Physical Activity, Muscle Oxidative Capacity, and Coronary Artery Calcium in Smokers with and without COPD.

Introduction: Severe chronic obstructive pulmonary disease (COPD) is partly characterized by diminished skeletal muscle oxidative capacity and concurrent dyslipidemia. It is unknown whether such metabolic derangements increase the risk of cardiovascular disease. This study explored associations among physical activity (PA), muscle oxidative capacity, and coronary artery calcium (CAC) in COPDGene participants. Methods: Data from current and former smokers with COPD (n = 75) and normal spirometry (n = 70) were retrospectively analyzed. Physical activity was measured for seven days using triaxial accelerometry (steps/day and vector magnitude units [VMU]) along with the aggregate of self-reported PA amount and PA difficulty using the PROactive D-PPAC instrument. Muscle oxidative capacity (k) was assessed via near-infrared spectroscopy, and CAC was assessed via chest computerized tomography. Results: Relative to controls, COPD patients exhibited higher CAC (median [IQR], 31 [0-431] vs 264 [40-799] HU; p = 0.003), lower k (mean ± SD = 1.66 ± 0.48 vs 1.25 ± 0.37 min-1; p < 0.001), and lower D-PPAC total score (65.2 ± 9.9 vs 58.8 ± 13.2; p = 0.003). Multivariate analysis-adjusting for age, sex, race, diabetes, disease severity, hyperlipidemia, smoking status, and hypertension-revealed a significant negative association between CAC and D-PPAC total score (ß, -0.05; p = 0.013), driven primarily by D-PPAC difficulty score (ß, -0.03; p = 0.026). A 1 unit increase in D-PPAC total score was associated with a 5% lower CAC (p = 0.013). There was no association between CAC and either k, steps/day, VMU, or D-PPAC amount. Conclusion: Patients with COPD and concomitantly elevated CAC exhibit greater perceptions of difficulty when performing daily activities. This may have implications for exercise adherence and risk of overall physical decline.

The Relationship of Physical Activity and Dietary Quality and Diabetes Prevalence in US Adults: Findings from NHANES 2011-2018.

This study aimed to examine the relationship of physical activity and/or dietary quality and diabetes prevalence in the general population and within specific age groups. It was a cross-sectional study using 2011−2018 National Health and Nutrition Examination Survey and the US Department of Agriculture's Food Patterns Equivalents data (n = 15,674). Physical activity was measured by Global Physical Activity questionnaire; dietary quality was analyzed using the Healthy Eating Index 2015; diabetes prevalence was determined by reported diagnosis and glycohemoglobin or fasting glucose. Data were analyzed using multiple logistic regression adjusted for demographic variables and weight status. Results revealed that although no statistically significant or non-substantial relationships were observed between dietary quality or physical activity and diabetes prevalence, respondents who did not meet physical activity recommendations regardless of dietary quality had a higher odds of diabetes prevalence than those who met physical activity recommendations and had a higher dietary quality (p < 0.05). In conclusion, meeting physical activity recommendations is an important protective factor for diabetes especially in combination with a higher quality diet. A healthy lifestyle appears to have the greater impact on diabetes prevention in middle-aged men and women.

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans.

The final steps of the O2 cascade during exercise depend on the product of the microvascular-to-intramyocyte P O 2 ${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ( D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ ). Non-invasive methods to determine D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW ), and hypothesized that: (i) k in well oxygenated muscle (kHIGH ) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH  - kLOW ) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s-1  mg-1 (∼5.8 ml min-1  100 g-1 ). CD ranged 348 to 586 mm-2 . kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min-1 , P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = -0.10, P = 0.755). Δk ranged -0.26 to -2.55 min-1 , and correlated with CD (r = -0.68, P = 0.015). m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ . Assessment of muscle k and ∆k using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity. KEY POINTS: We determined post-exercise recovery kinetics of quadriceps muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) measured by near-infrared spectroscopy (NIRS) in humans under conditions of both non-limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables. The m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (kHIGH ) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity. kHIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80). ∆k was negatively correlated with capillary density (r = -0.68) of biopsy samples. NIRS provides non-invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo.

Identifying a Heart Rate Recovery Criterion After a 6-Minute Walk Test in COPD.

