LETTERS to the EDITORCystic fibrosis, breath pentane, and lipid peroxidation
References (5)
- Pm Guyan et al.
Heightened free radical activity in pancreatitis
Free Radical Biol Med
(1990) - D. Bilton et al.
High breath pentane levels in patients with cystic fibrosis
Clin Sci
(1990)
Cited by (16)
Methods for measuring ethane and pentane in expired air from rats and humans
2000, Free Radical Biology and MedicineNumerous studies in animals and humans provide evidence that ethane and pentane in expired air are useful markers of in vivo lipid peroxidation. The measurement of breath hydrocarbons, being noninvasive, is well suited for routine use in research and clinical settings. However, the lack of standardized methods for collecting, processing, and analyzing expired air has resulted in the use of a wide variety of different methods that have yielded highly disparate results among investigators. This review outlines the methods that we have developed and validated for measuring ethane and pentane in expired air from rats and humans. We describe the advantages of these methods, their performance, as well as potential errors that can be introduced during sample collection, concentration, and analysis. A main source of error involves contamination with ambient-air ethane and pentane, the concentrations of which are usually much greater and more variable than those in expired air. Thus, it appears that the effective removal of ambient-air hydrocarbons from the subject’s lungs before collection is an important step in standardizing the collection procedure. Also discussed is whether ethane or pentane is a better marker of in vivo lipid peroxidation.
Oxidative Stress in Cystic Fibrosis: Does It Occur and Does It Matter?
1996, Advances in PharmacologyCystic fibrosis (CF) is a multiorgan system disease arising from a single biochemical abnormality in a protein encoded by a gene located on chromosome 7 (band q31-32). This protein (the cystic fibrosis transmembrane conductance regulator, CFTR) appears to couple ATP hydrolysis with transmembrane chloride (Cl-) conductance across apical epithelial surfaces under the control of CAMP-dependent proteinkinaseA regulation. The defect in CF impairs the normal movement of water and electrolytes across various epithelial surfaces, most notably in the respiratory tract (RT) but also in the pancreatohepatobililary system, the gastrointestinal tract, and the sweat excretion system. There is decreased C1- secretion and an increased sodium absorption, inadequate hydration of the respiratory tract secretions. This predisposes the CF patient to impaired mucociliary clearance, chronic lung infection, and bronchiectasis. The lung infection and the ensuing inflammatory-immune responses of the lung lead to the progressive lung destruction responsible for the pulmonary morbidity and mortality of CF. The infectious inflammatory-immune processes in the lungs of CF patients cause oxidative stress and related effects on the antiprotease/protease balance. This chapter discusses the evidence that oxidative stress occurs in CF and in the lung, and assesses whether oxidative stress contributes to the disease pathology and whether antioxidants might have useful therapeutic effects. There is speculation on the potential for antioxidant therapy and dilemma of administering aerosolized thiols or ascorbic acid. This chapter has focused on the roles that oxidative stress may contribute to the pathophysiology of CF, on how the balance between reactive oxidative species and nitrogen species may interact with biomolecular constituents at RT surfaces.
Altered antioxidant status and increased lipid peroxidation in children with cystic fibrosis
1995, American Journal of Clinical NutritionCystic fibrosis often combines an infectious pathology with a syndrome of malabsorption, both potentially capable of favoring the deleterious effects of reactive oxygen species. This study was a simultaneous evaluation of the main antioxidant systems dependent on micronutrients and of lipid peroxidation products in 27 children with cystic fibrosis and 17 healthy children. Plasma of cystic fibrosis patients showed very low concentrations of beta-carotene (0.30 +/- 0.2 vs 1.63 +/- 0.5 mumol/g cholesterol, P < 0.0001) and a lower activity of selenium-dependent glutathione peroxidase (263.6 +/- 42 vs 296.9 +/- 57 U/L, P = 0.028). In parallel, the higher plasma concentrations of organic hydroperoxides (171.5 +/- 54.4 vs 122.6 +/- 23.3 mumol/L, P = 0.001) and of thiobarbituric acid reactants (2.9 +/- 0.6 vs 2.4 +/- 0.3 mumol/L, P = 0.004) reflected oxidative stress in this pathology. In addition, in these patients the major substrates of lipoperoxidation were significantly lower, whether they be linoleic acid (2.26 +/- 0.8 vs 3.60 +/- 0.9 mmol/L, P < 0.0001) or arachidonic acid (0.55 +/- 0.2 vs 0.74 +/- 0.2 mmol/L, P = 0.006). These results suggested that nutritional deficiencies resulting from malabsorption could considerably amplify disorders related to toxicity of reactive oxygen species. These nutritional deficits could also be aggravated by the destruction of antioxidant compounds by the inflammatory process.
Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients
1995, Clinica Chimica ActaLipid peroxidation was assessed in 27 cystic fibrosis children during a double-blind selenium supplementation study (2.8 μg of sodium selenite per kg per day) with a placebo control and inversion of treatment periods. Simultaneously, 17 healthy children living in the same area were also investigated as control subjects. Before any treatment whatsoever and despite a selenium status close to those of control subjects, cystic fibrosis patients showed significant increase in plasma lipid peroxidation markers. Thiobarbituric acid reactants (TBARs) were normalized after the first treatment period of 5 months in both cystic fibrosis groups receiving either selenium supplementation or placebo. In this latter group, TBARs were reduced despite a significant decrease in plasma selenium concentrations as compared with the control group. Organic hydroperoxide concentrations were also simultaneously normalized in both cystic fibrosis groups at the end of the second treatment period. These results showed that improvement of lipid peroxidation markers was not related to the selenium supplementation. Nevertheless, oxidative stress sustained by cystic fibrosis children must be taken into account so that it does not aggravate the prognosis of the disease.
The potential of the hydrocarbon breath test as a measure of lipid peroxidation
1994, Free Radical Biology and MedicineThe straight chain aliphatic hydrocarbons ethane and pentane have been advocated as noninvasive markers of free-radical induced lipid peroxidation in humans. In in vitro studies, the evolution of ethane and pentane as end products of n-3 and n-6 polyunsaturated fatty acids, respectively, correlates very well with other markers of lipid peroxidation and even seems to be the most sensitive test available. In laboratory animals the use of both hydrocarbons as in vivo markers of lipid peroxidation has been validated extensively. Although there are other possible sources of hydrocarbons in the body, such as protein oxidation and colonic bacterial metabolism, these apparently are of limited importance and do not interfere with the interpretation of the hydrocarbon breath test. The production of hydrocarbons relative to that of other end products of lipid peroxidation depends on variables that are difficult to control, such as the local availability of iron(II) ions and dioxygen. In addition, hydrocarbons are metabolized in the body, which especially influences the excretion of pentane. Because of the extremely low concentrations of ethane and pentane in human breath, which often are not significantly higher than those in ambient air, the hydrocarbon breath test requires a flawless technique regarding such factors as: (1) the preparation of the subject with hydrocarbon-free air to wash out ambient air hydrocarbons from the lungs, (2) the avoidance of ambient air contamination of the breath sample by using appropriate materials for sampling and storing, and (3) the procedures used to concentrate and filter the samples prior to gas chromatographi determination. For the gas chromatographic separation of hydrocarbons, open tubular capillary columns are preferred because of their high resolution capacity. Only in those settings where expired hydrocarbon levels are substantially higher than ambient air levels might washout prove to be unnecessary, at least in adults. Although many investigators have concentrated on one marker, it seems preferable to measure both ethane and pentane concurrently.
The results of the hydrocarbon breath test are not influenced by prior food consumption, but both vitamin E and β-carotene supplementation decrease hydrocarbon excretion. Nevertheless, the long-term use of a diet high in polyunsaturated fatty acids, such as in parenteral nutrition regimens, may results in increased hydrocarbon exhalation. Hydrocarbon excretion slightly increases with increasing age. Short-term increases follow physical and intellectual stress and exposure to hyperbaric dioxygen. Several other factors require further evaluation, including normal ranges in infants and children and the effects on the test of altered diffusion and local lipid peroxidation as a consequence of lung disease. The test seems to be unreliable in smokers, because smoking cigarettes results in impressive increase in ethane and penthane exhalation.
Hydrocarbon excretion is increased in a great variety of conditions in which lipid peroxidation was thought to be involved, which confirms both the reliability and the nonspecific nature of the test. Abnormal excretion has been documented in alcoholic and cholestatic liver disease, vitamin E deficiency, pulmonary disease, autoimmune disease, inflammatory bowel disease, ischemia-reperfusion injury, and neurologic disease. In many, if not most, conditions, increased lipid peroxidation is an epiphenomenon instead of playing a pathogenetic role. Therefore, the results of the hydrocarbon breath test should not be regarded in isolation but in the light of clinical and laboratory parameters, including other markers of lipid peroxidation.
In conclusion, the hydrocarbon breath test, being noninvasive, has great potential for the assessment of the role of lipid peroxidation in clinical conditions, as well as for the detection and follow-up of lipid peroxidation-induced disease in clinical practice. Because the test is time-consuming and requires a flawless technique, it is yet unclear whether the test will ever proceed to become a clinical tool.
Volatile organic compounds in the exhaled breath of young patients with cystic fibrosis
2006, European Respiratory Journal