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Pulmonary Vascular Function and Aerobic Exercise Capacity at Moderate Altitude


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Medicine & Science in Sports & Exercise: October 2017 - Volume 49 - Issue 10 - p 2131-2138
doi: 10.1249/MSS.0000000000001320
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The combination of low pulmonary vascular resistance (PVR), high pulmonary vascular distensibility, and high lung diffusing capacity (DL), defined as “pulmonary vascular reserve,” has been shown to be associated with a superior aerobic exercise capacity (23,24). These observations have been confirmed at high altitudes (>3000 m) where hypoxic pulmonary vasoconstriction (HPV) increases PVR and decreases pulmonary vascular distensibility (18,30), although the overwhelming determinant of decreased maximum oxygen uptake (V˙O2max) and maximum workload then becomes a decrease in arterial O2 content (CaO2) (4).

Altitude exposure is associated with a hyperbolic decrease in atmospheric pressure and inspired partial pressure of O2 (PO2) (37). Because of the shape of the oxyhemoglobin dissociation curve, significant resting hypoxemia with a fall in arterial O2 content and thus a decrease in O2 transport to the tissues occur essentially at altitudes >2500 to 3000 m. Hence, the notion of “high altitude” is defined by altitudes >3000 m, indeed more commonly associated with hypoxia-related medical problems (37). However, a measurable decrease in V˙O2max already occurs at lower altitudes, and how exposure to moderate altitudes (<2500–3000 m) affects pulmonary vascular reserve and associated modulation of aerobic exercise capacity is not exactly known. This information may be relevant to the expanding practice of competitive or recreational sports at moderate altitudes (35) and altitude training strategies to improve aerobic performance of elite athletes (26). We therefore performed cardiopulmonary exercise tests (CPET) with measurements of pulmonary artery pressures (Ppa), cardiac output (), and DL for nitric oxide (NO) and carbon monoxide (CO) at sea level and again at the moderate altitude of 2250 m in healthy volunteers with the purpose to determine the respective contributions of pulmonary vascular reserve and decreased oxygenation on aerobic exercise capacity.


Study population

The study included 38 healthy nonsmoker subjects, 5 women and 33 men (mean ± SD; age = 38 ± 6 yr, weight = 71 ± 9 kg, height = 175 ± 7 cm, body mass index = 23 ± 2 kg·m−2) with a range of exercise capacities as assessed by previous V˙O2max ranging from 27 to 67 mL·min−1·kg−1. None of the subjects took any drug. Before their enrollment in the study, all volunteers received written information regarding the nature and purpose of the experimental protocol. After an opportunity to ask any questions, a written statement of consent was signed. The study was approved by the ethical committee of the Administracio Esportiva de Catalunya, Spain.

Experimental protocol

All the subjects underwent a clinical examination and then an exercise stress echocardiography in a semirecumbent position coupled with DLNO and DLCO measurements, followed by an incremental cycle ergometer CPET after at least 1 h of rest and return of HR and blood pressure (BP) to baseline.

During exercise stress echocardiography, measurements of BP, Q˙, Ppa, left atrial pressure (Pla), DLCO, and DLNO were taken at rest and repeated at increasing levels of exercise until exhaustion. During CPET, ventilation (E), V˙O2, CO2 production (V˙CO2), and transcutaneous pulse oximetry (SpO2) were measured at rest and at increasing workloads until maximum, which is defined by a V˙O2max plateau.

This sequence of measurements was obtained at sea level, altitude of 76 m, in Girona (Spain) and repeated 1 wk later, 1 h after arrival at the moderate altitude of 2250 m in Masella (Spain) reached in 2 h by road. No medication was taken by any subject before or after the ascent.

Clinical assessment

The clinical assessment included a standard history and a clinical examination, including measurements of resting BP (sphygmomanometry), SpO2 (Nellcor Puritan Bennett Inc., Pleasanton, CA), and hemoglobin (Hb) level (EKF Diagnostics, Penarth, Cardiff, UK).


