Prophylactic Treatment Of Asthma Research Articles

Zafirlukast Inhibits Complexation of Lsr2 with DNA and Growth of Mycobacterium tuberculosis

The mycobacterial nucleoid-associated protein Lsr2 is a DNA-bridging protein that plays a role in condensation and structural organization of the genome and acts as a global repressor of gene transcription. Here we describe experiments demonstrating that zafirlukast inhibits the complexation between Lsr2 and DNA in vitro. Zafirlukast is shown to inhibit growth in two different species of mycobacteria tested but exhibits no growth inhibition of Escherichia coli. The Lsr2 inhibitory activity is reflected in vivo as determined by monitoring of transcription levels in Mycobacterium tuberculosis. These data suggest that zafirlukast inhibits Lsr2 function in vivo, promoting dysregulation of the expression of an array of genes typically bound by Lsr2 and hindering growth. Since zafirlukast likely operates by a mechanism distinct from current M. tuberculosis drugs and is currently used as a prophylactic treatment for asthma, it offers an intriguing lead for development of new treatments for tuberculosis.

The September Epidemic of Asthma in Israel

Background. The seasonality of asthma morbidity is well recognized. A peak in asthma exacerbations in September has been noted for years at our center. Objective. To examine the hypothesis that the increment in asthma exacerbations in September is influenced by the beginning of the kindergarten and school year. Methods. The monthly admission rate for asthma in patients of different ages was retrospectively evaluated in seven hospitals from various areas in Israel from January 2003 to December 2005. Results. Of the 408,242 hospital admissions during the study period, 8,011 were for asthma exacerbations: 4,091 in adults (1.3% of adult admissions) and 3,920 in children (3.8% of pediatric admissions). The asthma admission rates varied considerably throughout the year, with a peak of 4% of total admissions in the winter months and a nadir of 2% in the summer months. September was unique for its particularly high rate of admissions for asthma attacks in children (6% of total admissions), especially toddlers and the school-age group. In adults there was a progressive increase in asthma admissions from September through December without a unique peak in September. Conclusions. There is a characteristic increase in asthma exacerbations and admissions in September in the pediatric age group. This phenomenon might be explained by the increased exposure to respiratory viruses, to new allergen exposure in school or kindergarten, increased emotional stress due to start of the new school year, or poor compliance and withdrawal of treatment during the summer. Clinicians should consider administering prophylactic treatment for asthma in children before onset of the school year.

Prophylactic treatment of asthma

To review basic concepts, inhalation therapy, classification of asthma and peculiarities of asthma in developing countries. Direct search in the Medline, HighWire and MD Consult databases. Inhaled corticosteroids are the drugs of choice for the treatment of asthma. Alternatively, other drugs, such as long-acting beta-agonists and antileukotrienes could be considered. At an individual level, asthma treatment presents a satisfactory outcome. However, the great challenge for public health professionals and authorities is to provide treatment for asthmatic patients from low-income families living in developing countries.

Prophylactic treatment with loratadine versus cromolyn sodium in children with mild-to-moderate perennial allergic asthma

Abstract Although new antihistamines exert additional antiallergic properties besides blocking histamine 1 (H 1 ) receptors, their potential for prophylactic treatment of asthma has not been thoroughly investigated. This study compared the efficacy and tolerability of loratadine with those of cromolyn sodium, the nonsteroidal prophylactic treatment of choice for mild-to-moderate childhood perennial allergic asthma. A total of 122 children (mean age, 10 ± 2 years) with mild-to-moderate perennial allergic asthma were enrolled in a multicenter, double-masked, double-dummy, randomized, parallel-group study. They received either cromolyn sodium (two 5-mg puffs four times daily) or loratadine (10 mg if body weight was ⩽30 kg or 20 mg if >30 kg) for 8 weeks. The efficacy was assessed by wheezing, cough, and asthma symptom scores, overall assessment of asthma severity, peak expiratory flow recordings, forced expiratory volume in 1 second (FEV 1 ) measurements, and use of inhaled beta 2 -agonists. Tolerability was assessed by recording possible adverse reactions and blood test results. Wheezing decreased significantly in patients in both groups from day 0 to day 56; cough decreased significantly only in the loratadine group. Similarly, asthma score decreased significantly only in the loratadine group. Physicians and parents reported a highly significant reduction in asthma severity and in the number of patients using beta 2 -agonists in both groups. Peak-flow and FEV 1 values remained constant in both groups throughout the study. No statistically significant difference was observed between the treatment groups in any variable. In addition, tolerability was similar and satisfactory for both groups. Results of this study suggest that loratadine could be an alternative to cromolyn sodium in the treatment of mild-to-moderate childhood perennial allergic asthma.

Inhaled beclomethasone dipropionate downregulates airway lymphocyte activation in atopic asthma.

It is widely known that inhaled corticosteroids are highly efficacious in the prophylactic treatment of asthma, but the mechanism of this action is not known. In this study we have investigated the effect of 6 wk of therapy with inhaled beclomethasone dipropionate (BDP; daily dose 2,000 micrograms for 2 wk and 1,000 micrograms for 4 wk) in a group of symptomatic individuals with asthma on clinical and physiologic indices of disease activity and on T cell numbers and state of activation in peripheral blood and bronchoalveolar lavage (BAL). This course of treatment had a marked effect of improving all indices of disease activity including symptom scores, morning peak expiratory flow (PEF), variation in PEF, and methacholine PC20 (from a geometric mean of 0.62 to 4.6 mg/ml) but did not alter the total numbers of T cells, identified by the CD3 receptor, or the CD4+ and CD8+ subsets when analyzed in peripheral blood or BAL using flow cytometry. However, BDP treatment had a marked effect in reducing the expression of the activation markers CD25 and HLA-DR (p < 0.02) in T cells recovered by BAL in which these markers were upregulated. A small but significant (p < 0.02) downregulation of HLA-DR expression was also observed on peripheral blood T cells. These data add to the view that T cells are upregulated in the airways of individuals with asthma and are susceptible to inhibition by topical corticosteroids.

