Dead Space Breathing in Patients with Malignancies: Determination by Cardiopulmonary Exercise Testing

Rationale: Patients with cancer commonly experience dyspnea originating from ventilatory, circulatory and musculoskeletal sources, and dyspnea is best determined by cardiopulmonary exercise testing (CPET). Objectives: In this retrospective pilot study, we evaluated patients with hematologic and solid malignancies by CPET to determine the primary source of their dyspnea. Methods: Subjects were exercised on a cycle ergometer with increasing workloads. Minute ventilation, heart rate, breathing reserve, oxygen uptake (V’O2), O2-pulse, ventilatory equivalents for carbon dioxide and oxygen (V’E/V’CO2 and V’E/V’O2, respectively) were measured at baseline and peak exercise. The slope and intercept for V’E/V’CO2 was computed for all subjects. Peak V’O2 4% predicted indicated a circulatory or ventilatory limitation. Results: Complete clinical and physiological data were available for 36 patients (M/F 20/16);32 (89%) exhibited ventilatory or circulatory limitation as shown by a reduced peak V’O2 and 10 subjects with normal physiologic data. The largest cohort comprised the pulmonary vascular group (n = 18) whose mean ± SD peak V’O2 was 61% ± 17% predicted. There were close associations between V’O2 and spirometric values. Peak V’E/V’O2 and V’E/V’CO2 were highest in the circulatory and ventilatory cohorts, consistent with increase in dead space breathing. The intercept of the V’E-V’CO2 relationship was lowest in patients with cardiovascular impairment. Conclusion: Dyspneic patients with malignancies exhibit dead space breathing, many exhibiting a circulatory source for exercise limitation with a prominent pulmonary vascular component. Potential factors include effects of chemo- and radiation therapy on cardiac function and pulmonary vascular endothelium.

Cardiopulmonary exercise testing in the evaluation of high risk patients with lung cancer

Background It is still unclear whether pulmonary function tests （PFTs） are sufficient for predicting perioperative risk,and whether all patients or only a subset of them need a cardiopulmonary exercise test （CPET） for further assessment.Thus, this study was designed to evaluate the CPET and compare the results of CPET and conventional PFTs to identify which parameters are more reliable and valuable in predicting perioperative risks for high risk patients with lung cancer.Methods From January 2005 to August 2008, 297 consecutive lung cancer patients underwent conventional PFTs （spirometry ＋ single-breath carbon monoxide diffusing capacity of the lungs （DLCOsb） for diffusion capacity） and CPET preoperatively. The correlation of postoperative cardiopulmonary complications with the parameters of PFT and CPET was retrospectively analyzed using the chi-square test, independent sample t test and binary Logistic regression analysis.Results Of the 297 patients, 78 did not receive operation due to advanced disease stage or poor cardiopulmonary function. The remaining 219 underwent different modes of operations. Twenty-one cases were excluded from this study due to exploration alone （15 cases） and operation-related complications （6 cases）. Thus, 198 cases were eligible for evaluation. Fifty of the 198 patients （25.2%） had postoperative cardiopulmonary complications. Three patients （1.5%）died of complications within 30 postoperative days. The patients were stratified into groups based on VO2max/pred respectively. The rate of postoperative cardiopulmonary complications was significantly higher in the group with cardiopulmonary complications were significantly correlated with age, comorbidities, and poor PFT and CPET results.used to stratify the patients＇ cardiopulmonary function status and to predict the risk of postoperative cardiopulmonary predicting perioperative risk. If available, cardiopulmonary exercise testing is strongly suggested for high-risk lung cancer patients in addition to conventional pulmonary function tests, and both should be combined to assess cardiopulmonary function status.

Research hotspots and trends of cardiopulmonary exercise test:Visualization analysis based on citespace

The study aims to grasp the hot spots and trends of global cardiopulmonary exercise research.Web of Science(WoS)core collection and Derwent Innovation Index database were retrieved to collect literature from 2002 to 2022 with Cardiopulmonary Exercise Test(CPET)as the retrieval theme.CiteSpace was used to conduct bibliometrics and visual analysis of 6679 pieces of literature in the web of science core collection database and 251 patent data in the Derwent Innovation Index database.The results show that:(1)the number of CPET theme research papers is increasing year by year,and the main research fields are cardiology,respiratory system,sports science,etc.;(2)The main research hot spots of CPET include exercise prescription,exercise and heart failure,COVID-19 cardiopulmonary rehabilitation and evaluation,etc.;(3)The development trend of CPET technology is majorly in the direction of intelligence,portability,individualization and the integration of Virtual Reality(VR)technology and evidence-based research of CPET guiding clinical decision-making.

