fluticasone and Pulmonary-Eosinophilia

Treatment of canine idiopathic eosinophilic bronchopneumopathy mainly consists of long-term oral corticosteroid therapy. To avoid side effects, inhaled steroid therapy has been increasingly used but long-term clinical response and potential side effects are sparsely described.. Description of clinical response and side effects with long-term fluticasone in dogs with eosinophilic bronchopneumopathy.. Case series of dogs with eosinophilic bronchopneumopathy and treated with fluticasone monotherapy for at least 6 months. Clinical response and side effects assessed by physical examination, standardised questionnaire and ACTH (corticotropin) stimulation test.. Eight dogs were treated for between 6 months and 5 years. Cough initially improved in all dogs; two dogs remained free of clinical signs, three were well controlled, but three showed severe relapse. Pituitary-adrenal axis inhibition occurred in two dogs treated with fluticasone monotherapy for more than 2 years; only one dog had clinical signs of iatrogenic hyperadrenocorticism.. Fluticasone monotherapy allows initial improvement or remission in the majority of dogs but long-term treatment fails to resolve the cough in some individuals. In addition, such therapy may induce pituitary-adrenal axis inhibition. Prospective larger and randomised studies including both fluticasone and orally-treated dogs are needed to define the optimal treatment.

Topics: Administration, Inhalation; Animals; Bronchodilator Agents; Bronchopneumonia; Cough; Dog Diseases; Dogs; Female; Fluticasone; Follow-Up Studies; Male; Pulmonary Eosinophilia

Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma.. A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of > or =3.5%.. Eighteen patients received low dose fluticasone (250 mug/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV(1) (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not.. Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naive eosinophilic asthma.

Topics: Acetates; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Double-Blind Method; Eosinophils; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Patient Compliance; Pulmonary Eosinophilia; Quinolines; Sputum; Sulfides; Treatment Outcome

RATIONALE Airway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is conflicting regarding non-eosinophilic asthma (NEA). OBJECTIVES To assess the inflammatory cell phenotypes in asthma after eliminating potentially confounding effects; to compare steroid response in EA versus NEA; and to investigate changes in sputum cells with inhaled corticosteroid (ICS). METHODS Subjects undertook ICS withdrawal until loss of control or 28 days. Those with airway hyper-responsiveness (AHR) took inhaled fluticasone 1000 microg daily for 28+ days. Cut-off points were > or = or <2% for sputum eosinophils and > or = or <61% for neutrophils. RESULTS After steroid withdrawal (n=94), 67% of subjects were eosinophilic, 31% paucigranulocytic and 2% mixed; there were no neutrophilic subjects. With ICS (n=88), 39% were eosinophilic, 46% paucigranulocytic, 3% mixed and 5% neutrophilic. Sputum neutrophils increased from 19.3% to 27.7% (p=0.024). The treatment response was greater in EA for symptoms (p<0.001), quality of life (p=0.012), AHR (p=0.036) and exhaled nitric oxide (p=0.007). Lesser but significant changes occurred in NEA (ie, paucigranulocytic asthma). Exhaled nitric oxide was the best predictor of steroid response in NEA for AHR (area under the curve 0.810), with an optimum cut-off point of 33 ppb. CONCLUSIONS After eliminating the effects of ICS and smoking, a neutrophilic phenotype could be identified in patients with moderate stable asthma. ICS use led to phenotype misclassification. Steroid responsiveness was greater in EA, but the absence of eosinophilia did not indicate the absence of a steroid response. In NEA this was best predicted by baseline exhaled nitric oxide.

Topics: Adolescent; Adult; Aged; Androstadienes; Asthma; Breath Tests; Bronchial Provocation Tests; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Neutrophils; Nitric Oxide; Phenotype; Pulmonary Eosinophilia; Respiratory Hypersensitivity; Sputum; Young Adult

