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Emerging Concepts in the Evaluation of Ventilatory Limitation During Exercise*: The Exercise Tidal Flow-Volume Loop FREE TO VIEW

Bruce D. Johnson, PhD; Idelle M. Weisman, MD, FCCP; R. Jorge Zeballos, MD; Ken C. Beck, PhD
Author and Funding Information

*From the Division of Cardiovascular Disease (Dr. Johnson), and the Division of Thoracic Disease (Dr. Beck), Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN; Department of Clinical Investigation (Drs. Weisman and Zeballos), Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, TX.

Correspondence to: Bruce D. Johnson, PhD, Division of Cardiovascular Diseases, Baldwin 2B, Mayo Clinic and Foundation, Rochester, MN 55905; e-mail: johnson.bruce@mayo.edu



Chest. 1999;116(2):488-503. doi:10.1378/chest.116.2.488
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Traditionally, ventilatory limitation (constraint) during exercise has been determined by measuring the ventilatory reserve or how close the minute ventilation (V̇e) achieved during exercise (ie, ventilatory demand) approaches the maximal voluntary ventilation (MVV) or some estimate of the MVV (ie, ventilatory capacity). More recently, it has become clear that rarely is the MVV breathing pattern adopted during exercise and that the V̇e/MVV relationship tells little about the specific reason(s) for ventilatory constraint. Although it is not a new concept, by measuring the tidal exercise flow-volume (FV) loops (extFVLs) obtained during exercise and plotting them according to a measured end-expiratory lung volume (EELV) within the maximal FV envelope (MFVL), more specific information is provided on the sources (and degree) of ventilatory constraint. This includes the extent of expiratory flow limitation, inspiratory flow reserve, alterations in the regulation of EELV (dynamic hyperinflation), end-inspiratory lung volume relative to total lung capacity (or tidal volume/inspiratory capacity), and a proposed estimate of ventilatory capacity based on the shape of the MFVL and the breathing pattern adopted during exercise. By assessing these types of changes, the degree of ventilatory constraint can be quantified and a more thorough interpretation of the cardiopulmonary exercise response is possible. This review will focus on the potential role of plotting the extFVL within the MFVL for determination of ventilatory constraint during exercise in the clinical setting. Important physiologic concepts, measurements, and limitations obtained from this type of analysis will be defined and discussed.

Figures in this Article

Abbreviations: CHF = congestive heart failure; CPET = cardiopulmonary exercise testing; EELV = end-expiratory lung volume; EILV = end-inspiratory lung volume; extFVL = tidal exercise FV loop; FRC = functional residual capacity; FV = flow-volume; IC = inspiratory capacity; ILD = interstitial lung disease; MEF = maximal expiratory flow; MFVL = maximal flow-volume envelope; MVV = maximal voluntary ventilation; RV = residual volume; TE = estimated expiratory duration time; TLC = total lung capacity; ΔV = equal volume segments; VC = vital capacity; V̇e = minute ventilation; V̇eCAP = estimate of the ventilatory capacity based on the end-expiratory lung volume and the maximal expiratory/inspiratory flows available over the range of the tidal breath; V̇o2 = oxygen consumption; Vt = tidal volume; WOB = work of breathing

Cardiopulmonary exercise testing (CPET) is increasingly being utilized in many clinical settings for the diagnostic evaluation of dyspnea on exertion and exercise intolerance.1CPET provides an objective assessment of functional impairment and is valuable in identifying mechanisms of exercise limitation, typically of cardiac or pulmonary origin.24 One challenging task in the interpretation of CPET is the diagnosis of exercise limitation caused by ventilatory constraints. Assessing the degree of ventilatory constraint (limitation) has traditionally been based on the ventilatory reserve or on how close the peak minute ventilation (V̇e) achieved during exercise approaches the maximal voluntary ventilation (MVV) or some estimate of the MVV (typically the FEV1 multiplied by 35 or 40).

The ventilatory reserve is dependent on numerous factors, including the following: (1) ventilatory demand, which is dependent on factors such as metabolic demand, body weight, mode of testing, dead space ventilation, as well as neuroregulatory and behavioral factors; vs (2) maximal ventilatory capacity, which is affected by mechanical factors, ventilatory muscle function, genetic endowment, aging, and disease. Ventilatory capacity may also vary during exercise due to bronchodilation or bronchoconstriction,5 and it is dependent on the lung volume where tidal breathing occurs relative to total lung capacity (TLC) and residual volume (RV; ie, the regulation of end-inspiratory lung volume [EILV] and end-expiratory lung volume [EELV]). In the latter case, breathing at a low lung volume (near RV) limits the available ventilatory reserve due to the shape of the expiratory flow-volume (FV) curve and the reduced maximal available airflows, as well as a reduced chest wall compliance. Conversely, breathing at high lung volumes (near TLC) increases the inspiratory elastic load and therefore the work of breathing (WOB). The breathing reserve using the MVV therefore only provides limited information and does not provide insight on breathing strategy or the degree of expiratory or inspiratory flow constraints. Understandably, significant controversy thus surrounds the assessment of the ventilatory reserve in part because of a lack of a definitive measurement of ventilatory capacity.

More sophisticated techniques have thus been applied to assess the degree of ventilatory constraint during exercise.511 These have included the following: increased dead space loading12; hypercapnic stimulation8,1314; heliox administration1517; and negative pressure applied at the mouth.10 However, these techniques also provide little information on breathing strategy and, apart from the negative pressure technique, tell little about the specific source of ventilatory constraint.

Though not a new concept,1820 plotting the tidal exercise FV loops (extFVL) within the maximal FV envelope (MFVL) and assessing the degree of expiratory flow limitation have been used by several investigators to better assess and quantify the degree of ventilatory constraint.59,12,14,2123 This, of course, is critically dependent on the placement of the extFVL within the MFVL (to be discussed), but provides a unique visual index of ventilatory demand vs ventilatory capacity. Although this technique is gaining popularity as a means of assessing the degree of ventilatory limitation, (and complementary to the traditional estimates of breathing reserve) it remains technically more involved than traditional estimates and indices of limitation based on the extFVL need to be further defined, quantified, and assessed for utility in the clinical setting.

The following review will focus on the potential role of plotting the extFVL within the MFVL for determination of ventilatory constraint during exercise in the clinical setting. Based on previous studies, important physiologic concepts and measurements obtained from this type of analysis will be reviewed and defined. Advantages and limitations of the technique relative to traditional methods will be discussed, as well as technical concerns when performing the measurements. Examples of FV responses to exercise in health and disease will be examined, as well as suggestions for further investigation.

