Vasileios Andrianopoulos

An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease

Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results. Technical Standard document: standard operating procedures for the 6MWT, ISWT and ESWT in chronic respiratory disease http://ow.ly/Bq2B9

An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease

This systematic review examined the measurement properties of the 6-min walk test (6MWT), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with chronic respiratory disease. Studies that report the evaluation or use of the 6MWT, ISWT or ESWT were included. We searched electronic databases for studies published between January 2000 and September 2013. The 6-min walking distance (6MWD) is a reliable measure (intra-class correlation coefficients ranged from 0.82 to 0.99 in seven studies). There is a learning effect, with greater distance walked on the second test (pooled mean improvement of 26 m in 13 studies). Reliability was similar for ISWT and ESWT, with a learning effect also evident for ISWT (pooled mean improvement of 20 m in six studies). The 6MWD correlates more strongly with peak work capacity (r=0.59–0.93) and physical activity (r=0.40–0.85) than with respiratory function (r=0.10–0.59). Methodological factors affecting 6MWD include track length, encouragement, supplemental oxygen and walking aids. Supplemental oxygen also affects ISWT and ESWT performance. Responsiveness was moderate to high for all tests, with greater responsiveness to interventions that included exercise training. The findings of this review demonstrate that the 6MWT, ISWT and ESWT are robust tests of functional exercise capacity in adults with chronic respiratory disease. Systematic review: support for use of the 6MWT, ISWT and ESWT in adults with chronic respiratory disease http://ow.ly/Bq2Mz

Heliox increases quadriceps muscle oxygen delivery during exercise in COPD patients with and without dynamic hyperinflation

Some reports suggest that heliox breathing during exercise may improve peripheral muscle oxygen availability in patients with chronic obstructive pulmonary disease (COPD). Besides COPD patients who dynamically hyperinflate during exercise (hyperinflators), there are patients who do not hyperinflate (non-hyperinflators). As heliox breathing may differently affect cardiac output in hyperinflators (by increasing preload and decreasing afterload of both ventricles) and non-hyperinflators (by increasing venous return) during exercise, it was reasoned that heliox administration would improve peripheral muscle oxygen delivery possibly by different mechanisms in those two COPD categories. Chest wall volume and respiratory muscle activity were determined during constant-load exercise at 75% peak capacity to exhaustion, while breathing room air or normoxic heliox in 17 COPD patients: 9 hyperinflators (forced expiratory volume in 1 s = 39 ± 5% predicted), and 8 non-hyperinflators (forced expiratory volume in 1 s = 48 ± 5% predicted). Quadriceps muscle blood flow was measured by near-infrared spectroscopy using indocyanine green dye. Hyperinflators and non-hyperinflators demonstrated comparable improvements in endurance time during heliox (231 ± 23 and 257 ± 28 s, respectively). At exhaustion in room air, expiratory muscle activity (expressed by peak-expiratory gastric pressure) was lower in hyperinflators than in non-hyperinflators. In hyperinflators, heliox reduced end-expiratory chest wall volume and diaphragmatic activity, and increased arterial oxygen content (by 17.8 ± 2.5 ml/l), whereas, in non-hyperinflators, heliox reduced peak-expiratory gastric pressure and increased systemic vascular conductance (by 11.0 ± 2.8 ml·min(-1)·mmHg(-1)). Quadriceps muscle blood flow and oxygen delivery significantly improved during heliox compared with room air by a comparable magnitude (in hyperinflators by 6.1 ± 1.3 ml·min(-1)·100 g(-1) and 1.3 ± 0.3 ml O(2)·min(-1)·100 g(-1), and in non-hyperinflators by 7.2 ± 1.6 ml·min(-1)·100 g(-1) and 1.6 ± 0.3 ml O(2)·min(-1)·100 g(-1), respectively). Despite similar increase in locomotor muscle oxygen delivery with heliox in both groups, the mechanisms of such improvements were different: 1) in hyperinflators, heliox increased arterial oxygen content and quadriceps blood flow at similar cardiac output, whereas 2) in non-hyperinflators, heliox improved central hemodynamics and increased systemic vascular conductance and quadriceps blood flow at similar arterial oxygen content.

