Dual bronchodilation with tiotropium/olodaterol further reduces activity-related breathlessness versus tiotropium alone in COPD.

The 3-min constant speed shuttle test (CSST) was used to examine the effect of tiotropium/olodaterol compared with tiotropium at reducing activity-related breathlessness in patients with chronic obstructive pulmonary disease (COPD).This was a randomised, double-blind, two-period crossover study including COPD patients with moderate to severe pulmonary impairment, lung hyperinflation at rest and a Mahler Baseline Dyspnoea Index <8. Patients received 6 weeks of tiotropium/olodaterol 5/5 µg and tiotropium 5 µg in a randomised order with a 3-week washout period. The speed for the 3-min CSST was determined for each patient such that an intensity of breathing discomfort ≥4 ("somewhat severe") on the modified Borg scale was reached at the end of a completed 3-min CSST.After 6 weeks, there was a decrease in the intensity of breathlessness (Borg dyspnoea score) at the end of the 3-min CSST from baseline with both tiotropium (mean -0.968, 95% CI -1.238- -0.698; n=100) and tiotropium/olodaterol (mean -1.325, 95% CI -1.594- -1.056; n=101). The decrease in breathlessness was statistically significantly greater with tiotropium/olodaterol versus tiotropium (treatment difference -0.357, 95% CI -0.661- -0.053; p=0.0217).Tiotropium/olodaterol reduced activity-related breathlessness more than tiotropium in dyspnoeic patients with moderate to severe COPD exhibiting lung hyperinflation.

Prospective validation of the endurance shuttle walking test in the context of bronchodilation in COPD.

This study focused on repeatability data and minimal important difference (MID) estimates of the endurance shuttle walking test (ESWT). 255 chronic obstructive pulmonary disease patients (forced expiratory volume in 1 s 54.7±13.2% predicted) completed four ESWTs at different times during the 8-week study: two under baseline conditions with tiotropium (1 week apart), one after a single dose and one after 4 weeks of either fluticasone propionate/salmeterol combination or placebo in addition to tiotropium. 97 patients performed all the tests with a portable metabolic system. Reproducibility of test performance and cardiorespiratory response was investigated with the data obtained on the first two ESWTs. The mean differences between the first two ESWT performances (-6.7±72.2 s and -7.3±113.1 m for endurance time and walking distance, respectively) were not statistically significant. The between-test end-exercise and isotime values for each cardiorespiratory parameter were not significantly different from each other. With the exception of arterial oxygen saturation by pulse oximetry, the repeatability of cardiorespiratory adaptations to ESWT was also confirmed with strong Pearson and intraclass correlation coefficients. Finally, changes of 56-61 s and 70-82 m in endurance time and distance walked, respectively, were perceived by patients. This study provides methodological information supporting the reliability of the ESWT and suggests MID estimates for this test.

Acute Cardiopulmonary and Muscle Oxygenation Responses to Normocapnic Hyperpnea Exercise in COPD.