By aligning the extFVL within the MFVL, specific information is provided on the following: (1) the degree of expiratory flow limitation; (2) breathing strategy (ie, changes in EELV); (3) elastic load, as represented by the EILV as a percent of TLC (EILV/TLC) or the tidal volume (Vt) relative to inspiratory capacity (IC); (4) inspiratory flow reserve; and (5) a theoretical estimate of the ventilatory capacity based on the EELV and the maximal expiratory/inspiratory flows available over the range of the tidal breath (V̇eCAP).5,18,20

Definition of Expiratory Flow Limitation and EELV

The degree of expiratory flow limitation (or impending flow limitation) during exercise has been previously expressed as the percent of the Vt (obtained from the extFVL) that meets or exceeds the expiratory boundary of the MFVL5,78 (as shown in Figure 1 ). The degree of expiratory airflow limitation is therefore a balance between ventilatory demand and ventilatory capacity combined with the way subjects “choose” to regulate their EELV. The EELV differs from the resting functional residual capacity (FRC) in that the FRC is the lung volume achieved with a passive expiration and is thought to be an equilibrium volume between the chest wall forces expanding the lungs and the recoil forces of the lungs; the EELV, on the other hand, is dynamically determined (dynamic FRC) based on expiratory and inspiratory muscle recruitment and timing. A drop in EELV requires expiratory muscle recruitment and has been proposed to optimize inspiratory muscle length (for force development). In addition, it helps keep the tidal FV loop on the linear portion of the pressure-volume relationship of the lung and chest wall to reduce the elastic load of breathing (keeps EILV at a lower percent of TLC), provided that Vt remains constant.,7,2425 In addition, the energy stored (elastic and gravitational energy) in the chest wall (rib cage, abdomen, and diaphragm) because of active expiration may provide some passive recoil at the initiation of the ensuing inspiration.2426 On the other hand, a drop in EELV that is too great will cause expiratory-flow limitation near EELV due to the fall in maximal available air flow as lung volume decreases. In most normal subjects (average fitness; < 35 years old; no disease), EELV decreases with exercise, and expiratory airflow limitation generally averages < 25% of the Vt at peak exercise workloads,5,27 and generally occurs only over the lower lung volumes, near EELV.

Breathing Strategy (Regulation of EELV)

During exercise, in the absence of expiratory flow limitation, EELV typically falls; however, when the degree of expiratory airflow limitation becomes significant (> 40 to 50% of the tidal breath), such as may occur with heavier exercise, EELV typically increases,5,7,14 sometimes back to resting values or higher (dynamic hyperinflation). This is not typically observed in healthy individuals of average fitness and thus represents a change in the normal breathing strategy during exercise. An acute increase in EELV decreases inspiratory muscle length, increases the work and oxygen cost of breathing, and decreases inspiratory muscle endurance time.28 Thus the change in EELV (as noted above) likely is another index of ventilatory constraint. This has generally been expressed as a relative change from rest; however, it may be as important to observe the change in EELV with increasing workloads, because some subjects may demonstrate an initial decrease followed by a substantial increase.7 Studies examining changes in EELV with exercise have reported this as a change in EELV, IC, or they have expressed the EELV or IC in relationship to fixed lung volumes, such as the TLC or vital capacity (VC). The IC relative to VC gives a good index of where subjects are breathing within their operational limits.

Change in EILV

EILV is defined as the lung volume at the end of a tidal inspiratory breath and is usually expressed as a percent of the TLC (EILV/TLC). Studies that do not determine TLC express this as a percent of full inflation volume VC, or may express Vt relative to IC. Previous studies have demonstrated that EILV reaches 75 to 90% of TLC in heavy exercise in normal subjects.14,29 As EILV approaches TLC, lung compliance begins to fall,29 and thus the inspiratory elastic load increases. A high EILV (> 90%) relative to TLC may also be a marker of ventilatory constraint and an index of increased ventilatory muscle work.23,30 As ventilatory demand increases and the subject increases EELV in order to avoid expiratory flow limitation and to take advantage of the higher available maximal expiratory airflows, EILV increases in order to preserve the exercise Vt. A failure to increase EILV in the presence of significant expiratory flow limitation may represent inspiratory muscle fatigue, inspiratory muscle weakness, or coexistent elastic loading due to increased lung recoil or constraints imposed by the chest wall. A breathing strategy where EILV does not increase with increasing exercise intensity usually results in an increase in the respiratory rate to augment ventilation. This strategy may initially decrease the WOB, decrease intrathoracic pressure perturbations, and alleviate unpleasant respiratory sensations associated with high lung volumes. However, the increased breathing frequency causes higher flow rates which, in turn, may further increase the degree of expiratory flow limitation. This is an example where it is important to examine multiple variables, including breathing frequency and degree of dyspnea in order to accurately interpret the extFVL.

Inspiratory Flow Capacity

Few studies have investigated the degree to which inspiratory flows approach inspiratory flow capacity during heavy exercise.8,14,21,23,31 Because maximal inspiratory flows are limited mainly by the ability of the inspiratory muscles to develop pressure, it is likely that an index of exercise inspiratory flow relative to maximal volitional inspiratory flows would provide an assessment of inspiratory muscle constraint. The ability of the inspiratory muscles to produce pressure (force) falls with higher lung volumes (shorter muscle lengths) and higher flow rates (increased velocity of muscle shortening).8,3132 Previous studies8,14 have suggested that the fall in the ability to produce inspiratory pressure decreases from 0.65 to 0.97% for every 1% increase in lung volume above FRC, and decreases from 4 to 5% for every 1 L/s increase in inspiratory flow rate above resting.

The lung volume where exercise inspiratory flow rates are closest to maximal may not be where peak inspiratory flows are produced (typically at mid to lower lung volumes), but may occur at the higher lung volumes (70 to 85% of TLC) where demand for increased flow rates remains high during exercise but where capacity is reduced due to shortened muscle lengths.8,14 An example is shown in Figure 2 of the extFVL within the MFVL: the point where tidal inspiratory flows come closest to capacity typically occur at the higher lung volumes with heavy exercise (right, B), although at the lower ventilatory demands (left, A), significant reserve is observed throughout inspiration. A fall in maximal volitional inspiratory flows (at a given lung volume) during or after exercise would suggest inspiratory muscle fatigue, or less likely a change in peripheral airway diameter,33 or laryngeal dysfunction (although patient effort may also contribute significantly). Tidal inspiratory flows produced during exercise that come close to or meet those obtained during maximal volitional effort at rest would imply an inspiratory pressure demand near to capacity.14 In normal subjects, flows during exercise typically only reach 50 to 70% of the maximal volitional inspiratory flows at the closest point during the inspiratory cycle (Fig 2, left, A).,8,14 Expiratory flow limitation and a rising EELV would clearly reduce the available inspiratory reserves if Vt remained unchanged (Fig 2, right, B).

