Doses Of Fluticasone Propionate Research Articles

Comparative clinical pharmacology of mometasone furoate, fluticasone propionate and fluticasone furoate

AimsTo investigate the pharmacokinetics and effects on the hypothalamic-pituitary-adrenal (HPA) axis of mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). MethodsStudy 1: Fourteen healthy participants received inhaled and intravenous MF (inhaled dose via Twisthaler) and FP (inhaled dose via Diskus), both given at 400 μg, using a randomised, single-dose, four-way crossover design. Study 2: Twenty-seven participants with mild to moderate asthma, who discontinued their corticosteroid medication for 5 days to obtain a baseline 24 h serum cortisol, received inhaled MF Twisthaler and FP Diskus, both given at 400 μg twice daily (BID), using a randomised, 14-day repeat dose, two-way crossover design. Study 3: Forty-four healthy participants were randomised to a double-blind, placebo-controlled, five-period crossover study where the following treatments were administered via the inhaled route for 7 days: FP Diskus (250, 500, 1000 μg BID), FF Diskus (100, 200, 400, 800, 1600 μg once daily [QD]) or placebo Diskus. In each study, 24-h serial blood samples were collected and assayed to assess concentrations of MF, 6β-hydroxy mometasone, mometasone, FP, FF and cortisol. Pharmacokinetic and serum cortisol parameters were estimated as geometric means and 95% confidence intervals (CI). ResultsStudy 1: For intravenous MF and FP, respectively: absolute bioavailability was 11.4% (95% CI: 7.5, 17.6) and 7.8% (6.3, 9.6); plasma clearance was 47 L/h (41, 52) and 60 L/h (52, 69); half-life was 7.4 h (6.9, 8.0) and 7.2 h (6.5, 8.0); and volume of distribution was 499 L (439, 567) and 623 L (557, 698). Inhalation of single dose MF or FP did not significantly affect serum cortisol (<10% reduction from baseline), whereas intravenous administration of MF or FP each changed serum cortisol by approximately −50% from baseline. Study 2: For MF and FP, respectively: area under the curve up to the last measurable concentration on Day 1 was 421 pg h/mL (270, 659) and 248 pg h/mL (154, 400), and on Day 14 was 1092 pg h/mL (939, 1269) and 591 pg h/mL (501, 696); absolute bioavailability was 12.8% (11.2, 14.2) and 8.9% (7.7, 10.2). On Day 14, 24-h serum cortisol change from baseline was −35% (−44%, −26%) and −18% (−28%, −5%) for MF and FP, respectively; the reduction was significantly greater for MF than FP (ratio for geometric adjusted mean serum cortisol concentration: 1.28 [1.04, 1.56]). Low plasma concentrations of 6β-hydroxy mometasone were detected after intravenous dosing (Study 1) and after multiple inhaled dosing (Study 2); mometasone was not detected in any samples. Study 3: Inhaled FP and FF had similar systemic bioavailability estimates (12.0% [11.0, 13.2] and 15.0% [12.0, 17.3], respectively), but a differential effect on the HPA axis which was in agreement with the known 1.7-fold higher glucocorticoid receptor-binding affinity of FF versus FP. However, for FP 250 μg BID and FF 100, 200 and 400 μg QD, reduction in serum cortisol was not significantly different from placebo. For higher doses, FP 500 and 1000 μg BID, and FF 800 and 1600 μg QD, changes in serum cortisol concentration relative to placebo were −30%, −70%, −41% and −90%, respectively. Repeat inhaled dosing of FP 1000 μg/day (within the therapeutic dose range) resulted in comparable cortisol suppression to MF in the therapeutic range (30% reduction); whereas for FF this occurred at more than 3-fold above the therapeutic dose range (644 μg/day). ConclusionsSingle inhaled and intravenous doses of MF and FP (400 μg) resulted in similar bioavailability and reductions in serum cortisol. Repeat dosing of inhaled MF and FP in the therapeutic range (800 μg/day) resulted in greater systemic exposure for MF, and a 35% reduction in serum cortisol that was 2-fold greater than for FP. The higher glucocorticoid receptor-binding affinity and bioavailability, lower clearance and the presence of active metabolites may contribute to the greater systemic exposure and effect on cortisol for MF. Repeat dosing of inhaled FP and FF resulted in similar systemic bioavailability but differed in terms of the dose required for comparable cortisol suppression to MF in the therapeutic range. Unlike FP and FF, MF has active metabolites that may contribute to its systemic effects, while device/formulation performance differences also exist between MF-containing products.

