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Original Research: PHYSIOLOGIC TESTING |

Do Maximum Flow-Volume Loops Collected During Maximum Exercise Test Alter the Main Cardiopulmonary Parameters? FREE TO VIEW

Maurizio Bussotti, MD; PierGiuseppe Agostoni, MD, PhD; Alberto Durigato, MD; Carlo Santoriello, MD; Stefania Farina, MD; Vito Brusasco, MD; Riccardo Pellegrino, MD
Author and Funding Information

*From the Istituto di Cardiologia dell'Università degli Studi di Milano (Drs. Bussotti, Agostoni, and Farina), Centro Cardiologico, Istituto di Ricovero e Cura a Carattere Scientifico, Centro di Studio per le Ricerche Cardiovascolari del Centro Di Studio per le Ricerche, Milan, Italy; SC Pneumologia (Dr. Durigato), Ospedale Cà Foncello, Treviso, Italy; OUC Fisiopatologia Respiratoria (Dr. Santoriello), Ospedale Cava De'Tirreni (SA), Tirreni, Italy; Cattedra di Fisiopatologia Respiratoria (Dr. Brusasco), DISM, Università di Genova, Genoa, Italy; and Centro di Fisiopatologia Respiratoria (Dr. Pellegrino), Azienda Sanitaria Ospedaliera S Croce e Carle, Cuneo, Italy.

Correspondence to: Maurizio Bussotti, MD, Centro Cardiologico Monzino, Department of Cardiology, Via Parea 4, Milan 20138, Italy; e-mail: maurizio.bussotti@ccfm.it


The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(2):425-433. doi:10.1378/chest.08-1477
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Background:  Traditionally, ventilatory limitation to exercise is assessed by measuring the breathing reserve (BRR) [ie, the difference between minute ventilation at peak exercise and maximum voluntary ventilation measured at rest]. Recent studies have however, documented important abnormalities in ventilatory adaptation with a remarkable potential to limit exercise even in the presence of a normal BRR. Among these abnormalities is lung hyperinflation and expiratory flow limitation. This was documented by comparing tidal to maximum flow-volume loops (FVLs) collected throughout the test. In the present study, we wondered whether the advantages of using such a technique within the classic cardiopulmonary exercise test (CPET) might be obscured by the maneuvers interfering with the main functional parameters of the test, and eventually with interpretation of the CPET.

Methods:  We studied 18 healthy subjects, 19 patients affected by COPD, and 19 patients with chronic heart failure during a maximum exercise test on three different study days in a random order. On one occasion, the CPET was conducted with no FVLs (control test [CTRL]), whereas on the other occasions FVLs were incorporated every 1 min during exercise (FVL1-min) or every 2 min during exercise (FVL2-min).

Results:  None of the classic cardiovascular parameters recorded at ventilatory anaerobic threshold or at peak exercise differed between the study days (by analysis of variance). Furthermore, the coefficients of variation of the main parameters between FVL1-min and FVL2-min days vs CTRL day were well within the natural variability thresholds reported in the literature.

Conclusions:  The FVLs appear to not interfere with the main functional parameters used for the interpretation of CPET.

Figures in this Article

The traditional evaluation of ventilatory limitation during a cardiopulmonary exercise test (CPET) is based on the measurement of the breathing reserve (BRR) [ie, the difference between minute ventilation (V̇e) at maximum exercise and maximum voluntary ventilation (MVV)]. The latter is deemed to be a surrogate of the potential the respiratory system may generate during exercise.1 Any difference > 15 L/min or 20 to 40% predicted in favor of MVV is interpreted as consistent with exercise not being limited by ventilation. Babb et al2 were the first to report that patients affected by mild-to-moderate COPD exhibited an abnormal and significant increase in functional residual capacity (FRC) during exercise and tidal expiratory flow encroaching on maximum flow as a result of the respiratory disease despite BRR was normal. Their study was performed by comparing tidal flow-volume loops (FVLs) recorded at some steps during exercise with maximum loops at baseline, as originally proposed by Olaffson and Hyatt.3 Further evidence that the ventilatory response may be abnormal during exercise despite normal BRR was brought later in studies of very fit individuals,4 aging,5,6 bronchial asthma,7 COPD,810 chronic heart failure (CHF),11,12 and pulmonary fibrosis.13 Because both lung hyperinflation and expiratory flow limitation are well known to be seriously capable of impairing exercise by causing fatigue of the inspiratory muscles14 and impairing the cardiovascular system,15 it becomes clear that BRR is insufficient for a comprehensive and precise assessment of the contribution of the respiratory system to physical exercise in physiologic and disease conditions. As a matter of fact, MVV can overestimate maximum ventilation generated at peak exercise either because the very high breathing frequency and operational lung volumes at which the maneuver is conducted permit greater ventilation than with exercise or because the duration of the maneuver is too short to be reasonably extrapolated to 1 min. In addition, it is recalled that the MVV maneuver is performed prior to the test, thus ignoring the potential and substantial changes of bronchomotor tone occurring with exercise.

