Lung Function in Provoked Asthma: Responses to Inhaled Urea, Methacholine and Isoprenaline

Abstract

1. Lung function was studied in fifty-six symptom-free asthmatic subjects after the inhalation of urea, an agent not previously used for asthma provocation. The effects of urea were compared with those produced by the inhalation of methacholine and of isoprenaline.2. After urea ventilatory capacity was impaired in 68% of subjects and improved in 16%. This response was a relatively constant phenomenon in the same subject. Urea appears to possess the unusual property of being able to produce both bronchoconstriction and bronchodilatation. The response could not be related to any of the clinical or other physiological variables examined.3. Mild hypoxaemia, ventilation-blood-flow inequality and impairment of gas transfer also occurred after urea administration.4. Methacholine produced considerable impairment of ventilatory capacity with consistent hyperinflation but with variable changes in ventilatory pattern and distribution of ventilation. 5. Isoprenaline rapidly and completely reversed the changes which occurred after urea and methacholine administration.

A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized13C-Urea

“…Study part II would then proceed, contingent on favorable safety of aerosolized 13 C-urea in the control group. Study part II was designed to determine the safety and dose-response of aerosolized 13 C-urea 20 mg and 50 mg in detecting urease producing bacteria in the lungs of participants with CF with a confirmed P. aeruginosa colonization.…”

“…Study part II was designed to determine the safety and dose-response of aerosolized 13 C-urea 20 mg and 50 mg in detecting urease producing bacteria in the lungs of participants with CF with a confirmed P. aeruginosa colonization. The 13 C-urea Breath Test Kit in this study contained 13 Curea lyophilized in a 10 mL glass vial with an aluminum crimp closure containing 20 mg or 50 mg of active ingredient (Coldstream Laboratories, Lexington, KY) to be diluted with 3 mL of sterile water and nebulized by PARI LC Sprint nebulizer (PARI, Midlothian, VA).…”

“…Study part I was designed to determine the safety of aerosolized 13 C-urea 20 mg and 50 mg in healthy participants (control group). Study part II would then proceed, contingent on favorable safety of aerosolized 13 C-urea in the control group.…”

“…[5][6][7][8][9][10] Urease activity is the basis of the breath test used to determine stomach colonization by Helicobacter pylori in which stable isotopelabeled measured. Two key features make it highly attractive to investigate whether alternate delivery routes of 13 C-urea may be useful to assess other infections: commercial availability of U.S. Food and Drug Administration (FDA)-approved analysis instrumentation for breath 13 CO 2 and commercial availability of 13 C-urea at good manufacturing practice grade. In a parallel animal study, several of the current authors and colleagues used direct lung delivery of 13 C-urea to detect Mycobacterium tuberculosis and the dose-response of the bacterial load to treatment in infected rabbits as a result of M. tuberculosis urease production of 13 CO 2 .…”

“…We selected CF patients colonized with P. aeruginosa to ensure the presence of at least one urease producing bacteria in the lungs. We performed a ''proof of concept'' study to determine whether inhalation of 13 C-urea could be safely administered, and then if it could be used to detect urease producing bacteria, including but not limited to P. aeruginosa, in the airways of patients with CF.…”