Spirometric changes in children with asthma exposed to environmental tobacco smoke and treated with inhaled corticosteroids

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 &lt; 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 &lt; 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 &lt; 0.05). After the FP treatment, both groups improved all spirometric parameters (p &lt; 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 &lt; 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 &lt; 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.

The efficacy of fluticasone propionate nebulizer therapy in children with laryngotracheitis

Objective. To determine the efficacy of fluticasone propionate (FP) nebulizer therapy in children with laryngotracheitis (LT) Methods. There were children with LT and laryngotracheobronchitis (LTB) aged 0–13 years under observation. 97 children with an initial Westley score 1-5 received nebulized FP 0.5 mg every 6 hours up to no stridor. 104 controls matched by age, sex and severity received systemic glucocorticoids intramuscularly or intravenously. The efficacy of treatment was assessed with a total dose of glucocorticoids used and with duration of treatment up to Westley score 0. We compared effectiveness of therapy in both groups Results. FP treatment was associated with a significant improvement in symptoms in patients with mild LT and LTB (Westley score 1-3) at 6 hours, in patients with moderate LT and LTB (Westley score 4-5) – at 12 hours. The improvement was slower in case of LTB than in LT. A total dose of FP used in children with mild LT and LTB up to Westley score 0 was 0,68±0,42 mg, in children with moderate LT and LTB – 1,1±0,81 mg versus 3,23±3,69 mg / kg and 4,43±3,77 mg / kg respectively as to prednisolone equivalent doses of systemic glucocorticoids in controls. The duration of treatment up to Westley score 0 was shorter in children treated with FP compared to controls Conclusion. Nebulized FP is effective in relieving the symptoms of mild to moderate LT and LTB

Abnormal Chemokine Receptor Profile on Circulating T Lymphocytes from Nonallergic Asthma Patients

Background: T lymphocytes are involved in the pathogenesis of nonallergic asthma. The objective of this study was to characterize the subset distribution and pattern of chemokine receptor expression in circulating T lymphocyte subsets from nonallergic asthma patients. Methods: Forty stable nonallergic asthma patients and 16 sex- and age-matched healthy donors were studied. Twelve patients did not receive inhaled steroids (untreated patients), 16 received 50-500 μg b.i.d. of inhaled fluticasone propionate (FP) (standard-dose patients), and 12 received over 500 μg b.i.d. of inhaled FP (high-dose patients) for at least 12 months prior to the beginning of this study and were clinically well controlled. Flow cytometry was performed using a panel of monoclonal antibodies (4 colors). Results: Nonallergic asthma patients treated with high doses of inhaled FP showed a significant reduction in the percentages of CD3+ T lymphocytes compared to healthy controls. Untreated patients showed a significant increase in CCR6 expression in CD8+CD25+ and CD8+CD25+bright T cells compared to healthy controls. The results were similar for CXCR3 and CCR5 expression. In patients treated with standard doses of FP, CCR5 expression was significantly increased in CD3+ T lymphocytes relative to healthy controls. Conclusions: The different groups of clinically stable nonallergic asthmatic patients showed distinct patterns of alterations in subset distribution as well as CCR6, CXCR3, and CCR5 expression on circulating T lymphocytes.

Inhaler reminders improve adherence with controller treatment in primary care patients with asthma

Poor adherence contributes to uncontrolled asthma. Pragmatic adherence interventions for primary care settings are lacking. To test the effectiveness of 2 brief general practitioner (GP)-delivered interventions for improving adherence and asthma control. In a 6-month cluster randomized 2 × 2 factorial controlled trial, with GP as unit of cluster, we compared inhaler reminders and feedback (IRF) and/or personalized adherence discussions (PADs) with active usual care alone; all GPs received action plan and inhaler technique training. GPs enrolled patients prescribed combination controller inhalers, with suboptimal Asthma Control Test (ACT) scores (ACT score ≤19). Inhaler monitors recorded fluticasone propionate/salmeterol adherence (covertly for non-IRF groups) and, in IRF groups, provided twice-daily reminders for missed doses, and adherence feedback. PAD GPs received communication training regarding adherence. Outcomes collected every 2 months included ACT scores (primary outcome) and severe exacerbations. Intention-to-treat mixed-model analysis incorporated cluster effect and repeated measures. A total of 43 GPs enrolled 143 patients with moderate-severe asthma (mean age, 40.3± 15.2 years; ACT score, 14.6± 3.8; fluticasone propionate dose, 718± 470 μg). Over 6 months, adherence was significantly higher in the IRF group than in non-IRF groups (73%± 26% vs 46%± 28% of prescribed daily doses; P< .0001), but not between PAD and non-PAD groups. Asthma control improved overall (mean change in ACT score, 4.5± 4.9; P< .0001), with no significant difference among groups (P= .14). Severe exacerbations were experienced by 11% of the patients in IRF groups and 28% of the patients in non-IRF groups (P= .013; after adjustment for exacerbation history; P= .06). Inhaler reminders offer an effective strategy for improving adherence in primary care compared with a behavioral intervention or usual care, although this may not be reflected in differences in day-to-day asthma control.