Doppler echocardiography measurements were performed with a portable ultrasound system (CX50 CompactXtreme Ultrasound System; Philips, Amsterdam, Netherlands) at rest and during an incremental exercise test on a semirecumbent cycle ergometer laterally tilted by 20° to 30° to the left, as previously reported (2,15,18,24). For optimal echocardiographic conditions, workload was increased by 30–50 W every 2 min to reach maximal exercise capacity in more than five steps (for at least five Ppa– coordinates) and to allow for the echocardiography and coupled DL measurements to be performed during the second minute at each workload. was estimated from the left ventricular outflow tract diameter, time velocity integral, and HR. Systolic Ppa was estimated from a trans-tricuspid pressure gradient calculated from the maximum velocity of continuous Doppler tricuspid regurgitation and corrected for right atrial pressure assumed constant at 5 mm Hg. The quality of the tricuspid regurgitant jet signal was evaluated without scoring or injection of contrast. Pla was estimated from the ratio of Doppler mitral to tissue Doppler mitral velocities. Mean Ppa (mPpa) was calculated as 0.61 × systolic Ppa + 2 mm Hg (5). PVR was calculated as (mPpa − Pla)/ and total PVR (TPR) as mPpa/. An incremental PVR was defined by the slope of the best linear fit of each multipoint mPpa– relationship. BP was measured at each workload, and SpO2 was continuously monitored.

DL measurements

DLCO and DLNO were measured in the semirecumbent position with corrections for Hb and inspired partial pressure of oxygen, using an automated device for calibrations, mixing of gases, and online calculations (Hyp’Air compact; Medisoft, Dinant, Belgium) as previously reported (7,11,18,24) and in agreement with recent update and recommendations for standardization of an Expert Task Force of the European Respiratory Society (40). Mixed gas was inspired (40 ppm of NO, 2800 ppm of CO, 14% of helium, and 21% of O2 in nitrogen) with a breath holding time of 4 s, and the composition of expired gas was analyzed with the first 0.8 L of expired gas discarded. Measurements were repeated two to three times, with the aim to obtain DLCO values within 5% and DLNO values within 10% of each other, and averaged. Alveolar volume (VA) was measured with helium dilution. KCO and KNO representing the rates of uptake of CO and NO, respectively, from alveolar gas per unit pressure of CO and NO were calculated as DLCO or DLNO divided by VA.

The Roughton and Forster (34) equation states that 1/DL = 1/Dm + 1/θVc, where DL is the diffusing capacity of the lung for a specific gas, Dm is its membrane component, Vc is the capillary blood volume, and θ is the blood conductance for this gas. The interest of the double gas technique is that Vc can be estimated from the two DL measurements using CO and NO as tracer gases by solving a system of two equations with two unknowns (19). Because the reaction of NO with hemoglobin is quasi-instantaneous, it was previously assumed that θNO is infinite so that the transfer factor for NO with correction for the NO/CO ratio of diffusivity allows for the calculation of Dm and, hence, Vc (19). However, it was recently shown experimentally that θNO has actually a finite value of 4.5 mL NO·mL blood−1·min−1·mm Hg−1 (3). Accordingly, although this has not been confirmed in humans, it appears reasonable to calculate Dm and Vc with this finite value of θNO (40), which was therefore implemented in the present study. Relative changes in Dm and Vc were also indirectly assessed by the DLNO/DLCO ratio (17,21). A thinning of the capillary sheet increases the DLNO/DLCO ratio, whereas a thickening of the blood sheet decreases the DLNO/DLCO ratio (17,21).

The coefficient relating DLNO and Dm was set at 1.97 according to the solubility and molecular weights of both gases. Assuming linearity between 1/θCO and PO2, an equation proposed by Forster (14) was used to calculate the blood conductance of CO (θCO) as a function of capillary PO2:

where PcapO2 is the capillary partial pressure of O2 estimated as alveolar PO2 − V˙O2/DLO2 with partial pressures (mm Hg), V˙O2 (mL·min−1), and DLO2 (mL·min−1·mm Hg−1). Alveolar PO2 was calculated from the local barometric pressure and the mixed expired end-tidal fraction of O2. Oxygen uptake was calculated by taking the mass balance of oxygen between inspiration and expiration during the maneuver. The fraction of oxygen in the residual volume preceding the inspiration was assumed to be similar to that found in the expired sample (mean = 16.4%). DLCO × 1.23 was used as surrogate for DLO2.

Hemoglobin concentrations were measured from venous blood samples and DLCO values corrected accordingly for standard concentrations of Hb of 14.6 g·dL−1 for men and 13.4 g·dL−1 for women.

