Methods for assessing swallowing motor function

Abstract

The present invention relates to methods for assessing swallowing motor function in a subject. The methods rely on obtaining intraluminal impedance and pressure measurements from the pharynx and/or esophagus of the subject during clearance of a bolus from the mouth and/or throat of the subject. The intraluminal impedance and pressure measurements are combined to derive a value for one or more pressure-flow variables in the pharynx and/or esophagus of the subject. The value of the one or more pressure-flow variables is compared to a predetermined pharyngeal and/or esophageal reference value for the one or more pressure-flow variables in order to provide an assessment of swallowing motor function in the subject. The intraluminal impedance and pressure measurements can also be combined to generate a swallow risk index for the subject or to generate an obstructive risk index for the subject based on a combination of a value of more than one pressure-flow variable in the pharynx and/or esophagus of the subject. In this way, swallowing motor function in the subject can be assessed by comparing the swallow risk index or obstructive risk index for the subject to a predetermined reference swallow index or predetermined reference obstructive index, respectively. Products which make use of these methods are also encompassed by the present invention.

1 . A method for assessing swallowing motor function in a subject, the method including:
 (a) accessing intraluminal impedance measurements and pressure measurements obtained from the pharynx and/or esophagus of the subject during clearance of a bolus from the mouth and/or throat of the subject;   (b) combining and analysing the intraluminal impedance and pressure measurements to derive a value for one or more pressure-flow variables in the pharynx and/or esophagus of the subject; and   (c) assessing swallowing motor function in the subject by comparing the value of the one or more pressure-flow variables with a predetermined pharyngeal and/or esophageal reference value for the one or more pressure-flow variables.   
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The method according to  claim 1 , wherein combining and analysing the intraluminal impedance and pressure measurements includes measuring the nadir of the impedance waveform, and wherein the nadir of the impedance waveform is used as a time marker for analysis of the pressure waveform. 
     
     
         9 . The method according to  claim 8 , wherein one of the pressure-flow variables is the pressure at the nadir of the impedance waveform (PNadImp) in the pharynx and/or esophagus of the subject and wherein a higher PNadImp in the subject compared to the predetermined pharyngeal and/or esophageal PNadImp reference value is indicative of ineffective swallowing and/or risk of aspiration in the subject. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . The method according to  claim 1 , wherein one of the pressure-flow variables is the peak pressure of the pressure waveform (PeakP) in the pharynx and/or esophagus of the subject and wherein a lower PeakP in the subject compared to the predetermined pharyngeal and/or esophageal PeakP reference value is indicative of ineffective swallowing and/or risk of aspiration in the subject. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The method according  claim 1 , wherein one of the pressure-flow variables is the time from the nadir of the impedance waveform to the peak pressure (TNadImp−PeakP) in the pharynx and/or esophagus of the subject and wherein a shorter TNadImp−PeakP in the subject compared to the predetermined pharyngeal and/or esophageal TNadImp−PeakP reference value is indicative of ineffective swallowing and/or risk of aspiration in the subject. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The method according to  claim 1 , wherein one of the pressure-flow variables is the duration of the drop in intraluminal impedance during bolus clearance (Flow Interval) in the pharynx and/or esophagus of the subject and wherein a longer Flow Interval in the subject compared to the predetermined pharyngeal and/or esophageal Flow Interval reference value is indicative of ineffective swallowing and/or risk of aspiration in the subject. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method according to  claim 1 , wherein values of two or more pressure-flow variables are derived and then combined to generate a swallow risk index for the subject. 
     
