Hydrogen Sulfide, Nitric Oxide and a Molecular Mass 66 u Substance in the Exhaled Breath of Chronic Pancreatitis Patients

doi:10.1159/000108967

Pancreatology

Volume 7, Issues 5–6, October 2007, Pages 497-504

https://doi.org/10.1159/000108967 Get rights and content

Abstract

Background/Aims: Human exhaled breath contains many molecules either present as gases or occurring in a soluble form in the vapor of the breath. This study was designed to evaluate the substances present in the exhaled breath of chronic pancreatitis (CP) patients. Subjects: Thirty-one consecutive CP patients (11 with exocrine insufficiency) and 31 healthy subjects (HS) were studied. Methods: Ninety-eight different substances were analyzed using a mass spectrometer on a breath sample from all subjects and on each respective ambient air sample. Results: H₂S, NO and a substance having a molecular mass of 66 u (M66) were those which had significantly higher concentrations in CP patients than in HS after adjustment for the ambient air; the estimated increases attributable to the disease were 14% (p = 0.040) for H₂S, 84% (p = 0.006) for M66 and 50% (p = 0.033) for NO, but the three volatile compounds showed poor diagnostic accuracy in differentiating CP patients from HS (AUC-ROC: 0.664, 0.715, and 0.602 for H₂S, M66, and NO, respectively). Finally, no significant differences of H₂S, M66, and NO were found between patients with and without alcoholic pancreatitis as well as between patients with and without pancreatic insufficiency. Conclusions: Exhaled breath analysis can rapidly and easily assess the presence of volatile compounds (H₂S, NO and a substance having a molecular mass of 66 u) which may have properties capable of explaining, at least in part, the pathogenesis of CP.

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Hydrogen sulfide (H₂S) has recently been recognised as the third important gas-signalling molecule, besides nitric oxide and carbon monoxide. H₂S has been reported to be produced by many cell types in mammalian tissues and organs throughout the actions of H₂S-generating enzymes or redox reactions between the oxidation of glucose and element of sulfur. Although the pathological role of H₂S has not yet been fully elucidated, accumulative data suggest that H₂S may have biphasic effects. Briefly, it mainly has anti-inflammatory and antioxidant roles, although it can also have pro-inflammatory effects under certain conditions where rapid release of H₂S in tissues occur, such as sepsis. To date, there have been several clinical studies published on H₂S in respiratory disorders, including asthma and chronic obstructive pulmonary disease (COPD). According to previous studies, H₂S is detectable in serum, sputum, and exhaled breath, although a gold standard method for detection has not yet been established. In asthma and COPD, H₂S levels in serum and sputum can vary depending on the underlying conditions such as an acute exacerbation. Furthermore, sputum H₂S in particular correlates with sputum neutrophils and the degree of airflow limitation, indicating that H₂S has potential as a novel promising biomarker for neutrophilic airway inflammation for predicting current control state as well as future risks of asthma. In the future, concurrent measures of H₂S with conventional inflammatory biomarkers (fractional exhaled nitric oxide, eosinophils etc) may provide more useful information regarding the identification of inflammatory phenotypes of asthma and COPD for personalised treatment.
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Advanced stages of chronic pancreatitis and pancreatic cancers (PCs) are very serious diseases with very poor prognosis. Therefore, identification of reliable and specific biomarker(s) at early stages of the diseases could be key to their early prevention and therapy. In this chapter, currently used and putative biomarkers of acute and chronic pancreatitis and PC are summarized. Total serum lipase and/or amylase are most widely used biomarkers of acute pancreatitis; lipase assay being more sensitive and specific than that of amylase. Imaging technologies provide key support for the diagnosis of both acute and chronic pancreatitis. Biomarkers of chronic pancreatitis are poorly developed and remain challenging because of impaired secretory components of exocrine pancreas. The focus of future clinical diagnosis of chronic pancreatitis and PC lies in identification of biomarkers using omics and microRNA arrays along with imaging technologies in well-defined experimental models and their validation in patients diagnosed with various stages of chronic pancreatitis and PC.
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Lastly, H2S is exhaled through the lung. In healthy individuals, very little H2S is eliminated through the lung as alveolar air only contains 25–50 ppb H2S [26,27]. The liver plays a key role in glucose and lipid metabolism, xenobiotic metabolism, and antioxidant defence.
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Pancreatitis and pancreatic cancers are very serious diseases with very poor prognosis, and many patients die before even reaching the clinical stage. Therefore, identification of reliable and specific biomarkers at early stages of pancreatitis and pancreatic cancers could be the key to their early prevention and therapy. In this chapter, currently used and putative biomarkers of acute and chronic pancreatitis are summarized. Serum total amylase and lipase in combination or individually remain the most widely used biomarkers for clinical diagnostics of acute pancreatitis. Definitely, lipase assay has an advantage over amylase in clinical diagnostics of acute pancreatitis rather than chronic pancreatitis and appears to have greater specificity. However, imaging technologies strongly support the diagnosis of both acute and chronic pancreatitis. Identification and development of biomarkers of chronic pancreatitis remain challenging because of the impaired secretory component of the exocrine pancreas due to slow destruction of the gland during chronic pancreatitis, particularly at later stages. Therefore, the focus of future research lies in identification of molecular biomarkers by utilizing proteomic, metabolomic, and microRNA array technologies in well-defined experimental models followed by their confirmation in large cohorts of patient populations with acute and various stages of chronic pancreatitis.
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¹: Raffaele Pezzilli Department of Gastrointestinal Diseases and Internal Medicine Sant'Orsola-Malpighi Hospital, Via Massarenti, 9 IT-40138 Bologna (Italy) Tel./Fax +39 051 549 653

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Hydrogen Sulfide, Nitric Oxide and a Molecular Mass 66 u Substance in the Exhaled Breath of Chronic Pancreatitis Patients

Abstract

Pancreatology

Pancreatology

Gastroenterology

Gastroenterology

Pancreatology

Gastroenterology

Dig Liver Dis

Am J Gastroenterol

Gastroenterology

Biochem Biophys Res Commun

Biochem Pharmacol

Meth Enzymol

Gastroenterology

J Biol Chem

Breath analysis: potential for clinical diagnosis and exposure assessment

Clin Chem

Fecal weight determination can unfortunately not replace unpopular and costly fecal fat estimation in the diagnosis of steatorrhea

Int J Pancreatol

13C labelled cholesteryl octanoate breath test for assessing pancreatic exocrine insufficiency

Gut

The pancreatitis classification of Marseilles-Rome 1988

Scand J Gastroenterol

Fecal elastase 1 determination in chronic pancreatitis

Dig Dis Sci

Chronic pancreatitis: faces, facets, and facts

Swiss Med Wkly

A framework for the aetiogenesis of chronic pancreatitis

Digestion

Oxygen radicals mediate depletion of pancreatic sulfhydryl compounds in rats with cerulein-induced acute pancreatitis

Digestion

Changes in lipid peroxide and oxygen radical scavengers in cerulein-induced acute pancreatitis

Digestion