Cardiopulmonary exercise test

Exercise capacity was estimated by a standard incremental CPET performed in an upright sitting position on an electronically braked cycle ergometer (Kettler, Ense-Parsit, Germany), as previously reported (12,15,18). Before the start of the test, the subjects had rested during 1 h after the exercise stress echocardiography, and all HR and BP were back to baseline. Initial workload was set at 30 or 60 W during 6 min, and work rate was increased by 30 W·min−1 (according to previously known exercise capacity and predicted decrease by 15% at moderate altitude) so that the test would last 10–12 min until exhaustion. Breath-by-breath data were collected and analyzed every 5 s using a metabolic system (K4; Cosmed, Rome, Italy) calibrated with room air and standardized gas. Ventilatory efficiency was assessed by the E/V˙CO2 ratio at the anaerobic threshold (AT). V˙O2max was considered to be achieved when three of the following criteria were met: an increase in oxygen consumption of less than 100 mL·min−1 with a further increase in workload, an RER greater than 1.1, an age-predicted maximal HR, and the incapacity of the subject to maintain the assigned pedaling frequency despite maximum effort and verbal encouragement. The AT was determined by the V-slope method. SpO2 was continuously monitored with an ear pulse oximeter (Nonin, Plymouth, MN).

CaO2 was calculated at rest and at maximal exercise with Hb × 1.36 SpO2 + 0.003 PaO2, with resting Hb (g·dL−1), SpO2 (%), and PaO2 (mm Hg) estimated from the alveolar PO2 calculated as mentioned previously.

Data analysis and statistics

The best linear adjustment of individual multipoint mPpa– relationships was calculated to define their slopes. Average slopes of mPpa– were calculated from pooled mPpa– relationships of each altitude level using an adjustment for individual variability as reported by Poon (31).

Because multipoint mPpa– relationships are actually slightly curvilinear, these measurements were also fitted in a mathematical distensibility model of the pulmonary circulation (25). This model allows for an improved PVR equation by the incorporation of a resistive vessel distensibility coefficient α, expressed as the percentage of increase in the diameter of the resistive vessels of the pulmonary circulation per millimeters of mercury of increase of the transmural pressure during exercise:

with resting and exercise measurements of Ppa, Pla, TPR, and of each subject, as previously reported for invasive (32) or noninvasive measurements (2,15,18,24). The distensibility coefficient α was calculated by solving the equation using the method of successive iterations. With given values for TPR and the measured values for Pla and at rest and during exercise, α was varied until minimal average difference and SD between measured and calculated mPpa over the whole range of available were found.

Repeated-measures ANOVA and Student’s paired t-tests were used to compare maximal exercise to rest and altitude to sea level.

A univariate linear regression was performed to determine the significant variables associated with V˙O2max in normoxia (sea level) and hypoxia (moderate altitude) or the difference (ΔV˙O2max) from normoxia to hypoxia, followed by a multivariable linear regression to find the independent variables associated with V˙O2max in normoxia and hypoxia or ΔV˙O2max from normoxia to hypoxia.

Results are expressed as mean ± SD. P values <0.05 were considered significant.


Altitude was well tolerated as no participant complained of any side effects, and clinical examination remained unremarkable. Systemic BP and HR were similar to sea level, whereas end-tidal CO2 pressure (PetCO2), SpO2, and CaO2 slightly decreased (Table 1). Sufficient quality echocardiographic images until maximal exercise were obtained in 29 of the 38 subjects (5 women/23 men; mean ± SD, age = 38 ± 6 yr, weight = 70 ± 8 kg, height = 175 ± 7 cm, body mass index = 23 ± 2 kg·m−2).

Cardiopulmonary exercise testing at sea level and at 2250 m (N = 38).

Pulmonary circulation

Moderate altitude exposure at rest was associated with slightly higher mPpa and PVR and no change in stroke volume (SV), Pla, and α, whereas at maximum exercise, , mPpa, Pla, and α were not different from sea level, but PVR was higher (Table 2). As illustrated in Figure 1, there was no significant difference in Poon-adjusted multipoint mPpa– between sea level and moderate altitude.

Resting and exercise echocardiography (N = 29).
Poon-adjusted linearly fitted mPpa– relationships. Pressure–flow relationships were shifted to slightly higher pressure (P < 0.001) at moderate altitude. The average slope of linearized mPpa– remained unchanged (1.5–1.6 mm Hg·L−1·min−1).