Treatment of severe steroid dependent preschool asthma with nebulised budesonide suspension.

The steroid sparing effect of nebulised budesonide suspension was assessed in a double blind placebo controlled parallel group study of 36 preschool children with severe asthma who were dependent on treatment with oral steroids. Nebulised budesonide suspension significantly reduced the requirement for treatment with oral steroids, and produced a marked improvement in overall health as scored on a visual analogue scale during the clinic visits. This study shows a significant step forward in the prophylactic treatment of asthma in children under the age of 3 years, in whom the efficacy of many other nebulised treatments has been questioned.

Pharmacological modulation of a model of bronchial inflammation after aerosol-induced active anaphylactic shock in conscious guinea pigs

Twenty-four hours after an active anaphylactic shock induced by inhalation of antigen in conscious guinea pigs sensitized by a large dose of ovalbumin in complete Freund's adjuvant, a noteworthy bronchial inflammation, characterized by increased numbers of neutrophils, mononuclear cells and eosinophils in the bronchoalveolar lavage fluid, was observed. Some drugs administered after the anaphylactic shock were investigated using this model. Disodium cromoglycate primarily reduced the number of mononuclear cells and eosinophils. Dexamethasone and theophylline decreased the number of eosinophils. Salbutamol and mepyramine increased neutrophils. Indomethacin did not give rise to any significant effect. This test appears to be of use for the investigation of anti-inflammatory compounds in the prophylactic treatment of asthma.

Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice.

To compare a peak flow self management plan for asthma with a symptoms only plan. Randomisation to one of the self management plans and follow up for a year. Four partner, rural training practice in Norfolk. 115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic. The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol. Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups. The results were similar for children and adults. The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60). The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group. The peak flow meter was not the crucial ingredient in the improved illness of the two groups. Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma. Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.

Nedocromil sodium: an overview

In recent years there has been increased awareness of the importance of preventative therapy in the management of asthma (1). In the U.K. inhaled corticosteroids are the principal prophylactic drug used for the treatment of adult asthma whereas sodium cromoglycate is less commonly prescribed in adults. Recently, nedocromil sodium, a nonbronchodilator antiasthmatic drug, was introduced as a prophylactic treatment for asthma. This overview of nedocromil sodium will attempt to answer the following questions about the drug: Does it possess anti-inflammatory properties? Can it attenuate the response to different bronchoconstrictor stimuli in man? How do the pharmacological properties of nedocromil sodium compare with those of sodium eromoglycate? Do the results of currently published therapeutic trials suggest a place for nedocromil sodium in the management of adult asthma?

Treatment of Bronchial Asthma in Latin America

The therapeutic approach to asthma can be systematized from a practical point of view, as follows: 1. symptomatic treatment of respiratory obstruction, a) acute, and b) chronic; 2. prophylactic treatment of asthma; 3. specific treatment (immunotherapy). The way the different therapeutic resources are applied differs from patient to patient and constitutes what could be defined as the therapeutic strategy of asthma.

β-adrenergic tachyphylaxis in the rat and its reversal and prevention by ketotifen

A strong, long-lasting and reproducible tachyphylaxis was produced in rats by implantation of osmotic minipumps delivering isoprenaline continously. The degree of tachyphylaxis was determined by measuring the inhibitory effect of isoprenaline on the passive cutaneous anaphylaxis (PCA). One dose of ketotifen given 1 h before the PCA test reversed this in vivo tachyphylaxis, as did dexamethasone given 24 h earlier. Implantation of a second minipump containg ketotifen prevented the development of tachphylaxis. Weak tachphylaxis was induced in guinea-pig trachea in vitro by incubation with a high concentration of isoprenaline, the effect being estimated by measuring the relaxation of carbachol-contracted trachea. Ketotifen partially restored the sensitivity of the trachea but this was considered to be a direct potentiation of isoprenaline effects rather than a reversal of tachphylaxis since the same effect was seen in non-pretreated trachea. It is thought that the reversal of experimental β-adrenergic tachyphylaxis by ketotifen could have implications for its use in the prophylactic treatment of asthma.

The Clinical Effect of Ketotifen in Bronchial Asthma

A therapeutical trial using ketotifen, a prophylactic agent for the long-term treatment of bronchial asthma, was undertaken. Twenty-nine patients with a mean age of 33 years and suffering from bronchial asthma for six months to 20 years (mean 8.6 years) were treated for three months. Ketotifen demonstrated good results in alleviating the impact of the disease on the asthmatic patient. The lowering of the frequency of asthmatic attacks, their duration and the degree of dyspnoea was accompanied by a normalization of lung function parameters. An analysis of further respiratory investigations showed that the best results are to be obtained in the uncomplicated asthmatic. The need for the prophylactic treatment of asthma with an agent such as ketotifen is stressed, as only in this way can irreversible changes be prevented.