GB2509922A - Measuring Respiratory Exchange Ratio (RER) using a portion of expired breath - Google Patents

Abstract

An apparatus passively collects a portion (e.g. 1%) of expired breaths via a small nasal or oral sampling tube 8, and directs the subsequent gas flow to an appropriately sized small mixing chamber 2 where sensitive oxygen and carbon dioxide sensors 4, 5 measure O2 and CO2 gas concentrations. Respiratory Exchange Ratio (RER) is calculated. Valves are provided. The apparatus is portable, and is suitable for exercise testing. RER is an increasingly important physiological parameter of relevance to sports physiology, nutrition and medicine. The apparatus allows calculation of RER without the added complexity and expense involved in measuring breathing volumes.

Description

Method and Apparatus for Estimation of Respiratory Exchange Ratio

Field of the Invention

The present invention relates to a method and apparatus to collect and measure mixed expired air for estimating a person's respiratory exchange ratio (RER) or respiratory quotient (RQ) and other Respiratory Gas Exchange parameters.

Background of the Invention

Respiratory Exchange Ratio (RER) is a valuable physiological parameter that has been measured for over a century for use in determining relative amounts of substrates used to generate energy from the metabolism of living organisms including man. The term RER has been used interchangeably with Respiratory Quotient, RQ is the term for the ratio of C02 production and 02 consumption at the cellular level and RER is quantity of C02 produced, divided by the quantrty of 02 consumed calculated from the difference between inspired and expired air. However, RER and RQ frequently differ as there is around 100 times more C02 than 02 stored in the body and the C02 content in expired air may not represent cellular C02 production under certain physiological conditions: for example RER > RQ with deep breaths and hyperventilation as more C02 is released from the lungs than is generated by cellular C02 metabolism. In addition, RER> RQ when lactate production from muscle increases during intense exercise. The method described herein measures RER and in the field of sports physiology RER has special utility in detecting lactate threshold in addition to its use as an important indicator of the difference n substrate utilization between fats and carbohydrates. Development and popularization of the present invention has the potential to bring significant benefits to public health particularly in view of the alarming global increase in obesity and diseases due to aging and metabolic disturbances. The present invention is a simpler, less expensive RER monitoring instrument than has heretofore been described. It is intended to be used under any circumstances where RER/RQ is desired to be measured but especially during exercise and exercise testing as it is portable and relatively unobtrusive. RQ measurement is important in nutrition research, exercise research, athletic training, cardio-pulmonary exercise testing, nutritional evaluations in hospitals by doctors and nutritionists, weight loss, wellness, disease prevention and treatment. Specifically in athletic training the instrument can be used to detect lactate threshold (LT) during exercise testing or during training as the present method is intended to be used as a portable device simple enough to be used during vigorous exercise such as cycling or running and to give the user an immediate feedback as to his RER at any time. Additional important benefits of RQ measurement have come to light with recent advances in our understanding of the metabolic conditions that govern transcription of proteins associated with autophagy and mitochondrial energy production. The well-known life extending benefits of calorie restriction are dependent on basal autophagy, an intracellular "house cleaning" process. Aging and age related diseases are associated with impairment of mitochondrial energy production and autophagy. Low RQ is associated with the secretion of the hormone glucagon which enhances autophagy and mitochondrial biogenesis. A high RQ is associated with insulin secretion and cell signaling that decreases production of proterns involved in autophagy and mitochondrial energy production. Because RQ illustrates the metabolic switch between these two contrasting circumstances it can be useful to help guide lifestyle and nutritional choices that favour health, fitness, weight control, and healthy aging. By ensuring RQ at rest and after meals is sufficiently low the presently described RER/RQ monitor can be used to help manage treatments requiring ketogenic diets for example epilepsy management. In addition recent evidence suggests neurodegenerative diseases and dementias can be improved by ketogenic diets through enhancement of mitochondrial function. Regarding prevention of obesity, RQ monitoring is an objective guide to effective treatment no matter what strategy is employed, calorie restriction, fat restriction, carbohydrate restriction, ketogenic diets,

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exercise, or a combination of the above: in any event weight loss must be achieved through a lengthy period of increased fat oxidation as evidenced by low RQ.

