Effect of Supplemental Oxygen on Physiological Responses to Exercise in Fibrotic Interstitial Lung Disease.

PURPOSE: We studied the effect of O2 supplementation on physiological response to exercise in patients with moderate to severe interstitial lung disease (ILD). METHODS: 13 patients (age 66 ± 10 yrs., 7 males) with ILD (TLC 71 ± 22% predicted, carbon monoxide diffusion capacity (DLCO) 44 ± 16% predicted) and 13 healthy individuals (age 50 ± 17 yrs., 7 males) were tested. ILD patients performed symptom-limited cardiopulmonary exercise tests and constant work-rate tests (CWRTs) at 80% of the work-rate (WR) at the gas exchange threshold (GET). Tests breathing room air (RA, 21% O2) were compared to tests performed breathing 30% O2. Oxygen-uptake (V̇O2) kinetics were calculated from the CWRT results. RESULTS: In the ILD group, peak WR, peak V̇O2 and V̇O2 at the GET improved significantly when breathing 30% O2 compared to RA (mean ± SD 66 ± 23 vs 75 ± 26 watts, 15 ± 2 vs 17 ± 4 ml/kg/min and 854 ± 232 vs 932 ± 245 ml/min; p = 0.004, p = 0.001 and p = 0.01, respectively). O2 saturation (SPO2%) at peak exercise was higher with 30% O2 (97 ± 4% vs 88 ± 9%, p = 0.002). The time constant (tau) of V̇O2 kinetics was faster in ILD patients while breathing 30% O2 (41 ± 10 sec) compared to RA (52 ± 14 sec, p = 0.003). There was a negative linear relation between tau and SPO2% with RA (r = -0.76, p = 0.006) and while breathing 30% O2 (r = -0.68, p = 0.02). CONCLUSIONS: Using a clinically applicable level of O2 supplementation (30%) improved maximal, aerobic exercise capacity and V̇O2 kinetics in ILD patients, likely due to increased blood O2 content subsequently increasing the O2 delivery to the working muscles.

The role of inspiratory capacity and tidal flow in diagnosing exercise ventilatory limitation in Cystic Fibrosis.

BACKGROUND: Exercise ventilatory limitation conventionally defined by reduced breathing reserve (BR) may underestimate the effect of lung disease on exercise capacity in patients with mild to moderate obstructive lung diseases. OBJECTIVE: To investigate whether ventilatory limitation may be present despite a normal BR in Cystic Fibrosis (CF). METHODS: Twenty adult CF patients (age 16-58y) with a wide range of pulmonary obstruction severity completed a symptom-limited incremental exercise test on a cycle ergometer. Operating lung volumes were derived from inspiratory capacity (IC) measurement during exercise and exercise tidal flow volume loop analysis. RESULTS: six patients had a severe airway obstruction (FEV1<45% predicted) and conventional evidence of ventilatory limitation (low BR). Fourteen patients had mild to moderate-severe airway obstructive (FEV1 46-103% predicted), and a normal BR [12-62 L/min, BR% (17-40)]. However, dynamic respiratory mechanics demonstrated that even CF patients with mild to moderate-severe lung disease had clear evidence of ventilatory limitation during exercise. IC was decreased by (median) 580 ml (range 90-1180 ml) during exercise, indicating dynamic hyperinflation. Inspiratory reserve volume at peak exercise was 445 ml (241-1350 ml) indicating mechanical constraint on the respiratory system. The exercise tidal flow met or exceeded the expiratory boundary of the maximal flow volume loop over 72% of the expiratory volume (range 40-90%), indicating expiratory flow limitation. CONCLUSION: Reduced BR as a sole criterion underestimates ventilatory limitation during exercise in mild to moderate-severe CF patients. Assessment of dynamic respiratory mechanics during exercise revealed ventilatory limitation, present even in patients with mild obstruction.

Oxygen uptake kinetics during exercise reveal central and peripheral limitation in patients with iliofemoral venous obstruction.

