Danilo Cortozi Berton

Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics

Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O(2) uptake (Vo(2)(p)) kinetics during exercise, which may stem from inadequate muscle O(2) delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O(2) delivery to uptake during exercise. We tested the hypothesis that, along with slowed Vo(2)(p) kinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Qt) following the onset of heavy-intensity exercise. We measured Vo(2)(p), Qt (impedance cardiography), and muscle deoxygenation (near-infrared spectroscopy) during heavy-intensity exercise performed to the limit of tolerance by 10 patients with moderate-to-severe COPD and 11 age-matched sedentary controls. Variables were analyzed by standard nonlinear regression equations. Time to exercise intolerance was significantly (P < 0.05) lower in patients and related to the kinetics of Vo(2)(p) (r = -0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of Vo(2)(p) (42 +/- 13 vs. 73 +/- 24 s) and Qt (67 +/- 11 vs. 96 +/- 32 s), and faster overall kinetics of muscle deoxy-Hb (19.9 +/- 2.4 vs. 16.5 +/- 3.4 s). Consequently, the time constant ratio of O(2) uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O(2) delivery. In conclusion, our data show that patients with moderate-to-severe COPD have impaired central and peripheral cardiovascular adjustments following the onset of heavy-intensity exercise. These cardiocirculatory disturbances negatively impact the dynamic matching of O(2) delivery and utilization and may contribute to the slower Vo(2)(p) kinetics compared with age-matched controls.

Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation (P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.

Effects of Expiratory Positive Airway Pressure on Dynamic Hyperinflation During Exercise in Patients With COPD

BACKGROUND: Expiratory positive airway pressure (EPAP) is a form of noninvasive positive-pressure ventilatory support that, in spite of not unloading respiratory muscles during inspiration, may reduce the inspiratory threshold load and attenuate expiratory dynamic airway compression, contributing to reduced expiratory air-flow limitation in patients with COPD. We sought to determine the effects of EPAP on operational lung volumes during exercise in COPD patients. METHODS: This was a nonrandomized, experimental comparison of 2 exercise conditions (with and without EPAP); subjects completed a treadmill exercise test and performed, before and immediately after exercise, lung volume measurements. Those who overtly developed dynamic hyperinflation (DH), as defined by at least a 15% reduction from pre-exercise inspiratory capacity (IC), were invited for an additional research visit to repeat the same exercise protocol while receiving EPAP through a spring loaded resistor face mask. The primary outcome was IC variance (pre-post exercise) comparison under the 2 exercise conditions. RESULTS: Forty-six subjects (32 males), a mean 65.0 ± 8.2 years of age, and with moderate to severe COPD (FEV1 = 38 ± 16% predicted) were initially enrolled. From this initial sample, 17 (37%) presented overt DH, as previously defined. No significant difference was found between these subjects and the rest of the initial sample. Comparing before and after exercise, there was significantly less reduction in IC observed when EPAP was used (−0.18 ± 0.35 L vs −0.57 ± 0.45 L, P = .02), allowing greater IC final values (1.45 ± 0.50 L vs 1.13 ± 0.52 L, P = .02). CONCLUSIONS: The application of EPAP reduced DH, as shown by lower operational lung volumes after submaximal exercise in COPD patients who previously manifested exercise DH.

Physiological and clinical relevance of exercise ventilatory efficiency in COPD

Exercise ventilation (V′E) relative to carbon dioxide output (V′CO2) is particularly relevant to patients limited by the respiratory system, e.g. those with chronic obstructive pulmonary disease (COPD). High V′E−V′CO2 (poor ventilatory efficiency) has been found to be a key physiological abnormality in symptomatic patients with largely preserved forced expiratory volume in 1 s (FEV1). Establishing an association between high V′E−V′CO2 and exertional dyspnoea in mild COPD provides evidence that exercise intolerance is not a mere consequence of detraining. As the disease evolves, poor ventilatory efficiency might help explaining “out-of-proportion” breathlessness (to FEV1 impairment). Regardless, disease severity, cardiocirculatory co-morbidities such as heart failure and pulmonary hypertension have been found to increase V′E−V′CO2. In fact, a high V′E−V′CO2 has been found to be a powerful predictor of poor outcome in lung resection surgery. Moreover, a high V′E−V′CO2 has added value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of COPD severity. Documenting improved ventilatory efficiency after lung transplantation and lung volume reduction surgery provides objective evidence of treatment efficacy. Considering the usefulness of exercise ventilatory efficiency in different clinical scenarios, the V′E−V′CO2 relationship should be valued in the interpretation of cardiopulmonary exercise tests in patients with mild-to-end-stage COPD. Ventilatory efficiency is a key measurement for the interpretation of cardiopulmonary exercise testing in COPD http://ow.ly/1nsY307pbz8

