Category Archives: Publications

Impact of COVID-19 on exercise pathophysiology. A combined cardiopulmonary and echocardiographic exercise study.

Baratto C; Caravita S; Faini A; Perego GB; Senni M;Badano LP; Parati G;

Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2021 Mar 25. Date of Electronic Publication: 2021 Mar 25.

Background: Survivors from COVID-19 pneumonia can present with persisting multisystem involvement (lung, pulmonary vessels, heart, muscle, red blood cells) that may negatively affect exercise capacity.
Methods: We sought to determine the extent and the determinants of exercise limitation in COVID-19 patients at the time of hospital discharge.
Results: Eighteen consecutive patients with COVID-19 and 1:1 age-, sex-, and body mass index- matched controls underwent: spirometry, echocardiography, cardiopulmonary exercise test and exercise echocardiography for the study of pulmonary circulation. Arterial blood was sampled at rest and during exercise in COVID-19 patients. COVID-19 patients lie roughly on the same oxygen consumption isophlets than controls both at rest and during submaximal exercise, thanks to supernormal cardiac output (p<0.05). Oxygen consumption at peak exercise was reduced by 30% in COVID-19 (p<0.001), due to a peripheral extraction limit. Additionally, within COVID-19 patients, hemoglobin content was associated with peak oxygen consumption (R 2 =0.46, p=0.002)Respiratory reserve was not exhausted (median [IRQ], 0.59 [0.15]) in spite of moderate reduction of forced vital capacity (79±40%)Pulmonary artery pressure increase during exercise was not different between patients and controls. Ventilatory equivalents for carbon dioxide were higher in COVID-19 patients than in controls (39.5 [8.5] vs 29.5 [8.8], p<0.001), and such an increase was mainly explained by increased chemosensitivity.
Conclusions: When recovering from COVID-19, patients present with reduced exercise capacity and augmented exercise hyperventilation. Peripheral factors, including anemia and reduced oxygen extraction by peripheral muscles were the major determinants of deranged exercise physiology. Pulmonary vascular function seemed unaffected, despite restrictive lung changes.

Differences in V˙O2max Measurements Between Breath-by-Breath and Mixing-Chamber Mode in the COSMED K5.

Winkert K; Kirsten J; Kamnig R; Steinacker JM; Treff G

International journal of sports physiology and performance [Int J Sports Physiol Perform] 2021 Mar 26, pp. 1-6. Date of Electronic Publication: 2021 Mar 26.

Purpose: Automated metabolic analyzers are frequently utilized to measure maximal oxygen consumption (V˙O2max). However, in portable devices, the results may be influenced by the analyzer’s technological approach, being either breath-by-breath (BBB) or dynamic micro mixing chamber mode (DMC). The portable metabolic analyzer K5 (COSMED, Rome, Italy) provides both technologies within one device, and the authors aimed to evaluate differences in V˙O2max between modes in endurance athletes.
Methods: Sixteen trained male participants performed an incremental test to voluntary exhaustion on a cycle ergometer, while ventilation and gas exchange were measured by 2 structurally identical COSMED K5 metabolic analyzers synchronously, one operating in BBB and the other in DMC mode. Except for the flow signal, which was measured by 1 sensor and transmitted to both devices, the devices operated independently. V˙O2max was defined as the highest 30-second average.
Results: V˙O2max and V˙CO2@V˙O2max were significantly lower in BBB compared with DMC mode (-4.44% and -2.71%), with effect sizes being large to moderate (ES, Cohen d = 0.82 and 1.87). Small differences were obtained for respiratory frequency (0.94%, ES = 0.36), minute ventilation (0.29%, ES = 0.20), and respiratory exchange ratio (1.74%, ES = 0.57).
Conclusion: V˙O2max was substantially lower in BBB than in DMC mode. Considering previous studies that also indicated lower V˙O2 values in BBB at high intensities and a superior validity of the K5 in DMC mode, the authors conclude that the DMC mode should be selected to measure V˙O2max in athletes.

Efficacy of Prehabilitation Including Exercise on Postoperative Outcomes Following Abdominal Cancer Surgery: A Systematic Review and Meta-Analysis

Jamie Waterland, Orla McCourt, Lara Edbrooke, Catherine L. Granger, Hilmy Ismail,
Bernhard Riedel
Linda Denehy
Front. Surg., 19 March 2021 | https://doi.org/10.3389/fsurg.2021.628848

Objectives: This systematic review set out to identify, evaluate and synthesise the evidence examining the effect of prehabilitation including exercise on postoperative outcomes following abdominal cancer surgery.

