MFVL
EELV
HEAVY EXERCISE MVV
VOLUME VOLUME
proaches the maximal voluntary ventilation (MVV) or some estimate of the MVV that is used as an index of ventilatory capacity. The standard maximal voluntary ventilation (MVV) test is obtained at rest by having a patient breathe in and out of a spirometer as hard as possi-ble for 12–15 s [5, 6, 11]. A rough estimate of the MVV can be obtained from the FEV1 obtained from spirometry multiplied by about 35–40 [68]. As there is considerable variability in the relationship of MVV to FEV1 among subjects, especially those with lung disease [68], the ‘cal-culated’ MVV should be used only when directly mea-sured MVV or other direct methods (see below) are not available.
Although the MVV is practical, simple, and widely applied, it most probably overestimates ‘true’ ventilatory capacity for two reasons: (1)the maneuver is a short high intensity effort that cannot be sustained [69], and (2)the breathing pattern adopted by most subjects is different from exercise ventilation in that breathing occurs at high-er lung volumes and at highhigh-er respiratory rates (fig. 3) [70, 71], and involves a different pattern of muscle activation [72].
There has been a growing trend in both research and clinical laboratories to find alternative ways to evaluate ventilatory limitation during exercise [73]. This results from the appreciation that patients may discontinue exer-cise due to ventilatory constraints and dyspnea prior to achieving the classic indices associated with ventilatory limitation (i.e. minute ventilation (V˙E) that reached the
maximum voluntary ventilation (MVV) or a rise in PaCO2) and that ventilatory limitation is not an ‘all or none’ phenomenon. One approach that has gained popu-larity is the measurement of the exercise tidal flow volume loop (extFVL) and plotting it within the maximal flow volume loop (MFVL) [74–78]. This technique provides a good visual index of the degree of ventilatory constraint, allows a more detailed approach to defining ventilatory limitation (relative to the V˙E/MVV relationship), and has gained popularity due to the ease of measurement using many of the commercially available automated exercise systems. Figure 4 shows an example of the rest and peak exercise flow volume responses in a healthy, average fit adult plotted within the MFVL.
Table 10 lists indices of ventilatory constraint using extFVL plotted within the MFVL [73]. In addition, other parameters can be devised that provide more continuous information, such as the area between the extFVL and the MFVL. Further work must be done to determine which parameters in addition to visual inspection of the loops are useful diagnostic tools.
Another method for determining degree of flow limita-tion is the ‘negative expiratory pressure’ or NEP method [79–81]. This technique requires a negative pressure source to be connected at the mouth so that at randomly selected times during exercise, mouth pressure can be forced to be negative, usually about –10 cm H2O, during expiration of one breath. An increase in expiratory flow during a breath where the NEP is applied compared with
Exercise Testing Methodology 57
a normal breath is taken as evidence that flow limitation is not present.
Each of these techniques assesses ventilatory limita-tion in different ways. extFVL analysis is hampered by the fact that the MFVL determined by routine spirometry is affected by gas compression within the chest during the maximal expiratory effort [82–84], and that the MFVL curve itself can be affected by exercise [81, 84, 85]. In turn, the NEP technique is essentially an ‘all or none phe-nomenon’ unable to detect the approach to flow limita-tion, but rather only when flow limitation is present; fur-thermore, NEP by itself does not document changes in breathing strategy in response to actual or impending flow limitation [73]. Both techniques have their technical diffi-culties: the NEP requires additional instrumentation and means for measuring and generating the negative mouth pressures during expiration only, whereas the MFVL curve analysis requires drift-free volume and flow signals, and each measurement must be accompanied by a full inspiratory effort from the patient to determine inspirato-ry capacity [86]. The IC measurement, as a reflection of end-expiratory lung volume and overall operational lung volumes is becoming increasingly important in clinical decision-making [35, 75, 87]. A combination of the NEP technique and the use of extFVL/MFVL may provide the greatest amount of information on ventilatory constraints imposed by the lung and chest wall.
Acknowledgements
Supported by a General Clinical Research Center grant from the National Institutes of Health (MO1-RR00585) and NHLBI grants HL-52230 and HL064368.
Fig. 4. Calculation of flow limitation (FL) and inspiratory capacity (IC) from exercise test flow-volume loops (ext FVL) and maximal flow-volume loops (MFVL). Flow limitation is quantified by measur-ing the volume over which the ext FVL flows meet or exceed the MFVL flows (Vol of FL) expressed as a % of the tidal volume. Anoth-er useful index of exAnoth-ercise adaptation is the change in inspiratory capacity (IC), here indicate for rest (rest IC) and exercise (ext IC). In this normal individual, the IC gets larger during exercise as end-expi-ratory lung volume (EELV) drops. In patients, EELV may rise as FL occurs earlier in exercise, causing IC to fall.
