fluticasone and Eosinophilia

People with eosinophilic esophagitis (EE) have clinical symptoms of esophageal disease, an elevated intraepithelial eosinophil count (15 in one or more high power field at endoscopy), consistent endoscopic findings and failure to respond to gastric acid suppressants. The cause of EE is unknown, however dietary, environmental and immunological factors may contribute. Current medical therapies include steroids, dietary manipulation, mast cell inhibitors, leukotriene receptor antagonists and immune modulators; however there is no universal approach to treatment.. To evaluate the benefits and harms of medical interventions for EE.. We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register (The Cochrane Library Issue 1, 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (1966 to February 2009) and EMBASE (1980 to February 2009).. Randomised controlled trials (RCTs) comparing a medical or dietary intervention for EE with a placebo or with another medical intervention.. Two reviewers independently screened the titles of abstracts.. Three RCTs fulfilled inclusion criteria, two in children and one in adults. In one trial, topical fluticasone decreased vomiting more than placebo (67% versus (vs) 27%, P<0.05) but did not improve dysphagia. Histological remission was reported in fluticasone group compared with placebo group (50% vs 9%, P=0.05; RR 5.5, 95%CI 0.81 to 37.49). One recipient of fluticasone developed oral candidiasis. In trial comparing fluticasone with oral prednisone, symptom resolution and improvement of esophagitis were similar. Majority of participants were symptom free at four weeks with no difference between groups (RR 1.03, 95%CI 0.95 to 1.11). Symptom relapse usually occurred within six weeks of stopping therapy and 45% had symptom relapse at six month follow-up with no difference between groups. With prednisone, 40% suffered adverse effects and three withdrew early from treatment with severe adverse effects (hyperphagia, weight gain, cushingoid features). With fluticasone, 15% developed esophageal candidiasis and 45% had relapse in symptoms at week 24. Histological improvement occurred in majority at four weeks with no difference between groups. In the third trial comparing mepolizumab to placebo, there was no difference in symptom response with mepolizumab compared to placebo, but decrease in esophageal eosinophil count was greater with mepolizumab than placebo (67% vs 25%).. As only three relevant RCTs were identified, we have limited capacity to compare the benefits and harms of medical interventions currently used for treating EE. Further RCTs on therapies for EE are required.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child; Eosinophilia; Esophagitis; Fluticasone; Humans; Prednisone; Randomized Controlled Trials as Topic

Eosinophilic oesophagitis is a chronic inflammatory disease of the esophagus, frequently associated with allergic syndromes and increasingly diagnosed in patients presenting with episodic dysphagia. Topical steroid therapy and endoscopic dilation achieve control of symptoms and a good quality of life in most of patients.

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Diagnosis, Differential; Diet; Eosinophilia; Esophagitis; Esophagoscopy; Fluticasone; Humans; Immunologic Factors

Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have overlapping clinical, manometric, endoscopic and histopathologic features. The diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per high power field (eo/HPF) in esophageal biopsies. We report the cases of two young males suffering from dysphagia and recurrent food impaction with reflux esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of which became asymptomatic on proton pump inhibitor (PPI) therapy. The first patient also achieved a histologic response, while EE remained in the other patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring. Topical steroid therapy combined with PPI led to complete remission in this latter patient. GERD and EE may be undistinguishable, even by histology, so diagnosis of EE should only be established after a careful correlation of clinical, endoscopic and pathologic data obtained under vigorous acid suppression. These diagnostic difficulties are maximal when both diseases overlap. Limited data are available about this topic, and the interaction between EE and GERD is a matter of debate. In this setting, upper-mid esophagus step biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to evaluate the role of each disease. A PPI trial is mandatory in patients with a histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE should be suggested. However, a clinical response to PPI may not rule out quiescent EE, as shown in this report.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Eosinophilia; Esophagitis; Esophagitis, Peptic; Esophagus; Fluticasone; Humans; Male; Proton Pump Inhibitors

To review recently published studies presenting novel and relevant information on some esophageal infectious, inflammatory and injurious diseases.. In the treatment of Candida esophagitis, fluconazole remains the treatment of choice, but clinical failures indicate new therapeutic opportunities, like two new echinocandins, micafungin and anidulafungin. Eosinophilic esophagitis is an increasingly recognized entity. New therapeutic insights come from a six-food elimination diet in children and from fluticasone propionate in adults; humanized monoclonal IgG antibody anti-interlukin-5, mepolizumab, has been shown to decrease eosinophilia and ameliorate symptoms. There has been some advance in microscopic characterization of lymphocytic esophagitis. Esophagitis is found to be present in 67% of patients with pemphigo vulgaris, in 32.3% of patients with systemic sclerosis and to be associated with thoracic neoplasias. In the case of caustic ingestion, endoscopic ultrasound with miniprobes has proven not to be better than videoendoscopy. Recent evidence shows that systemic steroids might even be harmful. Mitomycin C applied on fresh wounds is currently being evaluated. Stenting of the stricture has been proposed for contrasting esophageal remodeling.. These recent findings, together with a better understanding of diseases such as eosinophilic or lymphocytic esophagitis, allow new diagnostic and therapeutic approaches.

Topics: Androstadienes; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antineoplastic Agents; Biomarkers; Candidiasis; Caustics; Diet; Eosinophilia; Esophagitis; Esophagus; Fluticasone; Humans; Radiotherapy

Patients with eosinophilic oesophagitis (EO) present with difficulty swallowing, vomiting, regurgitation, chest and/or abdominal pain. People with EO frequently fail to respond to treatment with gastric acid suppressants or anti-reflux surgery.. To evaluate the benefits and harms of medical interventions for eosinophilic oesophagitis.. We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register (The Cochrane Library Issue 1, 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February 2004) and EMBASE (1980 to February 2004).. Randomised controlled trials were included if they compared a medical or dietary intervention for eosinophilic oesophagitis with a placebo or one medical intervention with another medical intervention.. Two reviewers independently screened the title of abstracts.. No completed RCTs were found in the published literature. We found one abstract reporting preliminary data from an RCT (not completed) comparing oral prednisolone with topical (swallowed metered dose) fluticasone in children. In this study (50 children enrolled to date) healing rates of oesophagitis and symptom resolution with fluticasone were similar to those with prednisolone. For another ongoing RCT, comparing the efficacy of swallowed fluticasone with placebo for eosinophilic oesophagitis in males and females aged 3 to 21 years no results are available.. The lack of completed RCT's makes it impossible to compare the relative benefits and harms of the wide range of medical interventions currently used for treating EO. Published case series suggest that an elemental diet, oral steroids and topical steroids all offer some benefits. However, lack of a comparison group in these studies makes it impossible to evaluate the effect of these interventions.

Topics: Androstadienes; Anti-Inflammatory Agents; Eosinophilia; Esophagitis; Fluticasone; Humans; Prednisone

Although response to intranasal corticosteroid therapy has been reported in patients with nonallergic rhinitis with eosinophilic syndrome (NARES), efficacy specifically in non-NARES patients has not been fully characterized.. To evaluate the efficacy of intranasal fluticasone propionate (FP) in the treatment of patients with perennial nonallergic rhinitis, with and without nasal eosinophilia.. Data from 983 patients in three randomized, double-blind, placebo-controlled PNAR trials were integrated. Patients received a total daily dose of FP 200 microg (n = 332), FP 400 microg (n = 325), or placebo (n = 326) for 28 days. Patients were > or =12 years of age with perennial rhinitis and negative skin tests to all allergens relevant to the geographic region. Nasal eosinophils were evaluated using a five-point scale. Patients were classified as non-NARES with a point score of 0 (n = 674; 69%); patients with a point score between I and 4 were classified as NARES (n = 309; 31%). Efficacy of FP was evaluated by the mean change in total nasal symptom score (TNSS), a sum of patient ratings of nasal obstruction, postnasal drip, and rhinorrhea.. Patients with either NARES or non-NARES had similar statistically significant improvement with FP 200 microg or 400 microg compared with placebo; thus, the total group comprising both varieties of rhinitis responded to FP. In the total population, both FP treatment groups showed significantly greater improvement in TNSS compared with placebo during each week of treatment (P < or = 0.002), with mean changes in TNSS for day 22 to day 28 ranging from -84 and -85 in the FP 200 microg and FP 400 microg groups, respectively, to -64 in the placebo group. The three study treatment groups had similar proportions of non-NARES (68 to 69%) and NARES (31 to 32%) patients at baseline. In the non-NARES subgroup, mean changes in TNSS for each treatment group were similar to changes seen in the total population. In the NARES subgroup, mean changes in TNSS for the FP 200 microg and placebo groups were similar to changes seen in the total population; mean change in TNSS for the FP 400 microg group was somewhat greater than changes seen in the total population.. Intranasal FP is an effective treatment for perennial nonallergic rhinitis with or without nasal eosinophilia (NARES or non-NARES).