A method for assessing heterogeneity of blood flow and metabolism in exercising normal human muscle by near-infrared spectroscopy

Heterogeneity in the distribution of both blood flow (Q̇) and O2 consumption (V̇O2) has not been assessed by near-infrared spectroscopy in exercising normal human muscle. We used near-infrared spectroscopy to measure the regional distribution of Q̇ and V̇O2 in six trained cyclists at rest and during constant-load exercise (unloaded pedaling, 20%, 50%, and 80% of peak Watts) in both normoxia and hypoxia (inspired O2 fraction = 0.12). Over six optodes over the upper, middle, and lower vastus lateralis, we recorded 1) indocyanine green dye inflow after intravenous injection to measure Q̇; and 2) fractional tissue O2 saturation (StiO2) to estimate local V̇O2-to-Q̇ ratios (V̇o2/Q̇). Varying both exercise intensity and inspired O2 fraction provided a (directly measured) femoral venous O2 saturation range from about 10 to 70%, and a correspondingly wide range in StiO2. Mean Q̇-weighted StiO2 over the six optodes related linearly to femoral venous O2 saturation in each subject. We used this relationship to compute local muscle venous blood O2 saturation from StiO2 recorded at each optode, from which local V̇O2/Q̇ could be calculated by the Fick principle. Multiplying regional V̇O2/Q̇ by Q̇ yielded the corresponding local V̇O2. While six optodes along only in one muscle may not fully capture the extent of heterogeneity, relative dispersion of both Q̇ and V̇O2 was ∼0.4 under all conditions, while that for V̇O2/Q̇ was minimal (only ∼0.1), indicating in fit young subjects 1) a strong capacity to regulate Q̇ according to regional metabolic need; and 2) a likely minimal impact of heterogeneity on muscle O2 availability.

Exercise-induced oxygen desaturation in COPD patients without resting hypoxemia

Exercise-induced oxygen desaturation (EID) is associated with increased risk of mortality in chronic obstructive pulmonary disease (COPD). Several screening tests have been proposed to predict EID, including FEV1, DLCO and baseline-SpO2. We aimed to validate a proposed cut-off of baseline-SpO2 ≤95% as simple screening procedure to predict EID during six-minute walk test (6MWT). In addition, we studied the prevalence and characteristics of patients exhibited EID to SpO2nadir ≤88%. 402 non-hypoxemic COPD patients performed 6MWT. Sensitivity and specificity of baseline SpO2 ≤95% as a cut-off to predict EID and determinants of EID were investigated. 158 patients (39%) exhibited EID. The sensitivity of baseline-SpO2 ≤95% to predict EID was 81.0%, specificity 49.2%, positive and negative predictive values were 50.8% and 80.0%, respectively. In a multivariate model, DLCO <50%, FEV1 <45%, PaO2 <10kPa, baseline-SpO2 <95%, and female sex were the strongest determinants of EID. Baseline oxygen saturation solely is inaccurate to predict EID. A combination of clinical characteristics (DLCO, FEV1, PaO2, baseline-SpO2, sex) increases the odds for EID in COPD.

Cerebral cortex oxygen delivery and exercise limitation in patients with COPD

In healthy humans, cerebral oxygen desaturation during exercise affects motor unit recruitment, while oxygen supplementation enhances cerebral oxygenation and work capacity. It remains unknown whether in patients with chronic obstructive pulmonary disease (COPD), the well-documented improvement in exercise tolerance with oxygen supplementation may also be partly due to the increase in cerebral oxygenation. Using near infrared spectroscopy, we measured both frontal cerebral cortex blood flow (CBF) using indocyanine green dye and cerebrovascular oxygen saturation (St,O2) in 12 COPD patients during constant-load exercise to exhaustion at 75% of peak capacity. Subjects exercised while breathing air, 100% oxygen or normoxic heliox, the latter two in balanced order. Time to exhaustion while breathing air was less than for either oxygen or heliox (mean±sem 394±35 versus 670±43 and 637±46 s, respectively). Under each condition, CBF increased from rest to exhaustion. At exhaustion, CBF was higher while breathing air and heliox than oxygen (30.9±2.3 and 31.3±3.5 versus 26.6±3.2 mL·min−1 per 100 g, respectively), compensating for the lower arterial oxygen content (Ca,O2) in air and heliox, and leading to similar cerebral cortex oxygen delivery (CQO2 for air was 5.3±0.4, for oxygen was 5.5±0.6 and for heliox was 5.6±1.0 mL O2 per min per 100 g). In contrast, end-exercise St,O2 was greater while breathing oxygen compared with air or heliox (67±4 versus 57±3 and 53±3%, respectively), reflecting Ca,O2 rather than CQO2. Prolonged time to exhaustion by breathing oxygen and heliox, despite these having a similar CQO2 to air, a lower St,O2 with heliox than oxygen, and yet similar endurance time and similar St,O2 in air and heliox despite greater endurance with heliox, do not support the hypothesis that an improvement in cerebral cortex oxygen availability plays a contributing role in increasing exercise capacity with oxygen or heliox in patients with COPD.

Prognostic value of variables derived from the six-minute walk test in patients with COPD: Results from the ECLIPSE study.

