[ 15 N 2 ]Arginine as a First Potential Inhaled Diagnostic Agent to Characterize Respiratory Diseases

Abstract

Conventional diagnosis of the pulmonary tract uses physical methods such as spirometry and oscillometry. However, the inhalation of a chemical diagnostic agent ought to provide novel ways of more specific diagnosis, for instance of inflammatory states of the bronchial and lung mucosa. The stable isotope technique using a (15)N-labeled substrate appears to be a suitable tool for this application. In a pilot study, defined amounts of the amino acid L-[guanidino-(15)N(2)]arginine monohydrochloride (aqueous solution, 20 atom % (15)N) were inhaled as a diagnostic agent by healthy volunteers and pulmonary patients suffering from asthma bronchiale. The amino acid is resorbed and partly metabolized to (15)NO. The exhaled air was collected under defined conditions in 10-L breath bags and analyzed for NO using chemiluminescence. Under standardized test conditions, healthy persons (n = 6) exhaled 0.97 +/- 0.08 micromol NO/m(3) and asthmatic patients (n = 7) 1.17 +/- 0.14 micromol NO/m(3). A better distinction was expected comparing the (15)NO exhalation. The (15)N abundance of NO was determined using a Cryotrap gas chromatography - mass spectrometry set-up. Between 30 and 80 minutes after inhaling 700 mg [(15)N]arginine, a maximum with a plateau of the (15)NO abundance was found in the exhaled air. At this time, healthy and asthmatic subjects exhibited clear differences in their exhaled (15)NO amounts. Under standardized test conditions, the healthy persons (n = 6) exhaled 102.3 +/- 6.7 nmol (15)NO/m(3), whereas asthmatic patients (n = 7) exhaled only 76.1 +/- 10.9 nmol (15)NO/m(3). It is concluded that (15)NO yielded after the inhalation of (15)N-labeled arginine could be a potential marker for demonstrating pathophysiological changes in the lung epithelium. This method could pave a new diagnostic principle of "inhalative breath test."

Real-Time Analysis of Exhaled Breath via Resonance-Enhanced Multiphoton Ionization-Mass Spectrometry with a Medium Pressure Laser Ionization Source: Observed Nitric Oxide Profile

“…14,15 Measurement of biosynthetic 15 N 16 O in breath has been measured using an off-line sampling technique, i.e., it lacks temporal resolution and thus cannot distinguish between the alveolar and deadspace portion of each breath. 16 Since a rapid equilibrium exists between the liquid-phase concentration of NO within the capillary bed of the lung and the gas-phase concentration in the air above the epithelial tissue, a sample of exhaled air is an accurate and timely indicator of NO production from the capillary bed. During the inhalation and rest phases of breathing, the concentration of NO accumulates within the airway dead space.…”