Table 10. Indices of ventilatory constraint using ext FVL plotted within the MFVL
Index How it is assessed Role in ventilatory contraints
Expiratory flow limitation (%FL)% of ext FVL that meets or exceeds the MFVL
FL may indicate airway collapse, increasing WOB, and could trigger reflexes, increasing sensation of dyspnea
Elastic load EILV/TLC ratio high WOB, increased load on respiratory muscles
Dynamic rise in EELV Fall in IC (EELV = TLC – IC)reduces inspiratory muscle length, and increases elastic load Inspiratory flow reserve area between inspiratory limb of
extFVL and MFVL
a measure of breathing reserve
EILV = End-inspiratory lung volume; TLC = total lung capacity; IC = inspiratory capacity; WOB = work of breathing.
Other terms defined in text or figure 4. Table adapted from Johnson et al. [73].
58 Beck/Weisman
References
1 Weisman IM, Zeballos RJ: Cardiopulmonary exercise testing – the need for standardization:
Pulmonary perspectives. Am Coll Chest Phys 1992;8:5–8.
2 Zeballos RJ, Weisman IM: Behind the scenes of cardiopulmonary exercise testing. Clin Chest Med 1994;15:193–213.
3 American College of Sports Medicine: Guide-lines for Exercise Testing and Prescription, ed 6. Philadelphia, Lippincott Williams & Wil-kins, 2000.
4 Astrand PO: Textbook of Work Physiology.
New York, McGraw-Hill, 1977.
5 Wasserman K, Hansen JE, Sue DY, Casaburi R, Whipp BJ: Principles of Exercise Testing and Interpretation, ed 3. Philadelphia, Lippin-cott Williams & Wilkins, 1999.
6 Jones NL: Clinical Exercise Testing, ed 4. Phil-adelphia, Saunders, 1997.
7 Weisman IM, Zeballos RJ: An integrated ap-proach to the interpretation of cardiopulmo-nary exercise testing. Clin Chest Med 1994;15:
421–445.
8 Mitchell JH, Sproule BJ, Chapman CB: The physiological meaning of the maximal oxygen intake test. J Clin Invest 1958;37:538–547.
9 Hughson RL, Kowalchuk JM, Prime WM, Green HJ: Open-circuit gas exchange analysis in the non-steady-state. Can J Applied Sports Sci 1980;5:15–18.
10 Beaver WL, Wasserman K, Whipp BJ: On-line computer analysis and breath-by-breath graph-ical display of exercise function tests. J Appl Physiol 1973;34:128–132.
11 American Thoracic Society: Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995;152:1107–1136.
11A Wanger J, Crapo RO, Irvin CG: Pulmonary function laboratory management and proce-dure manual: A project of the American Tho-racic Society. American ThoTho-racic Society, New York, NY, 1998/2001.
12 Beaver WL: Water vapor corrections in oxygen consumption calculations. J Appl Physiol 1973;35:928–931.
13 Proctor DN, Beck KC: Time delays adjustment to minimize errors in breath-by-breath mea-surement of V˙O2 during exercise. J Appl Physiol 1996;81:2495–2499.
14 Hughson RL, Northey DR, Xing HC, Dietrich BH, Cochrane JE: Alignment of ventilation and gas fraction for breath-by-breath respirato-ry gas exchange calculations in exercise. Comp Biomed Res 1991;24:118–128.
15 Beaver WL, Lamarra N, Wasserman K:
Breath-by-breath measurement of true alveolar gas exchange. J Appl Physiol 1981;51:1662–
1675.
16 Sciurba FC, Owens GR, Ondriezek J: The effect of sample interval on maximal values obtained during incremental exercise. Am Rev Respir Dis 1991;143:A176.
17 Slivka WA: Sciurba FC: Parameters and power to measure a therapeutic effect (lung reduction surgery – LVRS) in advanced emphysema. Am J Respir Crit Care Med 1998;157:A92.
18 Myers J, Walsh D, Sullivan M, Froelicher V:
Effect of sampling on variability and plateau in oxygen uptake. J Appl Physiol 1990;68:404–
410.
19 Marciniuk DD, Watts R, Gallagher CG: Re-producibility of incremental maximal cycle er-gometer testing in patients with restrictive lung disease. Thorax 1993;48:894–898.
20 Garrard CS, Emmons C: The reproducibility of the respiratory responses to maximum exer-cise. Respiration 1986;49:94–100.
