Semin Respir Crit Care Med 2023; 44(05): 661-680
DOI: 10.1055/s-0043-1770362
Review Article

Exercise Physiology and Cardiopulmonary Exercise Testing

Kathy E. Sietsema
1   Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Torrance, California
,
Harry B. Rossiter
1   Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Torrance, California
› Institutsangaben
Funding Harry B. Rossiter is supported by grants from National Institutes of Health (grant numbers: R01HL151452, R01HL153460, P50HD098593, R01DK122767) and the Tobacco Related Disease Research Program (grant number: T31IP1666).

Abstract

Aerobic, or endurance, exercise is an energy requiring process supported primarily by energy from oxidative adenosine triphosphate synthesis. The consumption of oxygen and production of carbon dioxide in muscle cells are dynamically linked to oxygen uptake (V̇O2) and carbon dioxide output (V̇CO2) at the lung by integrated functions of cardiovascular, pulmonary, hematologic, and neurohumoral systems. Maximum oxygen uptake (V̇O2max) is the standard expression of aerobic capacity and a predictor of outcomes in diverse populations. While commonly limited in young fit individuals by the capacity to deliver oxygen to exercising muscle, (V̇O2max) may become limited by impairment within any of the multiple systems supporting cellular or atmospheric gas exchange. In the range of available power outputs, endurance exercise can be partitioned into different intensity domains representing distinct metabolic profiles and tolerances for sustained activity. Estimates of both V̇O2max and the lactate threshold, which marks the upper limit of moderate-intensity exercise, can be determined from measures of gas exchange from respired breath during whole-body exercise. Cardiopulmonary exercise testing (CPET) includes measurement of V̇O2 and V̇CO2 along with heart rate and other variables reflecting cardiac and pulmonary responses to exercise. Clinical CPET is conducted for persons with known medical conditions to quantify impairment, contribute to prognostic assessments, and help discriminate among proximal causes of symptoms or limitations for an individual. CPET is also conducted in persons without known disease as part of the diagnostic evaluation of unexplained symptoms. Although CPET quantifies a limited sample of the complex functions and interactions underlying exercise performance, both its specific and global findings are uniquely valuable. Some specific findings can aid in individualized diagnosis and treatment decisions. At the same time, CPET provides a holistic summary of an individual's exercise function, including effects not only of the primary diagnosis, but also of secondary and coexisting conditions.



Publikationsverlauf

Artikel online veröffentlicht:
10. Juli 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Bowen TS, Benson AP, Rossiter HB. The coupling of internal and external gas exchange during exercise. In: Zoladz JA. ed. Muscle and Exercise Physiology. New Amsterdam: Elsevier; 2018: 217-249
  • 2 Pette D, Staron RS. Myosin isoforms, muscle fiber types, and transitions. Microsc Res Tech 2000; 50 (06) 500-509
  • 3 Roca J, Agusti AG, Alonso A. et al. Effects of training on muscle O2 transport at VO2max. J Appl Physiol 1992; 73 (03) 1067-1076
  • 4 Knight DR, Schaffartzik W, Poole DC, Hogan MC, Bebout DE, Wagner PD. Effects of hyperoxia on maximal leg O2 supply and utilization in men. J Appl Physiol 1993; 75 (06) 2586-2594
  • 5 McClaran SR, Harms CA, Pegelow DF, Dempsey JA. Smaller lungs in women affect exercise hyperpnea. J Appl Physiol 1998; 84 (06) 1872-1881
  • 6 Rogers MA, Evans WJ. Changes in skeletal muscle with aging: effects of exercise training. Exerc Sport Sci Rev 1993; 21: 65-102
  • 7 Cannon DT, Coelho AC, Cao R. et al. Skeletal muscle power and fatigue at the tolerable limit of ramp-incremental exercise in COPD. J Appl Physiol 2016; 121 (06) 1365-1373
  • 8 Ade CJ, Broxterman RM, Moore AD, Barstow TJ. Decreases in maximal oxygen uptake following long-duration spaceflight: Role of convective and diffusive O2 transport mechanisms. J Appl Physiol 2017; 122 (04) 968-975
  • 9 Esposito F, Mathieu-Costello O, Shabetai R, Wagner PD, Richardson RS. Limited maximal exercise capacity in patients with chronic heart failure: partitioning the contributors. J Am Coll Cardiol 2010; 55 (18) 1945-1954