     
         22 . The method according to  claim 21 , wherein the pressure flow variables for which values are derived include Flow Interval, pressure at the nadir of an impedance waveform (PNadImp), peak pressure of a pressure waveform (PeakP), and time from the nadir of an impedance waveform to the peak pressure (TNadImp−PeakP), and wherein the swallow risk index includes a ratio between (Flow Interval×PNadImp) and (PeakP×TNadImp−PeakP) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . The method according to  claim 1 , wherein one of the pressure flow variables is intrabolus pressure (IBP) in the pharynx and/or esophagus of the subject and wherein a higher IBP in the subject compared to the predetermined pharyngeal and/or esophageal IBP reference value is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . The method according to  claim 1 , wherein one of the pressure flow variables is intrabolus pressure slope (IBP Slope) in the pharynx and/or esophagus of the subject and wherein an elevated IBP Slope in the subject compared to the predetermined pharyngeal and/or esophageal IBP Slope reference value is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . The method according to  claim 1 , wherein one of the pressure flow variables is time from the nadir of the impedance waveform to the peak pressure (TNadImp−PeakP) in the pharynx and/or esophagus of the subject and a shorter TNadImp−PeakP in the subject compared to the predetermined pharyngeal and/or esophageal TNadImp−PeakP reference value is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         35 . (canceled) 
     
     
         36 . The method according to  claim 1 , wherein the values of more than one pressure-flow variable are derived and then combined to generate a dysphagia risk index for the subject. 
     
     
         37 . The method according to  claim 36 , wherein the pressure flow variables for which values are derived include interbolus pressure (IBP), interbolus pressure slope (IBP Slope), and time from a nadir of an impedance waveform to a peak pressure (TNadImp−PeakP), and the dysphagia risk index has the following formula:
   IBP×IBP Slope×TNadImp−Peak P  
 
 
       wherein a dysphagia risk index which is higher than a predetermined reference dysphagia index is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . The method according to  claim 1 , wherein one of the pressure flow variables is a nadir of an impedance waveform preceding peak pressure (Zn) in the pharynx and/or esophagus of the subject and wherein a higher Zn in the subject compared to the predetermined pharyngeal and/or esophageal Zn reference value is indicative of ineffective swallowing and/or risk of aspiration in the subject. 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . The method according to  claim 1 , wherein one of the pressure flow variables is impedance at the time of peak pressure (ZPp) in the pharynx and/or esophagus of the subject and wherein a lower ZPp in the subject compared to the predetermined pharyngeal and/or esophageal ZPp reference value is indicative of ineffective swallowing and/or risk of aspiration in the subject. 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . The method according to  claim 1 , wherein one of the pressure flow variables is a nadir of an impedance waveform preceding peak pressure Zn and another of the pressure flow variables is impedance at the time of peak pressure (ZPp), and wherein a ZPp value that is lower than the Zn value in the subject is an indicator that the ineffective swallowing is due to an obstruction in the pharynx and/or esophagus of the subject. 
     
     
         50 . (canceled) 
     
     
         51 . The method according to  claim 49 , including generating an obstructive risk index according to the following formula:
   Zn/ZPp   
       wherein an obstructive risk index which is higher than a predetermined reference obstructive index indicates that the ineffective swallowing is due to an obstruction in the pharynx and/or esophagus of the subject. 
     
     
         52 . (canceled) 
     
     
         53 . (canceled) 
     
     
         54 . (canceled) 
     
     
         55 . (canceled) 
     
     
         56 . The method according to  claim 1 , including identifying a location of an obstruction in the subjects pharynx and/or esophagus that causes ineffective swallowing by determining one of the pressure flow variables to be the minimum impedance at the time of peak pressure (min ZPp) in the pharynx and/or esophagus of the subject during clearance of the bolus from the mouth and/or throat of the subject and wherein the position of the min ZPp in the pharynx and/or esophagus of the subject is indicative of the position of the obstruction. 
     
     
         57 . (canceled) 
     
     
         58 . The method according to  claim 1 , including identifying a location of an obstruction in the subjects pharynx and/or esophagus that causes ineffective swallowing by determining the one or more pressure flow variables are the nadir of the impedance waveform preceding peak pressure (Zn) in the pharynx and/or esophagus of the subject during clearance of the bolus from the mouth and/or throat of the subject, and the impedance at the time of peak pressure (ZPp) in the pharynx and/or esophagus of the subject during clearance of the bolus from the mouth and/or throat of the subject, and wherein the position of the maximum Zn/ZPp in the pharynx and/or esophagus of the subject is indicative of the position of the obstruction. 
     