Estimated V̇eCAP

A number of techniques have been used to estimate a ventilatory capacity.5,7,1213,16,20 One technique (V̇eCAP) calculates a theoretical maximal exercise ventilation based on the maximal available inspiratory and expiratory airflows over the range of the tidal exercise breath placed at the measured EELV.,5,12,20 Such an estimate of V̇eCAP is not dependent on volitional effort to the same extent as the MVV, and it takes into account the breathing pattern and the dynamic changes in airway function (if MFVLs are obtained near to the time the extFVLs are obtained). The methods used for the determination of V̇eCAP are shown in Figure 3 . Briefly, the extFVL is aligned within the MFVL according to the measured EELV. The tidal breath is divided into equal volume segments (ΔV; typically 50 segments). An estimated expiratory duration time (TE) is determined by dividing each ΔV by the average maximal expiratory flow (MEF) within each volume segment and summing all such times (ΣTe) over the expiratory phase of Vt. Measured inspiratory to total breathing cycle time is used to estimate inspiratory time. The sum of minimal inspiratory time and TE gives a minimal breathing cycle time and maximal breathing frequency. The product of maximal breathing frequency and measured Vt equals V̇eCAP. V̇eCAP determined in this manner has been shown to decrease with low level exercise in normal subjects (secondary to a decrease in EELV) and to subsequently increase significantly as Vt increases through encroachment on the inspiratory reserve volume.,5 This technique represents a true maximal V̇eCAP for a given breathing strategy. Typically, the V̇eCAP will be related to the degree of expiratory flow limitation; however, if no flow limitation exists (ie, tidal expiratory flows do not meet or exceed the maximal available flows at any point throughout expiration), this gives an independent index of the available ventilation for a given breathing pattern.

The traditional use of the MVV or some estimate of the MVV such as the FEV1 multiplied by 35 or 40 relative to the exercise ventilation as an assessment of breathing reserve has several advantages. It provides a general (although variable) approximation of ventilatory capacity, it is readily and widely applied, it is easily understood, and it requires minimal analysis. However, the use of the MVV to estimate the available ventilatory capacity during exercise and to determine whether or not individuals have a mechanical limitation to their ventilation has many shortcomings. For example, Figure 4 illustrates the FV loops obtained while a subject performs the typical 12- to 15-s MVV maneuver vs the same subject exercising near maximum on a stationary cycle ergometer. Significant differences exist in the breathing patterns, highlighting the difference between a voluntary and a reflex-mediated hyperpnea. Typically, the MVV is performed above the resting FRC, EILV approaches TLC, and expiratory flows reach maximum even at the highest lung volumes.34 Although not shown, the expiratory pleural pressures needed to produce such high flows early in expiration are excessive and over the mid to lower lung volumes, often two to three times those necessary to produce maximal flows. The high EILV/TLC greatly increases the elastic load to breathing, and tidal inspiratory flows often equal those produced during a maximal maneuver over a significant portion of the tidal breath. Thus the MVV does not represent that pattern typically observed or even available to the typical patient during exercise.34 A previous study by Klas and Dempsey34 in 1989 demonstrated that the WOB associated with the MVV maneuver greatly exceeded that achieved when the hyperpnea was reflexly driven as occurs during exercise. Other studies have shown that the MVV cannot be carried out for > 15 to 30 s, confirming the excessive work and cost associated with the maneuver.28,32,34 Use of the exercise V̇e relative to the MVV also does not tell specific information about the source or type of ventilatory constraint (eg, expiratory flow limitation, inspiratory flow limitation, or high inspiratory elastic load). The MVV also is motivationally dependent, and it is unclear if a consistent relationship exists between the exercise ventilation and the MVV that represents enough ventilatory constraint to influence the perception of dyspnea or exercise tolerance.

Plotting the extFVL within the boundaries imposed by the MFVL allows specific assessment and quantification of the sources of mechanical constraint, and it complements other measurements obtained during CPET (eg, breathing frequency and Vt). It is not as motivationally dependent as the MVV maneuver, but it does add a degree of complexity to the testing and analysis. The technique is also highly dependent on accurate assessment of EELV, and although many studies have reported reproducible measurements based on IC maneuvers in various patient populations, its reproducibility in the typical clinical setting remains to be determined. Improving technology has minimized many of the difficulties in data collection; however, precautions need to be taken to ensure the accurate placement of the tidal loops, to correct for drift in flow signals, and to determine the optimal maximal volitional FV envelope. These later issues remain critical in the use of the extFVL to assess ventilatory constraint, and they are reviewed in greater detail in the Appendix.

As the sophistication of conventional exercise systems improve, it will become easier to measure and to assess the degree of flow limitation as well as changes in EELV and EILV, with minimal changes in the standard clinical exercise protocol. Conventional exercise metabolic systems have evolved using the pneumotachograph, hot wire anemometer, and turbine (bi-directional rotating vane) technology that provide software to evaluate tidal breathing FV loops relative to a MFVL. Although there are currently potential sources of error in these systems and in this type of analysis, a careful systematic approach will help eliminate many of these problems.

Baseline MFVL and EELV

The majority of studies using the extFVL to assess V̇e constraint have had subjects perform several pre-exercise maximal expiratory and inspiratory maneuvers between TLC and RV to define the reference MFVL. The largest MFVL is determined in accordance with the American Thoracic Society standards (ie, the MFVL with the largest combination of FEV1 and FVC).35 In addition to performing these maximal maneuvers, a series of four or five expiratory maneuvers performed between TLC and RV at different efforts can be performed to help correct for possible expiratory gas compression (see Appendix, “Defining the MFVL” section). However, this adds an additional degree of complexity to the testing and analysis, and its necessity in all patient populations is undetermined.

To assess variations in EELV during exercise, several IC maneuvers are also performed at rest until several reproducible measurements are obtained. The initial instructions at rest are important for optimal measurements of EELV during exercise. The resting FV loops are obtained when the subject is relaxed and in a regular breathing pattern (several tidal breaths are recorded prior to obtaining an IC maneuver), typically with the subject in the standing or sitting position (depending on the use of a treadmill or cycle ergometer).

Exercise Measurements

Most clinical exercise protocols consist of an incremental study with stages of 1 to 3 min. Incremental changes in work intensity require changes in breathing strategy as ventilatory demands increase and constraints are approached. Plotting changes over the course of the study will allow a detailed assessment of the breathing strategies chosen. Constant work exercise studies are also becoming more frequent in the clinical setting, as workloads may be sought that more closely match the metabolic demands associated with tasks of daily living. Unlike incremental exercise, the variations in ventilatory demand during constant work exercise are limited unless the workload chosen is of a sufficient intensity (nonsteady state).

Tidal exercise breaths can be obtained over the last portion (eg, 30 s) of each exercise stage in the incremental protocols (less frequent in fitter subjects or in stages < 2 min.). Several tidal breaths are collected, followed by an IC maneuver to determine any exercise induced change in EELV. To correct for possible inequalities in inspiratory and expiratory volume due to drift, a second IC maneuver is performed after 5 to 10 additional breaths (see Appendix, “Measurement of the extFVL” section). MFVL maneuvers have been used in conjunction with the IC maneuvers if there is concern over the lability of airway tone (ie, bronchodilation or bronchoconstriction during exercise). Performing the IC maneuvers or even a single MFVL has minimal impact on measurements of oxygen consumption (V̇o2), carbon dioxide production, and V̇e if data are obtained during exercise with averages ≥ 30 s.78,14

Postexercise Measurements

We previously assessed MFVLs similar to baseline measurements within the first 2 min after exercise to correct for a potential bronchodilation that may have occurred during exercise.8,14 Although significant changes were noted in maximal expiratory airflow in older healthy adults (age, ∼ 70 years old), minimal changes were observed after exercise in healthy younger subjects. A previous study by Warren et al36 in 1984 demonstrated that an exercise-induced bronchodilation persisted for up to 4 min after exercise.

