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Biomedical subjects

F M de Benedictis

Publications and source records attributed to F M de Benedictis.

At least 19 recordsLinked to original sources
PubMed2006

Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children.

The effect over time of regular treatment with montelukast (MNT) in inhibiting exercise-induced bronchoconstriction (EIB) has never been evaluated in children. The aim of the present study was to examine the preventive effect of MNT against EIB in children at different time-points over a 4-week treatment period. Thirty-two asthmatic children (aged 6-12 yrs) were enrolled in a double-blinded, randomised, parallel group design to receive a 4-week treatment with MNT (5 mg chewable tablets administered once daily in the evening) or placebo. Exercise challenge was performed at baseline and after 3, 7 and 28 days of treatment, 20-24 h after dosing. MNT was significantly more protective than placebo against EIB at each time. The mean percentage drop of forced expiratory volume in one second (FEV1) was 24.6, 13.6, 12.0 and 11.6 for MNT, and 24.4, 22.4, 21.8 and 21.0 for placebo, at baseline and after 3, 7 and 28 days, respectively. For each drug, no significant difference in the percentage drop of FEV1 was found between different days. Regular treatment with montelukast provided significant protection against exercise-induced bronchoconstriction in asthmatic children over a 4-week period with no tolerance to the bronchoprotective effect.

Acetates↗
PubMed2004

Biological effects of montelukast, a cysteinyl-leukotriene receptor-antagonist, on T lymphocytes.

BACKGROUND: Montelukast (MNT), a cysteinyl-leukotriene receptor (Cys-LTR) antagonist, has anti-inflammatory activity in the treatment of allergic diseases. If this effect is due only to blocking leukotrienes or also owing to inhibiting proliferation and survival of inflammatory cells, is actually unknown. OBJECTIVE: Testing the hypothesis that MNT could influence T lymphocyte functional behaviour in vitro. METHODS: Normal T lymphocytes were analysed for surface expression of Cys-LTR(1) and Cys-LTR(2) by means of monoclonal antibodies (mAbs), in the resting state and after activation with T helper type 2 cytokine or T cell receptor (TcR) stimulation. Proliferative activity, as well as IL-4 andIFN-gamma production, were simultaneously determined in samples exposed to molar concentrations of MNT from 10(-8) to 10(-5). Programmed cell death in cultured samples was evaluated by means of propidium iodide and fluorescein isothiocyanate-conjugated anti-Annexin V mAb staining. The complementary DNA microarray technique was adopted to identify gene products involved in apoptosis induction. RESULTS: Resting T cells expressed low levels of Cys-LTR. Upon anti-CD3 mAb activation, a progressive increase in Cys-LTR(1) and -LTR(2) expression was observed. Exposure to MNT reduced proliferative response to TcR engagement, increased IFN-gamma production and led to apoptosis at minimal concentrations of 10(-6) M. A progressive loss in BAD and B cell lymphoma/leukaemia-2 activities, and an increase in the expression of CD27, TRAF3, TRAIL, p53 and Fas genes were also observed. CONCLUSIONS: Biological effects of MNT delineate a complex picture of gene activation and repression, probably induced by Cys-LTR blockade. The induction of apoptosis in allergen-specific T cell population, as a final result, appears fundamental in the treatment of asthma.

Acetates↗
PubMed2001

Effects of 2 inhaled corticosteroids on growth: results of a randomized controlled trial.