Exercise Ventilation in COPD: Influence of Systolic Heart Failure

ABSTRACT Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; ‘overlap’ (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2 (PETCO2) (P < 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation (E)-CO2 output CO2) intercept, E-CO2 slope, peak E/CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61–22.65), P < 0.001] plus E-CO2 slope ≥ 34 [2.18 (0.73–6.50), P = 0.14] or peak E/CO2 ratio ≥ 37 [5.35 (1.96–14.59), P = 0.001] plus peak PETCO2 ≤ 31 mmHg [5.73 (1.42–23.15), P = 0.01] were indicative of overlapping. Heart failure increases the ventilatory response to metabolic demand in COPD. Variables reflecting excessive ventilation might prove useful to assist clinical interpretation of CPET responses in COPD patients presenting heart failure as co-morbidity.

Effectiveness of Pulmonary Rehabilitation in Exercise Capacity and Quality of Life in Chronic Obstructive Pulmonary Disease Patients With and Without Global Fat-Free Mass Depletion

OBJECTIVE To investigate the effectiveness of pulmonary rehabilitation (PR) in exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD) with and without global fat-free mass (FFM) depletion. DESIGN Retrospective case-control. SETTING Outpatient clinic, university center. PARTICIPANTS COPD patients (N=102) that completed PR were initially evaluated. INTERVENTION PR including whole-body and weight training for 12 weeks, 3 times per week. MAIN OUTCOME MEASURES St. George Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and FFM evaluation applied before and after PR. RESULTS Patients were stratified according to their FFM status measured by bioelectric impedance. They were considered depleted if the FFM index was ≤ 15 kg/m(2) in women and ≤ 16 kg/m(2) in men. From the initial sample, all depleted patients (n=31) composed the FFM depleted group. It was composed predominantly by women (68%) with a mean age ± SD of 64.4 ± 7.3 years and a forced expiratory volume in 1 second of 33.6%=-13.2% predicted. Paired for sex and age, 31 nondepleted patients were selected from the initial sample to compose the nondepleted group. Improvement in the 6MWD was similar in these 2 groups after PR. Both groups improved SGRQ scores, although the observed power was small and did not allow adequate comparison between depleted and nondepleted patients. There was no difference between groups in weight change, whereas FFM tended to be greater in depleted patients. This increase had no correlation with the 6MWD or the SGRQ. CONCLUSIONS Benefits of PR to exercise capacity were similar comparing FFM depleted and nondepleted COPD patients. Although FFM change tended to be greater in depleted patients, this increase had no definite relation with clinical outcomes.

O trabalho de caminhada dos seis minutos não se correlaciona com o grau de obstrução do fluxo aéreo em doentes portadores de Doença Pulmonar Obstrutiva Crónica (DPOC)

Abstract Abstract Abstract Abstract Introduction: The six-minute walking test distance, despite being considered the main parameter, does not consider body weight which is known to in- fluence exercise capacity. A body of evidence

Exercise Ventilatory Inefficiency Adds to Lung Function in Predicting Mortality in COPD

ABSTRACT Severity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO2 output (VCO2) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO2 nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan–Meier analyses showed that survival time was particularly reduced when ventilation/VCO2 nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease.

Excess Ventilation in Chronic Obstructive Pulmonary Disease–Heart Failure Overlap. Implications for Dyspnea and Exercise Intolerance

Rationale: An increased ventilatory response to exertional metabolic demand (high &OV0312;e/&OV0312;co2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure. Objectives: We aimed to determine the mechanisms underlying high &OV0312;e/&OV0312;co2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients. Methods: Twenty‐two ex‐smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection. Measurements and Main Results: Regardless of the chosen metric (increased &OV0312;e‐&OV0312;co2 slope, &OV0312;e/&OV0312;co2 nadir, or end‐exercise &OV0312;e/&OV0312;co2), ventilatory inefficiency was closely related to PcCO2 (r values from −0.80 to −0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise PcCO2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between‐group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting PaCO2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional PcO2. The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05). Conclusions: Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased “wasted” ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease‐heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea.

Six-minute walk distance and work relationship with incremental treadmill cardiopulmonary exercise test in COPD

Introduction:  Cardiopulmonary exercise testing (CPET) is increasingly used to evaluate the overall impact of the illness on patients with chronic obstructive pulmonary disease (COPD). While laboratory tests of exercise performance are costly, the 6‐min walk test (6‐MWT) can be more easily performed. Although the main outcome commonly used in this field test is the distance walked in 6 min (6‐MWD), this measure does not account for differences in body weight. Previous studies showed a good correlation between the work performed during the 6‐MWT with incremental cycling CPET, an exercise modality more associated with quadriceps fatigability and with lower peak oxygen consumption than incremental walking tests.