Plotting the Data

Reference MFVL: The best pre- and postexercise MFVLs are plotted and set to TLC (or VC) to compare potential changes in inspiratory and expiratory flow and volume. The MFVL with the largest expiratory and inspiratory envelope is used for the reference loop. If MFVLs were obtained during exercise, these can also be compared with the pre- and postexercise MFVL to determine the largest reference loop, or each extFVL can be referenced to the relevant MFVL produced during exercise.5

Tidal Breaths: The tidal breaths prior to the IC or MFVL maneuver obtained at rest or during each stage of exercise are viewed (for outliers), computer averaged, and plotted within the reference MFVL according to the measured IC.5 We have previously performed the averaging of the tidal loops by dividing each Vt into 50 ΔVs and assigning a mean flow value. The flow values are then averaged for each volume segment of each Vt and are plotted according to the mean Vt and measured EELV (TLC − IC).,5 Previous studies have averaged from 2 to > 20 tidal breaths for individual subjects.5,8,14 This greatly reduces the breath-to-breath variability and the potential for error.

Defining the Degree of Constraint

Ventilatory limitation has typically been viewed as an“ all-or-nothing” occurrence. However, past and present literature suggests that the degree of ventilatory constraint incurred during exercise is progressive.5,89,1314,21,23 As the degree of expiratory flow limitation increases, EELV typically rises (dynamic hyperinflation) and the inspiratory elastic load increases. The degree of constraint necessary to influence exercise performance or contribute to the sensation of dyspnea is unclear.30 However, the oxygen cost associated with breathing during exercise rises dramatically as ventilatory constraints (eg, flow limitation) are approached.,9 Also, as ventilatory limits are approached with exercise, the ventilatory response to increased levels of inspired carbon dioxide or reduced levels of inspired oxygen are reduced or absent.8,1314 Thus, clearly the constraints to flow and volume begin to contribute to limiting ventilation and a rising cost of breathing prior to achieving a ventilation that matches the MVV or which may result in a rise in arterial carbon dioxide.

By defining and quantifying the suggested indexes of constraint, a more precise assessment of the degree of mechanical limitation to breathing can be applied. Using these indexes, the degree of constraint can be defined as no or minimal constraint, mild, moderate, or severe rather than the all-or-nothing assessment that is often associated with the MVV (see Table 1 ). Subsequent studies will be necessary to assess the validity of such an assessment in various clinical populations. Use of hypercapnic inspired air, dead space, and helium oxygen mixtures may help confirm the validity of such an assessment to define the degree of constraint.

The following section will review the tidal FV responses to exercise in various representative clinical examples contrasted with responses observed in the healthy young and older adults. It should be emphasized that the degree of ventilatory constraint is indeed a balance between ventilatory demands and the available capacities. Thus, even the healthy young adult may approach severe ventilatory limitations, albeit at a metabolic and ventilatory demand that far exceeds the patient populations.

Healthy Subjects

The ventilatory response to progressive exercise in the typical, average, fit subject (age, 30 years; peak Vo2, 42 mL/kg/min; peak V̇e, 100 L/min) is shown in Figure 5 , left, A.5,14 Little change (from rest) was noted in the expiratory boundary of the MFVL during or after exercise, suggesting little change in airway caliber. Flow limitation was present near peak exercise but over < 20% of the tidal breath and only near EELV. EELV fell by approximately 0.7 L, and EILV increased to 80% of the TLC. Exercise V̇e expressed as a percent of the MVV (estimated from FEV1 × 40) averaged 68% at peak exercise. By visual inspection, it can be seen that substantial room exists to increase both flow and volume. Inspiratory flow only approached 65% of the available inspiratory flow at the closest point of the inspiratory phase. Thus, in young, healthy subjects with average fitness, typically little ventilatory constraint exists during exercise.

Healthy Aged

Aging causes mild to moderate declines in ventilatory capacity as a result of decreased lung elastic recoil (the average FEV1 of a 70-year-old person is 70% of that of an average 25-year-old person). However, this is typically balanced with a fall in demand (ie, decreased peak V̇o2 due to reasons that are not fully appreciated (eg, decreased maximal heart rate, muscle mass, etc).37Figure 5, middle, B shows the mean tidal exercise FV responses in a group of older subjects (age, 70 years old) with an exercise capacity approximately twice age predicted (n = 29; V̇o2, 43 mL/kg/min; V̇e, 119 L/min) but similar metabolic and ventilatory demands as the young average fit adult (shown in Figure 5, left, A) at peak exercise. Thus, this group of older subjects represents a group with relatively high ventilatory demands but with mildly reduced capacities. Flow limitation begins to occur at a lower ventilation than noted in the younger subjects shown in Figure 5, left, A (∼40 L/min) and at peak exercise > 50% of the tidal breath meets or exceeds the expiratory boundary of the MFVL. EELV initially decreases but then begins to increase with these moderate V̇e demands. At peak exercise, EELV is above the resting FRC, EILV reaches > 90% of TLC, and inspiratory flows approach > 90% of the inspiratory flow capacity, indicating little reserve available to increase V̇e and moderate to severe ventilatory constraint. In the more severely constrained subjects, ventilation did not increase with increased levels of inspired carbon dioxide during heavy exercise.,8

Endurance Athlete

To emphasize the fact that ventilatory constraint is not only dependent on ventilatory capacities but also on ventilatory demand, the average response to progressive exercise in group of endurance athletes is shown in Figure 5, right, C (n = 8, age, 25 years old; maximal V̇o2, 74 mL/kg/min; peak V̇e, 170 L/min).14The young athlete represents a group with normal pulmonary function (ie, lung volumes and flow rates) for their age but with excessively high metabolic and thus ventilatory demands. To date, there is little data to suggest that exercise training increases maximal lung volumes or flow rates; however, the ability to sustain a high V̇e may be increased.15 The responses are quite similar to the average fit adult up to a ventilation of approximately 110 to 120 L/min (ie, EELV falls; < 20% Vt is expiratory flow limited; tidal inspiratory flows < 65% of capacity; and EILV < 80% TLC). However, with heavier exercise and the increased ventilatory demands, expiratory flow limitation increases to> 50% of the Vt, EELV begins to increase (approaching the resting FRC), and EILV approaches > 85% of the TLC. Inspiratory flow rates with exercise are closest in proximity to the maximal available inspiratory flow rates at 75% of TLC reaching 6.0 L/s and 95% of the available flow. In this particular group of athletes, the addition of hypoxic and hypercapnic gases during maximal exercise did not significantly increase V̇e further than that achieved breathing room air during maximal exercise, implying a significant ventilatory load and moderate to severe mechanical ventilatory constraint.