The maneuvers necessary for the FVLs require the measurement of some tidal regular breaths, a partial forced expiratory maneuver initiated from about the end-inspiratory lung volume and of sufficient duration to adequately cover the range of tidal volume, and a fast inspiration to total lung capacity (TLC) to locate the position of the tidal loops with respect to maximum lung inflation.8,16 However, if on one hand the FVLs collected during exercise serve to assess whether and how the respiratory system may limit exercise, on the other hand they could disturb the main respiratory, cardiovascular, and metabolic parameters used for final interpretation of the test. Large and fast variations in lung expansion, intrathoracic pressures, and inspiratory and expiratory times can indeed, modify ventilation, gas exchange, and venous return and pulmonary blood volume, or distract the attention from the workload to sustain, thus reducing the accuracy of the measurements of the main parameters.1

Therefore, we investigated whether multiple FVLs may be incorporated into the traditional CPET without affecting the main cardiorespiratory parameters. Our hypothesis was that to support the routine clinical use of the FVLs during CPET even in naive subjects, (1) the main cardiovascular and respiratory parameters measured at the ventilatory anaerobic threshold (AT) and peak exercise should not be modified by the maneuvers and (2) the differences between study days with and without FVLs should remain within the coefficients of day-to-day variation reported for these categories of subjects.1720

Subjects

Eighteen healthy subjects, 19 COPD patients, and 19 CHF patients took part in the study after giving informed consent, as approved by the local Ethics Committee. To participate in the study, the healthy subjects had to be physically active in recreational or competitive physical activities and had to not be affected by diseases that contraindicated participating in the test. The COPD patients had to have received a diagnosis achieved according to the current guidelines21 and to be in a clinical state for at least 4 weeks prior to the study. None of the bronchodilator medications were withheld for the study. The CHF patients had to have a history of congestive heart failure, determined according to the current guidelines,22 and to be in stable clinical condition during the month prior to the study. Exclusion criteria included primary pulmonary disease, peripheral vascular disease, primary pulmonary hypertension, primary valvular disease, artificial pacemaker, and exercise-induced arrhythmias.

Protocol
Measurements:

The classic spirometric indexes (FEV1 and FVC) were measured in triplicate through a mass flow sensor (V̇max; SensorMedics; Yorba Linda, CA) according to the international guidelines.23 MVV was measured in duplicate prior to the study.23 Predicted values are from Quanjer et al24 and Jones.25

Screening Day:

The subjects attended the laboratory for give a clinical history, and undergo a physical examination and spirometry. The CHF patients also underwent an ECG and echocardiography study. A CPET was performed on a cycle ergometer with a ramp protocol in order for the participants to become familiar with instruments, seat of the cycle, breathing through a mouthpiece, unexpected difficulties or discomfort, maneuvers, and staff,1 and to assess maximum exercise capacity.26

Study Days:

The subjects attended the laboratory in the mid-afternoon after eating a light meal. Spirometry was performed in triplicate through the mass flow sensor. BP and heart rate (HR) were measured.

The CPET was performed on an electronically braked cycle ergometer (Ergometrics 800S; SensorMedics), with the subject wearing a nose clip and breathing through a mass flow sensor (dead space, 75 mL) connected to a saliva trap. V̇e, oxygen consumption (V̇o2), and carbon dioxide output (V̇co2) were measured breath by breath (V̇max, SensorMedics), and a 12-lead ECG (MAX1; SensorMedics) continuously recorded data. After 3 min of resting and 2 min of warm up, the exercise load was increased every 1 min by 10 or 15 W for the CHF and COPD patients, depending on the previous exercise test, and by 25 W for healthy subjects until exhaustion. The subjects pedaled at about 50 to 60 revolutions per min.