As shown in Table 3, moderate altitude increased VA, DLCO, DLNO, KCO, and Dm without change in DLNO/DLCO, KNO, and Vc. Exercise increased VA, DLCO, DLNO, KCO, KCO, Dm, and Vc, with a decrease in the DLNO/DLCO ratio. Differences in DL measurements and derived calculations between sea level and moderate altitude disappeared at maximal exercise. However, the changes in DLCO and DLNO with exercise were smaller at moderate altitude compared with sea level.

Lung diffusion capacity measured at rest and at maximal exercise, at 0 and at 2250 m (N = 38).

Cardiopulmonary exercise test

Aerobic exercise capacity was lower at moderate altitude, as assessed by a decreased V˙O2max by 16% ± 10%. At maximal exercise, workload, HR, PetCO2, SpO2, CaO2, and O2 pulse decreased at moderate altitude, with earlier AT and increased RER and E/V˙CO2 slope, whereas BP remained unchanged (Table 1).

Univariate and multivariable analysis of variables associated with V˙O2max

At sea level, the univariate analysis showed that V˙O2max was significantly associated with lower E/V˙CO2, mPpa/ slope, mPpa, and TPR at maximal exercise or higher indexed SV (SVI), Dm, Vc, DLNO or KNO, and DLCO or KCO measured at rest. The multivariable analysis showed that only lower mPpa/ slope (P < 0.01), higher resting SVI (P < 0.01), and higher resting DLNO (P < 0.05) were significantly associated with V˙O2max (Fig. 2) (adjusted R2 of the model = 0.46, SEE = 4.9).

Exercise capacity (V˙O2max) as a function of the slope of the mPpa/ relationship (A), resting SVI (B), and resting lung diffusion capacity for NO (DLNO) (C) at sea level (SL) and at moderate altitude (MA). Lower mPpa/ slopes, higher SVI, and DLNO are associated with proportionally higher V˙O2max (P < 0.01, P < 0.001, and P < 0.01, respectively).

At moderate altitude, the univariate analysis showed that V˙O2max was significantly associated with lower E/V˙CO2 at AT, mPpa/ slope, TPR at maximal exercise, and higher SVI, α, Dm, Vc, DLNO or KNO, and DLCO or KCO. The multivariable analysis showed that lower mPpa/ slope (P < 0.001) and higher resting SVI (P < 0.001) and resting DLNO (P < 0.01) were independently associated with V˙O2max (Fig. 2) (adjusted R2 of the model = 0.70, SEE = 7.1).

The magnitude of the decrease in V˙O2max at moderate altitude was greater in fittest subjects (R = 0.49, P < 0.001) and associated with the changes in resting SVI (P < 0.05) and decrease of SpO2 or CaO2 at the peak of exercise in hypoxia (independent variable, P < 0.001) (Fig. 3) (multivariate adjusted R2 of the model = 0.58, SEE = 16.1).

Change in exercise capacity (V˙O2max) from sea level to moderate altitude as a function of change in oxygen pulse oximetry (SpO2) during exercise at moderate altitude. The magnitude of the decrease in V˙O2max at moderate altitude is independently correlated to the exercise-induced reduction in SpO2 at moderate altitude (P < 0.01).

At both altitudes, KNO was inversely correlated to the E/V˙CO2 slope (not shown) (R = 0.36, P < 0.05).


The present results show that aerobic exercise capacity in healthy subjects at moderate altitude is decreased in relation to exercise-induced hypoxemia with no or trivial change in pulmonary vascular function.

Pulmonary vascular reserve

It has been previously shown that a lower PVR with higher pulmonary vascular distensibility, higher DL for NO and CO, and greater derived Vc are associated with a higher V˙O2max at lower ventilatory equivalents for CO2 in normoxia (23,24) as well as at high altitudes (11,18,30). This observation strongly suggests that exercise capacity is modulated by the functional state of the pulmonary circulation. This is confirmed by the present results at moderate altitude, with lower mPpa/ slope and higher resting DLNO-independent predictors of a higher V˙O2max at both altitudes. However, although PVR was slightly increased and ventilatory efficiency reduced, moderate altitude did not change the Vc, the Ppa– relationship, and the distensibility of pulmonary capillary vessels, suggesting moderate participation of the pulmonary vascular reserve in the reduction of aerobic exercise capacity with ascent to moderate altitude.

