Beyond the Lungs: O 2 Supplementation Improves Cerebral Oxygenation and Fatigue during Exercise in Interstitial Lung Disease.

PURPOSE: Cerebral hypoxia may exacerbate the perception of fatigue. We previously demonstrated that exercise-related hypoxemia, a hallmark of fibrotic interstitial lung disease ( f -ILD), dose dependently impairs cerebral oxygenation in these patients. It is unknown whether normalizing cerebral oxygenation with O 2 supplementation would be associated with positive changes in a relevant patient-centered outcome during exercise in f -ILD, such as improved perceived fatigue. METHODS: Fourteen patients (12 males, 72 ± 8 yr, 8 with idiopathic pulmonary fibrosis, lung diffusing capacity for carbon monoxide = 44% ± 13% predicted) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) breathing medical air. Fourteen controls cycled up to Tlim of an age- and sex-matched patient. Patients repeated the test on supplemental O 2 (fraction of inspired O 2 = 0.41 ± 0.08) for the same duration. Near-infrared spectroscopy and the rating-of-fatigue (ROF) scale assessed prefrontal cortex oxygenation and perceived fatigue, respectively. RESULTS: Patients showed severe exertional hypoxemia (Tlim O 2 saturation by pulse oximetry = 80% ± 8%); they had poorer cerebral oxygenation (e.g., oxy-deoxyhemoglobin difference [HbDiff] = -3.5 ± 4.7 [range = -17.6 to +1.9] vs +1.9 ± 1.7 µmol from rest) and greater fatigue (ROF = 6.2 ± 2.0 vs 2.6 ± 2.3) versus controls under air ( P < 0.001). Reversal of exertional hypoxemia with supplemental O 2 led to improved HbDiff (+1.7 ± 2.4 µmol from rest; no longer differing from controls) and lower ROF scores (3.7 ± 1.2, P < 0.001 vs air) in patients. There was a significant correlation between O 2 -induced changes in HbDiff and ROF scores throughout exercise in f -ILD ( rrepeated-measures correlation = -0.51, P < 0.001). CONCLUSIONS: Supplemental O 2 improved cerebral oxygenation during exercise in f -ILD, which was moderately associated with lower ratings of perceived fatigue. Reversing cerebral hypoxia with O 2 supplementation may thus have positive effects on patients' disablement beyond those expected from lower ventilation and dyspnea in this patient population.

The relationship between perceived and performance fatigability in severe fibrotic interstitial lung disease: a prospective, cross-sectional study.

This study suggests that interventions geared to improve peripheral factors of performance fatigability during exercise in interstitial lung disease may prove valuable to decrease patients' perceived fatigability, since both seem closely related https://bit.ly/3lpIUPs.

Quantifying leg muscle deoxygenation during incremental cycling in hypoxemic patients with fibrotic interstitial lung disease.

BACKGROUND: Hypoxaemia and cardiocirculatory abnormalities may impair muscle oxygen (O2 ) delivery relative to O2 requirements thereby increasing the rate of O2 extraction during incremental exercise in fibrotic interstitial lung disease (f-ILD). Using changes in deoxyhaemoglobin concentration ([HHb]) by near-infrared spectroscopy (NIRS) as a proxy of O2 extraction, we investigated whether a simplified (double-linear) approach, previously tested in heart failure, would provide useful estimates of muscle deoxygenation in f-ILD. METHODS: A total of 25 patients (23 men, 72 ± 8 years; 20 with idiopathic pulmonary fibrosis, lung diffusing capacity for carbon monoxide = 44 ± 11% predicted) and 12 age- and sex-matched healthy controls performed incremental cycling to symptom limitation. Changes in vastus lateralis [HHb] assessed by NIRS were analysed in relation to work rate (WR) and O2 uptake throughout the exercise. RESULTS: Patients showed lower exercise capacity than controls (e.g., peak WR = 67 ± 18% vs. 105 ± 20% predicted, respectively; p < 0.001). The [HHb] response profile was typically S-shaped, presenting three distinct phases. Exacerbated muscle deoxygenation in patients versus controls was evidenced by: (i) a steeper mid-exercise [HHb]-WR slope (0.30 ± 0.22 vs. 0.11 ± 0.08 µmol/W; p = 0.008) (Phase 2), and (ii) a larger late-exercise increase in [HHb] (p = 0.002) (Phase 3). Steeper [HHb]-WR slope was associated with lower peak WR (r = -0.70) and greater leg discomfort (r = 0.77; p < 0.001) in f-ILD. CONCLUSION: This practical approach to interpreting [HHb] during incremental exercise might prove useful to determine the severity of muscle deoxygenation and the potential effects of interventions thereof in hypoxemic patients with f-ILD.

Clinical Interpretation of Cardiopulmonary Exercise Testing: Current Pitfalls and Limitations.