  • 10 Owles WH. Alterations in the lactic acid content of the blood as a result of light exercise, and associated changes in the co(2)-combining power of the blood and in the alveolar co(2) pressure. J Physiol 1930; 69 (02) 214-237
  • 11 van der Vaart H, Murgatroyd SR, Rossiter HB, Chen C, Casaburi R, Porszasz J. Selecting constant work rates for endurance testing in COPD: the role of the power-duration relationship. COPD 2014; 11 (03) 267-276
  • 12 Wasserman K. Coupling of external to cellular respiration during exercise: the wisdom of the body revisited. Am J Physiol 1994; 266 (4, Pt 1): E519-E539
  • 13 Goodwin ML, Harris JE, Hernández A, Gladden LB. Blood lactate measurements and analysis during exercise: a guide for clinicians. J Diabetes Sci Technol 2007; 1 (04) 558-569
  • 14 Koike A, Weiler-Ravell D, McKenzie DK, Zanconato S, Wasserman K. Evidence that the metabolic acidosis threshold is the anaerobic threshold. J Appl Physiol 1990; 68 (06) 2521-2526
  • 15 Neill WA, Jensen PE, Rich GB, Werschkul JD. Effect of decreased O2 supply to tissue on the lactate: pyruvate ratio in blood. J Clin Invest 1969; 48 (10) 1862-1869
  • 16 Ekblom B, Wilson G, Astrand PO. Central circulation during exercise after venesection and reinfusion of red blood cells. J Appl Physiol 1976; 40 (03) 379-383
  • 17 Spriet LL, Gledhill N, Froese AB, Wilkes DL. Effect of graded erythrocythemia on cardiovascular and metabolic responses to exercise. J Appl Physiol 1986; 61 (05) 1942-1948
  • 18 van Hall G, Calbet JA, Søndergaard H, Saltin B. The re-establishment of the normal blood lactate response to exercise in humans after prolonged acclimatization to altitude. J Physiol 2001; 536 (Pt 3): 963-975
  • 19 Benedetto D, Rao CM, Cefalù C. et al. Effects of blood transfusion on exercise capacity in thalassemia major patients. PLoS One 2015; 10 (05) e0127553
  • 20 Wasserman K, McIlroy MB. Detecting the threshold of anaerobic metabolism in cardiac patients during exercise. Am J Cardiol 1964; 14: 844-852
  • 21 Stanley WC, Gertz EW, Wisneski JA, Morris DL, Neese RA, Brooks GA. Systemic lactate kinetics during graded exercise in man. Am J Physiol 1985; 249 (6, Pt 1): E595-E602
  • 22 Poole DC, Rossiter HB, Brooks GA, Gladden LB. The anaerobic threshold: 50+ years of controversy. J Physiol 2021; 599 (03) 737-767
  • 23 Proctor DN, Koch DW, Newcomer SC, Le KU, Leuenberger UA. Impaired leg vasodilation during dynamic exercise in healthy older women. J Appl Physiol 2003; 95 (05) 1963-1970
  • 24 Proctor DN, Parker BA. Vasodilation and vascular control in contracting muscle of the aging human. Microcirculation 2006; 13 (04) 315-327
  • 25 Mortensen SP, Dawson EA, Yoshiga CC. et al. Limitations to systemic and locomotor limb muscle oxygen delivery and uptake during maximal exercise in humans. J Physiol 2005; 566 (Pt 1): 273-285
  • 26 Laughlin MH, Davis MJ, Secher NH. et al. Peripheral circulation. Compr Physiol 2012; 2 (01) 321-447
  • 27 Rowell LB. Human Circulation. New York, NY: Oxford University Press; 1986
  • 28 Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol 2001; 37 (01) 153-156
  • 29 Green AL, Wang S, Purvis S. et al. Identifying cardiorespiratory neurocircuitry involved in central command during exercise in humans. J Physiol 2007; 578 (Pt 2): 605-612
  • 30 Krogh A, Lindhard J. The regulation of respiration and circulation during the initial stages of muscular work. J Physiol 1913; 47 (1–2): 112-136
  • 31 Cornwell WK, Tran T, Cerbin L. et al. New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis. J Physiol 2020; 598 (13) 2575-2587
  • 32 Rowell LB. Human Cardiovascular Control. New York, NY: Oxford University Press; 1993
  • 33 Lalande S, Luoma CE, Miller AD, Johnson BD. Effect of changes in intrathoracic pressure on cardiac function at rest and during moderate exercise in health and heart failure. Exp Physiol 2012; 97 (02) 248-256
  • 34 Hainsworth R, Drinkhill MJ. Counterpoint: active venoconstriction is not important in maintaining or raising end-diastolic volume and stroke volume during exercise and orthostasis. J Appl Physiol 2006; 101 (04) 1264-1265 , discussion 1265–1266, 1270
  • 35 Rothe CF. Point: active venoconstriction is/is not important in maintaining or raising end-diastolic volume and stroke volume during exercise and orthostasis. J Appl Physiol 2006; 101 (04) 1262-1264 , discussion 1265–1266, 1270
  • 36 Fisher JP, Young CN, Fadel PJ. Autonomic adjustments to exercise in humans. Compr Physiol 2015; 5 (02) 475-512
