Exertional ventilation/carbon dioxide output relationship in COPD: from physiological mechanisms to clinical applications

There is well established evidence that the minute ventilation (V′E)/carbon dioxide output (V′CO2) relationship is relevant to a number of patient-related outcomes in COPD. In most circumstances, an increased V′E/V′CO2 reflects an enlarged physiological dead space (“wasted” ventilation), although alveolar hyperventilation (largely due to increased chemosensitivity) may play an adjunct role, particularly in patients with coexistent cardiovascular disease. The V′E/V′CO2 nadir, in particular, has been found to be an important predictor of dyspnoea and poor exercise tolerance, even in patients with largely preserved forced expiratory volume in 1 s. As the disease progresses, a high nadir might help to unravel the cause of disproportionate breathlessness. When analysed in association with measurements of dynamic inspiratory constraints, a high V′E/V′CO2 is valuable to ascertain a role for the “lungs” in limiting dyspnoeic patients. Regardless of disease severity, cardiocirculatory (heart failure and pulmonary hypertension) and respiratory (lung fibrosis) comorbidities can further increase V′E/V′CO2. A high V′E/V′CO2 is a predictor of poor outcome in lung resection surgery, adding value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of disease severity. Considering its potential usefulness, the V′E/V′CO2 should be valued in the clinical management of patients with COPD.

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Effects of a high-intensity pulmonary rehabilitation program on the minute ventilation/carbon dioxide output slope during exercise in a cohort of patients with COPD undergoing lung resection for non-small cell lung cancer

Jornal Brasileiro de Pneumologia ◽

10.1590/1806-3713/e20180132 ◽

2019 ◽

Vol 45 (6) ◽

Cited By ~ 5

Author(s):

Fabio Perrotta ◽

Antonio Cennamo ◽

Francesco Saverio Cerqua ◽

Francesco Stefanelli ◽

Andrea Bianco ◽

...

Keyword(s):

Lung Cancer ◽

Carbon Dioxide ◽

High Intensity ◽

Pulmonary Rehabilitation ◽

Minute Ventilation ◽

Lung Resection ◽

Small Cell ◽

Small Cell Lung ◽

Carbon Dioxide Output ◽

The Mean

ABSTRACT Objective: Preoperative functional evaluation is central to optimizing the identification of patients with non-small cell lung cancer (NSCLC) who are candidates for surgery. The minute ventilation/carbon dioxide output (VE/VCO2) slope has proven to be a predictor of surgical complications and mortality. Pulmonary rehabilitation programs (PRPs) could influence short-term outcomes in patients with COPD undergoing lung resection. Our objective was to evaluate the effects of a PRP on the VE/VCO2 slope in a cohort of patients with COPD undergoing lung resection for NSCLC. Methods: We retrospectively evaluated 25 consecutive patients with COPD participating in a three-week high-intensity PRP prior to undergoing lung surgery for NSCLC, between December of 2015 and January of 2017. Patients underwent complete functional assessment, including spirometry, DLCO measurement, and cardiopulmonary exercise testing. Results: There were no significant differences between the mean pre- and post-PRP values (% of predicted) for FEV1 (61.5 ± 22.0% vs. 62.0 ± 21.1%) and DLCO (67.2 ± 18.1% vs. 67.5 ± 13.2%). Conversely, there were significant improvements in the mean peak oxygen uptake (from 14.7 ± 2.5 to 18.2 ± 2.7 mL/kg per min; p < 0.001) and VE/VCO2 slope (from 32.0 ± 2.8 to 30.1 ± 4.0; p < 0.01). Conclusions: Our results indicate that a high-intensity PRP can improve ventilatory efficiency in patients with COPD undergoing lung resection for NSCLC. Further comprehensive prospective studies are required to corroborate these preliminary results.

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Minute ventilation-to-carbon dioxide slope is associated with postoperative survival after anatomical lung resection

Lung Cancer ◽

10.1016/j.lungcan.2018.10.003 ◽

2018 ◽

Vol 125 ◽

pp. 218-222 ◽

Cited By ~ 3

Author(s):

Takuro Miyazaki ◽

Matthew E.J. Callister ◽

Kevin Franks ◽

Padma Dinesh ◽

Takeshi Nagayasu ◽

...

