European Respiratory Society
Clinical Exercise Testing

In the last 10 years, the use of clinical exercise testing in respiratory medicine has grown significantly and, if used in the appropriate context, it has been demonstrated to provide clinically useful and relevant information. However, as its implementation and interpretation can be complicated, it should be used alongside previous medical evaluation (including medical history, physical examination and other appropriate complementary tests) and should be interpreted with the results of these additional tests in mind. This timely ERS Monograph aims to provide a comprehensive update on the contemporary uses of exercise testing to answer clinically relevant questions in respiratory medicine. The book covers: equipment and measurements; exercise testing in adults and children; cardiac diseases; interstitial lung disease; pulmonary vascular disease; chronic obstructive pulmonary disease; pre-surgical testing; and much more.

  • ERS Monograph
  1. Page v
  2. Page vi
  3. Page x
  4. Page 1
    Abstract
    Susan A. Ward, Human Bio-Energetics Research Centre, Crickhowell, Powys NP8 1AT, UK. E-mail: saward@dsl.pipex.com

    Exercise intolerance, or the inability to sustain muscular exercise, is a cardinal feature of many cardiopulmonary diseases. It is dependent in large part on the constraints and limitations placed on O2 transport to its intramuscular site of utilisation as the terminal oxidant of the mitochondrial electron transport chain. These reflect the onset of operational failure within the normally coordinated interaction between skeletal muscle energetics and the cardiocirculatory and respiratory systems in response to exertional stress. The goal of clinical exercise testing is to establish the underlying contributions of these systems to exercise intolerance, using appropriately designed exercise-test formats. This chapter considers the normal operation of these systems in terms of their intensity-related and temporally related response profiles to incremental (ramp) and constant-WR exercise performed to the limit of tolerance.

    Cite as: Ward SA. Determinants of the physiological systems responses to muscular exercise in healthy subjects. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 1–33 [https://doi.org/10.1183/2312508X.10010917].

  5. Page 34
    Abstract
    J. Alberto Neder, 102 Stuart Street, Kingston, ON, Canada K7L 2V6. E-mail: alberto.neder@queensu.ca

    CPET is helpful in uncovering the causes of exercise intolerance in patients with cardiorespiratory diseases. In respirology practice, CPET is usually requested as part of the work-up for unexplained or “out-of-proportion” dyspnoea (relative to resting lung function impairment). However, the test rarely pinpoints a specific diagnosis; thus, it is better viewed as an initial screening procedure to guide further investigative efforts. This is particularly true in the modern clinical scenario in which referred subjects present with multiple comorbidities in addition to polypharmacy, obesity and extreme sedentarism. Using a syndromic approach, this chapter highlights the clusters of findings indicative of: 1) normal maximal and submaximal tests, 2) obesity, 3) O2 delivery/utilisation impairment, 4) mechanical ventilatory impairment, 5) pulmonary gas-exchange impairment and 6) dysfunctional breathing hyperventilation disorder. In each of these contexts, we emphasise some interpretative hints and pitfalls that might prove valuable to the busy physician in charge of reading CPET results in pulmonary function testing laboratories.

    Cite as: Neder JA, Berton DC, Rocha A, et al. Abnormal patterns of response to incremental CPET. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 34–58 [https://doi.org/10.1183/2312508X.10011017].

  6. Page 59
    Abstract
    Janos Porszasz, Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute, 1124 W. Carson Street, Torrance, CA 90502, USA. E-mail: porszasz@ucla.edu

    CPET relies on a number of devices and sensors that need to function correctly in order to make sure that all assessments are valid. This chapter outlines the most important aspects of the measurement techniques and methods, and gives a practical model for adequate quality control for the CPET laboratory. In addition to choosing the appropriate ergometer to be utilised in any particular application, it is important to choose an adequate testing methodology for the given clinical population. In most cases, the pattern of gas-exchange and cardiovascular responses inform clinical judgement, whether it is diagnostic or follow-up after a therapeutic intervention or prognostication. Although wearable devices are not strictly related to CPET, they are widely used to assess activity levels, and as in some instances these are involved in health assessments, we give a short review of these only to point out that adequate quality control and validation is needed before using these in clinical studies. The accuracy of clinical judgement considering the results of CPET will be assured only if the user is confident in the accuracy of the measurements made.

    Cite as: Porszasz J, Stringer W, Casaburi R. Equipment, measurements and quality control. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 59–81 [https://doi.org/10.1183/2312508X.10011117].