On day 1 (control test [CTRL]), no FVLs were recorded during exercise. On days 2 and 3, the subjects first were taught how to perform partial forced expiratory maneuvers and then practiced until the results were reproducible. The CPET was performed on 1 day with FVLs collected in triplicate at rest and at the end of every minute during loading (FVL1-min), and on the other day with the FVLs collected once again in triplicate at rest but every 2 min during loading (FVL2-min). The last maneuver at maximum exercise was performed within the first 40 s of the recovery phase in order to avoid any interference with the parameters at peak exercise. Specifically, the FVLs were obtained as follows: after at least four regular breaths, the subjects were asked to forcefully expire from end-tidal inspiratory volume to a volume slightly below FRC and then to take a deep breath to TLC (Figure 1). Soon after, they were invited to resume regular breathing.9 The three CPETs were conducted in a random order with an interval of at least 3 days between the tests.

Figure Jump LinkFigure 1 Schematic adimensional representation of the tidal and forced FVLs at baseline (upper panels) and peak exercise (lower panels) in the study. Lower panels: baseline tracings are superimposed as dotted gray lines to document the differences with peak exercise. On the left, the maneuvers are shown as volume plotted vs time, and on the right as flow vs volume. TLC and FRC are indicated by the oblique arrows. The maneuver is initiated after four regular tidal breaths, with the subject performing a forced expiration from end-tidal inspiration to a volume slightly below FRC (darker line in bold) immediately followed by a deep breath to TLC. The latter allows superimposition of the loops at maximum volume, assuming that TLC does not change with exercise. Note the decrease of FRC at peak exercise on both spirometric and flow-volume tracings as well as the increase in maximum forced expiratory flow, thus suggesting bronchodilation (small vertical arrows).Grahic Jump Location
Data Analysis and Calculations

The measurements taken during the last 20 s of peak exercise were averaged to estimate maximum V̇o2 (V̇o2max), maximum V̇e (V̇emax), maximum respiratory rate (RRmax), maximum workload (ie, the load sustained at AT or peak exercise), maximum HR (HRmax), O2 pulse at peak exercise (V̇o2max/HRmax), maximum end-tidal Po2 (Peto2max), and maximum end-tidal Pco2 (Petco2max). V̇e/V̇co2 ratio was measured according to the criteria of Whipp et al.27 AT was measured according to V-slope analysis and was confirmed by examining the increments of ventilatory equivalent for O2 and end-tidal O2 pressure. The slope of V̇o2 vs workload (in Watts) was calculated according to Wasserman et al.1 For the exercise tests with the FVLs, the analysis was conducted after manually excluding the forced partial expiration, the large breath to TLC, and the next two tidal breaths.

Statistical Analysis

Analysis of variance (ANOVA) was used to assess the effects of the FVLs between days within groups on the following main variables: V̇o2max; V̇emax; RRmax; maximum workload; HRmax; V̇o2max/HRmax ratio; Peto2max; Petco2max; V̇e/V̇co2 ratio; slope of V̇o2 workload; and V̇o2, RR, and workload at AT. Duncan post hoc analysis was used whenever the F test result was significant. The χ2 test was used for comparison of frequencies. A p value < 0.05 was considered to be statistically significant.

For each subject, the mean and SD of the difference of each variable between FVL1-min day and CTRL day, and between FVL2-min day and CTRL day were calculated. The coefficient of variation was then obtained by dividing the SD by the mean. The sample size of 18 subjects per group provided the power (90%) to detect differences in CV for the main variables at peak exercise greater than 2.4 points above the average value of 7–8 reported in the literature,1720 with alpha = 0.05. All values are expressed as the mean ± SD.

The main characteristics of the subjects of the three groups are reported in Table 1. There were anthropometric differences between groups due to age and height. The causes of heart disease in the CHF patients were ischemic dilated cardiomyopathy (three cases) or primary dilated cardiomyopathy (all other cases). According to the New York Heart Association classification, 2 patients were in class 1, 14 patients were in class 2, and 4 patients were in class 3. All patients were receiving pharmacologic treatment with digitalis (n = 6), diuretics (n = 13), angiotensin-converting enzyme inhibitors (n = 14), and β-blockers (n = 13).

