fluticasone and Hypersensitivity

Topics: Anti-Allergic Agents; Biosensing Techniques; Confidentiality; Exhalation; Fluticasone; Health Communication; Humans; Hypersensitivity; Medical Informatics; Monitoring, Physiologic; Nitric Oxide; Patient Compliance; Salmeterol Xinafoate; Self-Management; Smartphone; Spirometry

Single-dose inhaled corticosteroids (ICS) induce direct anti-inflammatory effects in asthma thereby improving airway hyperresponsiveness (AHR). A novel enhanced-affinity ICS, fluticasone furoate (FF), demonstrated a prolonged duration of action in vitro. The aim of this study was to evaluate the efficacy and duration of action of a single dose of FF by studying protection against AHR to adenosine 5'-monophosphate (AMP) and effects on exhaled nitric oxide (eNO).. A randomized, double-blind, placebo-controlled, 6-way crossover study (FFA10026) was performed in 24 patients with allergic asthma (mean age 32.8 years, FEV(1) ≥ 70% predicted and PC(20) AMP ≤ 50 mg/ml). Each subject received a single dose of FF 1000 μg, fluticasone proprionate (FP) 1000 μg, or placebo at 2 (FF only), 14 or 26 h prior to AMP challenge and eNO measurement.. FF significantly improved PC(20) AMP compared to placebo, the difference in doubling concentrations being 2.18 (95% confidence interval: 1.13-3.23), 1.54 (0.48-2.59), and 1.30 (0.26-2.34) at 2, 14 and 26 h. FP improved PC(20) AMP significantly at 14 h compared to placebo, but not at the 26-hour time point, the difference in doubling concentrations being 1.72 (0.70-2.75) and 0.33 (-0.69-1.34). There was no significant effect on eNO after either FF or FP at all time points. FF was well tolerated and there were no serious adverse events.. The new inhaled corticosteroid FF, but not FP, demonstrates prolonged protection up to 26 h against AHR to AMP in asthma patients.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Exhalation; Female; Fluticasone; Humans; Hypersensitivity; Male; Nitric Oxide; Respiratory Function Tests

Adding a long-acting beta(2)-agonist to inhaled corticosteroids results in better symptomatic asthma control than increasing the dose of inhaled corticosteroids.. Investigating whether adding the long-acting beta(2)-agonist salmeterol to the inhaled corticosteroid fluticasone propionate has an effect on allergen-induced allergic inflammation in asthma.. Bronchial allergen challenges were performed in 26 patients with allergic asthma, pretreating them with a single dose of either fluticasone/salmeterol (100/50 microg) or fluticasone alone (100 microg), in a double-blind, randomized, cross-over design. Sputum and serum markers of bronchial inflammation were measured after allergen challenge, as well as lung function parameters. Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein.. Asthmatic responses after allergen challenge were significantly reduced after pretreatment with fluticasone/salmeterol relative to fluticasone alone. Sputum inflammatory markers after allergen challenge were not significantly affected by fluticasone/salmeterol pretreatment. By contrast, serum IL-5 was significantly reduced (geometric mean serum IL-5 [SEM]: 0.5 [0.3] vs 1.1 [0.3] pg/mL 1 hour and 0.6 [0.3] vs 1.1 [0.3] pg/mL 6 hours after challenge with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P values < .05). Also, peripheral blood eosinophils were significantly reduced (geometric mean number x 10(6)/L [SEM]: 172 [0.1] vs 237 [0.1] at 6 hours and 271 [0.1] vs 351 [0.1] at 24 hours with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P < .05).. Adding salmeterol to fluticasone reduces allergen-induced serum IL-5 and peripheral blood eosinophils. This phenomenon may contribute to the improved clinical outcomes that result from adding a long-acting beta(2)-agonist to inhaled corticosteroids.

Topics: Administration, Inhalation; Albuterol; Allergens; Androstadienes; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Eosinophils; Fluticasone; Humans; Hypersensitivity; Interleukin-5; Leukocyte Count; Salmeterol Xinafoate; Time Factors

Allergic sensitisation of the airways occurs in the mucosa of the shock organ, or in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa in humans is the adenoid. Pediatric adenoidal obstruction of the nasal airway is associated with significant morbidity and is a frequent indication for surgery. Because efficacious medical alternatives to adenoidectomy are lacking, we assessed the potency of standard-dose topical nasal fluticasone propionate and Cetirizine in reduction of adenoidal obstruction of the nasal airway. To examine the influence of these medicines on the adenoid hypertrophy (AH) we studied 43 children ages 4 to 9 years, who had AH and house dust mite allergy. Properly administered aqueous nasal fluticasone propionate and Cetirizine in standard doses can significantly reduce adenoidal hypertrophy and nasal airway obstructive symptoms in atopic children.