  • 37 Miki K, Yoshimoto M. Exercise-induced modulation of baroreflex control of sympathetic nerve activity. Front Neurosci 2018; 12: 493
  • 38 Hearon Jr CM, Dinenno FA. Regulation of skeletal muscle blood flow during exercise in ageing humans. J Physiol 2016; 594 (08) 2261-2273
  • 39 Stringer W, Wasserman K, Casaburi R, Pórszász J, Maehara K, French W. Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise. J Appl Physiol 1994; 76 (04) 1462-1467
  • 40 Poole DC, Copp SW, Hirai DM, Musch TI. Dynamics of muscle microcirculatory and blood-myocyte O(2) flux during contractions. Acta Physiol (Oxf) 2011; 202 (03) 293-310
  • 41 Harms CA, Babcock MA, McClaran SR. et al. Respiratory muscle work compromises leg blood flow during maximal exercise. J Appl Physiol 1997; 82 (05) 1573-1583
  • 42 Johnson BD, Weisman IM, Zeballos RJ, Beck KC. Emerging concepts in the evaluation of ventilatory limitation during exercise: the exercise tidal flow-volume loop. Chest 1999; 116 (02) 488-503
  • 43 Gagnon P, Bussières JS, Ribeiro F. et al. Influences of spinal anesthesia on exercise tolerance in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186 (07) 606-615
  • 44 Morin D, Viala D. Coordinations of locomotor and respiratory rhythms in vitro are critically dependent on hindlimb sensory inputs. J Neurosci 2002; 22 (11) 4756-4765
  • 45 Haouzi P, Bell HJ. Respiratory effects of changing the volume load imposed on the peripheral venous system. Respir Physiol Neurobiol 2010; 171 (03) 175-180
  • 46 Lovering AT, Eldridge MW, Stickland MK. Counterpoint: exercise-induced intrapulmonary shunting is real. J Appl Physiol 2009; 107 (03) 994-997
  • 47 Hopkins SR, Olfert IM, Wagner PD. Point: exercise-induced intrapulmonary shunting is imaginary. J Appl Physiol 2009; 107 (03) 993-994
  • 48 Constantini K, Tanner DA, Gavin TP, Harms CA, Stager JM, Chapman RF. Prevalence of exercise-induced arterial hypoxemia in distance runners at sea level. Med Sci Sports Exerc 2017; 49 (05) 948-954
  • 49 Dempsey JA, Wagner PD. Exercise-induced arterial hypoxemia. J Appl Physiol 1999; 87 (06) 1997-2006
  • 50 Dominelli PB, Sheel AW. Exercise-induced arterial hypoxemia; some answers, more questions. Appl Physiol Nutr Metab 2019; 44 (06) 571-579
  • 51 Robertson HT. Dead space: the physiology of wasted ventilation. Eur Respir J 2015; 45 (06) 1704-1716
  • 52 Wasserman K, Van Kessel AL, Burton GG. Interaction of physiological mechanisms during exercise. J Appl Physiol 1967; 22 (01) 71-85
  • 53 Wagner PD, Gale GE, Moon RE, Torre-Bueno JR, Stolp BW, Saltzman HA. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 1986; 61 (01) 260-270
  • 54 Rossiter HB. Exercise: kinetic considerations for gas exchange. Compr Physiol 2011; 1 (01) 203-244
  • 55 Thurber C, Dugas LR, Ocobock C, Carlson B, Speakman JR, Pontzer H. Extreme events reveal an alimentary limit on sustained maximal human energy expenditure. Sci Adv 2019; 5 (06) eaaw0341
  • 56 Cannon DT, White AC, Andriano MF, Kolkhorst FW, Rossiter HB. Skeletal muscle fatigue precedes the slow component of oxygen uptake kinetics during exercise in humans. J Physiol 2011; 589 (Pt 3): 727-739
  • 57 Keir DA, Copithorne DB, Hodgson MD, Pogliaghi S, Rice CL, Kowalchuk JM. The slow component of pulmonary O2 uptake accompanies peripheral muscle fatigue during high-intensity exercise. J Appl Physiol 2016; 121 (02) 493-502
  • 58 de Almeida Azevedo R, Keir DA, Forot J, Iannetta D, Millet GY, Murias JM. The effects of exercise intensity and duration on the relationship between the slow component of V̇O2 and peripheral fatigue. Acta Physiol (Oxf) 2022; 234 (02) e13776
  • 59 Coyle EF, Coggan AR, Hemmert MK, Ivy JL. Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate. J Appl Physiol 1986; 61 (01) 165-172
  • 60 Ozyener F, Rossiter HB, Ward SA, Whipp BJ. Influence of exercise intensity on the on- and off-transient kinetics of pulmonary oxygen uptake in humans. J Physiol 2001; 533 (Pt 3): 891-902
  • 61 Coats EM, Rossiter HB, Day JR, Miura A, Fukuba Y, Whipp BJ. Intensity-dependent tolerance to exercise after attaining V(O2) max in humans. J Appl Physiol 2003; 95 (02) 483-490
  • 62 Hill AV, Lupton H. Muscular exercise, lactic acid, and the supply and utilization of oxygen. QJM 1923; 16 (62) 135-171
  • 63 Poole DC, Ward SA, Gardner GW, Whipp BJ. Metabolic and respiratory profile of the upper limit for prolonged exercise in man. Ergonomics 1988; 31 (09) 1265-1279