COST-effectiveness of salmeterol/fluticasone propionate combination (Advair®) in uncontrolled asthma in Canada

To evaluate the cost-utility of the treatment with a long acting beta-agonist (LABA) and inhaled corticosteroid (ICS) combination inhaler [salmeterol xinafoate (SAL)/fluticasone propionate (FP) combination inhaler (SFC) (Advair(®))] to continuing on current ICS dose (no ICS dose change) or increased ICS dose [fluticasone propionate (FP)] in patients with uncontrolled asthma in Canada. A cost-utility analysis was conducted from a Canadian public healthcare perspective with a one year time horizon. In the no FP dose change scenarios, remaining on daily low (FP 100ugBID) or medium (FP 200-250ugBID) or high dose (FP 500ugBID) was considered. In the increased FP dose scenarios, doubling the FP dose from low to medium dose and from medium to high dose regimens were considered. A decision model was developed with two health states: "symptom free" or "with symptoms". Clinical efficacy was based on a meta-analysis of relevant randomized controlled trials. Over the one year time horizon the percentage with symptom free days (SFD) was used as the measure of differential treatment scenario effectiveness. Drug costs and non-drug costs were incorporated into the analysis. Utilities, derived from EQ5D scores and health services resource use based on patient diaries for 'symptom free' and 'with symptoms' were based on regression analyses of individual patient data from the Gaining Optimal Asthma controL (GOAL) trial. Costs were assessed by assigning unit cost for each health services resource use for each patient. The incremental cost-utility ratios (ICUR) for SFC vs no FP dose change or increased FP dose were estimated using descriptive statistics. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis (PSA). Over one year, SFC resulted in an incremental cost per patient of $544-$655 compared to no FP dose change and $47-$380 per year compared to increased FP dose. SFC results in incremental QALYs per patient of 0.0100-0.0149 compared to no FP dose change and 0.0136-0.0152 compared to increased FP dose. The one year ICURs were $43,000 to $54,400 per QALY gained for SFC compared to no FP dose change and $25,000 to $3500 per QALY gained compared to increased FP dose scenarios. The probability of SFC being cost-effective at $50,000 per QALY gained was greater than 75% compared to increased FP dose scenarios and compared to no dose change for patients on low or medium dose FP. The results were robust to changes in assumptions within the model. In Canadian patients with inadequately controlled asthma on FP, it is cost-effective to use SFC for patients 12 years and over compared to doubling their FP dose. It is also cost-effective to use SFC for patients on low or medium dose FP compared to remaining on the current FP dose in patients with uncontrolled asthma.

Efficacy, Dose Reduction, and Resistance to High-Dose Fluticasone in Patients With Eosinophilic Esophagitis

We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms. We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants age 3-30 years with active EoE. Twenty-eight participants received FP, and 14 participants received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary end point was histologic evidence for CR. Secondary end points were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness. After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P = .0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR, and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P = .041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects who did not respond to FP and preliminary evidence for transcripts predictive of FP responsiveness. Daily administration of a high dose of FP induces histologic remission in 65%-77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%-93% of patients who initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283.

PD51 ‐ Children with asthma exposed to Environmental Tobacco Smoke (ETS) and inhaled corticosteroids treatment

Results There were 59.9% of boys and 50.1% of girls (mean age 10.83). Average dose of Fluticasone propionate (FP) was 225.11±119.98mcg per day per child. Among ETSE children, 208 were with one, 129 with both smoking parents, 228 had smoking mother and 238 had smoking father. ETSE children received statistically higher dose of FP, and dose of FP incresed with increasing of number of smokers in the family (F=45.41, p<0.001). ETSE children had lower lung function parameters before and after the IC, and the influence of mother and both smoking parents on lung function was more pronounced than fathers alone. After the 6 months of IC, both groups of children significantly improved lung function tests, no difference between groups.

