐life setting among patients from Denmark. These results align with EU and ARIA objectives and support the effectiveness of MP‐AzeFlu for the treatment of AR in real life. [ABSTRACT FROM AUTHOR]

Objective: Periostin, a matricellular protein, is produced from airway epithelial cells and lung fibroblasts by IL-13. It has been suggested that periostin is involved in allergic inflammation and fibrosis. However, the usefulness of serum periostin measurement in the assessment of airway inflammation and remodeling and management of asthmatic patients is still debated. We aimed to determine whether serum periostin levels reflect eosinophilic airway inflammation and airway remodeling in asthma. Methods: We examined the relationship of serum periostin levels with clinical features, biomarkers for eosinophilic airway inflammation, fraction of exhaled nitric oxide (FeNO) levels and blood eosinophil counts, and pulmonary functions in 235 well-controlled asthmatic patients on inhaled corticosteroids (ICS) treatment. Results: Serum periostin levels were positively correlated with blood eosinophil counts (%) and age (r = 0.36 and 0.23, respectively), and were negatively correlated with body weight and FEV1/FVC (%) (r = −0.24 and − 0.23, respectively) in well-controlled asthmatic patients on ICS treatment (daily dose of 453 µg equivalent to fluticasone propionate). Blood eosinophil counts and serum periostin levels were similarly associated with increased FeNO levels (≥40 ppb) in the asthmatics. Serum periostin levels were better associated with fixed airflow limitation (FEV1/FVC ratio <70%) than FeNO levels, blood eosinophil counts or total IgE levels in the asthmatics. Multivariate analysis showed that fixed airflow limitation was significantly associated with high serum periostin levels (≥97 ng/ml) (Odds ratio 3.2). Conclusions: Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics on ICS treatment. [ABSTRACT FROM AUTHOR]

Background/Aim. Corticosteroids are the most frequently prescribed anti-inflammatory treatment in asthma. A purpose of this study was to compare the spirometric parameters as a response to inhaled fluticasone propionate (FP) treatment in children with asthma, exposed and nonexposed to environmental tobacco smoke (ETS). Methods. The study included 527 children aged between 1 and 16 years with persistent asthma divided into the groups of ETS exposed (ETSE, n = 337) and ETS free (ETSF, n = 190) children. Spirometry was performed before (1st set of results) and after 6 months of FP treatment (2nd set of results). Good lung function (GLF) was defined as forced expiratory volume in one second (FEV1) = 85%, and "poor lung function" (PLF) as FEV1 < 85%. Results. Among the ETSE children, 208 had one smoking parent, 129 had two, 228 had smoking mothers and 238 smoking fathers. The ETSE children received a higher FP dose (p < 0.0001) which was increased with the increase of the number of smokers in the family. The ETSE children had significantly lower lung function both in the 1st and 2nd sets of tests compared to the ETSF children (p < 0.05). After the FP treatment, both groups improved all spirometric parameters (p < 0.001). In the 2nd set of the spirometric tests, the children of smoking mothers had lower spirometry values compared to the children of smoking fathers (p < 0.05). The proportion of the children improving from the PLF to GLF after 6 months of FP was much higher among the ETSF than the ETSE children (p < 0.05). Conclusions. The ETSE children had lower spirometric values before FP. After 6-months of the FP treatment children in both groups improved the spirometric values, but the improvement was higher in the ETSF children. [ABSTRACT FROM AUTHOR]

Background: Fluticasone propionate 50 μg/salmeterol xinafoate 25 μg (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. [ABSTRACT FROM AUTHOR]

