Exercise and the IC, EELV and Vt/IC ratio

Determining whether a subject has a ventilatory limitation to exercise used to be fairly simple since it was based solely on the maximum minute ventilation (Ve) as a percent of predicted. There has been some mild controversy about how the predicted maximum ventilation is derived (FEV1 x 35, FEV1 x 40 or measured MVV) but these don’t affect the overall approach. Several decades ago however, it was realized that subjects with COPD tended to hyperinflate when their ventilation increased and that this hyperinflation could act to limit their maximum ventilation at levels below that predicted by minute ventilation alone.

The fact that FRC could change during exercise was hypothesized by numerous investigators but the ability to measure FRC under these conditions is technically difficult and this led to somewhat contradictory results. About 25 years ago it was realized that it wasn’t necessary to measure FRC, just the change in FRC and that this could be done with an Inspiratory Capacity (IC) measurement.

The maximum ventilatory capacity for any given individual is generally limited by their maximum flow-volume loop envelope. When a person with normal lungs exercises both their tidal volume and their inspiratory and expiratory flow rates increase.

Exercise_FVL_Normal

Exercise_VT_Normal

Even when maximum exercise has been attained however, flow rates tend to remain well within the maximal flow-volume loop envelope. and ventilation tends to remain around FRC.

Note: The end-exhalation volume during exercise in individuals with normal lung function often decreases below the resting FRC. Although this requires an additional expiratory effort, the elasticity of the rib cage and deformation of the abdominal wall causes this energy to be recovered during inhalation which allows tidal volume to increase with little increase in energy expenditure.

The increased compliance seen in COPD causes an increase in the time constant for lung emptying and this is due to a decrease in static lung recoil pressure and an increase in airway resistance. Expiratory flow limitation (EFL), if not already present at rest, will usually occur with relatively low increases in tidal volume and expiratory flow rates. When ventilation increases during exercise the time available for exhalation is usually not sufficient for the end-expiratory lung volume (EELV) to return to its resting level. When this occurs it is usually referred to as dynamic hyperinflation.

Exercise FVL COPD

Exercise_VT_COPD

In patients with COPD, the increases in tidal volume that occur during exercise occur primarily within the IC. An individual with COPD may already be hyperinflated at rest which limits the available IC, and with dynamic hyperinflation IC will decrease further. In addition, as end-inspiration approaches TLC, the work of breathing increases rapidly (and this applies to everyone, not just those with COPD) due to decreasing compliance, an increasing elastic load and to the fact the respiratory muscle fibers are maximally shortened, and this acts as a further limitation to increases in tidal volume.

During exercise a subject’s FRC is referred to as the End-Expiratory Lung Volume (EELV). Changes in EELV are monitored by having a subject perform an IC maneuver at rest and then at regular intervals during testing, but it should not be performed more frequently than once every two to three minutes. This is partly because these extra deep breaths will alter gas exchange (VO2, VCO2 and RER) and partly because it is necessary to give the subject time to return to their normal EELV.

Since changes in EELV are being determined by relatively few measurements, the quality of each measurement is important. The most common issue causing suboptimal IC measurements is likely cuing the subject to start the IC improperly, and most specifically, cuing the subject after inspiration has already started. It should be remembered that it takes time for anybody to process verbal commands and for this reason, the instruction to start the IC maneuver should be completed just before the end of the subject’s exhalation. This gives them time to comprehend the request and then to be able to perform an IC maneuver without any hesitation. If the subject is cued once inspiration has already started, then the IC maneuver will likely include a significant hesitation and may be underestimated.

FVL_Late_IC

Most CPET systems that allow IC maneuvers to be performed will display the subject’s tidal flow-volume loops, often within the individual’s maximal flow-volume loop if that was obtained on the same testing system. The position of the tidal flow-volume loop is determined by the IC and the tidal flow-volume loops that precede and follow the IC maneuver will be recorded along with the IC maneuver. Although CPET system software will usually attempt to measure and report the EELV and IC automatically, this always needs to be verified. One factor that can make this verification difficult is a combination of volume integration drift and collecting too many tidal loops either before or after the IC maneuver.

Specifically, all CPET systems use a flow sensor of one kind or another. The flow signal needs to be integrated to derive tidal volume and there are differences in temperature, humidity and gas composition between inhaled and exhaled air. Ideally, a flow sensor should be characterized with sufficient accuracy so that the inspiratory and expiratory volumes are equal and the EELV remains constant. Practically speaking however, this is exceptionally difficult and there is usually some discrepancy between inspiratory and expiratory volumes and for this reason there is usually some drift in the position of the EELV.

IC maneuvers must be verified visually and depending on the resolution of the graphics (whether displayed on-screen or printed) and how many tidal loops were collected either before or after the IC maneuver, it can be difficult to determine where EELV was actually located.

FVL_Drift

Once accurate IC measurements have been obtained there are a number of informative calculations can be made.

FVL_Lung_Volume_Subdivisions

ΔEELV:

An EELV measured during exercise should be compared to the baseline IC made at rest:

A positive ΔEELV indicates that the EELV has increased and depending on the amount of change, could be considered a sign of dynamic hyperinflation. Currently, there is no standard for the amount of increase that is definitive for dynamic hyperinflation, but a number of investigators have indicated that an increase in EELV at peak exercise that is 0.20L is probably within normal limits and one that is 0.25 L is likely significant. A negative ΔEELV indicates that the EELV has decreased below the resting FRC and this frequently seen in individuals with normal lung function.

Vt/IC ratio:

The Tidal Volume/Inspiratory Capacity ratio (Vt/IC) can be used as an aid in determining ventilatory reserves. In individuals with normal lung function the Vt/IC ratio at peak exercise is usually between 0.60 and 0.75. A Vt/IC ratio above 0.75 indicates the individual has a limited ability to increase their tidal volume and above 0.85 their end-inspiration is near TLC and the work of breathing is quite high.