PURPOSE: This study aimed to investigate cardiorespiratory responses and intercostal muscle oxygenation during normocapnic hyperpnea exercise in chronic obstructive pulmonary disease (COPD). METHODS: Twenty-two patients with COPD performed a cardiopulmonary cycling exercise test to assess peak oxygen consumption (V˙O2peak) and minute ventilation (V˙Epeak). They also performed a normocapnic hyperpnea exercise alone, at 50%-60% of V˙Epeak to exhaustion, using a respiratory device (Spirotiger) connected to a gas analyzer to monitor V˙O2, V˙E, and end-tidal CO2 partial pressure. Cardiac output, and intercostal and vastus lateralis muscle oxygenation were continuously measured during exercise using finger photoplethysmography and near-infrared spectroscopy, respectively. Arterial blood gases (arterial PCO2) and inspiratory capacity were obtained at rest and at the end of hyperpnea exercise. RESULTS: The hyperpnea exercise lasted 576 ± 277 s at a V˙E of 34.5 ± 12.1 L·min-1 (58% ± 6% of V˙Epeak), a respiratory rate of 22 ± 4 breaths per minute, and a tidal volume of 1.43 ± 0.43 L. From rest to the end of hyperpnea exercise, V˙O2 increased by 0.35 ± 0.16 L·min-1 (P < 0.001), whereas end-tidal CO2 partial pressure and arterial PCO2 decreased by ~2 mm Hg (P = 0.031) and ~5 mm Hg (P = 0.002, n = 13), respectively. Moreover, inspiratory capacity fell from 2.44 ± 0.84 L at rest to 1.96 ± 0.59 L (P = 0.002). During the same period, heart rate and cardiac output increased from 69 ± 12 bpm and 4.94 ± 1.15 L·min-1 at rest to 87 ± 17 bpm (P = 0.002) and 5.92 ± 1.58 L·min-1 (P = 0.007), respectively. During hyperpnea exercise, intercostal deoxyhemoglobin and total hemoglobin increased by 14.26% ± 13.72% (P = 0.001) and 8.69% ± 12.49% (P = 0.003) compared with their resting value. However, during the same period, vastus lateralis oxygenation remained stable (P > 0.05). CONCLUSIONS: In patients with COPD, normocapnic hyperpnea exercise provided a potent cardiorespiratory physiological stimulus, including dynamic hyperinflation, and increased intercostal deoxyhemoglobin consistent with enhanced requirement for muscle O2 extraction.

The Physiological Burden of the 6-Minute Walk Test Compared With Cardiopulmonary Exercise Stress Test in Patients With Severe Aortic Atenosis.

BACKGROUND: Management of aortic stenosis (AS) relies on symptoms. Exercise testing is recommended for asymptomatic patients with significant AS but is often experienced as forbidding and/or technically unrealistic for patients who are often frail, deconditioned, and intimidated by the exercise test. We compared the physiological burden assessed with gas exchange assessments to gauge and respiratory exchange ratio (RER) of a 6-minute walk test (6MWT) to a cardiopulmonary exercise stress test (CPET) in patients with severe AS. peak oxygen utilization. METHODS: Adults with equivocal symptoms and severe AS (1-aortic valve area [AVA] ≤ 1.0 cm2 or AVA index ≤ 0.6 cm2/m2, 2-peak aortic jet velocity ≥ 4.0 m/sec, 3-mean transvalvular pressure gradient ≥ 40 mm Hg by rest or dobutamine stress echocardiography, or 4-aortic valve calcification ≥ 1200 in women or ≥ 2000 AU in men) were studied. All participants completed both a 6MWT and symptom-limited progressive bicycle exercise testing. Breath-by-breath gas analysis and 12-lead electrocardiography were completed during 6MWT and CPET. Results: Eleven patients were studied. Patients walked on average 330 ± 75 m during the 6MWT and achieved a maximal workload of 48 ± 14 watts during the CPET. During the 6MWT, peak maximal oxygen uptake ( V ˙ O2peak) was 12.8 ± 2.5 vs 10.8 ± 4.2 mL/kg/min during the CPET. Respiratory exchange ratio exceeded 1.1 in both the 6MWT and CPET indicating similarly high exertion. Compared with the CPET, a larger proportion of the 6MWT was performed at a high intensity level (78% ± 28% vs 33% ± 24% at > 85% V̇O2peak; P = 0.004). CONCLUSIONS: The 6MWT with breath-by-breath gas analysis was well tolerated and able to achieve a physiological intense RER and V ˙ O2peak that are similar to symptom-limited CPET in patients with severe AS.