Previously used Methods to measure RER/RQ Commercially available methods to calculate RER use volume of C02 produced and the volume of oxygen consumed from gas exchange in the lungs employing gas flow measurement of breathing and the equation RER = VCO2/V02. These gas collection methods use a complex breath by breath analysis or a mixing chamber, both need an associated device to measure breathing volumes and require collection and accurate measurement of the totality of a subject's expired breath using a tightly fitting mask or mouthpiece; UK patent 0623245.8 describes such a device.

The breath by breath techniques as exemplified in US Patent 4,463,764, August1984 have the added disadvantage of not only measuring inspired and expired flow but accurately phase matching flow and concentrations of C02 and 02 and then integrating instantaneous measurements over a breath to compute VCO2 and V02 for each breath, a method that produces highly variable results for RER that have to be averaged over time in any event. The mixing chamber techniques require collection of large volumes of expired gas using wide bore tubing and a large (2 litre) remotely situated mixing chamber. Because of their expense and complexity such methods are generally confined to clinical investigation and laboratory settings.

A seldom used method employing gas fractions alone without measuring volumes has been described but heretofore has never been commercially implemented and the present invention applies to this methodology. The Gas Fraction Methods of calculating RER/RQ were first described by Rahn and Fenn, American Physiological Society, 1955. Leigh et al published the equations used in the present invention in 1972. The principle has been validated most recently by a Danish group in "Assessment of the RER by a standard anaesthetic gas analyzer". Waldau et al, Acta Anaes Scand 2002.

US patent 6,884,222 describes a volumeless method to be applied to the measurement of respiratory quotient in the resting state only. The method requires collection and sampling of all expired gas via a completely sealed face mask and measuring instantaneous values of C02 and 02 in order to derive their end tidal values. The described technique uses equations that only approximate RQ as they do not take into consideration the difference in volume of inspired breath and expired breath that occurs when RQ is less than or greater than unity. The measurement method described in US patent 6,884,222 is more complex and costly than the present method as it involves rapid response sensors that are phase matched and computerized wave form analysis for the determination of simultaneous fractions of end-tidal C02 (FETCO2) and FETO2 and inspired (El) C02 and 02 and applying the equation: R = (FETCO2 -FICO2)/(F102 -FETO2).

This method was found to be inadequate for several reasons: a) The requirement for a tight fitting mask is obtrusive, uncomfortable and causes the subject to adopt abnormal breathing patterns that are not reflective of RQ at rest.

b) The method described teaches a complicated technique of conscious "normal breathing" followed by breath holding for several seconds and then applying the mask to give a forced expiration through it, a technique that gives a wholly distorted and elevated value of RQ.

c) The method involving wearing a face mask is not suitable for prolonged, continuous measurement and is not suitable for ambulant situations involving exercise, running or cycling.

d) One of the most important applications of the present method is exercise physiology for the detection of lactate threshold for which US patent 6,884,222 is wholly unsuited.

5ujnmrycfthcdnyerition In order to overcome the failings of US patent 6,884,222, the present invention uses constant sampling of a small proportion of expired breathing via an inconspicuous sampling tube (8 in figures i & 2) directed to a suitably proportioned mixing chamber (2) where sensors for CO2 and Oz (4 & ) measure a steady mixture of expired gas. The mixture so collected is similar to mixed expired gas concentrations but does not necessarily correspond to the official scientific definition of mixed expired gas as that value is not a limitation to the accurate calculation of RER by the fractional method described by Leigh et al, Brit J Anaesth. 1972, 44, 662

Description of the Invention

The invention is an apparatus functioning as a system illustrated in the schematic drawing figure i. The components consist of plastic disposable parts (1,2,7,8,g,io) interfacing with permanent electronic sensors, a circuit board, display, power supply and communications ports, housed in a case (6). Figure 2 differs from figure 1 only in the method of sampling a breath via a tube positioned In front of the mouth while figure i shows a nasal cannula.