OBJECTIVE: Pulmonary oxygen uptake (V˙O2) kinetics measured during the initiation of exercise mirror energetic transition during daily activity. The aim of this study was to elucidate the pathophysiological mechanisms of exercise limitation of patients with chronic iliofemoral vein obstruction after deep vein thrombosis by measuring V˙O2 kinetics compared with patients with peripheral arterial disease (PAD) and healthy individuals. METHODS: Eleven patients with iliofemoral vein obstruction (7 men; age, 20-65 years), seven patients with PAD (all men; age 44-60 years) and eight healthy participants (5 men; age 28-58 years) were studied. Participants performed upper and lower limb symptom-limited cardiopulmonary exercise tests on cycle ergometers; and four repeat lower limb tests at a constant work rate corresponding with 90% of the gas exchange threshold for determining V˙O2 kinetics. RESULTS: Phase I V˙O2 amplitude in the constant work rate tests (percent increase over resting V˙O2), representing the initial surge in cardiac output caused by the emptying of leg veins, was 59 ± 19% in the iliofemoral vein obstruction group, 73 ± 22% in PAD, and 85 ± 26% in healthy participants (P = .055 for iliofemoral vein obstruction vs healthy). Phase II V˙O2 kinetics, which largely reflect the kinetics of O2 consumption in the exercising muscles, were slower in iliofemoral vein obstruction (tau = 42 ± 6 seconds), and PAD (tau = 49 ± 19 seconds), compared with healthy participants (23 ± 4 seconds; P < .01). CONCLUSIONS: Slow phase II V˙O2 kinetics reflect a slow onset of muscular aerobic metabolism in both iliofemoral vein obstruction and PAD. The low amplitude phase I of V˙O2 kinetics observed in iliofemoral vein obstruction suggests a damped cardiodynamic phase, consistent with decreased venous return from the obstructed veins. These abnormalities of V˙O2 kinetics may contribute to exercise intolerance in iliofemoral vein obstruction and PAD.

A Machine Learning Approach to the Interpretation of Cardiopulmonary Exercise Tests: Development and Validation.

OBJECTIVE: At present, there is no consensus on the best strategy for interpreting the cardiopulmonary exercise test's (CPET) results. This study is aimed at assessing the potential of using computer-aided algorithms to evaluate CPET data for identifying chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). METHODS: Data from 234 CPET files from the Pulmonary Institute, at Sheba Medical Center, and the Givat-Washington College, both in Israel, were selected for this study. The selected CPET files included patients with confirmed primary CHF (n = 73), COPD (n = 75), and healthy subjects (n = 86). Of the 234 CPETs, 150 (50 in each group) tests were used for the support vector machine (SVM) learning stage, and the remaining 84 tests were used for the model validation. The performance of the SVM interpretive module was assessed by comparing its interpretation output with the conventional clinical diagnosis using distribution analysis. RESULTS: The disease classification results show that the overall predictive power of the proposed interpretive model ranged from 96% to 100%, indicating very high predictive power. Furthermore, the sensitivity, specificity, and overall precision of the proposed interpretive module were 99%, 99%, and 99%, respectively. CONCLUSIONS: The proposed new computer-aided CPET interpretive module was found to be highly sensitive and specific in classifying patients with CHF or COPD, or healthy. Comparable modules may well be applied to additional and larger populations (pathologies and exercise limitations), thereby making this tool powerful and clinically applicable.

High-intensity interval training accelerates oxygen uptake kinetics and improves exercise tolerance for individuals with cystic fibrosis.