Note: A Vt/IC ratio > 1.00 most likely means that the IC measurement was underestimated since by definition Vt cannot be greater than IC.

Due to hyperinflation, individuals with COPD may reach their maximum ventilatory capacity at a minute ventilation below what is traditionally considered as ventilatory limit (i.e. Ve > 85% of predicted) and this should be considered as a likelihood when their Vt/IC ratio is 0.85.

Conversely, there are individuals with more normal lung function that will have a Vt/IC ratio below 0.60 at peak exercise. This can mean a variety of things, first of which is that their primary limitation to exercise is cardiovascular, neuromuscular or musculo-skeletal rather than pulmonary, or it can just mean poor motivation.

Note: Interestingly, there are also individuals that adopt a low tidal volume, high respiratory rate response to exercise. Possible reasons for this include a reduced lung compliance, an increased respiratory drive or psychogenic causes. Regardless, it is an inefficient ventilatory response to exercise with a high Vd/Vt that will also skew Ve/VCO2 upwards. These individuals will have a low Vt/IC, high RR and a normal-ish maximum minute ventilation.

EILV/TLC:

If lung volumes are measured prior to exercise, then the End-Inspiratory Lung Volume/Total Lung Capacity ratio (EILV/TLC) can also be calculated. EILV is calculated from Vt and EELV as:

where:

Or alternately:

where:

An EILV/IC ratio >0.90 is similar, but perhaps more precise than a Vt/IC ratio >0.85 in that indicates that the end of inspiration is occurring at lung volume with an exceptionally high work of breathing. At least one study has indicated that the dyspnea during exercise was primarily related to the EILV/TLC ratio and IRV and only secondarily related to increases in EELV.


As with all pulmonary function measurements, a certain amount of care is necessary in performing and evaluating exercise IC measurements. Submaximal IC measurements will cause an apparent increase in EELV that is not real so it should be remembered that changes in IC are usually not abrupt. In addition, at the highest levels of exercise, when ventilatory demands are the greatest, it may be difficult for a patient to perform an IC maneuver correctly. When dynamic hyperinflation occurs, it usually occurs steadily from one IC measurement to the next. For these reasons, if there is a significant increase in EELV but this only occurs at peak exercise it should probably be ignored.

Some researchers have advocated measuring how much of the tidal expiratory loop contacts the maximal expiratory flow-volume loop envelope and using this a method for determining the degree of expiratory flow limitation. The position of the tidal flow-volume loop however, is highly dependent on the quality of the IC measurement. This, and the fact that the clinical significance that the amount of EFL gives (other than being present or absent) is unclear has meant that this type of measurement not commonly made.

Expiratory flow limitation and dynamic hyperinflation can occur in any individual with airway obstruction. Studies have shown this occurring in patients with asthma and cystic fibrosis as well as those with emphysema. My lab performs IC measurements on all CPET patients regardless of whether they have airway obstruction or not, and have found the additional information is always useful to one degree or another. At the very least it provides insight into the trajectory of increases in ventilation (Vt, RR, Ve) during exercise. More importantly, dynamic hyperinflation is both a powerful contributor to dyspnea and a significant limiting factor to an individual’s maximum exercise capacity. Decreases in IC during exercise can clearly identify those patients for whom this occurs.

Note: One final comment and that is I’ve had the chance to work with CPET systems from only a small number of manufacturers. For this reason I am far from sure how universal a findings this is but none of them have allowed the ability to modify any of the automatically measured IC’s and so the ΔEELV‘s and Vt/IC ratios that appear in the CPET system reports are often wrong. It’s not clear how this should be corrected and I suppose the answer, if there is one, will differ from one system to another. My approach to correcting this (and many of the other problems with CPET reports) is time consuming and highly idiosyncratic, and I will save it for a general discussion of tests with reporting problems.

References:

ATS/ACCP Statement on cardiopulmonary exercise testing. Amer J Respir Crit Care Med 2003; 167(1): 211-277.

Gagnon P, Guenette JA, Langer D, Laviolette L, Mainguy V, Maltais F, Ribeiro F, Saey D. Pathogenesis of hyperinflation in chronic obstructive pulmonary disease. Int J COPD 2014; 9: 187-201.

Guenette JA, Webb KA, O’Donnell DE. Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD? Eur Respir J 2012; 40: 322-329

Henke KG, Sharratt M, Pegelow D, Dempsey JA. Regulation of end-expiratory lung volume during exercise. J Appl Physiol 1988; 64(1): 135-146.

Johnson BD, Weisman IM, Zeballos RJ, Beck KC. Emerging concepts in the evaluation of ventilatory limitation during exercise: The exercise tidal flow-volume loops. Chest 1999; 116: 488-503.

Kosmas EN, Milic-Emili J, Polychronaki A, Dimitroulis I, Retsou S, Gaga M, Koutsoukou A, Rousshos C, Koulouris NG. Exercise-induced flow limitation, dynamic hyperinflation and exercsie capacity in patients with bronchial asthma. Eur Respir J 2004; 24: 378-384.

O’Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 158: 1557-1565.

O’Donnell DE, Laveneziana P. Physiology and consequences of lung hyperinflation in COPD. Eur Respir Rev 2006; 15: 61-67.

O’Donnell DE. Hyperinflation, dyspnea and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006; 3: 180-184.

Pellegrino R, Brusasco V, Rodarte JR, Babb TG. Expiratory flow limitation and regulation of end-expiratory lung volume during exercise. J Appl Physiol 1993; 74(5): 2552-2558.

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