Method for diagnosis of
A rapid, non-invasive breath-test method and device for diagnosing the presence or absence of H. pylori in a subject without administration of isotopic tracers is described. The device consists of a highly sensitive colorimetric ammonia sensor placed in contact with sampled subject breath. The sensor is measured using appropriate reflection spectroscopy instrumentation. The breath-test method consists of measuring a basal ammonia level with the device, administering non-isotopic urea and continuing measurement of the ammonia content in a plurality of consecutive breaths. Diagnostic differences in breath ammonia are identified between H. pylori infected and uninfected individuals.
1. A method for detecting the presence or absence of H. pylori infection in an individual comprising:
a) exposing at least one ammonia sensitive sensor to expiration of an individual, wherein where more than one sensor is exposed, the sensors are exposed to identical samples of respiration;
b) deriving, based on response of the at least one sensor to the exposure, a basal ammonia measure of expired ammonia over a basal measurement period; and
c) comparing the basal ammonia measure against a normative value that reflects at least one of a H. pylori positive population measure and a H. pylori negative population measure, wherein the H. pylori status of the individual is determined.
2. The method of claim 1 , further comprising:
a) administering a H. pylori urease enzyme substrate following determination of the basal ammonia measure;
b) deriving a post-substrate ammonia measure of expired ammonia over a post-urea measurement period of about 10 minutes to about 90 minutes after the administration of the substrate; and
c) comparing at least one measure of expired ammonia selected from the group consisting of the absolute measure of the post-substrate period, the absolute difference between the measures of the basal period and post-substrate period, the relative change between the measures of the basal period and post-substrate period, and, the rate of change in expired ammonia measures during the post-substrate period, against a normative value that reflects at least one of a H. pylori positive and a H. pylori negative population measures, wherein the H. pylori status of the individual is determined.
3. The method of claim 2 , further comprising:
a) administering an agent intended to increase expired ammonia either coincident or subsequent to administration of the H. pylori urease enzyme substrate;
b) deriving a post-substrate and post-agent ammonia measure of expired ammonia over a post-agent measurement period of about 10 minutes to about 90 minutes after ingestion of the substrate and agent; and
c) comparing at least one measure of expired ammonia selected from the group consisting of the absolute measure of the post-agent period, the absolute difference between the measure of the basal period, post-urea period and post-agent period, the relative change between the measures of the basal period, post-urea period, and post-agent period, and, the rate of change in expired ammonia measures during the basal period, post-substrate period, and post-agent period, against a normative value that reflects at least one of a H. pylori positive and H. pylori negative population values, wherein the H. pylori status of the individual is determined.
4. The method of claim 3 , wherein the agent intended to increase expired ammonia either coincident or subsequent to administration of the H. pylori urease enzyme substrate is an antacid.
5. The method of claim 3 , wherein the agent intended to increase expired ammonia either coincident or subsequent to administration of the H. pylori urease enzyme substrate comprises about 2 g aluminum hydroxide and about 2 g magnesium hydroxide.
6. The method of claim 1 , 2 or 3 , wherein the individual undergoing testing fasts for at least 8 hours before initiation of the method.
7. The method of claim 1 , wherein the at least one ammonia sensitive sensor has a sensitivity to ammonia in the range of about 0.05 ppm to about 5 ppm.
8. The method of claim 1 , wherein the ammonia sensitive sensor is an optical sensor for expired ammonia, comprising:
a solid substrate; and
an ammonia sensitive indicator dye having measurable spectral characteristics immobilized in or on the solid substrate so that exposure of the dye to expired ammonia causes a change in the spectral characteristics of the ammonia-sensitive indicator dye.
9. The method of claim 8 , wherein the substrate is polytetrafluorethylene.
10. The method of claim 8 , wherein the indicator dye is a non-water soluble pH indicator dye.
11. The method of claim 8 , wherein the substrate is an ammonia permeable solid-phase film.
12. The method of claim 10 , wherein the indicator dye is a weak acid compound that undergoes changes in its absorption spectra upon acid/base dissociation.
13. The method of claim 12 wherein the weak acid compound is selected from the group consisting of bromocresol green and bromophenol purple.
14. The method of claim 8 , wherein the substrate is a gas permeable hydrophobic polymer.
15. The method of claim 14 , wherein the hydrophobic polymer is a substituted ethylenic polymer.
16. The method of claim 8 , wherein the substrate is porous.
17. The method of claim 1 , wherein comparing the basal ammonia measure in c) comprises comparing a basal ammonia measure selected from the group consisting of: an absolute value measurement; a rate of change measurement; and combinations thereof.
18. The method of claim 1 , wherein where more than one sensor is exposed, the sensors are exposed to the identical respiration samples within a single chamber.
19. The method of claim 1 , wherein where more than one sensor is exposed, the sensors are exposed to identical respiration samples in different chambers.