mesna and Cystic-Fibrosis

Twenty-seven patients with cystic fibrosis completed a controlled trial comparing the effects of an inhaled mucolytic drug, sodium-2-mercaptoethane sulphonate (Mistabron, UCB Pharmaceutical Division, Brussels, Belgium), with inhaled iso-osmolar hypertonic saline. As a group the 22 patients with chronic sputum production showed small but statistically significant improvement in pulmonary function tests after Mistabron therapy, both when compared with a control period, and with iso-osmolar saline results. Subjective measurements by diary card failed to show any changes. No significant changes were found in five patients with no measurable sputum production. The inhalations were given after physiotherapy and were well tolerated. There were no significant side effects. The results suggest that Mistabron has a beneficial therapeutic effect unrelated to its high osmolality, and the intermittent inhalation of Mistabron may have a role in the treatment of selected patients with cystic fibrosis.

Topics: Adolescent; Aerosols; Child; Clinical Trials as Topic; Cystic Fibrosis; Double-Blind Method; Female; Humans; Lung; Male; Mercaptoethanol; Mesna; Respiratory Therapy; Saline Solution, Hypertonic; Sputum

The cystic fibrosis transmembrane conductance regulator (CFTR) is a tightly regulated anion channel that mediates secretion by epithelia and is mutated in the disease cystic fibrosis. CFTR forms macromolecular complexes with many proteins; however, little is known regarding its associations with membrane lipids or the regulation of its distribution and mobility at the cell surface. We report here that secretagogues (agonists that stimulate secretion) such as the peptide hormone vasoactive intestinal peptide (VIP) and muscarinic agonist carbachol increase CFTR aggregation into cholesterol-dependent clusters, reduce CFTR lateral mobility within and between membrane microdomains, and trigger the fusion of clusters into large (3.0 µm

Topics: Amitriptyline; Apoptosis; Carbachol; Cell Line; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Humans; Membrane Lipids; Membrane Microdomains; Mesna; Protein Transport; Signal Transduction; Sphingomyelin Phosphodiesterase; Vasoactive Intestinal Peptide

Modifications of bronchial secretions in cystic fibrosis patients account for the long-lasting use of mucolytic agents, despite the lack of adequately controlled clinical studies supporting this approach. Hyperviscosity of bronchial secretions mainly depend on their high DNA content, as a result of degradation of polymorphonuclear neutrophils mobilized by infection and inflammation. This phenomenon has led to the treatment of respiratory complications with human recombinant deoxyribonuclease (dornase alfa). In the present study, we compared the clinical and respiratory outcome in patients receiving mucolytic agents followed by dornase alfa, each for 1 year.. Fifty-four patients, aged 5 years or more, have been prospectively followed for 2 years. They received first a 12-month association of mesna (two nebulisations per day) and oral ambroxol (60 mg per day, divided in two doses), followed by a 12-month treatment with one daily aerosol of dornase alfa only (2.5 mg per day). The primary end-points were the results of pulmonary function tests. Secondary end-points were subjective symptoms, bacterial colonization, consumption of antibiotics, and clinical tolerance.. At the end of the 12-month mucolytic therapy, a significant decrease of forced expiratory volume/second (FEV1, -10.5% as compared to baseline values) and forced vital capacity (FVC, -12.8%) was observed. At the end of 12-month dornase alfa, FEV1 and FVC had increased by 7.7 and 5.3%, respectively. This change was statistically significant only for FEV1 in most severely disabled patients. However, forced expiratory flow 25-75% (FEF 25-75) decreased during the 2 year period of observation, by 5.6% the first year and 4.9% the second year. The mean number of days with parenteral antibiotics did not statistically differ between both treatments, except for patients more than 15 years of age. In this subgroup, the mean number decreased from 40 days in the first year to 27 in the second year (P < 0.05). Acceptability of treatment by the patients themselves was better with dornase alfa than with mucolytic therapy. However, several episodes of hemoptysis, frequent in only one case, were associated with the treatment by dornase alfa.. Dornase alfa was associated with a stabilisation, and even a trend to improvement in pulmonary function tests. This stabilisation is by itself a very encouraging result. Long-term comparative studies are needed to evaluate the benefits of dornase alfa in the treatment of respiratory complications of cystic fibrosis and specify the optimal modalities of its use. Synergistic combinations with mucolytic therapy and/or anti-inflammatory drugs could be viewed as a future prospect.

Topics: Adolescent; Adult; Ambroxol; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Deoxyribonuclease I; Drug Therapy, Combination; Expectorants; Forced Expiratory Volume; Humans; Mesna; Prospective Studies; Recombinant Proteins; Vital Capacity

The minimal inhibitory concentration of azlocillin for Pseudomonas aeruginosa is appreciably reduced when combined with the mucolytic agent mesna (Mistabron) because of an independent bacteriostatic effect of mesna. Bactericidal activity of azlocillin is unaltered by mesna. Mesna inhalations alone or combined with azlocillin may benefit cystic fibrosis patients with pseudomonas lung infections.

Topics: Azlocillin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Mercaptoethanol; Mesna; Penicillins; Pseudomonas Infections