Topics: Adenoids; Administration, Intranasal; Administration, Topical; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Cetirizine; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Fluticasone; Humans; Hypersensitivity; Hypertrophy; Male; Pyroglyphidae

This study was performed in patients with allergic rhinitis/conjunctivitis to birch pollen to determine whether patients with additional hypersensitivity to nuts and apples differed from patients without such hypersensitivity; the determination was in terms of results of skin prick test (SPT), specific IgE antibodies (RAST), and symptoms during the pollen season. Forty-seven patients with birch pollen allergy were investigated by RAST against birch and hazel pollen and by SPT. They were treated in a randomized, double-blind, placebo-controlled study with fluticasone propionate aqueous nasal spray or placebo. The area of the SPTs was larger and the specific IgE values higher in patients with hypersensitivity to nuts and apples. These patients also had more symptoms during the pollen season. We conclude that hypersensitivity to nuts is an indication of a more severe allergy in patients with birch pollen allergic rhinitis.

Topics: Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Food Hypersensitivity; Fruit; Humans; Hypersensitivity; Immunoglobulin E; Male; Middle Aged; Nuts; Pollen; Radioallergosorbent Test; Severity of Illness Index; Skin Tests; Trees

Topics: Albuterol; Animals; Asthma; Bronchodilator Agents; Child; Diagnosis, Differential; Fluticasone; Guinea Pigs; Humans; Hypersensitivity; Immunoglobulin E; Male; Respiratory Sounds; Rhinitis, Allergic; Spirometry

Omalizumab has been shown to reduce exacerbation rates in moderate to severe allergic asthma. Our aim was to evaluate omalizumab efficacy and safety in a real-life setting in severe asthmatic children. 104 children (aged 6-18 years), followed up in paediatric pulmonary tertiary care centres, were included at the beginning of omalizumab treatment. Asthma control levels, exacerbations, inhaled corticosteroid dose, lung function and adverse events were evaluated over 1 year. Children were characterised by allergic sensitisation to three or more allergens (66%), high IgE levels (mean 1125 kU · L(-1)), high rate of exacerbations (4.4 per year) and healthcare use during the previous year, and high inhaled corticosteroid dose (mean 703 μg equivalent fluticasone per day). Asthma control levels defined as good, partial or poor, improved from 0%, 18% and 82% at entry to 53%, 30% and 17% at week 20, and to 67%, 25% and 8% at week 52, respectively (p<0.0001). Exacerbation and hospitalisation rates dropped by 72% and 88.5%, respectively. At 12 months, forced expiratory volume in 1 s improved by 4.9% (p=0.023), and inhaled corticosteroid dose decreased by 30% (p<0.001). Six patients stopped omalizumab for related significant adverse events. Omalizumab improved asthma control in children with severe allergic asthma and was generally well tolerated. The observed benefit was greater than that reported in clinical trials.

Topics: Administration, Oral; Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Asthma; Child; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Hypersensitivity; Immunoglobulin E; Male; Omalizumab; Respiratory Function Tests; Treatment Outcome

