Improvement of alveolar glutathione and lung function but not oxidative state in cystic fibrosis.

Department of Pediatric Ludwig -Maximilians-University, Munich, Germany.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 04/2004; 169(7):822-8. DOI: 10.1164/rccm.200308-1104OC
Source: PubMed

ABSTRACT 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.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.
    International Journal of COPD 01/2014; 9:1207-1224.
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper explores the introduction of a screening test to highlight impaired immune system status for newborn infants and its efficacy as a preventative clinical measure. Moreover, it is suggested that screening of the infantile immune system has the potential to highlight susceptibility to a range of infant and childhood diseases, bestowing an opportunity to introduce early intervention to reduce the incidence of these diseases. Development of the neonatal immune system is an important health issue, implicated in many childhood problems such as allergies, infection, and autoimmunity. The neonate has a limited immune system and ability to combat bacteria. Depleted levels of the tripeptide reduced glutathione (GSH) have been linked to numerous conditions and its intracellular level is acknowledged as an indicator of immune system function. Introduction of an immune system screening programme for infants is formally reviewed and assessed. Several benefits are reported in the treatment of impaired immune systems, a trial screening programme is proposed for at-risk infants to gather further evidence as to its efficacy. Infants at risk of impaired immune system function include cystic fibrosis, premature infants, and low birth weight infants. The interventions include breastfeeding, milk banks, and appropriate formula to support the immune system.
    Australasian Medical Journal 07/2014; 7(7):272-84.
  • European Respiratory Journal 07/2014; 44(1):17-9. · 7.13 Impact Factor

Full-text (2 Sources)

Available from
Jun 5, 2014