INTRODUCTION: La prise en charge de la sténose aortique (SA) dépend des symptômes. L'épreuve d'effort est recommandée aux patients asymptomatiques qui ont une SA significative, mais elle est souvent perçue comme dangereuse et/ou théoriquement irréaliste chez ces patients qui sont souvent fragiles, en mauvaise forme et craintifs par l'épreuve d'effort. Nous avons comparé le fardeau physiologique calculé par la consommation maximale de l'oxygène ( V ˙ O2max) et le quotient respiratoire (QR) d'un test de marche de 6 minutes (TM6) et d'une épreuve d'effort maximal chez des patients avec une SA sévère. MÉTHODES: Tous les patients présentaient une SA symptomatique et sévère (1-aire valvulaire aortique [AVA] ≤ 1,0 cm2 ouAVA ≤ 0,6 cm2/m2, 2-une vélocité maximale du flux aortique ≥ 4,0 m/sec, 3-un gradient de pression transvalvulaire moyen ≥ 40 mmHg au repos ou à l'échocardiographie à l'effort sous dobutamine ou 4-une calcification valvulaire aortique (AU) ≥ 1200 chez les femmes ou ≥ 2000 AU chez les hommes). Les participants ont effectué un TM6 et une 'épreuve d'effort maximal de type rampe sur vélo. L'analyse des échanges gazeux respiration par respiration et un électrocardiogramme à 12 dérivations ont été effectués durant le TM6 et l'épreuve d'effort maximal. RÉSULTATS: Un total de 11 patients ont participé à l'étude. Les patients ont marché en moyenne 330 ± 75 m durant le TM6 et ont atteint une charge de travail maximale de 48 ± 14 watts durant l'épreuve d'effort maximal. Durant le TM6, le V ˙ O2max était de 12,8 ± 2,5 vs 10,8 ± 4,2 ml/kg/min durant l'épreuve d'effort maximal. Le QR était supérieur à 1,1 au TM6 ainsi qu'à l'épreuve d'effort maximal. Comparativement à l'épreuve d'effort maximal, un pourcentage plus important au TM6 a été réalisée à une intensité élevée (78 % ± 28 % vs 33 % ± 24 % à > 85 % V̇O2max; P = 0,004). CONCLUSIONS: Le TM6 avec mesure directe des échanges gazeux était bien toléré et susceptible d'atteindre des valeurs physiologiques d'intensité élevée pour le QR et le V ˙ O2max. Les valeurs atteintes au TM6 étaient semblables à celles de l'épreuve d'effort maximal chez les patients avec une SA sévère.

Determinants of Cardiorespiratory Fitness After Bariatric Surgery: Insights From a Randomised Controlled Trial of a Supervised Training Program.

BACKGROUND: Severely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgery-induced weight loss improves CRF, but the determinants of this improvement are not well known. We aimed to assess the determinants of CRF before and after bariatric surgery and the impact of an exercise training program on CRF after bariatric surgery. METHODS: Fifty-eight severely obese patients (46.1 ± 6.1 kg/m2, 78% women) were randomly assigned to either an exercise group (n = 39) or usual care (n = 19). Exercise training was conducted from the 3rd to the 6th months after surgery. Anthropometric measurements, abdominal and mid-thigh computed tomographic scans, resting echocardiography, and maximal cardiopulmonary exercise testing was performed before bariatric surgery and 3 and 6 months after surgery. RESULTS: Weight, fat mass, and fat-free mass were reduced significantly at 3 and 6 months, without any additive impact of exercise training in the exercise group. From 3 to 6 months, peak aerobic power (V̇O2peak) increased significantly (P < 0.0001) in both groups but more importantly in the exercise group (exercise group: from 18.6 ± 4.2 to 23.2 ± 5.7 mL/kg/min; control group: from 17.4 ± 2.3 to 19.7 ± 2.4 mL/kg/min; P value, group × time = 0.01). In the exercise group, determinants of absolute V̇O2peak (L/min) were peak exercise ventilation, oxygen pulse, and heart rate reserve (r2 = 0.92; P < 0.0001), whereas determinants of V̇O2peak indexed to body mass (mL/kg/min) were peak exercise ventilation and early-to-late filling velocity ratio (r2 = 0.70; P < 0.0001). CONCLUSIONS: A 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery.

Validation and Cardiorespiratory Response of the 1-Min Sit-to-Stand Test in Interstitial Lung Disease.