21 Russell JC, Dale JD: Dynamic torquemeter calibration of bicycle ergometers. J Appl Physi-ol 1986;61:1217–1220.
22 Van Praagh E, Bedu M, Roddier P, Coudert J:
A simple calibration method for mechanically breaked cycle ergometers. Int J Sports Med 1992;13:27–30.
23 Huszczuk A, Whipp BJ, Wasserman K: A re-spiratory gas exchange simulator for routine calibration in metabolic studies. Eur Respir J 1990;3:465–468.
24 Otsuka T, Kurihara N, Fujii T, Fujimoto S, Yoshikawa J: Effect of exercise training and detraining on gas exchange kinetics in patients with chronic obstructive pulmonary disease.
Clin Physiol 1997;17:287–297.
25 Whipp BJ, Davis JA, Torres F, Wasserman K:
A test to determine parameters of aerobic func-tion during exercise. J Appl Physiol 1981;50:
217–221.
26 Zhang YY, Johnson MC, Chow N, Wasserman K: Effect of exercise testing protocol on param-eters of aerobic function. Med Sci Sports Exerc 1991;23:625–630.
27 Myers J, Buchanan N, Walsh D, Kraemer M, McAuley P, Hamilton-Wessler M, Froelicher VF: Comparison of the ramp versus standard exercise protocols. J Am Coll Cardiol 1991;17:
1334–1342.
28 Tanner CS, Heise CT, Barber G: Correlations of the physiologic parameters of a continuous ramp versus an incremental James exercise protocol in normal children. Am J Cardiol 1991;67:309–312.
29 Bader DS, Maguire TE, Balady GJ: Compari-son of ramp versus step protocols for exercise testing in patients 1 or = 60 years of age. Am J Cardiol 1999;83:11–14.
30 Miyahara N, Eda R, Takeyama H, Maeda T, Aoe K, Kunichika N, Kohara H, Harad M:
Cardiorespiratory responses during cycle er-gometer exercise with different ramp slope in-crements in patients with chronic obstructive pulmonary disease. Int Med 2000;39:15–19.
31 Nishime EO, Cole CR, Blackstone EH, Pash-kow FJ, Lauer MS: Heart rate recovery and treadmill exercise score as predictors of mortal-ity in patients referred for exercise ECG.
JAMA 2000;284:1392–1398.
32 Cole CR, Foody JM, Blackstone EH, Lauer MS: Heart rate recovery after submaximal ex-ercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Int Med 2000;132:552–555.
33 Buchfuhrer MJ, Hansen JE, Robinson TE, Sue DY, Wasserman K, Whipp BJ: Optimizing the exercise protocol for cardiopulmonary assess-ment. J Appl Physiol 1983;55:1558–1564.
34 Roston WL, Whipp BJ, Davis JA, Cunning-ham DA, Effors RM, Wasserman K: Oxygen uptake kinetics and lactate concentration dur-ing exercise in humans. Am Rev Respir Dis 1987;135:1080–1084.
35 O’Donnell DE, Lam M, Webb KA: Spirometric correlates of improvement in exercise perfor-mance after anticholinergic therapy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:542–549.
36 Oga T, Nishimura K, Tsukino M, Hajiro T, Ikeda A, Izumi T: The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary dis-ease. A comparison of three different exercise tests. Am J Respir Crit Care Med 2000;161:
1897–1901.
37 Zeballos RJ, Weisman IM, Connery SM: Com-parison of pulmonary gas exchange measure-ments between incremental and constant work exercise above the anaerobic threshold. Chest 1998;113:602–611.
38 Bruce RA, Kusumi F, Hosmer D: Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascu-lar disease. Am Heart J 1973;85:546–562.
39 Froelicher VE Jr, Brammell H, Davis G, No-guera I, Stewart A, Lancaster MC: A compari-son of the reproducibility and physiologic re-sponse to three maximal treadmill exercise pro-tocols. Chest 1974;65:512–517.
40 Bruce RA, McDonough JR: Stress testing in screening for cardiovascular disease. Bull NY Acad Med 1969;45:1288–1305.
41 Nagle FS, Balke B, Naughton JP: Gradational step tests for assessing work capacity. J Appl Physiol 1965;20:745–748.
42 Pollock ML, Wilmore JH, Fox SM III: Exercise in Health and Disease. Philadelphia, Saunders, 1984.
43 Zeballos RJ, Weisman IM: Reliability of non-invasive oximetry in black subjects during ex-ercise and hypoxia. Am Rev Resp Dis 1991;
144:1240–1244.
44 Hansen JE, Cassaburi R: Validity of ear oxime-try in clinical exercise testing. Chest 1987;91:
333–337.