BACKGROUND: Exercise training provides benefits for individuals with cystic fibrosis; however, the optimal program is unclear. High-intensity interval training is safe and effective for improving 'functional capacity' in these individuals with peak rate of O2 uptake typically referenced. The ability to adjust submaximal rate of oxygen uptake (V̇O2 kinetics) might be more important for everyday function because maximal efforts are usually not undertaken. Moreover, the ability of high-intensity training to accelerate V̇O2 kinetics for individuals with cystic fibrosis could be enhanced with O2 supplementation during training. METHODS: Nine individuals with cystic fibrosis completed incremental cycling to limit of tolerance followed by 8 weeks of high-intensity interval cycling (2 sessions per week x ~ 45 min per session) either with (n = 5; O2+) or without (AMB) oxygen supplementation (100%). Each session involved work intervals at 70% of peak work rate followed by 60 s of recovery at 35%. For progression, duration of work intervals was increased according to participant tolerance. RESULTS: Both groups experienced a significant increase in work-interval duration over the course of the intervention (O2+, 1736 ± 141 v. 700 ± 154 s; AMB, 1463 ± 598 v. 953 ± 253 s; P = 0.000); however, the increase experienced by O2+ was greater (P = 0.027). During low-intensity constant-work-rate cycling, the V̇O2 mean response time was shortened post compared to pre training (O2+, 34 ± 11 v. 44 ± 9 s; AMB, 39 ± 14 v. 45 ± 17 s; P = 0.000) while during high-intensity constant-work-rate cycling, time to exhaustion was increased (O2+, 1628 ± 163 v. 705 ± 133 s; AMB, 1073 ± 633 v. 690 ± 348 s; P = 0.002) and blood [lactate] response was decreased (O2+, 4.5 ± 0.9 v. 6.3 ± 1.4 mmol. L- 1; AMB, 4.5 ± 0.6 v. 5.2 ± 1.4 mmol. L- 1; P = 0.003). These positive adaptations were similar regardless of gas inspiration during training. CONCLUSION: Eight weeks of high-intensity interval training for patients with cystic fibrosis accelerated V̇O2 kinetics and increased time to exhaustion. This provides some evidence that these patients may benefit from this type of exercise. TRIAL REGISTRATION: This study was retrospectively registered in the ISRTCN registry on 22/06/2019 (#ISRCTN13864650).

Chronic iliofemoral vein obstruction - an under-recognized cause of exercise limitation.

Local symptoms of chronic venous insufficiency after deep vein thrombosis (DVT) are well described, but little is known about the effect of residual venous obstruction on exercise capacity. We tested our hypothesis that chronic residual iliofemoral vein occlusion (IFVO) after DVT may impair exercise capacity. Nine post-DVT patients with residual IFVO and effort intolerance were studied; a comparison cohort consisted of 11 healthy volunteers. Exercise tolerance was assessed by bimodality incremental symptom-limited cardiopulmonary testing, using leg and arm ergometers. In healthy subjects, leg vein obstruction was modelled by application to the thighs of cuff tourniquets inflated to 30-40 mmHg. Leg exercise tolerance as measured by oxygen uptake at peak exercise (peak ⩒'O2) was reduced in patients (median 50% predicted (range 36-83%) vs. 88% predicted (67-129%) in normal subjects, p < 0.001). Arm exercise tolerance was also reduced in patients, but less severely than in the legs - the median arm: leg ratio of peak ⩒'O2 was 0.95 (0.77-1.43) in patients vs. a normal ratio of 0.73 (0.6-1.0) in healthy subjects (p < 0.003). In healthy subjects, bilateral leg vein obstruction by tourniquets reduced peak ⩒'O2 in leg exercise to 76% predicted (range 55-108%; p < 0.001 vs. standard test). In conclusion, the comparison of arm vs. leg exercise capacity in post-DVT patients with residual IFVO and the effect of experimental venous obstruction (thigh tourniquets) in healthy subjects suggest that reduced exercise capacity in patients was at least partially caused by reduced venous return. Chronic venous obstruction should be recognized as a cause of exercise limitation.

The Effects of Maximal Intensity Exercise on Cognitive Performance in Children.