PURPOSE: To assess the 1-min sit-to-stand test (1STS) test-retest reliability and construct validity and its associated cardiorespiratory response in comparison to the 6-min walk test (6MWT) and symptom-limited cycling cardiopulmonary exercise test (CPET) in people with interstitial lung disease (ILD). METHODS: Fifteen participants with ILD performed two 1STS tests, a 6MWT and a CPET. The three tests were administered on three separate visits, and cardiorespiratory parameters were continuously recorded during the tests. RESULTS: The number of repetitions during both 1STS tests was 22 ± 4 and 22 ± 4 (mean difference of 0.53 ± 2.00 repetitions, P = 0.32) with an intraclass correlation of 0.937 (95% confidence interval, 0.811-0.979]) and a minimal detectable change of 2.9 repetitions. The number of 1STS repetitions was highly correlated with the 6MWT distance (r = 0.823, P < 0.001) and with the peak cycling power output expressed in % predicted values (r = 0.706, P < 0.003). Oxygen consumption (V˙O2) peak during the 1STS reached 83% and 78% of V˙O2 peak during 6MWT and CPET, respectively. Peak 1STS HR, minute ventilation (V˙E,), V˙O2 values, as well as nadir SpO2 were achieved during the recovery phase of the test, whereas peak 6MWT and CPET HR, V˙E, V˙O2 and nadir SpO2 always occurred at the end of the test. The three tests elicited a similar fall in SpO2 ranging between 8% and 12%. Symptom scores after the 1STS were similar to those seen at the end of the 6MWT but lower than those of CPET. CONCLUSIONS: The 1STS showed excellent test-retest reliability in patients with ILD in whom it elicited a substantial, but submaximal cardiorespiratory response. Our data also support the construct validity of the 1STS to assess functional exercise capacity in patients with ILD and to detect exercise-induced O2 desaturation.

An unusual cause of exertional dyspnea in a 55 years old man.

A 55-year-old former professional athlete reported out of proportion dyspnea on exertion. After a detailed cardiac investigation, a cardiopulmonary exercise test on an ergocycle demonstrated an abnormal and non-physiological ventilatory response characterized by a sharp rise in ventilation followed by a decrease while exercise workload was progressively increasing. This was accompanied by noisy breathing. A laryngoscopy with direct visualisation of larynx and vocal cord during voluntary eucapnic hyperventilation confirmed the diagnosis of exercise-induced laryngeal obstruction. The patient was treated with speech therapy and all the symptoms resolved. A second cardiopulmonary exercise test showed a normalisation of the ventilatory pattern during exercise. This case demonstrates the importance of recognizing the symptoms of an exercise-induced laryngeal obstruction regardless of age, and the effectiveness of the speech therapy on symptoms and on exercise testing.

Relieving exertional dyspnea during the 3-min constant speed shuttle test in patients with COPD with indacaterol/glycopyrronium versus tiotropium: the RED trial.

BACKGROUND: Exertional dyspnea is a cardinal feature of chronic obstructive pulmonary disease (COPD) and a major cause of activity limitation. Although dual bronchodilation is more effective than bronchodilator monotherapy at improving resting pulmonary function, it is unclear to which extent this translates into superior relief of exertional dyspnea. METHODS: We conducted a randomized controlled, double-blind, cross-over trial comparing indacaterol 110 µg/glycopyrronium 50 µg once daily (OD) with tiotropium 50 µg OD in patients with moderate to severe COPD and resting hyperinflation (functional residual capacity >120% of predicted value). The primary outcome was Borg dyspnea score at the end of a 3-min constant speed shuttle test after 3 weeks of treatment. Secondary outcomes included changes in Borg dyspnea score after the first dose of study medication, expiratory flows and lung volumes. Statistical analysis was conducted using a cross-over analysis of variance model with repeated measurements. RESULTS: A total of 50 patients with COPD and a mean forced expiratory volume in 1 s of 54 ± 11% (mean ± SEM) predicted participated in the cross-over phase of the trial. Compared with baseline, there was a decrease in dyspnea after the first dose of medication with indacaterol/glycopyrronium [mean -1.00, 95% confidence interval (CI) -1.49 to -0.52] but not with tiotropium alone (mean -0.36, 95% CI -0.81 to 0.08). The reduction in dyspnea after the first dose was statistically significant between the two treatments (mean difference of -0.64, 95% CI -1.11 to -0.17). Despite indacaterol/glycopyrronium providing further bronchodilation and lung deflation throughout the trial, the reduction in dyspnea was not sustained at 3 weeks of treatment (mean between-treatment difference at 3 weeks of 0.09, 95% CI -0.44 to 0.61). CONCLUSION: In comparison with bronchodilator monotherapy, indacaterol/glycopyrronium provided greater immediate exertional dyspnea relief, although this difference was not sustained after 3 weeks of therapy despite evidence of further bronchodilation and lung deflation.The reviews of this paper are available via the supplemental material section.