The mild changes observed in the pulmonary vascular function suggest that the altitude of 2250 m was not associated with a sufficient decrease in arterial oxygenation to trigger HPV at rest as SpO2 remaining higher than 90% corresponding to alveolar PO2 was associated with no or only slight increase in pulmonary vascular tone (28). HPV could have occurred at lower alveolar PO2 suggested by lower SpO2 during exercise, but associated shift of the mPpa– relationship to higher mPpa was minimal, and pulmonary vascular distensibility was not affected. More severe or more chronic hypoxic exposure would be needed to increase PVR and decrease pulmonary vascular distensibility (18,32).

Pulmonary resistive vessels are distensible, which explains the slight curvilinearity of multipoint mPpa– relationships (32). This was modeled on isolated perfused lungs by Linehan et al. (25) and transposed into an improved PVR equation integrating a distensibility coefficient α by Reeves et al. (32). The coefficient α can be calculated from a set of measurements of Ppa, Pla, and to compare pulmonary vascular distensibility at rest versus at exercise, or from measurement at rest and at several levels of exercise to assess the effects of moderate altitude. In the present study, α decreased with increasing levels of exercise, indicating progressive decrease in distensibility at increasing levels of flow and transmural pressure (2). Acute exposure to moderate altitude did not affect α, confirming previous studies in healthy subjects acutely exposed by normobaric or hypobaric hypoxia (18,32). Chronic hypoxic exposure is needed to decrease α, probably because of progressive pulmonary vascular remodeling (18).

Why a more distensible pulmonary circulation may be related to a higher aerobic exercise capacity remains incompletely understood (6,38). A shallower slope of mPpa– may allow for a higher maximum and O2 delivery to the tissues with relative unloading of the right ventricle as indicated by higher ejection fraction and lower levels of circulating brain natriuretic peptide (23). However, in the present study, maximum and SV were not different at moderate altitude compared with sea level. An increased capillary blood volume may also preserve gas exchange at lower levels of ventilation (8), as suggested by an inverse correlation between DL and E/V˙CO2 slope shown in a meta-analysis (30) and confirmed in the present study.

Lung diffusion and exercise capacity

Moderate altitude exposure was associated with an increase in both DLNO and DLCO, and thus with derived calculations of Vc and Dm, confirming previous reports in acute hypoxic exposure or altitude-acclimatized subjects (1,18,30). There has been a recent study that showed a disproportionate increase in DLNO, suggesting an improved Dm with no change in Vc, possibly related to an intense HPV (36). In that study too, DL was expectedly correlated to V˙O2max (36). In the present study, the increase in DLNO and DLCO was proportional in keeping with no or trivial relative changes in the components of lung diffusion. However, DLNO and not DLCO independently predicted V˙O2max. This may be related to a proportionally greater numerical values of DLNO compared with DLCO. Increased DLCO reported in most studies is probably the consequence of increased pulmonary perfusion pressure to recruit and distend pulmonary capillaries. At higher altitudes, an increased pulmonary venous resistance might also contribute (27).

The DLNO/DLCO ratio of 5.0 at rest in normoxia reached the upper limit of 4.9 proposed by Hughes and van der Lee (21) but is consistent with previous studies on younger adults (39) taken into account a semirecumbent body position probably associated with some degree of pulmonary vascular recruitment. During exercise at various intensities, DLCO and DLNO have been shown to increase in proportion to workload, with a slight decrease in the DLNO/DLCO ratio ranging from −2% to −16% (40). The present data confirm a decrease of 3.5% ± 5.6% or 3.2% ± 5.2% at sea level and at moderate altitude, respectively, suggesting a predominant effect of increased capillary blood volume (17,20).

As aerobic exercise capacity is inversely correlated to increased pulmonary vascular tone, there has been the idea of pulmonary vasodilating interventions as an ergogenic aid, particularly during high altitude exposure when HPV is activated. Phosphodiesterase-5 inhibitors sildenafil and tadalafil and endothelin receptor blockers, bosentan or sitaxsentan, either slightly improved or did not affect exercise capacity, Ppa or DL (7,10,12,13,16,20,22,29,33). The most convincing improvement in aerobic exercise capacity at high altitude was reported with preventive administration of a high dose of corticosteroids, which improved arterial oxygenation and V˙O2max along with an almost complete ablation of HPV (13). However, the effects of corticosteroids in hypoxia are multiple, and one does not know which one is determinant (13). Thus, at this stage, whether a pharmacological decrease in pulmonary vascular tone improves exercise capacity at moderate altitude is uncertain, and reported effects at high altitudes are controversial.