Moderate COPD

Patients with moderate airflow obstruction have a reduced ventilatory capacity, and at rest, they may be hyperinflated with some gas tapping.6,23Figure 6 is an example of the typical response observed in a subject with moderate airflow obstruction.6,2223,30 As shown, EELV may increase even with light activity due to the early degree of expiratory flow limitation. Due to the steepness of change in the available expiratory airflows, small increases in EELV (dynamic hyperinflation) will yield significant increases in the available ventilation (V̇eCAP). By peak exercise, flow limitation is present over the entirety of expiration, and inspiratory flows are produced that nearly overlap the maximal inspiratory flows achieved immediately after exercise. In addition, EILV approaches > 95% of TLC. This particular subject had a near normal exercise tolerance for age, but because of the reduced ventilatory capacity, he clearly could not increase V̇e further (V̇e/V̇eCAP > 95%). In patients with more severe COPD and marked hyperinflation, an increase in EELV may not occur due to the very high Vt/IC ratios at rest and during low levels of exercise. In these subjects, the finding that the extFVL coincides with the entire MFVL boundary at low levels of exercise is not uncommon.,18,2223

Interstitial Lung Disease

Patients with interstitial lung disease (ILD) have a reduced VC and EELV at rest.21,38 An example of patients with a history of ILD is shown in Figure 7 . Many patients with ILD have little room for an exercise-induced decline in EELV (due to a reduced expiratory reserve volume and little room for a marked increase in Vt). Thus, they are more dependent on an increase in breathing frequency (and flow) to increase ventilation. In seven patients tested using the extFVL analysis (peak V̇o2 averaged 1.36 L/min; 57% predicted), the majority of patients did not change EELV during exercise.,38 Furthermore, significant expiratory flow limitation and a high EILV/TLC was present in those patients stopping exercise due to dyspnea, whereas no flow limitation was observed in patients stopping exercise due to a complaint of leg fatigue.12 This implies that expiratory flow limitation in some of the ILD patients contributes to the dyspnea of exercise, although additional studies would be necessary to corroborate these findings. Interestingly, despite room to decrease EELV in the patients that did not complain of dyspnea, EELV did not fall. It has been suggested38 that hypoxemia in this population may play a role in altering the more typical regulation of EELV (ie, decrease expiratory muscle activity resulting in a higher EELV).

Congestive Heart Failure

Patients with congestive heart failure (CHF) often have restrictive changes in pulmonary function. Breathing pattern is altered secondary to ventricular dysfunction, increased left ventricular size, muscle weakness, and chronic pulmonary congestion. Although CHF represents a heterogeneous population, recent studies in our laboratory39 have demonstrated that many of these patients breathe at rest near RV and are expiratory flow limited with little or minimal exercise. Figure 8 is an example of FV responses (rest through peak exercise) in a representative subject with New York Heart Association class III CHF (from a study on 11 patients; average peak V̇o2, 17 mL/kg/min; peak V̇e, 56 L/min; ejection fraction< 24%).,39 It is unclear why these patients breathe at reduced lung volumes, but it may be secondary to increased respiratory drive and activation of expiratory muscles, or due to inspiratory muscle weakness. Thus, it is possible that the breathing at the lower lung volumes leading to dynamic compression of airways may contribute to the increased dyspnea associated with exercise; however, like the ILD patients, further studies would be necessary to determine more formally the significance of the expiratory flow limitation. Interestingly, in this patient population, the V̇e/MVV relationship remains within the normal range, suggesting little ventilatory constraint; however, by plotting the extFVL within the MFVL, the expiratory flow constraint is evident.

Additional Applications of the extFVL

In patients with single lung transplantation, EELV increases with the encroachment of expiratory flow limitation (observed in four of seven patients), whereas in patients with double lung transplantation, a more normal decrease in EELV is seen with expiratory flow limitation observed in only one of the patients tested.22

Recent application of the extFVL analysis to lung volume reduction surgery has demonstrated that successful lung volume reduction improves lung recoil and respiratory muscle function as a result of a reduction in dynamic hyperinflation (ie, ↓ EELV and EILV relative to TLC).40

Studies have also used the extFVL to evaluate ventilatory constraint in obesity and asthma.5,41 Interestingly, in the small number of studies performed to date, the data suggest that some obese subjects breathe at extremely low lung volumes at rest and often during exercise despite significant room in the inspiratory reserve volume and substantial expiratory flow limitation. The expiratory flow limitation may contribute to the dyspnea in these obese subjects. Interestingly, this is a group of subjects (like some of the heart-failure patients shown) where the V̇e/MVV relationship suggests significant reserve, when in fact little room exists to increase expiratory flow. Asthmatic subjects, using the extFVL analysis during exercise, experienced greater expiratory flow limitation than age-matched control subjects, but they attempted to defend ventilatory reserve by altering bronchomotor tone and increasing EELV.,5

The use of the extFVL has also been applied to study mechanisms of exertional dyspnea. Several authors23,4244 have demonstrated that dynamic hyperinflation manifested by an increased EELV and EILV relative to TLC and the resultant increased respiratory muscle impedance are major factors responsible for breathlessness during exercise in patients with COPD. In patients with acute bronchoconstriction, the fall in IC (↑ EELV) during exercise showed the strongest correlation with increases in dyspnea and perceived inspiratory difficulty. Patients also complained mostly of inspiratory rather than expiratory difficulty.44

The extFVL analysis is also being used in the evaluation of therapeutic interventions. The acute administration of inhaled albuterol significantly reduced breathlessness during exercise in patients with COPD as a result of decreasing dynamic hyperinflation (↓EILV/TLC and↓ EELV/TLC).23 In addition, there may be a clinical utility to using the change in operational lung volume to determine bronchodilator responsiveness in situations where resting spirometric values do not change appreciably after bronchodilator treatment.

Over the last 30 years, little progress has been made in the typical clinical setting in trying to better define mechanisms of exercise intolerance and dyspnea, particularly when associated with the possibility of mechanical constraints imposed by the respiratory system. The classic MVV, while easily applied, is variable and has proved to be limited in its overall usefulness of advancing our understanding of ventilatory limitation during exercise. As such, investigational studies have attempted other techniques to better assess and quantify the specific type of ventilatory constraint incurred during exercise. Among these techniques, plotting the extFVL within the MFVL, defining specific indexes of constraint based on the relationship of the tidal loops with the constraints imposed by the maximal volitional FV envelope, and attempting to quantify the degree of constraint have the potential to provide unique insights into the role of pulmonary mechanics in the exercise intolerance in various populations.

