Dyspnea in COPD: New Mechanistic Insights and Management Implications

O’Donnell, Denis E.; Milne, Kathryn M.; James, Matthew D.; de-Torres, Juan P.; Neder, J. Alberto

doi:10.1007/s12325-019-01128-9

Cited by 157 publications

(135 citation statements)

References 112 publications

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“…End-inspiratory lung volume during exercise is typically midway between FRC and TLC or even higher ( Younes and Burks, 1985 ; Neder et al, 2003 ). Inspirations during exercise hyperpnea in highly trained athletes and patients with expiratory flow limitation such as in patients with chronic obstructive pulmonary disease are initiated at or above FRC and end-inspiratory lung volume will approach TLC ( Johnson et al, 1992 ; Dempsey et al, 2008 ; McKenzie, 2012 ; O’Donnell et al, 2019 ). In addition, shortening velocity of the respiratory muscles has to increase during exercise hyperpnea ( Prioux et al, 2000 ; Neder et al, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

Training Specificity of Inspiratory Muscle Training Methods: A Randomized Trial

2020

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IntroductionInspiratory muscle training (IMT) protocols are typically performed using pressure threshold loading with inspirations initiated from residual volume (RV). We aimed to compare effects of three different IMT protocols on maximal inspiratory pressures (PImax) and maximal inspiratory flow (V̇Imax) at three different lung volumes. We hypothesized that threshold loading performed from functional residual capacity (FRC) or tapered flow resistive loading (initiated from RV) would improve inspiratory muscle function over a larger range of lung volumes in comparison with the standard protocol.Methods48 healthy volunteers (42% male, age: 48 ± 9 years, PImax: 110 ± 28%pred, [mean ± SD]) were randomly assigned to perform three daily IMT sessions of pressure threshold loading (either initiated from RV or from FRC) or tapered flow resistive loading (initiated from RV) for 4 weeks. Sessions consisted of 30 breaths against the highest tolerable load. Before and after the training period, PImax was measured at RV, FRC, and midway between FRC and total lung capacity (1/2 IC). V̇Imax was measured at the same lung volumes against a range of external threshold loads.ResultsWhile PImax increased significantly at RV and at FRC in the group performing the standard training protocol (pressure threshold loading from RV), it increased significantly at all lung volumes in the two other training groups (all p < 0.05). No significant changes in V̇Imax were observed in the group performing the standard protocol. Increases of V̇Imax were significantly larger at all lung volumes after tapered flow resistive loading, and at higher lung volumes (i.e., FRC and 1/2 IC) after pressure threshold loading from FRC in comparison with the standard protocol (all p < 0.05).ConclusionOnly training with tapered flow resistive loading and pressure threshold loading from functional residual capacity resulted in consistent improvements in respiratory muscle function at higher lung volumes, whereas improvements after the standard protocol (pressure threshold loading from residual volume) were restricted to gains in PImax at lower lung volumes. Further research is warranted to investigate whether these results can be confirmed in larger samples of both healthy subjects and patients.

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Section: Discussionmentioning

confidence: 99%

Training Specificity of Inspiratory Muscle Training Methods: A Randomized Trial

2020

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“…Unlike the V E :dyspnea relationship, which is limited when respiratory mechanics are impaired, EMGdi %max robustly correlates with dyspnea in health and across disease severity ( 50 , 74 ). Dyspnea is thought to reflect awareness of the mismatch that results when increased IND does not or cannot result in an adequate mechanical or ventilatory response ( 75 ). While not present during resting tidal breathing in health, the stressor of exercise or pathophysiologic processes of disease typically provoke sensations of dyspnea ( 76 ).…”

Section: Neural Drive In the Evaluation Of The Breathless Patientmentioning

confidence: 99%

“…This, in turn, further increases IND and ventilation. When paired with a rapid, shallow breathing pattern increasing dead space, and underlying expiratory flow limitation leading to dynamic hyperinflation and encroachment of tidal volume on critical inspiratory reserve ( Figure 2E ) ( 119 , 120 ), early cessation of exercise and a higher symptom burden for a given work rate ensue ( 75 ). In ILD, low diffusing capacity and low pulmonary compliance result in increased ventilatory drive and a rapid, shallow breathing pattern due to limited V T expansion, ultimately also leading to premature termination of exercise and exaggerated dyspnea ( 55 ).…”

Section: Neural Drive In the Evaluation Of The Breathless Patientmentioning

confidence: 99%

Clinical Utility of Measuring Inspiratory Neural Drive During Cardiopulmonary Exercise Testing (CPET)

