Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis:A pilot study

Background: Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin. However, nebulized colistin can cause bronchoconstriction in CF patients. Therefore, in the progress of developing a dry powder formula, the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects. To investigate the side effects, a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF-patients. Methods: Nine CF-patients chronically infected with P. aeruginosa participated in a double blind, randomized cross over study. On two visits to the outpatient clinic, patients were submitted to either nebulized colistin sulphate or colistin sulphomethate solution. Lung function tests were performed immediately before and 15 and 30 min after nebulization. Results: Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate. A significant decrease in mean changes (SD) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3% (8.6%), -5.7% (7.3%) and -8.4% (7.5%) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate (

The effects of oxygen concentration on cell death, anti-oxidant transcription, acute inflammation, and cell proliferation in precision-cut lung slices

Although animal models are often used in drug research, alternative experimental models are becoming more popular as they reduce animal use and suffering. Of particular interest are precision-cut lung slices, which refer to explants - with a reproducible thickness and diameter - that can be cultured ex vivo. Because lung slices (partially) reflect functional and structural features of whole tissue, they are often applied in the field of immunology, pharmacology, toxicology, and virology. Nevertheless, previous research failed to adequately address concerns with respect to the viability of lung slices. For instance, the effect of oxygen concentration on lung slice viability has never been thoroughly investigated. Therefore, the main goal of this study was to investigate the effect of oxygen concentration (20 vs. 80% O-2) on the degree of cell death, anti-oxidant transcription, acute inflammation, and cell proliferation in lung slices. According to the results, slices incubated at 20% O-2 displayed less cell death, antioxidant transcription, and acute inflammation, as well as more cell proliferation, demonstrating that these slices were considerably more viable than slices cultured at 80% O-2. These findings expand our knowledge on lung slices and their use as an alternative experimental model in drug research