Robert Cao

Physiologic Effects of an Ambulatory Ventilation System in Chronic Obstructive Pulmonary Disease

RATIONALE Exercise intolerance limits the ability of patients with chronic obstructive pulmonary disease (COPD) to perform daily living activities. Noninvasive ventilation reduces dyspnea and improves exercise performance, but current systems are unsuitable for ambulatory use. OBJECTIVES In patients with COPD experiencing exercise-induced desaturation, we evaluated improvements in exercise tolerance facilitated by a wearable, 1-lb, noninvasive open ventilation (NIOV) system featuring a nasal pillow interface during constant work rate (CWR) cycle ergometer exercise and associated effects on dyspnea, respiratory muscle activation, and pulmonary gas exchange efficiency. METHODS Fifteen men with COPD (FEV₁ = 32.2 ± 12.0% predicted; FEV₁/FVC = 31.6 ± 7.1%; exercise oxygen saturation as measured by pulse oximetry [Spo₂] = 86.5 ± 2.9%) participated. After incremental testing establishing peak work rate, subjects completed three visits in which they performed CWR exercise to tolerance at 80% peak work rate: (1) unencumbered breathing room air, (2) using NIOV+compressed air, (3) using NIOV+compressed O₂, or (4) using O₂ via nasal cannula. Assessments included exercise duration, surface inspiratory muscle EMG, Spo₂, transcutaneous Pco₂, and Borg dyspnea scores. MEASUREMENTS AND MAIN RESULTS Exercise endurance was 17.6 ± 5.7 minutes using NIOV+O₂, greatly prolonged compared with unencumbered (5.6 ± 1.9 min), nasal O₂ (11.4 ± 6.8 min), and NIOV+Air (6.3 ± 4.1 min). Isotime Spo₂ was higher and intercostal, scalene, and diaphragmatic EMG activity was reduced using NIOV+O₂ compared with unencumbered, nasal O₂, and NIOV+Air, signifying respiratory muscle unloading. Isotime dyspnea reduction correlated with isotime EMG reduction (r = 0.42, P = 0.0053). There were no significant differences in isotime VD/VT or transcutaneous Pco₂ among treatments. CONCLUSIONS NIOV+O₂ yielded substantial exercise endurance improvements accompanied by respiratory muscle unloading and dyspnea reductions in patients with severe hypoxemic COPD.

Reproducibility of NIRS assessment of muscle oxidative capacity in smokers with and without COPD

Low muscle oxidative capacity contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). Near-infrared spectroscopy (NIRS) allows non-invasive determination of the muscle oxygen consumption (mV̇O2) recovery rate constant (k), which is proportional to oxidative capacity assuming two conditions are met: 1) exercise intensity is sufficient to fully-activate mitochondrial oxidative enzymes; 2) sufficient O2 availability. We aimed to determine reproducibility (coefficient of variation, CV; intraclass correlation coefficient, ICC) of NIRS k assessment in the gastrocnemius of 64 participants with (FEV1 64±23%predicted) or without COPD (FEV1 98±14%predicted). 10-15s dynamic contractions preceded 6min of intermittent arterial occlusions (5-10s each, ∼250mmHg) for k measurement. k was lower (P<0.05) in COPD (1.43±0.4min-1; CV=9.8±5.9%, ICC=0.88) than controls (1.74±0.69min-1; CV=9.9±8.4%; ICC=0.93). Poor k reproducibility was more common when post-contraction mV̇O2 and deoxygenation were low, suggesting insufficient exercise intensity for mitochondrial activation and/or the NIRS signal contained little light reflected from active muscle. The NIRS assessment was well tolerated and reproducible for muscle dysfunction evaluation in COPD.

Effect of tiotropium on spontaneous expiratory flow–volume curves during exercise in GOLD 1-2 COPD

This substudy of a large, randomized, controlled trial (NCT01072396) examined tiotropium (18 μg qd) effects on dynamic hyperinflation during constant work rate treadmill exercise. Areas-under-the-spontaneous expiratory flow-volume (SEFV)-curves were compared in 20 COPD patients and 16 age-matched untreated controls, using rectangular area ratio (RAR) between peak intrabreath and end-expiratory flow. Seven patients exhibited SEFV curve concavity with RAR ≤ 0.5 (RARlow) in ≥1 test without tiotropium; (mean ± SD FEV1: 1.60 ± 0.59 L; 63.4 ± 14.0%predicted). In RARlow patients, tiotropium increased end-exercise inspiratory capacity (IC, 2.10 ± 0.05 vs. 1.89 ± 0.05 L, tiotropium vs. placebo; p = 0.045) and RAR (0.57 ± 0.02 vs. 0.53 ± 0.02; p < 0.001). Patients without SEFV curve concavity with RAR > 0.5 (n = 13; RARhigh), had higher screening FEV1 (2.15 ± 0.47 L; 79.6 ± 10.1%predicted) versus RARlow patients and no difference in end-exercise IC and RAR between tiotropium and placebo (IC: 2.24 ± 0.03 vs. 2.17 ± 0.03 L; RAR: 0.63 ± 0.005 vs. 0.62 ± 0.005). RAR and%predicted IC at peak exercise were positively correlated in RARlow patients (R2 = 0.43, p = 0.0002). Tiotropium increased exercise RAR in GOLD 1-2 patients with SEFV curve concavity.