  • 64 Jones AM, Wilkerson DP, DiMenna F, Fulford J, Poole DC. Muscle metabolic responses to exercise above and below the “critical power” assessed using 31P-MRS. Am J Physiol Regul Integr Comp Physiol 2008; 294 (02) R585-R593
  • 65 Barker T, Poole DC, Noble ML, Barstow TJ. Human critical power-oxygen uptake relationship at different pedalling frequencies. Exp Physiol 2006; 91 (03) 621-632
  • 66 Gibbons RJ, Balady GJ, Bricker JT. et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Committee to Update the 1997 Exercise Testing Guidelines. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol 2002; 40 (08) 1531-1540
  • 67 Balady GJ, Arena R, Sietsema K. et al; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, Interdisciplinary Council on Quality of Care and Outcomes Research. Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation 2010; 122 (02) 191-225
  • 68 Fletcher GF, Ades PA, Kligfield P. et al; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Nutrition, Physical Activity and Metabolism, Council on Cardiovascular and Stroke Nursing, and Council on Epidemiology and Prevention. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation 2013; 128 (08) 873-934
  • 69 Rodgers GP, Ayanian JZ, Balady G. et al. American College of Cardiology/American Heart Association Clinical Competence Statement on Stress Testing. A Report of the American College of Cardiology/American Heart Association/American College of Physicians-American Society of Internal Medicine Task Force on Clinical Competence. Circulation 2000; 102 (14) 1726-1738
  • 70 American Thoracic Society, American College of Chest Physicians. ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003; 167 (02) 211-277
  • 71 Keteyian SJ, Isaac D, Thadani U. et al; HF-ACTION Investigators. Safety of symptom-limited cardiopulmonary exercise testing in patients with chronic heart failure due to severe left ventricular systolic dysfunction. Am Heart J 2009; 158 (4, Suppl): S72-S77
  • 72 Myers J, Forman DE, Balady GJ. et al; American Heart Association Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention of the Council on Clinical Cardiology, Council on Lifestyle and Cardiometabolic Health, Council on Epidemiology and Prevention, and Council on Cardiovascular and Stroke Nursing. Supervision of exercise testing by nonphysicians: a scientific statement from the American Heart Association. Circulation 2014; 130 (12) 1014-1027
  • 73 Nayor M, Shah RV, Tanguay M. et al. Feasibility, methodology, and interpretation of broad-scale assessment of cardiorespiratory fitness in a large community-based sample. Am J Cardiol 2021; 157: 56-63
  • 74 Myers J, Buchanan N, Walsh D. et al. Comparison of the ramp versus standard exercise protocols. J Am Coll Cardiol 1991; 17 (06) 1334-1342
  • 75 McKay GA, Banister EW. A comparison of maximum oxygen uptake determination by bicycle ergometry at various pedaling frequencies and by treadmill running at various speeds. Eur J Appl Physiol Occup Physiol 1976; 35 (03) 191-200
  • 76 Cockcroft A, Beaumont A, Adams L, Guz A. Arterial oxygen desaturation during treadmill and bicycle exercise in patients with chronic obstructive airways disease. Clin Sci (Lond) 1985; 68 (03) 327-332
  • 77 Hsia D, Casaburi R, Pradhan A, Torres E, Porszasz J. Physiological responses to linear treadmill and cycle ergometer exercise in COPD. Eur Respir J 2009; 34 (03) 605-615
  • 78 Sietsema KE, Sue DY, Stringer WW, Ward SA. Wasserman and Whipp's Principles of Exercise Testing and Interpretation. Philadelphia, PA: Wolters Kluwer; 2021
  • 79 Porszasz J, Casaburi R, Somfay A, Woodhouse LJ, Whipp BJ. A treadmill ramp protocol using simultaneous changes in speed and grade. Med Sci Sports Exerc 2003; 35 (09) 1596-1603
  • 80 Buchfuhrer MJ, Hansen JE, Robinson TE, Sue DY, Wasserman K, Whipp BJ. Optimizing the exercise protocol for cardiopulmonary assessment. J Appl Physiol 1983; 55 (05) 1558-1564
  • 81 Puente-Maestu L, Palange P, Casaburi R. et al. Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement. Eur Respir J 2016; 47 (02) 429-460
  • 82 Casaburi R, Merrill DD, Harding G. et al; CBQC Constant Work Rate Exercise Working Group. A conceptual framework for use of increased endurance time during constant work rate cycle ergometry as a patient-focused meaningful outcome in COPD clinical trials. Chronic Obstr Pulm Dis (Miami) 2022; 9 (02) 252-265