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of life.These complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality rates.Despite the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac surgery.Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength.Early mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance exercises.Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity.During the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac rehabilitation.By incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity

BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium.They also have low levels of endothelial progenitor cells(EPCs).EPCs are bone marrow derived cells involved in endothelium regeneration,homeostasis,and neovascularization.Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities.However,the effects of exercise on EPCs in different stages of CHF remain under investigation.AIM To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing(CPET)on EPCs in CHF patients of different severity.METHODS Forty-nine consecutive patients(41 males)with stable CHF[mean age(years):56±10,ejection fraction(EF,%):32±8,peak oxygen uptake(VO2,mL/kg/min):18.1±4.4]underwent a CPET on a cycle ergometer.Venous blood was sampled before and after CPET.Five circulating endothelial populations were quantified by flow cytometry:Three subgroups of EPCs[CD34+/CD45-/CD133+,CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2(VEGFR2)]and two subgroups of circulating endothelial cells(CD34+/CD45-/CD133-and CD34+/CD45-/CD133-/VEGFR2).Patients were divided in two groups of severity according to the median value of peak VO2(18.0 mL/kg/min),predicted peak VO2(65.5%),ventilation/carbon dioxide output slope(32.5)and EF(reduced and mid-ranged EF).EPCs values are expressed as median(25th-75th percentiles)in cells/106 enucleated cells.RESULTS Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:60(25-76)vs post CPET:90(70-103)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:1(1-4)vs post CPET:5(3-8)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133-[pre CPET:186(141-361)vs post CPET:488(247-658)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:2(1-2)vs post CPET:3(2-5)cells/106 enucleated cells,P<0.001],while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:42(19-73)vs post CPET:90(39-118)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:2(1-3)vs post CPET:6(3-9)cells/106 enucleated cells,P<0.001],CD34+/CD133+/VEGFR2[pre CPET:10(7-18)vs post CPET:14(10-19)cells/106 enucleated cells,P<0.01],CD34+/CD45-/CD133-[pre CPET:218(158-247)vs post CPET:311(254-569)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:1(1-2)vs post CPET:4(2-6)cells/106 enucleated cells,P<0.001].A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak,ventilation/carbon dioxide output slope and EF as well(P<0.05).However,there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison(P>0.05).CONCLUSION Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients,but this increase was not associated with syndrome severity.Further investigation,however,is needed.

Influence of age in estimating maximal oxygen uptake

Objective To assess the influence of age on the error of estimate （EE） of maximal oxygen uptake （VO2max） using sex and population specific-equations in cycle ergometer exercise testing, since estimated VO2 max is associated with a substantial EE, often exceeding 20%, possibly due to intrinsic variability of mechanical efficiency. Methods 1850 adults （68% men）, aged 18 to 91 years, underwent maximal cycle ergometer cardiopulmonary exercise testing. Cardiorespiratory fitness （CRF） was assessed relative to sex and age [younger （18 to 35 years）, middle-aged （36 to 60 years） and older （〉 60 years）]. VO2max [mL.（kg.min）-1] was directly measured by assessment of gas exchange and estimated using sex and population specific-equations. Measured and estimated values of VO2max and related EE were compared among the three age- and sex-specific groups. Results Directly measured VO2max of men and women were 29.5 ± 10.5 mL.（kg.min）-1 and 24.2 ± 9.0 mL.（kg·min） -1 （P 〈 0.01）. EE [mL·（kg·min）-1] and percent errors （%E） for men and women had similar values, 0.5 ± 3.2 and 0.4 ± 2.9 mL·（kg·min）-1, and -0.8 ± 13.1% and -1.7 ± 15.4% （P 〉 0.05）, respectively. EE and %E for each age-group were, respectively, for men： younger = 1.9 ± 4.1 mL·（kg·min）-1 and 3.8 ± 10.5%, middle-aged = 0.6 ± 3.1 mL.（kg·min）-1 and 0.4 ± 10.3%, older = -0.2 ± 2.7 mL·（kg·min） -1 and -4.2 ± 16.6% （P 〈 0.01）; and for women： younger = 1.2 ± 3.1 mL.（kg.min）-1 and 2.7 ±10.0%, middle-aged = 0.7 ± 2.8 mL·（kg·min）-1 and 0.5 ± 11.1%, older = -0.8 ± 2.3 mL-（kg·min）-1 and -9.5 ± 22.4% （P 〈 0.01）. Conclusion VO2max were underestimated in younger age-groups and were overestimated in older age groups. Age significantly influences the magnitude of the EE of VO2max in both men and women and should be considered when CRF is estimated using population specific equations, rather than directly measured.

