A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized 13 C-Urea.

This is a "proof of concept" study to determine whether inhalation of 13 C-urea can be safely used to detect the presence of urease producing bacteria in the airways of patients with cystic fibrosis (CF) by detecting 13 CO2 in breath. This was a prospective, 2-part, open label, single-center, single-arm, single-administration, dose-escalation investigational device exemption trial. First, the safety of 20 and 50 mg inhaled 13 C-urea was evaluated in 6 healthy adult participants. Then, 3 adult CF participants colonized with Pseudomonas aeruginosa were enrolled for each dose of inhaled 13 C-urea. The safety of inhaled 13 C-urea was assessed by spirometry and physical examination. 13 C-urea was administered using a jet nebulizer, followed by serial spirometry (10 min and 30 min post inhalation) and collection of exhaled breath at 5, 10, and 15 min post inhalation. There was no clinical significant change in any of the spirometry values compared to baseline in healthy participants and CF patients. Mean of 13 CO2 /12 CO2 delta over baseline (DOB) values in CF participants at 5, 10, and 15 min post inhalation was as follows: 20 mg dose 4‰ (2.2‰-4.9‰), 1‰ (1.0‰-1.4‰), and 1‰ (0.4‰-1.5‰); 50 mg dose: 10‰ (6.2‰-14.5‰), 3‰ (2.1‰-4.3‰), and 1.5‰ (0.6‰-2.3‰). Inhaled 13 C-urea for detection of urease producing bacteria was safe, and preliminary data suggest that 13 CO2 /12 CO2 DOB values may be higher in CF patients with P. aeruginosa at 5-10 min after inhalation of 13 C-urea. A future direction is to investigate use of inhaled 13 C-urea in young children who have difficulty producing sputum for culturing.