High intensity physical exercise has previously been found to lead to a decline in cognitive performance of adults. The aim of this study was to determine the effects of maximal intensity exercise on cognitive performance of children. Using a repeated-measures design, 20 children and adolescents aged 8-17 years completed a battery of tests measuring memory and attention. Forward and Backward Digit Span tests, the Rey Auditory-Verbal Learning Test (RAVLT) and the Digit Symbol Substitution Test (DSST) were performed at baseline, immediately after, and one hour after a maximal cardiopulmonary exercise test. Forward and Backward Digit Span scores significantly improved post-recovery compared with baseline measurements. There was a significant decrease in RAVLT scores post-exercise, which returned to baseline values after recovery. The DSST test scores were mildly elevated from post-exercise to after recovery. Maximal intensity exercise in children and adolescents may result in both beneficial and detrimental cognitive effects, including transient impairment in verbal learning. Cognitive functions applying short term memory improve following a recovery period. Parents, educators and coaches should consider these changes in memory and attention following high-intensity exercise activities in children.

Cardio-vascular reserve index (CVRI) during exercise complies with the pattern assumed by the cardiovascular reserve hypothesis.

OBJECTIVES: The Cardio-vascular reserve index (CVRI) had been empirically validated in diverse morbidities as a quantitative estimate of the reserve assumed by the cardiovascular reserve hypothesis. This work evaluates whether CVRI during exercise complies with the cardiovascular reserve hypothesis. DESIGN: Retrospective study based on a database of patients who underwent cardio-pulmonary exercise testing (CPX) for diverse indications. METHODS: Patient's physiological measurements were retrieved at four predefined CPX stages (rest, anaerobic threshold, peak exercise and after 2min of recovery). CVRI was individually calculated retrospectively at each stage. RESULTS: Mean CVRI at rest was 0.81, significantly higher (p<0.001) than at all other stages. CVRI decreased with exercise, reaching an average at peak exercise of 0.35, significant lower than at other stages (p<0.001) and very similar regardless of exercise capacity (mean CVRI 0.33-0.37 in 4 groups classified by exercise capacity, p>0.05). CVRI after 2min of recovery rose considerably, most in the group with the best exercise capacity and least in those with the lowest exercise capacity. CONCLUSIONS: CVRI during exercise fits the pattern predicted by the cardiovascular reserve hypothesis. CVRI decreased with exercise reaching a minimum at peak exercise and rising with recovery. The CVRI nadir at peak exercise, similar across groups classified by exercise capacity, complies with the assumed exhaustion threshold. The clinical utility of CVRI should be further evaluated.

High Mid-Flow to Vital Capacity Ratio and the Response to Exercise in Children With Congenital Heart Disease.

BACKGROUND: Pulmonary mechanics may play a role in exercise intolerance in patients with congenital heart disease (CHD). A reduced FVC volume could increase the ratio between mid-flow (FEF25-75%) and FVC, which is termed high dysanapsis. The relationship between high dysanapsis and the response to maximum-intensity exercise in children with CHD had not yet been studied. The aim of this work was to examine whether high dysanapsis is related to the cardiopulmonary response to maximum-intensity exercise in pediatric subjects with CHD. METHODS: We retrospectively collected data from 42 children and adolescents with CHD who had either high dysanapsis (ratio >1.2; n = 21) or normal dysanapsis (control) (n = 21) as measured by spirometry. Data extracted from cardiopulmonary exercise test reports included peak values of heart rate, work load, V̇O2 , V̇CO2 , and ventilation parameters and submaximum values, including ventilatory threshold and ventilatory equivalents. RESULTS: There were no significant differences in demographic and clinical parameters between the groups. Participants with high dysanapsis differed from controls in lower median peak oxygen consumption (65.8% vs 83.0% of predicted, P = .02), peak oxygen pulse (78.6% vs 87.8% of predicted, P = .02), ventilatory threshold (73.8% vs 85.3% of predicted, P = .03), and maximum breathing frequency (106% vs 121% of predicted, P = .035). In the high dysanapsis group only, median peak ventilation and tidal volume were significantly lower than 80% of predicted values. CONCLUSIONS: In children and adolescents with corrected CHD, high dysanapsis was associated with a lower ventilatory capacity and reduced aerobic fitness, which may indicate respiratory muscle impairments.

Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease.

Few previous studies have addressed exercise capacity in patients with corrected congenital heart disease (CHD) and significant anatomical residua. The aim of this study was to determine the aerobic fitness and peak cardiac function of patients with corrected CHD with complete or incomplete repairs, as determined by resting echocardiography. Children, adolescents and young adults (<40 years) with CHD from both sexes, who had previously undergone biventricular corrective therapeutic interventions (n = 73), and non-CHD control participants (n = 76) underwent cardiopulmonary exercise testing. The CHD group was further divided according to the absence/presence of significant anatomical residua on a resting echocardiogram ("complete"/"incomplete" repair groups). Aerobic fitness and cardiac function were compared between groups using linear regression and analysis of covariance. Peak oxygen consumption, O2 pulse and ventilatory threshold were significantly lower in CHD patients compared with controls (all p < 0.01). Compared with the complete repair group, the incomplete repair group had a significantly lower mean peak work rate, age-adjusted O2 pulse (expressed as % predicted) and a higher VE/VCO2 ratio (all p ≤ 0.05). Peak oxygen consumption was comparable between the subgroups. Patients after corrected CHD have lower peak and submaximal exercise parameters. Patients with incomplete repair of their heart defect had decreased aerobic fitness, with evidence of impaired peak cardiac function and lower pulmonary perfusion. Patients that had undergone a complete repair had decreased aerobic fitness attributed only to deconditioning. These newly identified differences explain why in previous studies, the lowest fitness was seen in patients with the most hemodynamically significant heart malformations.

Changes in fitness are associated with changes in body composition and bone health in children after cancer.

AIM: This study examined the effects of physical activity on the fitness, body composition and mental health of children after cancer or bone marrow transplantation. METHODS: We focused on 22 children aged from seven to 14 years who had received chemotherapy and/or bone marrow transplantation in our medical centre. Ten children took part in a six-month exercise programme, and 12 children who did not exercise formed the control group. At baseline and at the end of the trial, we measured aerobic fitness, body composition, bone density and assessed the child's mood and quality of life. We pooled all participants together post hoc to compare changes in fitness with the various study outcomes. RESULTS: We found no differences between groups in changes in fitness, body composition or mental health indices. Significant correlations were found between changes in aerobic fitness and changes in lean body mass (r = 0.74, p = 0.002), bone mineral content (r = 0.57, p = 0.026) and femoral neck bone mineral density (r = 0.59, p = 0.027) in all participants. CONCLUSION: Group-based exercise training did not improve aerobic fitness in children after cancer or bone marrow transplantation. However, changes in fitness throughout the study period were associated with changes in body composition and bone health in all participants.

[Aerobic fitness and cardiorespiratory function of pediatric cancer survivors].

INTRODUCTION: Overall, more than 80% of children diagnosed with cancer will survive their immediate disease. This growing group of childhood cancer survivors is at an increased risk for several chronic diseases and increased mortality. Physical activity is a well-known and powerful means to reduce such complications, yet many children are not active as recommended. Furthermore, the complex treatments might adversely affect the heart and lungs, possibly limiting physical performance. AIM: To measure aerobic fitness among childhood cancer survivors, while assessing maximal cardiac and respiratory functions. METHODS: Eighteen children (mean age 11.5 +/- 2.1 years, 50% males) who had completed medical treatment for cancer, and 16 healthy children, performed a cardiorespiratory exercise test on a bicycle ergometer until exhaustion. Peak oxygen uptake, O2 pulse and several ventilatory parameters were measured and compared between the groups. RESULTS: The mean maximal load obtained by the cancer survivor group was lower than expected, compared with controls (89% +/- 19 vs. 101/% +/- 18, p = 0.055). Peak oxygen consumption was also lower, with a marginal statistical significance (33.3 +/- 7.5 vs. 38.9 +/- 9.7 ml O2/kg/min, p = 0.075), yet was significantly lower when expressed as a percent of age- and sex- appropriate norms [78% +/- 15 vs. 94% +/- 16, p = 0.0081. Cardiac and respiratory functions were normal in all children, with no between-group differences. CONCLUSIONS: We conclude that aerobic fitness is lower in children who have survived cancer, with no evidence of significant cardiac or lung damage. Given the importance of regular physical activity for this at-risk population, it should be continuously encouraged, while administering a personally tailored exercise prescription.