To constitute an animal model of laryngeal allergy and evaluate the laryngeal effects of inhaled corticosteroids and ß2-agonists on the laryngeal mucosa in an allergic rat model.. Prospective randomized.. The Experimental Medical Research Institute (DETAE) at Istanbul University.. Wistar Albino rats (n = 32) were sensitized with ovalbumin. Unsensitized rats (n = 8) served as controls. The rats were exposed to aerosolized ovalbumin (1%). On days 28 through 42, every 2 days preceeding ovalbumin exposure, rats were further exposed to aerosolized phosphate buffered saline (n = 8), fluticasone propionate (n = 8), salbutamol (n = 8), and combined salbutamol+fluticasone propionate (n = 8). Inflammatory cell infiltration was graded semi-quantitatively. The quantitative data included mast cell count and degranulation. Ultrathin sections were investigated under transmission electron microscope.. The simultaneous and pairwise comparison of groups (Kruskal-Wallis) revealed statistically significant difference among groups at supraglottic level (critical P < .05, <.01) and no difference at glottic level. In ovalbumin+phosphate buffered saline exposed rats, the light microscopy of supraglottic mucosa revealed regular epithelium with severe inflammatory cell infiltration and increased mast cell count. Electron microscopy revealed increased mast cell degranulation. Increased inflammatory cell infiltration was detected along with reduced mast cell count among fluticasone propionate treated rats. Mild inflammatory cell infiltration was encountered in combined salbutamol+fluticasone propionate treated rats.. This study supported the presence of localized allergic reaction in the supraglottic laryngeal mucosa through the observation of increased mast cell number and degranulation. It was also shown that inhaled corticosteroids increase inflammation whereas combined inhaled corticosteroids and ß2-agonists minimize allergic and inflammatory reactions in supraglottic laryngeal mucosa providing a safer therapeutic option.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Animals; Disease Models, Animal; Fluticasone; Hypersensitivity; Laryngeal Mucosa; Mast Cells; Ovalbumin; Prospective Studies; Random Allocation; Rats; Rats, Wistar

To our knowledge, in Asia, data on utility of allergy tests in management of eosinophilic esophagitis are lacking. The objective of our study was to determine the role of allergy evaluation in management of Saudi children with eosinophilic esophagitis.. Children diagnosed as having eosinophilic esophagitis during the period from 2009 to 2012 were referred to an allergist for allergy evaluation. The allergy evaluation consisted of total IgE level, radio-allergosorbent assay, and skin prick test. Depending on the results of the allergy tests, a restricted or elemental diet was established. Swallowed fluticasone inhaler was prescribed to patients who rejected or failed to respond to the diet. Clinical, endoscopic, and histological evaluation was performed in 8 weeks to assess response.. Eighteen children with eosinophilic esophagitis were included (13 males; mean age 5 years, range 1-11). Sensitization to foods was demonstrated in 14 patients: 4 with a positive test for a single food (28.5%), 1 for 2 food allergens (7%), and 9 for ≥3 food allergens (64.5%). The most common food allergens were milk, soybean, wheat, egg, and nuts. Three young children out of the total 14 patients responded to elemental formula. Four of the 10 older children on the allergy testing guided-dietary restriction achieved partial remission and the remaining 6 did not respond. All 10 patients responded to a swallowed fluticasone inhaler.. Although food sensitizations in Saudi children with eosinophilic esophagitis are common, the allergy tests had limited predictive value for the response to dietary elimination.

Topics: Androstadienes; Anti-Allergic Agents; Child; Child, Preschool; Eosinophilic Esophagitis; Female; Fluticasone; Follow-Up Studies; Food Hypersensitivity; Food, Formulated; Humans; Hypersensitivity; Immunoglobulin E; Infant; Male; Predictive Value of Tests; Radioallergosorbent Test; Retrospective Studies; Skin Tests

Despite major efforts, factors that predict or correspond to the level of allergic symptoms remain elusive. Given our previous observations of mucosal interleukin-10 (IL-10) expression by local tissue cells and its described role as immune modulator, we hypothesized that, in allergic rhinitis, nasal mucosal IL-10 expression could influence the severity of symptoms.. In this study, we investigated endothelial IL-10 expression in nasal mucosa of healthy- and house dust mite allergic patients, both before and after provocation, and under nasal steroid therapy. Nasal turbinate biopsies were taken from healthy individuals as well as from house dust mite allergic patients, both before and after provocation. Allergic patients received fluticasone proprionate aqueous nasal spray or control treatment. In the allergic patients, endothelial IL-10 scores based on immunohistochemical stainings were correlated with allergic symptoms, measured by visual analog scores.. At baseline, variable levels of endothelial IL-10 were detected in nasal biopsies. After nasal provocation, but not at baseline, endothelial IL-10 expression corresponded very closely to the allergic symptoms after allergen provocation. Low symptom scores were correlated with high endothelial IL-10 scores. This correlation disappeared after fluticason propionate treatment.. There is a large variation in the level of endothelial IL-10 expression both in healthy individuals and in house dust mite allergic patients. Endothelial IL-10 expression may affect local immune reactions resulting in reduced levels of allergic symptoms.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Animals; Endothelium; Female; Fluticasone; Humans; Hypersensitivity; Interleukin-10; Male; Middle Aged; Nasal Mucosa; Nasal Provocation Tests; Pyroglyphidae; Young Adult