The technique can be easily integrated into the current CPET with the addition of pre/postmaximal FVC maneuvers as well as tidal FV breaths and serial IC maneuvers collected throughout the study. Critical shortcomings include the ability of subjects to perform adequate IC maneuvers for placement of the extFVL within the MFVL, and defining the optimal MFVL to account for bronchodilation, possible compression of airways, and/or bronchoconstriction. The use of the extFVL in conjunction with other techniques, such as a negative pressure applied at the mouth during expiration, may help circumvent the later potential drawback. In addition, although specific indexes of constraint were suggested, the optimal indexes to be used in clinical populations need further studies and discussion for their utility in the clinical setting. In addition, quantification of the degree of constraint based on the proposed indexes and their association with the degree of ventilatory limitation and symptoms needs further validation. A schema that provides a scaling of the degree of constraint based on the suggested indexes (eg, no limitation, mild, moderate, and severe) may provide more information than the current trend which tends to look at ventilatory limitation as an all-or-nothing phenomena; however, this also needs further investigation.

Measurement of the extFVL

Most clinical exercise testing laboratories today employ automated systems for measurement of gas exchange during exercise (eg, V̇e, V̇o2, and carbon dioxide production). The majority of these systems use a device for measuring flow (eg, pneumotachograph, mass-flow anemometer, turbine) and integrate a flow signal to obtain volume. Few of these automated systems, until recently, have offered continuous output of flow and volume in order to obtain the tidal FV data necessary for plotting the tidal exercise loops; and few, to date, have attempted to identify sources of constraint or to quantify the degree of ventilatory constraint when plotting the extFVL within the MFVL. Thus, the majority of studies examining FV data have been investigationally oriented.56,45 In these research studies, typically two techniques have been used to measure the exercise FV loop: the wedge spirometer (volume-displacement) or the flow-sensing pneumotachograph.67,12,21,23,38 The spirometer and the pneumotachograph as well as the other flow sensing devices each have potential advantages and disadvantages for assessing flow and volume during exercise; however, the majority can be used successfully if appropriately calibrated and utilized.46–49

“Drift” is a problem with all flow/volume sensing devices. Drift can occur in the signal due to electrical changes over time; nonlinearities in the pneumo-tachograph, anemometer, or turbine sensor; as well as physiologic changes (eg, temperature, gas density, viscosity, and humidity).50 Thus, within a breath, there may be significant variability in either inspiratory or expiratory flow and volume. Slight differences in calibration between the inspiratory and expiratory flow signal, acute changes in breathing pattern, and/or a small drift in either or both phases of the respiratory cycle will cause an unequal inspiratory to expiratory (or vice versa) volume and a tidal FV loop that does not fully close or meet (Fig 9 ). Thus, developing appropriate corrections to account for nonlinearities and accurate calibration as well as eliminating physiologic changes (correcting for temperature and humidity changes) will help eliminate drift.,8,50 During exercise, small amounts of drift (< 50 mL/min) can be corrected by performing paired-IC maneuvers at the beginning and end of a recording period.8,14,27 Assuming maximal inhalation volume is equal (TLC) during both maneuvers, the peaks can be aligned by performing an interpolated volume correction between the two points. An example of drift correction by aligning two IC maneuvers is shown in Figure 10, top, A, and bottom, B. Previous studies have demonstrated that TLC does not change significantly during exercise, and it is especially unlikely to change within a 10- to 20-s time period necessary to perform the maneuvers.,29 However, whether or not this holds true in disease populations such as asthma remains to be determined. Another potential source of error occurs when subjects are asked to perform an IC or MFVL maneuver immediately prior to the tidal loops obtained during exercise. Breathing pattern and likely EELV will change transiently after this maneuver; therefore, they should be performed after the tidal loops have been collected or at least separated by an adequate time interval.5,8,14

Placing the Tidal FV Loop Within the MFVL Envelope

The measurement of expiratory flow limitation, inspiratory flow capacity, EILV, EELV, and V̇eCAP are critically dependent on placement of the extFVL within the maximal volitional FV envelope. As noted previously, an IC maneuver can be performed to correct for drift of the volume signal by aligning at the full inflation lung volume (ie, TLC or VC); however, measurement of ICs also provide an index of change in EELV (TLC/IC = EELV) in order to place the extFVL within the MFVL. Changes in EELV have been well studied in a number of populations during exercise.58,29 Most studies have demonstrated an intensity related fall in EELV in normal subjects of 0.5 to 1.0 L.8,14,27 However, with expiratory flow limitation, EELV often rises, sometimes to levels above the resting FRC.67,51 Thus, a precise estimate of this lung volume is necessary, and a resting FRC cannot be used. If two IC maneuvers are performed to correct for small differences in the inspiratory to expiratory volumes (drift) and to place the tidal FV loops, an important assumption is that EELV is not altered by performing the maneuvers. Again, this could occur as subjects prepare to perform an IC or transiently after the maneuver is performed. Thus, two IC maneuvers should be separated by a substantial number of breaths to allow the“ true physiologic” EELV to be achieved, or several breaths should be measured prior to the patient being asked to perform the maneuver. Ideally, the patient is coached to perform the IC maneuver at the end of a normal exhalation, EELV.

Previous studies have used direct measurements of EELV during exercise by inert gas dilution techniques.27,52 The EELV obtained in this manner agrees well with changes in IC in healthy populations, but it may not be useful in patients with airway obstruction (secondary to flow limitation, and airways with varying mechanical time constants and ventilation maldistribution).27 Thus, in most cases, the change in IC likely represents a better estimate of the change in EELV with exercise if performed appropriately. Measurement of the EELV directly requires an increased degree of equipment sophistication relative to the IC maneuver and is not used in the majority of clinical exercise laboratories.27

A potential source of error in the IC maneuver is that subjects may not inspire fully to TLC. This would be particularly true in subjects with muscle weakness or obesity where fatigue and a large inspiratory load might play a role. Several studies have used an esophageal balloon to measure maximal inspiratory pressures during the IC maneuvers.8,14,21,23,27,29 If the maximal inspiratory pressure obtained during exercise (with an open glottis) is similar to that obtained repeatedly at full inflation (TLC) at rest, one is more confident that TLC was reached during the maneuvers.56,29 Failure to achieve the pre-exercise target pressures would require repeat IC maneuvers during exercise. End-expiratory esophageal pressure has also been monitored in several studies as an index of change in EELV prior to performing the IC maneuver.27 In the majority of patients, it is likely that adequate IC maneuvers can be performed (for placement of the FV loops) during exercise if sufficient time is spent prior to exercise performing the maneuvers.53

Defining the MFVL

MFVLs are plotted in association with the extFVLs to determine the degree of ventilatory constraint. Most studies have demonstrated a small bronchodilation early in exercise that may be exaggerated in aging and in subjects with mild to moderate COPD.57,45 During prolonged exercise in asthmatics, there may be a slight decrease in the MFVL after about 15 min.54 Thus, a pre-exercise MFVL may underestimate or overestimate the capacity available during exercise depending on the population. MFVLs may be difficult to perform during exercise, especially in some disease populations. They have, however, been performed successfully in normal subjects and asthmatics,5and in patients with mild to moderate COPD as well as in patients with CHF.6,39,53 Previous studies have suggested that in normals, the exercise-induced bronchodilation is present for a short period of time immediately after exercise and, thus, a postexercise MFVL may provide the simplest estimate of maximal available flows and volume during exercise.36 In asthmatics, the lability of airway tone may necessitate assessment of the MFVL as close to the time of measuring the extFVLs as possible.5,54