BACKGROUND: Slow heart rate recovery (HRR) after exercise is associated with autonomic dysfunction and increased mortality. What HRR criterion at 1-minute after a 6-minute walk test (6MWT) best defines pulmonary impairment?. STUDY DESIGN AND METHODS: A total of 5008 phase 2 COPDGene (NCT00608764) participants with smoking history were included. A total of 2127 had COPD and, of these, 385 were followed-up 5-years later. Lung surgery, transplant, bronchiectasis, atrial fibrillation, heart failure and pacemakers were exclusionary. HR was measured from pulse oximetry at end-walk and after 1-min seated recovery. A receiver operator characteristic (ROC) identified optimal HRR cut-off. Generalized linear regression determined HRR association with spirometry, chest CT, symptoms and exacerbations. RESULTS: HRR after 6MWT (bt/min) was categorized in quintiles: ≤5 (23.0% of participants), 6-10 (20.7%), 11-15 (18.9%), 16-22 (18.5%) and ≥23 (18.9%). Compared to HRR≤5, HRR≥11 was associated with (p<0.001): lower pre-walk HR and 1-min post HR; greater end-walk HR; greater 6MWD; greater FEV1%pred; lower airway wall area and wall thickness. HRR was positively associated with FEV1%pred and negatively associated with airway wall thickness. An optimal HRR ≤10 bt/min yielded an area under the ROC curve of 0.62 (95% CI 0.58-0.66) for identifying FEV1<30%pred. HRR≥11 bt/min was the lowest HRR associated with consistently less impairment in 6MWT, spirometry and CT variables. In COPD, HRR≤10 bt/min was associated with (p<0.001): ≥2 exacerbations in the previous year (OR=1.76[1.33-2.34]); CAT≥10 (OR=1.42[1.18-1.71]); mMRC≥2 (OR=1.42[1.19-1.69]); GOLD 4 (OR=1.98[1.44-2.73]) and GOLD D (OR=1.51[1.18-1.95]). HRR≤10 bt/min was predicted COPD exacerbations at 5-year follow-up (RR=1.83[1.07-3.12], P=0.027). CONCLUSION: HRR≤10 bt/min after 6MWT in COPD is associated with more severe expiratory flow limitation, airway wall thickening, worse dyspnoea and quality of life, and future exacerbations, suggesting that an abnormal HRR≤10 bt/min after a 6MWT may be used in a comprehensive assessment in COPD for risk of severity, symptoms and future exacerbations.

Vagal blockade suppresses the phase I heart rate response but not the phase I cardiac output response at exercise onset in humans.

PURPOSE: We tested the vagal withdrawal concept for heart rate (HR) and cardiac output (CO) kinetics upon moderate exercise onset, by analysing the effects of vagal blockade on cardiovascular kinetics in humans. We hypothesized that, under atropine, the φ1 amplitude (A1) for HR would reduce to nil, whereas the A1 for CO would still be positive, due to the sudden increase in stroke volume (SV) at exercise onset. METHODS: On nine young non-smoking men, during 0-80 W exercise transients of 5-min duration on the cycle ergometer, preceded by 5-min rest, we continuously recorded HR, CO, SV and oxygen uptake ([Formula: see text]O2) upright and supine, in control condition and after full vagal blockade with atropine. Kinetics were analysed with the double exponential model, wherein we computed the amplitudes (A) and time constants (τ) of phase 1 (φ1) and phase 2 (φ2). RESULTS: In atropine versus control, A1 for HR was strongly reduced and fell to 0 bpm in seven out of nine subjects for HR was practically suppressed by atropine in them. The A1 for CO was lower in atropine, but not reduced to nil. Thus, SV only determined A1 for CO in atropine. A2 did not differ between control and atropine. No effect on τ1 and τ2 was found. These patterns were independent of posture. CONCLUSION: The results are fully compatible with the tested hypothesis. They provide the first direct demonstration that vagal blockade, while suppressing HR φ1, did not affect φ1 of CO.

The Relationships between Total Protein Intake, Protein Sources, Physical Activity, and Lean Mass in a Representative Sample of the US Adults.