Table Graphic Jump Location
Table 1 Main Anthropometric Clinical and Functional Data*

*Values are given as the mean ± SD, unless otherwise indicated. BMI = body mass Index; LVEF = left ventricle ejection fraction; NS = not significant.

†Statistical significance (by post hoc analysis) at p < 0.0000 (healthy subjects vs COPD patients).

‡Statistical significance (by post hoc analysis) at p < 0.001 (healthy subjects vs CHF patients).

§Statistical significance (by post hoc analysis) at p < 0.001 (COPD patients vs CHF patients).

∥Statistical significance (by post hoc analysis) at p < 0.05 (healthy subjects vs CHF patients).

¶Statistical significance (by post hoc analysis) at p < 0.05 (COPD patients vs CHF patients).

Maximum Exercise Test

In no groups of subjects did the FVL1-min and FVL2-min during the test affect the main cardiopulmonary variables at AT and peak exercise, thus suggesting that the FVLs did not interfere with the main variables used in clinical practice for diagnostic purpose (Tables 24). Scatterplots of comparisons of four main parameters at peak exercise between CTRL vs FVL1-min and FVL2-min are shown in Figure 2 for healthy subjects, Figure 3 for COPD and Figure 4 for CHF patients.

Table Graphic Jump Location
Table 2 Main Respiratory and Cardiovascular Variables During Exercise in Healthy Subjects*

*Values are given as the mean ± SD, unless otherwise indicated. V̇o2/W = slope of V̇o2 vs workload; V̇e/V̇co2 = slope of V̇co2 vs V̇e.

Table Graphic Jump Location
Table 3 Main Respiratory and Cardiovascular Variables During Exercise in COPD Patients*

*Values are given as the mean ± SD, unless otherwise indicated. See Table 2 for definition of abbreviations not used in the text.

Table Graphic Jump Location
Table 4 Main Respiratory and Cardiovascular Variables During Exercise in CHF Patients*

*Values are given as the mean ± SD, unless otherwise indicated. See Table 2 for definition of abbreviations not used in the text.

Figure Jump LinkFigure 2 Scatter plots of oxygen consumption (V̇o2), external load, minute ventilation (V̇e), and heart rate (HR) at peak exercise at control day (CTRL) vs. when flow-volume loops were introduced every 1 or 2 min during exercise (FVL1–2min) (black circles and grey triangles, respectively) in healthy subjects.Grahic Jump Location
Figure Jump LinkFigure 3 Scatter plots of the same variables of figure 2 in patients affected by chronic obstructive pulmonary disease.Grahic Jump Location
Figure Jump LinkFigure 4 Scatter plots of the same variables of figure 2 in patients affected by chronic heart failure.Grahic Jump Location
Coefficients of Variation

The coefficients of variation for the main cardiovascular and respiratory variables between the tests with FVL1-min or FVL2-min and CTRL were on average well below the values of 10 to 12% and 7 to 8%, respectively, reported at AT and peak exercise for these categories of individuals (Table 5).1720

Table Graphic Jump Location
Table 5 Coefficients of Variation of the Main Variables*

*See Table 2 for definition of abbreviations not used in the text.

The main results of the study are that the incorporation of FVLs during a CPET in healthy subjects or in COPD and CHF patients did not significantly modify the main cardiopulmonary functional parameters. Because the FVLs appear to play an important role in the assessment of ventilatory limitation to exercise, our data suggest that the technique may be easily incorporated in the CPET evaluation in naive subjects and patients.

As anticipated in the introductory section of this article, ventilatory limitation due to exercise is generally assessed by using the BRR with the idea that values > 15 L/min or 20 to 40% predicted between MVV and V̇e may indeed suggest that the maximum workload is set by nonrespiratory mechanisms. Several important limits of BRR are now apparent. First, BRR may overestimate the respiratory reserve as a result of large values of MVV due to the higher lung volume at which it is conducted and the shorter time duration compared to exercise ventilation.8,16 Second, BRR ignores the frequent increase and sometimes decrease in bronchial tone observed with exercise.7,10,28 Third, BRR cannot capture the temporal dynamics of the constraints already occurring at levels of exercise well below the peak. In contrast, the FVLs are capable of detecting the progressive decrease in expiratory flow reserve within the tidal breathing range, thus documenting any early anomalous ventilatory adaptation and indicating whether any flow reserve is left at the end of exercise.513,16 More important, however, is, the capability of the FVLs to quantify two of the most important functional mechanisms now known to contribute to the limitation of exercise (ie, lung hyperinflation and expiratory flow limitation).14,15 Finally, we recall that the FVLs are easy to perform and acceptable even by naive individuals, and basically void of technical problems when using the new software and hardware. Typical examples in healthy subjects, and patients with COPD or CHF have been previously published.712,16,28