Maximal expiratory maneuvers resulting in excessive expiratory pleural pressure generation have been shown to underestimate the true maximal air flows at any given lung volume (< 70 to 80% of TLC) due to gas compression in the chest.5556 Thus, the true capacity for airflow generation at a given volume may be underestimated, particularly over the effort-independent portion of the MFVL. Although not an established technique, the potential for underestimating maximal available air flows may be circumvented by having subjects perform a series of three to five expiratory maneuvers at different efforts from TLC to RV and taking the highest flow obtained at each lung volume (Figure 11 ).,78,45,5556 These various effort loops can be aligned at TLC with the maximal effort loops and the expiratory boundary of the maximal effort loops increased in accordance with any increased expiratory flows noted with the submaximal efforts. MFVLs can also be performed in a volume displacement plethysmograph where a separate flow sensor compensates for the compression of gases when measured at the mouth. The ideal MFVL for comparison to the exercise data is difficult to determine, as the expiratory intrathoracic pressures produced during heavy exercise tidal breathing may also cause gas compression in some subjects. Thus, the maximal expiratory airflows obtained in a plethysmograph may not truly be available in some flow-limited subjects. For most subjects, the pre- or postexercise MFVL likely represents an adequate assessment of the maximal available flow.

Limits to Defining Expiratory Flow Limitation and V̇eCAP

As previously noted, the assessment of expiratory flow limitation and V̇eCAP (as defined) is dependent on an adequate assessment of MEFs and placement of the extFVL within the MFVL.

Whether or not the expiratory flow limitation described by the percent of the tidal breath that meets or exceeds the MFVL represents“ true” flow limitation is controversial.10,39 Previous studies that have examined the relationship of flow and transpulmonary pressure (at a given lung volume) demonstrated that flow begins to level off (pressure increasing out of proportion to flow) before a true limit (increase in pressure without an increase in flow) occurs.8,45,5556 Thus, despite the difficulty in defining the MEFs, the point where the tidal breath meets or exceeds the expiratory boundary of the MFVL likely represents at least mild flow limitation (a rising resistance to airflow) or “impending” flow limitation. Recent use of a brief negative pressure during expiration may more clearly define whether true expiratory flow limitation occurs; however, using this technique, it is difficult to quantify the percent of the breath that may be involved.10

The V̇eCAP (as defined) also assumes an instantaneous rise in flow at the onset of expiration. This is not typically observed during exercise and would tend to slightly overestimate ventilation for this reason.5 Additional algorithms may better define physiologic change in flow on the onset of expiration.

For editorial comment see page 277.

Figure Jump LinkFigure 1. Defining expiratory flow limitation. extFVLs are aligned within the MEFL according to a measured EELV. The percent of the tidal breath (VFL) that expiratory air flows meet or exceed the MEFs are used as an estimate as to the degree of expiratory flow limitation. ERV = expiratory reserve volume; IRV = inspiratory reserve volume.Grahic Jump Location
Figure Jump LinkFigure 2. Inspiratory flow reserve. The capacity for producing inspiratory flow declines at higher lung volumes (decreased inspiratory muscle length). Tidal inspiratory flows thus (typically) come closest to the maximal available flows at the higher lung volumes. At the closest point along the inspiratory tidal loop, flows usually only approach 50 to 70% of that which is available in the average adult near peak exercise (left, A). Expiratory flow limitation and a rising EELV (dynamic hyperinflation) significantly reduces the inspiratory flow reserve (right, B).Grahic Jump Location
Figure Jump LinkFigure 3. eCAP is determined by aligning extFVLs within the MFVL according to a measured EELV. The volume of the tidal breath is divided into ΔVs. An estimated expiratory duration (Te) was determined by dividing each ΔV by average MEF (MEFe) within each volume segment and summing all such times (ΣTe) over expiratory phase of Vt. Measured inspiratory to total breathing cycle time was used to estimate inspiratory time. The sum of minimal inspiratory time and TE gave a minimal breathing cycle time and maximal breathing frequency. The product of maximal breathing frequency and measured Vt equaled V̇eCAP.Grahic Jump Location
Figure Jump LinkFigure 4. MVV vs exercise hyperpnea. An example of the difference in breathing pattern when the MVV maneuver is performed (left) relative to the same subject near maximal exercise (right) using a commercially available system (Vmax; SensorMedics; Yorba Linda, CA). The MVV is performed at high lung volumes (increased EELV) resulting in a high elastic load to breathing and requires large expiratory pleural pressures to obtain the high flows early in expiration (increasing the WOB). In contrast, during exercise, EELV is reduced resulting in tidal breathing occurring at a more optimal position of the pressure volume relationship of the lung and chest wall with consequent less WOB (from R. Jorge Zeballos and Idelle M. Weisman, William Beaumont Army Medical Center, El Paso, TX).Grahic Jump Location
Table Graphic Jump Location
Table 1. Assessment of Ventilatory Constraint Based on the extFVL Relative to the MFVL
Figure Jump LinkFigure 5. Left, A: FV response to exercise in the average fit healthy young adult during incremental exercise plotted within the MFVL. In this population, EELV progressively decreases with exercise, and expiratory flow limitation is only present near EELV over a small portion of the Vt. Considerable room exists to increase ventilation even at peak exercise. Similar responses are also shown for the fit aged adult (middle, B) and the young endurance athlete (right, C). The older adult represents a group of subjects with a mild decline in lung function but maintenance of a high ventilatory demand. Flow limitation occurs at a low work intensity and VE demand (40 L/min) and EILV at peak exercise reaches a higher percent of TLC. This group has significant ventilatory constraint at peak exercise. The fit young athlete (right, C) represents a group of subjects with normal lung function but excessive ventilatory demands. EELV initially decreases during exercise like the average fit adult, but increases as significant expiratory flow limitation occurs. By peak exercise in the majority of these subjects, significant ventilatory constraint is observed similar to the aged, fit adult.Grahic Jump Location
Figure Jump LinkFigure 6. Patient with history of moderate COPD (forced expiratory flow at 50% of VC = 35% of predicted for age): EELV increases from the onset of exercise and expiratory flow limitation is present over > 80% of the Vt by peak exercise. Inspiratory flows approach those available over the higher lung volumes. Little room exists to increase ventilation.Grahic Jump Location
Figure Jump LinkFigure 7. ILD: Maximal and extFVL in patients with ILD. Left: patients who stopped secondary to dyspnea. Right: patients who stopped due to leg fatigue. Minimal change was observed in EELV in either group, with the group complaining of dyspnea demonstrated significant expiratory flow limitation (from Marciniuk et al38 in 1994).Grahic Jump Location
Figure Jump LinkFigure 8. Example of a patient with a history of CHF (New York Heart Association class III). EELV is reduced at rest and remains near RV throughout exercise despite significant expiratory flow limitation and apparent room to increase EELV to avoid the flow limitation.Grahic Jump Location
Figure Jump LinkFigure 9. Unequal inspiratory and expiratory volumes may occur because of electrical changes over time, to nonlinearities in the flow or volume sensing device, as well as to physiologic changes (temperature, humidity, gas density and viscosity, and turbulence). Large differences in expiratory and inspiratory volumes make it difficult to accurately place the tidal loops within the MVFL.Grahic Jump Location
Figure Jump LinkFigure 10. Top, A: Example of “drift” in volume over time. In this case, we note a consistent slope upward indicating a larger expiration than inspiration. Two IC maneuvers can be performed and volumes were aligned according to the ICs at TLC (bottom, B). Another option is to change the slope of the end expiratory lung volumes and reset to zero. However, this assumes that the EELV is not changing within this time period.Grahic Jump Location
Figure Jump LinkFigure 11. Correction for gas compression to obtain the maximal available expiratory flows: a series of expiratory maneuvers from TLC to RV at different efforts can be performed and a line extrapolated from the highest values obtained at each lung volume during the maneuvers used as the maximal available expiratory flows.Grahic Jump Location