OBJECTIVE: To compare the long-term effect of treatment with fluticasone propionate or beclomethasone dipropionate on growth in asthmatic children. DESIGN: Prospective, multicenter, randomized, double-blind, parallel-group study. SETTING: Children requiring regular treatment with inhaled corticosteroids and with a sexual maturity rating of Tanner stage 1 (prepubertal). PATIENTS: Three hundred forty-three children aged 4 to 11 years with asthma. The growth population (excluding patients with protocol violations likely to affect growth measurements) included 277 patients. INTERVENTIONS: Fluticasone propionate or beclomethasone dipropionate, both at a dosage of 200 microg administered twice daily via a dry powder inhaler (Diskhaler) for 12 months. MAIN OUTCOME MEASURES: Growth velocity, lung function, and serum and urinary cortisol levels. RESULTS: The adjusted mean growth velocity in the fluticasone group was significantly greater than that in the beclomethasone group (5.01 [SE, 0.14] vs 4.10 [SE, 0.15] cm/y; difference, 0.91 cm; 95% confidence interval, 0.63-1.20 cm; P<.001). Both treatments improved lung function, with significant differences in favor of fluticasone. Adverse events were similar in both groups, and there were no significant differences in effect on serum and urinary cortisol levels. CONCLUSIONS: The more favorable risk-benefit ratio of fluticasone indicates that this agent is preferable to beclomethasone for the long-term treatment of children with asthma, especially if moderate doses are required.

Androstadienes↗
PubMed2001

Rhinitis, sinusitis and asthma: one linked airway disease.

Understanding the relationship between upper and lower airways has greatly increased through epidemiological and pharmacological studies. Scientific evidence supports the concept that rhinosinusitis and asthma may be the expression of an inflammatory process which appears in different sites of the respiratory tract at different times. The implications are not only academic but are important for diagnostic and therapeutic purposes.

Asthma↗
PubMed2001

CD4+IL13+ T lymphocytes at birth and the development of wheezing and/or asthma during the 1st year of life.

BACKGROUND: Despite our knowledge that maternal inheritance influences the development of asthma in childhood, attempts to identify a clear-cut Th2-oriented cytokine production by T lymphocytes at birth have given conflicting results. The prognostic significance of these cells for asthma development later in life remains to be determined. METHODS: We evaluated at the single cell level Th1- and Th2-type cytokines in 208 randomly selected cord blood mononuclear cell (CBMC) samples obtained from pregnant women (group A, n = 68 with diagnosed respiratory allergic disease; group B, n = 140, with no evidence of atopy), and prospectively followed newborns for 1 year. RESULTS: There was no difference in IFN-gamma, IL-4 and IL-5 production at birth between both groups, whereas a correlation between CD4+IL13+ lymphocytes from CBMC samples derived from atopic mothers and the occurrence of wheezing and/or asthma during the 1st year of life was found. CONCLUSIONS: Our observations suggest that the intracellular cytokine profile of cord blood CD4+ cells, in terms of IL-13 production, could be considered a useful tool for a more accurate identification of newborns from atopic mothers who are at high risk of developing asthma.

Asthma↗
PubMed2000

Treatment of complicated pleural effusion with intracavitary urokinase in children.

Intrapleural administration of fibrinolytic agents such as urokinase (UK) has been advocated as an alternative method to manage complicated pleural effusion (CPE). Despite the increasing number of empyemas successfully treated with UK in adults, the experience in children is limited to a few cases. We report the results of image-guided catheter drainage (IGCD) with intracavitary instillation of UK in six children with CPE. Urokinase (25,000-100, 000 IU) was diluted in 20 mL of normal saline and instilled into the pleural cavity via a percutaneously placed drainage catheter. After 4 hr, the clamped catheter was released and connected to water-seal suction at a negative pressure of 20 cm H(2)O. UK instillation was repeated daily until no further drainage occurred. During IGCD, repeated radiographic and ultrasound imaging determined the location and amount of any remaining pleural fluid. Mean duration of hospital stay before initiating UK therapy was 4.3 days. Mean duration of catheter drainage before initiating UK therapy was 3.5 days, and the mean total drainage was 86 mL. All patients had an increase in chest tube drainage within 24 hr after the first instillation of UK. The mean net total drainage after UK instillation was 281 mL, most of the drainage being occurring in the first 2 days of treatment. Mean hospital stay following UK treatment was 5.8 days, and the average total duration of hospital stay was 13.8 days. No complications and no adverse events occurred during treatment with UK. Complete resolution of the consequences of the pleural effusion was observed in all patients at follow-up. Our results suggest that IGCD with adjunctive UK therapy is a reliable, simple, and safe approach to treat CPE, and it can reduce the risks associated with thoracotomy and decortication.