The results of the present study suggest that not only did the differences in the main cardiorespiratory functional parameters during exercise not reach any statistical significance, but they also remained well within the limits of natural variability reported in previous investigations. Studies1720 on the reproducibility of incremental maximum exercise tests in healthy subjects and patients affected by chronic cardiopulmonary diseases have reported coefficients of variation for the main parameters of not > 7 to 8% at peak exercise and 10 to 12% at AT. Our study proves that the introduction of the FVLs even at intervals as brief as 1 min during the CPET does not exceed such a variability. Though we do not have a clear explanation for this, we speculate that at low levels of exercise, the effects of the FVLs were of too short duration to affect the respiratory and cardiovascular parameters measured prior to and after at least 6 to 8 s from the end of the FVL. At high loads, the interference of the FVLs on the same parameters was even less probable because the maximum lung volume achieved with the FVLs was almost the same as that of the large tidal breaths.

Other aspects of this study may support the use of the FVLs within the classic CPET in the first-line assessment of the cardiopulmonary response to exercise. First, the subjects in our study likely reflect the general population tested for CPET because of the lack of any selective criteria other than presentation order to advertisements or visits and motivation and willingness to participate in the study. Second, as mentioned in the “Materials and Methods” section, the study was preceded by a learning and familiarization session to minimize the between-day differences.26 Third, the tests were conducted in random order at the same time of day, with no withholding of medications, and after a light meal. Four, the study covered all classes of severity of both COPD and CHF. Finally, the study was conducted in full agreement with all technical recommendations and protocols of international guidelines.26

In this study we did not give recommendations on how often to collect FVLs during a CPET. This depends on the answers to the functional questions addressed rather than a priori choice. In most of our previous studies,7,9,10 we used a frequency of 1 min to best investigate the ventilatory adaptation to the workload.

In conclusion, the popularity gained by the FVLs in the field of cardiopulmonary exercise testing may further increase by acknowledging that the maneuvers do not basically interfere with the main cardiorespiratory functional parameters used for the interpretation of the test. On this basis, we support the use of the FVLs as a simple and adjunctive parameter in the CPET for a comprehensive and physiologic assessment of the ventilatory response to exercise even in naive individuals.

ANOVA

analysis of variance

AT

ventilatory anaerobic threshold

BRR

breathing reserve

CHF

chronic heart failure

CPET

cardiopulmonary exercise test

CTRL

control test

FRC

functional residual capacity

FVL

flow-volume loop

FVL1-min

tidal and maximal flow-volume loops recorded every minute during exercise

FVL2-min

tidal and maximal flow-volume loops recorded every 2 min during exercise

HR

heart rate

HRmax

maximum heart rate

MVV

maximal voluntary ventilation

Petco2

end-tidal carbon dioxide pressure

Peto2

end-tidal oxygen pressure

RRmax

maximum respiratory rate

TLC

total lung capacity

co2

carbon dioxide output

e

minute ventilation

emax

maximum minute ventilation

o2

oxygen consumption

o2max

maximum oxygen consumption

o2max/HRmax

O2 pulse at peak exercise

Wasserman K, Hansen JE, Sue DY, et al. Principles of exercise testing and interpretation. 1987; Philadelphia, PA Lea & Febiger:30-32
 
Babb TG, Viggiano R, Hurley B, et al. Effect of mild-to-moderate airflow limitation on exercise capacity. J Appl Physiol. 1991;70:223-230. [PubMed]
 
Olaffson S, Hyatt RE. Ventilatory mechanics and expiratory flow limitation during exercise in normal subjects. J Clin Invest. 1969;48:564-573. [PubMed] [CrossRef]
 
Johnson BD, Saupe KW, Dempsey JA. Mechanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol. 1992;73:874-886. [PubMed]
 
