Chronic neutrophilic inflammation leads to oxidative damage, which may play an important role in the pathogenesis of cystic fibrosis lung disease. Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in patients with cystic fibrosis. Here we evaluated the effects of glutathione aerosol on lower airway glutathione levels, lung function, and oxidative status. Pulmonary deposition of a radiolabeled monodisperse aerosol generated with a Pari LC Star nebulizer (Allergy Asthma Technology, Morton Grove, IL) connected to an AKITA inhalation device (Inamed, Gauting, Germany) was determined in six patients. In 17 additional patients bronchoalveolar lavage fluid was assessed before and after 14 days of inhalation with thrice-daily doses of 300 or 450 mg of glutathione. Intrathoracic deposition was 86.3 +/- 1.4% of the emitted dose. Glutathione concentration in lavage 1 hour postinhalation was increased three- to fourfold and was still almost doubled 12 hours postinhalation. FEV(1) transiently dropped after inhalation but increased compared with pretreatment values after 14 days (p < 0.001). This improvement was not related to the lavage content of oxidized proteins and lipids, which did not change with treatment. These results show that, using a new inhalation device with high efficacy, glutathione treatment of the lower airways is feasible. Reversion of markers of oxidative injury may need longer treatment, higher doses, or different types of antioxidants.

Patients with hereditary a 1 -proteinase inhibitor (a 1 -PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, a 1 -PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug.In order to optimise this treatment approach, lung deposition of inhaled radiolabelled a 1 -PI (Prolastin1) was studied using four different commercial inhalation devices (PARI-LC Star1, HaloLite1, and AKITA1 system in combination with LC Star1 and Sidestream1) in six patients with a 1 -PI deficiency and mild-to-severe chronic obstructive pulmonary disease.The time required to deposit 50 mg of the Prolastin1 (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled a1-PI. This time was shortest for the AKITA1 system (18-24 min) and significantly higher for the PARI-LC Star1 (44 min) and the HaloLite1 (100 min).The higher efficiency of drug delivery using the AKITA1 system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.

Background:N-chlorotaurine (NCT), a long-lived oxidant produced by human leukocytes, can be synthesized chemically and used topically as a well-tolerated antiseptic to different body regions including sensitive ones. The aim of this study was to test the tolerability of inhaled 1% NCT in aqueous solution upon repeated application.Methods:The study was performed double-blind and randomized with a parallel test group (1% NCT) and control group (0.9% NaCl as placebo). There were two Austrian centres involved, the hospitals, Natters and Vöcklabruck. Healthy, full age volunteers were included, 12 in each centre. A total of 12 patients were treated with NCT, and 12 with placebo, exactly half of each group from each centre. The single dose was 1.2 ml inhaled over a period of 10 min using an AKITA JET nebulizer. One inhalation was done every day for five consecutive days. The primary criterion of evaluation was the forced expiratory volume in 1 second (FEV1). Secondary criteria were subjective sensations, further lung function parameters such as airway resistance, physical examination, and blood analyses (gases, electrolytes, organ function values, pharmacokinetic parameters taurine and methionine, immune parameters).Results:All included 15 females and 9 males completed the treatment and the control examinations according to the study protocol. FEV1 (100.83% ± 8.04% for NCT and 92.92% ± 11.35% for controls) remained unchanged and constant during the treatment and in control examinations 1 week and 3 months after the treatment (98.75% ± 7.37% for NCT and 91.17% ± 9.46% for controls, p > 0.082 between time points within each group). The same was true for all other objective parameters. Subjective mild sensations with a higher frequency in the test group were chlorine taste (p < 0.01) and occasional tickle in the throat (p = 0.057). Taurine and methionine plasma concentrations did not change within 60 min after inhalation or later on.Conclusions:Inhaled NCT is well tolerated as in other applications of different body regions. Side effects are mild, topical and transitory. The study was registered prospectively in the European Clinical Trials Database of the European Medicines Agency. The EudraCT number is 2012-003700-12.

The efficiency of two different dry powder inhaler systems for the application of the beta2-sympathomimetic drug Formoterol in the lungs has been tested in vitro. Particle size distributions for each device have been measured at four different flow rates (28.3, 40, 60, and 80 L/min) using an Andersen-Impactor. Mass median aerodynamic diameters (MMAD) of the dispersed powder and deposition of the drug in the respiratory tract was determined using a semiempirical lung deposition model. The optimum output for both devices determined by in vitro measurements is supposed to be achieved with flow rates of 40-60 L/min. The Oxis Turbuhaler delivers the smaller particles as the Foradil P Aerolizer and, thus, the Formoterol deeper into the lungs, but the high specific airflow resistance will influence the ability of patients with severe asthma and children to use the system.