Long-term, Randomized Safety Study of MP29-02 (a Novel Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate in an Advanced Delivery System) in Subjects With Chronic Rhinitis

MP29-02 is a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate (FP) in an advanced delivery system for the treatment of seasonal allergic rhinitis. The objective of this study was to evaluate the long-term safety of MP29-02 in subjects with chronic allergic (perennial) or nonallergic (vasomotor) rhinitis. This was a 1-year, randomized, open-label, active-controlled, parallel-group study in subjects with chronic allergic or nonallergic rhinitis. A total of 612 subjects were randomized in a 2:1 ratio to (1) MP29-02, one spray per nostril twice daily (total daily doses of azelastine hydrochloride and FP were 548 mcg and 200 mcg, respectively); or (2) FP, 2 sprays per nostril once daily (total daily dose 200 mcg). Safety and tolerability assessments were made at months 1, 3, 6, 9, and 12. The incidence of treatment-related adverse events was low with both MP29-02 (9.4%) and FP (11.1%), with no evidence of late-occurring adverse events. Nasal examinations showed no evidence of nasal mucosal ulcerations or septal perforations with MP29-02, and the overall incidence of adverse findings was reduced as the study progressed. There were no unusual or unexpected ocular examination findings and no clinically important laboratory findings or clinically important differences between groups in fasting AM serum cortisol levels after 12 months of treatment. MP29-02 was well tolerated. There were no safety findings that would preclude the long-term use of MP29-02 in the treatment of allergic rhinitis.

Health-care utilization and costs with fluticasone propionate and fluticasone propionate/salmeterol in asthma patients at risk for exacerbations

Although studies have established that adding long-acting beta agonists (LABA) to inhaled corticosteroid (ICS) monotherapy among patients with inadequately controlled asthma is associated with better outcomes than increasing ICS dosage, outcomes with ICS versus fixed-dose ICS/LABA combination among patients with recent asthma exacerbation or frequent use of rescue medication are unavailable. This study was designed to compare health-care utilization/costs among patients with recent asthma exacerbation or frequent rescue medication use who received fluticasone propionate (FP) alone versus fixed-dose FP/salmeterol combination (FSC). A retrospective cohort study was conducted using a large health insurance data set. Patients with one or more claims with asthma diagnosis, two or more prescriptions for FSC (250/50- or 100/50-mg formulations) or FP (220- or 110-mg formulations), and one or more asthma exacerbations or five or more short-acting beta agonist (SABA) prescriptions within 1 year before initial receipt of study medications were included. Health-care utilization/costs and controller therapy compliance were compared for patients receiving FSC versus FP using multivariate regression analysis controlling for FP dose and baseline characteristics. A total of 7779 patients met inclusion criteria (5769, FSC, and 2010, FP) with comparable mean follow-up (FSC, 685 days; FP, 670 days; p = 0.151). Controlling for FP dosage and baseline characteristics, FSC patients had lower risks of asthma-related exacerbations, fewer SABAs and systemic corticosteroids, higher costs of asthma medications and total asthma-related health care, and lower total asthma-related health-care costs excluding study medication cost. In asthma patients with recent exacerbation or frequent SABA use, receipt of FSC reduced asthma-related exacerbation risks and rescue medication use versus receipt of FP.

GLCCI1 rs37973 does not influence treatment response to inhaled corticosteroids in white subjects with asthma

GLCCI1 rs37973 does not influence treatment response to inhaled corticosteroids in white subjects with asthma