In addition to the six-min walk distance (6 MWD), other six-min walk test (6 MWT) derived variables, such as mean walk-speed (6MWSpeed), 6-min walk-work (6 MWW), distance-saturation product (DSP), exercise-induced oxygen desaturation (EID), and unintended stops may be useful for the prediction of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). We studied the association between 6 MWT-derived variables and mortality as well as hospitalization in COPD patients and compared it with the BODE index. A three-year prospective study (ECLIPSE) to evaluate the prognostic value of 6 MWT-derived variables in 2010 COPD patients. Coxs proportional-hazard regressions were performed to estimate 3-year mortality and hospitalization. During the follow-up, 193 subjects died and 622 were hospitalized. An adjusted Coxs regression model of hazard ratio [HR] for impaired 6 MWT-derived variables was significant referring to: mortality (6 MWD ≤334 m [2.30], 6MWSpeed ≤0.9 m/sec [2.15], 6 MWW ≤20000 m kg [2.17], DSP ≤290 m% [2.70], EID ≤88% [1.75], unintended stops [1.99]; and hospitalization (6 MWW ≤27000 m kg [1.23], EID ≤88% [1.25], BODE index ≥3 points [1.40]; all p ≤ 0.05). The 6 MWT-derived variables have an additional predictive value of mortality in patients with COPD. The 6 MWW, EID and the BODE index refine the prognosis of hospitalization.

Exercise Training in Pulmonary Rehabilitation

Exercise training remains a cornerstone of pulmonary rehabilitation (PR) in patients with chronic respiratory disease. The choice of type of exercise training depends on the physiologic requirements and goals of the individual patient as well as the available equipment at the PR center. Current evidence suggests that, at ground walking exercise training, Nordic walking exercise training, resistance training, water-based exercise training, tai chi, and nonlinear periodized exercise are all feasible and effective in (subgroups) of patients with chronic obstructive pulmonary disease. In turn, these exercise training modalities can be considered as part of a comprehensive, interdisciplinary PR program.

Quadriceps muscle blood flow and oxygen availability during repetitive bouts of isometric exercise in simulated sailing

Abstract In this study, we wished to determine whether the observed reduction in quadriceps muscle oxygen availability, reported during repetitive bouts of isometric exercise in simulated sailing efforts (i.e. hiking), is because of restricted muscle blood flow. Six national-squad Laser sailors initially performed three successive 3-min hiking bouts followed by three successive 3-min cycling tests sustained at constant intensities reproducing the cardiac output recorded during each of the three hiking bouts. The blood flow index (BFI) was determined from assessment of the vastus lateralis using near-infrared spectroscopy in association with the light-absorbing tracer indocyanine green dye, while cardiac output was determined from impedance cardiography. At equivalent cardiac outputs (ranging from 10.3±0.5 to 14.8±0.86 L · min−1), the increase from baseline in vastus lateralis BFI across the three hiking bouts (from 1.1±0.2 to 3.1±0.6 nM · s−1) was lower (P = 0.036) than that seen during the three cycling bouts (from 1.1±0.2 to 7.2±1.4 nM · s−1) (Cohens d: 3.80 nM · s−1), whereas the increase from baseline in deoxygenated haemoglobin (by ∼17.0±2.9 μM) (an index of tissue oxygen extraction) was greater (P = 0.006) during hiking than cycling (by ∼5.3±2.7 μM) (Cohens d: 4.17 μM). The results suggest that reduced vastus lateralis muscle oxygen availability during hiking arises from restricted muscle blood flow in the isometrically acting quadriceps muscles.

Six-minute walk distance in patients with chronic obstructive pulmonary disease: Which reference equations should we use?

The use of different 6-min walk distance (6MWD) reference equations probably results in different predicted 6MWD reference values. We wished to investigate the impact of several 6MWD reference equations for adults in patients with chronic obstructive pulmonary disease (COPD) and factors accountable for different 6MWD% predicted values. Twenty-two 6MWD reference equations were applied to a data set of 2757 patients with COPD. The predicted 6MWD reference value of Troosters and colleagues was used as the point of reference. Four out of 21 remaining equations resulted in comparable 6MWD% predicted, 16 equations resulted in significantly higher 6MWD% predicted and 1 equation resulted in a significantly lower 6MWD% predicted. Similar differences in 6MWD% predicted were observed after stratification by sex. Body mass index and global initiative for chronic obstructive lung disease (GOLD) stage classification demonstrated varying results within and between the groups; 9 out of 21 equations resulted in comparable 6MWD% predicted in underweight patients but only 1 equation demonstrated comparable result in obese. Eight equations in GOLD I, whilst 5 out of 21 equations in GOLD IV resulted in comparable 6MWD% predicted. Existing 6MWD reference equations will give varying results. The choice of 6MWD reference equation should consider the consistency of 6-min walk test operating procedures and at least be specific for the country/region of origin.