2020

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Cardiopulmonary exercise testing (CPET) has traditionally included ventilatory and metabolic measurements alongside electrocardiographic characterization; however, research increasingly acknowledges the utility of also measuring inspiratory neural drive (IND) through its surrogate measure of diaphragmatic electromyography (EMGdi). While true IND also encompasses the activation of non-diaphragmatic respiratory muscles, the current review focuses on diaphragmatic measurements, providing information about additional inspiratory muscle groups for context where appropriate. Evaluation of IND provides mechanistic insight into the origins of dyspnea and exercise limitation across pathologies; yields valuable information reflecting the integration of diverse mechanical, chemical, locomotor, and metabolic afferent signals; and can help assess the efficacy of therapeutic interventions. Further, IND measurement during the physiologic stress of exercise is uniquely poised to reveal the underpinnings of physiologic limitations masked during resting and unloaded breathing, with important information provided not only at peak exercise, but throughout exercise protocols. As our understanding of IND presentation across varying conditions continues to grow and methods for its measurement become more accessible, the translation of these principles into clinical settings is a logical next step in facilitating appropriate and nuanced management tailored to each individual's unique physiology. This review provides an overview of the current state of understanding of IND measurement during CPET: its origins, known patterns of behavior and links with dyspnea in health and major respiratory diseases, and the possibility of expanding this approach to applications beyond exercise.

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“…Assuming stability of TLC, the resting IC and inspiratory reserve (IRV) showed the operating position of V T relative to TLC. The smaller the resting IC, the shorter the exercise time before V T reached plateau and dyspnea abruptly escalates [38]. A four-year longitudinal study reported that significant reductions in peak VȮ 2 and V̇E were related to a decrease in resting IC [39].…”

Section: Discussionmentioning

confidence: 99%

Intercept of minute ventilation vs. carbon dioxide output relationship in chronic obstructive pulmonary disease: utility as an index of ventilatory inefficiency

Wang

Lin

Nie

et al. 2020

Preprint

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Background: Ventilatory inefficiency is known to be a contributor to exercise intolerance in chronic obstructive pulmonary disease (COPD). The intercept of the minute ventilation (V̇E) vs. carbon dioxide output (V̇CO2) plot is a key ventilator inefficiency parameter. However, its relationships with lung hyperinflation (LH) and airflow limitation are not known. This study aimed to evaluate the correlations between the V̇E/V̇CO2 intercept and LH in COPD to determine its utility as an index of functional impairment.Methods: We conducted a retrospective analysis of data from 53 COPD patients and 14 healthy controls performed incremental cardiopulmonary exercise tests and resting pulmonary function. Ventilatory inefficiency was represented by parameters reflecting the V̇E/V̇CO2 nadir and slope (linear region), and intercept of the V̇E/V̇CO2 plot. Their correlations with measures of LH and airflow limitation were evaluated.Results: Compared to the control, the slope (30.58±3.62) and intercept (4.85±1.11) higher in COPDstages1-2, leading to a higher nadir (31.47±4.47) (p<0.05). Despite an even higher intercept in COPDstages3-4 (7.16±1.41), the slope diminished with disease progression (from 30.58±3.62 in COPDstages1-2 to 28.36±4.58 in COPDstages3-4). Compared to the V̇E/V̇CO2 nadir and V̇E/V̇CO2 slope, the intercept was better correlated with peak V̇E/maximal voluntary ventilation (MVV) (r=0.489, p<0.001) and peak V̇O2/watt (r=0.354, p=0.003). The intercept was also significantly correlated with RV/TLC (r=0.588, p<0.001), IC/TLC (r=-0.574, p<0.001), peak VT/TLC (r=-0.585, p<0.001); and airflow limitation forced expiratory volume in 1s (FEV1) % predicted (r=-0.606, p<0.001) and FEV1/forced vital capacity (FVC) (r=-0.629, p<0.001).Conclusion: V̇E/V̇CO2intercept was consistently better correlated with worsening static and dynamic lung hyperinflation and airflow limitation in COPD. V̇E/V̇CO2 intercept emerged as a useful index of ventilatory inefficiency across the severity spectrum of COPD patients.

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Dyspnea in COPD: New Mechanistic Insights and Management Implications

Cited by 157 publications

References 112 publications

Training Specificity of Inspiratory Muscle Training Methods: A Randomized Trial

Training Specificity of Inspiratory Muscle Training Methods: A Randomized Trial

Clinical Utility of Measuring Inspiratory Neural Drive During Cardiopulmonary Exercise Testing (CPET)

Intercept of minute ventilation vs. carbon dioxide output relationship in chronic obstructive pulmonary disease: utility as an index of ventilatory inefficiency

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