Diagnosis and treatment methods for entry of gastrointestinal contents into respiratory tract

Abstract

A method of diagnosing in a subject for the purpose of determining if the subject's gastrointestinal contents has entered the subject's respiratory tract. The qualitative analysis can be also expanded into quantitative analysis, enabling the estimation of either the concentration, or the amount, or both, of the gastrointestinal contents that entered the respiratory tract. The invention also provides methods of treatment based on the identification of aspiration using the methods of the invention.

That which is claimed is: 
     
         1 . A method of determining the amount of gastric contents in the respiratory fluid of a subject, comprising:
 a) orally administering to a subject a diagnostic formulation comprising cromolyn or a cromolyn salt;   b) allowing the diagnostic formulation to remain in the subject over a period of time during which the subject would be expected to aspirate the diagnostic formulation from the gastrointestinal tract into the respiratory tract;   c) obtaining a sample of a body fluid selected from urine, blood or a blood product; and   d) analyzing the body fluid to determine the amount of cromolyn or cromolyn salt in the body fluid, wherein the amount of cromolyn or cromolyn salt in the body fluid is indicative of the amount of aspiration of gastrointestinal contents into the respiratory tract.   
     
     
         2 . The method of  claim 1 , wherein the body fluid in step c) is urine. 
     
     
         3 . The method of  claim 1 , wherein the body fluid in step c) is blood or a blood product. 
     
     
         4 . The method of  claim 1 , further comprising:
 e) administering a control formulation comprising cromolyn or cromolyn salt to the subject;   f) allowing the control formulation to remain in the subject over a period of time during which the subject would not be expected to aspirate the control formulation from the gastrointestinal tract into the respiratory tract;   g) obtaining a sample of a body fluid body fluid selected from urine, blood or a blood product from the subject following the administration of the control formulation;   h) analyzing the body fluid of step g) to determine the level of the diagnostic agent;   i) comparing the level of diagnostic agent from step d) to the level of diagnostic agent of step h); and   j) determining if the level of diagnostic agent detected following administration of the diagnostic formulation is indicative of a disease associated with aspiration of gastrointestinal contents into the respiratory tract using the compared levels of diagnostic agent in step i).   
     
     
         5 . The method of  claim 4 , wherein the control formulation is administered orally. 
     
     
         6 . The method of  claim 4 , wherein the control formulation is administered by inhalation. 
     
     
         7 . A method of determining the amount of gastric contents in the respiratory fluid of a subject, comprising: (a) orally administering to the mammal a diagnostic formulation comprising a diagnostic agent that is not absorbed from the gastrointestinal tract of the mammal but is absorbed from the respiratory tract of the mammal;
 (b) allowing the diagnostic formulation to remain in the mammal over a period of time during which the mammal would be expected to aspirate the formulation from the gastrointestinal tract into the respiratory tract;   (c) obtaining a sample of a body fluid selected from urine, blood or a blood product; and   (d) analyzing the body fluid to detect the level of the diagnostic agent in the body fluid; and   (e) determining if the fluid contains a level of the diagnostic agent indicative of aspiration of gastrointestinal contents into the respiratory tract.   
     
     
         8 . The method of  claim 7 , wherein the administered diagnostic agent is selected from the group consisting of cromolyn salts, cromolynic acid, nedocromil, nedocromil salts and muscarinic acid receptor antagonists. 
     
     
         9 . The method of  claim 7 , wherein the administered agent is a cromolyn salt. 
     
     
         10 . The method of  claim 7 , further comprising:
 (g) administering a control formulation comprising the same diagnostic agent as found in the diagnostic formulation to the subject at an occasion different to that when the orally administered diagnostic formulation is administered;   (h) obtaining the body fluid of  claim 1  from the subject following the administration of the control formulation, wherein the body fluid is blood, serum, plasma or urine;   (i) analyzing the body fluid to determine if the body fluid contains the diagnostic agent; and   (j) determining if the level of diagnostic agent detected following administration of the diagnostic formulation is indicative of aspiration of gastrointestinal contents into the respiratory tract by comparison of the level of the diagnostic agent detected in the body fluid following administration of the diagnostic formulation to the level of diagnostic agent detected in the body fluid following administration of the control formulation.   
     
     
         11 . The method of  claim 7 , wherein the control formulation is administered orally. 
     
     
         12 . The method of  claim 7 , wherein the control formulation is administered by inhalation. 
     
     
         13 . The method of  claim 7 , wherein the body fluid is obtained following the administration of the control formulation and prior to analyzing the body fluid. 
     
     
         14 . The method of  claim 7 , wherein the control formulation is administered during a period of time when the subject is not expected to experience aspiration of gastrointestinal contents into the respiratory tract. 
     
     
         15 . The method of  claim 7 , further comprising:
 (g) administering a control formulation comprising the same diagnostic agent as found in the diagnostic formulation to the subject at an occasion different to that when the diagnostic formulation is administered;   (h) obtaining a body fluid from the subject following the administration of the control formulation, wherein the body fluid is urine, blood or a blood product;   (i) analyzing the body fluid to determine if the body fluid contains the diagnostic agent; and   (j) determining if the level of diagnostic agent detected following administration of the diagnostic formulation is indicative of aspiration of gastrointestinal contents into the respiratory tract by comparison of the level of the diagnostic agent detected in the body fluid following administration of the diagnostic formulation to the level of diagnostic agent detected in the body fluid following administration of the control formulation.   
     
     
         16 . The method of  claim 15 , wherein the control formulation is administered orally. 
     
     
         17 . The method of  claim 15 , wherein the control formulation is administered by inhalation. 
     
     
         18 . The method of  claim 15 , wherein the body fluid is obtained following the administration of the control formulation and prior to analyzing the body fluid. 
     
     
         19 . The method of  claim 15 , wherein the control formulation is administered during a period of time when the subject is not expected to experience aspiration of gastrointestinal contents into the respiratory tract. 
     
     
         20 . The method of  claim 15 , further comprising detecting a level of the diagnostic agent indicative of aspiration of gastrointestinal contents into the respiratory tract based on the level of the diagnostic agent observed following administration of the control formulation.