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Patients with mild chronic obstructive pulmonary disease (COPD) and lower resting diffusing capacity for carbon monoxide (DLCO) often report troublesome dyspnea during exercise although the mechani...

INTRODUCTION Evaluation of the intensity and quality of activity-related dyspnea is potentially useful in people with chronic obstructive pulmonary disease (COPD). The present study sought to examine associations between qualitative dyspnea descriptors, dyspnea intensity ratings, dynamic respiratory mechanics, and exercise capacity during cardiopulmonary exercise testing (CPET) in COPD and healthy controls. METHODS In this cross-sectional study, 261 patients with mild-to-very severe COPD (forced expiratory volume in 1 s, 62 ± 25%pred) and 94 age-matched controls (forced expiratory volume in 1 s, 114 ± 14%pred) completed an incremental cycle CPET to determine peak oxygen uptake (V˙O2peak). Throughout exercise, expired gases, operating lung volumes, and dyspnea intensity were assessed. At peak exercise, dyspnea quality was assessed using a modified 15-item questionnaire. RESULTS Logistic regression analysis revealed that among 15 dyspnea descriptors, only those alluding to the cluster "unsatisfied inspiration" were consistently associated with an increased likelihood for both critical inspiratory mechanical constraint (end-inspiratory lung volume/total lung capacity ratio ≥0.9) during exercise and reduced exercise capacity (V˙O2peak < lower limit of normal) in COPD (odds ratio (95% confidence interval), 3.26 (1.40-7.60) and 3.04 (1.24-7.45), respectively; both, P < 0.05). Thus, patients reporting "unsatisfied inspiration" (n = 177 (68%)) had an increased relative frequency of critical inspiratory mechanical constraint and low exercise capacity compared with those who did not select this descriptor, regardless of COPD severity or peak dyspnea intensity scores. CONCLUSIONS In patients with COPD, regardless of disease severity, reporting descriptors in the unsatisfied inspiration cluster complemented traditional assessments of dyspnea during CPET and helped identify patients with critical mechanical abnormalities germane to exercise intolerance.

The purpose of this study was to examine the physiological mechanisms of persistent dyspnoea in COVID-19 survivors. Non-critical patients (n = 186) with varying degrees of COVID-19 severity reported persistent symptoms using a standardized questionnaire and underwent pulmonary function and 6-minute walk testing between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n = 70) and without (n = 116) persistent dyspnoea. Patients with persistent dyspnoea had significantly lower FVC (p = 0.03), FEV1 (p = 0.04), DLCO (p = 0.01), 6-minute walk distance (% predicted, p = 0.03), and end-exercise oxygen saturation (p

The female diaphragm develops less fatigue after high-intensity exercise compared with males. Diaphragm fatigability is typically defined as a decrease in transdiaphragmatic twitch pressure (Pdi,TW) and represents the contractile function of the muscle. However, it is unclear whether this sex difference persists when examining changes in voluntary activation, which represents a neural mechanism contributing to fatigability.This study aimed to determine if high-intensity cycling results in a decrease in diaphragm voluntary activation (D-VA) and to explore if the decrease in D-VA is different between sexes.Twenty-five participants (15 females) completed a single bout of high-intensity constant load cycling. D-VA and Pdi,TW were measured before and after exercise using cervical magnetic stimulation of the phrenic nerves to assess diaphragm fatigability.Participants were of similar aerobic fitness when expressed relative to predicted values (females: 114% ± 25% predicted, males: 111% ± 11% predicted; P = 0.769). Pdi,TW decreased relative to baseline to 85.2% ± 16.7% and 70.3% ± 12.4% baseline (P = 0.012) in females and males, respectively, immediately after exercise. D-VA also decreased in both females and males immediately after exercise. The decrease in D-VA was less in females compared with males (95.4% ± 4.9% baseline vs 87.4% ± 10.8% baseline, respectively; P = 0.018).D-VA decreases after whole-body exercise in both females and males, although the magnitude of the decrease is not as large in females compared with males. The findings of this study suggest that the female diaphragm is more resistant to both contractile and neural mechanisms of fatigability after whole-body exercise.

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DlCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DlCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (V̇o2), DlCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DlCO [i.e., CO was associated with peak V̇o2 ( P = 0.006), peak work-rate ( P = 0.005), and dyspnea/V̇o2 slope ( P < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV1 and IC tertiles, peak V̇o2 and work rate were lower ( P < 0.05) in low versus normal DlCO groups. Across all tertiles, low DlCO groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal DlCO group (all P < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, DlCOCO. The higher dyspnea ratings and earlier exercise termination in low DlCO groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. NEW & NOTEWORTHY Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (DlCO) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal DlCO.

