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.

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.

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.

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.

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.

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.

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.

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.

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.