Rationale: Patients with COPD have an increased risk for community-acquired pneumonia, which is further increased by inhaled corticosteroids. Objective: To assess effects of the corticosteroids, budesonide and fluticasone propionate, on macrophage bacterial responses in COPD. Methods: Monocyte-derived macrophages (MDMs) generated from blood monocytes from 10 non-smoker controls (NoS), 20 smokers without COPD (Sm), and 40 subjects with moderate to severe COPD (21 ex-smokers (COPD-ES) and 19 current smokers (COPD-S)) were pre-treated with budesonide or fluticasone (10 nM—1 μM) and challenged with live non-typeable Haemophilus influenzae (NTHI) or Streptococcus pneumoniae (SP). Cell surface bacterial recognition receptor expression (flow cytometry) and cytokine release (bead array) were analyzed. Results: NTHI and SP reduced bacterial recognition receptor expression on MDMs from COPD and Sm, but not NoS (except TLR4). SR-AI and MARCO were reduced by both NTHI and SP, whereas other receptors by either NTHI or SP. Among COPD subjects, COPD-ES demonstrated a greater number of reductions as compared to COPD-S. NTHI reduced SR-AI, MARCO, CD11b, CD35 and CD206 in COPD-ES while only SR-AI and CD11b in COPD-S. SP reduced SRA-1, CD1d, TLR2 and TLR4 in both COPD-ES and COPD-S, and reduced MARCO and CD93 only in COPD-ES. All receptors reduced in COPD by NTHI and most by SP, were also reduced in Sm. Budesonide counteracted the receptor reductions induced by both NTHI (CD206 p = 0.03, MARCO p = 0.08) and SP (SR-AI p = 0.02) in COPD-ES. Fluticasone counteracted only SP-induced reductions in TLR2 (p = 0.008 COPD-ES and p = 0.04 COPD-S) and TLR4 (p = 0.02 COPD-ES). Cytokine release was equivalently reduced by both corticosteroids. Conclusions: Reduction in macrophage bacterial recognition receptors during bacterial exposure could provide a mechanism for the increased pneumonia risk in COPD. Differential effects of budesonide and fluticasone propionate on macrophage bacterial recognition receptor expression may contribute to the higher pneumonia incidence reported with fluticasone propionate. [ABSTRACT FROM AUTHOR]

Introduction: There is a paucity of data describing prescribing patterns and adherence to therapy of inhaled corticosteroids (ICS) in combination with long-acting β2-agonists (LABA) in the Japanese population in clinical practice.Methods: This was a non-interventional, retrospective, cohort study of patients who were prescribed medication for asthma, using data from the Japan Medical Data Center Claims Database. Data from patients aged ≥ 15 years with a prescription of asthma drugs between December 2014 and October 2015 (Day 0, the index date when asthma medication was initiated) were analysed in 12-month pre-index and post-index periods. Part 1 focused on baseline characteristics and epidemiological outcomes in the pre- and post-index period in the overall asthma population, whereas comparing medication adherence [number of prescribed days per year and proportion of days covered (PDC)] between ICS/LABA-naïve patients treated with once-daily fluticasone furoate/vilanterol (FF/VI) and twice-daily fluticasone propionate/salmeterol (FP/SAL) was the primary endpoint in Part 2.Results: Of the available patient data (N = 2,953,652), 28,699 patients were identified as having asthma. ICS/LABA was the main asthma treatment prescribed; 11,167 (38.9%) patients were continuous ICS/LABA users. In ICS/LABA-naïve asthma patients, treatment with once-daily FF/VI was associated with higher medication adherence compared with twice-daily FP/SAL; mean [standard deviation (SD)] number of prescribed days per year was 97.8 (115.9) for FF/VI versus 80.5 (92.7) for FP/SAL (p = 0.04), mean (SD) PDC was 26.7% (31.5) for FF/VI versus 21.9% (24.8) for FP/SAL (p = 0.04). FF/VI was also associated with a lower rate of treatment discontinuation and no difference in use of short-acting beta2-agonists or oral corticosteroids compared with FP/SAL.Conclusions: ICS/LABA was the major prescribed asthma treatment in Japan. Medication adherence was greater with FF/VI, which may indicate that patients are more likely to adhere to once-daily FF/VI versus twice-daily FP/SAL.Funding: This study was funded by GSK (study sponsor).Study Registration: GSK Study No. 207264, GSK Study Register site: https://www.gsk-clinicalstudyregister.com/search/?search_terms=207264. [ABSTRACT FROM AUTHOR]