DeLorey DS, Babb TG. Progressive mechanical ventilatory constraints with aging. Am J Res. pir Crit Care Med. 1999;160:169-177
 
Johnson BD, Reddan WG, Pegelow DF, et al. Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am Rev Respir Dis. 1991;143:960-967. [PubMed]
 
Crimi E, Pellegrino R, Smeraldi A, et al. Exercise-induced bronchodilation in natural and induced asthma: effects on ventilatory response and performance. J Appl Physiol. 2002;92:2353-2360. [PubMed]
 
Johnson BD, Beck KC, Zeballos RJ, et al. Advances in pulmonary laboratory testing. Chest. 1999;116:1377-1387. [PubMed]
 
Pellegrino R, Brusasco V, Rodarte JR, et al. Expiratory flow limitation and regulation of end-expiratory lung volume during exercise. J Appl Physiol. 1993;74:2552-2558. [PubMed]
 
Pellegrino R, Villosio C, Milanese U, et al. Breathing during exercise in subjects with mild-to-moderate airflow obstruction: effects of physical training. J Appl Physiol. 1999;87:1697-1704. [PubMed]
 
Johnson BD, Beck KC, Olson LJ, et al. Ventilatory constraints during exercise in patients with chronic heart failure. Chest. 2000;117:321-332. [PubMed]
 
Agostoni PG, Pellegrino R, Conca C, et al. Exercise hyperpnea in chronic heart failure: relationships to lung stiffness and expiratory flow. J Appl Physiol. 2002;92:1409-1416. [PubMed]
 
Marciniuk DD, Sridhar G, Clemens RE, et al. Lung volumes and expiratory flow limitation during exercise in interstitial lung disease. J Appl Physiol. 1994;77:963-973. [PubMed]
 
O'Donnell DE. Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3:180-184. [PubMed]
 
Aliverti A, Macklem PT. How and why exercise is impaired in COPD. Respiration. 2001;68:229-239. [PubMed]
 
Johnson BD, Weisman IM, Zeballos RJ, et al. Emerging concepts in the evaluation of ventilatory limitation during exercise: the exercise tidal flow-volume loop. Chest. 1999;116:488-503. [PubMed]
 
Garrard CS, Emmons C. The reproducibility of the respiratory responses to maximum exercise. Respiration. 1986;49:94-100. [PubMed]
 
Noseda A, Carpiaux JP, Prigogine T, et al. Lung function, maximum and submaximum exercise testing in COPD patients: reproducibility over a long interval. Lung. 1989;167:247-257. [PubMed]
 
Meyer K, Westbrook S, Schwaibold M, et al. Short-term reproducibility of cardiopulmonary measurements during exercise in patients with severe chronic heart failure. Am Heart J. 1997;134:20-26. [PubMed]
 
Janicki JS, Gupta S, Ferris ST, et al. Long-term reproducibility of respiratory gas exchange measurements during exercise in patients with stable cardiac failure. Chest. 1990;97:12-17. [PubMed]
 
Pauwels RA, Buist S, Calverley PMA, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD). Am J Respir Crit Care Med. 2001;163:1256-1276. [PubMed]
 
Hunt SA. American College of Cardiology, American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for Evaluation and Management of Heart Failure) ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005;46:e1-e82. [PubMed]
 
Miller M, Hankinson J, Brusasco V, et al. Standardization of spirometry. Eur Respir J. 2005;26:319-338. [PubMed]
 
Quanjer PH, Tammeling GJ, Cotes JE, et al. Standardized lung function testing. Eur Respir J. 1993;6:1-99
 
Jones NL. Clinical exercise testing. 1988;3rd ed. Philadelphia, PA WB Saunders:306-311
 
American Thoracic Society, American College of Chest Physicians ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167:221-277
 
Whipp BJ, Davis JA, Wasserman K. Ventilatory control of the “isocapnic buffering” region in rapidly incremental exercise. Respir Physiol. 1989;76:357-367. [PubMed]
 
