Article

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: 11.04). 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
 · 
97 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n = 24) or large airway deposition (n = 25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF(75%)). FEF(75%) increased significantly by 0.7 sd (5.2% predicted) in the large airways group and 1.2 sd (8.8% pred) in the small airways group. Intention-to-treat analysis did not show a significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p = 0.06) in FEF(75%) Z-score and a significant difference (p = 0.04) between groups in absolute FEF(75%) (L · s(-1)) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF(75%) in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition.
    European Respiratory Journal 07/2011; 38(6):1328-35. · 6.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation is a major component of the vicious cycle characterizing cystic fibrosis (CF) pulmonary disease. If untreated, this inflammatory process irreversibly damages the airways, leading to bronchiectasis and ultimately respiratory failure. Anti-inflammatory drugs for CF lung disease appear to have beneficial effects on disease progression. These agents include oral corticosteroids and ibuprofen, as well as azithromycin, which, in addition to its antimicrobial effects, also possess anti-inflammatory properties. Inhaled corticosteroids, antioxidants, nutritional supplements, and protease inhibitors have a limited impact on the disease. Adverse effects limit therapy with oral corticosteroids and ibuprofen. Azithromycin appears to be safe and effective, and is thus the most promising anti-inflammatory therapy available for patients with CF. Pharmacologic therapy with anti-inflammatory agents should be started early in the disease course, before extensive irreversible lung damage has occurred. To optimize anti-inflammatory therapy, it is necessary to understand the mechanism of action of these agents in the CF lung, to determine which of these agents would provide the most benefit to patients with CF, and to determine which therapies should be initiated at what age or stage of lung disease.
    Paediatric Drugs 06/2011; 13(3):141-7. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small airway obstruction is important in the pathophysiology of cystic fibrosis (CF) lung disease. Additionally, many CF patients lose lung function in the long term as a result of respiratory tract exacerbations (RTEs). No trials have been performed to optimize mucolytic therapy during a RTE. We investigated whether specifically targeting dornase alfa to the small airways improves small airway obstruction during RTEs. In a multi-center, double-blind, randomized controlled trial CF patients hospitalized for a RTE and on maintenance treatment with dornase alfa were switched to a smart nebulizer. Patients were randomized to small airway deposition (n = 19) or large airway deposition (n = 19) of dornase alfa for at least 7 days. Primary endpoint was forced expiratory flow at 75% of forced vital capacity (FEF75 ). Spirometry parameters improved significantly during admission, but the difference in mean change in FEF75 between treatment groups was not significant: 0.7 SD, P = 0.30. FEF25-75 , FEV1 , nocturnal oxygen saturation and diary symptom scores also did not differ between groups. This study did not detect a difference if inhaled dornase alfa was targeted to small versus large airways during a RTE. However, the 95% confidence interval for the change in FEF75 was wide. Further studies are needed to improve the effectiveness of RTE treatment in CF. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 07/2013; · 2.38 Impact Factor

Full-text (2 Sources)

View
105 Downloads
Available from
Jun 5, 2014