To determine the value of inhaled corticosteroids in the management of chronic inflammatory airway disease in dogs.. Medical records of dogs that were presented for the investigation of respiratory disease were reviewed retrospectively. Criteria for inclusion were knowledge of previous medical treatment including side effects, diagnosis of the underlying disease, use of inhaled corticosteroids and at least two-months follow-up data.. Thirteen dogs that fulfilled the criteria were identified. Ten dogs were diagnosed with chronic bronchitis and three with eosinophilic bronchopneumopathy. Four dogs had not previously received corticosteroid treatment for their respiratory disease, and all these showed a reduction or a resolution of clinical signs without obvious side effects after inhaled corticosteroid therapy. Nine dogs had previously received oral or parenteral corticosteroids for treatment of their respiratory disease, and all had exhibited side effects. Five of these dogs were treated with inhaled corticosteroids alone, and all exhibited an improvement in clinical signs without observable side effects. The remaining four dogs were treated with a combination of inhaled and oral corticosteroids, and all showed improvement in clinical signs and reduction in side effects. Inhaled medication was well tolerated in all dogs.. Inhaled corticosteroids were used for the management of chronic bronchitis and eosinophilic bronchopneumopathy in 13 dogs, and these may have the advantage of reducing side effects associated with oral corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Animals; Anti-Inflammatory Agents; Beclomethasone; Bronchitis; Bronchopneumonia; Chronic Disease; Dog Diseases; Dogs; Female; Fluticasone; Male; Pulmonary Eosinophilia; Respiratory Tract Diseases; Retrospective Studies; Treatment Outcome

Recent data demonstrate that atopic inflammation might enhance airway responses to inhaled LPS in individuals with atopic asthma by increasing CD14 expression on airway macrophages. We sought to determine whether blunting airway eosinophilic inflammation decreases CD14 expression and the subsequent airway polymorphonuclear neutrophil (PMN) response to inhaled LPS in subjects with atopic asthma. Twelve such subjects underwent a 2-week, placebo-controlled trial of inhaled steroid (440 microg fluticasone propionate [FP] twice per day); this was followed 48 hours later by an inhaled LPS (5 microg) challenge. A comparison of LPS-induced inflammatory cells in sputum, CD14 expression, and methacholine responsiveness with FP or placebo was conducted. Flow cytometry was used to analyze membrane-bound CD14 expression (mean fluorescence intensity) on sputum macrophages. We report that 48 hours before inhaled LPS challenge (baseline), FP significantly blunted airway eosinophils (cells per milligram; P =.04) and mCD14 expression (mean fluorescence intensity; P =.03) but did not decrease the number of PMNs (cells per milligram). Six hours after LPS challenge, airway PMNs and mCD14 expression were significantly decreased for FP in comparison with placebo (P =.04). Our data suggest that decreasing airway allergic inflammation with corticosteroids results in both decreased expression of CD14 on airway monocytic cells and a decreased PMN response to inhaled LPS.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cell Count; Female; Fluticasone; Humans; Hypersensitivity, Immediate; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Middle Aged; Neutrophils; Pulmonary Eosinophilia; Sputum

In this study, we examined the effects of fluticasone propionate (FP) and pentamidine isethionate (PI) on antigen-induced lung inflammation and airway hyperreactivity in guinea pigs. Male guinea pigs were sensitized on days 0 and 14 with 10 micrograms of ovalbumin (OVA) plus 1 mg of Al(OH)3. On day 21, animals were challenged with a 2% OVA aerosol inhalation until they developed pulmonary obstruction. Animals were treated with aerosol inhalation of FP (2 ml of 0.5 mg/ml, five consecutive doses at 12-hr intervals with the last dose given 6 hr before OVA challenge) or PI (30 mg/ml for 30 min 1 hr before OVA challenge), and control animals received no drug before OVA challenge. Airway reactivity to methacholine (MCh) was assessed before sensitization and 18 hr after OVA challenge. At 18 hr after challenge, histological sections of trachea and lung were examined for eosinophil, dendritic cell (DC) and macrophage cell densities in the airways. In control animals, OVA evoked airway hyperreactivity to MCh in conjunction with pulmonary eosinophilia and increases in DC prevalence in the trachea and bronchi. Treatment with FP or PI abolished the OVA-induced hyperresponsiveness and significantly reduced the OVA-induced increases in eosinophils and DCs in the airways. FP and PI had no effect on saline-treated animals. Our study indicates that both inhaled FP and inhaled PI reduce antigen-induced airway hyperreactivity and pulmonary inflammation in guinea pigs. The results also suggest that the DC is a target of the anti-inflammatory effects of these drugs in the airways.

Topics: Androstadienes; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Dendritic Cells; Fluticasone; Guinea Pigs; Male; Ovalbumin; Pentamidine; Pulmonary Eosinophilia