Significant exercise limitations after recovery from MIS-C related myocarditis

Background Myocarditis is one of the presentations of multisystemic infammatory syndrome in children(MIS-C)following coronavirus disease 2019(COVID-19).Although the reported short-term prognosis is good,data regarding medium-term functional capacity and limitations are scarce.This study aimed to evaluate exercise capacity as well as possible cardiac and respiratory limitations in children recovered from MIS-C related myocarditis.Methods Fourteen patients who recovered from MIS-C related myocarditis underwent spirometry and cardiopulmonary exercise testing(CPET),and their results were compared with an age-,sex-,weight-and activity level-matched healthy control group(n=14).Results All participants completed the CPET with peak oxygen uptake(peak.V O2),and the results were within the normal range(MIS-C 89.3%±8.9%and Control 87.9%±13.7%predicted.V O2).Five post-MIS-C patients(35%)had exerciserelated cardio-respiratory abnormalities,including oxygen desaturation and oxygen-pulse fattening,compared to none in the control group.The MIS-C group also had lower peak exercise saturation(95.6±3.5 vs.97.6±1.1)and lower breathing reserve(17.4%±7.5%vs.27.4%±14.0%of MVV).Conclusions Patients who recovered from MIS-C related myocarditis may present exercise limitations.Functional assessment(e.g.,CPET)should be included in routine examinations before allowing a return to physical activity in post-MIS-C myocarditis.Larger,longer term studies assessing functional capacity and focusing on physiological mechanisms are needed.

Effect of yelling on maximal aerobic power during an incremental test of cycling performance

Background：People experiencing strong feelings of fatigue during exercise sometimes subconsciously yell to refocus their efforts and,thus,maintain exercise performance.The present study examined the influenc of yelling during high-intensity exercise by analysing cardiorespiratory reactions and integrated electromyography（i EMG） changes in the vastus lateralis during a cycle ergometer test.Methods：A total of 23 moderately trained people were recruited.The cycling test began with a resistance of 25 W/min,which was gradually increased.During the experimental trial,the participants were required to yell at least 3 times when they felt exhausted;during the controlled trial,they were not allowed to produce any yelling sounds.The testing order was randomly assigned and the 2 trials were completed within an interval between 3–10 days.Two-way repeated measures ANOVA was applied to analyse the differences within and between the trials,and interaction of trial and time.Results：The peak power and time to exhaustion（p〈0.01） in the yelling trial were higher than those in the control trial.However,the vastus lateralis iE MG values of both trials at peak power were not significant y different.During the yelling period at 90%–100% of the maximal effort,a significan time-by-trialinteraction（p〈0.05）wasobservedinoxygenconsumption（VO2）,CO2 production,O2 pulse,ventilation,andrespiratoryrate. Alltheabove measures showed a significan between-trial difference（p〈0.02）.However,heart rate,respiratory exchange ratio,end-tidal oxygen pressure,and ventilatory equivalent for oxygen showed only significan between-trial difference（p〈0.05）,but without interaction of trial and time.Conclusion：Yelling enhances the peak O2 pulse and VO2 and maintains CO2-exclusion efficien y during high-intensity exercise.It may enable maintaining muscle activation without stronger EMG signals being required during high-intensity exercise.

Effect of Maximal Oxygen Pulse on Patients with Chronic Obstructive Pulmonary Disease

Objective This study evaluated the effect of maximal oxygen pulse(O_(2)P_(max))on patients with chronic obstructive pulmonary disease(COPD)and confirmed the predictive effect on acute exacerbations of COPD(AECOPD).Methods This retrospective study included 91 participants who underwent cardiopulmonary exercise testing(CPET),lung function testing,a dyspnea scale assessment,and a 3-year follow-up.The participants were divided into two groups according to the O_(2)P_(max)value.Exercise capacity,ventilatory conditions,gas exchange efficiency,and dyspnea symptoms were compared,and the correlations between O_(2)P_(max)and these indices were evaluated.The ability of O_(2)P_(max)to predict AECOPD was examined.Results Exercise capacity,ventilatory conditions,and gas exchange efficiency were lower,and dyspnea symptom scores were higher in the impaired O_(2)P_(max)group(P<0.05).O_(2)P_(max)was positively correlated with forced vital capacity(FVC)%,forced expiratory volume in 1 sec(FEV_(1))%,FEV_(1)/FVC%,anaerobic threshold(AT),work rate(WR)%,aximal oxygen uptake(VO_(2))%,VO_(2)/kg_(max),VO_(2)/kg_(max)%,WR_(AT),WR_(max),VO_(2AT),VO_(2max),and V,and was negatively correlated with EqCO_(2AT),and EqCO_(2max)(P<0.05).Most importantly,O_(2)P_(max)could be used to predict AECOPD,and the best cut-off value was 89.5%(area under the curve,0.739;95%CI,0.609–0.869).Conclusion O_(2)P_(max)reflected exercise capacity,ventilation capacity,gas exchange capacity,and dyspnea symptoms in patients with COPD and may be an independent predictor of AECOPD.