Oxygen delivery to the tissues

The magnitude of the decrease in V˙O2max with ascent to moderate altitude was associated with the decrease of SpO2 or CaO2 at the peak of exercise, suggesting oxygen transport to tissues to be a major limiting factor. Although in the present study V˙O2max was independently associated with a higher lung diffusion capacity, associated improved gas exchange was not sufficient to prevent exercise-induced hypoxemia at moderate altitude. Exercise-induced hypoxemia results from a combination of altered ventilation/perfusion matching and diffusion limitation for O2 and eventual mechanical constraints on the respiratory system (9). In the present study, the fall in SpO2 at maximum exercise at sea level was of an average of 4%, whereas at moderate altitude, SpO2 decreased by an average of 10% and fell less than 90%, indicating marked end exercise hypoxemia (9). The reasons for this difference are not entirely clear, as mPpa, Pla, maximum Q˙, and DLNO were not different, excluding the possible onset of interstitial lung edema during exercise at moderate altitude. A possible explanation may be that exercise at moderate altitude started at lower alveolar PO2 and that DLO2 would have decreased because of a decreased driving pressure through the alveolocapillary membrane. However, the study was not designed to explore the mechanisms of exercise-induced hypoxemia and, thus, offers no data supporting this explanation.


This study has several limitations. 1) Pulmonary vascular function was evaluated by Doppler echocardiographic estimates of mPpa, Pla, and , which may lack accuracy and precision as compared with invasive measurements. Furthermore, sufficient quality signals for these determinations could not be obtained in nine subjects (24%). However, similar pulmonary vascular pressure–flow relationships have been reported by invasive and noninvasive studies in normal subjects (23,24,28). Accordingly, a noninvasive approach of the pulmonary circulation can be assumed to be reasonable, although direct validation by concomitant invasive measurements was not available and in fact not possible for practical and ethical reasons in the present study. 2) There were no arterial blood gases measurements so that the effects of normoxic or hypoxic exercise on alveolar-to-arterial PO2 gradients could not be evaluated. However, exercise-induced hypoxemia was evaluated by SpO2 measurements as recommended (9). 3) Respiratory patterns during exercise at moderate altitudes were not explored. However, there is no reported evidence of altered respiratory patterns as a cause of decreased exercise capacity at altitudes. 4) Possible increases of HbCO or HbNO levels due to repetitive measurements were not checked for, and Hb was not measured during exercise. However, the effect of Hb, HbCO, and HbNO on the present results would be reasonably assumed to be negligible (40). 5) There may be some persisting disagreements about the optimal single breath DLNO and DLCO measurements and derived Dm and Vc calculations. In this study, we followed the most recently published recommendations of an expert task force of the European Respiratory Society (40). A still debated matter may be the use of a finite value of 4.5 mL NO·mL blood−1·min−1·mm Hg−1 for θNO, which was actually determined from in vitro experiments and a limited number of measurements in dogs (3) and may thus not be sufficiently validated for humans. We therefore recalculated Dm and Vc with an infinite value of θNO. This did not affect the statistical significance of altitude or exercise-related changes, but the absolute values for recalculated Dm and Vc were obviously markedly different. It may therefore be preferable to focus on the DLNO/DLCO ratio to identify predominantly alveolocapillary membrane or pulmonary capillary blood volume changes, as was also recently recommended (21).


In conclusion, the present results show that aerobic exercise capacity at sea level as well as at moderate altitude is modulated by pulmonary vascular reserve, but essentially determined by O2 delivery to the tissues at moderate altitude more than at sea level.

M. Vicenzi was a recipient of a Long-Term Research Fellowship (LTRF 94-2012) of the European Respiratory Society. The authors thank JP Belgrado and JJ Moraine for their technical support and encouragement.

The authors disclose professional relationships with companies or manufacturers who will benefit from the results of the present study.

The authors state that the results of the present study do not constitute endorsement by the American College of Sports Medicine.

The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

V. F., R. N., and G. De.: significant manuscript writer. M. V., F. D., A. F. G., E. R., and E. S.: significant manuscript reviewer/reviser. R. N., G. Do., E. S., E. R., F. D., G. D., V. F., and M. V.: concept and design. G. Do., B. S., I. H., E. S., E. R., F. D., G. De., V. F., M. V., and A. F. G.: data acquisition. R. N., F. D., G. De., V. F., M. V., A. F. G., and B. S.: data analysis and interpretation. V. F. and R. N: statistical expertise.


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