Several shortcomings on cardiopulmonary exercise testing (CPET) interpretation have shed a negative light on the test as a clinically useful tool. For instance, the reader should recognize patterns of dysfunction based on clusters of variables rather than relying on rigid interpretative algorithms. Correct display of key graphical data is of foremost relevance: prolixity and redundancy should be avoided. Submaximal dyspnea ratings should be plotted as a function of work rate (WR) and ventilatory demand. Increased work of breathing and/or obesity may normalize peak oxygen uptake (V̇O2) despite a low peak WR. Among the determinants of V̇O2, only heart rate is measured during non-invasive CPET. It follows that in the absence of findings suggestive of severe impairment in O2 delivery, the boundaries between inactivity and early cardiovascular disease are blurred in individual subjects. A preserved breathing reserve should not be viewed as evidence that "the lungs" are not limiting the subject. In this context, measurements of dynamic inspiratory capacity are key to uncover abnormalities germane to exertional dyspnea. A low end-tidal partial pressure for carbon dioxide may indicate either increased "wasted" ventilation or alveolar hyperventilation; thus, direct measurements of arterial (or arterialized) PO2 might be warranted. Differentiating a chaotic breathing pattern from the normal breath-by-breath noise might be complex if the plotted data are not adequately smoothed. A sober recognition of these limitations, associated with an interpretation report free from technicalities and convoluted terminology, is crucial to enhance the credibility of CPET in the eyes of the practicing physician.

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.

The Exercising Brain: An Overlooked Factor Limiting the Tolerance to Physical Exertion in Major Cardiorespiratory Diseases?

"Exercise starts and ends in the brain": this was the title of a review article authored by Dr. Bengt Kayser back in 2003. In this piece of work, the author highlights that pioneer studies have primarily focused on the cardiorespiratory-muscle axis to set the human limits to whole-body exercise tolerance. In some circumstances, however, exercise cessation may not be solely attributable to these players: the central nervous system is thought to hold a relevant role as the ultimate site of exercise termination. In fact, there has been a growing interest relative to the "brain" response to exercise in chronic cardiorespiratory diseases, and its potential implication in limiting the tolerance to physical exertion in patients. To reach these overarching goals, non-invasive techniques, such as near-infrared spectroscopy and transcranial magnetic stimulation, have been successfully applied to get insights into the underlying mechanisms of exercise limitation in clinical populations. This review provides an up-to-date outline of the rationale for the "brain" as the organ limiting the tolerance to physical exertion in patients with cardiorespiratory diseases. We first outline some key methodological aspects of neuromuscular function and cerebral hemodynamics assessment in response to different exercise paradigms. We then review the most prominent studies, which explored the influence of major cardiorespiratory diseases on these outcomes. After a balanced summary of existing evidence, we finalize by detailing the rationale for investigating the "brain" contribution to exercise limitation in hitherto unexplored cardiorespiratory diseases, an endeavor that might lead to innovative lines of applied physiological research.

Influence of exertional hypoxemia on cerebral oxygenation in fibrotic interstitial lung disease.

It is unknown whether hypoxemia, a hallmark of fibrotic interstitial lung disease (f-ILD), may impair cerebral oxygenation during exercise in these patients. Twenty-seven patients [23 males, 72 ± 8 years, lung diffusing capacity for carbon monoxide (DLCO) = 44 ± 11 % predicted] and 12 controls performed an incremental bicycle test. Prefrontal oxygenation [tissue saturation index (TSI)] was assessed by near-infrared spectroscopy. Patients showed lower arterial O2 saturation (SpO2) and larger fall in cerebral TSI during exercise vs controls (p < 0.05). However, changes (Δ) from rest to peak-exercise in SpO2 (-2.2 % to -26.9 %) and TSI (1.4 % to -16.6 %) varied substantially among patients. In the 16 patients showing significant cerebral deoxygenation (Δ TSI ≥ 4% based on controls), SpO2 decreased more (-12.6 ± 6.7 % vs -5.7 ± 2.8 %, p = 0.001) and peak O2 uptake was lower (68.3 ± 19.2 % vs 87.8 ± 24.8 % predicted, p = 0.03) vs their 11 counterparts. In association with DLCO and forced vital capacity, Δ cerebral TSI independently predicted peak O2 uptake on multivariable regression analysis (R2 = 0.54). Exertional hypoxemia impairs cerebral oxygenation in a dose-dependent fashion in f-ILD. Future studies are warranted to investigate whether this potentially reversible abnormality play a contributory role in limiting exercise tolerance in these patients.

The role of peripheral muscle fatigability on exercise intolerance in COPD.

INTRODUCTION: Exercise limitation in chronic obstructive pulmonary disease (COPD) is multi-factorial; however, growing evidence indicates that muscle dysfunction may contribute in some patients. AREAS COVERED: This work outlines current evidence for and against increased peripheral muscle fatigability in COPD through a comprehensive review of relevant literature available on PubMed/MEDLINE until May 2020. The authors first discuss key methodological issues relative to muscle fatigue assessment by non-volitional techniques, particularly magnetic stimulation. The authors then provide a detailed discussion of critical studies to have objectively measured skeletal muscle fatigue in individuals with COPD. EXPERT OPINION: Current evidence indicates that localized (knee extension) and cycling exercise are associated with increased quadriceps fatigability in most COPD patients. Increased fatigability, however, has not been consistently found in response to walking, likely reflecting the tendency of 'central' respiratory constraints to overshadow potential functional impairments in the appendicular muscles in this form of exercise. Thus, addressing skeletal muscle abnormalities may be critical to translate improvements in lung mechanics (e.g., due to bronchodilator therapy) into better exercise tolerance. The positive effects of pulmonary rehabilitation on muscle fatigability are particularly encouraging and suggest a role for these measurements to test the efficacy of emerging adjunct training strategies focused on the peripheral muscles.