Adolescent↗
PubMed1998

Combination drug therapy for the prevention of exercise-induced bronchoconstriction in children.

BACKGROUND: Sequential administration of a beta-agonist and cromolyn or nedocromil before exercise is recommended for patients whose symptoms are not controlled by beta-agonists alone; however, this practice reduces compliance. OBJECTIVE: To evaluate the effectiveness of a new pre-combined aerosol formulation (salbutamol and nedocromil) in preventing exercise-induced bronchoconstriction and to compare it to salbutamol alone. METHODS: Twelve children with asthma were studied in a double-blind, double-dummy, randomized, crossover, placebo-controlled design to compare the protective effect of salbutamol and a new pre-combined salbutamol/nedocromil formulation against exercise-induced bronchoconstriction. The drugs were delivered by a metered-dose inhaler (salbutamol, 200 microg; salbutamol/nedocromil, 200 microg/4 mg; placebo, 2 puffs) 20 minutes before exercise. RESULTS: Both active drugs were significantly more protective than placebo but there was no difference between them. Complete protection was obtained in 12/12, 10/12, and 1/12 subjects for the salbutamol/nedocromil combination, salbutamol alone and placebo, respectively. CONCLUSIONS: Although inhaled beta-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction, a minority of patients exists for whom a combined treatment with salbutamol and nedocromil is advantageous. This group may represent a subpopulation of subjects who release more, or different, mediators in response to exercise.

Adolescent↗
PubMed1996

Nebulized flunisolide in infants and young children with asthma: a pilot study.

The role of nebulized flunisolide solution in controlling recurrent respiratory symptoms was assessed in a double-blind placebo-controlled parallel study on 23 infants and small children (mean age, 14.2 months) with bronchial asthma. Five of the 12 children in the placebo group and 1 of the 11 patients on active treatment had to be withdrawn from the study. Flunisolide significantly improved symptom scores of wheezing and cough. The rescue treatments with salbutamol did not differ between the two groups during the study. Parents considered the active treatment effective in all the patients, while the placebo was considered useful in 4 of 7 children. No side effects were detected with either treatments. This study indicates that nebulized flunisolide may be an effective treatment for infants with recurrent wheezing and cough.

Airway Resistance↗
PubMed1996

The role of corticosteroids in respiratory diseases of children.

Glucocorticosteroids are potent anti-inflammatory agents and have an important role in a variety of respiratory diseases. Although their exact mode of action is unknown, it is thought that they exert their effects by binding to cytoplasmic glucocorticoid receptors. In certain conditions, such as asthma, the value of steroids cannot be questioned, and inhaled steroids have revolutionized management. In other situations, such as interstitial lung disease, the true role of steroids is still to be defined. In the management of diseases such as tuberculosis, the use of steroids is solely based on anecdotal experience.

Adrenal Cortex Hormones↗
PubMed1996

Salmeterol in exercise-induced bronchoconstriction in asthmatic children: comparison of two doses.

Since the optimal dose of salmeterol in asthmatic children has not yet been clearly defined, we compared the efficacy and duration of the protective effect of two doses of salmeterol (25 and 50 micrograms) against exercise-induced bronchoconstriction. Twelve children (aged 7-14 yrs) with asthma were studied in a double-blind, cross-over, placebo-controlled design. On three separate days, exercise tests were performed 1 h and 12 h after administration of the drug. Pulmonary function measurements were performed before drug inhalation, before every exercise test and 1, 5, 10, 15 and 30 min after the end of exercise. The response was expressed as maximal decrease in forced expiratory volume in one second (FEV1). Both doses of salmeterol provided significant bronchodilation for up to 12 h, with no difference between them. Maximal exercise-induced decrease in FEV1 (% fall) 1 h after pretreatment was (mean +/- SD) 35 +/- 16, 10 +/- 10 and 4 +/- 3% for placebo, 25 and 50 micrograms salmeterol, respectively. At 12 h after pretreatment these values were 31 +/- 14, 19 +/- 12 and 15 +/- 13%, respectively. Individual protection against exercise-induced bronchoconstriction at 1 and 12 h did not vary between the dosages (p < 0.05), even though the protection obtained by 25 micrograms at 12 h was no longer significant versus placebo. We conclude that 25 micrograms of inhaled salmeterol provides equally effective long-lasting bronchodilation and acute protection against exercise-induced bronchoconstriction as 50 micrograms, and may be a suitable dose for most asthmatic children.

