Chest
Volume 100, Issue 5, November 1991, Pages 1397-1403
Journal home page for Chest

Clinical Investigations in Critical Care
Deficiency of Alveolar Fluid Glutathione in Patients with Sepsis and the Adult Respiratory Distress Syndrome

https://doi.org/10.1378/chest.100.5.1397 Get rights and content

The adult respiratory distress syndrome (ARDS) is a devastating clinical illness characterized by refractory hypoxemia and high-permeability pulmonary edema. Reactive oxygen species such as hydrogen peroxide and hypochlorous acid may play a key role in the pathogenesis of the acute lung injury. Glutathione (GSH) is a tripeptide that is able to react with and effectively neutralize oxidants such as hydrogen peroxide and hypochlorous acid. The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total GSH compared to normal subjects (21.7μmol ± 7.8 μmol vs 91.8μmo1 ± 14.5μmo1; p = 0.002). In addition, if GSH was measured in unconcentrated bronchoalveolar lavage (BAL) fluid and indexed to total BAL protein, there was also a deficiency in patients with ARDS compared to normal subjects (0.004 ± 0.003 nmol of CSH per microgram of total protein vs 0.026 ± 0.005 nmol of GSH per microgram of total protein; p=0.002). Since patients with ARDS are subjected to an increased burden of oxidants in the alveolar fluid, principally released by recruited neutrophils, this deficiency of CSH may predispose these patients to enhanced lung cell injury.

Section snippets

Subjects and Protocol

Young, healthy nonsmoking volunteers were recruited from the campus of Ohio State University. All of the subjects had normal findings on history, physical examination, chest roentgenogram, and forced expiratory spirometry. The subjects were not receiving any medications or drugs. There were six male and four female subjects, with an average age of 25 ± 2 years.

Ten patients with ARDS were recruited from the medical intensive care unit at Ohio State University Hospital. There were seven women and

Clinical Correlations

There was no correlation between BAL fluid concentrations or ELF concentrations of GSH and the lung injury score, the percentage of BAL neutrophils, or the BAL total protein. In addition, there was no correlation between the percentage of BAL neutrophils and the lung injury score. Two correlations approached but did not reach statistical significance. As total protein increased, the percentage of BAL neutrophils also increased in a linear fashion (p = 0.06; data not shown). In addition, as

Discussion

The ARDS remains a formidable and potentially catastrophic clinical problem with an estimated 150,000 cases per year and mortality in excess of 50 percent.33 Despite major improvements in the ability to care for these patients over the past 10 to 15 years (mechanical ventilators, pulmonary artery catheters, PEEP, and others), mortality has remained essentially unchanged. Thus, it seems probable that further improvement in mortality will only come through advances in the understanding of the

REFERENCES (43)

  • HeffnerJE et al.

    Pulmonary strategies of antioxidant defense.

    Am Rev Respir Dis

    (1989)
  • PrattPC.

    Pathology of adult respiratory distress syndrome.

  • WeilandJE et al.

    Lung neutrophils in the adult respiratory distress syndrome: clinical and pathophysiologic significance.

    Am Rev Respir Dis

    (1986)
  • HarlanJM et al.

    Neutrophil-mediated endothelial injury in vitro.

    J Clin Invest

    (1981)
  • ShasbyDM et al.

    Granulocytes mediate acute edematous lung injury in rabbits and in isolated rabbit lungs perfused with phorbol myristate acetate: role of oxygen radicals.

    Am Rev Respir Dis

    (1982)
  • FlickMR et al.

    Leukocytes are required for increased lung microvascular permeability after microembolization in sheep.

    Circ Res

    (1981)
  • TateRM et al.

    Oxygen-radical-mediated permeability edema and vasoconstriction in isolated perfused rabbit lungs.

    Am Rev Respir Dis

    (1982)
  • JohnsonKJ et al.

    In vivo damage of rat lungs by oxygen metabolites.

    J Clin Invest

    (1981)
  • MartinWJ et al.

    Oxidant injury of lung parenchymal cells.

    J Clin Invest

    (1981)
  • CochraneCG et al.

    Pathogenesis of the adult respiratory distress syndrome: evidence of oxidant activity in bronchoalveolar lavage fluid.

    J Clin Invest

    (1983)
  • MeisterA et al.

    Glutathione.

    Ann Rev Biochem

    (1983)
  • Cited by (0)

    Supported by grant 21571-55-00 from the American Lung Association and grant 8707 from the Bremer Foundation.

    View full text