  7. Page 82
    Abstract
    Luis Puente-Maestu, Hospital General Universitario Gregorio Marañón, Servicio de Neumología, c/ Doctor Ezquerdo 46 28007 Madrid, Spain. E-mail: lpuen01@ucm.es

    To decide whether a measured exercise response is normal or not, observations have to be compared with mean reference values obtained from large samples of supposedly healthy populations. Biological variability among individuals usually follows a normal distribution, and hence the criterion to decide whether a response as abnormal is one or two times the SD or the standard error of the estimates (regression equations).When selecting reference values, one important consideration we must bear in mind is whether the individual we are testing matches the population in which the reference values were obtained. This chapter intends to comprehensively evaluate the most relevant reference values, describing values or equations with brief methodological notes and information about the variability of the estimates (SEs) and the strength of the relationship (R2) when provided by the authors.

    Cite as: Puente-Maestu L, García de Pedro J, Benedetti PA, et al. Reference values in adults. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 82–106 [https://doi.org/10.1183/2312508X.10011217].

  8. Page 107
    Abstract
    D.E. O'Donnell, Division of Respiratory Medicine, 102 Stuart Street, Kingston, ON, Canada K7L 2V6. E-mail: odonnell@queensu.ca

    Dyspnoea and exercise limitation are among the most common symptoms experienced by patients with COPD and are linked to poor perceived health status and increased mortality. CPET provides a unique opportunity to objectively evaluate the ability of the respiratory system to respond to measured physiological stress across the spectrum of disease severity. In symptomatic mild COPD, the combined abnormalities of increased wasted ventilation leading to increased ventilatory demand and critical erosion of the dynamic IRV lead to intolerable respiratory discomfort and early exercise limitation. In moderate-to-severe COPD, these major physiological abnormalities that culminate in a pronounced demand–capacity imbalance of the respiratory system and dyspnoea, become further amplified and are evident at relatively low exercise intensities. In this group, exercise intolerance is often further compounded by the effects of generalised skeletal muscle deconditioning and worsening cardiocirculatory dysfunction. Identification of specific physiological derangements exposed with CPET, facilitates an individualised approach to management in COPD.

    Cite as: O'Donnell DE, Elbehairy AF, Domnik NJ, et al. Patterns of cardiopulmonary response to exercise in COPD. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 107–127 [https://doi.org/10.1183/2312508X.10011317].

  9. Page 128
    Abstract
    Jordan A. Guenette, Centre for Heart Lung Innovation, St Paul's Hospital, 166-1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6. E-mail: jordan.guenette@hli.ubc.ca

    ILDs are a pathologically distinct group of disorders characterised by alveolar and interstitial damage leading to chronic fibrosis. Poor exercise tolerance is a cardinal feature in fibrotic ILD. Exercise intolerance in fibrotic ILD patients is related to a variety of factors including impaired pulmonary gas exchange, abnormalities in lung mechanics and cardiocirculatory function, and potentially skeletal muscle dysfunction. Typical findings in CPET include hypoxaemia, an increased ventilatory response, a rapid and shallow breathing pattern, low IRV, and increased sensations of dyspnoea and leg effort/discomfort. In practice, CPET might be useful to confirm whether a patient's symptoms and exercise intolerance can be ascribed to the underlying fibrotic ILD, comorbidities, deconditioning and/or ageing. CPET can also be useful in patients with worsening dyspnoea that cannot be explained satisfactorily by changes in pulmonary function or chest imaging. CPET might also provide valuable prognostic information and may assist pre-rehabilitation assessment and exercise prescription.

    Cite as: Molgat-Seon Y, Guenette JA, Schaeffer MR, et al. Patterns of cardiopulmonary response to exercise in fibrotic ILD. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 128–145 [https://doi.org/10.1183/2312508X.10020317].

  10. Page 146
    Abstract
    Piergiuseppe Agostoni, Dept of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Via Parea, 4 20138 Milan, Italy. E-mail: piergiuseppe.agostoni@unimi.it

    In cardiac disease, CPET is currently frequently used for diagnostic and prognostic reasons, as well as for evaluating therapeutic efficacy. Indeed, CPET-derived parameters such as VO2 at peak and the anaerobic threshold or VE/VCO2 have a pivotal role in the assessment of heart failure, while VE/VCO2 and PETCO2 are of relevant importance in pulmonary hypertension, and the ΔVO2–ΔWR relationship combined with the O2 pulse is a cornerstone of ischaemic heart disease assessment. CPET may be implemented by simultaneous measurements of cardiac output and VO2. This is particularly useful in assessment of therapeutic interventions in chronic heart failure such as physical training, resynchronisation therapy and mitral valve repair.

    Cite as: Agostoni P, Cattadori G. Patterns of cardiopulmonary response to exercise in cardiac diseases. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 146–159 [https://doi.org/10.1183/2312508X.10011417].