The purpose ol the invention is to passively collect a portion of expired breaths via a small nasal or oral sanipling tube(s) and direct the subsequent gas flow via low resistance tubing () to an appropriately sized small mixing chamber (7). The mixing chamber (2) would typicaily be disposable and 5i connected to a sensing chamber () contained within the housing unit (6) of the sensors, circuit board and display. Contained within the case (6) are sensitive oxygen and carbon dioxide sensors (4 & 5) that measure gas concentrations witnin the sensing tube (3) in order br tile computer housed in (6) to calculate respiratory exchange ratio (F. ER) by applying the following formulae: RS = FECO2 / FIO2-FEO2 and RER = RS(1-F102) / 1(RS*FlO2) Alternatively: RER = FECO2 I [FIO2(1-FEO2-FECO2/1-FIO2) -FEO2] 2. Expired gas is directed passively to the mixing chamber (2) by virtue of positive pressure at the orifice of the sample tub-c(S) created by expired gas flow, Reverse gas flow back towards the nose or mouth to be expected with negative pressure during inspiration is prevented by one way valve action at the exit (7) of the sensing chamber (i) and/or in the tubing (i) before the entrance to the mixing chamber (2).

3. The valve (i) at the exit to the sensor chamber () is the preferred embodiment as it acts to prevent dilution of expired gas from ambient air at the outflow of the sensor chamber (3).

4. The volume ol the expired gas flow sampled is controlled by the resistance to flow by virtue of varying the length and internal radius of the sample tubes (i & 8). The expected flow from the saniple tube is a function of the resistance to flow and the force of breathing at the nose or mouth. Resistance to flow in the apparatus is inversely proportional to the internal radius cubed and directly proportional to the length of the sampie tube. Experiments with prototypes have confirmed that % of expired air can be sampled and adequate;*y mixed with a time constant of around 2 minutes with the presently described apparatus.

5. Breath collection can be from nose breathing or mouth breathing and an ear harness () can be used to secure the position of an oral or nasal cannula with the addition of a small elastic headband (ii).

6. Downstream from the one way valve (7) exiting; the sensing chamber () is a variable control restrictor (10) that can he used to increase the resistance to flow through the system. The purpose of increasing the restriction is to decrease the sampling Flow rate which might he necessary when exercising where the force 01 expiration and minute ventilation are anticipated to increase dramatically arid might resuit in poor mixing and oscllatng gas concentrations.

7. The size of the mixing chamber must be proportionate to the expected flow from the sample tube, for exan pIe: Collection of i% of the expired air provdes approximately 70 mI/mm flow rate (i% of the expired minute ventilation of a typical 7 L]min at rest) and therefore a mixing chamber size of at least 35 ml would be required to provide steady concentrations of mixed expred gas in the mixing chamber with a tme constant of around 30 seconds (where 95% of a step change occurs within 3 times constants).

8. The volume ol the mixing chamber can be reduced by filling the chamber with filtemjdehumnidifier material that adds added function by protecting the sensors from contamnation and humidity.

9. A functioning prototype has produced consistently steady gas concentrations with a step change to 95% within 2 to 3 minutes using a wide bore nasal cannula (8) connected to a 2 meter samnpe (i) tube internal diameter 6 mm and a fluxing chamber (2) consisting of a o ml filter connected to a sensing chamber () and downstream from the sensing chamber a low resistance 2mm one way valve (7) has prevented any reverse flow through the system.

The method of empoyment Measurements of RER are most usefully performed continuously and unobtrusively in the most comfortable way possible for the subject. Several sampling techniques are acceptable and can be guided by user preference and experience. Nasal cannulas (figure 1, 8) are acceptable For the resting condition and the oral cannula (figure 2, 8) or the adjustable (possibly wire reinforced) collection tube with ear harness () are useful For exercise. The printed circuit board can be programmed to automatically quality contr*-l the measurements; such as agunthms set to display a valid REP. if C02 exceeds 2% and give an alarm if It is below that level (this ensures that an adequate sample of expired air is being: collected and directed to the mixing chamber). In addition the circuit board can be set to alarm if undue oscillations of C02 are detected which vvould signify a mismatch between bypass flow and mixing chamber volume which would require adjusting the restrictor to decrease flow until C.02 levels do not oscillate with each breath. The system is capable of unobtrusive, automatic and continuous monitoring. As long as the collection tubes or cannula are satisfactorily placed breath sampling and RER calculations can proceed indefinitely as required by the user in an automated fashion. Because the collection tubes are inconspicuous it aflcws the subject to quickly forget about conscious breathing which is necessary to achieve a steady state where RER closely approximates RQ. During exercise testing the subjects breathing will be driven by metabolic demands and RER data can he obtained automatically with no particular manipulations as described as necessary in US patent 6,884,222.