[ 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 μ molNO/m 3 and asthmatic patients (n = 7) 1.17 ± 0.14 μ molNO/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 700mg [ 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."

• Inhalative Diagnosis
• 15no Exhalation
• Stable Isotope-LABELED Arginine