     
         59 . A method for assessing swallowing motor function in a subject, the method including:
 (a) accessing intraluminal impedance measurements and pressure measurements obtained from the pharynx and/or esophagus of the subject during clearance of a bolus from the mouth and/or throat of the subject;   (b) combining the intraluminal impedance and pressure measurements;   (c) generating a swallow risk index for the subject based on a combination of a value of more than one pressure-flow variable in the pharynx and/or esophagus of the subject, wherein the value is derived from an analysis of the combined intraluminal impedance and pressure measurements; and   (d) assessing swallowing motor function in the subject by comparing the swallow risk index for the subject to a predetermined reference swallow index.   
     
     
         60 . (canceled) 
     
     
         61 . (canceled) 
     
     
         62 . (canceled) 
     
     
         63 . (canceled) 
     
     
         64 . (canceled) 
     
     
         65 . The method according to  claim 59 , including generating an impedance waveform of the bolus clearance from the impedance measurements. 
     
     
         66 . The method according to  claim 59 , including generating a pressure waveform of the bolus clearance from the pressure measurements. 
     
     
         67 . The method according to  claim 59 , including generating an impedance waveform from the impedance measurements, generating a pressure waveform from the pressure measurements, measuring the nadir of the impedance waveform, and using the nadir of the impedance waveform as a time marker for analysis of the pressure waveform. 
     
     
         68 . The method according to  claim 67 , wherein one of the pressure-flow variables is the pressure at the nadir of the impedance waveform (PNadImp) in the pharynx and/or esophagus of the subject, one of the pressure-flow variables is the peak pressure of the pressure waveform (PeakP) in the pharynx and/or esophagus of the subject, one of the pressure-flow variables is the time from the nadir of the impedance waveform to the peak pressure (TNadImp−PeakP) in the pharynx and/or esophagus of the subject, and one of the pressure-flow variables is the duration of the drop in intraluminal impedance during bolus clearance (Flow Interval) in the pharynx and/or esophagus of the subject, and wherein the swallow risk index includes a ratio of (Flow Interval×PNadImp) to (PeakP×(TNadImp−PeakP+1)). 
     
     
         69 . (canceled) 
     
     
         70 . (canceled) 
     
     
         71 . (canceled) 
     
     
         72 . The method according to  claim 68 , wherein a swallow risk index of about 10 or higher derived from the formula 
       
         
           
             
               
                 
                   ( 
                   
                     Flow 
                      
                     
                         
                     
                      
                     Interval 
                     × 
                     PNadImp 
                   
                   ) 
                 
                 
                   ( 
                   
                     PeakP 
                     × 
                     
                       ( 
                       
                         TNadImp 
                         - 
                         PeakP 
                         + 
                         1 
                       
                       ) 
                     
                   
                   ) 
                 
               
               × 
               100 
             
           
         
       
       is indicative of an ineffective swallow. 
     
     
         73 . (canceled) 
     
     
         74 . The method according to  claim 68 , wherein a swallow risk index of about 16 or higher derived from the formula 
       
         
           
             
               
                 
                   ( 
                   
                     Flow 
                      
                     
                         
                     
                      
                     Interval 
                     × 
                     PNadImp 
                   
                   ) 
                 
                 
                   ( 
                   
                     PeakP 
                     × 
                     
                       ( 
                       
                         TNadImp 
                         - 
                         PeakP 
                         + 
                         1 
                       
                       ) 
                     
                   
                   ) 
                 
               
               × 
               100 
             
           
         
       
       is indicative of an ineffective swallow and/or risk of aspiration. 
     