  11. Page 160
    Abstract
    Pierantonio Laveneziana, Service des Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée, Département “R3S” (Respiration, Réanimation, Réhabilitation, Sommeil), Pôle PRAGUES, Hôpital Universitaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), 47–83 Boulevard de l'Hôpital, 75013, Paris, France. E-mail: pierantonio.laveneziana@aphp.fr

    The most common pulmonary vascular diseases are PAH and chronic thromboembolic pulmonary hypertension, which lead to dyspnoea and exercise intolerance. The physiological derangements of pulmonary hypertension result in the characteristic abnormalities observed during dynamic exercise in these patients. Impaired cardiac function results in reduced aerobic capacity, low anaerobic threshold and reduced ΔVO2/ΔWR relationship. High physiological dead space and high chemosensitivity contribute to high VE/VCO2 during exercise testing. Consequently, resting hypocapnia with low PETCO2 throughout exercise is typically observed and is related to the severity of disease. Exertional hypoxaemia is also a variable but frequent finding during exercise, which can be related to ventilation–perfusion heterogeneity, low mixed-venous O2 content from impaired cardiac output, and right-to-left shunting through a patent foramen ovale. Even in the absence of significant resting airflow obstruction, dynamic hyperinflation can occur in pulmonary vascular diseases, which contributes to exertional dyspnoea and exercise intolerance. Peripheral muscle dysfunction is another common component of exercise pathophysiology in these conditions.

    Cite as: Weatherald J, Laveneziana P. Patterns of cardiopulmonary response to exercise in pulmonary vascular diseases. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 160–174 [https://doi.org/10.1183/2312508X.10011517].

  12. Page 175
    Abstract
    Sally J. Singh, Centre for Exercise and Rehabilitation Science, NIHR Leicester Biomedical Research Centre – Respiratory, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK. E-mail: sally.singh@uhl-tr.nhs.uk.

    There is a significant body of evidence to support the use of walk tests for the assessment of exercise capacity in patients with COPD. The 6MWT and incremental shuttle walk test (ISWT) are reliable measures, provided they are carried out in line with the international consensus, demonstrating a strong relationship with peak VO2. The test profiles differ, as the ISWT is externally paced and incremental, while the 6MWT is self-paced, but both achieve similar peak values and are sensitive to change. The endurance shuttle walk test complements the ISWT and is conducted at a constant speed. Constant-WR tests appear to be more sensitive to therapeutic interventions. Alternatively, functional performance can be assessed using the self-paced walk test and 4 m gait speed test. These tests have acceptable safety profiles, with few adverse events reported, and thus can be used in both research and clinical practice.

    Cite as: Singh SJ, Harvey-Dunstan TC. Walking for the assessment of patients with COPD. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 175–195 [https://doi.org/10.1183/2312508X.10011617].

  13. Page 196
    Abstract
    Tim Takken, Child Development and Exercise Center, Wilhelmina Children's Hospital UMC Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands. E-mail: t.takken@umcutrecht.nl

    CPET provides clinicians and researchers with a tool to evaluate medical complaints related to exercise, multi-organ function over time in specific disease states, and physical fitness. When performing CPET in children, it is important to consider the remarkable physiological, anatomical and psychological transformations due to growth, maturation and development affecting the physiology and the physiological response to exercise that occur during childhood and adolescence. In children, test performance will depend on exercise equipment and physiology sampling equipment that is easy for children to use and sensitive to the measurement of smaller absolute ventilatory signals. In children, test interpretation will depend on knowledge of the fairly constant HR response to exercise across age and sex, smaller stroke volume and VT, and higher arteriovenous O2 difference in comparison with adults. With respect to specific respiratory diseases, exercise testing can document the severity of airflow decline in exercise-induced bronchoconstriction, the quantity of glottic and supraglottic obstruction in patients with exercise-induced laryngeal obstruction, and the severity of respiratory impairment in bronchopulmonary dysplasia and cystic fibrosis.

    Cite as: Burghard M, Hulzebos EHJ, Olin JT, et al. Exercise testing in children with respiratory diseases. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 196–215 [https://doi.org/10.1183/2312508X.10011717].

  14. Page 216
    Abstract
    Paolo Palange, Dept of Public Health and Infectious Diseases, Sapienza University of Rome, Viale Università 37, 00185 Rome, Italy. E-mail: paolo.palange@uniroma1.it

    Cystic fibrosis (CF), the most frequent genetic disease in the Caucasian population, is characterised by absent or incorrect function of the channel that regulates chloride exchange at the cell surface. The lungs are particularly involved as the very thick and tenacious mucus leads to progressive airflow limitation, respiratory infections, bronchiectasis, lung destruction and, ultimately, respiratory failure. Despite the remarkable advances in treatment which translated into improved survival, most patients present with progressively poorer exercise tolerance. It follows that a growing number of CF patients will be referred to exercise-based evaluations in the forthcoming years. In particular, CPET is useful to determine the mechanisms of exercise intolerance in individual patients who may have treatment and prognostic implications. Moreover, the test is frequently valuable to assess the effects of therapeutic interventions, such as exercise-based rehabilitation programmes.