  • 83 Ward SA. Open-circuit respirometry: real-time, laboratory-based systems. Eur J Appl Physiol 2018; 118 (05) 875-898
  • 84 Roecker K, Prettin S, Sorichter S. Gas exchange measurements with high temporal resolution: the breath-by-breath approach. Int J Sports Med 2005; 26 (Suppl. 01) S11-S18
  • 85 Ramos-Álvarez JJ, Lorenzo-Capellá I, Calderón-Montero FJ. Disadvantages of automated respiratory gas exchange analyzers. Front Physiol 2020; 11: 19
  • 86 Bowen TS, Cannon DT, Begg G, Baliga V, Witte KK, Rossiter HB. A novel cardiopulmonary exercise test protocol and criterion to determine maximal oxygen uptake in chronic heart failure. J Appl Physiol 2012; 113 (03) 451-458
  • 87 Rossiter HB, Kowalchuk JM, Whipp BJ. A test to establish maximum O2 uptake despite no plateau in the O2 uptake response to ramp incremental exercise. J Appl Physiol 2006; 100 (03) 764-770
  • 88 Poole DC, Jones AM. Measurement of the maximum oxygen uptake V̇o2max: V̇o2peak is no longer acceptable. J Appl Physiol 2017; 122 (04) 997-1002
  • 89 Wilcox SL, Broxterman RM, Barstow TJ. Constructing quasi-linear V̇O2 responses from nonlinear parameters. J Appl Physiol 2016; 120 (02) 121-129
  • 90 Keir DA, Benson AP, Love LK, Robertson TC, Rossiter HB, Kowalchuk JM. Influence of muscle metabolic heterogeneity in determining the V̇o2p kinetic response to ramp-incremental exercise. J Appl Physiol 2016; 120 (05) 503-513
  • 91 Iannetta D, de Almeida Azevedo R, Keir DA, Murias JM. Establishing the V̇o2 versus constant-work-rate relationship from ramp-incremental exercise: simple strategies for an unsolved problem. J Appl Physiol 2019; 127 (06) 1519-1527
  • 92 Gimenes AC, Neder JA, Dal Corso S. et al. Relationship between work rate and oxygen uptake in mitochondrial myopathy during ramp-incremental exercise. Braz J Med Biol Res 2011; 44 (04) 354-360
  • 93 Belardinelli R, Lacalaprice F, Tiano L, Muçai A, Perna GP. Cardiopulmonary exercise testing is more accurate than ECG-stress testing in diagnosing myocardial ischemia in subjects with chest pain. Int J Cardiol 2014; 174 (02) 337-342
  • 94 Tanabe Y, Nakagawa I, Ito E, Suzuki K. Hemodynamic basis of the reduced oxygen uptake relative to work rate during incremental exercise in patients with chronic heart failure. Int J Cardiol 2002; 83 (01) 57-62
  • 95 Henderson Y, Prince AL. The oxygen pulse and the systolic discharge. Am J Physiol 1914; 35: 106-115
  • 96 Sirichana W, Neufeld EV, Wang X, Hu SB, Dolezal BA, Cooper CB. Reference values for chronotropic index from 1280 incremental cycle ergometry tests. Med Sci Sports Exerc 2020; 52 (12) 2515-2521
  • 97 Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol 1986; 60 (06) 2020-2027
  • 98 Blackie SP, Fairbarn MS, McElvaney NG, Wilcox PG, Morrison NJ, Pardy RL. Normal values and ranges for ventilation and breathing pattern at maximal exercise. Chest 1991; 100 (01) 136-142
  • 99 Boulding R, Stacey R, Niven R, Fowler SJ. Dysfunctional breathing: a review of the literature and proposal for classification. Eur Respir Rev 2016; 25 (141) 287-294
  • 100 Bansal T, Haji GS, Rossiter HB, Polkey MI, Hull JH. Exercise ventilatory irregularity can be quantified by approximate entropy to detect breathing pattern disorder. Respir Physiol Neurobiol 2018; 255: 1-6
  • 101 Lie AH, Grønnevik I, Frisk B. et al. Breathing patterns in people with exercise-induced laryngeal obstruction. Physiol Rep 2021; 9 (22) e15086
  • 102 Babb TG. Exercise ventilatory limitation: the role of expiratory flow limitation. Exerc Sport Sci Rev 2013; 41 (01) 11-18
  • 103 Guenette JA, Dominelli PB, Reeve SS, Durkin CM, Eves ND, Sheel AW. Effect of thoracic gas compression and bronchodilation on the assessment of expiratory flow limitation during exercise in healthy humans. Respir Physiol Neurobiol 2010; 170 (03) 279-286
  • 104 Koulouris NG, Dimopoulou I, Valta P, Finkelstein R, Cosio MG, Milic-Emili J. Detection of expiratory flow limitation during exercise in COPD patients. J Appl Physiol 1997; 82 (03) 723-731
  • 105 Ma S, Hecht A, Varga J. et al. Breath-by-breath quantification of progressive airflow limitation during exercise in COPD: a new method. Respir Med 2010; 104 (03) 389-396
  • 106 Milne KM, Domnik NJ, Phillips DB. et al. Evaluation of dynamic respiratory mechanical abnormalities during conventional CPET. Front Med (Lausanne) 2020; 7: 548
