Minimally-invasive measurement of esophageal inflammation
The methods and apparatus of the present invention allow the evaluation of inflammation of the esophagus. Measurements may be utilized, for example, to diagnose a disease of the esophagus, to monitor inflammation of the esophagus, or to access the treatment of a disease of the esophagus. In one embodiment, the invention comprises a method for measuring esophageal inflammation comprising deploying a device into the esophagus of a subject, removing the device after a predetermined period of time, analyzing the device for a diagnostic indicator of esophageal inflammation and evaluating the diagnostic indicator to diagnose esophageal inflammation.
1. A method for diagnosing gastroesophageal reflux disease (GERD) or eosinophilic esophagitis (EoE) comprising:
(a) deploying a capture element into the esophagus of a subject, said capture element being comprised in a pharmaceutical capsule having an opening, a malleable drag material within the capsule, and said capture element comprising a line embedded in the drag material and running through the opening of the capsule;
(b) removing the device after a predetermined period of time during which said capture element is disposed in the esophagus of said subject;
(c) analyzing the capture element for the presence of an inflammatory protein that is a diagnostic indicator of GERD or EoE; and
(d) evaluating the inflammatory protein to diagnose GERD or EoE.
2. The method of claim 1 , wherein the disease is GERD.
3. The method of claim 2 , wherein the inflammatory protein is IL-8 mRNA or IL-8 protein.
4. The method of claim 3 , wherein the IL-8 is IL-8 mRNA.
5. The method of claim 3 , wherein the IL-8 is IL-8 protein.
6. The method of claim 3 , wherein the predetermined time is between 15 minutes and 12 hours.
7. The method of claim 6 , wherein the predetermined time is 15 minutes.
8. The method of claim 6 , wherein the predetermined time is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, or 24 hours.
9. The method of claim 8 , wherein the predetermined period of time is 12 hours.
10. The method of claim 8 , wherein the predetermined period of time is 1 hour.
11. The method of claim 1 , wherein the disease is EoE.
12. The method of claim 11 , wherein the inflammatory protein is an eosinophil granule protein.
13. The method of claim 12 , wherein the eosinophil granule protein is a major basic protein (MBP), an eosinophil cationic protein (ECP), an eosinophil peroxidase (EPO), an eosinophil-derived neurotoxin (EDN), or Charcot-Leyden crystal protein/Galectin 10 (CLC/Gal-10).
14. The method of claim 13 , wherein the eosinophil granule protein is a major basic protein.
15. The method of claim 13 , wherein the major basic protein is major basic protein 1 (MBP1).
16. The method of claim 12 , wherein the eosinophil granule protein is IL-5 induced.
17. The method of claim 16 , wherein the IL-5 induced eosinophil granule protein is EPO, MBP1, or CLC/Gal-10.
18. The method of claim 11 , wherein the inflammatory protein is selected from the group consisting of a cytokine and a chemokine.
19. The method of claim 18 , wherein the chemokine is an eotaxin.
20. The method of claim 19 , wherein the eotaxin is eotxan-2 or eotaxin-3.
21. The method of claim 11 , further comprising assessing a cellular infiltrate or pH.
22. The method of claim 11 , wherein the inflammatory protein is a marker of an allergic response.
23. The method of claim 22 , wherein the marker of an allergic response is an IgE, a tryptase, CD23, FcR or an allergen.
24. The method of claim 11 , wherein the inflammatory protein comprises at least two of the group consisting of an eosinophil granule protein, a cytokine, a chemokine and a marker of an allergic response.
25. The method of claim 24 , wherein the predetermined time is between 15 minutes and 12 hours.
26. The method of claim 25 , wherein the predetermined time is 15 minutes.
27. The method of claim 25 , wherein the predetermined time is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, or 24 hours.
28. The method of claim 27 , wherein the predetermined period of time is 12 hours.
29. The method of claim 27 , wherein the predetermined period of time is 1 hour.
30. The method of claim 1 , further comprising quantifying the inflammatory protein.
31. The method of claim 30 , wherein quantifying the inflammatory protein is performed by ELISA or Mesoscale.
32. The method of claim 1 , wherein the opening is a perforated opening.
33. The method of claim 1 , wherein the pharmaceutical capsule is dissolvable.
34. The method of claim 1 , wherein the line comprises a distal segment and a proximal segment.
35. The method of claim 34 , wherein the proximal segment is made of string.
36. The method of claim 35 , wherein the string comprises an absorbent fiber.
37. The method of claim 35 , wherein the string comprises a textured fiber.
38. The method of claim 1 , wherein the capture element further comprises a capture agent for one or more inflammatory proteins.
39. A method for assessing gastroesophageal reflux disease (GERD) or eosinophilic esophagitis (EoE) comprising:
(a) deploying a capture element into the esophagus of a subject, said capture element comprised in a pharmaceutical capsule having an opening, a malleable drag material within the capsule, and said capture element comprising a line embedded in the drag material and running through the opening of the capsule;
(b) removing the device after a predetermined period of time during which said capture element is disposed in the esophagus of said subject;
(c) analyzing the capture element for the presence of an inflammatory protein that is a diagnostic indicator of GERD or EoE; and
(d) evaluating the inflammatory protein to assess prior or ongoing treatment of GERD or EoE.