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Eosinophilia; Female; Fluticasone; Humans; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Skin Tests

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).. 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.. 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).. The SS-OCT revealed that asthmatic children under inhaled corticosteroid treatment have lower RNFLT than healthy subjects.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child; Eosinophilia; Female; Fluticasone; Humans; Immunoglobulin E; Male; Skin Tests; Tomography, Optical Coherence

Two distinct, stable inflammatory phenotypes have been described in adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based on these phenotypes have been successful. This study evaluated sputum cytology in children with asthma to classify sputum inflammatory phenotypes and to assess their stability over time.. Sputum induction was performed in 51 children with severe asthma and 28 with mild to moderate asthma. Samples were classified as eosinophilic (>2.5% eosinophils), neutrophilic (>54% neutrophils); mixed granulocytic (>2.5% eosinophils, >54% neutrophils); or paucigranulocytic (≤2.5% eosinophils, ≤54% neutrophils). Sputum induction was repeated every 3 months in children with severe asthma (n=42) over a 1-year period and twice in mild to moderate asthma (n=17) over 3-6 months.. 62 children (78%) had raised levels of inflammatory cells in at least one sputum sample. In the longitudinal analysis 37 of 59 children (63%) demonstrated two or more phenotypes. Variability in sputum inflammatory phenotype was observed in both the severe and the mild to moderate asthma groups. Change in phenotype was not related to change in inhaled corticosteroid (ICS) dose or asthma control, nor was it reflected in a change in exhaled nitric oxide (FE(NO)). 24 children (41%) fulfilled the criteria for non-eosinophilic asthma on one occasion and eosinophilic on another. There were no differences in severity, asthma control, atopy, ICS dose or forced expiratory volume in 1 s between those who were always non-eosinophilic and those always eosinophilic.. Raised levels of inflammatory cells were frequently found in children with asthma of all severities. Sputum inflammatory phenotype was not stable in children with asthma.

Topics: Adolescent; Androstadienes; Asthma; Child; Dose-Response Relationship, Drug; Eosinophilia; Female; Fluticasone; Glucocorticoids; Humans; Inflammation; Longitudinal Studies; Male; Neutrophils; Phenotype; Severity of Illness Index; Sputum; Treatment Outcome

Symptomatic, steroid-naïve asthmatic patients may have low sputum eosinophil numbers. The aim of the study was to determine whether low sputum eosinophil numbers persisted over time, during treatment with salmeterol monotherapy.. Forty steroid-naïve, symptomatic asthmatic patients, with sputum eosinophils <3%, were randomized to receive open-label salmeterol (50 µg twice a day, n = 30) or fluticasone (125 µg twice a day, n = 10) and were then assessed at 1, 3 and 6 months. All patients underwent spirometry, a methacholine challenge test and sputum induction at each visit. Symptom scores and peak expiratory flow were recorded throughout the study. Patients were permitted to withdraw from the study at any time, if they experienced exacerbations or deterioration of symptoms.. The average sputum eosinophil percentage remained normal (≤1.9%) in both groups over the study period. The eosinophil percentages were ≤1.9% in 65 of the 80 samples obtained from salmeterol-treated patients throughout the study period. Eight patients had an asthma exacerbation or deterioration, during which one developed sputum eosinophilia. Twelve patients, 11 of whom were randomized to salmeterol and one to fluticasone, developed transient sputum eosinophilia at least once during the study. This was not associated with asthma exacerbation (except for one patient). Sputum neutrophil percentage did not change in either group.. Low sputum eosinophil numbers persisted over 6 months in a majority of patients with non-eosinophilic asthma who received salmeterol monotherapy. However, transient sputum eosinophilia occurred in 40% indicating that non-eosinophilic asthma may not be a stable phenotype.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Eosinophilia; Female; Fluticasone; Humans; Male; Methacholine Chloride; Middle Aged; Neutrophils; Salmeterol Xinafoate; Sputum; Young Adult

Both gastroesophageal reflux disease and allergy/atopy have been implicated in the pathogenesis of eosinophilic esophagitis (EoE). There are no prospective studies comparing treatment of EoE with acid suppression versus topical corticosteroids.. To determine the outcome of adult eosinophilic esophagitis patients treated with esomeprazole versus topical fluticasone.. Prospective randomized controlled trial.. Academic medical center.. Adults (18-80) diagnosed with EoE by symptoms of dysphagia and esophageal biopsies with >or=15 eosinophils/hpf.. Subjects were randomized to esomeprazole (40 mg by mouth every morning) or aerosolized, swallowed fluticasone (440 mcg by mouth twice a day) for 8 weeks.. Improvement in dysphagia (8-point scale), esophageal eosinophil infiltration before and after treatment, prevalence of GERD measured by validated questionnaire and baseline pH study.. About 56% (14/25) had acid reflux by pH study. There was no difference between treatment groups in improvement in dysphagia scores [3/12 (25%) of the esomeprazole group versus 6/12 (50%) in the fluticasone group, P = 0.40]. Eosinophil infiltration decreased with treatment in both groups, and there was no difference in the amount of decrease between groups (P = 0.70).. Small sample size, unexpectedly high drop-out rate.. Gastroesophageal reflux disease is common in adult eosinophilic esophagitis patients. Dysphagia improves and esophageal eosinophilic infiltration decreases with either treatment. There was no difference in degree of improvement in dysphagia or eosinophil infiltration in patients treated with either topical fluticasone or oral esomeprazole. GERD may be important in the pathogenesis of adult EoE.

Topics: Administration, Oral; Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Inflammatory Agents; Anti-Ulcer Agents; Eosinophilia; Esomeprazole; Esophagitis; Female; Fluticasone; Humans; Male; Middle Aged; Prospective Studies; Statistics, Nonparametric; Treatment Outcome

Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation.. To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists.. Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation.. Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p

Topics: Acetates; Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchi; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Eosinophilia; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Quinolines; Sulfides; Treatment Outcome

Bronchodilator reversibility (BDR) is common in smoking-related COPD, but the airway pathology underlying this has not been described. In particular, it is not known whether BDR is associated with underlying airway eosinophilia and whether BDR is predictive of a better response to inhaled corticosteroid (ICS) treatment.. A double-blind, placebo-controlled, randomized 2:1 study of fluticasone propionate (FP), 500 microg twice daily versus placebo over 6 months was performed in subjects with mild to moderate COPD. Subjects with a clinical history of asthma were excluded, but not on BDR criteria alone. Induced sputum, BAL and endobronchial biopsies (EBB) were performed in 36 subjects at baseline, and 30 of these provided a second full set of samples (FP, n = 19; placebo, n = 11).. Baseline BDR was not related to airway eosinophilia and did not predict response to ICS. Post-bronchodilator FEV(1) increased in the FP group compared with the placebo group (P = 0.05), and there were within-treatment group reductions in total symptom scores with FP (P < 0.05). Compared with placebo, FP reduced macrophage numbers but increased neutrophil numbers in EBB (P = 0.01 and P = 0.003, respectively). BAL neutrophil and epithelial cell numbers were also reduced with FP (P = 0.03 for both). There were within-treatment group reductions in the numbers of EBB mast cells and CD8+ve lymphocytes with FP (P = 0.007).. BDR was not related to any particular inflammatory phenotype or any clinical or anti-inflammatory response to ICS in these subjects with mild to moderate COPD.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Cell Count; Cross-Sectional Studies; Double-Blind Method; Eosinophilia; Female; Fluticasone; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Respiratory Mucosa; Sputum; Treatment Outcome

To evaluate whether hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) controls eosinophilic inflammation, including that in the distal airways, more effectively than fluticasone propionate (FP) Diskus.. Fifty patients with well-controlled mild to moderate persistent asthma using FP for more than 6 months were randomly assigned to FP and HFA-BDP groups, and the treatment regimens of the two groups were switched twice between FP and HFA-BDP in a double cross-over manner at 3-month intervals after 2-week washout periods. Evidence of eosinophilic inflammation in blood and induced sputum samples was assessed, together with pulmonary function testing and an Asthma-related Quality of Life Questionnaire (AQLQ) survey after each treatment period.. The peripheral blood differential eosinophil count and sputum levels of eosinophil cationic protein (ECP) showed reciprocal changes during the study periods in both groups. The blood differential eosinophil count was significantly lower during the HFA-BDP than during the FP treatment period in both the FP (p = 0.004) and the HFA-BDP (p = 0.020) group. The late-phase induced sputum ECP level was significantly decreased during the HFA-BDP treatment period in both the FP (p = 0.016) and the HFA-BDP group (p = 0.023). The significant elevation of surfactant protein D values in the late-phase sputum observed in both groups indicated that late-phase sputum was obtained mainly from proximal peripheral airways. Both symptom and activity limitation domains of the AQLQ in the HFA-BDP group significantly increased after switching from FP to HFA-BDP. There were no significant changes in pulmonary function indices in either group at any time during the study.. HFA-BDP improved residual eosinophilic inflammation in asthmatic airways, including distal airways, more effectively than FP.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Eosinophil Cationic Protein; Eosinophilia; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Quality of Life; Sputum