  • 107 O'Donnell DE, Voduc N, Fitzpatrick M, Webb KA. Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease. Eur Respir J 2004; 24 (01) 86-94
  • 108 Yamaya Y, Bogaard HJ, Wagner PD, Niizeki K, Hopkins SR. Validity of pulse oximetry during maximal exercise in normoxia, hypoxia, and hyperoxia. J Appl Physiol 2002; 92 (01) 162-168
  • 109 Ascha M, Bhattacharyya A, Ramos JA, Tonelli AR. Pulse oximetry and arterial oxygen saturation during cardiopulmonary exercise testing. Med Sci Sports Exerc 2018; 50 (10) 1992-1997
  • 110 Neder JA, Berton DC, Phillips DB, O'Donnell DE. Exertional ventilation/carbon dioxide output relationship in COPD: from physiological mechanisms to clinical applications. Eur Respir Rev 2021; 30 (161) 200190
  • 111 Robertson HT. Gas exchange consequences of left heart failure. Compr Physiol 2011; 1 (02) 621-634
  • 112 Van Iterson EH, Johnson BD, Borlaug BA, Olson TP. Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure. Eur J Heart Fail 2017; 19 (12) 1675-1685
  • 113 Sullivan MJ, Higginbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. Circulation 1988; 77 (03) 552-559
  • 114 Piepoli M, Clark AL, Volterrani M, Adamopoulos S, Sleight P, Coats AJ. Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure: effects of physical training. Circulation 1996; 93 (05) 940-952
  • 115 Ponikowski P, Banasiak W. Chemosensitivity in chronic heart failure. Heart Fail Monit 2001; 1 (04) 126-131
  • 116 Woods PR, Olson TP, Frantz RP, Johnson BD. Causes of breathing inefficiency during exercise in heart failure. J Card Fail 2010; 16 (10) 835-842
  • 117 West JB. Ventilation-perfusion inequality and overall gas exchange in computer models of the lung. Respir Physiol 1969; 7 (01) 88-110
  • 118 Hansen JE, Ulubay G, Chow BF, Sun XG, Wasserman K. Mixed-expired and end-tidal CO2 distinguish between ventilation and perfusion defects during exercise testing in patients with lung and heart diseases. Chest 2007; 132 (03) 977-983
  • 119 Sietsema KE, Cooper DM, Perloff JK. et al. Control of ventilation during exercise in patients with central venous-to-systemic arterial shunts. J Appl Physiol 1988; 64 (01) 234-242
  • 120 Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Gas exchange detection of exercise-induced right-to-left shunt in patients with primary pulmonary hypertension. Circulation 2002; 105 (01) 54-60
  • 121 Lewis DA, Sietsema KE, Casaburi R, Sue DY. Inaccuracy of noninvasive estimates of VD/VT in clinical exercise testing. Chest 1994; 106 (05) 1476-1480
  • 122 Cao M, Stringer WW, Corey S. et al. Transcutaneous PCO2 for exercise gas exchange efficiency in chronic obstructive pulmonary disease. COPD 2021; 18 (01) 16-25
  • 123 Hoffmann U, Essfeld D, Stegemann J. Comparison of arterial, end-tidal and transcutaneous PCO2 during moderate exercise and external CO2 loading in humans. Eur J Appl Physiol Occup Physiol 1990; 61 (1–2): 1-4
  • 124 Grant S, Aitchison T, Henderson E. et al. A comparison of the reproducibility and the sensitivity to change of visual analogue scales, Borg scales, and Likert scales in normal subjects during submaximal exercise. Chest 1999; 116 (05) 1208-1217
  • 125 O'Donnell DE, Guenette JA, Maltais F, Webb KA. Decline of resting inspiratory capacity in COPD: the impact on breathing pattern, dyspnea, and ventilatory capacity during exercise. Chest 2012; 141 (03) 753-762
  • 126 Puente-Maestu L, García de Pedro J, Benedetti PA, López JJG, Giron-Matute WI. Reference values in adults. In: Palange P, Laveneziana P, Neder JA, Ward SA. eds. Clinical Exercise Testing. Lausanne: European Respiratory Society; 2018: 82-106
  • 127 Andersson GBJ, Cocchiarella L. Guides to the Evaluation of Permanent Impairment. 5th ed.. Chigcao, IL: American Medical Association; 2000
  • 128 Inuzuka R, Diller GP, Borgia F. et al. Comprehensive use of cardiopulmonary exercise testing identifies adults with congenital heart disease at increased mortality risk in the medium term. Circulation 2012; 125 (02) 250-259
  • 129 Stout KK, Daniels CJ, Aboulhosn JA. et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 139 (14) e698-e800
  • 130 Keteyian SJ, Patel M, Kraus WE. et al; HF-ACTION Investigators. Variables measured during cardiopulmonary exercise testing as predictors of mortality in chronic systolic heart failure. J Am Coll Cardiol 2016; 67 (07) 780-789
  • 131 Faselis C, Doumas M, Pittaras A. et al. Exercise capacity and all-cause mortality in male veterans with hypertension aged ≥70 years. Hypertension 2014; 64 (01) 30-35