The authors would like to thank Kathy O’Malley and Sean M. Connery for technical assistance associated with several of the studies reviewed in the manuscript. In addition we appreciate the work of Audrey Schroeder in preparing the manuscript.

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Figures

Figure Jump LinkFigure 1. Defining expiratory flow limitation. extFVLs are aligned within the MEFL according to a measured EELV. The percent of the tidal breath (VFL) that expiratory air flows meet or exceed the MEFs are used as an estimate as to the degree of expiratory flow limitation. ERV = expiratory reserve volume; IRV = inspiratory reserve volume.Grahic Jump Location
Figure Jump LinkFigure 2. Inspiratory flow reserve. The capacity for producing inspiratory flow declines at higher lung volumes (decreased inspiratory muscle length). Tidal inspiratory flows thus (typically) come closest to the maximal available flows at the higher lung volumes. At the closest point along the inspiratory tidal loop, flows usually only approach 50 to 70% of that which is available in the average adult near peak exercise (left, A). Expiratory flow limitation and a rising EELV (dynamic hyperinflation) significantly reduces the inspiratory flow reserve (right, B).Grahic Jump Location
Figure Jump LinkFigure 3. eCAP is determined by aligning extFVLs within the MFVL according to a measured EELV. The volume of the tidal breath is divided into ΔVs. An estimated expiratory duration (Te) was determined by dividing each ΔV by average MEF (MEFe) within each volume segment and summing all such times (ΣTe) over expiratory phase of Vt. Measured inspiratory to total breathing cycle time was used to estimate inspiratory time. The sum of minimal inspiratory time and TE gave a minimal breathing cycle time and maximal breathing frequency. The product of maximal breathing frequency and measured Vt equaled V̇eCAP.Grahic Jump Location
Figure Jump LinkFigure 4. MVV vs exercise hyperpnea. An example of the difference in breathing pattern when the MVV maneuver is performed (left) relative to the same subject near maximal exercise (right) using a commercially available system (Vmax; SensorMedics; Yorba Linda, CA). The MVV is performed at high lung volumes (increased EELV) resulting in a high elastic load to breathing and requires large expiratory pleural pressures to obtain the high flows early in expiration (increasing the WOB). In contrast, during exercise, EELV is reduced resulting in tidal breathing occurring at a more optimal position of the pressure volume relationship of the lung and chest wall with consequent less WOB (from R. Jorge Zeballos and Idelle M. Weisman, William Beaumont Army Medical Center, El Paso, TX).Grahic Jump Location
Figure Jump LinkFigure 5. Left, A: FV response to exercise in the average fit healthy young adult during incremental exercise plotted within the MFVL. In this population, EELV progressively decreases with exercise, and expiratory flow limitation is only present near EELV over a small portion of the Vt. Considerable room exists to increase ventilation even at peak exercise. Similar responses are also shown for the fit aged adult (middle, B) and the young endurance athlete (right, C). The older adult represents a group of subjects with a mild decline in lung function but maintenance of a high ventilatory demand. Flow limitation occurs at a low work intensity and VE demand (40 L/min) and EILV at peak exercise reaches a higher percent of TLC. This group has significant ventilatory constraint at peak exercise. The fit young athlete (right, C) represents a group of subjects with normal lung function but excessive ventilatory demands. EELV initially decreases during exercise like the average fit adult, but increases as significant expiratory flow limitation occurs. By peak exercise in the majority of these subjects, significant ventilatory constraint is observed similar to the aged, fit adult.Grahic Jump Location
Figure Jump LinkFigure 6. Patient with history of moderate COPD (forced expiratory flow at 50% of VC = 35% of predicted for age): EELV increases from the onset of exercise and expiratory flow limitation is present over > 80% of the Vt by peak exercise. Inspiratory flows approach those available over the higher lung volumes. Little room exists to increase ventilation.Grahic Jump Location
Figure Jump LinkFigure 7. ILD: Maximal and extFVL in patients with ILD. Left: patients who stopped secondary to dyspnea. Right: patients who stopped due to leg fatigue. Minimal change was observed in EELV in either group, with the group complaining of dyspnea demonstrated significant expiratory flow limitation (from Marciniuk et al38 in 1994).Grahic Jump Location
Figure Jump LinkFigure 8. Example of a patient with a history of CHF (New York Heart Association class III). EELV is reduced at rest and remains near RV throughout exercise despite significant expiratory flow limitation and apparent room to increase EELV to avoid the flow limitation.Grahic Jump Location
Figure Jump LinkFigure 9. Unequal inspiratory and expiratory volumes may occur because of electrical changes over time, to nonlinearities in the flow or volume sensing device, as well as to physiologic changes (temperature, humidity, gas density and viscosity, and turbulence). Large differences in expiratory and inspiratory volumes make it difficult to accurately place the tidal loops within the MVFL.Grahic Jump Location
Figure Jump LinkFigure 10. Top, A: Example of “drift” in volume over time. In this case, we note a consistent slope upward indicating a larger expiration than inspiration. Two IC maneuvers can be performed and volumes were aligned according to the ICs at TLC (bottom, B). Another option is to change the slope of the end expiratory lung volumes and reset to zero. However, this assumes that the EELV is not changing within this time period.Grahic Jump Location
Figure Jump LinkFigure 11. Correction for gas compression to obtain the maximal available expiratory flows: a series of expiratory maneuvers from TLC to RV at different efforts can be performed and a line extrapolated from the highest values obtained at each lung volume during the maneuvers used as the maximal available expiratory flows.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Assessment of Ventilatory Constraint Based on the extFVL Relative to the MFVL

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