Impact of bariatric surgery--induced weight loss on heart rate variability.

Obesity is associated with an increased risk of sudden death that may be due to abnormal cardiac vagal modulation reflected by reduced heart rate variability (HRV). Few studies have been conducted analyzing the effect of bariatric surgery-induced weight loss on HRV assessed by 24-hour Holter monitoring. The aim of this study was to assess weight loss effect after bariatric surgery on HRV and ventricular size and function. Ten morbidly obese patients, 6 women and 4 men aged 24 to 47 years, underwent bariatric surgery. Seven morbidly obese patients without active obesity treatment were used as controls. Twenty-four-hour Holter monitoring and echocardiogram were obtained before and at 6 to 12 months after surgery or at follow-up in control patients. Changes in minimal, maximal, and mean heart rate along with HRV during daytime and nighttime were compared before and after surgery. Baseline characteristics in the control group did not differ significantly from the treatment group. Average weight in the treatment group was 141 +/- 31 kg (mean +/- SD) at baseline and decreased to 101 +/- 18 kg at follow-up, corresponding to a body mass index of 52.3 +/- 7.6 kg/m(2) at baseline and 37.7 +/- 5.3 kg/m(2) at follow-up. There was a decrease in minimal heart rate (48 +/- 10 vs 40 +/- 6 beats per minute, P = .021) and mean heart rate (82 +/- 7 vs 66 +/- 10 beats per minute, P < .001) during the Holter monitoring. Spectral analysis showed a significant enhancement in HRV parameters (high- and low-frequency power) because there was an increase in the standard deviation of normal to normal R-R intervals (116 +/- 25 vs 174 +/- 56 milliseconds, P < .001), the standard deviation of the mean R-R intervals calculated over a 5-minute period (104 +/- 25 vs 148 +/- 45 milliseconds, P < .001), the square root of the mean of the squared differences between adjacent normal R-R intervals (25 +/- 8 vs 50 +/- 20 milliseconds, P < .001), and the percentage of differences between adjacent normal R-R intervals exceeding 50 milliseconds (5% +/- 5% vs 22% +/- 13%, P < .001). Echocardiographic measures remained unchanged when comparing the groups. Weight loss after bariatric surgery enhances HRV and decreases mean and minimal heart rate during Holter monitoring through a better cardiac parasympathetic modulation.

Uncoupling between cerebral perfusion and oxygenation during incremental exercise in an athlete with postconcussion syndrome: a case report.

High-intensity exercise may pose a risk to patients with postconcussion syndrome (PCS) when symptomatic during exertion. The case of a paralympic athlete with PCS who experienced a succession of convulsion-awakening periods and reported a marked increase in postconcussion symptoms after undergoing a graded symptom-limited aerobic exercise protocol is presented. Potential mechanisms of cerebrovascular function failure are then discussed.

Use of facemask and mouthpiece to assess constant-workrate exercise capacity in COPD.

PURPOSE: To compare the response to constant-workrate cycling exercise between the mouthpiece and the facemask in patients with chronic obstructive pulmonary disease (COPD). METHODS: Ten patients with COPD (FEV1: 48 +/- 14% pred, mean +/- SD) performed two symptom-limited constant-workrate cycling exercise tests at 80% of their predetermined peak exercise capacity. One test was performed using a mouthpiece and the other with a facemask, in a random order. The endurance time to constant-workrate exercise was compared between the two interfaces. VO2, VCO2, ventilation (VE), inspiratory capacity, dyspnea Borg score, and heart rate responses during exercise were also compared. RESULTS: Endurance time was similar between the two interfaces (mean difference +/- SD, 30 +/- 74 s, P = 0.23). Except for the end-exercise values, which were lower with the facemask, the VO2, VCO2, and VE responses to submaximal exercise were similar between the two interfaces. Perception of dyspnea, inspiratory capacity, and heart rate kinetics were similar during the two exercise tests. No clear preference about either interface was expressed by the patients. CONCLUSION: The mouthpiece and the facemask can be used with comparable results to determine the endurance time to constant-workrate cycling exercise in patients with COPD. Compared with the mouthpiece, the end-exercise values for VO2, VCO2, and VE were underestimated when a facemask was used. The similar responses in heart rate and symptom perception suggest that this could be due to an air leak at end-exercise with the facemask.