GATA-3 plays a critical role in regulating the expression of the cytokines interleukin (IL)-4, IL-5, and IL-13 from T helper-2 (Th2) cells and therefore is a key mediator of allergic diseases. Corticosteroids are highly effective in suppressing allergic inflammation, but their effects on GATA-3 are unknown. We investigated the effect of the corticosteroid fluticasone propionate on GATA-3 regulation in human T-lymphocytes in vitro and in vivo.. In a T lymphocyte cell line (HuT-78) and peripheral blood mononuclear cells stimulated by anti-CD3 and anti-CD28 in vitro we demonstrated that fluticasone inhibits nuclear translocation of GATA-3 and expression of Th2 cytokines via a mechanism independent of nuclear factor-kappaB and is due, in part, to competition between GATA-3 and the ligand-activated glucocorticoid receptor for nuclear transport through the nuclear importer importin-alpha. In addition, fluticasone induces the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), the endogenous inhibitor of p38 MAPK, which is necessary for GATA-3 nuclear translocation. These inhibitory effects of fluticasone are rapid, potent, and prolonged. We also demonstrated that inhaled fluticasone inhibits GATA-3 nuclear translocation in peripheral blood lymphocytes of patients with asthma in vivo.. Corticosteroids have a potent inhibitory effect on GATA-3 via two interacting mechanisms that potently suppress Th2 cytokine expression. This novel mechanism of action of corticosteroids may account for the striking clinical efficacy of corticosteroids in the treatment of allergic diseases.

Topics: Active Transport, Cell Nucleus; Administration, Inhalation; Adrenal Cortex Hormones; alpha Karyopherins; Androstadienes; Anti-Allergic Agents; Asthma; Cell Line; Cytokines; Dual Specificity Phosphatase 1; Fluticasone; GATA3 Transcription Factor; Gene Expression Regulation; Humans; Hypersensitivity; Interleukin-4; Leukocytes, Mononuclear; Phosphorylation; Receptors, Glucocorticoid; Th2 Cells

Topics: Adult; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Deglutition Disorders; Eosinophilia; Esophagitis; Fluticasone; Humans; Hypersensitivity; Male; Recurrence; Time Factors

Fluticasone furoate (FF) is a novel enhanced-affinity glucocorticoid that has been developed as topical therapy for allergic rhinitis. The pharmacological properties of FF have been investigated using a number of in vitro experimental systems. FF demonstrated very potent glucocorticoid activity in several key pathways downstream of the glucocorticoid receptor (GR) as follows: the transrepression nuclear factor-kappaB (NF-kappaB) pathway, the transactivation glucocorticoid response element pathway, and inhibition of the proinflammatory cytokine tumor necrosis factor-alpha. Furthermore, FF showed the greatest potency compared with other glucocorticoids for preserving epithelial integrity and reducing epithelial permeability in response to protease- and mechanical-induced cell damage. FF showed a 30- to >330,000-fold selectivity for GR-mediated inhibition of NF-kappaB vs. the other steroid hormone receptors, substantially better than a number of other clinically used glucocorticoids. In studies examining the respiratory tissue binding properties of glucocorticoids, FF had the largest cellular accumulation and slowest rate of efflux compared with other clinically used glucocorticoids, consistent with greater tissue retention. The in vivo anti-inflammatory activity of FF was assessed in the Brown Norway rat ovalbumin-induced lung eosinophilial model of allergic lung inflammation. At a dose of only 30 microg, FF achieved almost total inhibition of eosinophil influx in the lung, an inhibition that was greater than that seen with the same dose of fluticasone propionate. In conclusion, the potent and selective pharmacological profile of FF described here could deliver an effective, safe, and sustained topical treatment of respiratory inflammatory diseases such as allergic rhinitis and asthma.