Inhaled long-acting β2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD

Combination inhaled therapy with long-acting β2 agonists (LABAs) and corticosteroids is beneficial in treating asthma and chronic obstructive pulmonary disease (COPD). In asthma, LABAs enhance glucocorticoid receptor (GR) nuclear translocation in the presence of corticosteroids. Whether this biological mechanism occurs in COPD, a relatively corticosteroid-resistant disease, is uncertain. Eight patients with mild/moderate COPD participated in a double-blind, placebo-controlled, crossover study and inhaled single doses of fluticasone propionate (FP) 100 μg, FP 500 μg, salmeterol xinafoate (SLM) 50 μg, and combination FP 100 μg + SLM 50 μg. One hour postinhalation, sputum was induced, nuclear proteins isolated from purified macrophages, and levels of activated nuclear GR quantified by using a GR-glucocorticoid response element ELISA-based assay. Nuclear GR significantly increased after the inhalation of FP 500 μg (P < .01), but not after the inhalation of FP 100 μg or SLM 50 μg, compared with placebo. Interestingly, SLM in combination with FP 100 μg increased nuclear GR levels equivalent to those of FP 500 μg alone. This was significantly greater than either FP 100 μg (P < .05) or SLM 50 μg (P < .01) alone. In vitro in a human macrophage cell line, SLM (10(-8) mol/L) enhanced FP (10(-9) mol/L)-induced mitogen-activated protein kinase phosphatase-1 mRNA (5.8 ± 0.6 vs 8.4 ± 1.1 × 10(-6) copies, P < .05) and 2 × glucocorticoid response element-luciferase reporter gene activity (250.1 ± 15.6 vs 103.1 ± 23.6-fold induction, P < .001). Addition of SLM (10(-9) mol/L) to FP (10(-11) mol/L) significantly enhanced FP-mediated suppression of IL-1β-induced CXCL8 (P < .05). Addition of SLM 50 μg to FP 100 μg enhanced GR nuclear translocation equivalent to that seen with a 5-fold higher dose of FP in sputum macrophages from patients with COPD. This may account for the superior clinical effects of combination LABA/corticosteroid treatment compared with either as monotherapy observed in COPD.

Airway responsiveness to adenosine after a single dose of fluticasone propionate discriminates asthma from COPD

BackgroundRegular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperresponsiveness (AHR) to adenosine 5′-monophosphate (AMP) in asthma even after a single dose of fluticasone propionate (FP). AimTo determine whether this rapid protective effect of a single dose of FP is also present in COPD. Methods23 mild asthmatic and 24 COPD subjects with documented AHR to both AMP and methacholine took part in a randomized, double-blind, placebo-controlled, crossover study to measure AHR to inhaled AMP and methacholine 2 h after either 1000 μg FP or matched placebo. ResultsIn subjects with asthma, 1000 μg FP in a single dose significantly attenuated the constrictor response to AMP, geometric mean (range) PC20AMP values increasing from a 19.2 (1.3–116.3) to 81.5 (9.6–1600.0) (p < 0.001; post-placebo vs post-FP) mg/ml. Change in the airways response to inhaled AMP after FP was well within test variability in patients with COPD, with PC20AMP values 59.6 (11.3–183.9) and 76.3 (21.0–445.3) (p = 0.022; post-placebo vs post-FP) mg/ml. Additionally, FP failed to significantly attenuate the bronchial response to methacholine in both asthma and COPD subjects. A change in doubling dilution, between placebo and following a single dose of FP, in AMP had a better sensitivity and specificity of 95.8% and 65.2%, compared to methacholine of 79.2% and 43.5% respectively in delineating between COPD and asthma. ConclusionA single dose of 1000 μg FP rapidly improves AHR to AMP in asthmatics but not in COPD subjects. This may provide a convenient way by which provocation challenge with inhaled AMP may help in discriminating asthma from COPD.

Understanding risk in asymptomatic carotid stenosis

Drug delivery by inhalation is used to maximize the therapeutic effect in the lung while minimizing systemic exposure. However, to achieve the best possible treatment we need to understand where a targets is expressed in the lung and assure retention of drugs at the relevant location. Currently, our models regard the lung as a uniform unit and do not distinguish between different tissue structures and hence we need to increase our understanding of what structures are targeted by inhalation and if all benefit from inhaled delivery equally. In the present study, we used RNAscope in-situ hybridization to systemically examine how the administration route influences which part of the lung respond to fluticasone propionate (FP). Together with an automated image analysis, developed specifically to adress the different sub-compartments of the lung, we were able to measure mRNA expression of Zbtb16 in epithelium, sub-epithelium, alveolar bed and blood vessels. Spleenic Zbtb16 expression, measured by qPCR, was used to assess systemic responses. The results show that inhaled and i.v. administration give different distinct spatial responses. Inhalation of FP provides superior targeting of the airway epithelium and sub-epithelium regions but not alveolar space or vasculature compared to systemic administration. Finally, the analysis shows that exclusive targeting of lung epithelium by inhalation can be achieved with very low doses of FP.

