A DEVICE AND METHOD TO DETERMINE THE MEAN/AVERAGE CONTROL OF ASTHMA/COPD OVER TIME AND COMPLIANCE TO TREATMENT

Abstract

A method to assess the disease status, determine the mean/average control of the disease and monitor the compliance to treatment over a period of time of a respiratory disease, comprising of predicting the degree of airway inflammation and disease activity by measuring the inflammatory markers, evaluating the mucosal integrity/damage by measuring the moisture levels of the exhaled air, evaluating the breathing function and obstruction by measuring the FEV1 value, and evaluating the symptom control by determining the COPD Score.

Claims

1. A method to predict the disease status, determine the mean/average control of the disease or monitor the compliance to treatment over a period of time of respiratory diseases, the method comprising of a. predicting the degree of airway inflammation and disease activity by measuring the inflammatory markers; b. evaluating the mucosal integrity/damage by measuring the moisture levels of the exhaled air; c. evaluating the breathing function and obstruction by measuring the FEV1 value; and d. evaluating the symptom control by determining the COPD Score.

2. The method according to claim 1, wherein the degree of airway inflammation and disease activity is predicted by measuring the inflammatory markers comprising of FeNO (fractional exhaled nitric oxide), H2O2 content of exhaled air, pH of the exhaled air, volatile organic compounds and air exchange & alveolar volume using CO.

3. The method according to claim 1, wherein the respiratory disease is COPD or asthma.

4. A device to assess the disease status, determine the mean/average control of the disease and monitor the compliance to treatment over a period of time of respiratory diseases on a real time basis, comprising of a mouth piece/air inlet, exhaled air outlet, spirometer, multiple sensors, display screen and means for input.

5. The device according to claim 4, wherein the multiple sensors comprise of moisture measurement sensor, H2O2 sensor, pH sensor, FeNO sensor, eCO sensor and VOC sensor.

6. The device according to claim 5, wherein the sensors are electronic nano sensors for measurement of respective markers.

7. The device according to claim 4 is a running spirometer capable of measuring FEV1 and other functional lung markers.

8. The device according to claim 4, further comprises of a software program which can take inputs of previous FEV1, store and retrieve the same.

9. The device according to claim 4, further comprises of a software program which can take inputs of COPD assessment score or CAT score, store and retrieve the same.

10. The device according to claim 4, further comprises of a software program which provides a single instant score to assess the present status of all etiopathogenic parameters along with the parameters of functional assessment.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0025] FIG. 1

[0026] FIG. 1 shows the detailed schematic representation of the device.

DESCRIPTION OF EMBODIMENTS

[0027] The invention disclosed herein provides a method to assess the disease status, determine the mean/average control of the disease and monitor the compliance to treatment over a period of time of respiratory diseases, comprising of predicting the degree of airway inflammation and disease activity by measuring the inflammatory markers; evaluating the mucosal integrity/damage by measuring the moisture levels of the exhaled air; evaluating the breathing function and obstruction by measuring the FEV1 value; and evaluating the symptom control by determining the COPD Score. The degree of airway inflammation and disease activity in the method described herein is evaluated by measuring the inflammatory markers comprising of FeNO (fractional exhaled nitric oxide), H.sub.2O.sub.2 content of exhaled air, pH of the exhaled air, volatile organic compounds and air exchange & alveolar volume using CO.

[0028] The method as described herein can be used to predict the risk population of respiratory diseases even in cases where there are no signs/symptoms of the disease are observed and therefore would help in prevention of irreversible damage to lungs, thereby improving the quality of life and public health. Further, the method as described herein provides an single instant score which helps the medical practitioner to categorize the patients into (a) well controlled, (b) average/moderately controlled and (c) poorly controlled, which can be used in newly diagnosed patients to assess the degree of inflammation and helps to plan a treatment titration. The single instant score provides the current status of all etiopathogenic agents as well as their status over a given period of time in contrast to the functional assessment only. Furthermore, the method as described herein helps to determine the mean/average control of the disease and monitor the compliance to treatment over a period of time by response prediction to therapy and accordingly change the treatment regime to achieve quick responses to therapy or to quickly control the symptoms, in already diagnosed patient who are undergoing therapy/treatment.