45 Ries AL, Fedullo PF, Clausen JL: Rapid changes in arterial blood gas levels after exer-cise in pulmonary patients. Chest 1983;83:
454–456.
46 Rasmussen PH, Staats BA, Driscoll DJ, Beck KC, Bonekat HW, Wilcox WD: Direct and indirect blood pressure during exercise. Chest 1985;87:743–748.
47 Robinson TE, Sue DY, Huszczuk A, Weiler-Ravell D, Hansen JE: Intra-arterial and cuff blood pressure responses during incremental cycle ergometry. Med Sci Sports Exerc 1988;
20:142–149.
48 Sinex JE: Pulse oximetry: Principles and limi-tations. Am J Emerg Med 1999;17:59–67.
Exercise Testing Methodology 59 49 Ralston AC, Webb RK, Runciman WB:
Poten-tial errors in pulse oximetry. III. Effects of interference, dyes, dyshaemoglobins and other pigments. Anaesthesia 1991;46:291–295.
50 Am Assoc Resp Care (AARC): Clinical practice guideline: Exercise testing for evaluation of hypoxemia and/or desaturation. Respir Care 1992;37:907–912.
51 Hansen JE, Sue DY, Wasserman K: Predicted values for clinical exercise testing. Am Rev Respir Dis 1984;129(suppl):S49–S55.
52 Lewis DA, Sietsema KE, Casaburi R, Wasser-man K: Inaccuracy of non-invasive estimates of VD/VT in clinical exercise testing. Chest 1994;106:1476–1480.
53 Borg GAV: Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982;14:377–
381.
54 Borg GAV: Perceived exertion as an indicator of somatic stress. Scan J Rehab Med 1970;2–3:
92–98.
55 Froelicher VF, Marcondes GD: Manual of Ex-ercise Testing. St Louis, Mosby Year Book, 1989.
56 Zavala DC: Manual on Exercise Testing: A Training Handbook, ed 3. Iowa City, Universi-ty of Iowa, 1993.
57 Pina IL, Balady GJ, Hanson P, Labovitz AJ, Madonna DW, Myers J: Guidelines for clinical exercise testing laboratories: A statement for healthcare professionals from the Committee on Exercise and Cardiac Rehabilitation, Amer-ican Heart Association. Circulation 1995;91:
912–921.
58 American College of Obstetricians and Gyne-cologists Technical Bulletin: Exercise during pregnancy and the postpartum period. 1994;
Number 189.
59 Mason RE, Likar I: Experimental and laborato-ry reports: A new system of multiple-lead exer-cise electrocardiography. Am Heart J 1966;71:
196–205.
60 Gamble P, McManus H, Jensen D, Froelicher V: A comparison of the standard 12-lead elec-trocardiogram to exercise electrode place-ments. Chest 1984;85:616–622.
61 Lollgen H, Ulmer H-V, Crean P (eds): Eur Heart Assoc Report of the Task Force Confer-ence on Ergometry. Recommendations and standard guidelines for exercise testing. Eur Heart J 1988;9(suppl K):1–37.
62 Am College Card/Am Heart Assoc Guidelines for exercise testing: A report of the American College of Cardiology/American Heart Asso-ciation Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol 1997;30:260–311.
63 Shephard RJ: Test of maximum oxygen intake:
A critical review. Sports Med 1984;1:99–124.
64 Stuart RJ Jr, Ellestad MH: National Survey of exercise stress testing facilities. Chest 1980;77:
94–97.
65 Scherer D, Kaltenbach M: Frequency of life-threatening complications associated with stress testing. Dtsch Med Wochenschr 1979;
104:1161–1165.
66 American Heart Association: Exercise stan-dards. A statement for healthcare profession-als. Circulation 1995;91:580–615.
67 Myers J, Voodi L, Umann T, Froelicher VF: A survey of exercise testing: Methods, utilization, interpretation, and safety in the VAHCS. J Cardiopulm Rehab 2000;20:251–258.
68 Beck KC: Evaluating exercise capacity and air-way function in the athlete; in Weiler JM (ed):
Allergic and Respiratory Disease in Sports Medicine. New York, Marcel Dekker, 1997.
69 Freedman S: Sustained maximum voluntary ventilation. Resp Physiol 1970;8:230–244.
70 Hyatt RE: The interrelationships of pressure, flow and volume during various respiratory maneuvers in normal and emphysematous sub-jects. Am Rev Respir Dis 1961;83:676–683.
71 Olafsson S, Hyatt RE: Ventilatory mechanics and expiratory flow limitation during exercise in normal subjects. J Clin Invest 1969;48:564–
573.