The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000microg bid) (Group A, n=18) or a reducing course of oral P (Group B, n=19). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV(1) (from 53.9%+/-16.8 at Visit 1 to 76.4%+/-21.2 at Visit 2, p=0.0001) and reduced the percentage of sputum eosinophils (from 38%[0-78] to 3%[1-31, p=0.0008) as well as oral P (FEV(1): from 51.5%+/-14.4 to 83.6%+/-21.1, p=0.0001; sputum eosinophils: from 52%[1-96] to 11%[0-64], p=0.0003). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Androstadienes; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophil Cationic Protein; Eosinophilia; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nausea; Oximetry; Prednisone; Recurrence; Severity of Illness Index; Sputum; Treatment Outcome

Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency.. We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers.. Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of > or = 2.5% entered a 6-week sequential, placebo-controlled, patient-blinded, cumulative dose-response study. After 7 days of placebo, they received incremental doses of fluticasone propionate (FP), 50, 100, 200, and 400 microg/d, each for 7 days. Measurements were made of sputum and blood eosinophils, exhaled nitric oxide, spirometry, airway responsiveness to methacholine (methacholine PC20), and symptom scores before and after each dose.. Sputum eosinophils and exhaled nitric oxide were extremely sensitive to the effects of FP, and exhibited significant dose-dependent reductions of 99.4% and 99.8 parts per billion, respectively, where each variable was expressed per 100 microg/d FP. This compared with a 0.5 doubling dose increase of airway responsiveness to methacholine and a 0.3 decrease in symptom scores. Airway responsiveness to methacholine was the only variable that increased throughout the study.. These results suggest that the model of eosinophilic bronchitis could be used to compare the effect of cumulative doses of an inhaled corticosteroid delivered by different types of delivery systems or preparations using a relatively small number of patients.. Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Biomarkers; Bronchitis; Dose-Response Relationship, Drug; Eosinophil Cationic Protein; Eosinophilia; Fibrinogen; Fluticasone; Humans; Nitric Oxide; Serine Endopeptidases; Single-Blind Method; Sputum; Tryptases

Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic, histologic, and allergic features. Although several therapies are advocated, no placebo-controlled trials have been conducted. We aimed to determine the efficacy of swallowed fluticasone propionate (FP) in the treatment of eosinophilic esophagitis.. We conducted a randomized, double-blind, placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis. Thirty-six patients were randomly assigned to receive either 880 mug of FP (21 patients) or placebo (15 patients) divided twice daily for 3 months. The primary end point was histologic remission, defined by a peak eosinophil count of

Topics: Adolescent; Age Factors; Androstadienes; Body Height; Body Weight; CD8-Positive T-Lymphocytes; Child; Child, Preschool; Double-Blind Method; Eosinophilia; Esophagitis; Female; Fluticasone; Humans; Hyperplasia; Infant; Male

Eosinophilic esophagitis (EoE) is a disorder characterized by a severe, isolated eosinophilic infiltration of the esophagus unresponsive to aggressive acid blockade but responsive to the removal of dietary antigens. We present information relating to our 10-year experience in children diagnosed with EoE.. We conducted a retrospective study between January 1, 1994, and January 1, 2004, to evaluate all patients diagnosed with EoE. Clinical symptoms, demographic data, endoscopic findings, and the results of various treatment regimens were collected and evaluated.. A total of 381 patients (66% male, age 9.1 +/- 3.1 years) were diagnosed with EoE: 312 presented with symptoms of gastroesophageal reflux; 69 presented with dysphagia. Endoscopically, 68% of patients had a visually abnormal esophagus; 32% had a normal-appearing esophagus despite a severe histologic esophageal eosinophilia. The average number of esophageal eosinophils (per 400 x high power field) proximally and distally were 23.3 +/- 10.5 and 38.7 +/- 13.3, respectively. Corticosteroids significantly improved clinical symptoms and esophageal histology; however, upon their withdrawal, the symptoms and esophageal eosinophilia recurred. Dietary restriction or complete dietary elimination using an amino acid-based formula significantly improved both the clinical symptoms and esophageal histology in 75 and 172 patients, respectively.. Medications such as corticosteroids are effective; however, upon withdrawal, EoE recurs. The removal of dietary antigens significantly improved clinical symptoms and esophageal histology in 98% of patients.

Topics: Administration, Oral; Androstadienes; Anti-Inflammatory Agents; Biopsy; Child; Cromolyn Sodium; Endoscopy, Gastrointestinal; Eosinophilia; Esophagitis; Female; Fluticasone; Follow-Up Studies; Humans; Male; Methylprednisolone; Retrospective Studies; Treatment Outcome

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P<0.02 and P<0.01) and rhinorrhea (P<0.01) than levocabas tine. In addition, fewer patients treated with FPANS used rescue medication (P<0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 microg, once daily, provides a better clinical effect than levocabastine 200 microg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Double-Blind Method; Eosinophilia; Female; Fluticasone; Histamine H1 Antagonists; Humans; Hydrocortisone; Male; Piperidines; Rhinitis, Allergic, Seasonal

Nasal allergen provocation in patients with allergic rhinitis leads to expression of the proeosinophilic cytokines IL-5 and GM-CSF and tissue eosinophilia.. We sought to examine the effect of natural seasonal allergen exposure on IL-5 and GM-CSF mRNA expression and nasal eosinophilia and to evaluate the effects of topical corticosteroid therapy on these responses.. Nasal biopsy specimens were collected from 46 grass pollen-sensitive patients with seasonal rhinitis before the grass pollen season. A second biopsy specimen was collected during the pollen season, by which time patients had received 6 weeks treatment with either fluticasone propionate (200 micro(g) twice daily) or placebo nasal spray.. Fluticasone treatment was clinically effective (P <.005). Patients receiving placebo, but not fluticasone, showed increased numbers of epithelial and submucosal EG2+ eosinophils (P <.005) and IL-5 and GM-CSF mRNA-expressing cells (P <.0001) during the pollen season. Colocalization experiments showed that greater than 80% of IL-5 mRNA-expressing cells were submucosal CD3+ T cells in both groups. The numbers of submucosal CD3+ T cells did not increase during the pollen season or decrease with fluticasone treatment. Fluticasone also inhibited IL-5 secretion by grass pollen-stimulated peripheral blood T cells from patients with seasonal rhinitis (n = 5, inhibitory concentration of 50% = 10(-9) to 10(-10) mol/L).. These results suggest that topical corticosteroids may reduce eosinophilia in seasonal rhinitis by inhibiting T cell IL-5 production.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Biopsy; CD3 Complex; Cells, Cultured; Eosinophilia; Fluticasone; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; In Situ Hybridization; Interleukin-5; Nasal Mucosa; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; RNA, Messenger; Skin Tests; T-Lymphocytes

Allergen-induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2-type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage-colony stimulating factor (GM-CSF) may contribute to late-responses and tissue eosinophilia and is inhibitable by topical corticosteroid.. Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM-CSF.. Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5-fold increase in cells expressing mRNA for GM-CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM-CSF mRNA+ cells were co-localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM-CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM-CSF.. The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM-CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM-CSF from T lymphocytes or reducing autocrine production of GM-CSF from eosinophils.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Antisense Elements (Genetics); Biopsy; Eosinophilia; Epithelium; Female; Fluticasone; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immune System; Immunohistochemistry; Immunophenotyping; In Situ Hybridization; Male; Nasal Mucosa; Placebos; Rhinitis, Allergic, Seasonal; RNA Probes; RNA, Messenger; Time Factors; Up-Regulation

We performed a double-blind, crossover, placebo-controlled study on the effect of fluticasone propionate (FP) treatment on chronic eosinophilic rhinosinusitis in 15 patients with aspirin-induced asthma (AIA). There were 10 women and five men aged 32-60 years; average: 45 years. After a 10-day run-in period, patients underwent two 4-week treatment courses (FP vs placebo), separated by a 2-week washout interval. Clinical activity of FP was evaluated by daily measurement of peak nasal inspiratory flow (PNIF) and a scoring system of subjective symptoms. Nasal challenges with E-lysine aspirin, using active anterior rhinomanometry, were performed at the entry and on the last day of each treatment period. Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. On average, the reactions evoked by aspirin nasal challenge were significantly shorter and milder after treatment with FP than with placebo. In 8/13 patients, FP completely prevented aspirin-precipitated nasal reaction, whereas protection after placebo was observed in only 2/12 subjects (P = 0.004). We conclude that intranasal FP is an effective therapy for chronic eosinophilic rhinitis in patients with AIA.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Allergic Agents; Aspirin; Asthma; Chronic Disease; Cross-Over Studies; Double-Blind Method; Eosinophilia; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Provocation Tests; Rhinitis

