Exercise-induced respiratory muscle fatigue: implications for performance

It is commonly held that the respiratory system has ample capacity relative to the demand for maximal O-2 and CO2 transport in healthy humans exercising near sea level. However, this situation may not apply during heavy-intensity, sustained exercise where exercise may encroach on the capacity of the respiratory system. Nerve stimulation techniques have provided objective evidence that the diaphragm and abdominal muscles are susceptible to fatigue with heavy, sustained exercise. The fatigue appears to be due to elevated levels of respiratory muscle work combined with an increased competition for blood flow with limb locomotor muscles. When respiratory muscles are prefatigued using voluntary respiratory maneuvers, time to exhaustion during subsequent exercise is decreased. Partially unloading the respiratory muscles during heavy exercise using low-density gas mixtures or mechanical ventilation can prevent exercise-induced diaphragm fatigue and increase exercise time to exhaustion. Collectively, these findings suggest that respiratory muscle fatigue may be involved in limiting exercise tolerance or that other factors, including alterations in the sensation of dyspnea or mechanical load, may be important. The major consequence of respiratory muscle fatigue is an increased sympathetic vasoconstrictor outflow to working skeletal muscle through a respiratory muscle metaboreflex, thereby reducing limb blood flow and increasing the severity of exercise-induced locomotor muscle fatigue. An increase in limb locomotor muscle fatigue may play a pivotal role in determining exercise tolerance through a direct effect on muscle force output and a feedback effect on effort perception, causing reduced motor output to the working limb muscles

Social isolation, loneliness and physical performance in older-adults: fixed effects analyses of a cohort study

Isolation and loneliness are related to various aspects of health. Physical performance is a central component of health. However, its relationship with isolation and loneliness is not well understood. We therefore assessed the relationship between loneliness, different aspects of social isolation, and physical performance over time. 8,780 participants from the English Longitudinal Study of Ageing, assessed three times over 8 years of follow-up, were included. Measures included physical performance (Short Physical Performance Battery), loneliness (modified UCLA Loneliness Scale), and isolation considered in three ways (domestic isolation, social disengagement, low social contact). Fixed effects regression models were used to estimate the relationship between changes in these parameters. Missing data were imputed to account for variable response and ensure a representative sample. Loneliness, domestic isolation and social disengagement were longitudinally associated with poorer physical performance when accounting for both time-invariant and time-variant confounders (loneliness: coef = - 0.06, 95% CI - 0.09 to - 0.02; domestic isolation: coef = - 0.32, 95% CI - 0.46 to - 0.19; social disengagement: coef = - 0.10, 95% CI - 0.12 to - 0.07). Low social contact was not associated with physical performance. These findings suggest social participation and subjectively meaningful interpersonal interactions are related to physical performance, and highlight additional considerations regarding social distancing related to COVID-19 control measures

Exercise response to oxygen supplementation is not associated with survival in hypoxemic patients with obstructive lung disease

Purpose: Hypoxemia is associated with more severe lung disease and worse outcomes. In some patients with chronic obstructive lung diseases who desaturate on exertion, supplemental oxygen improves exercise capacity. The clinical significance of this exercise response to oxygen supplementation is not known. Patient and methods: We identified chronic obstructive lung disease patients at our center who underwent a six-minute walking test (6MWT) for ambulatory oxygen assessment and who desaturated breathing air and therefore had an additional walk test on supplemental oxygen, between August 2006 and June 2016. Responders were defined as walking >26m further with oxygen. Survival was determined up to 1st February 2017. We compared survival in oxygen responders and non-responders in patients with obstructive lung diseases. Results: 174 patients were included in the study, median age 70 years. 77(44.3%) of the patients were oxygen responders. Borg dyspnea score improved by 1.4(±1.4) units (P<0.0005) on oxygen. Median survival was 66 months with death occurring in 84(48.2%) patients. Kaplan-Meier analysis revealed no survival difference between both responders and non-responders (P=0.571). Cox regression analysis showed that more 6MWT desaturation, lower 6MWD on room air, male gender, lower hemoglobin and BMI were associated with higher mortality risk. Conclusion: Acute exercise response to supplemental oxygen is not associated with long-term survival in patients with obstructive lung disease. This supports the use of ambulatory oxygen treatment for symptomatic purposes only

Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAs

RATIONALE: The molecular mechanisms underlying the muscle atrophy of intensive care unit-acquired weakness (ICUAW) are poorly understood. We hypothesised that increased circulating and muscle growth and differentiation factor-15 (GDF-15) causes atrophy in ICUAW by changing expression of key microRNAs. OBJECTIVES: To investigate GDF-15 and microRNA expression in patients with ICUAW and to elucidate possible mechanisms by which they cause muscle atrophy in vivo and in vitro. METHODS: In an observational study, 20 patients with ICUAW and seven elective surgical patients (controls) underwent rectus femoris muscle biopsy and blood sampling. mRNA and microRNA expression of target genes were examined in muscle specimens and GDF-15 protein concentration quantified in plasma. The effects of GDF-15 on C2C12 myotubes in vitro were examined. MEASUREMENTS AND MAIN RESULTS: Compared with controls, GDF-15 protein was elevated in plasma (median 7239 vs 2454 pg/mL, p=0.001) and GDF-15 mRNA in the muscle (median twofold increase p=0.006) of patients with ICUAW. The expression of microRNAs involved in muscle homeostasis was significantly lower in the muscle of patients with ICUAW. GDF-15 treatment of C2C12 myotubes significantly elevated expression of muscle atrophy-related genes and down-regulated the expression of muscle microRNAs. miR-181a suppressed transforming growth factor-β (TGF-β) responses in C2C12 cells, suggesting increased sensitivity to TGF-β in ICUAW muscle. Consistent with this suggestion, nuclear phospho-small mothers against decapentaplegic (SMAD) 2/3 was increased in ICUAW muscle. CONCLUSIONS: GDF-15 may increase sensitivity to TGF-β signalling by suppressing the expression of muscle microRNAs, thereby promoting muscle atrophy in ICUAW. This study identifies both GDF-15 and associated microRNA as potential therapeutic targets

Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic PEEP in COPD?

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume–time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild–moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV(1) in the whole cohort (r=−0.71, p<0.001) and patients alone (r=−0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=−0.55, p=0.0015) and patients (r=−0.71, p<0.001) and peak exercise tidal volume (r=−0.58, p=0.0062 and r=−0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=−0.65, p<0.001) and patients considered alone (r=−0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=−0.69, p<0.001) and patients (r=−0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity