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Muscle oxidative capacity is a major determinant of maximum oxygen uptake (V·O2max). V · O2max predicts survival in humans. Muscle oxidative capacity is low in chronic obstructive pulmonary disease (COPD) and can be assessed from the muscle oxygen consumption recovery rate constant (k) by near-infrared spectroscopy. We hypothesized that 11 SNPs, previously associated with the increase in V ·O2max following exercise training, would correlate with k in 152 non-Hispanic White and African American smokers with and without COPD. Associations were adjusted for age, weight, FEV1% predicted, steps/day, and principal components of genetic ancestry. No SNPs were significantly associated with k. rs2792022 within BTAF1 (β = 0.130, P = 0.053) and rs24575771 within SLC22A3 (β = 0.106, P = 0.058) approached nominal significance. Case-control stratification identified three SNPs nominally associated with k in moderate-to-severe COPD (rs6481619 within SVIL β = 0.152, P = 0.013; BTAF1 β = 0.196, P = 0.046; rs7386139 within DEPTOR β = 0.159, P = 0.047). These data support further study of the genomic contributions to skeletal muscle dysfunction in COPD. [ABSTRACT FROM AUTHOR]

Background: Individuals with cerebral palsy (CP) report physical fatigue as a main cause of limitation, deterioration and eventually cessation of their walking ability. A consequence of higher level of fatigue in individuals with CP leads to a less efficient and long-distance walking ability.Research Question: This systematic review investigates the difference in 1) walking energy expenditure between individuals with CP and age-matched typically developing (TD) individuals; and 2) energetics of walking across Gross Motor Function Classification System (GMFCS) levels and age.Methods: Five electronic databases (PubMed, Web of Science, CINAHL, ScienceDirect and Scopus) were searched using search terms related to CP and energetics of walking.Results: Forty-one studies met inclusion criteria. Thirty-one studies compared energy expenditure between CP and age-matched controls. Twelve studies correlated energy expenditure and oxygen cost across GMFCS levels. Three studies investigated the walking efficiency across different ages or over a time period. A significant increase of energy expenditure and oxygen cost was found in individuals with CP compared to TD age-matched individuals, with a strong relationship across GMFCS levels.Significance: Despite significant differences between individuals with CP compared to TD peers, variability in methods and testing protocols may play a confounding role. Analysis suggests oxygen cost being the preferred/unbiased physiological parameter to assess walking efficacy in CP. To date, there is a knowledge gap on age-related changes of walking efficiency across GMFCS levels and wider span of age ranges. Further systematic research looking at longitudinal age-related changes of energetics of walking in this population is warranted. [ABSTRACT FROM AUTHOR]

Background and Aims: Abdominal adiposity indices have stronger associations with cardiometabolic risk factors compared to anthropometric measures but are rarely used in large scale studies due to the cost and efficiency. The aim of this study is to establish sex and race/ethnicity specific reference equations using anthropometric measures., Methods and Results: A secondary data analysis (n = 6589) of healthy adults was conducted using data from National Health and Nutrition Examination Survey 2011-2018. Variables included in the analyses were anthropometric measures (height; weight; waist circumference, WC) and abdominal adiposity indices (android percent fat; android to gynoid ratio, A/G ratio; visceral adipose tissue area, VATA; visceral to subcutaneous adipose area ratio, VSR). Multivariable prediction models were developed using quantile regression. Bland-Altman was used for external validation of prediction models. Reference equations to estimate android percent fat, A/G ratio, VATA and VSR from anthropometric measurements were developed using a randomly selected subsample of 4613. These reference equations for four abdominal adiposity indices were then cross-validated in the remaining subsample of 1976. The measured and predicted android percent fat, A/G ratio, VATA and VSR were not statistically different (p > 0.05) except for the A/G ratio in Asian males and VSR in White females. The results of Bland-Altman further revealed that ≥93% of predicted abdominal adiposity indices fell within the limits of agreement (±1.96 standard deviation)., Conclusion: The sex and race/ethnicity specific reference equations for abdominal adiposity indices established using anthropometrics in the present study have strong predictive ability in US healthy adults., Competing Interests: Conflicts of interest The authors report no conflicts of interest., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Purpose: To determine whether kinetic chain pattern during knee extensor strength training influences quadriceps femoris center of mass and moment of inertia about the hip in a predictable manner as such changes can affect running economy. Methods: Twelve participants completed 8 weeks of both unilateral open (OKC) and closed (CKC) kinetic chain resistance training on opposing legs. Changes in quadriceps femoris muscle volume (VOL QF ), center of mass location (CoM QF ), and moment of inertia ( I QF ) about the hip were determined from magnetic resonance images scans. Regional hemodynamics of the vastus lateralis taken at 30% and 70% of muscle length during OKC and CKC bouts early in the training program were measured using near-infrared spectroscopy (NIRS) and used post hoc to predict changes in CoM QF . Results: While increases in VOL QF were similar between OKC (Δ79.5 ± 87.9 cm 3 ) and CKC (Δ60.2 ± 110.5 cm 3 , p = 0.29), the patterns of hypertrophy differed; a distal shift in CoM QF (Δ2.4 ± 0.4 cm, p < 0.001) and increase in I QF (Δ0.017 ± 0.014 kg m 2 , p < 0.001) occurred in OKC but not in CKC (CoM QF : Δ-2.2 ± 2.0 cm, I QF : Δ-0.022 ± 0.020 kg m 2 , p > 0.05). Regional hemodynamics assessed by NIRS during a single training session displayed similar exercise and regional differences and predicted 39.6% of observed changes in CoM QF . Conclusions: Exercise selection influences muscle shape sufficiently to affect CoM QF and I QF , and these changes may be predicted in part from NIRS measurements during a single workout. Given I QF is inversely related to running economy and since CKC exercise provides a more proximal pattern of hypertrophy than OKC, it may be more preferential for running. The results from the present study also highlight the potential of NIRS as a tool for predicting patterns of hypertrophy between different exercises and exercise conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Earp, Angelino, Hatfield, Colantuono, Jackson, Morgan, Adami, Melanson and Blazevich.)