Methods: Five electronic databases (MEDLINE 1946-2020, EMBASE 1947-2020, CINAHL 1937-2020, PEDro 1999-2020, and Cochrane Central Registry of Controlled Trials 1991-2020) were systematically searched (until August 2020) for randomised controlled trials (RCTs) that investigated the effects of prehabilitation interventions in patients undergoing abdominal cancer surgery. This review included any form of prehabilitation either unimodal or multimodal that included whole body and/or respiratory exercises as a stand-alone intervention or in addition to other prehabilitation interventions (such as nutrition and psychology) compared to standard care.

Results: Twenty-two studies were included in the systematic review and 21 studies in the meta-analysis. There was moderate quality of evidence that multimodal prehabilitation improves pre-operative functional capacity as measured by 6 min walk distance (Mean difference [MD] 33.09 metres, 95% CI 17.69–48.50; p = <0.01) but improvement in cardiorespiratory fitness such as preoperative oxygen consumption at peak exercise (VO2 peak; MD 1.74 mL/kg/min, 95% CI −0.03–3.50; p = 0.05) and anaerobic threshold (AT; MD 1.21 mL/kg/min, 95% CI −0.34–2.76; p = 0.13) were not significant. A reduction in hospital length of stay (MD 3.68 days, 95% CI 0.92–6.44; p = 0.009) was observed but no effect was observed for postoperative complications (Odds Ratio [OR] 0.81, 95% CI 0.55–1.18; p = 0.27), pulmonary complications (OR 0.53, 95% CI 0.28–1.01; p = 0.05), hospital re-admission (OR 1.07, 95% CI 0.61–1.90; p = 0.81) or postoperative mortality (OR 0.95, 95% CI 0.43–2.09, p = 0.90).

Conclusion: Multimodal prehabilitation improves preoperative functional capacity with reduction in hospital length of stay. This supports the need for ongoing research on innovative cost-effective prehabilitation approaches, research within large multicentre studies to verify this effect and to explore implementation strategies within clinical practise.

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.

Lammi MR; Ghonim MA; Johnson J; D’Aquin J; Zamjahn JB; Pellett A; Okpechi SC; Romaine C; Pyakurel K; Luu HH; Shellito JE; Boulares AH; deBoisblanc BP;

Respiratory medicine [Respir Med] 2021 Mar 08; Vol. 180, pp. 106354. Date of Electronic Publication: 2021 Mar 08.

Background and Objective: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH).
Methods: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV 1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 μg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime.
Results: Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost.
Conclusions: A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.

Characteristics and reference values for cardiopulmonary exercise testing in the adult Chinese population – The Xiangya hospital exercise testing project (the X-ET project).

Dun Y; Olson TP; Li C; Qiu L; Fu S; Cao Z; Ripley-Gonzalez JW; You B; Li Q; Deng L; Li Q; Liu S;

International journal of cardiology [Int J Cardiol] 2021 Mar 12. Date of Electronic Publication: 2021 Mar 12.

Background: Reference values of cardiopulmonary exercise testing (CPX) vary with race/ethnicity. Chinese Americans are the fastest-growing racial/ethnic group in the United States. However, there is limited information about the reference values of cardiopulmonary exercise testing (CPX) variables in the Chinese population.
Methods: As part of the Xiangya Hospital Exercise Testing project (the X-ET project), this cross-sectional study screened 20,696 consecutive CPXs performed by 17,802 unique individuals at Xiangya Hospital of Central South University, China, from January 1, 2002, to December 31, 2019. A total of 964 unique healthy adults/tests (42% female) aged 49 ± 12 who completed a maximal ramp incremental CPX with cycle ergometry were included in this study. The reference values of primary CPX variables were expressed as the lower limit or upper limit of normal. Stepwise linear regression was used to fit the equations of key CPX variables. Predictive accuracy analysis for the equations with a comparison between present and previous studies were performed.
Results: Peak oxygen consumption (V̇O 2 ), carbon dioxide production, ventilation/min, work rate, and V̇O 2 at the anaerobic threshold were regressed on age, height, weight, and sex. These predictive equations showed good in- and out-sample predictive accuracy. Comparison with prior research revealed that prediction equations of peak V̇O 2 resultant from studies in which populations were entirely or primarily Caucasian had overestimated our subjects’ actual values.
Conclusion: The reference values and predicted equations of CPX variables in this study may provide a more appropriate framework to interpret the response to maximal ramp incremental cycle ergometry in the Chinese adult population.

Continuous positive airway pressure acutely increases exercise duration in children with severe therapy-resistant asthma: a randomized crossover trial.

Schindel CS; Schiwe D; Heinzmann-Filho JP; Campos NE; Pitrez PM; Donadio MVF;

World journal of pediatrics : WJP [World J Pediatr] 2021 Mar 17. Date of Electronic Publication: 2021 Mar 17.