Relationship between Coronary Artery Tortuosity and Cardiorespiratory Fitness in Patients without Obstructed Coronaries

Objective This study aimed to analyze the relationship between cardiorespiratory fitness(CRF)and the increasing severity of coronary artery tortuosity(CAT)in patients with non-stenosed coronaries.Methods A total of 396 patients who underwent coronary angiography and cardiopulmonary exercise testing(CPET)between August 2020 and July 2021 were included in this single-center retrospective study after excluding patients with significant coronary artery disease(≥50%stenosis).Patients were divided into two groups:no or mild coronary artery tortuosity(N/M-CAT)and moderate to severe coronary artery tortuosity(M/S-CAT)and laboratory electrocardiographic,echocardiographic,and CPET parameters were compared between two groups.Results M/S-CAT was found in 46.9%of the study participants,with 66.7%being women.M/S-CAT was significantly associated with advanced age(P=0.014)and females(P=0.001).Diastolic dysfunction parameters,E velocity(P=0.011),and E/A ratio(P=0.004)also revealed significant differences between the M/S-CAT group and N/M-CAT group.VO2@peak(1.22±0.39 vs.1.07±0.39,P<0.01)and VO2@AT(0.77±0.22 vs.0.71±0.21,P=0.017)were significantly lower in the M/S-CAT group than in the N/M-CAT group.Multivariate logistic regression analysis identified females(OR=0.448;95%CI,0.296–0.676;P=0.000)and E/A ratio(OR=0.307;95%CI,0.139–0.680;P=0.004)to be independent risk factors of M/S-CAT and showed no association of CPET parameters to M/S-CAT.Conclusion The results indicate that increasing severity of CAT is strongly associated with female gender and E/A ratio and is not directly correlated with decreasing CRF.Further research with a larger patient population and a longer follow-up time is required to fully comprehend the impact of CAT on CRF.

Effects of an active lifestyle on the physical frailty of liver transplant candidates

BACKGROUND Liver transplantation is the most important therapeutic intervention for end-stage liver disease(ELD).The prioritization of these patients is based on the model for end-stage liver disease(MELD),which can successfully predict short-term mortality.However,despite its great validity and value,it cannot fully incorporate several comorbidities of liver disease,such as sarcopenia and physical frailty,variables that can sufficiently influence the survival of such patients.Subsequently,there is growing interest in the importance of physical frailty in regard to mortality in liver transplant candidates and recipients,as well as its role in improving their survival rates.AIM To evaluate the effects of an active lifestyle on physical frailty on liver transplant candidates.METHODS An observational study was performed within the facilities of the Department of Transplant Surgery of Aristotle University of Thessaloniki.Twenty liver transplant candidate patients from the waiting list of the department were included in the study.Patients that were bedridden,had recent cardiovascular incidents,or had required inpatient treatment for more than 5 d in the last 6 mo were excluded from the study.The following variables were evaluated:Activity level via the International Physical Activity Questionnaire(IPAQ);functional capacity via the 6-min walking test(6MWT)and cardiopulmonary exercise testing;and physical frailty via the Liver Frailty Index(LFI).RESULTS According to their responses in the IPAQ,patients were divided into the following two groups based on their activity level:Active group(A,10 patients);and sedentary group(S,10 patients).Comparing mean values of the recorded variables showed the following results:MELD(A:12.05±5.63 vs S:13.99±3.60;P>0.05);peak oxygen uptake(A:29.78±6.07 mL/kg/min vs S:18.11±3.39 mL/kg/min;P<0.001);anaerobic threshold(A:16.71±2.17 mL/kg/min vs S:13.96±1.45 mL/kg/min;P<0.01);6MWT(A:458.2±57.5 m vs S:324.7±55.8 m;P<0.001);and LFI(A:3.75±0.31 vs S:4.42±0.32;P<0.001).CONCLUSION An active lifestyle can be associated with better musculoskeletal and functional capacity,while simultaneously preventing the evolution of physical frailty in liver transplant candidates.This effect appears to be independent of the liver disease severity.