Topics: Androstadienes; Animals; Cell Line, Tumor; Cell Membrane Permeability; Chlorocebus aethiops; Disease Models, Animal; Epithelial Cells; Fluticasone; Glucocorticoids; Humans; Hypersensitivity; Inflammation; Lipopolysaccharides; NF-kappa B; Pancreatic Elastase; Rats; Rats, Inbred BN; Receptors, Steroid; Respiration Disorders; Tumor Necrosis Factor-alpha

Due to common features of asthma and allergic rhinitis, a single therapeutic approach to treating both of these conditions has been proposed.. To compare and contrast the use of rhinitis medications in a group of children initiating various controller therapies for asthma.. A retrospective, observational study using an integrated managed care database of children aged 4-17 years with an initial medical claim for asthma and an initial pharmacy claim for fluticasone propionate (FP) and salmeterol in a single inhaler (FSC), FP alone, montelukast (MON), or combination FP + MON. Outcomes included the percentage of children initiating controller asthma therapy with prescriptions for non-sedating antihistamine (NSA) and intranasal corticosteroids (INCS) and the mean number of prescriptions for NSA and INCS.. A total of 5247 children were included. The percentage of children who filled prescriptions for NSA or INCS and the mean number of prescriptions dispensed was similar among children treated with FSC, FP, MON, and FP + MON. There were no significant differences in the relative risk of dispensing either a NSA or INCS across cohorts. Observational studies are limited by their use of administrative data and lack of access to patient records.. Children started on common asthma controller therapy are frequent users of rhinitis medications. The quantity and frequency of these medications is not different between dispensed asthma regimens.

Topics: Acetates; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cyclopropanes; Drug Combinations; Drug Prescriptions; Fluticasone; Fluticasone-Salmeterol Drug Combination; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Leukotriene Antagonists; Quinolines; Retrospective Studies; Rhinitis; Sulfides

We report a case of a 16-year-old male patient who presented with postprandial fullness and nausea. He had a history of seasonal allergies, asthma, and peripheral eosinophilia. Endoscopy of the stomach with mucosal biopsies revealed predominate eosinophils. A diagnosis of eosinophilic gastroenteritis was made. The patient's disease course and management is described in this article.

Topics: Adolescent; Androstadienes; Anti-Inflammatory Agents; Biopsy; Diagnosis, Differential; Eosinophilia; Fluticasone; Gastroenteritis; Humans; Hypersensitivity; Male; Nausea; Postprandial Period

Corticosteroid administration produces multiple immunomodulatory effects, including down-regulation of cytokine production by CD4 T lymphocytes. Fluticasone propionate (FP) (Glaxo Smith&Kline, Greenford, UK), a highly lipophilic topical corticosteroid, has been shown to be safe and effective in the treatment of asthma and of both seasonal and perennial rhinitis.. To gain insight into the mechanisms of FP therapeutic effects, we evaluated interleukin (IL)-13 (a type 2 cytokine that seemingly plays a pivotal role in allergic mechanisms) production by mitogen-stimulated peripheral blood mononuclear cells (MNC) in vitro, treated or not with FP.. MNC from 10 healthy subjects and 10 asthmatic atopic patients with Parietaria allergy were stimulated v/v with phytohaemagglutinin (PHA) (50 gamma/ml) or with complete medium alone as a control. Culture supernatants, in vitro treated or not with 10(-7) or 10(-8) M FP, were collected after 48 or 72 h incubation. IL-13 production was assessed by enzyme-linked immunosorbent assay. In random selected samples, after 4 or 24 h of cell cultures, RNA was extracted and IL-4 and IL-5 reverse transcriptase-polymerase chain reaction (RT-PCR) products analyzed.. At 48 h, there were no differences in IL-13 concentration in PHA-stimulated cultures between healthy subjects and asthmatic patients (93.6 +/- 18.9 versus 111.0 +/- 25.1 pg/ml). At 72 h, similar results were obtained (63.9 +/- 3.0 versus 73.3 +/- 2.5 pg/ml, respectively). At this time, however, IL-13 concentrations were significantly decreased versus 48 h both in asthmatics (p < 0.001) and in controls (p < 0.001). Treatment with 10(-7) M FP significantly reduced IL-13 production in healthy subjects and asthmatic patients both at 48 h (93.6 +/- 18.9 versus 50.50 +/- 10.6 pg/ml, p < 0.001, and 111.0 +/- 25.1 versus 59.3 +/- 13.6 pg/ml, p < 0.001, respectively) and at 72 h (63.9 +/- 9.6 versus 35.5 +/- 4.4 pg/ml, p < 0.001, and 73.3 +/- 8.0 versus 40.7 +/- 4.5 pg/ml, p < 0.001, respectively). Similar results were obtained with 10(-8) M FP at 48 and 72 h. Accordingly, evaluation of RT-PCR products from selected cell samples showed a FP dosage-dependent inhibition of IL-4 and IL-5 mRNA production both for healthy subjects and asthmatic patients.. FP in vitro impairs IL-13 production by PHA-stimulated MNC from asthmatic and control subjects. This strengthens previous suggestions that IL-13 inhibition by steroids may, at least in part, account for their therapeutic effects.