Fatigue is a common, debilitating, and poorly understood symptom post-COVID-19. We sought to better characterize differences in those with and without post-COVID-19 fatigue using cardiopulmonary exercise testing. Despite elevated dyspnoea intensity ratings, V̇O

BACKGROUND AND OBJECTIVE The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DLCO ) and ventilatory efficiency (increased ventilatory requirement for CO2 clearance [V˙E /V˙CO2 ]) has been linked to exertional dyspnoea and exercise intolerance in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are poorly understood. The current study examined if low resting DLCO and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD. METHODS In this retrospective analysis, we compared V˙E /V˙CO2 , dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DLCO at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n = 44]) or (2) below the

The purpose of this study was to examine the physiological mechanisms of persistent dyspnoea in COVID-19 survivors. Non-critical patients (n = 186) with varying degrees of COVID-19 severity reported persistent symptoms using a standardized questionnaire and underwent pulmonary function and 6-minute walk testing between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n = 70) and without (n = 116) persistent dyspnoea. Patients with persistent dyspnoea had significantly lower FVC (p = 0.03), FEV1 (p = 0.04), DLCO (p = 0.01), 6-minute walk distance (% predicted, p = 0.03), and end-exercise oxygen saturation (p < 0.001), and higher Borg 0-10 ratings of dyspnoea and fatigue (both p < 0.001) compared to patients without persistent dyspnoea. We have shown that dyspnoea is a common persistent symptom across varying degrees of initial COVID-19 severity. Patients with persistent dyspnoea had greater restriction on spirometry, lower DLCO, reduced functional capacity, and increased exertional desaturation and symptoms. This suggests that there is a true physiological mechanism that may explain persistent dyspnoea after COVID-19.

Lung function testing has undisputed value in the comprehensive assessment and individualized management of chronic obstructive pulmonary disease, a pathologic condition in which a functional abnormality, poorly reversible expiratory airway obstruction, is at the core of its definition. After an overview of the physiologic underpinnings of the disease, the authors outline the role of lung function testing in this disease, including diagnosis, assessment of severity, and indication for and responses to pharmacologic and nonpharmacologic interventions. They discuss the current controversies surrounding test interpretation with these purposes in mind and provide balanced recommendations to optimize their usefulness in different clinical scenarios.

COPD is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal death. Overnight deterioration of inspiratory capacity (IC) and FEVWhat is the effect of evening dosing of dual, long-acting bronchodilation on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND)?A double-blind, randomized, placebo-controlled crossover study assessed the effects of evening long-acting bronchodilation (aclidinium bromide/formoterol fumarate dihydrate: 400/12 μg) or placebo on morning trough IC (12 h after the dose; primary outcome) and serial overnight measurements of spirometry, dynamic respiratory mechanics, and IND (secondary outcomes). Twenty participants with COPD (moderate/severe airway obstruction and lung hyperinflation) underwent serial measurements of IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures, and diaphragm electromyography (diaphragmatic electromyography as a percentage of maximum; IND) at 6 time points from 0 to 12 h after the dose and compared with sleeping IND.Compared with placebo, evening bronchodilation was not associated with increased morning trough IC 12 h after the dose (P = .48); however, nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12 h after the dose, and IC for 10 h after the dose were improved (P .05). During placebo, total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings all increased significantly overnight compared with baseline evening values; however, each of these parameters improved with bronchodilator treatment (P .05) with no change in ventilation or breathing pattern.Respiratory mechanics significantly deteriorated at night during placebo. Although the morning trough IC was unchanged, evening bronchodilator treatment was associated consistently with sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02429765.

Many patients with severe chronic obstructive pulmonary disease (COPD) report an unpleasant respiratory sensation at rest, which is further amplified by adoption of a supine position (orthopnoea). The mechanisms of this acute symptomatic deterioration are poorly understood.Sixteen patients with advanced COPD and a history of orthopnoea and 16 age- and sex-matched healthy controls underwent pulmonary function tests (PFTs) and detailed sensory–mechanical measurements including inspiratory neural drive (IND) assessed by diaphragm electromyography (EMGdi), oesophageal pressure (Pes) and gastric pressure (Pga), in both sitting and supine positions.Patients had severe airflow obstruction (forced expiratory volume in 1 s (FEV1): 40±18% pred) and lung hyperinflation. Regardless of the position, patients had lower inspiratory capacity (IC) and higher IND for a given tidal volume (VT) (i.e.greater neuromechanical dissociation (NMD)), higher intensity of breathing discomfort, higher minute ventilation (V′E) and higher breathing frequency (fB) compared with controls (all pversussitting erect, with a small drop inV′E, mainly due to reducedfB(all pCLdyn) decreased (pIn COPD, onset of orthopnoea coincided with an abrupt increase in elastic loading of the inspiratory muscles in recumbency, in association with increased IND and greater NMD of the respiratory system.

Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This “dyspnea spiral” is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients’ benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand–capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual.