[0029] The exhaled breath condensate (EBC), collected from the exhaled breath contains components like condensed water vapor, volatile molecules/compounds (such as nitric oxide, carbon monoxide and hydrocarbons) and non-volatile molecules/compounds (such as urea, GSH, leukotrienes, prostanoids and cytokines). The exhaled breath condensate (EBC) composition reflects the metabolic processes in lungs and is used as a marker for the assessment of airway affection, activity of the inflammatory process and the treatment efficacy. The quantitative composition of EBC gives an indication of the presence of respiratory diseases and also the phase and severity of the disease. A number of inflammatory markers present in the EBC act as biomarkers of disease activity.

[0030] Many pulmonary diseases alter the endogenous airway pH homeostasis which induces respiratory symptoms like cough, wheeze, dyspnea and apnea. The air way/EBC pH measurement can be used as a biomarker to assess the endogenous airway acidification in patients with respiratory diseases including stable COPD. In ex-smokers, the airway/EBC pH levels were found to be associated with static hyperinflation, air trapping and diffusing capacity for carbon monoxide. But, no such association is found in the current smokers. The endogenous airway acidification is related to parameters expressing hyperinflation and air trapping in ex-smokers and is indicative of the disease severity. The airway/EBC pH is measured by using electrochemical nano sensor.

[0031] The oxygen and nitrogen reactive species or their derivatives in the EBC can be used as indicators of oxidative stress or inflammation and therefore can be used as biomarkers in many lung/respiratory diseases. Carbon monoxide (CO), a low molecular weight gas which is produced endogenously in the human body as a byproduct of heme metabolism, binds to hemoglobin, resulting in decreased oxygen delivery to bodily tissues at toxic concentrations. At physiological concentrations, CO may act as a potential signaling mediator in vascular function and cellular homeostasis. The exhaled CO (eCO), a candidate breath biomarker of pathophysiological states, including smoking status and inflammatory diseases of the lung was chosen. The eCO values is a potential breath biomarker of inflammation in asthma, stable COPD and AECOPD, lung cancer etc. The eCO levels in exhaled breath are measured with the electrochemical (chemiluminescence)/nano technology. The eCO levels are detected by the use of sensors which are sensitive in the range of about 1-500 ppm. According to one embodiment the sensor is a gas sensor adapted from a controlled potential electrolysis method. Alternatively techniques based on infrared laser spectroscopic methods can also be used for the detecting the levels of eCO in the exhaled air.

[0032] One of the biomarker in the EBC to measure the oxidative destruction in lung and inflammation of the airways is H2O2. The lung is highly susceptible to oxidative stress in the form of reactive oxygen species/oxygen metabolites like hydrogen peroxide, hydroxyl radical and super oxide ion due to its constant exposure to oxygen. Elevated levels of H2O2 in EBC are indicative of airway inflammation and can be used as an early predictor of the ongoing inflammatory process measured using nano/electrochemical sensor.

[0033] Fractional exhaled Nitric Oxide (FeNO) is a measure of airway inflammation and is used as a biomarker for eosnophilic airway inflammation in asthma and other airway diseases. Measurement of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. The magnitude of FeNO increases proportionately to bronchial wall inflammation or induced-sputum eosinophilia as well as to airway hyper-responsiveness. The FeNO is measured by using electrochemical nano sensor.

[0034] Exhaled air of a human contains many volatile organic compounds (VOCs) produced during the metabolic processes. The characterization of the exhaled VOCs in patients with respiratory diseases provides the qualitative and quantitative differences in the chemical composition of the exhaled air. The VOCs found in the exhaled air/breath are small organic molecules that are volatile at ambient temperature and include compounds such as hydrocarbons and compounds containing nitrogen, oxygen and sulfur. The exhaled VOCs are characterized by using a sensor or sensor system. According to one embodiment, the senor is an electronic sensor system based on arrays of partially selective gas sensors system. The electronic sensor(s) provide the information about the respiratory profile characterized by a set of various VOCs.

[0035] The invention disclosed herein provides a device to assess the disease status, determine the mean/average control of the disease and monitor the compliance to treatment over a period of time of respiratory diseases on a real time basis, comprising of a mouth piece/air inlet, exhaled air outlet, spirometer, multiple sensors, display screen and means for input. The device as described herein comprises of moisture measurement sensor, H2O2 sensor, pH sensor, FeNO sensor, eCO sensor and VOC sensor. The sensors as described herein are electronic nano sensors.