     
         75 . (canceled) 
     
     
         76 . The method according to  claim 60 , wherein one of the pressure flow variables is intrabolus pressure (IBP) in the pharynx and/or esophagus of the subject and wherein a higher IBP in the subject compared to the predetermined pharyngeal and/or esophageal IBP reference value is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         77 . (canceled) 
     
     
         78 . (canceled) 
     
     
         79 . The method according to  claim 60 , wherein one of the pressure flow variables is intrabolus pressure slope (IBP Slope) in the pharynx and/or esophagus of the subject and wherein an elevated IBP Slope in the subject compared to the predetermined pharyngeal and/or esophageal IBP Slope reference value is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         80 . (canceled) 
     
     
         81 . (canceled) 
     
     
         82 . The method according to  claim 60 , wherein one of the pressure flow variables is time from the nadir of the impedance waveform to the peak pressure (TNadImp−PeakP) in the pharynx and/or esophagus of the subject and wherein a shorter TNadImp−PeakP in the subject compared to the predetermined pharyngeal and/or esophageal TNadImp−PeakP reference value is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         83 . (canceled) 
     
     
         84 . (canceled) 
     
     
         85 . The method according to  claim 60 , wherein the value of more than one pressure-flow variable is combined to generate a dysphagia risk index (DRI) for the subject by determining interbolus pressure (IBP), interbolus pressure Slope (IBP Slope), and time from the nadir of the impedance waveform to peak pressure (TNadImp−PeakP) and determining the DRS according to the formula:
   DRI=IBP×IBP Slope×TNadImp−Peak P   −1  
 
 
       and predicting that dyphagia will occur in the subject based on a DRI value calculated according to the formulate that is higher than a predetermined reference dysphagia index. 
     
     
         86 . (canceled) 
     
     
         87 . The method according to  claim 85  or  claim 86 , wherein a dysphagia risk index which is higher than a predetermined reference dysphagia index is a predictor for the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         88 . (canceled) 
     
     
         89 . (canceled) 
     
     
         90 . (canceled) 
     
     
         91 . A method for assessing swallowing motor function in a subject, the method including:
 (a) accessing intraluminal impedance measurements and pressure measurements obtained from the pharynx and/or esophagus of the subject during clearance of a bolus from the mouth and/or throat of the subject;   (b) combining the intraluminal impedance and pressure measurements;   (c) generating an obstructive risk index for the subject based on a combination of a value of more than one pressure-flow variable in the pharynx and/or esophagus of the subject, wherein the value is derived from an analysis of the combined intraluminal impedance and pressure measurements; and   (d) assessing swallowing motor function in the subject by comparing the obstructive risk index for the subject to a predetermined reference obstructive index.   
     
     
         92 . (canceled) 
     
     
         93 . The method according to  claim 91 , wherein swallowing motor function includes ineffective swallowing in the subject due to an obstruction in the pharynx and/or esophagus of the subject. 
     
     
         94 . The method according to  claim 93 , wherein the obstructive risk index for the subject being higher than the predetermined reference obstructive index indicates ineffective swallowing in the subject, wherein said ineffective swallowing is due to an obstruction in the pharynx and/or esophagus of the subject. 
     
     
         95 . (canceled) 
     
     
         96 . The method according to  claim 91 , including using the pressure measurements to generate a pressure waveform of the bolus clearance and using the intraluminal impedance measurements are used to generate an impedance waveform of the bolus clearance. 
     
     
         97 . (canceled) 
     
     
         98 . The method according to  claim 96 , wherein one of the pressure flow variables is the nadir of the impedance waveform preceding peak pressure (Zn) in the pharynx and/or esophagus of the subject and another one of the pressure flow variables is the impedance at the time of peak pressure (ZPp) in the pharynx and/or esophagus of the subject, and wherein the obstructive risk index includes a ratio between Zn and ZPp. 
     
     
         99 . (canceled) 
     
     
         100 . The method according to  claim 99 , including determining the swallow motor function includes an ineffective swallow by the obstructive risk index of the subject derived from the formula Zn/ZPp being greater than 1. 
     