Supervised exercise training (EXT) as part of pulmonary rehabilitation is arguably the most effective intervention for improving exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). In the current review, we focus on the physiological rationale for EXT and the expected physiological benefits that can be achieved in patients who can be exposed to sufficiently high training stimuli. Thus, after a brief consideration of the mechanisms of exercise limitation and their sensory consequences, we expose the potential beneficial effects of EXT on respiratory mechanical and peripheral muscular adaptations to exercise. The available evidence indicates that changes in exertional ventilation, breathing pattern, operating lung volumes and static respiratory muscle strength after EXT are modest and often inconsistent. Inspiratory muscle training may have a role in patients showing inspiratory weakness pre-rehabilitation. Beneficial changes in peripheral muscles can be seen in those who can tolerate higher training intensity, particularly using combined resistance and dynamic (including interval) exercise. It should be recognised, however, that it might not be feasible to reach meaningful physiological training effects in many frail elderly patients with advanced respiratory mechanical and pulmonary gas exchange derangements with serious co-morbidities (such as cardiac and peripheral vascular disease). These potential shortcomings should not discourage the use of pulmonary rehabilitation as an effective strategy to improve patients' capacity to tolerate physical activity. Currently, the greatest challenge is to develop effective strategies to ensure that these important gains in functional capacity are translated into sustained increases in daily physical activity for patients with COPD.

Unexplained dyspnea presents a significant diagnostic challenge. Dyspnea arises when inspiratory neural drive (IND) to the respiratory muscles is increased and the respiratory system fails to meet this increased demand. Cardiopulmonary exercise testing (CPET) is a valuable tool to unravel the causes of exertional dyspnea in the individual. Moreover, analysis of breathing pattern, operating lung volumes and flow-volume loops allows characterization of abnormal dynamic mechanical response to increased IND - an important source of breathing discomfort. We illustrate the clinical utility of this approach which examines respiratory sensation, ventilatory control, respiratory mechanics and cardio-circulatory responses in cases of unexplained dyspnea.

Dyspnea, the most common symptom in chronic obstructive pulmonary disease (COPD), often becomes disabling in advanced stages of the disease. Chronic dyspnea erodes perceived health status and diminishes engagement in physical activity, often leading to skeletal muscle deconditioning, anxiety, depression, and social isolation. Broader understanding of the pathophysiologic underpinnings of dyspnea has allowed us to formulate a sound rationale for individualized management. This review examines recent research and provides historical context. The overarching objectives are to consider current constructs of the physiologic mechanisms of activity-related dyspnea and identify specific targets amenable to therapeutic manipulation in patients with COPD.

Background The purpose of this study was to determine if altered central chemoreceptor characteristics contributed to the elevated ventilation relative to carbon dioxide production (VE/VCO2) response during exercise in mild chronic obstructive pulmonary disease (COPD). Methods Twenty-nine mild COPD and 19 healthy age-matched control participants undertook lung function testing followed by symptom-limited incremental cardiopulmonary exercise testing . On a separate day, basal (non-chemoreflex) ventilation (VEB), the central chemoreflex ventilatory recruitment threshold for CO2 (VRTCO2), and central chemoreflex sensitivity (VES) were assessed using the modified Duffin’s CO2 rebreathing method. Resting arterialized blood gas data were also obtained. Results At standardized exercise intensities, absolute VE and VE/VCO2 were consistently elevated and the end-tidal partial pressure of CO2 was relatively decreased in mild COPD versus controls (all p 0.05). Conclusion These data have established that excessive exercise ventilation in mild COPD is not explained by altered central chemosensitivity.

Frailty is the age-related accumulation of deficits that decrease the ability to respond to biological stress. Patients with fibrotic interstitial lung disease (ILD) may be frail due to consequences of ILD, age, co-morbidities and adverse effects of pharmacotherapies. The objective of this study was to examine the prevalence and predictors of frailty in fibrotic ILD.Fibrotic ILD patients were recruited from a specialized clinic. Patients with ILD secondary to a systemic disease were excluded. Frailty was determined using the Frailty Index based on the presence or absence of multiple deficits, including co-morbidities, symptoms and functional limitations. The Frailty Index was based on the proportion of deficits present, with frailty defined as a score0.21. Cronbach's alpha was used to estimate the internal consistency of the Frailty Index. Dyspnoea was measured using the University of California San Diego Shortness of Breath Questionnaire. Multivariate analysis was used to determine independent predictors of frailty.The definition of frailty was met in 50% of the 129 patients. Cronbach's alpha for the Frailty Index was 0.87. The Frailty Index was associated with forced vital capacity (FVC), forced expiratory volume in 1 s (FEVFrailty is highly prevalent and is strongly and independently associated with dyspnoea severity, demonstrating that dyspnoea is a more important determinant of frailty than pulmonary function.