Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated.
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Prospective animal study.
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In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients.
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Receptor-ligand interactions of fluticasone propionate (FP), a glucocorticoid used for inhalation therapy, were determined and compared with dexamethasone, budesonide, and beclomethasone-17-monopropionate, the active metabolite of beclomethasone dipropionate. Two approaches, evaluation of binding kinetics and competition assays, were applied to obtain relative receptor affinities (RRAs) with dexamethasone as reference. A higher association rate constant and a distinctly lower dissociation rate constant for FP compared with the other glucocorticoids resulted in an equilibrium dissociation constant (Kd) of 0.49 nmol/l. Kd dexamethasone was 9.36 nmol/l; derived RRA of FP was 1910. The calculated half-time of the FP-receptor complex was 10 h, thus exceeding the half-times of all other glucocorticoids as well as their RRAs. Competition assays clearly confirmed the rank order of the tested glucocorticoids, although RRAs were generally lower than those found in kinetic assays and strongly dependent on the assay conditions. The high receptor affinity of FP is reflected by clinical trials demonstrating its superiority to other glucocorticoids. For therapeutic application, the long half-time of the FP-receptor complex should support the practicality of longer dose-intervals.
Whether small airways dysfunction persists in patients with asthma receiving standard community treatment is unknown. Impulse oscillometry (IOS) is a sensitive measure of small airways function.
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A model-based approach using non-linear mixed-effects analyses was used to assess data from studies 1 and 2.
In a double-blind, crossover study, 100 patients were randomized to MFNS microg followed by FPNS 200 microg, or vice versa. Patients rated the study drugs by completing an individual product sensory attributes questionnaire at the end of each period of drug administration. An overall sensory preference questionnaire was completed following crossover.
The response to ACTH for groups 1 and 2 did not differ from that of control subjects. Group 3 had lower peak, increment, and area under curve cortisol responses than those in controls, whereas group 4 had lower baseline, peak, and area under curve cortisol responses. Eight patients failed the LDST (peak cortisol <500 nmol/L and increment <200 nmol/L): controls = 0/14, group 1 = 0/7, group 2 = 1/17, group 3 = 4/4, and group 4 = 3/7. Treatment score (based on GC potency, area treated, and duration) was the only factor to influence peak cortisol response on LDST (r(2) = 24%). In group 4, only 1 of 7 patients had a cortisol profile within the normal range but he failed the LDST. In the 5 subjects with an 08.00 hours cortisol <300 nmol/L, the matched ACTH level was inappropriately low.
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Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihistamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis.
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This article reviews the association between pneumonia and chronic obstructive pulmonary disease (COPD) and the possible role of inhaled corticosteroids in increasing the risk of pneumonia in patients with COPD. An increased risk of pneumonia with inhaled corticosteroids was first reported from the Toward Revolution in COPD Health (TORCH) study, a large randomized clinical trial comparing fluticasone, salmeterol, or a combination of the two medications with placebo. We carried out a large observational study using a health care administrative database of information on hospitalizations and medication use among patients older than 65 years of age in Quebec. We found an excess of pneumonia requiring hospitalization and an excess of pneumonia hospitalizations leading to death in relation to current use of inhaled corticosteroids, especially at high doses. Here, we explore the potential mechanisms of this association and try to weigh the benefits and risks of therapy with inhaled corticosteroids in patients with COPD.
Numbers of patients identified were 284 beginning fluticasone propionate; 302, montelukast; and 195, zafirlukast. Fluticasone propionate treatment was associated with significantly (p<0.001) lower risk-adjusted asthma-related charges compared with montelukast and zafirlukast treatment: $528, $967, and $1359, respectively In this cohort, fluticasone propionate also was associated with fewer hospitalizations, less need for additional controller agents, and longer maintenance on the index drug compared with montelukast and zafirlukast.
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The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs.
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Of the 45 enrolled subjects, 38 subjects completed the study, including 20 subjects in the placebo group and 18 subjects in the drug group. There was no significant difference in the amount of induration between drug and placebo groups for any of the three periods tested.
We identified patients initiating therapy with either budesonide/formoterol or fluticasone/salmeterol after May 2001 in a clinical database. We compared asthma medication and health care utilisation over the subsequent year.
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SLM, FP, and DSCG reduced symptoms and need for rescue medication (P <.04). Both SLM and FP improved PEF and increased PD15FEV(1) to histamine by 2.8 and 5.2 doubling dose units, respectively. Both compounds reduced BHR more than placebo (P <.05). Both SLM and placebo had no effect on any inflammatory cell type. In both FP-treated and DSCG-treated patients, the number of EG2-positive eosinophils in the airway mucosa decreased (P =.002 and P <.05, respectively).
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A case-control nested cohort study was performed to assess the association of asthma with nontuberculous mycobacterium (NTM) infection.
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New Zealand prescription database can be a potential source to identify ADRs engaging the PSSA method, and this could complement pharmacovigilance surveillance in NZ. The PSSA can be an important method for post-marketing surveillance and monitoring of ADRs which have relatively short latency. However, the predictive validity of PSSA will be compromised in certain scenarios, particularly when sample size is small, when new drugs are in the market and data are sparse.
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There was marked volatility in the types of asthma medication used over the 6 years. Reciprocal trends leading to increased use of spacers and decreased use of nebulisers are in accord with national guidelines for better asthma management. The increasing use of products containing a combination of salmeterol and fluticasone requires ongoing monitoring.
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To investigate the dosage and duration of inhaled steroids prescribed to children and to compare the prescribed doses with recommended doses for the treatment of asthma in children.
Salmeterol/fluticasone propionate 50mug /100mug twice daily was significantly more effective than budesonide 400mug twice daily in improving lung function and reducing symptoms and use of rescue medication in Chinese asthmatic patients who were poorly controlled on low-dose inhaled corticosteroids. This confirms the findings of superior efficacy of this combination product over budesonide in other populations.
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The % profiles of dissolution and permeation were apparent first-order or pseudo-zero-order, reaching varying 1.9-95.0% by 5 h. Their kinetics overall conformed to the ICS aqueous solubility. With increasing aerosol mass, however, the profiles decelerated, attributed to undissolved ICSs left by the limited dissolution fluid capacity. The profiles could be also product-specific, as beclomethasone dipropionate aerosols from QVAR dissolved faster than those from VANCERIL, whereas fluticasone propionate aerosols from two different inhaler products exhibited comparable profiles. The 2.1-3.3 mum aerosols dissolved faster than the 4.7-5.8 mum aerosols.