Fluticasone propionate aqueous nasal spray, a new topical corticosteroid, has been proved to be an effective treatment for seasonal allergic rhinitis.. We studied the effect of fluticasone propionate on nasal symptoms, circulating eosinophils, and nasal inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Moreover, we examined its efficacy in preventing the increase in bronchial responsiveness to methacholine (PD20) during the pollen season.. We conducted a double-blind, placebo-controlled, parallel-group study in patients who had a history of allergic rhinitis in response to pollens of grass and Parietaria species and were living in northern Italy. After a run-in period of 2 weeks, 24 patients were treated with fluticasone propionate (200 micrograms, once daily), and 26 patients received matched placebo for 6 weeks, starting from the beginning of the pollen season. Assessment of efficacy was based on scores of daily nasal symptoms. Nasal lavage was performed at the end of the season, and differential cell count was expressed as percent of total cells. PD20 methacholine was measured at the beginning and end of the season and after the season had ended.. Fluticasone propionate significantly reduced nasal obstruction, itching, and rhinorrhea. Eosinophils in blood (p < 0.01) and nasal lavage (p < 0.001) were also reduced. Moreover, fluticasone significantly attenuated the decrease in mean PD20 methacholine (from 1.95 to 0.89 mg) compared with placebo (from 1.38 to 0.37 mg: p < 0.01). After the season, no difference in PD20 methacholine was found between treatment groups.. The results of this study indicate that fluticasone propionate is effective in decreasing nasal symptoms and eosinophil inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Our results also demonstrate that treatment with fluticasone propionate partially prevents the increase in bronchial responsiveness provoked by the inhalation of seasonal pollens in allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Blood Proteins; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Drug Administration Schedule; Eosinophil Granule Proteins; Eosinophilia; Female; Fluticasone; Humans; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Nasal Lavage Fluid; Pollen; Rhinitis, Allergic, Seasonal; Ribonucleases; Seasons

Esophageal eosinophilia and eosinophilic esophagitis (EoE) are increasingly recognized and prevalent conditions, which now represent common clinical problems encountered by gastroenterologists, pathologists, and allergists. The study of EoE has become a dynamic field with an evolving understanding of the pathogenesis, diagnosis, and treatment. Although there are limited data supporting management decisions, clinical parameters are needed to guide the care of patients with eosinophilic-esophageal disorders. In this evidence-based review, recommendations developed by adult and pediatric gastroenterologists are provided for the evaluation and management of these patients. New terminology is emphasized, particularly the concepts of esophageal eosinophilia and proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) as entities distinct from EoE.

Topics: Adult; Algorithms; Androstadienes; Anti-Inflammatory Agents; Biopsy; Clinical Trials as Topic; Diagnosis, Differential; Endpoint Determination; Eosinophilia; Eosinophilic Esophagitis; Esophagoscopy; Esophagus; Evidence-Based Medicine; Fluticasone; Gastroesophageal Reflux; Humans; Prednisone; Proton Pump Inhibitors

A 56-year-old woman was referred to our hospital because of dyspnea, wheezing, and a productive cough. Eight years before presentation, bronchial asthma was diagnosed and the patient received inhaled corticosteroids plus antiasthmatic agents (a long-acting inhaled beta2-agonist, leukotriene modifiers, and theophylline). Chest radiography showed small diffuse nodular shadows, and a computed tomographic scan showed thickening of the bronchi and bronchioles, with diffuse centrilobular nodules in both lung fields. A blood test and microscopic examination of the bronchoalveolar fluid revealed marked eosinophilia. Transbronchial lung biopsy and transbronchial biopsy showed eosinophilic bronchitis and bronchiolitis. After treatment with oral prednisolone (40 mg daily) and inhaled corticosteroids, the symptoms, blood eosinophilia, and radiographic findings improved. Recently, several similar cases of eosinophilic bronchiolitis have been reported. Studies of further cases and elucidation of the pathophysiology of eosinophilic bronchiolitis are necessary to establish a concept for this disease and to determine whether it should be classified as a subtype of bronchial asthma or as a distinct entity.

Topics: Androstadienes; Asthma; Bronchiolitis; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cough; Diagnosis, Differential; Dyspnea; Eosinophilia; Female; Fluticasone; Hematologic Tests; Humans; Middle Aged; Prednisolone; Radiography, Thoracic; Respiratory Function Tests; Respiratory Sounds

We report a case of a 43 year old male patient, who was admitted with recurring esophageal bolus impactions. Since his childhood he has been complaining about dysphagia and was unable to swallow medication. He also complained about heartburn. The last esophageal bolus impaction was some weeks ago. After elimination of the bolus impaction with a rigid endoscope we found a high grade stenosis in the proximal esophagus that could not even be passed with a children's endoscope. An initial treatment of eosinophil esophagitis would be the therapy with a local corticoid for 6-9 month. In patients with typical rings or stenosis a dilation therapy might be necessary.

Topics: Administration, Oral; Adult; Androstadienes; Catheterization; Combined Modality Therapy; Deglutition Disorders; Diagnosis, Differential; Endoscopy, Digestive System; Eosinophilia; Esophageal Stenosis; Esophagitis; Fluticasone; Heartburn; Humans; Male; Prednisolone; Recurrence

Eosinophilic esophagitis (EE) involves marked accumulation of eosinophils in the esophageal mucosa that responds to swallowed fluticasone propionate (FP) in a subset of patients.. We aimed to uncover the mechanism of action of swallowed FP in patients with EE by providing evidence for a topical effect in the esophagus by identifying a molecular signature for FP exposure in vivo.. Global microarray expression profiles, immunofluorescence microscopy, and cell signaling in esophageal tissue and cell lines were analyzed.. Thirty-two transcripts exhibited altered expression in patients who responded to swallowed FP treatment. Esophageal FK506-binding protein 5 (FKBP51) mRNA levels were increased (P < .05) in FP responders compared with those seen in control subjects and patients with untreated active EE. After FP treatment of esophageal epithelial cells, FKBP51 mRNA and protein levels were increased in a dose- and time-dependent manner by FP treatment in vitro. FP-induced FKBP51 was steroid receptor dependent because RU486 completely inhibited gene and protein induction. The half-life of FKBP51 mRNA was 16 to 18 hours independent of FP treatment. FKBP51 overexpression reduced FP action as assessed by FP inhibition of IL-13-induced eotaxin-3 promoter activity.. Our results suggest that swallowed glucocorticoid treatment directly affects esophageal gene expression in patients with EE. In particular, increased FKBP51 transcript levels identify glucocorticoid exposure in vivo and distinguish FP responders from untreated patients with active EE and patients without EE. In addition, FKBP51 reduces glucocorticoid-mediated inhibition of IL-13 signaling in epithelial cells in vitro, suggesting that FKBP51 might influence FP responsiveness. We propose that esophageal FKBP51 levels have diagnostic and prognostic significance in patients with EE.

Topics: Adolescent; Androstadienes; Cell Line; Cells, Cultured; Child; Child, Preschool; Eosinophilia; Epithelial Cells; Esophagitis; Esophagus; Female; Fluticasone; Gene Expression Profiling; Gene Expression Regulation; Glucocorticoids; Humans; Infant; Interleukin-13; Male; Oligonucleotide Array Sequence Analysis; Proteins; Tacrolimus Binding Proteins; Young Adult

Eosinophilic esophagitis (EE) is an emerging disorder with poorly understood pathogenesis.. Whereas prior studies have primarily focused on the role of eosinophils in disease diagnosis and pathogenesis, this study investigates the involvement of mast cells.. Total and degranulated mast cell counts were correlated to microarray and RT-PCR data to generate transcriptome expression profiles related to mast cell number and degranulation in patients with EE and healthy control subjects.. Esophageal mastocytosis and mast cell degranulation were readily apparent in patients with EE compared with control subjects (P < .01), as assessed by staining for total mast cells and the presence of extracellular mast cell tryptase (P < .01). Microarray analysis revealed that mast cell levels correlated with the dysregulation of 0.8% (301 genes) of the genome, which was partially distinct from the genes that correlated with tissue eosinophilia. The expression of transcripts for the mast cell proteases carboxypeptidase A3 and tryptase, but not chymase, correlated with mast cell levels and distinguished patients with EE from control subjects. Suprabasilar mast cell counts (P < .01) and degranulation (P < .01) were proportional with KIT ligand mRNA expression. Treatment of patients with EE with swallowed fluticasone propionate normalized levels of mast cells and the mast cell-related transcriptome in responder patients.. Herein we have identified local mastocytosis and mast cell degranulation in the esophagi of patients with EE; identified an esophageal mast cell-associated transcriptome that is significantly divergent from the eosinophil-associated transcriptome, with carboxypeptidase A3 mRNA levels serving as the best mast cell surrogate marker; and provided evidence for the involvement of KIT ligand in the pathogenesis of EE.

Topics: Adolescent; Adult; Androstadienes; Carboxypeptidases A; Cell Degranulation; Child; Child, Preschool; Eosinophilia; Esophagitis; Female; Fluticasone; Gene Expression Profiling; Humans; Infant; Male; Mast Cells; Stem Cell Factor

Eosinophilic esophagitis (EE) is a motility disorder of the esophagus that typically presents with dysphagia. The objective of the present study was to explore patient characteristics, clinical and endoscopic features, and response to treatment of patients with EE. Patients were selected retrospectively based on a review of biopsy results from previous endoscopies performed between 2004 and 2008. A total of 54 patients (41 men and 13 women) with biopsy-proven EE were included in the study. Further information regarding the patients' clinical and endoscopic features, and response to treatment were obtained through chart reviews and patient telephone interviews. The mean age of the patients at symptom onset was 30 years. All patients complained of dysphagia, 81% had a history of bolus obstruction, 43% had a history of asthma and 70% had a history of environmental allergies. Thirty-three per cent had a family history of asthma, while 52% had a family history of food or seasonal allergies. The most common endoscopic findings were rings and⁄or corrugations, which were found in 63% of patients. Swallowed fluticasone therapy resulted in symptom resolution in 74% of patients; however, 79% of these patients relapsed after discontinuing fluticasone therapy and required repeat treatments. Esophageal dilation was complication free and resulted in improvement in 80% of patients. However, 83% of those reporting improvement relapsed within one year. The clinical and endoscopic findings were similar to those found in the literature, with most patients requiring ongoing, repeated therapies. Further studies are needed to assess the safety and efficacy of treatment modalities ideally suited to patients with EE.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Deglutition Disorders; Dilatation; Eosinophilia; Esophagitis; Esophagoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Treatment Outcome; Young Adult

A 17-year-old patient was transferred to the emergency room with an impacted food bolus by colleagues from the Department of Otorhinolaryngology. The examination of ear, nose and throat revealed significant amounts of saliva in both recessus piriformis, a radiologic examination of the esophagus showed a foreign body with a diameter of 1.6 cm in the region of the transitional zone of esophagus and stomach with a support level of the contrast medium. Clinical examination and laboratory tests showed no abnormalities. An emergency gastroscopy was performed. The foreign body, already evident in the barium swallow, was found in the distal esophagus. The foreign body was identified as a food bolus and gently advanced into the stomach with the aid of the gastroscope. In the stomach further food residues were detected and the examination was aborted because of increased risk of aspiration. On the next day, an elective gastroscopy was performed. Several biopsies were obtained from the esophagus because eosinophilic esophagitis (EE) was suspected due to clinical symptoms. Histological work-up showed a significant amount of eosinophilic granulocytes (> 15 eosinophils/HPF, 400 x) and reactive changes in the distal esophagus. Therefore, EE was diagnosed. Fluticasone therapy led to amelioration of symptoms and there was no evidence of recurring bolus impaction during follow-up.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Biopsy; Bread; Diagnosis, Differential; Eosinophilia; Esophagitis; Esophagogastric Junction; Fluticasone; Foreign Bodies; Gastric Mucosa; Gastroscopy; Humans; Male; Recurrence; Respiratory Hypersensitivity

Eosinophilic esophagitis (EE) is a clinical entity that is recognized increasingly in children. The treatment of EE has been debated since its identification as a clinical entity separate from reflux esophagitis. We hypothesize that the treatment with a high-dose proton pump inhibitor (HDPPI) helps differentiate EE from noneosinophilic esophagitis (NEE).. Retrospective review of 2221 patients who underwent esophagogastroduodenoscopy (EGD) with biopsies was undertaken. Sixty-nine patients had more than or equal to 15 eosinophils/high-power field (eos/HPF) in 1 or more esophageal levels. Of those, 36 were initially treated with HDPPI for 3 months followed by repeat EGD. Patients who demonstrated histologic response were classified as NEE. Patients with no histologic response were diagnosed as having EE and treated with HDPPI+swallowed fluticasone for 3 months followed by repeat EGD.. Of the 36 patients, histologic response was seen in 14 (39%) after treatment with HDPPI; 95% confidence interval (0.23-0.54). Swallowed fluticasone was added to the treatment of the 22 patients who did not show histologic response to HDPPI alone. Of those, 15 patients underwent repeat endoscopies. Seven patients were lost to follow-up or did not have repeated EGDs. Histologic response was observed in 9 of 15 (60%) patients. Of the nonresponders (6 of 15), 5 of 6 (83%) self-reported noncompliance with the swallowed fluticasone. Patients with more than or equal to 15 eos/HPF at all 3 levels (25 of 36) were less likely to respond to HDPPI alone and more likely to be categorized as EE (18 of 25), P=or<0.043. Symptomatically, 28 of 36 patients reported resolution of symptoms after HDPPI therapy alone, P=or<0.0001, regardless of histology. Visual endoscopic findings during the first and second EGDs did not show any significance in differentiating EE from NEE, P=0.625 and P=0.2405, respectively.. The study demonstrates that HDPPI can be used to help differentiate EE from NEE histologically. Moreover, patients with more than or equal to 15 eos/HPF at all 3 levels are less likely to respond to HDPPI than patients with more than or equal to 15 eos/HPF at fewer than 3 levels. Therefore, having more than or equal to 15 eos/HPF at 1 or 2 biopsy levels does not necessarily establish the diagnosis of EE. Symptomatic response to HDPPI does not correlate with histologic findings. Clinical management guided by EGD with biopsy helps distinguish patients with EE from those with NEE.

Topics: Adolescent; Androstadienes; Anti-Inflammatory Agents; Biopsy; Child; Child, Preschool; Endoscopy, Digestive System; Eosinophilia; Eosinophils; Esophagitis; Female; Fluticasone; Humans; Male; Proton Pump Inhibitors; Retrospective Studies

Endoscopic findings of an 18-year old man with intermittent dysphagia showed widespread white exudations of the oesophagus. First misinterpreted as oesophageal candidiasis the mucosal biopsies revealed the histological features of a severe eosinophilic oesophagitis. Under treatment with topical steroids the symptoms dissolved. The control endoscopy showed a histological remission with absence of eosinophilic granulocytes, too. The eosinophilic oesophagitis is a rare allergy-like inflammation of the oesophagus especially seen in young men with increasing incidence. Without treatment the long-term risk of eosinophilic oesophagitis is the induction of severe oesophageal strictures.

Topics: Administration, Oral; Adolescent; Androstadienes; Anti-Allergic Agents; Antifungal Agents; Biopsy; Candidiasis; Deglutition Disorders; Diagnosis, Differential; Dose-Response Relationship, Drug; Eosinophilia; Esophagitis; Esophagoscopy; Esophagus; Fluticasone; Humans; Male; Miconazole

Eosinophilic esophagitis (EE) is a clinicopathologic syndrome comprising isolated eosinophilic inflammation of the esophagus, with symptoms of dysphagia, and possibly, reflux. It was initially described in children, and in recent years, there is a heightened awareness in adults. The etiology is not completely understood. The treatments include dietary manipulation, topical corticosteroids, systemic corticosteroids, Montelukast, and endoscopic dilation. In adults, there are no randomized trials demonstrating the efficacy of any particular treatment, and no prospective studies describing the natural history of the disease following treatment.. We performed an interval follow-up of patients treated with a swallowed corticosteroid inhaler. We contacted 51 adult patients who were diagnosed with EE and treated with a swallowed corticosteroid inhaler between September 1, 1999, and May 31, 2003. All patients had received 6 wk of treatment with fluticasone 220 mEq/puff, four puffs swallowed twice daily for 6 wk.. Thirty-two patients replied (63%) with a mean follow-up duration of 3.3 yr. Ninety-one percent of patients reported recurrent symptoms; a mean of 8.8 months after treatment was completed. Sixty-nine percent of patients repeated treatment with the steroid inhaler at least once.. It appears that EE is a chronic remitting disorder that requires more than one topical steroid treatment course.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Deglutition Disorders; Eosinophilia; Esophagitis; Female; Fluticasone; Follow-Up Studies; Humans; Male; Nebulizers and Vaporizers; Recurrence; Treatment Outcome

A 19-year-old white woman presented with a 6-month history of progressively worsening dysphagia.. Esophagogastroduodenoscopy, esophageal biopsies followed by histological evaluation of biopsy samples including immunohistochemical staining for herpes simplex virus.. Herpes esophagitis with concurrent eosinophilic esophagitis.. Valaciclovir and fluconazole.

Topics: Androstadienes; Anti-Inflammatory Agents; Antiviral Agents; Eosinophilia; Esophagitis; Female; Fluticasone; Herpes Simplex; Humans; Young Adult

Our aim was to evaluate the changes induced by topical steroid treatment to the esophageal epithelial inflammatory eosinophilic and T-cell infiltrate and to IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 esophageal gene expression levels in patients with eosinophilic esophagitis (EE).. Esophageal biopsies were taken from eight adult patients at the moment of diagnosis and after 3-month treatment with fluticasone propionate. Eosinophils, CD8, and CD4 T cells were examined by immunohistochemistry. IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression levels were measured by real-time PCR. Eight control samples were also analyzed.. A significant decrease in the eosinophil infiltrate and in CD8(+) T-cell density was observed in the esophageal epithelium from the patients upon steroid treatment. IL-5 was not detected in control samples, and expression levels were variably downregulated after treatment in six of the patients. Gene expression of eotaxin-1/CCL11 showed relevant downregulation in four cases and a modest twofold decrease in three of the patients studied. Mean CCL11 expression values upon steroid treatment were similar to control samples (19.4 +/- 28.6 vs 8.42 +/- 5, P= 0.7). Eotaxin-3/CCL26 gene expression levels were significantly increased in EE. Although they were significantly downregulated upon steroid treatment, control expression levels were not reached in any of the cases analyzed (580.9 +/- 943.9 vs 1.45 +/- 1.0, P= 0.001).. Our results confirm that eotaxin-3/CCL26 is significantly increased in EE esophageal samples. However, the individual analysis of IL-5, CCL11, and CCL26 expression data suggests that several cytokines and chemokines could participate in the physiopathology of EE in humans.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Biopsy; Case-Control Studies; Chemokine CCL11; Chemokine CCL26; Chemokines, CC; Down-Regulation; Eosinophilia; Esophagitis; Esophagus; Female; Fluticasone; Gene Expression; Humans; Interleukin-5; Linear Models; Lymphocyte Count; Male; Reverse Transcriptase Polymerase Chain Reaction

We describe the first detailed case of eosinophilic esophagitis associated with esophageal intramural pseudodiverticulosis and gastro-esophageal reflux disease in a 24-year-old man, who suffered from recurrent dysphagia since the age of 3 years. He presented with symptoms of dysphagia, food impaction and malnutrition. An esophagogram revealed a high-grade stenosis in the proximal part of the esophagus. Histological evaluation of esophageal mucosal biopsies demonstrated more than 20 eosinophil granulocytes per high power field, indicative of eosinophilic esophagitis. Additionally, esophago-gastro-duodenoscopy showed pseudodiverticulosis in the distal portion of the esophagus. A therapeutic regimen consisting of topical steroid intake, antihistamines, proton-pump-inhibition and specific food avoidance led to significant clinical improvement within 6 weeks.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Allergic Agents; Catheterization; Deglutition Disorders; Diverticulum, Esophageal; Eosinophilia; Esophageal Stenosis; Esophagitis; Fluticasone; Gastroscopy; Humans; Male; Manometry

Dermatophagoides farinae are known to be a common environmental allergen causing allergic asthma; however, little is known about their pathophysiological effect via the allergenicities in vivo. Therefore, we first established a mouse model of asthma induced by repeated instillations of D. farinae. Second, to investigate whether the asthmatic responses are Th2-dependent, we examined the effect of the deficiency of interleukin-4 (IL-4) receptor alpha chain gene. Finally, we examined the effect of fluticasone propionate on this model. Mice were instilled with D. farinae without additional adjuvants into the trachea 8 times. After the final allergen instillation, the airway responsiveness to acetylcholine was measured, and bronchoalveolar lavage and histological examination were carried out. The instillation of the allergen-induced airway hyperresponsiveness, the accumulation of inflammatory cells and increases in the levels of Th2 cytokines and transforming growth factor-beta(1) production in the bronchoalveolar lavage fluid dose dependently. The number of goblet cells in the epithelium and the extent of the fibrotic area beneath the basement membrane were also increased in the morphometric study. In contrast, the defect of IL-4/IL-13 signaling through IL-4 receptor alpha chain completely abrogated all these responses. Furthermore, the simultaneous instillation of fluticasone propionate with the allergen showed significant inhibition or an inhibitory tendency of these changes. These findings demonstrate that the repetitive intratracheal instillations of D. farinae can induce airway remodeling through Th2-type inflammation, and that fluticasone propionate inhibits D. farinae-induced airway remodeling in mice, and this model would be useful for studying mechanisms involved in the development of allergic asthma.

Topics: Acetylcholine; Androstadienes; Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Dermatophagoides farinae; Disease Models, Animal; Eosinophilia; Fluticasone; Goblet Cells; Interleukin-4; Male; Mice; Mice, Inbred BALB C; Th2 Cells; Transforming Growth Factor beta1

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

To describe the manometric findings detected in adult patients with dysphagia that were diagnosed of eosinophilic oesophagitis, and to compare with the cases of eosinophilic infiltration of the oesophagus reported in the literature.. We present 12 adult patients diagnosed as suffering from this disorder in our department in a 1.5-year period, according to histological criteria and discarding any other cause of eosinophilic infiltration of the oesophagus. Stationary oesophageal manometry using a hydropneumocapillary perfusion system was performed in every case. The recommendations of the Spanish Group of Digestive Motility were followed for the interpretation of the results. In seven patients who presented motor disorder in manometric evaluation, treatment with steroid oesophageal lavage using fluticasone propionate was carried out and these patients were subsequently re-evaluated.. All patients were young predominantly men, and the first endoscopic examination showed regular concentric stenosis or a 'ring oesophagus'. Six patients had a severe nonspecific oesophageal motor disorder characterized by up to 80% of nontransmitted or very low-amplitude waves in the lower two-thirds of the organ. Three patients presented a manometric disturbance characterized by hyperkinetic peristaltic waves in distal oesophageal third. One patient had an alteration of the oesophageal motor dynamics characterized by 80% of deglutory complexes formed by a primary simultaneous wave in the two lower oesophageal thirds followed by a secondary peristaltic wave in 50% of cases that had a normal duration and amplitude. The remaining two patients had normal oesophageal motility. The upper oesophageal sphincter showed no alterations, and the manometric evaluation of the lower oesophageal sphincter tone proved normal in 10 patients, with slight hypotension in two cases. In seven of the nine patients who presented an oesophageal motor disorder, treatment with steroid oesophageal lavage using fluticasone propionate was administered and a new oesophageal manometry was performed afterwards, in which the motor disorder was clearly improved as soon as dysphagia, endoscopic lesions and histopathologic alteration disappeared.. In the literature, 61 cases of eosinophilic infiltration of the oesophageal mucosa subjected to oesophageal manometric study had been described, and 60.6% of them showed evidence of different types of manometric alterations, mainly with spastic or hypercontractility characteristics. Although six of our cases showed very deficient peristalsis with very low-amplitude or nontransmitted waves, and in another three high-amplitude peristaltic waves were recorded. Motor disorders improved parallel to the disappearance of the eosinophilic infiltration of the mucosa. These data suggest that motor disorders in eosinophilic oesophagitis are a consequence of eosinophil infiltration of the oesophagus and should be considered in the differential diagnosis of dysphagia. These manometric alterations could be considered as primary nonspecific disorders and included in the 'ineffective oesophageal motility' group.

Topics: Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Deglutition Disorders; Eosinophilia; Esophageal Motility Disorders; Esophagitis; Esophagus; Female; Fluticasone; Humans; Male; Manometry; Middle Aged; Peristalsis

Eosinophilic esophagitis is an inflammatory condition of the esophagus characterized by eosinophilic infiltration. It is a condition mainly affecting children; the adult form has only recently gained recognition as a distinct entity. The major symptom among adults with eosinophilic esophagitis is dysphagia. It is often misdiagnosed as gastroesophageal reflux disease because of the similarity in symptoms. An endoscopic biopsy is required to distinguish between the conditions. The cause of eosinophilic esophagitis is poorly understood, but food allergy has been implicated. Topical steroids are the most effective and convenient method for the treatment of eosinophilic esophagitis in adults. The long-term prognosis of eosinophilic esophagitis is uncertain; however, data suggests a benign course. We herein present two eosinophilic esophagitis cases that were the first to be diagnosed in our clinic.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Biopsy; Deglutition Disorders; Eosinophilia; Esophagitis; Esophagoscopy; Esophagus; Female; Fluticasone; Heartburn; Humans; Male

Eosinophilic oesophagitis is an emerging disease, well known also in paediatric age, probably caused by both IgE and non-IgE mediated food allergies, diagnosed by upper endoscopy with biopsy. The most severe complication is oesophageal stenosis. The identification of the offending allergens is often difficult; therapy is focused to eliminate the supposed antigenic stimulus, to control the acute symptoms and to induce long-term remission.. We report the clinical outcome and the typical endoscopic findings of children and adolescents affected by eosinophilic oesophagitis, referring a proposal of diagnostic and treatment protocol.. Twelve patients, affected by eosinophilic oesophagitis with a histological diagnosis, underwent radiographic upper gastro-intestinal series, 24 h pH-probe and standardised allergic testing; they were treated with steroids (oral prednisone and swallowed aerosolised fluticasone) and elimination diet. Dilations were performed when eosinophilic oesophagitis was not yet diagnosed, or in patients resistant to conventional treatment.. Two patients were lost to follow up (mean follow up: 1 year 11 months); seven patients have no symptoms and normal histology, five of them on restricted diet (without cow's milk protein) and two patients on elemental diet (amino acid formula). In two patients (no allergens identified), mild dysphagia and eosinophilic infiltration persist; one patients underwent Nissen fundoplication for Barrett's oesophagus: he has no symptoms and normal oesophagus, on restricted diet (without cow's milk/eggs protein and wheat).. The recognition of typical endoscopic picture with careful biopsies extended to the whole oesophagus, even in emergency, could more quickly lead to the correct diagnosis and avoid severe complications of eosinophilic oesophagitis in children, as stricture and failure to growth. Elimination diet is the key of resolution when the allergens are identified. A great challenge remains the relation between gastro-oesophageal reflux disease and eosinophilic oesophagitis, which should however be explained.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Aerosols; Androstadienes; Anti-Inflammatory Agents; Biopsy; Catheterization; Child; Child, Preschool; Endoscopy, Digestive System; Eosinophilia; Esophageal pH Monitoring; Esophagitis; Female; Fluticasone; Food Hypersensitivity; Humans; Immunoglobulin E; Infant; Male; Prednisone; Prospective Studies; Retrospective Studies; Skin Tests; Upper Gastrointestinal Tract

Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery. The condition is usually complicated by asthma, and many eosinophils are present in the sinus mucosa. One conservative treatment method is the administration of glucocorticoids locally or systematically. To evaluate the efficacy and tolerability of intranasal fluticasone propionate for the treatment of chronic sinusitis with eosinophils, seven patients with chronic sinusitis with eosinophils were treated over a 12-week period using a fluticasone propionate aqueous nasal spray (800 microg per day in each nostrilz). The Symptons of 7 patients, especially nasal discharge and nasal obstructions, improved and an expanded air space was observed on paranasal CT images. The percent of drug systemically available after intranasal administration varied by less than 1% for intranasal fluticasone propionate. Therefore, even if intranasal fluticasone propionate is administerved at double the usual dose, it is unlikely to cause systemic side effects. Fluticasone propionate aqueous nasal spray at double the usual dose is effective for the treatment of chronic sinusitis with eosinophils.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Chronic Disease; Eosinophilia; Female; Fluticasone; Humans; Male; Middle Aged; Sinusitis; Treatment Outcome

A 40-year-old white male with atopy presented to our department in March 2004 with a history of chronic heartburn and solid-food dysphagia since 1994. The patient was taking on-demand salbutamol for asthma and ranitidine for mild heartburn, occurring less than once per week. Eight years previously, he had undergone esophageal dilatation for a Schatzki's ring.. Physical examination, laboratory investigations, video esophagram, upper endoscopy with mid-esophageal biopsies, and skin testing for a number of food and environmental allergens. Diagnosis Eosinophilic esophagitis.. Topical steroids with a fluticasone 220 microg multiple-dose inhaler, four puffs swallowed twice a day for 6 weeks.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Chronic Disease; Deglutition Disorders; Diagnosis, Differential; Endoscopy, Gastrointestinal; Eosinophilia; Esophagitis; Fluticasone; Gastroesophageal Reflux; Humans; Male

Topics: Acetates; Adult; Androstadienes; Anti-Inflammatory Agents; Biopsy; Cyclopropanes; Diagnosis, Differential; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Eosinophilia; Esophagitis; Fluticasone; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

Eosinophilic esophagitis (EE) is a clinical-pathological disorder which is being increasingly diagnosed. It is etiologically associated with hypersensitivity to airborne allergens and/or dietary components. However, immediate hypersensitivity to foods has rarely been proven as the etiologic cause of the disorder. Two patients are presented with a history of rhinoconjunctivitis, allergic asthma, atopic dermatitis and food allergies which are currently under control and who show specific IgE to pulses and chicken respectively. These patients developed acute dysphagia and vomiting immediately after ingesting these foods and following appropriate examination were diagnosed as suffering from EE. The study also showed signs of blood hypereosinophilia while the esophageal manometry revealed a motor disorder characterized by aperistalsis and non-propulsive simultaneous waves affecting the lower two-thirds of the organ composed of smooth muscle. Topical treatment with fluticasone propionate was administered over a period of 3 months, in addition to a diet abstaining from the aforementioned foods and this led to remission of dysphagia and normalization of the endoscopic, histological and manometric studies of the esophagus. This situation remained stable for a considerable length of time after steroid treatment was discontinued, which showed that exposure to foods seemed to be the cause of the esophageal disorder. Similarly, allergies to inhalants and other digestive symptoms which appear upon immediate ingestion of the foods involved would not justify the sudden onset of dysphagia. We offer a pathophysiological explanation for the mechanisms of the disease based on the activation of eosinophils and mast cells by IgE and their ability to disturb the dynamic behavior of the neural and muscle components of the esophageal wall.

Topics: Adolescent; Androstadienes; Animals; Anti-Allergic Agents; Chickens; Deglutition Disorders; Eosinophilia; Esophagitis; Fabaceae; Female; Fluticasone; Food Hypersensitivity; Humans; Immunoglobulin E; Male

Three men, aged 20, 24 and 42 years, reported difficulties in passing food through the oesophagus. The diagnosis of eosinophilic oesophagitis was made after endoscopic investigation, laboratory tests and histological tests. In all three patients the symptoms disappeared: respectively spontaneously, during systemic treatment with corticosteroids due to a kidney complaint, and after topical corticosteroid treatment lasting 6 weeks. Eosinophilic oesophagitis occurs in particular in young men. There are complaints about the passage of food through the oesophagus, with frequent food impaction, also without any obvious stenosis. Endoscopic features are subtle and comprise a vulnerable oesophageal mucosa with a ringed appearance or small white spots on the oesophageal mucosa. Histopathology reveals an eosinophilic infection infiltrate in the oesophageal epithelium. Food allergies may play a causal role. With respect to the treatment, favourable results have been described for oral fluticasone, while endoscopic treatment may consist of dilation.

Topics: Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Deglutition Disorders; Eosinophilia; Esophagitis; Fluticasone; Humans; Male; Treatment Outcome

Topics: Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Deglutition Disorders; Eosinophilia; Esophagitis; Female; Fluticasone; Humans; Male; Middle Aged

Topics: Androstadienes; Anti-Inflammatory Agents; Bronchitis; Cough; Eosinophilia; Female; Fluticasone; Humans; Male; Prognosis; Treatment Outcome

In asthma a dysregulation of eosinophil apoptosis and an imbalance of metalloproteinase-9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) play an important role in airway inflammation and remodelling. We evaluated the effects of a low dose of inhaled fluticasone proprionate (FP) (100 microg bid by Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma, symptomatic and with a sputum eosinophilia >or=3% on clinical outcomes and inflammatory markers such as the induced sputum eosinophils, the induced sputum apoptotic eosinophils, the levels of MMP-9 and TIMP-1 and their molar ratio in the induced sputum supernatants. After FP treatment forced expiratory volume (FEV1) and FEV1/forced vital capacity values, PEF (L/min), sputum apoptotic eosinophils, and MMP-9/TIMP-1 molar ratio in sputum supernatants of asthmatic subjects were significantly increased in comparison with baseline, while sputum eosinophils significantly decreased. Change (Delta) in FEV1 after treatment with FP negatively correlated with the Delta in sputum eosinophils, while the Delta in MMP-9 values positively correlated with Delta in TIMP-1 values. This study shows that the clinical improvement achieved by the use of low doses of FP in asthmatics is related, at least in part, to the resolution of eosinophilic inflammation and the downregulation of remodelling markers.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Apoptosis; Asthma; Down-Regulation; Eosinophilia; Eosinophils; Female; Fluticasone; Humans; Inflammation; Male; Matrix Metalloproteinase 9; Middle Aged; Tissue Inhibitor of Metalloproteinase-1; Treatment Outcome

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

Eosinophilic esophagitis (EE) is a recently recognized clinical disorder that is understood poorly. We aimed to determine the efficacy of swallowed fluticasone propionate on the immunopathologic features associated with EE.. A retrospective analysis was performed on 20 pediatric patients with EE. Inclusion criteria specified a peak eosinophil density of > or =24 cells per 400x field in the esophagus and treatment with swallowed fluticasone between 2 endoscopic assessments. Histologic specimens were examined for eosinophil and CD8(+) lymphocyte infiltration, papillary lengthening, and proliferation of the basal layer as determined by monoclonal anti-Ki-67 (MIB-1) antibody staining.. The mean time interval between endoscopic assessments was 4.8 months. The patients were divided equally between allergic and nonallergic groups based on the results of skin-prick testing. All of the nonallergic patients responded to fluticasone propionate. The endoscopic appearance of the mucosa improved and microscopic evaluation showed markedly reduced eosinophil infiltration, reduced basal layer hyperplasia documented by a reduced number of MIB-1(+) cells, and a reduced number of CD8(+) lymphocytes. However, allergic patients were relatively refractory to therapy; 20% had a partial response, whereas 20% had no detectable improvement. Esophageal eosinophil levels before and after therapy in all patients strongly correlated with the level of epithelial cell proliferation as measured by MIB-1 staining.. Collectively, these results suggest that patients treated with swallowed fluticasone have improved endoscopic, histologic, and immunologic parameters associated with EE. However, patients with identifiable allergies who fail dietary elimination may have a blunted response to treatment.