Background: Lower exercise tolerance is an important component of asthma and the possible effects of non-invasive ventilation on exercise capacity in individuals with severe therapy-resistant asthma (STRA) are unknown. This study aimed to evaluate the immediate effect of continuous positive airway pressure (CPAP) on exercise tolerance in children with STRA.
Methods: We performed a controlled, randomized, crossover clinical trial including subjects aged 6 to 18 years old diagnosed with STRA. Clinical, anthropometric and lung function data were collected. The participants in the intervention group (IG) used CPAP (PEEP 10cmH 2 O and FiO 2 0.21) for a period of 40 min. Subjects in the control group (CG) used CPAP with minimum PEEP at 1 cmH 2 0 also for 40 min. Afterwards, subjects from both groups underwent cardiopulmonary exercise testing (CPET). After a 15-day washout period, on a subsequent visit, subjects participated in the opposite group to the initial one.
Results: Thirteen subjects with a mean age of 12.30 ± 1.7 years were included. The variables of peak expiratory flow (PEF) and forced expiratory volume in the first second (FEV 1 ) before using CPAP and after performing CPET did not show significant differences. Regarding CPET results, there was no significant difference (P = 0.59) between groups at peak exercise for oxygen consumption-VO 2 (CG: 33.4 ± 6.3 and IG: 34.5 ± 5.9, mL kg -1  min -1 ). However, the IG (12.4 ± 2.1) presented a total test time (min) significantly (P = 0.01) longer than the CG (11.5 ± 1.3).
Conclusion: The results suggest that the use of CPAP before physical exercise increases exercise duration in children and adolescents with STRA.

Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6 Months in People With COVID-19 Who Survived Hospitalization – A Pilot Study.

Debeaumont D; Boujibar F; Ferrand-Devouge E; Artaud-Macari E; Tamion F; Gravier FE; Smondack A; Cuvelier A; Muir JF; Alexandre K; Bonnevie T;

Physical therapy [Phys Ther] 2021 Mar 18. Date of Electronic Publication: 2021 Mar 18.

Objective: The aim of this pilot study was to assess physical fitness and its relationship with functional dyspnea in survivors of Covid-19, 6 months after their discharge from the hospital.
Methods: Data collected routinely from people referred for cardiopulmonary exercise testing (CPET) following hospitalization for Covid-19 were retrospectively analyzed. Persistent dyspnea was assessed using the modified Medical Research Council dyspnea (mMRC) scale.
Results: Twenty-three people with persistent symptoms were referred for CPET. Mean mMRC dyspnea score was 1 (SD = 1) and was significantly associated with VO2peak (%) (rho = -0.49). At 6 months, those hospitalized in the general ward had a slightly reduced VO2peak (87% [SD = 20]), whereas those who had been in the intensive care unit (ICU) had a moderately reduced VO2peak (77% [SD = 15]). Of note, the results of the CPET revealed that, in all patients, respiratory equivalents were high, power-to-weight ratios were low, and those who had been in the ICU had a relatively low ventilatory efficiency (mean VE/VCO2 slope = 34 [SD = 5]). Analysis of each individual showed that none had a breathing reserve <15% or 11 L/min, all had a normal exercise electrocardiogram, and 4 had a heart rate above 90%.
Conclusion: At 6 months, persistent dyspnea was associated with reduced physical fitness. This study offers initial insights into the mid-term physical fitness of people who required hospitalization for Covid-19. It also provides novel pathophysiological clues about the underlaying mechanism of the physical limitations associated with persistent dyspnea. Those with persistent dyspnea should be offered a tailored rehabilitation intervention, which should probably include muscle reconditioning, breathing retraining, and perhaps respiratory muscle training.
Impact: This study is the first to show that a persistent breathing disorder (in addition to muscle deconditioning) can explain persistent symptoms 6 months after hospitalization for Covid-19 infection and suggests that a specific rehabilitation intervention is warranted.

Breathing training improves exercise capacity in patients with tetralogy of Fallot: a randomised trial.

Hock J; Remmele J; Oberhoffer R; Ewert P;Hager A;

Heart (British Cardiac Society) [Heart] 2021 Mar 18. Date of Electronic Publication: 2021 Mar 18.

