Oxygen supplementation during exercise improves leg muscle fatigue in chronic fibrotic interstitial lung disease.

BACKGROUND: Exercise-induced hypoxaemia is a hallmark of chronic fibrotic interstitial lung disease (f-ILD). It remains unclear whether patients' severe hypoxaemia may exaggerate locomotor muscle fatigue and, if so, to what extent oxygen (O2) supplementation can ameliorate these abnormalities. METHODS: Fifteen patients (12 males, 9 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) while breathing medical air. Fifteen age-matched and sex-matched controls cycled up to patients' Tlim. Patients repeated the exercise test on supplemental O2 (42%±7%) for the same duration. Near-infrared spectroscopy assessed vastus lateralis oxyhaemoglobin concentration ((HbO2)). Pre-exercise to postexercise variation in twitch force (∆Tw) induced by femoral nerve magnetic stimulation quantified muscle fatigue. RESULTS: Patients showed severe hypoxaemia (lowest O2 saturation by pulse oximetry=80.0%±7.6%) which was associated with a blunted increase in muscle (HbO2) during exercise vs controls (+1.3±0.3 µmol vs +4.4±0.4 µmol, respectively; p<0.001). Despite exercising at work rates ∼ one-third lower than controls (42±13 W vs 66±13 W), ∆Tw was greater in patients (∆Tw/external work performed by the leg muscles=-0.59±0.21 %/kJ vs -0.25±0.19 %/kJ; p<0.001). Reversal of exertional hypoxaemia with supplemental O2 was associated with a significant increase in muscle (HbO2), leading to a reduced decrease in ∆Tw in patients (-0.33±0.19 %/kJ; p<0.001 vs air). Supplemental O2 significantly improved leg discomfort (p=0.005). CONCLUSION: O2 supplementation during exercise improves leg muscle oxygenation and fatigue in f-ILD. Lessening peripheral muscle fatigue to enhance exercise tolerance is a neglected therapeutic target that deserves clinical attention in this patient population.

High oxygen extraction and slow recovery of muscle deoxygenation kinetics after neuromuscular electrical stimulation in COPD patients.

PURPOSE: It was hypothesized that patients with chronic obstructive pulmonary disease (COPD) would exhibit a slow muscle deoxygenation (HHb) recovery time when compared with sedentary controls. METHODS: Neuromuscular electrical stimulation (NMES 40 and 50 mA, 50 Hz, 400 µs) was employed to induce isometric contraction of the quadriceps. Microvascular oxygen extraction (µO2EF) and HHb were estimated by near-infrared spectroscopy (NIRS). Recovery kinetic was characterized by measuring the time constant Tau (HHb-τ). Torque and work were measured by isokinetic dynamometry in 13 non-hypoxaemic patients with moderate-to-severe COPD [SpO2 = 94.1 ± 1.6 %; FEV1 (% predict) 48.0 ± 9.6; GOLD II-III] and 13 age- and sex-matched sedentary controls. RESULTS: There was no desaturation in either group during NMES. Torque and work were reduced in COPD versus control for 40 and 50 mA [torque (Nm) 50 mA = 28.9 ± 6.9 vs 46.1 ± 14.2; work (J) 50 mA = 437.2 ± 130.0 vs. 608.3 ± 136.8; P < 0.05 for all]. High µO2EF values were observed in the COPD group at both NMES intensities (corrected by muscle mass 50 mA = 6.18 ± 1.1 vs. 4.68 ± 1.0 %/kg; corrected by work 50 mA = 0.12 ± 0.05 vs. 0.07 ± 0.02 %/J; P < 0.05 for all). Absolute values of HHb-τ (50 mA = 31.11 ± 9.27 vs. 18.08 ± 10.70 s), corrected for muscle mass (50 mA 3.80 ± 1.28 vs. 2.05 ± 1.45 s/kg) and corrected for work (50 mA = 0.08 ± 0.04 vs. 0.03 ± 0.02 s/J) were reduced in COPD (P < 0.05 for all). The variables behaviour for 40 mA was similar to those of 50 mA. CONCLUSIONS: COPD patients exhibited a slower muscle deoxygenation recovery time after NMES. The absence of desaturation, low torque and work, high µO2EF and high values for recovery time corrected by muscle mass and work suggest that intrinsic muscle dysfunction has an impact on muscle recovery capacity.

Exercise capacity in polycystic kidney disease.