Topics: Administration, Oral; Adolescent; Androstadienes; Anti-Inflammatory Agents; Biopsy, Needle; Child; Child, Preschool; Cohort Studies; Eosinophilia; Esophagitis; Esophagoscopy; Female; Fluticasone; Follow-Up Studies; Humans; Immunohistochemistry; Male; Probability; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Androstadienes; Anti-Inflammatory Agents; Dilatation; Endoscopy; Eosinophilia; Esophageal Perforation; Esophagitis; Fluticasone; Humans

We studied 223 outpatients who presented between October 2001 and June 2003 with persistent cough of more than 3 weeks' duration. Eosinophilic airway disorders (EAD), including atopic cough and cough variant asthma, were clinically diagnosed in 119 patients, on the basis of the following factors: history of atopic disease, duration of cough, history of previous prolonged cough, or presence of forced expiration wheeze. Since eosinophils are frequently found in the sputum of patients with EAD, a positive test strongly suggests the presence of EAD. In this study, the test was positive in 86% of the patients with EAD. The patients with clinically diagnosed EAD, including those with no eosinophils in the sputum, were treated with inhaled fluticasone 400 or 800 microg/day. Fluticasone was effective in 97% of the patients with EAD and was more effective than bronchodilators or antiallergic drugs. When we compared the results of fluticasone 400 microg/day with those of 800 microg/day doses, the cough disappeared within 1 week in 28% of the patients who received 400 microg/day, whereas in 76% with 800 microg/day. Among the patients with diagnosed EAD, bronchial asthma developed in 6 patients during the observation period. Most of these patients had forced expiration wheeze and lower FEV 1 at the initial visit. This study showed that EAD could be diagnosed in the early stage on the basis of thorough history-taking, the presence of forced expiration wheeze and detection of eosinophils in the sputum. It is important to diagnose and treat EAD as early as possible since inhaled steroid is highly effective.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchitis; Cough; Eosinophilia; Female; Fluticasone; Gastroesophageal Reflux; Humans; Male; Retrospective Studies

Topics: Androstadienes; Antacids; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antirheumatic Agents; Aspirin; Barrett Esophagus; Child; Cross-Over Studies; Cyclooxygenase Inhibitors; Deglutition Disorders; Diagnosis, Differential; Double-Blind Method; Dyspepsia; Endoscopy; Eosinophilia; Esophagitis; Esophagitis, Peptic; Family Practice; Fluticasone; Gastroesophageal Reflux; Heartburn; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Middle Aged; Omeprazole; Prednisone; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Surveys and Questionnaires; Time Factors

Eosinophilic airway inflammation is one of the hallmarks of asthma. Sputum eosinophilia has been suggested as a predictor of the response to inhaled corticosteroids in asthma. This study sought to investigate the proportion of steroid-naive uncontrolled asthmatics without significant sputum eosinophilia (< or = 1%) and to examine whether sputum eosinophilia could predict the response to inhaled corticosteroids. A total of 51 mild uncontrolled steroid-naive asthmatics who had not been treated with oral or inhaled corticosteroids for at least 3 months were investigated. The evaluation included a spirometry, methacholine inhalation challenge and sputum induction on two occasions, one at baseline and the other after 1 month of treatment with 250 microg twice-daily fluticasone propionate. Of the 51 subjects, 15 had an eosinophil count < or = 1%, and 46 completed the two visits. Patients with baseline sputum eosinophils < or = 1% (n=14) were compared with those with sputum eosinophils > 1% (n=32). The baseline characteristics of these two groups were similar. After 1 month of treatment, respiratory symptoms, quality of life, forced expiratory volume in one second (FEV1) and provocative concentration causing a 20% fall in FEV1 improved in both groups. The absence of sputum eosinophilia does not seem to be an indicator of poor response to inhaled corticosteroid treatment in steroid-naive asthmatics. However, this finding needs to be investigated further in a double-blind, placebo-controlled study, entirely designed to answer this question.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Eosinophilia; Female; Fluticasone; Humans; Male; Spirometry; Sputum

Eosinophilic esophagitis (EE) shares symptoms with gastroesophageal reflux disease but has distinctive pathologic features and unknown immunopathology. Treatments with antigen restriction or systemic immunosuppression pose problems with compliance and side effects. Topically applied steroids offer an attractive alternative treatment. The aims of this study were to determine the immunopathologic features of EE and the effectiveness of antigen-specific diet restriction (DR) and topical immunosuppression.. A prospective trial was conducted examining the impact of DR and swallowed fluticasone propionate (FP) on pediatric patients with EE. Clinicopathologic features, including immunohistochemical analysis of the esophageal mucosa, were measured before and after treatment.. Immunohistochemical analysis of 11 prospectively identified children showed a significantly greater number of mucosal CD3 and CD8 lymphocytes, as well as CD1a antigen-presenting cells compared with normal controls. DR did not induce clinical improvement in any patients, whereas all children who completed treatment with FP had resolution of symptoms. Posttreatment analysis of proximal and distal esophageal mucosa showed a significant reduction in the number of eosinophils, as well as CD3(+) and CD8(+) lymphocytes compared with pretreatment sections.. EE is characterized by immunologically active esophageal mucosa. FP, not DR, effectively relieves symptoms. FP significantly reduces mucosal inflammation associated with EE.

Topics: Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Antigens, CD1; Child; Child, Preschool; Diet; Eosinophilia; Esophagitis; Female; Fluticasone; Humans; Infant; Male; Prospective Studies; T-Lymphocytes

Local corticosteroids are currently the most efficient safe anti-allergic treatment, which attenuate eosinophilic tissue inflammation through several mechanisms. We evaluated the effect of local airways corticosteroid on repeated allergen exposure-induced bone marrow activation and airway eosinophilia using the number of eosinophils in bone marrow, bronchoalveolar lavage fluid (BALf) and airways tissue as study end-points. Male BALB/c mice were sensitized by intraperitoneal injections of aluminum-precipitated ovalbumin (OVA) on two different days (5 days apart). Eight days after the second sensitization, the animals were challenged intranasally with OVA or phosphate-buffered saline (PBS) on 5 consecutive days. Concomitantly with challenges mice were treated with fluticasone propionate or respective vehicle. OVA exposures induced a significant increase in eosinophil numbers in bone marrow, BALf and airways tissue (P<0.005). Treatment with fluticasone propionate significantly reduced the increase of absolute number of mature bone marrow eosinophils (P=0.014) and showed a tendency towards decrease in the immature bone marrow eosinophil number (P=0.057) compared to controls. However, fluticasone propionate had no significant effect on BALf and airways tissue eosinophils (P=0.28 and 0.07, respectively). In this murine allergy model intranasal corticosteroid reduced number of bone marrow mature eosinophils, but did not significantly affect airways cell populations.

Topics: Allergens; Androstadienes; Animals; Anti-Inflammatory Agents; Bone Marrow; Eosinophilia; Fluticasone; Male; Mice; Mice, Inbred BALB C

In allergic rhinitis, allergenic stimulation causes the release of various mediators that induce symptoms and the development of chronic inflammation, which, in turn, is caused by cells involved in the late phase of inflammation, such as eosinophils. The eosinophils also cause damage at the mucosal level through the secretion of eosinophil cationic protein and other preformed factors contained in their granules. The objective was to verify the efficacy of fluticasone propionate aqueous nasal spray in patients with allergic rhinitis; in a retrospective study, we have evaluated mediators of inflammation, making correlations with the clinical symptoms score during and outside the pollen season.. Forty patients with allergic rhinitis and 15 normal controls were included in our study. Eosinophil cationic protein, eosinophil chemotactic activity, and blood and nasal lavage eosinophil count were evaluated as laboratory parameters.. We found a significant increase in nasal lavage levels of eosinophil cationic protein in allergic patients, and this was strictly correlated with the clinical symptoms score. No differences were found in the eosinophil count of allergic patients and in the serum eosinophil cationic protein of patients sensitized to seasonal allergens in comparison with normal subjects. By contrast, an increase in serum eosinophil cationic protein level was found in patients sensitized to perennial allergens. After topical administration of fluticasone propionate aqueous nasal spray, a reduction in nasal lavage eosinophil cationic protein secretion was obtained with a reduction of eosinophil chemotactic activity at the local level. This reduction correlated with an improvement of clinical symptoms.. The clinical improvement and reduction in nasal lavage eosinophil cationic protein and eosinophil chemotactic activity after administration of fluticasone propionate aqueous nasal spray further confirms the role of this treatment in allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Blood Proteins; Chemotaxis; Child; Eosinophil Granule Proteins; Eosinophilia; Eosinophils; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Lavage Fluid; Retrospective Studies; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Ribonucleases

Topics: Acetates; Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Churg-Strauss Syndrome; Cyclopropanes; Dose-Response Relationship, Drug; Eosinophilia; Fluticasone; Humans; Nebulizers and Vaporizers; Prednisolone; Quinolines; Sulfides

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Eosinophilia; Esophageal Diseases; Fluticasone; Glucocorticoids; Humans

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Child; Eosinophilia; Esophagitis; Female; Fluticasone; Glucocorticoids; Humans; Male