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 φ 1 amplitude (A 1 ) for HR would reduce to nil, whereas the A 1 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]O 2 ) 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 (φ 1 ) and phase 2 (φ 2 )., Results: In atropine versus control, A 1 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 A 1 for CO was lower in atropine, but not reduced to nil. Thus, SV only determined A 1 for CO in atropine. A 2 did not differ between control and atropine. No effect on τ 1 and τ 2 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 φ 1 , did not affect φ 1 of CO., (© 2021. The Author(s).)

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 FEV 1 %pred; lower airway wall area and wall thickness. HRR was positively associated with FEV 1 %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 FEV 1 <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., Competing Interests: Summary conflict of interest statements: The authors report funding from the NIH in direct support of this work; other support, including consultancy, advisory board fees and contracted research from industry is outside the submitted work. A full list of disclosures is provided. Dongxing Zhao has no disclosures to report. Asghar Abbasi is supported by a postdoctoral fellowship from the Tobacco-Related Disease Research Program (28FT-0017). Richard Casaburi reports personal fees from Glaxo Smith Kline, Boehringer Ingelheim, Astra Zeneca, Regeneron and Genentech and contracted clinical research support from Astra Zeneca, Boehringer Ingelheim, Glaxo Smith Kline, Genentech and Regeneron outside the submitted work. Alessandra Adami is supported by a grant from NIH/NHLBI (R01HL151452). Nicholas B. Tiller is supported by a postdoctoral fellowship from the Tobacco-Related Disease Research Program (T31FT1692). Wei Yuan has no disclosures to report. Christopher Yee has no disclosures to report. Nicholas Jendzjowsky reports grant funding from AazeinTx, outside the submitted work; is a Parker B Francis Fellowship Recipient; reports US provisional patent, application no. 59263173-179 outside the submitted work; has patent 62/534,638 pending to University of Calgary. David MacDonald has no disclosures to report. Ken Kunisaki reports grants from NIH, during the conduct of the study, personal fees from Nuvaira for data safety and monitoring board services, and contracted clinical research support from Sanofi outside the submitted work. William Stringer reports research funding from AstraZeneca and consultancy for GlaxoSmithKline outside the submitted work. Janos Porszasz reports contracted clinical research support with United Therapeutics, Genentech and Regeneron outside the submitted work. Barry Make reports (related to the general topic of COPD over the last three years) grants from NHLBI, Pearl Research, Circassia, GlaxoSmithKline and AstraZeneca; advisory board fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Verona, Third Pole, and Phillips; consulting fees from AstraZeneca; medical board member, grants, non-financial support, grant funds provided to and controlled by National Jewish Health for/from Astra Zeneca, grants and CME activity for/from Glaxo Smith Kline, CME activity for Wolters Kluwer Health, Spiration, CME activity for Sunovion, Mt Sinai, Web MD, National Jewish Health, Novartis, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, Medscape, Ultimate Medical Academy, Eastern Pulmonary Society, Catamount Medical, Eastern VA Medical Center, and Academy Continued Health Care Learning, grants from Pearl Research (funds provided to and controlled by National Jewish Health), medical advisory board for Verona, Boehringer Ingelheim, Theravance, Phillips, and Science 24/7, non-financial support from Circassia, personal fees from Third Pole and Takeda, and grants from NHLBI, outside the submitted work. Russ Bowler has no disclosures to report. Harry Rossiter is supported by grants from NIH (R01HL151452, P50HD098593, R01DK122767, P2CHD086851) and the Tobacco Related Disease Research Program (T31IP1666). He reports consulting fees from Omniox Inc., and is involved in contracted clinical research with Boehringer Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Astellas, United Therapeutics, Genentech and Regeneron. The authors report no other potential conflicts of interest for this work., (© 2021 Zhao et al.)

Purpose: Chronic obstructive pulmonary disease (COPD) is associated with altered metabolism and body composition that accompany poor outcomes. We aimed to determine whether metabolic derangements in COPD are associated with skeletal muscle deconditioning and/or physical inactivity, independent of pulmonary obstruction., Methods: We characterized serum metabolites associated with muscle oxidative capacity or physical activity in 44 COPD patients (forced expiratory volume in 1 s [FEV1] = 61% ± 4% predicted) and 63 current and former smokers with normal spirometry (CON) (FEV1 = 93% ± 2% predicted). Medial gastrocnemius oxidative capacity was assessed at rest from the recovery rate constant (k) of muscle oxygen consumption using near-infrared spectroscopy. Step counts and physical activity (average vector magnitude units [VMU] per minute) were measured over 5-7 d using triaxial accelerometry. Untargeted prime and lipid metabolites were measured using liquid chromatography and mass spectrometry., Results: Muscle k (1.12 ± 0.05 vs 1.68 ± 0.06 min, P < 0.0001, d = 1.58) and VMU per minute (170 ± 26 vs 450 ± 50 VMU per minute, P = 0.004, d = 1.04) were lower in severe COPD (FEV1 < 50% predicted, n = 14-16) compared with CON (n = 56-60). A total of 129 prime metabolites and 470 lipids with known identity were quantified. Using sex as a covariate, lipidomics revealed 24 differentially expressed lipids (19 sphingomyelins) in COPD, consequent to a diminished sex difference of sphingomyelins in COPD (false discovery rate [FDR] < 0.05, n = 44). Total, and some individual, fatty acid concentrations were greater in severe COPD than CON (FDR < 0.05, n = 16, d = 0.56-1.02). After adjusting for FEV1% predicted, we observed that grouped diacylglycerides (ρ = -0.745, FDR = 0.03) and triacylglycerides (ρ = -0.811, FDR = 0.01) were negatively associated with muscle oxidative capacity, but not physical activity, in severe COPD (n = 14)., Conclusion: Strong negative associations relate impaired mitochondrial function to the accumulation of serum aclyglycerides in severe 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.

Skeletal muscle deoxygenated hemoglobin and myoglobin concentration ([HHb]), assessed by near-infrared spectroscopy (NIRS), is commonly used as a surrogate of regional O2 extraction (reflecting the O2 delivery-to-consumption ratio, Q̇/V̇o2). However, [HHb] change (Δ[HHb]) is also influenced by capillary-venous heme concentration, and/or small blood vessel volume (reflected in total heme; [THb]). We tested the hypotheses that Δ[HHb] is associated with O2 extraction, and insensitive to [THb], over a wide range of Q̇/V̇o2 elicited by passive head-up tilt (HUT; 10-min, 15° increments, between -10° and 75°). Steady-state common femoral artery blood flow (FBF) was measured by echo-Doppler, and time-resolved NIRS measured [HHb] and [THb] of vastus lateralis (VL) and gastrocnemius (GS) in 13 men. EMG confirmed muscles were inactive. During HUT in VL [HHb] increased linearly (57 ± 10 to 101 ± 16 μM; P < 0.05 above 15°) and was associated (r(2) ∼ 0.80) with the reduction in FBF (618 ± 75 ml/min at 0° to 268 ± 52 ml/min at 75°; P < 0.05 above 30°) and the increase in [THb] (228 ± 30 vs. 252 ± 32 μM; P < 0.05 above 15°). GS response was qualitatively similar to VL. However, there was wide variation within and among individuals, such that the overall limits of agreement between Δ[HHb] and ΔFBF ranged from -35 to +19% across both muscles. Neither knowledge of tissue O2 saturation nor vascular compliance could appropriately account for the Δ[HHb]-ΔFBF dissociation. Thus, under passive tilt, [HHb] is influenced by Q̇/V̇o2, as well as microvascular hematocrit and/or tissue blood vessel volume, complicating its use as a noninvasive surrogate for muscle microvascular O2 extraction., (Copyright © 2015 the American Physiological Society.)