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Cells, Cultured; Fluticasone; Glucocorticoids; Humans; Hypersensitivity; Interleukin-13; Lymphocytes; Phytohemagglutinins; RNA

Glucocorticoids block the local allergic response in a variety of ways. However, studies have also shown that glucocorticoids increase in vitro IgE synthesis and that treatment with corticosteroids may result in elevated serum IgE concentrations. The ability of topical glucocorticoids to modulate the mucosal IgE response has not been elucidated. We studied the effect of topical steroid (fluticasone propionate) treatment on the local allergic antibody response induced by challenge with either allergen or diesel exhaust particles (DEP). A parallel group study was performed with ragweed-allergic subjects, each subject serving as his/her own control. Nasal provocation challenges were performed on three groups. One group received ragweed allergen, another diesel exhaust particles, and the third saline. The study was repeated following 1 week of treatment with intranasal fluticasone propionate. Each group received the same challenge as before. The concentrations of total immunoglobulins (IgE, IgG, IgA, and IgM), anti-ragweed antibody, IgE- and IgA-secreting cells, epsilon (epsilon) mRNA, and cytokine mRNAs (IL-2, -4, -5, -6, TNF-alpha, INF-gamma) were measured in nasal lavages performed before and at various time points after challenge. Treatment with fluticasone propionate for 7 days caused a decrease in the concentrations of nasal IgE protein, IgE-producing cells, total epsilon mRNA, and all the cytokine mRNAs tested. Furthermore, treatment with fluticasone propionate inhibited the production of allergen-specific IgE and cytokine mRNAs following challenge with ragweed antigen. However, fluticasone treatment did not significantly inhibit the enhancement of mucosal IgE production or cytokine mRNAs observed following nasal challenge with DEP. These results indicate that 1-week treatment with topical fluticasone propionate was effective in blocking local effects of allergen exposure but was unable to inhibit the adjuvant-like effect of DEP.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibody Specificity; Cytokines; Female; Fluticasone; Glucocorticoids; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-4; Interleukin-5; Male; Middle Aged; Nasal Mucosa; Plant Proteins; Pollen; RNA Splicing; RNA, Messenger; Vehicle Emissions

Neuropeptides may be involved in the pathogenesis of asthma by evoking neurogenic inflammation. Since the effects of neuropeptides are limited by peptidases, reduced activity of peptidases may contribute to the inflammatory process.. We hypothesized that soluble peptidase activities are decreased in asthmatics and that inhaled glucocorticoids exert part of their anti-inflammatory action by increasing soluble peptidase activities.. Serum and bronchoalveolar lavage (BAL) fluid was obtained from non-smoking and smoking volunteers and from allergic asthmatics both before and after treatment for 12 weeks with placebo or inhaled fluticasone propionate. Activities of neutral endopeptidase (NEP), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV) were determined using colourometric assays.. Reduced DPP IV activity in serum and reduced NEP activity in BAL fluid were found in healthy smokers compared with non-smokers. In contrast, no differences in peptidase activities in serum or BAL fluid were observed between allergic asthmatics and healthy non-smokers. Fluticasone propionate treatment did not affect peptidase activities in the asthmatic patients.. We conclude that reduced peptidase activities in serum or BAL fluid can be found in healthy smokers, but not in allergic asthmatics, and that inhaled glucocorticoids do not affect peptidase activities in BAL fluid or serum of asthmatics. Our results do not support the hypothesized dysfunction of peptidases in the asthmatic airways.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; CD13 Antigens; Dipeptidyl Peptidase 4; Female; Fluticasone; Glucocorticoids; Humans; Hypersensitivity; Male; Middle Aged; Neprilysin; Reference Values; Smoking