BACKGROUND: Although dietary protein and physical activity play essential roles in developing and preserving lean mass, studies exploring these relationships are inconsistent, and large-scale studies on sources of protein and lean mass are lacking. Accordingly, the present study examined the relationship between total protein intake, protein sources, physical activity, and lean mass in a representative sample of US adults. METHODS: This cross-sectional study analyzed data from 2011-2016 US National Health and Nutrition Examination Survey and corresponding Food Patterns Equivalents Database (n = 7547). Multiple linear regression models were performed to examine the sex-specific associations between total protein intake, protein sources (Dairy, Total Protein Foods, Seafood, and Plant Proteins), physical activity, and lean mass adjusting for demographics, weight status, and total daily energy intake. RESULTS: Total protein intake was inversely related to lean mass in females only (Lean mass index: ß= -0.84, 95%CI: -1.06--0.62; Appendicular lean mass index: ß= -0.35, 95%CI: -0.48--0.22). However, protein sources and physical activity was positively associated with lean mass in males and/or females (p < 0.05). CONCLUSION: Study results suggest that consuming more protein daily had a detrimental influence on lean mass in females whereas eating high-quality sources of proteins and being physically active are important for lean mass for men and women. However, the importance of specific protein sources appears to differ by sex and warrants further investigation.

Relationships of Physical Activity and Diet Quality with Body Composition and Fat Distribution in US Adults.

OBJECTIVE: This study aimed to investigate the relationships among physical activity (PA), diet quality, body composition, and fat distribution in a representative sample of US adults. METHODS: A cross-sectional analysis was conducted using publicly accessible data from the 2011 to 2016 National Health and Nutrition Examination Survey and the Food Patterns Equivalents Database (n = 7,423). Variables from the data sets were analyzed for this study, including PA, two 24-hour dietary recalls, and dual-energy x-ray absorptiometry outputs. RESULTS: For men, PA and diet quality were inversely associated with the percentage of body fat (ß = -0.0042, 95% CI: -0.0084 to -0.0001; ß = -0.28, 95% CI: -0.42 to -0.14) and fat mass index (ß = -0.0125, 95% CI: -0.0209 to -0.0041; ß = -0.56, 95% CI: -0.81 to -0.32); meeting the PA recommendation and having good diet quality provided an additive effect on body fat. A similar pattern was observed in women. Additionally, diet quality was inversely associated with all fat distribution measures in both sexes, whereas PA was positively associated with lean mass measures in men only. CONCLUSIONS: Increased PA and/or better diet quality were associated with reduced body fat, a healthier fat distribution, and increased lean mass. Further research examining how changes in PA or diet quality influence body composition and fat distribution in adults is warranted.

Muscle Oxidative Capacity Is Reduced in Both Upper and Lower Limbs in COPD.

INTRODUCTION: Skeletal muscle atrophy, weakness, mitochondrial loss, and dysfunction are characteristics of chronic obstructive pulmonary disease (COPD). It remains unclear whether muscle dysfunction occurs in both upper and lower limbs, because findings are inconsistent in the few studies where upper and lower limb muscle performance properties were compared within an individual. This study determined whether muscle oxidative capacity is low in upper and lower limbs of COPD patients compared with controls. METHODS: Oxidative capacity of the forearm and medial gastrocnemius was measured using near-infrared spectroscopy to determine the muscle O2 consumption recovery rate constant (k, min) in 20 COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2/3/4, n = 7/7/6) and 20 smokers with normal spirometry (CON). Muscle k is linearly proportional to oxidative capacity. Steps per day and vector magnitude units per minute (VMU·min) were assessed using triaxial accelerometry. Differences between group and limb were assessed by two-way ANOVA. RESULTS: There was a significant main effect of group (F = 11.2, ηp = 0.13, P = 0.001): k was lower in both upper and lower limb muscles in COPD (1.01 ± 0.17 and 1.05 ± 0.24 min) compared with CON (1.29 ± 0.49 and 1.54 ± 0.60 min). There was no effect on k of limb (F = 1.8, ηp = 0.02, P = 0.18) or group-limb interaction (P = 0.35). (VMU·min) was significantly lower in COPD (-38%; P = 0.042). Steps per day did not differ between COPD (4738 ± 3194) and CON (6372 ± 2107; P = 0.286), although the difference exceeded a clinically important threshold (>600-1100 steps per day). CONCLUSIONS: Compared with CON, muscle oxidative capacity was lower in COPD in both upper (-20%) and lower (-30%) limbs. These data suggest that mitochondrial loss in COPD is not isolated to locomotor muscles.

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.