Renato Testi

Once daily intranasal fluticasone propionate (200 μg) reduces nasal symptoms and inflammation but also attenuates the increase in bronchial responsiveness during the pollen season in allergic rhinitis

BACKGROUND Fluticasone propionate aqueous nasal spray, a new topical corticosteroid, has been proved to be an effective treatment for seasonal allergic rhinitis. OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Novel Anti-inflammatory Effects of the Inhaled Corticosteroid Fluticasone Propionate During Lung Myofibroblastic Differentiation

Asthma is characterized by an irreversible subepithelial fibrosis with the appearance of myofibroblasts, which can be now considered important early participants in inflammatory responses as well as potential targets for anti-inflammatory drugs. In this study, we show that fluticasone propionate (FP), a powerful inhaled corticosteroid (ICS), displays novel anti-inflammatory effects on human lung fibroblasts during their myofibroblastic differentiation. Indeed, FP inhibits in lung myofibroblasts, at a very early stage of differentiation, the activation of Janus kinase/STAT pathways induced by IL-13 (tyrosine kinase 2, STAT1, STAT3, STAT6, mitogen-activated protein kinase). Contrarily, in mildly or fully differentiated myofibroblastic cultures, FP still displays a potential anti-inflammatory activity even if it only inhibits tyrosine kinase 2 phosphorylation. Moreover, FP inhibits constitutive and TGF-β-induced expression of α-smooth muscle actin, the main marker of myofibroblastic differentiation, both in very early and in mild differentiated myofibroblasts. Finally, FP displays an additional powerful anti-inflammatory effect, decreasing nuclear translocation of NF-κB independent of the degree of myofibroblastic differentiation. These data 1) suggest that myofibroblasts are priority targets for ICS, which is able to revert them to a normal phenotype even if they appear to be already engaged in their differentiation, and 2) may help to explain why asthma is improved by an early ICS treatment, whereas advanced asthma is more resistant to these drugs.

Nebulized Fluticasone Propionate vs. Budesonide as Adjunctive Treatment in Children with Asthma Exacerbation

Objectives: To compare the effects of nebulized fluticasone propionate (FP) and nebulized budesonide (BUD) in addition to inhaled salbutamol in children with mild asthma exacerbation. Methods: The study was a multicenter, randomized, single-blind, parallel group design. One hundred and sixty-eight children, aged 4–15 years, were randomly allocated to receive either nebulized FP (250 mcg) or nebulized BUD (500 mcg) twice daily for 10 days. On presentation, at the end of treatment, and after a 7-day follow-up, clinical assessment and pulmonary function measurements were performed. Daytime and nighttime asthma symptom scores, the use of rescue salbutamol, and morning/evening peak expiratory flow (PEF) values were recorded at home during the treatment period. Morning cortisol concentration (51 children) and overnight urinary cortisol excretion (30 children) were also measured in six centers at the start and at the end of the treatment. Results: Improvement of morning PEF was significantly higher in patients treated with FP (p = 0.032). The percentage of symptom-free nights was significantly higher in the BUD group (p = 0.006), but no difference was found in symptom-free days. No intergroup difference was detected in the percentage of days/nights free from rescue medication and in pulmonary function tests performed in outpatient settings. There was no evidence of hypothalamo-pituitary-adrenal axis suppression. Conclusions: A short course of nebulized FP has the same effects as a double dose of nebulized BUD, when either drug is added to bronchodilator therapy in children with mild asthma exacerbation.

The level of control of mild asthma in general practice: an observational community-based study

Abstract Objective: The aim of the present community-based study was to evaluate the level of asthma control in patients with mild asthma, regularly treated with inhaled steroids (ICS). Method: This observational cross-sectional study included patients registered in the general practitioner (GP) database and with at least three prescriptions of ICS in the last 12 months. Patients were asked to refer to the doctor’s office for a standardised interview. The level of asthma control was self-measured by the patients using the Asthma Control Test (ACT)™ (Quality Metric, Inc.). Results: The study included 950 asthmatic patients, referred by 540 GPs: 54.5% were females, mean age was 51 (±19.1) years; 59.5% were non-smokers, 22.5% were current smokers and 18.0% were former smokers; 81.1% of the patients were on ICS in the last 4 weeks. Only 38.6% of patients had a spirometry in the last 12 months. According to the ACT, 13.7% of the asthmatic patients were totally controlled, 51.0% well controlled, and 35.3% poorly controlled. Smoking habit, older age (>60) and living in Central or Southern Italy were associated with poorer control. In the last 12 months 4.5% of patients had an asthma-related hospitalisation, 5.3% an emergency visit and 18.9% a specialist visit. Conclusions: More than one of three patients had poor asthma control, despite being considered by their GPs as mild asthmatics and treated with ICS. Asthmatic patients need to be regularly re-evaluated. Treatment is often inadequate and should be targeted to improve control and reduce asthma morbidity (SAM104964).