Introduction: Products based on inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations may provide different clinical benefits. This study was conducted to compare the rapid effects of three such combination products: formoterol/fluticasone (FFC) aerosol (pMDI), formoterol/budesonide (FBC) dry powder inhaler (DPI), and vilanterol/fluticasone furoate (VFC) DPI.Methods: The study design was a three-armed, randomized, crossover study. Patients included in the study had stable moderate asthma, defined as an Asthma Control Questionnaire (ACQ) score ≤ 0.75, and were undergoing step 2 or 3 asthma treatment as defined by JGL2015. Subjects were treated with fluticasone propionate inhaled via Diskus® during a 2-week washout period before randomization. At visit 2, subjects were randomly assigned in a 1:1:1 ratio to FFC, FBC, or VFC, and evaluated for changes in pulmonary function over time. At visits 3 and 4, the treatment was switched to another ICS/LABA combination in a crossover manner after a 1-week washout period. Spirometry was performed pre-dose and at 3, 10, and 30 min post-dose, and forced oscillation was implemented pre-dose and at 1, 7, 15, and 60 min post-dose.Results: Fifteen outpatients (63.3 ± 9.5 years, ACQ: 0.13 ± 0.19) completed the study. ∆FEV1 at 3 min did not significantly differ among the three groups. Significant increases in FEV1 and %FEV1 from baseline were observed in the FFC (p = 0.004, 0.003), FBC (p = 0.014, 0.011), and VFC (p = 0.032, 0.023) groups at 30 min. Improvements in respiratory resistance at 5-20 Hz from baseline at 60 min, resonant frequency, respiratory system reactance at 5 Hz, and low-frequency reactance area from baseline were observed at 1 min in the FFC group (p = 0.014, 0.002, 0.027, 0.018, respectively).Conclusion: FFC administered using a pMDI showed favorable delivery to peripheral airways and significantly more rapid action promptly after inhalation as compared with other ICS/LABA preparations inhaled using a DPI, thus broadening the potential therapeutic options for asthma.Trial Registration Number: UMIN000029379.Funding: Kyorin Pharmaceutical Co., Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Most allergic rhinitis (AR) patients have moderate‐to‐severe, persistent disease. Meda Pharma's AzeFlu (MP‐AzeFlu) combines intranasal azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a novel formulation in a single device to treat AR. This prospective, noninterventional study sought to assess the effectiveness of MP‐AzeFlu (one spray/nostril twice daily; 548 µg AZE/200 µg FP daily dose) in relieving AR symptom severity. Methods: A visual analogue scale (VAS) was used prior to MP‐AzeFlu treatment on days 0, 1, 3, 7, 14, 21, 28, 35, and 42 by 53 persistent AR (PER) patients seen in routine clinical practice in Ireland. An endoscopy was performed on days 0 and 28, and symptoms of edema, discharge, and redness were scored on a three‐point scale (for both nostrils). Results: Patients using MP‐AzeFlu experienced rapid VAS score reduction from 73.4 mm (standard deviation [SD], 20.3) at Day 0 to 31.5 mm (SD, 25.0) at day 28 (P < 0.0001) to 28.1 mm (SD, 24.1) at day 42 (P < 0.0001), a 45.3‐mm reduction. On average, patients achieved a clinically relevant VAS score cutoff of 50 mm before Day 7. Total endoscopy score decreased from 7.5 mm (SD, 3.1) at baseline to 3.5 mm (SD, 2.5) at Day 28. The incidence of severe edema on endoscopy decreased from 53.1% at baseline to 3.8% at Day 28. A similar reduction in the incidence of thick/mucousy discharge (from 28.3% to 4.8%) and severe redness (from 34.9% to 0%) was also observed. Conclusions: MP‐AzeFlu provided effective, rapid control of PER as assessed by VAS in a real‐world clinical setting in Ireland. Symptom improvement was observed at Day 1, sustained for 42 days, and associated with improved mucosal appearance after 28 days. These results confirm the safety of MP‐AzeFlu and exceed the efficacy demonstrated in phase 3 clinical studies for controlling AR in PER patients. Meda Pharma's AzeFlu (MP‐AzeFlu) comprises intranasal azelastine hydrochloride and fluticasone propionate in a novel formulation delivered in a single device. In this noninterventional prospective study, patients from a routine clinical practice in Ireland were prescribed MP‐AzeFlu and followed for 42 days. MP‐AzeFlu provided effective and rapid control of persistent allergic rhinitis in this real‐world clinical setting. [ABSTRACT FROM AUTHOR]