     
         101 . (canceled) 
     
     
         102 . Software for use with a computer that includes a processor and associated memory for storing the software, the software including a series of instructions executable by the processor to carry out steps for assessing swallowing motor function in a subject, including:
 (a) accept, as an input, intraluminal impedance and pressure measurements obtained from the pharynx and/or esophagus of a subject during clearance of a bolus from the mouth and/or throat of the subject;   (b) combine and analyse the intraluminal impedance and pressure measurements to derive a value for one or more pressure-flow variables in the pharynx and/or esophagus of the subject;   (c) assess swallowing motor function in the subject by performing a comparison between the value of the one or more pressure-flow variables with a redetermined pharyngeal and/or esophageal reference value for the one or more pressure-flow variables; and   (d) provide, as an output, an assessment of swallowing motor function in the subject on the basis of the comparison.   
     
     
         103 . A computer readable media containing software that includes a series of instructions executable by a computer processor to carry out steps for assessing swallowing motor function in a subject including:
 (a) accept, as an input, intraluminal impedance and pressure measurements obtained from the pharynx and/or esophagus of a subject during clearance of a bolus from the mouth and/or throat of the subject;   (b) combine and analyse the intraluminal impedance and pressure measurements to derive a value for one or more pressure-flow variables in the pharynx and/or esophagus of the subject;   (c) assess swallowing motor function in the subject by performing a comparison between the value of the one or more pressure-flow variables with a predetermined pharyngeal and/or esophageal reference value for the one or more pressure-flow variables; and   (d) provide, as an output, an assessment of swallowing motor function in the subject on the basis of the comparison.   
     
     
         104 . An apparatus for enabling an assessment of swallowing motor function in a subject, the apparatus including:
 (a) a processor;   (b) a memory; and   (c) software resident in memory accessible to the processor, the software executable by the processor to carry out a series of steps including   (a) accept, as an input, intraluminal impedance and pressure measurements obtained from the pharynx and/or esophagus of a subject during clearance of a bolus from the mouth and/or throat of the subject;   (b) combine and analyse the intraluminal impedance and pressure measurements to derive a value for one or more pressure-flow variables in the pharynx and/or esophagus of the subject;   (c) assess swallowing motor function in the subject by performing a comparison between the value of the one or more pressure-flow variables with a predetermined pharyngeal and/or esophageal reference value for the one or more pressure-flow variables; and   (d) provide, as an output, an assessment of swallowing motor function in the subject on the basis of the comparison.   
     
     
         105 . A computer readable media including a set of instructions in the form of a computer software program, the instructions being executable by a processing device on-board a programmed computer, wherein execution of the instructions causes the programmed computer to:
 (a) accept, as an input, intraluminal impedance and pressure measurements obtained from the pharynx and/or esophagus of a subject during clearance of a bolus from the mouth and/or throat of the subject;   (b) combine and analyse the intraluminal impedance and pressure measurements to derive a value for one or more pressure-flow variables in the pharynx and/or esophagus of the subject;   (c) assess swallowing motor function in the subject by performing a comparison between the value of the one or more pressure-flow variables with a predetermined pharyngeal and/or esophageal reference value for the one or more pressure-flow variables; and   (d) provide, as an output, an assessment of swallowing motor function in the subject on the basis of the comparison.   
     
     
         106 . The computer readable media according to  claim 105 , wherein the computer readable media further includes executable instructions which identify ineffective swallowing in the subject on the basis of the comparison. 
     
     
         107 . The computer readable media according to  claim 106 , wherein the computer readable media further includes executable instructions which determine risk of aspiration in the subject, diagnose an increased likelihood of aspiration in the subject, predict aspiration in the subject, and/or identify a subject susceptible to aspiration. 
     
     
         108 . The computer readable media according to  claim 107 , wherein the computer readable media further includes executable instructions which predict the occurrence of dysphagia in the subject following therapy and/or surgery. 
     
     
         109 . (canceled)