Athletes with mild post-COVID-19 symptoms experience increased respiratory and metabolic demands:А cross-sectional study

Coronavirus Disease 2019(COVID-19)has significantly affected different physiological systems,with a potentially profound effect on athletic performance.However,to date,such an effect has been neither addressed nor investigated.Therefore,the aim of this study was to investigate fitness indicators,along with the respiratory and metabolic profile,in post-COVID-19 athletes.Forty male soccer players,were divided into two groups:non-hospitalized COVID-19(n=20,Age:[25.2±4.1]years,Body Surface Area[BSA]:[1.9±0.2]m^(2),body fat:11.8%±3.4%)versus[vs]healthy(n=20,Age:[25.1±4.4]years,BSA:[2.0±0.3]m^(2),body fat:10.8%±4.5%).For each athlete,prior to cardiopulmonary exercise testing(CPET),body composition,spirometry,and lactate blood levels,were recorded.Differences between groups were assessed with the independent samples t-test(p<0.05).Several differences were detected between the two groups:ventilation(:Resting:[14.7±3.1]L·min^(−1)vs.[11.5±2.6]L·min^(−1),p=0.001;Maximal Effort:[137.1±15.5]L·min^(−1)vs.[109.1±18.4]L·min^(−1),p<0.001),ratio VE/maximal voluntary ventilation(Resting:7.9%±1.8%vs.5.7%±1.7%,p<0.001;Maximal Effort:73.7%±10.8%vs.63.1%±9.0%,p=0.002),ratioVE/BSA(Resting:7.9%±2.0%vs.5.9%±1.4%,p=0.001;Maximal Effort:73.7%±11.1%vs.66.2%±9.2%,p=0.026),heart rate(Maximal Effort:[191.6±7.8]bpm vs.[196.6±8.6]bpm,p=0.041),and lactate acid(Resting:[1.8±0.8]mmol·L^(−1)vs.[0.9±0.1]mmol·L^(−1),p<0.001;Maximal Effort:[11.0±1.6]mmol·L^(−1)vs.[9.8±1.2]mmol·L^(−1),p=0.009),during CPET.No significant differences were identified regarding maximal oxygen uptake([55.7±4.4]ml·min^(−1)·kg−1 vs.[55.4±4.6]ml·min^(−1)·kg−1,p=0.831).Our findings demonstrate a pattern of compromised respiratory function in post-COVID-19 athletes characterized by increased respiratory work at both rest and maximum effort as well as hyperventilation during exercise,which may explain the reported increased metabolic needs.

Is BMI Associated with Cardiorespiratory Fitness?A Cross-Sectional Analysis Among 8470 Apparently Healthy Subjects Aged 18-94 Years from the Low-Lands Fitness Registry

Objective The purpose of the present study was to investigate the association between cardiorespiratory fitness(CRF)measured as peak oxygen uptake(VO_(2peak),expressed in mL/min)and body mass index(BMI)in a large cohort of apparently healthy subjects.Methods BMI and VO_(2peak)were measured in a cross-sectional study of 8470 apparently healthy adults.VO_(2peak)(mL/min)was determined by an incremental cycle ergometer test to exhaustion.Linear regression analyses were performed to identify predictors of CRF.Results There was no difference in CRF between adults with a normal weight(BMI between 18.5-24.9 kg/m^(2))and those who were overweight(BMI 25.0-29.9 kg/m^(2)).Subjects who were underweight(BMI<18.5 kg/m^(2))as well as females who were obese(BMI≥30.0 kg/m^(2))showed a reduced CRF compared to the normal and overweight groups.Age,height,and gender were significant predictors of CRF(R^(2)=0.467,P<0.0001);BMI did not add significantly to this relationship.Conclusion Our findings indicate that BMI was not associated with CRF in addition to age,height,and gender.In subjects with a BMI<18.5 kg/m^(2),CRF was lower compared to subjects with a BMI between 18.5 and 29.9 kg/m^(2).In obese subjects,CRF was only lower in females compared to females with a BMI between 18.5 and 29.9 kg/m^(2).Correcting CRF for BMI may be beneficial for subjects with a low BMI,and females with a BMI≥30.0 kg/m^(2).The outcome of this study might help to improve the interpretation of exercise testing results in individuals with a low or high BMI.