The effect of inhaled corticosteroids on hypothalamic-pituitary-adrenal axis

Objectives:The aim of this study was to compare systemic effects of high-dose fluticasone propionate (FP) and beclomethasone dipropionate (BDP) via pressurized metered dose inhaler on adrenal and pulmonary function tests.Materials and Methods:A total of 66 patients with newly diagnosed moderate persistent asthma without previous use of asthma medications participated in this single blind, randomized, parallel design study. FP or BDP increased to 1 500 μg/d in 62 patients who had not received oral or IV corticosteroids in the previous six months. Possible effects of BDP and FP on adrenal function were evaluated by free cortisol level at baseline and after Synacthen test (250 μg). Fasting plasma glucose and pulmonary function tests were also assessed. Similar tests were repeated 3 weeks after increasing dose of inhaled corticosteroids to 1 500 μg/d.Results:No statistically significant suppression was found in geometric means of cortisol level post treatment in both groups. After treatment in FP group, mean forced expiratory volume in one second (FEV1) and mean forced vital capacity (FVC) values improved by 0.17 l (5.66% ± 13.91, P=0.031) and 0.18 l (5.09% ± 10.29, P=0.010), respectively. Although FEV1 and FVC improved in BDP group but was not statistically significant. Oral candidiasis and hoarseness were observed in 6.5% patients receiving BDP, but hoarseness was found in 3.2% patients in FP group (P=0.288).Conclusions:The results indicate that safety profiles of high doses of BDP and FP with respect to adrenal function are similar, but FP is more efficacious than that of BDP in improving pulmonary function test.

Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

BackgroundInhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients.MethodsPatients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed.ResultsThe intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml) to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p ≤ 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02).ConclusionsFF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose.Trial registrationClinicaltrials.gov; NCT00766090.

No effect of fluticasone propionate on linear growth in preschool children with asthma

Eighty percent of asthmatic children develop asthma symptoms by the age of 5 years. Inhaled corticosteroids (ICS), depending on dosage, may cause linear growth reduction and adrenal gland suppression. There are few studies about linear growth of preschool children with asthma. The aim of the present study was to investigate whether there is any effect of fluticasone propionate (FP) on linear growth and adrenal gland function. Twenty-eight children aged 18-52 months with persistent asthma receiving ICS FP 100-200 µg daily were studied for 1 year. Patients were divided into two groups according to clinical parameters: well (group 1) and poorly controlled (group 2). Height was measured every 3 months and expressed as height standard deviation score (SDS). Cumulative dose of FP expressed in mg was calculated for every patient. Early morning levels of serum adrenocorticotropic hormone (ACTH) and cortisol were assessed at the beginning and at the end of the study. Patients took FP for an average of 11 months in group 1 and 16 months in group 2, which was not statistically significantly different. At the end of the study height SDS difference was -0.0143 in group 1 and -0.2000 in group 2, which was not statistically significantly different (t= 0.6072, P= 0.5489). There was also no statistically significant difference for average cortisol (P= 0.4381) or ACTH (P= 0.5845) concentration at the end of the study. FP 100-200 µg daily had no effect on linear growth or on the hypothalamic-pituitary-adrenal gland axis but further follow up is necessary.

Effect of addition of salmeterol versus doubling the dose of fluticasone propionate on specific airway resistance in children with asthma

Based primarily on extrapolation from adult studies, current pediatric asthma guidelines advise the addition of long-acting beta₂-agonists for children symptomatic on low/moderate-dose inhaled corticosteroids before increasing the corticosteroid dose. This study was designed to compare the effect of combination salmeterol/fluticasone propionate (SFC) with doubling the dose of fluticasone propionate (FP) on specific airway resistance (sR(aw)) in moderate/severe persistent asthmatic children. A double-blind, randomized, controlled study was performed; children with asthma (4-11 years old; sR(aw) > 1.3 kPa·s) were randomized after a 2-week run-in (FP, 100 μg, b.i.d.) to either SFC (50 μg/100 μg b.i.d.) or FP (200 μg b.i.d.) via Diskus (GlaxoSmithKline, Stockley Park, U.K.) for 6 weeks. Lung function (sR(aw)-plethysmography and forced expiratory volume in 1 second [FEV₁]) was measured before run-in, at randomization, after 3 weeks, at the end of 6-week treatment, and after 48-hour washout. Symptom scores and rescue medication use were recorded throughout. Thirty-five children entered run-in and 24 were randomized (mean age, 7.3 ± 2.2 years; 50% boys). All children showed an improvement in sR(aw). After adjusting for age, gender, and baseline sR(aw,) children receiving SFC had a significantly greater improvement in sR(aw) compared with those receiving FP (adjusted means ratio [95% confidence interval {CI}], 0.81 [0.68-0.97]; p = 0.021). There was a significant interaction between treatment and gender (sR(aw), adjusted geometric mean [95% CI ]kPa·s, SFC versus FP: boys, 1.25 [1.10-1.41] [n = 7] versus 1.87 [1.61-2.17] [n = 5]; girls, 1.29 [1.10-1.52] [n = 5] versus 1.29 [1.13-1.47] [n = 7]; p = 0.008). There were no differences in FEV₁, symptoms, or rescue medication use between the groups. Addition of salmeterol provides greater improvement in sR(aw) than doubling the dose of FP in children with moderate/severe persistent asthma.

Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: A randomized controlled trial

Asthma control is now recognized as the main goal of asthma therapy. Guidelines recommend finding the lowest effective dose of inhaled corticosteroids in children with persistent asthma. The aim of this study was to investigate the efficacy of an allergen-specific immunotherapy with a high-dose hypoallergenic mite preparation (allergoid) as steroid-sparing agent in children with allergic asthma. Sixty-five children with asthma (Global Initiative for Asthma treatment levels II and III; 6-17 years old), after reaching asthma control with inhaled steroids during a 5-month baseline period, were randomized for subcutaneous mite allergoid immunotherapy (SCIT) plus fluticasone propionate (FP) or FP therapy alone for 2 years. During 2 subsequent 5-month winter periods, steroid therapy was adjusted according to predefined dose steps, determining and comparing the changes in FP dosages and the lowest FP dose sufficient to maintain asthma control. Immunologic and functional investigations were also carried out. Children treated with house dust mite SCIT plus FP were able to significantly reduce the FP dose by more steps (P < .05), compared with the control group on FP alone. The mean daily dose in the immunotherapy group decreased from 330.3 μg in the baseline period to 151.5 μg after 2 treatment years, whereas in the control group the dose decreased from 290.6 μg to 206.3 μg. Compared with the control group, significant improvement was also observed in morning peak expiratory flow (P = .0315). Significantly increased levels of specific IgG(1) (P = .0001) and IgG(4) (P < .0001) were also observed. Adding a mite allergoid SCIT to pharmacologic treatment is an effective and safe strategy to reduce corticosteroid doses while maintaining disease control in children with mite-induced allergic asthma.

Stepping down to fluticasone propionate or a lower dose of fluticasone propionate/salmeterol combination in asthma patients recently initiating combination therapy

Clinical guidelines recommend add-on therapy with long-acting beta2-agonists (LABA) in patients with mild-to-moderate persistent asthma whose disease is not adequately controlled with inhaled corticosteroids (ICSs) alone. For those achieving control with add-on therapy, careful reduction in ICS dose followed by withdrawal of LABA is recommended. This study was designed to compare asthma-related outcomes in patients receiving fluticasone propionate/salmeterol combination (FSC) who stepped down to a lower dose of FSC versus those who stepped down to fluticasone propionate (FP) at the same dose of FP. A retrospective observational cohort study was performed using two large health insurance claims databases spanning from January 2000 to June 2007. Subjects were age > or =12 and <65 years, had a diagnosis of asthma (International Classification of Diseases [ICD-493.xx]), and who within 1 year of initiating FSC either stepped down to a lower dose of FSC ("FSC patients") or to FP only at the same dose of FP ("FP patients"). FSC and FP patients were matched based on propensity scores to control for potential differences in baseline demographic and clinical characteristics and preindex asthma-related and costs. Of 4350 subjects identified, 3881 stepped down to a lower dose of FSC and 469 stepped down to FP. After matching, there were 447 pairs of FSC and FP patients. FSC patients had 30% fewer prescriptions for short-acting beta-agonists, a 26% lower risk of receiving systemic corticosteroids, and a 48% lower risk of asthma-related hospitalization or Emergency Department visit during follow-up. Stepping down to FP monotherapy is associated with worsening asthma symptoms and greater risk of severe asthma-related exacerbations compared with staying on FSC at a lower ICS dose.