72 Klas JV, Dempsey JA: Voluntary versus reflex regulation of maximal exercise flow: Volume loops. Am Rev Respir Dis 1989;139:150–156.
73 Johnson BD, Beck KC, Zeballos RJ, Weisman IM: Advances in pulmonary laboratory testing.
Chest 1999;116:1377–1387.
74 Johnson BD, Reddan WG, Seow KC, Dempsey JA: Mechanical constraints on exercise hyper-pnea in a fit aging population. Am Rev Respir Dis 1991;143:968–977.
75 Babb TG: Ventilatory response to exercise in subjects breathing CO2 or HeO2. J Appl Physi-ol 1997;82:746–754.
76 Johnson BD, Saupe KW, Dempsey JA: Me-chanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol 1992;73:
874–886.
77 Marciniuk DD, Watts R, Gallagher CG: Dead space loading and exercise limitation in pa-tients with interstitial lung disease. Chest 1994;
105:183–189.
78 Marciniuk DD, Sridhar G, Clemens RE, Zintel TA, Gallagher CG: Lung volumes and expira-tory flow limitation during exercise in intersti-tial lung disease. J Appl Physiol 1994;77:963–
973.
79 Eltayara L, Becklake MR, Volta CA, Milic-Emili J: Relationship between chronic dyspnea and expiratory flow limitation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;154:1726–1734.
80 Mota S, Casn P, Drobnic F, Giner J, Ruiz O, Sanchis J, Milic-Emili J: Expiratory flow limi-tation during exercise in competition cyclists. J Appl Physiol 1999;86:611–616.
81 Koulouris NG, Dimopoulou I, Valta P, Finkel-stein R, Cosio MG, Milic-Emili J: Detection of expiratory flow limitation during exercise in COPD patients. J Appl Physiol 1997;82:723–
731.
82 Coates AL, Desmond KJ, Demizio D, Allen P, Beaudry PH: Sources of error in flow-volume curves: Effect of expired volume measured at the mouth vs. that measured in a body plethys-mograph. Chest 1988;94:976–982.
83 Hyatt RE: Effort independence and forced ex-piratory flow. Chest 1980;77:246–248.
84 Rodarte JR: Detection of expiratory flow limi-tation during exercise in COPD patients (in-vited editorial). J Appl Physiol 1997;82:721–
722.
85 Johnson BD, Scanlon PD, Beck KC: Regula-tion of ventilatory capacity during exercise in asthmatics. J Appl Physiol 1995;79:892–901.
86 Johnson BD, Weisman IM, Zeballos RJ, Beck KC: Emerging concepts in the evaluation of ventilatory limitation during exercise: The ex-ercise tidal flow-volume loop. Chest 1999;116:
488–503.
87 Babb TG: Mechanical ventilatory constraints in aging, lung disease, and obesity: Perspective and brief review. Med Sci Sports Exerc 1999;
31(suppl):S12–S22.
88 Nordrehaug JE, Danielson R, Strangeland L, Rosland GA, Vik-Mo H: Respiratory gas ex-change during treadmill exercise testing: Re-producibility and comparison of different exer-cise protocols: Technical notes. Scand J Clin Lab Invest 1991;51:655–658.
89 Cox NJM, Hendriks JCM, Binkhorst RA, Fol-gering HTM, van Herwaarden CLA: Repro-ducibility of incremental maximal cycle ergom-eter tests in patients with mild to moderate obstructive lung disease. Lung 1989;167:129–
133.
90 Noseda A, Carpiaux JP, Prigogine T, Schmer-ber J: Lung function, maximum and submaxi-mum exercise testing in COPD patients: Re-producibility over a long interval. Lung 1989;
167:247–257.
91 Owens MW, Kinasewitz GT, Strain DS: Evalu-ating the effects of chronic therapy in patients with irreversible air-flow obstruction. Am Rev Respir Dis 1986;134:935–937.
92 Meyer K, Westbrook S, Schwaibold M, Hajric R, Peters K, Roskamm H: Short-term repro-ducibility of cardiopulmonary measurements during exercise testing in patients with severe chronic heart failure. Am Heart J 1977;134:
20–26.
Kenneth C. Beck, PhD
Physiological Imaging Laboratory Department of Radiology
University of Iowa Hospitals and Clinics 200 Hawkins Drive
Iowa City, IA 52242-1077 (USA)
Tel. +1 319 356 1381, Fax +1 319 356 1503 E-Mail [email protected]
Weisman IM, Zeballos RJ (eds): Clinical Exercise Testing.
Prog Respir Res. Basel, Karger, 2002, vol 32, pp 60–71
OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO