Author Archives: Paul Older

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.

The metabolic signature of cardiorespiratory fitness: a protocol for a systematic review and meta-analysis.

Carrard J; Guerini C; Appenzeller-Herzog C; Infanger D; Königstein K; Streese L; Hinrichs T; Hanssen H;
Gallart-Ayala H; Ivanisevic J; Schmidt-Trucksäss A;

BMJ open sport & exercise medicine [BMJ Open Sport Exerc Med] 2021 Feb 19; Vol. 7 (1), pp. e001008. Date of Electronic Publication: 2021 Feb 19 (Print Publication: 2021).

Introduction: A low cardiorespiratory fitness (CRF) is a strong and independent predictor of cardiometabolic, cancer and all-cause mortality. To date, the mechanisms linking CRF with reduced mortality remain largely unknown. Metabolomics, which is a powerful metabolic phenotyping technology to unravel molecular mechanisms underlying complex phenotypes, could elucidate how CRF fosters human health.
Methods and Analysis: This study aims at systematically reviewing and meta-analysing the literature on metabolites of any human tissue sample, which are positively or negatively associated with CRF. Studies reporting estimated CRF will not be considered. No restrictions will be placed on the metabolomics technology used to measure metabolites. PubMed, Web of Science and EMBASE will be searched for relevant articles published until the date of the last search. Two authors will independently screen full texts of selected abstracts. References and citing articles of included articles will be screened for additional relevant publications. Data regarding study population, tissue samples, analytical technique, quality control, data processing, metabolites associated to CRF, cardiopulmonary exercise test protocol and exercise exhaustion criteria will be extracted. Methodological quality will be assessed using a modified version of QUADOMICS. Narrative synthesis as well as tabular/charted presentation of the extracted data will be included. If feasible, meta-analyses will be used to investigate the associations between identified metabolites and CRF. Potential sources of heterogeneity will be explored in meta-regressions.

Percentage of age-predicted cardiorespiratory fitness and risk of sudden cardiac death: a prospective cohort study.

Laukkanen JA; Kurl S; IKhan H; Kunutsor SK;

Heart rhythm [Heart Rhythm] 2021 Mar 06. Date of Electronic Publication: 2021 Mar 06.

Background: The inverse associations between cardiorespiratory fitness (CRF) and vascular outcomes are previously established. However, there has been no previous prospective evaluation of the relationship between percentage of age-predicted CRF (%age-predicted CRF) and risk of sudden cardiac death (SCD).
Objective: We aimed to assess the association of %age-predicted CRF with SCD risk in a long-term prospective cohort study.
Methods: Cardiorespiratory fitness was assessed using the gold standard respiratory gas exchange analyser in 2,276 men who underwent cardiopulmonary exercise testing. The age-predicted CRF estimated from a regression equation for age was converted to %age-predicted CRF using (achieved CRF/age-predicted CRF)*100. Hazard ratios (HRs) (95% confidence intervals, CIs) were calculated for SCD.
Results: During a median follow-up of 28.2 years, 260 SCDs occurred. There was a dose-response relationship between age-predicted CRF and SCD. A 1 standard deviation increase in %age-predicted CRF was associated with a decreased risk of SCD in analysis adjusted for established risk factors (HR 0.60; 95% CI 0.53-0.70), which remained consistent on further adjustment for several potential confounders including alcohol consumption, physical activity, socioeconomic status and systemic inflammation (HR 0.73; 95% CI 0.62-0.85). The corresponding adjusted HRs (95% CIs) were 0.34 (0.23-0.50) and 0.52 (0.34-0.79) respectively, when comparing extreme quartiles of %age-predicted CRF levels. The HRs for the associations of absolute CRF levels with SCD risk in the same participants were similar.
Conclusions: Percentage of age-predicted CRF is continuously, strongly and independently associated with risk of SCD and it is comparable to absolute CRF as a risk indicator for SCD.

“You can leave your mask on”: effects on cardiopulmonary parameters of different airway protection masks at rest and during maximal exercise.

Mapelli M; Salvioni E; De Martino F; Mattavelli I; Gugliandolo P; Vignati C; Farina S; Palermo P; Campodonico J; Maragna R; Lo Russo G; Bonomi A; Sciomer S; Agostoni P;

The European respiratory journal [Eur Respir J] 2021 Mar 07. Date of Electronic Publication: 2021 Mar 07.

Background: During the COVID-19 pandemic, the use of protection masks is essential to reduce contagions. However, public opinion reports an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protection masks.
Methods: Twelve healthy subjects underwent three cardiopulmonary exercise tests: without wearing protection mask, with surgical and with FFP2 mask. Dyspnea was assessed by Borg Scale. Standard pulmonary function tests were also performed.
Results: All the subjects (40.8±12.4 years; 6 males) completed the protocol with no adverse event. At spirometry, from no mask to surgical to FFP2, a progressive reduction of FEV 1 and FVC was observed (3.94±0.91 l, 3.23±0.81 l, 2.94±0.98 l and 4.70±1.21 l, 3.77±1.02 l, 3.52±1.21 l, respectively, p<0.001). Rest ventilation, O 2 uptake (V̇O 2 ) and CO 2 production (VCO 2 ) were progressively lower with a reduction of respiratory rate. At peak exercise, subjects revealed a progressively higher Borg scale when wearing surgical and FFP2. Accordingly, at peak exercise, V̇O 2 (31.0±23.4, 27.5±6.9, 28.2±8.8 ml/kg/min, p=0.001), ventilation (92±26, 76±22, 72±21 l, p=0.003), respiratory rate (42±8, 38±5, 37±4, p=0.04) and tidal volume (2.28±0.72, 2.05±0.60, 1.96±0.65 l, p=0.001) were gradually lower. We did not observed a significant difference in oxygen saturation.
Conclusions: Protection masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to an increased airflow resistance. However, since exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.

Bicycle spiroergometry: comparison of standardized examination protocols for adolescents: is it necessary to define own standard values for each protocol?

Windhaber J; Steinbauer M; Holter M; Wieland A;Kogler K; Riedl R; Schober P; Castellani C; Singer G; Till H;

European journal of applied physiology [Eur J Appl Physiol] 2021 Mar 12. Date of Electronic Publication: 2021
Mar 12.

Purpose: To compare performance data of adolescents collected with five different bicycle spiroergometry protocols and to assess the necessity for establishing standard values for each protocol.
Methods: One-hundred-twenty adolescents completed two bicycle spiroergometries within 14 days. One of the two tests was performed based on our institutional weight-adapted protocol (P0). The other test was performed based on one out of four exercise protocols widely used for children and adolescents (P1, 2, 3 or 4) with 30 persons each. The two tests were performed in a random order. Routine parameters of cardiopulmonary exercise tests (CPET) such as VO 2 peak, maximum power, O 2 pulse, OUES, VE/VCO 2 slope as well as ventilatory and lactate thresholds were investigated. Agreement between protocols was evaluated by Bland-Altman analysis, coefficients of variation (CV) and intra-class correlation coefficients (ICC).
Results: None of the CPET parameters were significantly different between P0 and P1, 2, 3 or 4. For most of the parameters, low biases between P0 and P1-P4 were found and 95% confidence intervalls were narrow. CV and ICC values largely corresponded to well-defined analytical goals (CV < 10% and ICC > 0.9). Only maximal power (Pmax) showed differences in size and drift of the bias depending on the length of the step duration of the protocols.
Conclusion: Comparability between examination protocols has been shown for CPET parameters independent on step duration. Protocol-dependent standard values do not appear to be necessary. Only Pmax is dependent on the step duration, but in most cases, this has no significant influence on the fitness assessment.

Combined aerobic/resistance/inspiratory muscle training as the ‘optimum’ exercise programme for patients with chronic heart failure: ARISTOS-HF randomized clinical trial.

Laoutaris ID; Piotrowicz E; Kallistratos MS; Dritsas A; Dimaki N; Miliopoulos D; Andriopoulou M; Manolis AJ; Volterrani M; Piepoli MF; Coats AJS; Adamopoulos S;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec 02. Date of Electronic Publication: 2020 Dec 02.

Aims: An ‘optimum’ universally agreed exercise programme for heart failure (HF) patients has not been found. ARISTOS-HF randomized clinical trial evaluates whether combined aerobic training (AT)/resistance training (RT)/inspiratory muscle training (IMT) (ARIS) is superior to AT/RT, AT/IMT or AT in improving aerobic capacity, left ventricular dimensions, and secondary functional outcomes.
Methods and Results: Eighty-eight patients of New York Heart Association II-III, left ventricular ejection fraction  ≤ 35% were randomized to an ARIS, AT/RT, AT/IMT, or AT group, exercising 3 times/week, 180 min/week for 12 weeks. Pre- and post-training, peakVO2 was evaluated with cardiopulmonary exercise testing, left ventricular dimensions using echocardiography, walking distance with the 6-min walk test (6MWT), quality of life by the Minnesota Living with HF Questionnaire (MLwHFQ), while a programme preference survey (PPS) was used. Seventy-four patients of [mean 95% (confidence interval, CI)] age 66.1 (64.3-67.9) years and peakVO2 17.3 (16.4-18.2) mL/kg/min were finally analysed. Between-group analysis showed a trend for increased peakVO2 (mL/kg/min) [mean contrasts (95% CI)] in the ARIS group [ARIS vs. AT/RT 1.71 (0.163-3.25)(.), vs. AT/IMT 1.50 (0.0152-2.99)(.), vs. AT 1.38 (-0.142 to 2.9)(.)], additional benefits in circulatory power (mL/kg/min⋅mmHg) [ARIS vs. AT/RT 376 (60.7-690)*, vs. AT/IMT 423 (121-725)*, vs. AT 345 (35.4-656)*], left ventricular end-systolic diameter (mm) [ARIS vs. AT/RT -2.11 (-3.65 to (-0.561))*, vs. AT -2.47 (-4.01 to (-0.929))**], 6MWT (m) [ARIS vs. AT/IMT 45.6 (18.3-72.9)**, vs. AT 55.2 (27.6-82.7)****], MLwHFQ [ARIS vs. AT/RT -7.79 (-11 to (-4.62))****, vs. AT -8.96 (-12.1 to (-5.84))****], and in PPS score [mean (95% CI)] [ARIS, 4.8 (4.7-5) vs. AT, 4.4 (4.2-4.7)*] [(.) P ≤ 0.1; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001].
Conclusion: ARISTOS-HF trial recommends exercise training for 180 min/week and supports the prescription of the ARIS training regime for HF patients (Clinical Trial Registration: http://www.clinicaltrials.gov. ARISTOS-HF Clinical Trial number, NCT03013270).