Portable inhalers are used for delivering drugs to the lung in the form of aerosols and form the standard treatment for diseases such as Asthma, COPD, and cystic fibrosis. However, for aqueous drug formulations, spray nozzle chips have so far been restricted to cleanroom manufacture due to their small feature sizes. Here we present a spring-actuated 3D-printed swirl nozzle that sprays an aqueous drug solution, matching propellant-containing inhalers in aerosolization time. The use of two-photon polymerization enables the small nozzle feature size of 100 μm and device print times of only 4 min, making serial mass-fabrication a viable option. Our 35 bar spring-operated swirl nozzle prototype achieves mean volumetric particle sizes of 12.5 μm on doses of 100 μl, aerosolized in 270 ms, as fast as a propellant-driven inhaler. [2021-0002] [ABSTRACT FROM AUTHOR]

Bruce M Prenner Allergy Associates Medical Group, Inc., San Diego, CA, USA Abstract: A novel intranasal formulation of azelastine HCl (AZE, an antihistamine) and fluticasone propionate (FP, a corticosteroid) in a single spray (MP-AzeFlu [Dymista®]) was studied in four randomized, double-blind, placebo-controlled trials of patients with seasonal allergic rhinitis conducted in the US. Study sites were distributed so that all major US geographic regions and the prevalent pollens within these regions were represented. Spring and summer studies included patients aged 12 years and older with allergy to grass and tree pollens. Fall studies enrolled patients with allergy to weeds, in particular ragweed. In addition, a study was conducted during the winter months in patients with allergy to mountain cedar pollen in TX, USA. Regardless of allergy season or prevalent pollen, MP-AzeFlu improved nasal symptoms of allergic rhinitis (AR) to a significantly greater degree than AZE or FP, two treatments that currently are recommended as the first-line AR therapy. MP-AzeFlu improved all individual AR symptoms and was significantly better than FP and AZE for nasal congestion relief, which is generally accepted as the most bothersome symptom for AR patients. The onset of action was within 30 minutes. MP-AzeFlu also provided clinically important improvement in the overall Rhinoconjunctivitis Quality of Life Questionnaire score and significantly improved ocular symptoms of rhinitis compared to placebo. Favorable characteristics of the MP-AzeFlu formulation as well as superior clinical efficacy make it an ideal intranasal therapy for AR. Keywords: Dymista, seasonal allergic rhinitis, grass pollen, ragweed, Texas mountain cedar, intranasal therapy

Background: Several guidelines, including the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL), recommend salmeterol/fluticasone combination therapy (SFC) as step 3 to 4 treatment for moderate to severe asthma. However, the optimal step-down approach to SFC remains unclear. In the current study, we examined step-down approaches in asthmatic children whose symptoms had been stabilized by SFC 100/200 μg/day. Methods: This randomized, multicenter, open-label, parallel-group study was conducted over 12 weeks. For step-down therapy, subjects aged 5–15 years were randomly assigned to an SFC group (25/50 μg b.i.d.) or an FP group (100 μg b.i.d.), and treated for 12 weeks. Childhood Asthma Control Test (C-ACT) scores, lung function, and exhaled nitric oxide (FeNO) levels were monitored. Results: Of 131 enrolled subjects, 128 completed the study and were included in the analysis. Decreases in % peak expiratory flow rate and % forced expiratory flow at 50% of vital capacity (V50) were observed in the FP group at each time point. There was a significant difference between the two groups for the change in %V50 from its previous value at each time point. There were no significant changes in FeNO levels (range 15–20 ppb) or C-ACT scores (∼26 points) within or between groups. Conclusions: A high level of asthma control was maintained with both approaches. The use of SFC step-down resulted in somewhat better respiratory function, with no worsening of airway inflammation. However, halving the dose of SFC and switching to FP alone are both optimal step-down approaches.