Central versus peripheral cardiovascular limitation to exercise: the role of two-modality testing.

BACKGROUND: Uncertainty arises when physiological findings indicate a cardiovascular limitation but the limiting constituents within the cardiovascular system cannot be identified. OBJECTIVES: It was the aim of this study to investigate the value of two-modality exercise testing to assess effort intolerance when the cause remains obscure despite standard exercise testing. METHODS: A second modality maximal exercise test to fatigue, using either upper extremity or supine exercise, was performed following a nonconclusive standard sitting ergometry. Six patients (4 males) with a mean age of 56 +/- 22 years with severe exercise intolerance were enrolled in the study. RESULTS: In 4 of the patients, arm exercise capacity exceeded leg capacity, indicating peripheral limitation. In 1 of these patients, hemoglobin saturation decreased markedly only during sitting exercise while it remained normal during arm exercise, indicating a unique, iatrogenic abnormality. In another patient, supine leg exercise capacity exceeded sitting capacity, indicating peripheral venous limitation, and in an additional patient, leg capacity exceeded arm capacity pointing towards a central abnormality. In all 6 patients, the second modality test highlighted the correct diagnosis. CONCLUSIONS: Arm exercise that is added to a standard leg exercise may distinguish between central circulatory and peripheral vascular lower extremity limitation. Supine posture augments venous return to the heart and is useful when preload may be limiting. These modes of exercise may be added to a standard sitting or upright test in order to differentiate between central cardiovascular versus peripheral vascular (arterial or venous) causes of exercise limitation.

Ventilatory support during training improves training benefit in severe chronic airway obstruction.

BACKGROUND: One mechanism that may limit training effect in chronic obstructive pulmonary disease is the ventilatory limitation and associated dyspnea. OBJECTIVES: To minimize ventilatory limitation during training of patients with severe COPD by applying bi-level positive pressure ventilation during training in order to augment training intensity (and effect). METHODS: The study group comprised 19 patients (18 males, 1 female) with a mean age of 64 +/- 9 years. Mean forced expiratory volume in 1 second was 32 +/- 4% of predicted, and all were ventilatory-limited (exercise breathing reserve 3 +/- 9 L/min, normal > 15 L/min). The patients were randomized: 9 were assigned to training with BiPAP and 10 to standard training. All were trained on a treadmill for 2 months, twice a week, 45 minutes each time, at maximal tolerated load. Incremental maximal unsupported exercise test was performed before and at the end of the training period. RESULTS: BiPAP resulted in an increment of 94 +/- 53% in training speed during these 2 months, as compared to 41 +/- 19% increment in the control group (P < 0.005). Training with BiPAP yielded an average increase in maximal oxygen uptake of 23 +/- 16% (P < 0.005), anaerobic threshold of 11 +/- 12% (P < 0.05) and peak O2 pulse of 20 +/- 19% (P < 0.05), while peak exercise lactate concentration was not higher after training. Interestingly, in the BiPAP group, peak exercise ventilation was also 17 +/- 20% higher after training (P < 0.05). Furthermore, contrary to our expectation, at any given work rate, ventilation (and tidal volume) in the BiPAP group was higher in the post-training test as compared to the pre-training test, and the end tidal partial pressure of CO2 at 55 watts was lower, 40 +/- 4 and 38 +/- 4 mmHg respectively (P < 0.05). No improvement in exercise capacity was observed after this short training period in the control group. CONCLUSION: Pressure-supported ventilation during training is feasible in patients with severe COPD and it augments the training effect. The improved exercise tolerance was associated with higher ventilatory response and therefore lower P(ET)CO2 at equal work rates after training.