  • 132 Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002; 346 (11) 793-801
  • 133 Leeper NJ, Myers J, Zhou M. et al. Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease. J Vasc Surg 2013; 57 (03) 728-733
  • 134 Sietsema KE, Amato A, Adler SG, Brass EP. Exercise capacity as a predictor of survival among ambulatory patients with end-stage renal disease. Kidney Int 2004; 65 (02) 719-724
  • 135 Nixon PA, Orenstein DM, Kelsey SF, Doershuk CF. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med 1992; 327 (25) 1785-1788
  • 136 Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds Jr LH, Wilson JR. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991; 83 (03) 778-786
  • 137 Wagner J, Agostoni P, Arena R. et al. The role of gas exchange variables in cardiopulmonary exercise testing for risk stratification and management of heart failure with reduced ejection fraction. Am Heart J 2018; 202: 116-126
  • 138 Gitt AK, Wasserman K, Kilkowski C. et al. Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death. Circulation 2002; 106 (24) 3079-3084
  • 139 Cahalin LP, Chase P, Arena R. et al. A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure. Heart Fail Rev 2013; 18 (01) 79-94
  • 140 Nadruz Jr W, West E, Sengeløv M. et al. Prognostic value of cardiopulmonary exercise testing in heart failure with reduced, midrange, and preserved ejection fraction. J Am Heart Assoc 2017; 6 (11) e006000
  • 141 Lewis GD, Zlotoff DA. Cardiopulmonary exercise testing-based risk stratification in the modern era of advanced heart failure management. JACC Heart Fail 2021; 9 (03) 237-240
  • 142 Fleisher LA, Fleischmann KE, Auerbach AD. et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130 (24) 2215-2245
  • 143 Levett DZH, Jack S, Swart M. et al; Perioperative Exercise Testing and Training Society (POETTS). Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation. Br J Anaesth 2018; 120 (03) 484-500
  • 144 Snowden CP, Prentis J, Jacques B. et al. Cardiorespiratory fitness predicts mortality and hospital length of stay after major elective surgery in older people. Ann Surg 2013; 257 (06) 999-1004
  • 145 Moran J, Wilson F, Guinan E, McCormick P, Hussey J, Moriarty J. Role of cardiopulmonary exercise testing as a risk-assessment method in patients undergoing intra-abdominal surgery: a systematic review. Br J Anaesth 2016; 116 (02) 177-191
  • 146 Older P, Hall A, Hader R. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest 1999; 116 (02) 355-362
  • 147 Brunelli A, Kim AW, Berger KI, Addrizzo-Harris DJ. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143 (5, Suppl): e166S-e190S
  • 148 Brunelli A, Charloux A, Bolliger CT. et al; European Respiratory Society, European Society of Thoracic Surgeons Joint Task Force on Fitness For Radical Therapy. The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer. Eur J Cardiothorac Surg 2009; 36 (01) 181-184
  • 149 Colice GL, Shafazand S, Griffin JP, Keenan R, Bolliger CT. American College of Chest Physicians. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest 2007; 132 (3, Suppl): 161S-177S
  • 150 Chouinard G, Roy P, Blais MC. et al. Exercise testing and postoperative complications after minimally invasive lung resection: a cohort study. Front Physiol 2022; 13: 951460
  • 151 Magrì D, Limongelli G, Re F. et al. Cardiopulmonary exercise test and sudden cardiac death risk in hypertrophic cardiomyopathy. Heart 2016; 102 (08) 602-609
  • 152 Wensel R, Francis DP, Meyer FJ. et al. Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension. Int J Cardiol 2013; 167 (04) 1193-1198
  • 153 Ohuchi H, Tanabe Y, Kamiya C. et al. Cardiopulmonary variables during exercise predict pregnancy outcome in women with congenital heart disease. Circ J 2013; 77 (02) 470-476
  • 154 Lindley KJ, Bairey Merz CN, Asgar AW. et al; American College of Cardiology Cardiovascular Disease in Women Committee and the Cardio-Obstetrics Work Group. Management of women with congenital or inherited cardiovascular disease from pre-conception through pregnancy and postpartum: JACC Focus Seminar 2/5. J Am Coll Cardiol 2021; 77 (14) 1778-1798
  • 155 Houstis NE, Eisman AS, Pappagianopoulos PP. et al. Exercise intolerance in heart failure with preserved ejection fraction: diagnosing and ranking its causes using personalized O2 pathway analysis. Circulation 2018; 137 (02) 148-161
