SBIR-STTR Award

Indirect calorimetry is based on measurement of the exchange of respiratory gases. All aerobic energy-releasing re- actions in the body use oxygen; oxygen consumption, V_O2, is proportional to energy expenditure (EE). Research- grade indirect calorimetry systems measure V_O2, carbon dioxide production, V_CO2, and minute ventilation, V_E, breath by breath and then average results over multiple breaths to obtain accurate measures of cardiorespiratory function. The maximum attainable V_ O2 (i.e., V_ O2max) is the gold standard for assessing cardiorespiratory tness. In cardiac rehabilitation (CR), which is our focus herein, patients with coronary artery disease or chronic heart failure undergo supervised exercise training to improve heart health. Most CR is performed in outpatient settings, where the lack of equipment and specially-trained sta have precluded objective measurement of key values, such as peak oxygen uptake (V_O2peak), which is maximum V_O2 attained by the patient in a particular exercise stress test (which is not necessarily her/his maximum attainable V_ O2). Measurement of V_ O2peak is desired for tracking CR progress and for prescribing exercise intensities. Due to its nonavailability in most outpatient settings, suboptimal, semi-quantitative substitute measures (e.g., heart rate reserve, Borg ratings of perceived exertion, or 6-minute walk test) are often employed. Additionally, with measurement of V_ E, the e cacy of CR at improving measures of breathing efficiency (e.g., the ratios V_ E=V_ CO2 and V_ E=V_ O2) can be computed, which is especially important for patients with high initial values. Like V_ O2peak, these efficiency metrics are seldom available in CR practice due to equipment and personnel limitations. To obtain such measures, patients have to be scheduled for a cardiopulmonary exercise test (CPET), which is expensive and, beyond an initial test, generally not covered by insurance. The proposed Mobile Metabolic Measurement (M3) system will overcome these limitations and can be used during CR exercise sessions to track patient progress on a frequent basis. Objectively measured V_ O2peak values can be used (along with heart rate) to optimize exercise prescriptions to enable maximum safe progress. The M3 system will o er a huge advance in quantitative CR patient monitoring. The M3 system is a novel, cost-e ective, portable device for accurately and reliably measuring V_O2, V_CO2, V_E, V_E=V_CO2, V_E=V_O2, the respiratory exchange ratio (R=V_CO2=V_O2), and EE (e.g., METS or kilocalories). The proposed M3 system's \one-button" (turnkey) calibration-free operation and order-of-magnitude lower price compared to existing cart or mobile indirect calorimetry systems will make it practical and a ordable for use by non-experts in outpatient, hospital, laboratory, eld, educational, and even home settings. In addition to CR, other areas that could benefit from the M3 system include assessing the resting metabolic rate (RMR) of acutely ill and critically ill hospital patients to guide enteral and parenteral nutrition, monitoring the ventilatory status of patients being weaned from mechanical ventilators, and guiding weight loss by quantifying the impact of dietary and exercise regimens. Metabolic measurement is presently infeasible in many such applications.

Public Health Relevance Statement:
Narrative The proposed M3 system will address the current gap in the availability of an inexpensive, easy-to-use, and accurate system for measuring V_O2peak, V_E=V_CO2, V_E=V_O2, and R in cardiac rehabilitation (CR) settings for tracking patients' physiological responses to exercise and optimizing their exercise prescriptions. It is well documented in the literature that the key limitations of the gold-standard cardiopulmonary exercise test (CPET) are directly related to the expertise required to perform the test and its associated costs (both equipment and personnel). Even outside of CR applications, the proposed M3 system represents a transformative technology that will not only compete in existing markets, but will contribute to the creation of new markets (e.g., team sports, health and wellness applications, etc.), which will further drive down its cost. Terms:

Indirect calorimetry (IC) is based on measurement of the exchange of respiratory gases. All aerobic energy- releasing reactions in the body use oxygen; oxygen consumption, V.O2, is proportional to energy expenditure (EE). Research-grade IC systems measure V.O2, carbon dioxide production, V.CO2, and minute ventilation, V.E, breath by breath and then average results over multiple breaths to obtain accurate measures of cardiorespira- tory function. Subjects' V.O2max (i.e., maximum attainable V.O2) is the gold standard for assessing cardiorespiratory fitness (CRF). Indirect calorimetry is a part of cardiopulmonary exercise testing (CPET), providing a comprehen- sive assessment of physiology at rest and during stress. Further, derived variables (e.g., V.E=V.CO2, V.E=V.O2) have significant prognostic implications. For example, V.E=V.CO2 and V.E=V.O2, which can be obtained under maximal and submaximal conditions, provide measures of ventilatory efficiency; higher ratios indicate reduced breathing efficiency (e.g., due to pulmonary shunting or increased dead space ventilation). Like V.O2peak (i.e., the maximum V.O2 attained by a patient in an exercise stress test), V.E=V.CO2 and V.E=V.O2 improve with treatment/training. In cardiac rehabilitation (CR), for example, patients with coronary artery disease or chronic heart failure undergo supervised exercise training to improve heart health. Most CR is performed in outpatient settings, where the lack of equipment and specially-trained staff have precluded quantitative measurement of key values. To obtain such measures, patients have to be scheduled for CPET, which is expensive and generally not covered by insurance after an initial test. In practice, due to the nonavailability of V.O2peak and other derived measures in outpatient settings, suboptimal, semi-quantitative substitute measures are generally employed (e.g., 6-minute walk test). The Mobile Metabolic Measurement (M3) system will enable this limitation to be overcome, enabling objectively-measured V.O2, V.CO2, and V.E values to be available to provide CR patients with their initial exercise intensities, to track their progress, and to optimize their exercise prescriptions to maximize safe progress. The M3 system represents a substantial and practicable advance in quantitative CR patient monitoring. Phase I Results All Phase I objectives were successfully achieved. Specifically, the statistical equivalence of the M3 system's V.O2, V.CO2, and V.E measurements was demonstrated vis-à-vis two criterion systems: (1) the VacuMed Metabolic Simulator with Mass Flow Controller system [158]; and (2) the Oxycon Mobile system [49]. Phase II Goal Phase II will involve: (1) developing and validating the M3 system product using the VacuMed Metabolic Simulator, including the clinical software that will run on tablets and other computers; (2) evaluating M3 system performance in healthy adults; and (3) evaluating M3 system performance in patients with chronic stable coronary artery disease (CAD). Rigorous comparisons with commercial IC systems (viz., Oxycon Mobile and Vyntus CPX metabolic cart) will be made during aerobic exercise. Performance testing will be conducted in collaboration with the Arizona State University (healthy subjects) and the University of Virginia (CAD patients).