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Figures

Figure Jump LinkFigure 1 Schematic adimensional representation of the tidal and forced FVLs at baseline (upper panels) and peak exercise (lower panels) in the study. Lower panels: baseline tracings are superimposed as dotted gray lines to document the differences with peak exercise. On the left, the maneuvers are shown as volume plotted vs time, and on the right as flow vs volume. TLC and FRC are indicated by the oblique arrows. The maneuver is initiated after four regular tidal breaths, with the subject performing a forced expiration from end-tidal inspiration to a volume slightly below FRC (darker line in bold) immediately followed by a deep breath to TLC. The latter allows superimposition of the loops at maximum volume, assuming that TLC does not change with exercise. Note the decrease of FRC at peak exercise on both spirometric and flow-volume tracings as well as the increase in maximum forced expiratory flow, thus suggesting bronchodilation (small vertical arrows).Grahic Jump Location
Figure Jump LinkFigure 2 Scatter plots of oxygen consumption (V̇o2), external load, minute ventilation (V̇e), and heart rate (HR) at peak exercise at control day (CTRL) vs. when flow-volume loops were introduced every 1 or 2 min during exercise (FVL1–2min) (black circles and grey triangles, respectively) in healthy subjects.Grahic Jump Location
Figure Jump LinkFigure 3 Scatter plots of the same variables of figure 2 in patients affected by chronic obstructive pulmonary disease.Grahic Jump Location
Figure Jump LinkFigure 4 Scatter plots of the same variables of figure 2 in patients affected by chronic heart failure.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Main Anthropometric Clinical and Functional Data*

*Values are given as the mean ± SD, unless otherwise indicated. BMI = body mass Index; LVEF = left ventricle ejection fraction; NS = not significant.

†Statistical significance (by post hoc analysis) at p < 0.0000 (healthy subjects vs COPD patients).

‡Statistical significance (by post hoc analysis) at p < 0.001 (healthy subjects vs CHF patients).

§Statistical significance (by post hoc analysis) at p < 0.001 (COPD patients vs CHF patients).

∥Statistical significance (by post hoc analysis) at p < 0.05 (healthy subjects vs CHF patients).

¶Statistical significance (by post hoc analysis) at p < 0.05 (COPD patients vs CHF patients).

Table Graphic Jump Location
Table 2 Main Respiratory and Cardiovascular Variables During Exercise in Healthy Subjects*

*Values are given as the mean ± SD, unless otherwise indicated. V̇o2/W = slope of V̇o2 vs workload; V̇e/V̇co2 = slope of V̇co2 vs V̇e.

Table Graphic Jump Location
Table 3 Main Respiratory and Cardiovascular Variables During Exercise in COPD Patients*

*Values are given as the mean ± SD, unless otherwise indicated. See Table 2 for definition of abbreviations not used in the text.

Table Graphic Jump Location
Table 4 Main Respiratory and Cardiovascular Variables During Exercise in CHF Patients*

*Values are given as the mean ± SD, unless otherwise indicated. See Table 2 for definition of abbreviations not used in the text.

Table Graphic Jump Location
Table 5 Coefficients of Variation of the Main Variables*

*See Table 2 for definition of abbreviations not used in the text.

References

Wasserman K, Hansen JE, Sue DY, et al. Principles of exercise testing and interpretation. 1987; Philadelphia, PA Lea & Febiger:30-32
 
Babb TG, Viggiano R, Hurley B, et al. Effect of mild-to-moderate airflow limitation on exercise capacity. J Appl Physiol. 1991;70:223-230. [PubMed]
 
Olaffson S, Hyatt RE. Ventilatory mechanics and expiratory flow limitation during exercise in normal subjects. J Clin Invest. 1969;48:564-573. [PubMed] [CrossRef]
 
Johnson BD, Saupe KW, Dempsey JA. Mechanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol. 1992;73:874-886. [PubMed]
 
DeLorey DS, Babb TG. Progressive mechanical ventilatory constraints with aging. Am J Res. pir Crit Care Med. 1999;160:169-177
 
Johnson BD, Reddan WG, Pegelow DF, et al. Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am Rev Respir Dis. 1991;143:960-967. [PubMed]
 
Crimi E, Pellegrino R, Smeraldi A, et al. Exercise-induced bronchodilation in natural and induced asthma: effects on ventilatory response and performance. J Appl Physiol. 2002;92:2353-2360. [PubMed]
 
Johnson BD, Beck KC, Zeballos RJ, et al. Advances in pulmonary laboratory testing. Chest. 1999;116:1377-1387. [PubMed]
 
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