  • 156 Phillips DB, Neder JA, Elbehairy AF. et al; Canadian Respiratory Research Network. Qualitative components of dyspnea during incremental exercise across the COPD continuum. Med Sci Sports Exerc 2021; 53 (12) 2467-2476
  • 157 O'Donnell DE, Elbehairy AF, Domnik NJ. et al. Patterns of cardiopulmonary response to exercise in COPD. In: Palange P, Laveneziana P, Neder JA, Ward SA. eds. Clinical Exercise Testing. Lausanne: European Respiratory Society; 2018: 107-127
  • 158 Boerrigter BG, Bogaard HJ, Trip P. et al. Ventilatory and cardiocirculatory exercise profiles in COPD: the role of pulmonary hypertension. Chest 2012; 142 (05) 1166-1174
  • 159 Simon M, LeBlanc P, Jobin J, Desmeules M, Sullivan MJ, Maltais F. Limitation of lower limb VO(2) during cycling exercise in COPD patients. J Appl Physiol 2001; 90 (03) 1013-1019
  • 160 Maltais F, Simard AA, Simard C, Jobin J, Desgagnés P, LeBlanc P. Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD. Am J Respir Crit Care Med 1996; 153 (01) 288-293
  • 161 Broxterman RM, Hoff J, Wagner PD, Richardson RS. Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs. J Physiol 2020; 598 (03) 599-610
  • 162 Cheyne WS, Harper MI, Gelinas JC, Sasso JP, Eves ND. Mechanical cardiopulmonary interactions during exercise in health and disease. J Appl Physiol 2020; 128 (05) 1271-1279
  • 163 Waraich S, Sietsema KE. Clinical cardiopulmonary exercise testing: patient and referral characteristics. J Cardiopulm Rehabil Prev 2007; 27 (06) 400-406
  • 164 DePaso WJ, Winterbauer RH, Lusk JA, Dreis DF, Springmeyer SC. Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience. Chest 1991; 100 (05) 1293-1299
  • 165 Pratter MR, Curley FJ, Dubois J, Irwin RS. Cause and evaluation of chronic dyspnea in a pulmonary disease clinic. Arch Intern Med 1989; 149 (10) 2277-2282
  • 166 Sandberg J, Ekström M, Börjesson M. et al. Underlying contributing conditions to breathlessness among middle-aged individuals in the general population: a cross-sectional study. BMJ Open Respir Res 2020; 7 (01) e000643
  • 167 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respir Med 2011; 105 (07) 1014-1021
  • 168 Martinez FJ, Stanopoulos I, Acero R, Becker FS, Pickering R, Beamis JF. Graded comprehensive cardiopulmonary exercise testing in the evaluation of dyspnea unexplained by routine evaluation. Chest 1994; 105 (01) 168-174
  • 169 Morris MJ, Grbach VX, Deal LE, Boyd SY, Morgan JA, Johnson JE. Evaluation of exertional dyspnea in the active duty patient: the diagnostic approach and the utility of clinical testing. Mil Med 2002; 167 (04) 281-288
  • 170 Palange P, Ward SA, Carlsen KH. et al; ERS Task Force. Recommendations on the use of exercise testing in clinical practice. Eur Respir J 2007; 29 (01) 185-209
  • 171 O'Donnell DE, Milne KM, Vincent SG, Neder JA. Unraveling the causes of unexplained dyspnea: the value of exercise testing. Clin Chest Med 2019; 40 (02) 471-499
  • 172 Tervonen H, Niskanen MM, Sovijärvi AR, Hakulinen AS, Vilkman EA, Aaltonen LM. Fiberoptic videolaryngoscopy during bicycle ergometry: a diagnostic tool for exercise-induced vocal cord dysfunction. Laryngoscope 2009; 119 (09) 1776-1780
  • 173 Nedeljkovic I, Banovic M, Stepanovic J. et al. The combined exercise stress echocardiography and cardiopulmonary exercise test for identification of masked heart failure with preserved ejection fraction in patients with hypertension. Eur J Prev Cardiol 2016; 23 (01) 71-77
  • 174 Laufer-Perl M, Gura Y, Shimiaie J. et al. Mechanisms of effort intolerance in patients with rheumatic mitral stenosis: combined echocardiography and cardiopulmonary stress protocol. JACC Cardiovasc Imaging 2017; 10 (06) 622-633
  • 175 Berry NC, Manyoo A, Oldham WM. et al. Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice. Pulm Circ 2015; 5 (04) 610-618
  • 176 Huang W, Resch S, Oliveira RK, Cockrill BA, Systrom DM, Waxman AB. Invasive cardiopulmonary exercise testing in the evaluation of unexplained dyspnea: Insights from a multidisciplinary dyspnea center. Eur J Prev Cardiol 2017; 24 (11) 1190-1199
  • 177 Joseph P, Arevalo C, Oliveira RKF. et al. Insights from invasive cardiopulmonary exercise testing of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Chest 2021; 160 (02) 642-651
  • 178 Taivassalo T, Jensen TD, Kennaway N, DiMauro S, Vissing J, Haller RG. The spectrum of exercise tolerance in mitochondrial myopathies: a study of 40 patients. Brain 2003; 126 (Pt 2): 413-423