BACKGROUND: Reports about exercise performance in autosomal dominant polycystic kidney disease (ADPKD) are scarce. We aimed to evaluate exercise capacity and levels of nitric oxide and asymmetric dimethylarginine (ADMA) in normotensive patients with ADPKD. STUDY DESIGN: Prospective controlled cohort study. SETTING & PARTICIPANTS: 26 patients with ADPKD and 30 non-ADPKD control participants (estimated glomerular filtration rate>60 mL/min/1.73 m2, aged 19-39 years, and blood pressure [BP]<140/85 mmHg). We excluded smokers, obese people, and individuals with associated diseases. PREDICTOR: ADPKD versus control. OUTCOMES: Exercise capacity and nitric oxide and ADMA levels in response to exercise. MEASUREMENTS: Cardiopulmonary exercise testing and serum and urinary nitric oxide, plasma ADMA, and BP levels before and after exercise. RESULTS: Mean basal systolic and diastolic BP, estimated glomerular filtration rate, and age did not differ between the ADPKD and control groups (116±12 vs. 110±11 mmHg, 76±11 vs 71±9 mmHg, 113±17 vs. 112±9.6 mL/min/1.73 m2, and 30±8 vs. 28.9±7.3 years, respectively). Peak oxygen uptake and anaerobic threshold were significantly lower in the ADPKD group than in controls (22.2±3.3 vs. 31±4.8 mL/kg/min [P<0.001] and 743.6±221 vs. 957.4±301 L/min [P=0.01], respectively). Postexercise serum and urinary nitric oxide levels in patients with ADPKD were not significantly different from baseline (45±5.1 vs. 48.3±4.6 µmol/L and 34.7±6.5 vs. 39.8±6.8 µmol/mg of creatinine, respectively), contrasting with increased postexercise values in controls (63.1±1.9 vs. 53.9±3.1 µmol/L [P=0.01] and 61.4±10.6 vs. 38.7±5.6 µmol/mg of creatinine [P=0.01], respectively). Similarly, whereas postexercise ADMA level did not change in the ADPKD group compared to those at rest (0.47±0.04 vs. 0.45±0.02 µmol/L [P=0.6]), it decreased in controls (0.39±0.02 vs. 0.47±0.02 µmol/L [P=0.006]), as expected. A negative correlation between nitric oxide and ADMA levels after exercise was found in only the control group (r = -0.60; P<0.01). LIMITATIONS: Absence of measurements of flow-mediated dilatation and oxidative status. CONCLUSIONS: We found lower aerobic capacity in young normotensive patients with ADPKD with preserved kidney function and inadequate responses of nitric oxide and ADMA levels to acute exercise, suggesting the presence of early endothelial dysfunction in this disease.

Effects of Home-Based Electrical Stimulation on Plasma Cytokines Profile, Redox Biomarkers, and Metalloproteinases in the Heart Failure with Reduced Ejection Fraction: A Randomized Trial.

Background: Low-frequency electrical stimulation (LFES) is an adjuvant method for heart failure (HF) patients with restrictions to start an exercise. However, the impact on molecular changes in circulating is unknown. We investigated the effects of 10 weeks of home-based LFES on plasma cytokines profile, redox biomarkers, metalloproteinases (MMPs) activity, and exercise performance in HF patients. Methods: Twenty-four HF patients (52.45 ± 9.15 years) with reduced ejection fraction (HFrEF) (EF < 40%), were randomly assigned to a home-based LFES or sham protocol. Plasma cytokines profile was assessed through interleukins, interferon-gamma, and tumor necrosis factor levels. Oxidative stress was evaluated through ferric reducing antioxidant power, thiobarbituric acid-reactive substances, and inducible nitric oxide synthase. The MMPs activity were analyzed by zymography. Cardiorespiratory capacity and muscle strength were evaluated by cardiopulmonary test and isokinetic. Results: LFES was able to increase the active-MMP2 activity post compared to pre-training (0.057 to 0.163, p = 0.0001), while it decreased the active-MMP9 (0.135 to 0.093, p = 0.02). However, it did not elicit changes in cytokines, redox biomarkers, or exercise performance (p > 0.05). Conclusion: LFES protocol is a promising intervention to modulate MMPs activity in HFrEF patients, although with limited functional effects. These preliminary responses may help the muscle to adapt to future mechanical demands dynamically.

Sleep quality and architecture in COPD: the relationship with lung function abnormalities.

OBJECTIVE: Impaired respiratory mechanics and gas exchange may contribute to sleep disturbance in patients with COPD. We aimed to assess putative associations of different domains of lung function (airflow limitation, lung volumes, and gas exchange efficiency) with polysomnography (PSG)-derived parameters of sleep quality and architecture in COPD. METHODS: We retrospectively assessed data from COPD 181 patients ≥ 40 years of age who underwent spirometry, plethysmography, and overnight PSG. Univariate and multivariate linear regression models predicted sleep efficiency (total sleep time/total recording time) and other PSG-derived parameters that reflect sleep quality. RESULTS: The severity of COPD was widely distributed in the sample (post-bronchodilator FEV1 ranging from 25% to 128% of predicted): mild COPD (40.3%), moderate COPD (43.1%), and severe-very severe COPD (16.6%). PSG unveiled a high proportion of obstructive sleep apnea (64.1%) and significant nocturnal desaturation (mean pulse oximetry nadir = 82.2% ± 6.9%). After controlling for age, sex, BMI, apnea-hypopnea index, nocturnal desaturation, comorbidities, and psychotropic drug prescription, FEV1/FVC was associated with sleep efficiency (ß = 25.366; R2 = 14%; p < 0.001), whereas DLCO predicted sleep onset latency (ß = -0.314; R2 = 13%; p < 0.001) and rapid eye movement sleep time/total sleep time in % (ß = 0.085; R2 = 15%; p = 0.001). CONCLUSIONS: Pulmonary function variables reflecting severity of airflow and gas exchange impairment, adjusted for some potential confounders, were weakly related to PSG outcomes in COPD patients. The direct contribution of the pathophysiological hallmarks of COPD to objectively measured parameters of sleep quality seems to be less important than it was previously assumed.

