Chest
Volume 114, Issue 6, December 1998, Pages 1653-1659
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Clinical Investigations in Critical Care
Exhaled Breath Condensate Isoprostanes Are Elevated in Patients With Acute Lung Injury or ARDS

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Background

Oxidant stress is a purported mechanism of tissue damage in patients with ARDS and acute lung injury (ALI). Isoprostanes, prostanoid compounds primarily formed nonenzymatically via lipid peroxidation, are precise markers of in vivo oxidant stress. Plasma levels of metabolites of 8-iso-prostaglandin-F (8-iso-PGF) correlate with outcome in patients with ARDS.

Objective

To examine exhaled breath condensate levels of 8-iso-PGF as a noninvasive quantification of pulmonary oxidant stress in patients with, or at risk for, ARDS/ALI.

Methods

Breath condensate was collected from 22 patients with, or at risk for, ARDS/ALI by placing Tygon tubing submerged in an ice bath in line with the expiratory limb of the ventilator circuit. Ten patients without lung disease, who were intubated while undergoing minor surgical procedures, served as control subjects. Between 1 and 3 mL of condensate was collected over a 30- to 60-min period, then immediately frozen and stored at −70°C until analysis. The 8-iso-PGF was purified and derivatized, then quantified by stable isotope dilution in conjunction with gas chromatography/mass spectrometry.

Results

The mean level of exhaled 8-iso-PGF in the patients with ALI/ARDS, 87 ± 28 pg/mL, was significantly higher than the mean in the normal group, 7 ± 4 pg/mL (p = 0.007). The 8-iso-PGF levels were greater than two standard deviations above the mean of the normal group in 12 of 22 patients with or at risk for ARDS/ALI.

Conclusions

These results provide further evidence that lipid peroxidation does occur in patients with ARDS/ALI. The measurement of exhaled isoprostanes provides a novel, noninvasive method to quantify oxidant stress in such patients.

Section snippets

Patients

Patients with or at risk for ALI/ARDS due to severe sepsis were studied. Specific inclusion criteria included the presence of the systemic inflammatory response syndrome and at least one acute organ failure. To meet criteria for systemic inflammatory response syndrome, three or more of the following were demonstrated: core temperature ≥ 38°C (100.4°F) or ≤ 36°C (96.8°F); heart rate ≥ 90/min (in the absence of β-blocker therapy or complete heart block); respiratory rate ≥ 20/min or minute

Results

Twenty-two patients with or at risk for ALI/ARDS were studied. All patients met the criteria for severe sepsis as outlined in the Materials and Methods section, and all were mechanically ventilated. Twenty of the 22 met criteria for either ALI or ARDS. The mean age was 52 ± 3 years. Twelve were male and 10 were female. Seven patients also met criteria for shock, five for acute renal insufficiency, and three for coagulation dysfunction. The overall mortality of the patients with or at risk for

Discussion

The oxidant stress theory of ARDS proposes that an insult, such as severe sepsis, leads to activation of neutrophils and macrophages that subsequently release reactive oxygen species. These oxygen free radicals, while clearly beneficial in host defense, may result in lipid peroxidation of endothelial and epithelial cell membrane phospholipids, thereby altering the structure and function of the cell membrane. Such alterations could significantly compromise barrier function.

Attempts to quantify

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  • Cited by (221)

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    Supported by National Institutes of Health grants 5 ROI HL 55198, HL 43167, and HL 19153 (SCOR in ALI), and The PPH Cure Foundation.

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