    Cite as: Palange P, Graziano L, Onorati P, et al. Exercise testing in adults with cystic fibrosis. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 216–221 [https://doi.org/10.1183/2312508X.10011817].

  15. Page 222
    Abstract
    Pierantonio Laveneziana, Service d'Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée, Département ‘R3S’, Pôle PRAGUES, Hôpital Universitaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83 Boulevard de l'Hôpital, 75013, Paris, France. E-mail: pierantonio.laveneziana@aphp.fr

    Resting pulmonary function measurements, although of great diagnostic, discriminative and evaluative value, may not always accurately predict the prognosis in the numerous respiratory and cardiac diseases. Exercise tolerance and its cycle or treadmill CPET-derived variables, have long been recognised as good predictors of mortality in healthy subjects across ages, ranging from young adults to the elderly, and in a wide range of respiratory and cardiovascular diseases (including COPD, ILD, PAH, chronic thromboembolic pulmonary hypertension, chronic heart failure, cystic fibrosis) and, more recently, congenital heart diseases. The purpose of this chapter is to consider the value of CPET-related variables in establishing the prognosis of patients with chronic respiratory and cardiac diseases. Variables obtained with several other exercise testing modalities, such as 6MWT and the shuttle walk test, may have as much prognostic value as CPET-derived variables. However, they fall outside the scope of the present chapter and will not be discussed here.

    Cite as: Laviolette L, Laveneziana P. Exercise testing in the prognostic evaluation of patients with lung and heart diseases. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 222–234 [https://doi.org/10.1183/2312508X.10011917].

  16. Page 235
    Abstract
    Denis E. O'Donnell, Division of Respiratory Medicine, 102 Stuart Street, Kingston, ON, Canada, K7L 2V6. E-mail: odonnell@queensu.ca

    Laboratory exercise testing is uniquely poised to objectively evaluate the degree of physiological impairment, and the effects of therapeutic interventions in COPD in both clinical and research settings. This chapter focuses mainly on the value of constant WR (CWR) endurance testing, with measurement of lung volumes and dyspnoea ratings. This investigative approach has been shown to be both reproducible and responsive in clinical trial settings. The chapter considers the physiological mechanisms of improvement of dyspnoea and exercise endurance following inhaled bronchodilator therapy using CWR cycle ergometry. We present the evidence that reduced lung hyperinflation at rest following bronchodilator therapy provides a solid mechanistic rationale for observed symptomatic improvements in COPD. All classes of short- and long-acting bronchodilators have been shown to improve these efficacy measures at least in moderate-to-severe COPD but responses are somewhat variable. We discuss possible explanations for the variability in responses and consider refinements of the CWR cycle ergometry protocol to improve sensitivity.

    Cite as: O'Donnell DE, Elbehairy AF, Berton DC, et al. Exercise testing in the evaluation of pharmacotherapy in COPD. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 235–250 [https://doi.org/10.1183/2312508X.10012017].

  17. Page 251
    Abstract
    Denny Z.H. Levett, Critical Care Research Dept MP24, CE93, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK. E-mail: d.levett@soton.ac.uk

    Given the comorbid and elderly surgical population, the decision to operate is increasingly challenging. Reliable pre-operative risk stratification is vital to inform perioperative decision making. Reduced exercise capacity is associated with increased post-operative mortality and morbidity. CPET provides an objective measure of exercise capacity and identifies the causes of exercise limitation when exercise capacity is abnormal. CPET data can be used to estimate patient risk, inform consent and shared decision making, and direct pre-operative optimisation including prehabilitation and exercise training programmes, as well as triaging to appropriate levels of post-operative care. Further prospective studies are needed to improve the precision of risk estimates for different patient cohorts and to clarify the best combination of CPET variables to predict surgical outcome. Although early data is encouraging, multicentre trials are required to clarify the most effective type of pre-operative training to improve fitness and evaluate the effects of training programmes on short- and long-term surgical outcomes.

    Cite as: Harvie D, Levett DZH. Exercise testing for pre-operative evaluation. In: Palange P, Laveneziana P, Neder JA, et al., eds. Clinical Exercise Testing (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 251–279 [https://doi.org/10.1183/2312508X.10012117].

  18. Page 280
  19. Page 283
  20. Page 287
  21. Page 291