Public Health Relevance Statement:
Narrative The proposed M3 system will address the current gap in the availability of an inexpensive, easy-to-use, and accurate system for measuring key ventilatory quantities in healthy adults and cardiac rehabilitation (CR) settings for tracking patients' physiological responses to exercise and optimizing their exercise prescriptions. It is well documented in the literature that the key limitations of the gold-standard cardiopulmonary exercise test (CPET) are directly related to the expertise required to perform the test and its associated costs (both equipment and personnel). Outside of CR applications, the proposed M3 system will also provide a transformative technology that will not only compete in existing markets, but will serve to create new markets (e.g., hospital, sports, health and wellness applications, etc.), which will further reduce its relatively low cost due to economies of scale. Terms: <21+ years old; Adult Human; adulthood; Adult; Aerobic Activity; Aerobic Training; Aerobic fitness; Aerobic Exercise; Air; Arizona; Respiratory Aspiration; Respiratory Inspiration; inspiration; Breathing; Beds; Bicycling; Calibration; Respiration Calorimetry; Indirect Calorimetry; CO2; Carbonic Anhydride; Carbon Dioxide; Computers; Coronary Artery Disease; Coronary Artery Disorder; Coronary Atherosclerosis; atherosclerotic coronary disease; coronary arterial disease; Coronary Arteriosclerosis; Critically Ill; Critical Illness; Data Collection; Educational aspects; Education; Energy Expenditure; Energy Metabolism; Enteral Nutrition; Equipment; Exercise; Exercise stress test; Leakage; Spillage; Extravasation; faces; facial; Face; Flowmeters; Flushing; Gases; Goals; Health; Cardiac Failure Congestive; Heart Decompensation; chronic heart failure; Congestive Heart Failure; Hospitals; Humidity; Insurance; Literature; Lung Respiratory System; pulmonary; Lung; Marketing; Memory; Nose; Nasal; Nasal Passages Nose; Respiratory System, Nose, Nasal Passages; Outpatients; Out-patients; Oxygen; O element; O2 element; Oxygen Consumption; Parenteral Nutrition; Intravenous Feeding; Intravenous Hyperalimentation; Parenteral Feedings; hyperalimentation; hyperalimentation therapy; Patient Monitoring; Patients; Physiology; pressure; Production; Ramp; Reaction Time; Response RT; Response Time; psychomotor reaction time; Research; Rest; Running; Computer software; Software; Sports; Stress; Tablets; Technology; Temperature; Testing; Time; Translations; translation; Universities; Virginia; Body Weight decreased; Weight Loss; Weight Reduction; body weight loss; wt-loss; Work; Measures; Walking; Schedule; Clip; human subject; sensor; improved; Acute; Chronic; Clinical; Specified; Specific qualifier value; Phase; Variation; Variant; Physiologic; Physiological; prognostic; Training; Individual; barometric pressure; Measurement; Collaborations; Metabolic; lightweight; light weight; programs; Exhaling; Respiratory Expiration; Exhalation; Reaction; System; Cardiopulmonary; Performance; respiratory gas; success; voltage; Basal metabolic rate; Basal Metabolism; resting metabolic rate; novel; Human Resources; Manpower; personnel; performance tests; response; prevent; preventing; fitness; Aerobic; Data; Dryness; Collection; Facilities and Administrative Costs; Indirect Costs; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Preparation; preparations; Characteristics; Development; developmental; face mask; cost; prototype; commercialization; operation; operations; Cardiac rehabilitation; cardiac rehab; Tablet Computer; tablet device; exercise regimen; Exercise routine; exercise prescription; Prescribed exercise; exercise training; treadmill; cardiorespiratory fitness; cardiorespiratory health; Cardiac health; Heart health; Bluetooth; Atmosphere; ventilation; pressure sensor; Exercise Test; dietary; rechargeable battery