Administration, Inhalation↗
PubMed1995

Comparison of airway reactivity induced by cold air and metacholine challenges in asthmatic children.

Bronchial responsiveness to isocapnic hyperventilation with cold air (CAH) and to inhaled methacholine (MCH) was compared in 17 children with bronchial asthma. The response to cold air was expressed as the percent drop in FEV1 from baseline at 4 min. after the challenge (delta % FEV1 CAH), and the response to methacholine as the provocative concentration required to reduce the FEV1 by 20% from baseline (PC20MCH). Both tests were sensitive (94%) for detecting airway hyperreactivity. There was no statistically significant relationship between delta % FEV1 CAH and the log PC20MCH (r = 0.39; P = 0.12). In clinical practice, methacholine test is easier to perform, but in the research field cold air challenge may be preferable because it avoids potential drug effects.

Administration, Inhalation↗
PubMed1995

Cromolyn versus nedocromil: duration of action in exercise-induced asthma in children.

Cromolyn sodium (10 mg), nedocromil sodium (4 mg), and placebo, all delivered by a metered dose inhaler, were compared in their efficacy and duration of action in preventing exercise-induced asthma in children. After a screening test was performed, 13 patients with asthma performed standard exercise tests 20 minutes and 140 minutes after drug inhalation in a randomized, double-blind, crossover study. Both drugs were significantly more protective than placebo after 20 minutes, but no significant difference was seen between cromolyn sodium and nedocromil sodium. No difference between active drugs and placebo was found 140 minutes after inhalation. At these clinically recommended doses both cromolyn sodium and nedocromil sodium provide equal protection against exercise-induced asthma, and the duration of action of both lasts for less than 2 hours.

Adolescent↗
PubMed1994

Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children.

Seventeen children with asthma were studied in a double-blind, crossover, placebo-controlled study designed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma. All drugs were delivered through a metered-dose inhaler (cromolyn sodium, 10 mg; nedocromil sodium, 4 mg; placebo, two puffs). Nedocromil sodium and cromolyn sodium provided significant, comparable protection from exercise-induced asthma, and both drugs were better than placebo. We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children.

Adolescent↗
PubMed1993

Mild prematurity and respiratory functions.

Pulmonary function tests and bronchial reactivity to methacholine (MCH) were measured in 34 randomly selected prematures (21 males, 13 females; mean age 11.6 years; mean gestational age 34.9 weeks; mean birth weight 1980 g) and in 34 siblings (22 males, 12 females; mean age 12.5 years, mean gestational age 39.5 weeks; mean birth weight 3030 g). None had suffered neonatal respiratory distress syndrome or had been artificially ventilated. Prematurely born children had a residual volume (RV) and residual volume/total lung capacity (RV/TLC) significantly (P < 0.01) increased compared to controls, although the mean values of both groups were still within the upper limits of normal. Furthermore, an increase of closing volume/vital capacity and closing capacity/total lung capacity (CC/TLC) was observed in most patients with increased RV and RV/TLC. No significant difference was observed for bronchial responsiveness to MCH between prematurely born and control children (11.8% and 5.9% of hyperreactive subjects, respectively). Maternal smoking during pregnancy was prevalent in prematures with impaired respiratory functions. In conclusion clinically normal children of smoking mothers who have survived prematurity but present some respiratory function impairment compared to their born-at-term siblings, should be fully informed and protected from risk factors for chronic obstructive pulmonary disease (COPD) in adult life.

Bronchial Hyperreactivity↗