Kazuya Horiuchi, Keita Kasahara, Yusuke Kuroda, Haruna Morohoshi, Yosuke Hagiwara, Gen Ishii Respiratory Disease Center, Showa University Northern Yokohama Hospital, Yokohama-shi, Kanagawa-ken, Japan Purpose: A combination therapy with inhaled corticosteroid (ICS) and a long-acting β agonist (LABA) is the standard treatment for asthmatic patients, and step-down treatment is recommended once control has been achieved. However, little data exist that evaluate the long-term outcomes after step-down treatment. Objective: To compare the long-term outcomes of step-down therapy with ICS/LABA or ICS alone for asthmatic patients who have achieved well-controlled asthma by the ICS (250 µg fluticasone)/LABA (50 µg salmeterol) combination (SFC, two puffs per day). Patients and methods: We randomized 40 well-controlled patients with asthma receiving SFC (250 µg) to two groups; one group of patients received step-down therapy with low-dose SFC (100 µg, two puffs daily) and another group of patients received step-down therapy with high-dose fluticasone propionate (FP) alone (500 µg, daily). The two groups were monitored over 12 months for changes in asthma control test scores, respiratory function (percent forced expiratory volume in 1 second, maximal expiratory flow rate at 50% of the vital capacity [%FEF50], and maximal expiratory flow rate at 25% of the vital capacity [%FEF25]), and the concentration of fractional exhaled nitric oxide. Results: There was no significant difference in the dropout rate between the SFC and FP groups. Low-dose SFC maintained the stability of all parameters over 12 months, whereas the FP group exhibited a rapid 5% decrease in forced expiratory volume in 1 second within 2 months after discontinuation of salmeterol; furthermore, after 10 months, there was a gradual decrease in %FEF50 and %FEF25. Conclusion: This study suggests that a balanced step-down protocol, including both ICS and LABA, is essential in providing long-term stability to patients with mild-to-moderate well-controlled asthma. Keywords: long-term outcome, asthma, fluticasone propionate, salmeterol, step down

Chitosan (CS) is a natural polysaccharide, widely studied in the past due to its unique properties such as biocompatibility, biodegradability and non-toxicity. Chemical modification of CS is an effective pathway to prepare new matrices with additional functional groups and improved properties, such as increment of hydrophilicity and swelling rate, for drug delivery purposes. In the present study, four derivatives of CS with trans-aconitic acid (t-Acon), succinic anhydride (Succ), 2-hydroxyethyl acrylate (2-HEA) and acrylic acid (AA) were prepared, and their successful grafting was confirmed by FTIR and 1H-NMR spectroscopies. Neat chitosan and its grafted derivatives were fabricated for the encapsulation of fluticasone propionate (FLU) and salmeterol xinafoate (SX) drugs, used for chronic obstructive pulmonary disease (COPD), via the ionotropic gelation technique. Scanning electron microscopy (SEM) micrographs demonstrated that round-shaped microparticles (MPs) were effectively prepared with average sizes ranging between 0.4 and 2.2 μm, as were measured by dynamic light scattering (DLS), while zeta potential verified in all cases their positive charged surface. FTIR spectroscopy showed that some interactions take place between the drugs and the polymeric matrices, while X-ray diffraction (XRD) patterns exhibited that both drugs were encapsulated in MPs’ interior with a lower degree of crystallinity than the neat drugs. In vitro release studies of FLU and SX exposed a great amelioration in the drugs’ dissolution profile from all modified CS’s MPs, in comparison to those of neat drugs. The latter fact is attributed to the reduction in crystallinity of the active substances in the MPs’ interior.