Ventilatory and Near-Infrared Spectroscopy Responses Similarly Determine Anaerobic Threshold in Patients With Heart Failure.

PURPOSE: The present study compared the level of agreement of anaerobic threshold (AT) between ventilatory and near-infrared spectroscopy (NIRS) techniques in patients with chronic heart failure (CHF) and healthy subjects. METHODS: Patients with CHF (n = 9) and a control group (CG; n = 14) underwent cardiopulmonary exercise testing on a cycle ergometer until physical exhaustion. Determination of AT was performed visually by (1) ventilatory-expired gas analysis curves and (2) oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) curves assessed by NIRS. RESULTS: The CHF group presented significantly lower oxygen consumption (O2), heart rate, and workload at AT when compared with the CG measured by NIRS (P < .05). However, the effect size, measured by the Cohen d, revealed large magnitude (>0.80) in both techniques when compared between CHF patients and the CG. In addition, ventilatory and NIRS techniques demonstrated significant and very strong/strong correlations for relative O2 (r = 0.91) and heart rate (r = 0.85) in the detection of AT in the CHF group. CONCLUSION: Both ventilatory and NIRS assessments are correlated and there are no differences in the responses between CHF patients and healthy subjects in the determination of AT. These findings indicate both approaches may have utility in the assessment of submaximal exercise performance in patients with CHF.

Noninvasive Ventilation Accelerates Oxygen Uptake Recovery Kinetics in Patients With Combined Heart Failure and Chronic Obstructive Pulmonary Disease.

PURPOSE: Oxygen uptake (V˙o2) recovery kinetics appears to have considerable value in the assessment of functional capacity in both heart failure (HF) and chronic obstructive pulmonary disease (COPD). Noninvasive positive pressure ventilation (NIPPV) may benefit cardiopulmonary interactions during exercise. However, assessment during the exercise recovery phase is unclear. The purpose of this investigation was to explore the effects of NIPPV on V˙o2, heart rate, and cardiac output recovery kinetics from high-intensity constant-load exercise (CLE) in patients with coexisting HF and COPD. METHODS: Nineteen males (10 HF/9 age- and left ventricular ejection fraction-matched HF-COPD) underwent 2 high-intensity CLE tests at 80% of peak work rate to the limit of tolerance (Tlim), receiving either sham ventilation or NIPPV. RESULTS: Despite greater V˙o2 recovery kinetics on sham, HF-COPD patients presented with a faster exponential time constant τ (76.4 ± 14.0 sec vs 62.8 ± 15.2 sec, P < .05) and mean response time (MRT) (86.1 ± 19.1 sec vs 68.8 ± 12.0 sec, P < .05) with NIPPV and greater ΔNIPPV-sham (τ: 5.6 ± 19.5 vs -25.2 ± 22.4, P < .05; MRT: 4.1 ± 32.2 vs -26.0 ± 19.2, P < .05) compared with HF. There was no difference regarding Tlim between sham and NIPPV in both groups (P < .05). CONCLUSION: Our results suggest that NIPPV accelerated the V˙o2 recovery kinetics following high-intensity CLE to a greater extent in patients with coexisting HF and COPD compared with HF alone. NIPPV should be considered when the objective is to apply high-intensity interval exercise training as an adjunct intervention during a cardiopulmonary rehabilitation program.

Clinical value of anthropometric estimates of leg lean volume in nutritionally depleted and non-depleted patients with chronic obstructive pulmonary disease.

This study aimed to investigate the clinical usefulness of an anthropometrically based method for estimating leg lean volume (LLV) in patients with chronic obstructive pulmonary disease (COPD) who presented or not with nutritional depletion. We prospectively evaluated a group of forty-eight patients (thirty-eight males) with moderate to severe COPD (Global Initiative for Chronic Obstructive Lung disease stages II-IV) who underwent a 6 min walking test and knee isokinetic dynamometry. Leg lean mass (muscle mass plus bone) was determined by dual-energy X-ray absorptiometry (DEXA) with derivation of its respective volume: these values were compared with those obtained by the truncated cones method first described by Jones and Pearson in 1969. As expected, depleted patients (n 19) had reduced exercise capacity and impaired muscle performance as compared to non-depleted subjects (P < 0.01). The mean bias of the LLV differences between anthropometry and DEXA were 0.40 litre (95 % CI - 0.59, 1.39) and 0.50 litre (95 % CI - 1.08, 2.08) for depleted and non-depleted patients, respectively. Anthropometrically and DEXA-based estimates correlated similarly with muscle functional attributes. A ROC curve analysis revealed that leg height-corrected LLV values had acceptable sensitivity and specificity to identify depleted patients (area under the curve 0.93 (range 0.86-1.00); P < 0.001). Moreover, patients with LLV