Objective: Patients with tetralogy of Fallot (ToF) have limited pulmonary blood flow before corrective surgery and ongoing dysfunction of the pulmonary valve and right ventricle throughout life leading to lower exercise capacity and lung volumes in many patients. Inhalation training can increase lung volumes, improve pulmonary blood flow and consequently exercise capacity. This study tests whether home-based daily breathing training improves exercise capacity and lung volumes.
Methods: From February 2017 to November 2018, 60 patients (14.7±4.8 years, 39% female) underwent spirometry (forced vital capacity (FVC); forced expiratory volume in 1 s (FEV 1 )), cardiopulmonary exercise testing (peak oxygen uptake (peak [Formula: see text]O 2 )) and breathing excursion measurement. They were randomised into immediate breathing exercise or control group (CG) and re-examined after 6 months. The CG started their training afterwards and were re-examined after further 6 months. Patients trained with an inspiratory volume-oriented breathing device and were encouraged to exercise daily. The primary endpoint of this study was the change in peak [Formula: see text]O 2 . Results are expressed as mean±SEM (multiple imputations).
Results: In the first 6 months (intention to treat analysis), the training group showed a more favourable change in peak [Formula: see text]O 2 (Δ0.5±0.6 vs -2.3±0.9 mL/min/kg, p=0.011), FVC (Δ0.18±0.03 vs 0.08±0.03 L, p=0.036) and FEV 1 (Δ0.14±0.03 vs -0.00±0.04 L, p=0.007). Including the delayed training data from the CG (n=54), this change in peak [Formula: see text]O 2 correlated with self-reported weekly training days (r=0.282, p=0.039).
Conclusions: Daily inspiratory volume-oriented breathing training increases dynamic lung volumes and slows down deconditioning in peak [Formula: see text]O 2 in young patients with repaired ToF.

Clinical Interpretation of Cardiopulmonary Exercise Testing: Current Pitfalls and Limitations

Front. Physiol., 18 March 2021 | https://doi.org/10.3389/fphys.2021.552000
Several shortcomings on cardiopulmonary exercise testing (CPET) interpretation have shed a negative light on the test as a clinically useful tool. For instance, the reader should recognize patterns of dysfunction based on clusters of variables rather than relying on rigid interpretative algorithms. Correct display of key graphical data is of foremost relevance: prolixity and redundancy should be avoided. Submaximal dyspnea ratings should be plotted as a function of work rate (WR) and ventilatory demand. Increased work of breathing and/or obesity may normalize peak oxygen uptake (V̇O2) despite a low peak WR. Among the determinants of V̇O2, only heart rate is measured during non-invasive CPET. It follows that in the absence of findings suggestive of severe impairment in O2 delivery, the boundaries between inactivity and early cardiovascular disease are blurred in individual subjects. A preserved breathing reserve should not be viewed as evidence that “the lungs” are not limiting the subject. In this context, measurements of dynamic inspiratory capacity are key to uncover abnormalities germane to exertional dyspnea. A low end-tidal partial pressure for carbon dioxide may indicate either increased “wasted” ventilation or alveolar hyperventilation; thus, direct measurements of arterial (or arterialized) PO2 might be warranted. Differentiating a chaotic breathing pattern from the normal breath-by-breath noise might be complex if the plotted data are not adequately smoothed. A sober recognition of these limitations, associated with an interpretation report free from technicalities and convoluted terminology, is crucial to enhance the credibility of CPET in the eyes of the practicing physician.

Heart Failure With Preserved Ejection Fraction vs. Reduced Ejection Fraction - Mechanisms of Ventilatory Inefficiency During Exercise in Heart Failure.

Tsujinaga S; Iwano H; Chiba Y;Ishizaka S; Sarashina M; Murayama M; Nakabachi M; Nishino H; Yokoyama S;
Okada K; Kaga S; Anzai T;

Circulation reports [Circ Rep] 2020 Apr 07; Vol. 2 (5), pp. 271-279. Date of Electronic Publication: 2020 Apr 07.

Background: Ventilatory inefficiency during exercise assessed using the lowest minute ventilation/carbon dioxide production (V̇E/V̇CO 2 ) ratio was recently proven to be a strong prognostic marker of heart failure (HF) regardless of left ventricular ejection fraction (LVEF). Its physiological background, however, has not been elucidated.
Methods and Results: Fifty-seven HF patients underwent cardiopulmonary exercise testing and exercise-stress echocardiography. The lowest V̇E/V̇CO 2 ratio was assessed on respiratory gas analysis. Echocardiography was obtained at rest and at peak exercise. LVEF was measured using the method of disks. Cardiac output (CO) and the ratio of transmitral early filling velocity (E) to early diastolic tissue velocity (e’) were calculated using the Doppler method. HF patients were divided into preserved EF (HFpEF) and reduced EF (HFrEF) using the LVEF cut-off 40% at rest. Twenty-four patients were classified as HFpEF and 33 as HFrEF. In HFpEF, age (r=0.58), CO (r=-0.44), e’ (r=-0.48) and E/e’ (r=0.45) during exercise correlated with the lowest V̇E/V̇CO 2 ratio (P<0.05 for all). In contrast, in HFrEF, age (r=0.47) and CO (r=-0.54) during exercise, but not e’ and E/e’, correlated with the lowest V̇E/V̇CO 2 ratio. Conclusions: Loss of CO augmentation was associated with ventilatory inefficiency in HF regardless of LVEF, although lung congestion determined ventilatory efficiency only in HFpEF.