[0036] The device as described herein further comprises of a software program which provides a single instant score to assess the present status of all etiopathogenic parameters along with the parameters of functional assessment.

[0037] The device as described herein measures the chemical composition of the exhaled air via sensors and inbuilt software program (which is based on exhaled air parameters and flow) gives an instant single score which classifies patients into

[0038] Well controlled,

[0039] Average/moderately controlled, and

[0040] Poorly controlled categories

[0041] The inbuilt software program provides the instant single score by considering the measurements/reading obtained for the following markers/parameters:

[0042] FEV1 valueBaseline and previous values to calculate both frequency and amplitude of drifts/fluctuations as entered manually at the beginning of test upon prompting by the device,

[0043] Patient symptoms and COPD scoremanually entered before taking the test [present and previous values],

[0044] Moisture levels of exhaled aira marker of mucosal integrity/damage,

[0045] Markers of inflammation FeNO [Fractional exhaled nitric oxide] absolute value and a reduction from previous score either or considered,

[0046] H.sub.2O.sub.2 content of exhaled air [Range 2-11 micro molar],

[0047] pH sensor [3-9 range in exhaled air],

[0048] Volatile Organic Compounds, and

[0049] Air exchange and alveolar volume using CO.

[0050] The inbuilt software program is based on the daily measurement of the FEV1which indicates the asthma control and using a mathematical algorithm, correlated with the formula as described below:

FEV1 absolute value.sup.M+change from the previous value.sup.m+COPD score.sup.n+pH.sup.x+CO.sup.y+FeNo.sup.z+H2O2.sup.a+Volatile Organic Compounds.sup.K [0051] FEV I (Tiffeneau-Pinelli index, is a calculated ratio used in the diagnosis of obstructive and restrictive lung disease. It represents the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration to the full vital capacity.)measured as % of exhaled air. [0052] Change of FEV1 means=the present valueprevious value of FEV 1. [0053] M is a numeric ranging from 0.06 to 3.98. [0054] COPD score/CAT test (Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life. The difference between stable and exacerbation patients was five units)measured as numeric. [0055] N=a value ranging from 0.56-1.38. [0056] pHMeasured as numeric with outer limits capped at 3 to 9. [0057] X=a numeric ranging from 0.8-1.2 [0058] CO measured and represented in the range 1-500 ppm, more specifically between 5-36 ppm [0059] Y is any value between 0.1 to 2.3 [0060] FeNO measured as 6-38 ppbmore specifically 9-20 [0061] Z is a value ranging from 0.8-1.6 [0062] H.sub.2O.sub.2 measured 2.7-22.8 micro moles/Lit [0063] A is a value from 0.7-1.4 [0064] VOC (volatile organic compounds) 6 ppbv to 2 ppmv [0065] K is the value ranging from 0.6-1.4

[0066] The average control of COPD/asthma over a period of 6 weeks could be predicted with reasonable sensitivity and specificity with above formula.

[0067] This shall help physicians to take more informed decisions to adjust therapy thereby delay the progression rather than making decision on snap shot value of FEV1.

[0068] The device as disclosed herein measures the following parameters on a real time basis and provides an instant single score to assess the present status of all etiopathogenic agents as well as their status over a given period of time, classification of score to stratify patients, predict disease control in near future and potential complications, and Standardized score for response to therapy, in contrast to the functional assessment only.

[0069] Inflammatory markersto predict the degree of airway inflammation and disease activity.

[0070] Moisture levels of exhaled aira marker of mucosal integrity/damage.

[0071] FEV1 [variation from the baseline and average driftboth frequency and amplitude of drifts/fluctuations]Marker of breathing function and obstruction.

[0072] COPD Scorea marker of symptom control.

[0073] The instant single score provided by the device described herein reflects the accurate indication of average COPD/asthma status, recent past, existing and ongoing damage to tissue and to prevent irreversible damage to lungs by early intervention, response prediction to medical management of COPD/asthma and optimize treatment which will help the medical professional to avoid both over and under treatment.