Impact of exercise training on muscle function and ergoreflex in Fontan patients: a pilot study.

BACKGROUND: Several studies have demonstrated persistent reduced exercise capacity in Fontan patients even after surgical intervention. The purpose of this study was to evaluate if the skeletal muscle function of these patients is abnormal, if it correlates with exercise tolerance and if it can be improved by exercise training. METHODS: We evaluated the functional capacity of seven patients who underwent Fontan procedure (age:16+/-5 years, mean+/-SD) and seven healthy children (19+/-7 years) paired for age, sex, height and weight. Evaluation included pulmonary evaluation, neuromuscular function and exercise tolerance. Secondly, an 8-week exercise training program was performed by five of these patients. RESULTS: The ergoreflex contribution to absolute diastolic blood pressure was higher (12.5+/-4.8 vs. 5.6+/-4.2 mmHg; p=0.04) in Fontan patients vs. healthy subjects whereas a trend was encountered regarding the ergoreflex contribution to absolute systolic blood pressure (9.0+/-7.0 vs. 0.4+/-9.0 mmHg; p=0.09). Furthermore, time to fatigue of the non-dominant forearm muscles was shorter in Fontan patients vs. healthy subjects (431+/-290 vs. 847+/-347 s; p=0.03). Following exercise training, there was a significant reduction of the ergoreflex contribution to absolute values of systolic blood pressure (9.8+/-0.9 vs. 0.3+/-2.7 mmHg; p<0.05). There was an association between muscle strength and VO2 peak in Fontan patients (upper limb: r=0.895; p<0.01; lower limb: r=0.838; p<0.05, respectively). CONCLUSIONS: Skeletal muscle function in Fontan patients is abnormal which may have an impact in the reduced exercise tolerance encountered in these patients. Exercise training may have beneficial impacts on the skeletal muscle function in this population.

Prognostic Value of Oxygen Kinetics During Recovery From Cardiopulmonary Exercise Testing in Patients With Chronic Heart Failure.

BACKGROUND: Peak oxygen uptake (V˙O2peak) is a well-established prognostic marker in chronic heart failure (CHF). Cardiopulmonary exercise testing (CPET) provides physiological parameters other than V˙O2peak that might have prognostic value. We aimed at determining whether exercise recovery data kinetics have prognostic implications over V˙O2peak and Heart Failure Survival Score. METHODS: Exercise data from 200 consecutive CHF patients evaluated for possible heart transplantation and received CPET at our institution between 2004 and 2011 were analyzed. The rate of recovery of oxygen uptake (V˙O2) at 2 minutes after exercise (V˙O2-REC2) was calculated using the difference between V˙O2peak and V˙O2 at minute 2 of recovery and expressed as a percentage of V˙O2peak. The composite primary end point was the time from CPET to the first event including death, heart transplant, or mechanical heart implantation. RESULTS: Mean follow-up period was 1271 ± 61 days during which there were 108 first events including 35 deaths, 66 heart transplants, and 7 mechanical heart implantations. The strongest prognostic factors in the univariate analysis were V˙O2-REC2, V˙O2peak, V˙O2 efficiency slope, and ventilation to carbon dioxide excretion ratio slope (all P < 0.0001). Multivariate analysis showed that V˙O2-REC2 (P < 0.0001), ventilation to carbon dioxide excretion ratio slope (P = 0.0022), use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (P = 0.0042), presence of a defibrillator (P = 0.0127), and mean arterial pressure (P = 0.0151) were independent predictors of event-free survival time. CONCLUSIONS: V˙O2-REC2 was the strongest prognostic marker of death, heart transplantation, and mechanical heart implantation in severe CHF. This finding should be confirmed prospectively.