Keyword(s):

Carbon Dioxide ◽

Minute Ventilation ◽

Lung Resection ◽

Postoperative Survival

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Respiratory compensation point

A Practical Guide to the Interpretation of Cardiopulmonary Exercise Tests ◽

10.1093/med/9780198834397.003.0013 ◽

2021 ◽

pp. 93-96

Author(s):

William J.M. Kinnear ◽

James H. Hull

Keyword(s):

Carbon Dioxide ◽

Minute Ventilation ◽

Cardiopulmonary Exercise Test ◽

Compensation Point ◽

Respiratory Compensation Point ◽

Carbon Dioxide Output ◽

Respiratory Compensation ◽

Cardiopulmonary Exercise ◽

The Subject ◽

Maximal Effort

This chapter describes how acidaemia stimulates ventilation in the later stages of a cardiopulmonary exercise test (CPET). This happens after the anaerobic threshold, once the capacity of the blood to buffer lactic acid has been used up. The respiratory compensation point (RCP) can be identified from an increase in the slope when minute ventilation (VE) is plotted against carbon dioxide output (VCO2), or from a rise in the ventilatory equivalents for carbon dioxide (VeqCO2). The presence of a clear RCP indicates that the subject has made a fairly maximal effort during the CPET. An RCP also argues against significant lung disease, since it implies the ability to increase ventilation in response to acidaemia.

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Intratest reliability and test–retest reproducibility of the oxygen uptake efficiency slope in healthy participants

European Journal of Cardiovascular Prevention & Rehabilitation ◽

10.1097/hjr.0b013e32832c88a8 ◽

2009 ◽

Vol 16 (4) ◽

pp. 493-498 ◽

Cited By ~ 24

Author(s):

Christophe Van Laethem ◽

Johan De Sutter ◽

Wim Peersman ◽

Patrick Calders

Keyword(s):

Carbon Dioxide ◽

Oxygen Uptake ◽

Minute Ventilation ◽

Exercise Duration ◽

Peak Oxygen Uptake ◽

Exercise Tests ◽

Uptake Efficiency ◽

Carbon Dioxide Output ◽

Oxygen Uptake Efficiency Slope ◽

Healthy Participants

Background The oxygen uptake efficiency slope (OUES) is a newer ventilatory exercise parameter, used in the evaluation of healthy participants and patients with cardiovascular disease. However, few data about the reliability and reproducibility of OUES are available. Our study assessed intratest reliability and test-retest reproducibility of OUES in healthy participants. Design and methods Eighteen participants (age 28 ± 6 years, BMI 22.1 ± 1.9 kg/m2, 10 men) performed two identical maximal exercise tests on a bicycle ergometer. To assess test-retest reproducibility, we performed Bland-Altman analysis and calculated the coefficient of repeatability of the main ventilatory variables. Results OUES remained stable during the second part of the exercise test. Mean values varied 2.4 ± 4.0% between OUES calculated at 70% (OUES70) and at 100% of exercise duration. Mean variation decreased to 1.4 ± 2.3% when OUES was calculated at 90% of exercise duration (OUES90). The Bland-Altman 95% limits of agreement for OUES90 were +3 and –6%, those for OUES70 were +11 and –8%. The coefficient of repeatability for OUES was 597 ml/min or 18.7% of the average value of repeated OUES measurements. These results were similar to those of peak oxygen uptake and minute ventilation/carbon dioxide output. However, the test-retest reproducibility for submaximal-derived values of OUES was lower, as we noted higher coefficients of repeatability for OUES90 and OUES70, increasing up to 27% of the average of repeated values. Conclusion OUES shows excellent intratest reliability and has a test-retest reproducibility that is similar to that of peak oxygen uptake and minute ventilation/carbon dioxide output slope. However, its reproducibility becomes higher when it is calculated from increasing levels of achieved exercise intensity.

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Minute Ventilation-to-Carbon Dioxide Output (e/co2) Slope Is the Strongest Predictor of Respiratory Complications and Death After Pulmonary Resection

The Annals of Thoracic Surgery ◽

10.1016/j.athoracsur.2012.03.022 ◽

2012 ◽

Vol 93 (6) ◽

pp. 1802-1806 ◽

Cited By ~ 40

Author(s):

Alessandro Brunelli ◽

Romualdo Belardinelli ◽

Cecilia Pompili ◽

Francesco Xiumé ◽

Majed Refai ◽

...

Keyword(s):

Carbon Dioxide ◽

Pulmonary Resection ◽

Minute Ventilation ◽

Respiratory Complications ◽

Carbon Dioxide Output

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Intercept of minute ventilation versus carbon dioxide output relationship as an index of ventilatory inefficiency in chronic obstructive pulmonary disease

Journal of Thoracic Disease ◽

10.21037/jtd-20-2725 ◽

2021 ◽

Vol 13 (3) ◽

pp. 1553-1563

Author(s):

Fang Lin ◽

Shan Nie ◽

Ranran Zhao ◽

Min Cao ◽

Wei Yuan ◽

...

Keyword(s):

Carbon Dioxide ◽

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Minute Ventilation ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Carbon Dioxide Output

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Intercept of minute ventilation vs. carbon dioxide output relationship in chronic obstructive pulmonary disease: utility as an index of ventilatory inefficiency

10.21203/rs.3.rs-19544/v1 ◽

2020 ◽

Author(s):

Haoyan Wang ◽

Fang Lin ◽

Shan Nie ◽

Ranran Zhao ◽

Min Cao ◽

...

Keyword(s):

Carbon Dioxide ◽

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Minute Ventilation ◽

Airflow Limitation ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Lung Hyperinflation ◽

Carbon Dioxide Output ◽

Copd Patients

Abstract Background: Ventilatory inefficiency is known to be a contributor to exercise intolerance in chronic obstructive pulmonary disease (COPD). The intercept of the minute ventilation (V̇E) vs. carbon dioxide output (V̇CO2) plot is a key ventilator inefficiency parameter. However, its relationships with lung hyperinflation (LH) and airflow limitation are not known. This study aimed to evaluate the correlations between the V̇E/V̇CO2 intercept and LH in COPD to determine its utility as an index of functional impairment.Methods: We conducted a retrospective analysis of data from 53 COPD patients and 14 healthy controls performed incremental cardiopulmonary exercise tests and resting pulmonary function. Ventilatory inefficiency was represented by parameters reflecting the V̇E/V̇CO2 nadir and slope (linear region), and intercept of the V̇E/V̇CO2 plot. Their correlations with measures of LH and airflow limitation were evaluated.Results: Compared to the control, the slope (30.58±3.62) and intercept (4.85±1.11) higher in COPDstages1-2, leading to a higher nadir (31.47±4.47) (p<0.05). Despite an even higher intercept in COPDstages3-4 (7.16±1.41), the slope diminished with disease progression (from 30.58±3.62 in COPDstages1-2 to 28.36±4.58 in COPDstages3-4). Compared to the V̇E/V̇CO2 nadir and V̇E/V̇CO2 slope, the intercept was better correlated with peak V̇E/maximal voluntary ventilation (MVV) (r=0.489, p<0.001) and peak V̇O2/watt (r=0.354, p=0.003). The intercept was also significantly correlated with RV/TLC (r=0.588, p<0.001), IC/TLC (r=-0.574, p<0.001), peak VT/TLC (r=-0.585, p<0.001); and airflow limitation forced expiratory volume in 1s (FEV1) % predicted (r=-0.606, p<0.001) and FEV1/forced vital capacity (FVC) (r=-0.629, p<0.001).Conclusion: V̇E/V̇CO2intercept was consistently better correlated with worsening static and dynamic lung hyperinflation and airflow limitation in COPD. V̇E/V̇CO2 intercept emerged as a useful index of ventilatory inefficiency across the severity spectrum of COPD patients.

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Physiological and clinical relevance of exercise ventilatory efficiency in COPD

European Respiratory Journal ◽

10.1183/13993003.02036-2016 ◽

2017 ◽

Vol 49 (3) ◽

pp. 1602036 ◽

Cited By ~ 35

Author(s):

J. Alberto Neder ◽

Danilo C. Berton ◽

Flavio F. Arbex ◽

Maria Clara Alencar ◽

Alcides Rocha ◽

...

Keyword(s):

Lung Resection ◽

Forced Expiratory Volume ◽

Added Value ◽

Exercise Intolerance ◽

Chronic Obstructive ◽

Exercise Tests ◽

Ventilatory Efficiency ◽

Respiratory Mortality ◽

Clinical Scenarios ◽

Objective Evidence

Exercise ventilation (V′E) relative to carbon dioxide output (V′CO2) is particularly relevant to patients limited by the respiratory system, e.g. those with chronic obstructive pulmonary disease (COPD). High V′E−V′CO2 (poor ventilatory efficiency) has been found to be a key physiological abnormality in symptomatic patients with largely preserved forced expiratory volume in 1 s (FEV1). Establishing an association between high V′E−V′CO2 and exertional dyspnoea in mild COPD provides evidence that exercise intolerance is not a mere consequence of detraining. As the disease evolves, poor ventilatory efficiency might help explaining “out-of-proportion” breathlessness (to FEV1 impairment). Regardless, disease severity, cardiocirculatory co-morbidities such as heart failure and pulmonary hypertension have been found to increase V′E−V′CO2. In fact, a high V′E−V′CO2 has been found to be a powerful predictor of poor outcome in lung resection surgery. Moreover, a high V′E−V′CO2 has added value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of COPD severity. Documenting improved ventilatory efficiency after lung transplantation and lung volume reduction surgery provides objective evidence of treatment efficacy. Considering the usefulness of exercise ventilatory efficiency in different clinical scenarios, the V′E−V′CO2 relationship should be valued in the interpretation of cardiopulmonary exercise tests in patients with mild-to-end-stage COPD.

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